COMPLICATIONS—HYPOGLYCEMIA 2299-PO The Prediction of … · may help deﬁ ne strategies for basal insulin titration in Asia. We used a Generalized Estimating Equation Poisson model

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COMPLICATIONS—HYPOGLYCEMIA


2297-POUse of Insulin Analogues in Outpatient Setting in Italy: Pooled Anal-ysis of 3 Observational Studies on Type 2 DiabetesDOMENICO CUCINOTTA, SALVATORE CAPUTO, EDOARDO MANNUCCI, FABIO PELLEGRINI, PAOLO SBRACCIA, FABRIZIO CAVALLARI, GIUSI LASTORIA, PAOLO NICOZIANI, ANTONIO NICOLUCCI, Messina, Italy, Rome, Italy, Firenze, Italy, Santa Maria Imbaro, Italy

We performed a joint analysis of the Upgrade and the Italian arms of the Improve™, and Predictive™ studies. Overall, 6768 individuals with T2DM treated with insulin analogues in about 400 Diabetes Units were evaluated.

The three studies matched for duration (26 weeks), number and timing interval between visits and had similar study design, endpoints, hypoglycemia and SAE/SADR defi nition, allowing for a pooled analysis of the databases.

Baseline patient characteristics were (mean±SD): age 66.2±10.2 years, diabetes duration 16.1±9.9 years, insulin treatment duration 1.7±4.9 years, HbA1c 8.12±1.47, 77% of patients with HbA1c>7% and 47% with HbA1c>8%.

Among patients treated with 3-4 insulin injections/day, the most frequent regimens were Basal-Bolus (BB, 45.5%) and 2 boluses+1 mix (B-Mix, 30.5%) and the most common oral therapy combined with insulin was metformin (met) (28.7% in BB; 24.5% in B-Mix). Among patients treated with basal insu-lin + oral hypoglycemic agents (OHA) (basal oral therapy, BOT), 68% were treated with sulfonylurea (SU) of which 58% with SU+met and 10% with SU only.

The incidence of Severe Hypoglycemia (SH) at baseline was 0.37 ev/pt-y (0.11 night) with 3.3% of patients having at least 1 SH. SH was more frequent in patients with HbA1c<6.5% and highest in patients treated with BOT: 0.64 ev/pt-y (0.25 night). The incidence of Minor Hypoglycemia (MH) at baseline was 8.06 ev/pt-y (1.56 night) with 22.6% of patients having at least 1 MH.

A multivariate analysis indicated that MH but not SH were inversely cor-related with the likelihood of having a reduction of at least 1.0% of HbA1c during the follow-up (OR=0.78, p=0.016).

In the Italian outpatient setting, the BB regimen is largely used for the treatment of T2DM. The optimization of BOT by using basal insulin with physiologic profi le and reducing the use of SU may lower the risk of SH; in addition a greater attention to MH may help in safely achieving the HbA1c goal.

Supported by: Novo Nordisk, Inc.

2298-POValidity of the Hypoglycemia Perspectives Questionnaire: A Patient-Reported Outcomes Instrument to Assess HypoglycemiaSHALOO GUPTA, TIMOTHY W. VICTOR, MARCO D. DIBONAVENTURA, SIEW H. ONG, CHAD GWALTNEY, Princeton, NJ, New York, NY, Basel, Switzerland, Westerly, RI

Understanding the patient’s experience of hypoglycemia is essential in treatment development and clinical practice. The Hypoglycemia Perspectives Questionnaire (HPQ) is a new patient-reported outcome (PRO) instrument that provides a comprehensive assessment of the patient’s views on hypoglycemia. This study assessed the validity of the HPQ by examining its relationship to other instruments associated with hypoglycemia. It was administered online to 1,257 participants from the 2011 US National Health and Wellness Survey who reported a diagnosis of type 2 diabetes. Participants also completed the Hypoglycemia Fear Survey-II (HFS-II), Audit of Diabetes Dependent Quality of Life (ADDQoL) and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Known-groups validity, convergent validity, and incremental validity were examined. The mean age was 59.9 years (SD=11.0), 54.3% were male, 83% were white, and mean time since diagnosis was 10.6 years (SD=7.7). Patients who experienced a hypoglycemic event in the 7 days before the assessment reported higher scores (all p<.05) on all HPQ items. All four subscales of the HPQ were moderately-to-strongly correlated with the two subscales from the HFS-II (r=0.48 to 0.65), the “Perceived Frequency of Hypoglycemia” subscale of the DTSQ (r=-0.39 to -0.47), the ADDQoL total score (r=-0.37 to -0.48), and the DTSQ total score (r=-0.11 to -0.20). Three of the HPQ subscales were found to predict ADDQoL and/or DTSQ above and beyond the HFS-II subscales (p<0.05) supporting its incremental validity. The fi ndings support the validity of the HPQ for measuring experiences of and attitudes towards hypoglycemia. The content of the HPQ extends the assessment of hypoglycemia beyond what is available in other PRO instruments and makes it a valuable instrument for use in clinical trials and practice.

Supported by: Novartis Pharma AG

2299-POThe Prediction of Blood Creatinine and eGFR on Renal Dysfunction Induced by HypoglycemiaYU L.I. LEE, SHYI J. SHIN, KUN D. LIN, Kaohsiung, Taiwan

Hypoglycemia is reported to be associated with higher risks of microvas-cular events. However, no study using clinical data has been conducted to examine their association with the progression of renal dysfunction induced by hypoglycemia. In this study, we investigated the predictor of renal dysfunc-tion resulted from hypoglycemia in type 2 diabetic patients. A retrospective cohort study was conducted using the electronic medical records from Janu-ary 2004 to September 2012. One hundred one patients who hospitalized with a diagnosis of hypoglycemia and had complete clinical data prior to and on the date of hypoglycemia, and in a follow-up period of at least 3 months to one year were recruited. One hundred twenty eight control patients were selected by a simple random sampling method by matching mean values of baseline blood creatinine and diabetic duration. Baseline blood creatinine, eGFR, BP, HbA1c and lipid levels were not different in two groups. Multivari-ate logistic regression for the change of blood creatinine and eGFR was con-ducted. In full population, hypoglycemia event was associated with a sig-nifi cant increase in the adjusted risk of renal dysfunction (HR, 7.35; 95% CI, 3.4 to 16.1; and 6.98, 95% CI, 3.2 to 15.0 for blood creatinine and eGFR, respectively). In hypoglycemic group, baseline creatinine>1.4 mg/DL and eGFR<60 ml/min increased the risk of renal dysfunction in comparison with patients with Cr<1.4 mg/dL(HR, 9.13; 95%CI 1.8 to 45.4) and eGFR>60 ml/min(HR, 9.13; 95%CI 1.8 to 45.4), respectively. These results indicate that baseline blood Cr and eGFR can predict the risk of renal dysfunction induced by hypoglycemic event in type 2 diabetes.

2300-POHypoglycemia among 3132 Insulin-Treated Patients With Type 1 and Type 2 Diabetes: Frequency and Predictive Factors—Results from the Prospective DIALOG StudyBERTRAND CARIOU, MICHEL LIÉVRE, DOMINIQUE HUET, BERNARD CHARBON-NEL, CAROLINE SERT, DIDIER GOUET, Nantes, France, Lyon, France, Paris, France, La Rochelle, France

Few data are available on hypoglycemia (hypo) rates in real life. The obser-vational, multicenter, French DIALOG study examined the frequency of hypo in patients with type 1 (T1D) or type 2 (T2D) diabetes, insulin-treated for >1 year. Endocrinologists and general practitioners consecutively enrolled patients and gave them a prospective questionnaire for self-recording hypo over 1 month (using the ADA hypo defi nition). The primary objective was frequency of total confi rmed hypo. Characteristics for the 3132 patients with T1D /T2D were: age: 49.7±15.9 / 66.8±10.6 y, BMI: 25.4±4.3 / 31.0±5.9 kg/m2, HbA1c: 7.8±1.2 / 7.8±1.1%, duration of diabetes: 20.9±13.0 / 17.7±9.3 y. Hypo rates are shown in the table.

Type 1(N=1356)

Type 2(N=1776)

Frequency(% of

patients)

Events/patient/month

Frequency(% of

patients)

Events/patient/month

All 85.7 6.3 45.0 1.6Confi rmed severe 13.3 0.2 6.7 0.1Confi rmed (< 0.7 g/L) non severe 84.7 6.1 43.0 1.5Confi rmed (< 0.7 g/L) asymptomatic 27.4 0.9 8.2 0.2Nocturnal 40.1 0.7 11.2 0.2

Predictive factors (PF) were analyzed by a multivariate regression model in 912 T1D and 1677 T2D patients. Main PF in T1D were previous history of hypo (odds ratio [OR] 8.62), BMI <30 kg/m2 (OR 2.15), >2 daily insulin injections (OR 2.18), insulin therapy duration 10 y (OR 2.09). In T2D, main PF were previ-ous history of hypo (OR 3.89), insulin therapy duration >10 y (OR 1.60), >2 daily insulin injections (OR 2.12) and absence of coronary artery disease (OR 1.43).

DIALOG is a large prospective study of hypo in real life which demonstrates a high frequency of confi rmed hypos in both T1D and insulin-treated T2D. Previous history of hypo appears to be the main predictive factor for hypo.


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2301-POReduced Rate of Hypoglycemia With the Implementation of a New Subcutaneous Insulin Protocol in a Tertiary HospitalBRANDON M. MARKLEY, KENNETH IZUORA, GAGANDEEP KAUR, Las Vegas, NV

Hyperglycemia occurs commonly in hospitalized patients with and without diabetes. Although adequate blood glucose control is important, it has been demonstrated that intensive control of inpatient blood glucose often results in hypoglycemia and higher mortality. In our institution, high rates of hypo-glycemic events (blood glucose < 70 mg/dL) were noted with a previous sub-cutaneous insulin protocol targeting intensive glucose control (blood glucose 90 - 130 mg/dL) for non-ICU patients. Among all hospital patients, 41.8% had at least one hypoglycemic episode while on the old protocol. Taking this into account, along with recent evidence supporting less intensive glycemic goals, our institution decided to implement a less stringent subcutaneous insulin protocol for non-ICU adult patients with a glycemic goal of 150 - 200 mg/dL. Data was collected by a retrospective chart review, before and after the new protocol was implemented utilizing pharmacy records to identify eligible patients. Among the fi rst 48 patients treated with the new protocol, there was a total of 549 blood glucose readings of which 8 were between 50 and 70 mg/dL while only 2 were below 50 mg/dL. Ten patients (20.8%) had at least one hypoglycemic episode. This is about a 50% reduction in the number of patients with hypoglycemia compared to the old protocol. Other outcome measures that we are presently analyzing include impact of the change in protocol on other glycemic parameters (hyperglycemia and average blood glucose), mortality, and hospital length of stay. Our fi ndings so far suggest that the implementation of the new protocol resulted in a reduction in the incidence of hypoglycemia and we anticipate an improvement in the other outcome measures as a result.

2302-POAsian Treat to Target Lantus Study (ATLAS): Identifi cation of Clinical Predictors for Hypoglycemia in the Context of New Insulin Titration Strategies in AsiaNICK FREEMANTLE, MASATO ODAWARA, SATISH GARG, KARIM ADMANE, ATLAS STUDY GROUP, London, United Kingdom, Tokyo, Japan, Aurora, CO, Paris, France

Hypoglycemia is a limiting factor for insulin titration in type 2 diabetes (T2DM). The ATLAS study compared 2 titration methods with insulin glargine: patient-led vs physician-led; and confi rmed that basal therapy, along with oral agents, is safe and effective for managing Asian patients with T2DM. Iden-tifying clinical predictors of hypoglycemia was the goal of this analysis, as it may help defi ne strategies for basal insulin titration in Asia.

We used a Generalized Estimating Equation Poisson model with symptom-atic hypoglycemia as a response variable and site as clustering effect. Cova-riates selected on the basis of overall model fi t (Quasi likelihood under Inde-pendence model Criterion) comparing 2 candidate models were: treatment arm, baseline fasting blood glucose (FBG), duration of diabetes, BMI, sulfo-nylurea (SU) dose, metformin dose, gender, age, country, early FBG control (week 12), and rapid insulin dose increase. A signifi cant effect was obtained for patient-led titration, BMI, SU dose, and the countries India and the Philip-pines. These fi ndings suggest that patient involvement is key for management optimization, and that patient-led titration may deserve specifi c educational actions with the support of treating physicians. Limiting SU dose might be benefi cial, while BMI may be a critical factor to consider. Lastly, local condi-tions may also play an important role.

Supported by: Sanofi

2303-POHypoglycemia Early Prediction Systems Based on Recursive ModelsKAMURAN TURKSOY, ELIF S. BAYRAK, LAURIE QUINN, ELIZABETH LITTLEJOHN, ALI CINAR, Chicago, IL

Hypoglycemia is a major challenge of artifi cial pancreas systems and a signifi cant concern for the parents of young children with diabetes. Early warning systems (EWS) that alert the potential of hypoglycemia and provide enough time to take action to avoid it are very appealing. Subject-specifi c recursive models are used to predict future blood glucose concentrations (BGC). These models are then used in early hypoglycemia warning systems that notify patients 20-30 minutes in advance of the forecasted hypoglycemia episode.

The models developed and the hypoglycemia EWS are tested retrospec-tively using T1D subject data and in real time in clinical study. A Savitzky-Golay fi lter and a Kalman fi lter are used to reduce measurement noise. CGM data and physiological signals from a multi-sensor body monitor are used in predict-ing BGCs. The hypoglycemia EWS is developed by using future BGC predictions from recursive models. The fi gure illustrates the performance of the EWS based on 6-steps-ahead (30 min) prediction for data from a subject. A Savitzky-Golay fi lter with a fi rst-order polynomial and a 15-step window is used to smooth the data. There were 201 real hypoglycemic events in all data ana-lyzed. The performance of BGC predictions and EWS is evaluated with respect to raw data. For the 6-steps-ahead BGC predictions, hypoglycemic events were predicted with 89.05% sensitivity and 28.6 min average early detection time. The EWS has a good performance in predicting hypoglycemia and pre-venting of its occurrence.

Supported by: NIH/NIDDK (R01DK085611)

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2306-POIncidence of Severe Hypoglycemia Requiring Hospitalization in ItalyGIORGIA DE BERARDIS, FABIO PELLEGRINI, ANTONIO D’ETTORRE, LUCIA BISCE-GLIA, MONICA FRANCIOSI, FRANCESCO GIORGINO, VITO LEPORE, GIUSEPPE LUCISANO, FABIO ROBUSTO, ANTONIO NICOLUCCI, Santa Maria Imbaro, Italy, Bari, Italy

The aim of the study was to evaluate the incidence of hospitalization for severe hypoglycemia (SH) using the Administrative Databases related to 12 local Health Authorities of Region Puglia. We conducted a population-based cohort study using a record-linkage analysis of hospital discharge records, prescription databases, and civil registry, including data on 4.1 million citizens during the period 2002-2010. All subjects with pharmacologically treated diabetes were eligible regardless of gender, age and hypoglycemic treatment; 385,527 subjects (92% with type 2 diabetes) were included.

We identifi ed 10,362 hospitalizations relative to 9,021 subjects. SH was reported as primary and secondary diagnosis in 40.46% and 59.54% of hos-

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pitalizations, respectively. The overall incidence rate (IR) of hospitalization was 5.58 per 1000 person-years and the distribution by year showed a decrease of 42% over time (year 2003 vs. 2010). The highest IRs were observed in the younger (<20 years) and older (>80 years) age groups. However, the largest proportion of events was attributable to the 60-80 years age group.

Overall, 49% of patients were treated with oral hypoglycemic agents (OHA) alone in the 90 days before the event, while 51% were receiving insulin alone or in combination with OHA. In detail, 11% of the sample was treated with Basal Bolus (BB) insulin, 2% with premixed insulins, 21% with other insulin schemes, 4% with a Basal Oral Therapy (BOT), and the remaining 13% with OHA in association with other insulin schemes.

Among patients with type 2 diabetes, the relative contribution of BOT increased by 8 times over time, reaching 5% in 2010 and the contribution of BB increased by 3 times, while the proportion of episodes attributable to OHA or other therapeutic regimens slightly decreased.

In conclusion, SH remains an important problem in the management of patients with diabetes; if the data referred to Region Puglia were applied to Italy (3,000,000 of patients with diabetes), we estimate 15,000 hospitaliza-tions/year for SH.

2307-PO

2308-POFrequency of Hypoglycemia Is Associated With Retinopathy in 987 French Type 2 Diabetic Patients at Inclusion in the Gerodiab CohortJEAN-PIERRE LE FLOCH, JEAN DOUCET, CHRISTIANE VERNY, BERNARD BAUDU-CEAU, THE SFD-SFGG INTERGROUP, THE GERODIAB GROUP, Villecresnes, France, Rouen, France, Paris, France, Saint-Mandé, France

The observational Gerodiab cohort study aimed to describe mortality, mor-bidity and associated factors in 987 French type 2 diabetic patients aged 70 years and over, during a fi ve-year period. This study looked for factors associ-ated at baseline with the frequency of hypoglycemia during the previous 6 months. Hypoglycemia was assessed on clinical events and self-monitoring. Data (mean±SD) were analyzed using t-test and chi² test; multivariate analy-ses used the logistic model.

Patients with hypoglycemia (33.6%) had a longer duration of diabetes (21±11 vs.16±10 yr; P<0.001) but a similar age (77±5 vs. 77±5 yr; NS). They had a lower BMI (29±5 vs. 30±5 kg/m²; P<0.05), DBP (73±11 vs. 75±10 mmHg; P<0.05), LDL-cholesterol (90±32 vs. 100±37 mg/dL; P<0.001), MDRD (65±22 vs. 69±23 ml/min; P<0.01) and a slightly but not signifi cantly lower HbA1c (7.5±1.0 vs. 7.6±1.4%; NS). They had a higher frequency of retinopathy (36 vs. 21%; P<0.001), nephropathy (54 vs. 44%; P<0.05) and peripheral neuropathy (36 vs 24%; P<0.01), whilst the frequency of strokes, heart failure and cerebral involvement was similar in both groups. Scores of geriatric scales (Mini-Mental State Examination, Mini-Nutritional Assessment, Instrumental Activ-ity of Daily Living and Activity of Daily Life) were similar in both groups with the exception of the mini-Geriatric Depression Scale score which was more frequently impaired (42 vs. 31%; P<0.01). Insulin was the only treatment asso-ciated with increased frequency of hypoglycemia (75 vs. 48%; P<0.001). Using stepwise logistic regression, hypoglycemia was associated with retinopathy (P<0.01), LDL-cholesterol and the mini-GDS score (P<0.05), successively (con-cordance 44%; P<0.001).

These results underline the association between hypoglycemia and retin-opathy in elderly type 2 diabetic patients and support the importance of individualizing treatment goals in order to prevent hypoglycemic events.

Supported by: SFD; Novo-Nordisk, Inc.; Merck Serono

2309-POChanges of Heart Rate Variability Including QTc Interval and Elec-trolytes during Hypoglycemic State in Patients With Panhypopituitar-ism Undergoing Combined Pituitary Stimulation TestsJUNG HWA JUNG, JONG RYEAL HAHM, TAE SIK JUNG, SOO KYOUNG KIM, SUNGSU KIM, BYEONG TAK JEON, GU SEOB ROH, SOON IL CHUNG, Jinju, Repub-lic of Korea

There has been an increasing interest in associations between hypoglyce-mia and impaired automatic function. In addition, some recent studies reported that prolonged QT interval was observed in diabetic patients with severe hypoglycemia. Diabetic patients are particularly vulnerable to hypoglycemia because they have reduced glucagon secretion and combined automatic dys-function. Power spectral analysis is considered as the most quantitative and reliable method to analyze heart rate variability and it also provide continuous data on sympathetic-parasympathetic nervous system.

This study is prospectively conducted to assess 1) changes in serum elec-trolytes and QTc and RR intervals on ECG and 2) changes in autonomic nervous system through power spectral analysis (high frequency (HF), low frequency (LF) and LF/HF ratio) before and after hypoglycemia during combined pituitary stimulation test in patients with panhypopituitarism.

We analyzed six patients (5 females, 1 male; age 48±9.8 yrs; size of pituitary mass 1.3~2.5 cm, mean: 1.7±0.45 cm), who underwent combined pituitary stimulation test from November to December, 2012. During hypoglycemia (glucose 31±7.64 mg/dl), serum potassium was decreased by 0.68±0.33 mmol/L and QTc interval was increased by 31±20.79 msec. QTc interval was signifi cantly increased during hypoglycemia compare to the basal state (469.5±26.10 vs 438±12.57, p<0.05). In power spectral analysis, both LF and HF reduced during hypoglycemia, which suggest that both sympathetic and parasympathetic activities decrease.

This result shows that hypoglycemia during combined pituitary stimulation test might cause severe arrhythmia by QT prolongation. Also, this provides the change of autonomic nervous system during hypoglycemia might be affected by parasympathetic withdrawal than sympathetic overactivity.

Supported by: Cooperative Research Program for Agriculture Science & Technol-ogy Development

2310-POPredictors of Hypoglycemic Events in Type 2 Diabetic Patients on Basal Insulin, Oral Antidiabetic Treatment and a Single Daily Bolus of Insulin Glulisine (Basal-Plus)THORSTEN SIEGMUND, HELMUT BRATH, PETER BRAMLAGE, JOCHEN SEUFERT, München, Germany, Vienna, Austria, Mahlow, Germany, Freiburg, Germany

Background: Prevention of hypoglycemia is important in insulin treated patients. We aimed to identify predictors of hypoglycemia in patients with poorly controlled diabetes treated with a single daily bolus of insulin glulisine on top of insulin glargine and oral antidiabetic drugs (Basal-Plus).

Methods: We retrospectively analyzed four trials with type 2 diabetes (3507, 3511, 3514, and 4002). Predictors for symptomatic, severe, and noctur-nal hypoglycemia were identifi ed by multivariable logistic regression analyses, calculation of odds ratios, and Wald 95% confi dence intervals.

Results: A total of 713 patients (47% female) were analyzed with a mean age of 60±9.5 years, BMI of 32±6.0 kg/m2, and diabetes duration of 11±7.0 years. HbA1c at baseline was 7.6±0.9%. We identifi ed female gender, diabe-tes duration > 10 years, and higher basal insulin dose as predictors of noctur-nal and symptomatic, but not severe hypoglycemia. High BMI indicated a reduced risk for symptomatic hypoglycemia.

Conclusions: In retrospective analyses of 4 trials, patients with basalinsulin and oral antidiabetic treatment receiving a single bolus of insulin

glulisine, female gender, longer diabetes duration and higher basal insulin dose were associated with more nocturnal and/or symptomatic hypoglycemic events, while increased BMI reduced the risk of symptomatic episodes.

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Supported by: Sanofi

2311-POThe Impact of Hypoglycemic Events on use of Healthcare Resources: Results from the Prospective DIALOG StudyPIERRE FONTAINE, DIDIER GOUET, EVELINE ESCHWEGE, ANTOINE AVIGNON, MATTIEU GUERY, BERTRAND CARIOU, Lille, France, La Rochelle, France, L’Hay les Roses, France, Montpellier, France, Paris, France, Nantes, France

DIALOG is an observational survey assessing hypoglycemia in insulin-treated patients with type 1 (T1D) or type 2 (T2D) diabetes. This study aimed to investigate the consequences and impact of severe (SHE) and non-severe (NSHE) hypoglycemic episodes on use of healthcare resources. Patients with T1D (n=1356) or T2D (n=1776) completed a prospective self-assessment ques-tionnaire on the frequency and severity of hypoglycemic events over a 30-day period. NSHE were defi ned as symptomatic hypoglycemia confi rmed by blood glucose <70 mg/dL, and SHE as episodes requiring third-party assistance. Baseline demographics (means ±SD) were age, 49.7 ± 15.9 y, duration of diabetes 20.9 ± 13.0 y, BMI 25.4 ± 4.3 kg/m2 for T1D, and, 66.8 ± 10.6 y, 17.7 ± 9.3 y and 31.0 ± 5.9 kg/m2 for T2D. HbA1c at baseline was 7.8 ± 1.2% and 7.8 ± 1.1% in patients with T1D and T2D respectively. Over 30 days, 9.6% of patients experienced a SHE (467 episodes) and 61.0% reported NSHE (12,438 episodes). Whilst the majority of episodes requiring emergency treat-ment and/or hospitalization resulted from SHE, NSHE were responsible for a greater number of capillary tests and contacts with healthcare professionals (Table). The high frequency of NSHE compared with SHE requires the utiliza-tion of signifi cant healthcare resources, and is likely to have a considerable economic impact. This study demonstrates the importance of reducing the number of NSHE and SHE, to alleviate the burden on healthcare systems.

Type 1 diabetes Type 2 diabetes SHE NSHE SHE NSHE (N=289) (N=9513) (N=178) (N=2925)Loss of consciousness 27 0 11 0Transport to emergency room 6 0 4 1Hospitalization 2 1 7 3Additional capillary tests 35 461 32 233Contacts with healthcare professional 20 67 23 44––Consultations 5 26 5 11SHE, Severe hypoglycemic episode; NSHE, non-severe hypoglycaemic episode


2312-POCarotid Bodies and Hypoglycemia Unawareness in Type 1 DiabetesSIMMI DUBE, CHERYL SHONKWILER, ISABEL ERRAZURIZ CRUZAT, BRENT MCCO-NAHEY, ANANDA BASU, MICHAEL J. JOYNER, RITA BASU, Rochester, MN

Studies have demonstrated that carotid body (CB) chemoreceptors sense blood glucose and play a role in counterregulatory response to hypoglycemia in humans. The current studies were conducted to assess the role of CB in people with type 1 diabetes with hypoglycemia unawareness (HU) or awareness (HA). 5 HU and 8 HA based on clinical history,Clark’s hypoglycemia awareness survey matched for age, BMI, and HbA1c were subjected to two 180 min hyperinsulinemic (2 mU/kg FFM/min), hypoglycemic clamps one week apart with randomized exposure to normoxia or hypoxia (SpO2 98 ± 1 vs.85 ± 2% p<0.0001). Results were compared using means of last forty minutes of baseline and clamp data.

In the presence of matched glucose (3.3 mM) and insulin concentrations ( 834 pM) in HU and HA subjects during clamp on all study visits, the glucose infusion rate required to maintain hypoglycemia was signifi cantly higher (p< 0.0001) in HU subjects than HA subjects (Fig 1 top). Counterregulatory hor-

mones were lower in HU vs. HA on both days suggesting that CB sensitivity to hypoglycemia decreases in HU vs. HA (Fig1 bottom). However, in HU hor-mone responses to hypoglycemia were higher on hypoxia vs. normoxia sug-gesting that in the presence of hypoxia counterregulation to hypoglycemia in HU subjects is improved. These preliminary data suggest a) decreased CB sensitivity to hypoglycemia may contribute to HU in people with type 1 dia-betes and b) treatment strategies inducing mild hypoxia may be useful in ameliorating hypoglycemia.

Supported by: NIH RO1DK90541

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2314-PORelationships between Nocturnal Glycemic Variability and Sympa-thetic Activity in Diabetic Patients Being Treated With Insulin Ther-apy as Assessed by Both Continuous Glucose Monitoring and Holter Electrocardiogram (ECG) and the Effect of a DPP-4 Inhibitor on these ParametersYUKIKO TANIGUCHI, YUTAKA MORI, KAZUNORI SEZAKI, SHIGERU MIYAZAKI, Higashimurayama, Japan, Komae, Japan

Objective: Type 2 diabetic patients were examined for correlation between their nocturnal glucose variability and sympathetic activity as well as for changes in their sympathetic activity when given a DPP-4 inhibitor to fl atten their nocturnal glycemic fl uctuations.

Patients and Methods: The study included a total of 12 type 2 diabetic patients receiving insulin therapy. The patients were monitored by CGM and Holter ECG for heart rate variability analysis and the LF/HF ratio was assessed as an index of sympathetic activity at 5-minute intervals.

Results: While those who had nearly fl at nocturnal glycemic fl uctuations were found to have nearly fl at LF/HF ratios during the hours associated with glycemic fl uctuations, those who had acute falls in blood glucose during nighttime were found to have increased LF/HF ratios during the hours associated with acute falls in blood glucose. The [ mean LF/HF ratio between 21:00 and 08:00 ] / [ mean LF/HF ratio between 08:00 and 21:00 ] ratios was 0.68 ± 0.43 in those with fl at glycemic fl uctuations (n = 7) versus 1.32 ± 0.69 in those with acute falls in blood glucose (n = 5), thus showing increases in this parameter in those associated with acute falls in blood glucose. A comparison of changes in this parameter before and after 2 weeks of treatment with sitagliptin 50 mg/day showed that sitagliptin as add-on therapy not only fl attened the nocturnal glycemic fl uctua-tions but also suppressed increases in LF/HF ratio in these patients.

Conclusions: It was confi rmed that nocturnal acute falls in blood glucose are associated with increased sympathetic activity. It was suggested that sitagliptin could fl atten nocturnal glucose levels thus suppressing increases in sympathetic activity in diabetic patients on insulin therapy.

2315-PO

2316-POIs there a Need to Identify Patients Refusing Follow-Up Referral to Diabetes Specialist Care, Following a “Severe Hypoglycaemic Event” (SHE)?YAHYA MAHGOUB, MAUREEN E. CHADWICK, JITEN VORA, Liverpool, United King-dom

Aim: Examine the ability to identify those persons with diabetes utilising the local ambulance service for SHE, but subsequently refusing follow-up referral to the specialist diabetes services (SDS).

Method: A project carried out in the local geographical North Liverpool area (2010) identifi ed that some patients with diabetes used the local ambu-lance service following a SHE but then refused referral for follow-up from SDS. Contact was made and non-identifi able data (NID) numbers of all ‘dia-betes incidences’ (DI) in the area was obtained.

Using the local ambulance service in-house data collection tools; retrospec-tive anonymised data from April 2011- March 2012, revealed a total number of 968 non-identifi ed ‘diabetes incidences (DI)’ call outs, which were then sub-divided to the three main hospital emergency room (ER) departments in the North Liverpool area, where patients were admitted.

Results: Of the total 968 non-identifi ed transported persons; 470 persons were transported to emergency rooms across North Liverpool. Of these 470; 327 were taken to Royal Liverpool Hospital (RLH) which equated to 68%. After further investigation within the hospital protected data, of the total 327 per-sons, 154 experienced a SHE and became inpatients of the RLH.

From the remaining 486 NWAS call-outs; 112 (23%), identifi ed as diabetes incidences were not transported to an ER or had a follow-up referral.

Using the original previous percentage split of ER referrals to the three main ER departments in North Liverpool, 76 (68%) persons potentially could have been transported to RLH ER and query 24 (32%) persons may have had a positive SHE diagnosis and become inpatients.

Conclusion: A possible signifi cant number of 76 persons having the poten-tial of being admitted through the ER of a large Liverpool Teaching Hospital identifi es a potential need to know who these persons are.

2317-POLength of Hospital Bed Stay (LOS) Following Severe Hypoglycaemia Event (SHE): Is it Longer for the Older Person (Aged 60 and Over) Liv-ing in Care Homes?MAUREEN E. CHADWICK, JULIE BRAKE, JITEN VORA, Liverpool, United Kingdom

Aim: Examine collected twelve month SHE retrospective data (April 2011- March 2012) and identify the proportion of these persons with diabetes, living in care facilities (e.g. Nursing/Residential Homes) compared to the indepen-dent living population and evaluate the impact of age (>60 years) on the hospital LOS.Isthe LOSlonger for thosereturning in care facilities?

Method: 90 personswere identifi ed as having aSHE resulting in inpatient admissions to a large UK teaching hospital. This data was collected using in-house data collection tools andidentifi edthose living within care facilities and those who were independent at home; theLOS was calculated and com-pared between those discharged to care facilities and those of the same age discharged home. Of these 90 persons with diabetes admitted as inpatients after SHE; 58 persons are aged >60.

Result: For the total 58, mean age: 77years (age range 60-99). 37(mean age 75years (age range 62-93) (64%)) were discharged home- total LOS 157.54 days with an average mean LOS 4.26 days. 15(mean age: 82.6 years (age range 63-99) (26%)) discharged to care facilities - total LOS 105.43 days, average mean LOS 7 days; 6(mean age 74.5 (age range 60-89) (10%)) discharged to sheltered housing - total LOS 32.04 days, average mean 5.34.In those aged <60, the mean LOS was increased by 2 of the 6 inpatients with stays of 28 and 30 days due to a number of serious comorbidities

Conclusion: The total 58 persons aged >60, who were returning to care facilities did have a longer hospital LOS than of those returning home follow-ing a SHE. Calculating the total LOS of the total 90 inpatients admissions, the mean LOS is lowest for those living independently and returning home but rises for those living in sheltered housing and for those returning to in care facilities. The longer stay in hospital of such patients clearly has major impli-cations regarding the throughput of patients and cost of care.

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COMPLICATIONS—MACROVASCULAR—ATHEROSCLEROTIC CARDIOVASCULAR DISEASE AND HUMAN DIABETES

2318-POImplementation of a Basal/Bolus Insulin Regimen Dramatically Reduces Hypoglycemia in a Rural Community HospitalDARCY REID, RICHARD ZEPPIERI, ANN WATTS, Plattsburgh, NY

Purpose: To improve safety and clinical outcomes for patients requiring glycemic control in the hospital setting.

Method: A multidisciplinary team was formed including leadership, internal medicine, primary care, pharmacy, nursing, dietary and informatics. An exten-sive literature review was done. Policies and protocols were developed based on the literature and best practices that supported the use of basal-bolus insulin regimens, abolishing the sliding scale, and treatment and prevention of hypoglycemia. Extensive hospital-wide education was completed on car-bohydrate counting, appropriate use of antidiabetic medications in the inpa-tient setting, and the treatment and prevention of hypoglycemia and hyper-glycemia. The team was accepted to participate in the Society of Hospital Medicine’s Glycemic Control Mentored Implementation (GCMI) Program. Evaluation of timing from fi nger stick to meal delivery to insulin administration was conducted. Team members and pharmacy interns analyzed and made medication adjustment recommendations for patients with periods of hyper-glycemic and/or hypoglycemic events.

Results: A 54% reduction in the incidence of severe hypoglycemia (% of patient days with at least one BG < 40mg/dL) and a 43% reduction in the incidence of hypoglycemia (% of patient days with at least one BG < 70mg/dL) was observed. This was accomplished without a clinically signifi cant increase in the patient-day mean blood glucose.

2319-POEmergency Department and Outpatient/Ambulatory Visits, Hospital-izations, and Injuries Associated With Hypoglycemia in the United States (1993–2009)QIAN SHI, YINGNAN ZHAO ZHAO, VIVIAN FONSECA, LIZHENG SHI, New Orleans, LA, Hartford, CT

Understanding health care use associated with hypoglycemia is important to clinical practices and society for resource allocation. We characterized the epidemiology and national trends in emergency department (ED) visits and outpatient/ambulatory visits for hypoglycemia. We analyzed two national databases for year 1993-2009: the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the National Ambulatory Medical Care Survey (NAMCS). The NHAMCS has ED and outpatient department (OPD) components. There were 6,891,506 ED visits (3.78 per 1,000 ED visits), 1,209,872 OPD visit (0.84 per 1,000 OPD visit), and 11,890,900 ambulatory visit (0.83 per 1,000 ambulatory visit) in 1993-2009. The NHAMCS ED visits with hypoglycemia had very high risk of ensuing hospitalization (approximately 25.2%, with 4.43 days of hospital stay), injuries (9.5%, including 6.4% unintentional injuries) and 56.7% arrived at ED in ambulance. Very few NHAMCS OPD hypoglycemia visits led to hospital admissions (~2.6 per 1000), similar to 2.4 per 1000 NAMCS hypoglycemia visits. We identifi ed demographic disparities (age, gender, race, payer type, and region). Using the two national representative databases, the impact of hypoglycemia was documented in the United States. In particular, better control for hypoglycemia should be implemented to prevent ED visits, which are likely followed by hospital admissions.

Supported by: Bristol-Myers Squibb

COMPLICATIONS—MACROVASCULAR—ATHEROSCLEROTIC CARDIOVASCULAR DISEASE

AND HUMAN DIABETES

2320-POAssociation of Genetic Variants in Proprotein Convertase 1 Gene With the Risk of Coronary Artery Disease in Type 2 Diabetes in a Chinese Han PopulationXIAOWEI WEI, XIAOWEI MA, RAN LU, GE BAI, JIANWEI ZHANG, RUIFEN DENG, NAN FENG, NAN GU, JIANPING LI, XIAOHUI GUO, Beijing, China

Objective: It has been known that, glucagon-like peptide 1 (GLP-1) , con-verted by proprotein convertase 1 (PCSK1) from proglucagon, is associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of gene PCSK1 with the risk of CAD in the Chinese Han population with T2DM.

Methods: From HapMap phase II (r2<0.8 and MAF≥0.05, R#27) CHB data-base, 5 haplotype-tagging single nucleotide polymorphisms (SNPs), rs6230 (T>C), rs6233 (T>C), rs6234 (C>G), rs156019 (T>A) and rs3811951(A>G), in PCSK1 were genotyped in 683 unrelated Chinese Han subjects with T2DM, of whom 425 individuals were CAD-positive cases and other 258 were CAD-negative controls. The associations between the 5 SNPs and risk of CAD were tested by chi-square test and multivariate logistic regression analysis adjusted for confounders.

Results: The allele frequencies at rs3811951 were signifi cantly different in cases and controls (44.31% vs 59.30%), with the allele G at a decreased risk for CAD (OR=0.748,95%CI=0.59-0.94, p=0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR=0.504, 95%CI=0.31-0.82, p=0.005), even after adjusted for the other known CAD risk factors (OR’=0.430, 95%CI’=0.24-0.77, p’=0.004, after adjustment for gender, age, BMI and smok-ing status). At rs156019, the carriers of minor allele A had a higher risk(OR=1.575,95%CI=1.13-2.19,p=0.007; OR’=1.659, 95%CI’=1.101-2.502, p’=0.016 after adjustment) in dominant inheritance mode. We also found that the SNP rs6234 was associated with CAD risk, predominantly in women. Females carrying minor allele G at rs6234 had a ruduced risk in recessive inheritance mode (OR’=0.416, 95%CI’=0.18-0.95, p’=0.036 after adjust-ment).

Conclusion: The genetic variants in PCSK1 may be associated with CAD in the Chinese patients with T2DM.

2321-POAkt Mediated Signaling Pathway Is Associated With Antiinfl amma-tory and Antioxidative Effects of FGF21 in the Heart of Diabetic MiceCHI ZHANG, YI TAN, XIAO MIAO, YANG BAI, YING XIN, XIAOKUN LI, LU CAI, Wen-zhou, China, Louisville, KY, Jilin, China

The objective of the present study was to defi ne whether fi broblast growth factor (FGF) 21 attenuates diabetic lipotoxicity induced cardiac infl ammation, oxidative stress and fi brosis and whether the cardiac protection of FGF21 is associated with Akt/GSK3β signaling pathway. Cardiac H9C2 cells were exposed to FGF21 at 50 ng/µL for 15 hours, which signifi cantly increased Akt phosphorylation that reached the peak at 3 hours after treatment. To test this hypothesis that Akt mediated signaling pathway may play an important role in the biological function of FGF21 in the heart under diabetic condition, STZ-induced diabetic mice were treated with FGF21 for 10 days. FGF21 induced a signifi cant activation of Akt and inactivation of GSK3β under diabetic condi-tion, which was associated with the attenuation of the diabetes-induced infl ammation, oxidative stress and fi brotic response. In addition, in vivo admin-istration of FGF21 to acute fatty acid-treated mice also protected fatty acid-

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induced infl ammation and oxidative stress, along with signifi cant activation of Akt induced signaling pathway. More importantly, compared to WT mice, FGF21-KO mice are highly susceptible to diabetes-induced the early stage infl ammatory and oxidative stress, which could be prevented by administration of exogenous FGF21. These results strongly suggest that the administration of FGF21 at the early stage of diabetes may represent an anti-infl ammatory and anti-oxidative effect in the heart induced by diabetic lipotoxicity. The protective effects were closely associated with the activation of Akt followed by inactivation of GSK3β. Therefore, Akt mediated signaling pathway play a key role in FGF21-mediated cardiac protection against diabetic lipotoxicity.

2322-POExpression of Glucose Transporters 1 and 4 Mediate Hyperglycemia Pre-Accommodation in Myocardial CellQIAN LIU, QINGXIAN HUANG, WEIKAI HOU, KUN WANG, SHAN YU, LI CHEN, Jinan, China

The H9c2 (2-1) cells were exposed to various glucose concentrations (0.1, 5, 10, 15, 20mmol/L), with 5mmol/L as control group (NC). Compared to NC, the GLUT4 mRNA expression of 10 mmol/L group fl ared up and then rapid decreased (P<0.05), but the protein expression had no statistical change, and their expressions were both down regulated in lower glucose (0.1mmol/L) or higher glucose (15, 20mmol/l) group. In 0.1mmol/L group, the stimulated time had nothing to do with GLUT4 expression, however in higher glucose groups (15, 20mmol/l), its’ expressions were negatively correlated with glucose level and stimulate time (P<0.05). Compared to NC group, cells of 10mmol/L group grew faster, and other grew slower. Glucose concentration was detrimental to cell proliferation. Cell proliferation had the same variation tendency with GLUT4 mRNA and protein expressions in different glucose concentrations and times (P<0.05).

Diabetic model induced by streptozocin (STZ) was prepared in Wistar rats and their blood glucose levels were controlled by insulin Glargine. These rats were divided into four groups: Blood glucose >16.7mmol/L (DM1 group), 14~16.7mmol/L (DM2 group), 10~14mmol/L (DM3 group), <10mmol/L (DM4 group), with normal rats as control group (NC group). GLUT1&4 mRNA expres-sions had a negative correlation with the level of blood glucose (r=-0.909 and -0.914, P<0.01 ); GLUT1&4 protein expressions had a negative correlation with the level of blood glucose (r=-0.870 and -0.922, P<0.01). Compared to NC group, GLUT1&4 mRNA expressions decreased signifi cantly in all DM groups (P<0.01), GLUT1&4 protein expressions decreased signifi cantly in DM1, DM2, DM3 groups (P<0.01).

These results confi rmed the changes of GLUT1&4 expression in cardiac muscular tissue with hyperglycemia environment, namely down-regulation, as a compensatory mechanism of protection, which indicating that there is hyperglycemia pre-accommodation (HGPA).

Supported by: NSFC

2323-POVWF Levels Indicate Endothelial Infl ammation in Patients With Impaired Fasting Plasma GlucoseMUSTAFA CAKAR, SEVKET BALTA, SAIT DEMIRKOL, HAKAN SARLAK, SEYIT AHMET AY, MURAT KARAMAN, EROL ARSLAN, ERDINC CAKIR, Ankara, Turkey

Beyond the effects on coagulation, von Willebrand factor (vWF) may indi-cate the presence of microangiopathy and has been found independently associated with cardiovascular and all-cause mortality. Diabetic patients have higher levels of endothelial infl ammation. It is an important focus of discussion -from what time before diabetes- physicians should be alert about the future vascular risks of these patients. Here we aimed to investigate endothelial infl ammatory condition of patients with impaired fasting glucose (IFG).

40 patients have been recruited in the study. 20 had IFG and 20 were controls. 9(45%) of the IFG and 15(75%) of the control groups subjects were female. The mean ages of the IFG and control groups were 49,45±9,6 and 39,95±11,3 years, respectively. The mean fasting plasma glucose levels of the patient and control groups were 112,1±6,9 and 88,9±8,2 mg/dl, respectively. vWF levels were signifi cantly higher in patients with an IFG (2211,8±899 vs 1422,6±739 mU/mL, respectively; p=0,003). high sensitive C-reactive protein (hsCRP) levels of the patient and control groups were 2,98±2,45 and 1,2±0,94 mg/L, respectively (p=0,006). vWF levels were also correlated with serum hsCRP levels at the patient group (r=0,522, p=0,018).

In this study, we found that vWF levels were increased signifi cantly in patients with an IFG. vWF levels were also correlated with hsCRP levels indicating higher levels of endothelial infl ammation. We think that further studies should be made on the role of vWF representing endothelial infl am-mation in patients with IFG, who are candidates of diabetes in the future.

2324-PODiabetes Mellitus Does Not Increase Infl ammatory Response in Patients With First Myocardial Infarction With ST Segment ElevationAGATA BRONISZ, MAREK BRONISZ, PRZEMYSLAW MAGIELSKI, MAREK KOZIN-SKI, MALGORZATA PUJANEK, JACEK KUBICA, ROMAN JUNIK, Bydgoszcz, Poland, Inowroclaw, Poland

In acute myocardial infarction (AMI) strong infl ammatory response activa-tion occurs. In diabetes (DM) increased infl ammatory reaction is observed. We assessed if DM patients compared to those without DM have signifi cantly increased infl ammation in peri-infarct period, which may account for increased cardiovascular complications incidence. The study included 274 patients with fi rst AMI with ST segment elevation. DM before hospitalization had 12.4% (34) patients. In those without DM, before discharge and 3 months later oral glucose tolerance test was performed. 26 patients, with glycaemia ≥11.1 mmol/L in 120th minute of both tests, were included in DM group. On admis-sion (T0) glucose (AG), glycated hemoglobin (HbA1c), on day 1 and 2 mean blood glucose (MBG1 and MBG2 respectively) were determined. At T0, after 24h (24) and at discharge (AD) such cytokines were assessed: CRP, TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, MCP-1, MIP-1α, MIP-1β, RANTES. DM patients compared to those without DM had signifi cantly higher AG, HbA1c, MBG1 and MBG1 (median and quartile range: 11.4 (5.9) vs. 7.2 (1.8) mmol/L, 7.6 (2.3) vs. 5.8 (0.8) %, 9.3 (3.3) vs. 6.4 (1.2) mmol/L, 9.3 (2 , 9) vs. 6.8 (1.2) mmol/L, all p <0.0001).

Cytokines T0 24 ADWithout DM DM Without DM DM Without DM DM

CRP 1.7 (3.1) 3.2 (3.9) 11.5 (13.7) 13.8 (24.3) 10.1 (14.2) 14.1 (22.5)TNF-α 12.1 (39.7) 15.4 (35.6) 8.8 (34.5) 19.2 (53.9) 10.7 (27.5) 18.7 (53.6)IL-1β 22.7 (47.3) 18.0 (42.8) 23.1 (55.2) 30.2 (77.8) 23.6 (47.2) 23.6 (73.9)IL-6 17.6 (23.1) 20.1 (29.0) 30.4 (34.6) 37.1 (65.6) 19.1 (25.5) 27.4 (35.4)IL-8 22.8 (21.4) 28.1 (23.9) 23.5 (28.3) 25.8 (28.2) 19.6 (24.5) 23.4 (17.6)IL-10 18.3 (24.9) 22.9 (24.1) 18.5 (24.9) 16.7 (25.0) 16.7 (23.4) 17.1 (14.8)IL-12p70 39.7 (73.0) 54.1 (86.2) 41.0 (76.5) 55.6 (97.7) 36.1 (63.9) 56.4 (109.5)MCP-1 82.8 (160.9) 115.4 (205.4) 83.8 (179.4) 105.3 (290.9) 60.8 (150.4) 96.1 (200.3)MIP-1α 19.8 (48.0) 21.6 (40.3) 19.8 (42.2) 18.6 (41.2) 21.0 (39.6) 26.3 (63.5)MIP-1β 99.4 (177.8) 116.4 (170.6) 80.2 (140.4) 134.9 (305.5) 73.4 (103.4) 94.7 (269.0)RANTES 23120.4 (25762.9) 35835.6 (26740.5) 2145.3 (3255.7) 3306.0 (6290.8) 2747.1 (4175.1) 3233.3 (6106.2)

CRP - mg/L, other cytokines - pg/mL; median (quartile range)p <0.03

In patients with fi rst MI, diabetes does not cause increased infl ammatory response, despite persistence of signifi cantly higher glycaemia in the whole peri-infact period.

2325-POAssessment of the Utility of an Annual ECG in Patients With Diabetes MellitusAOIFE M. EGAN, KATHLEEN CAHILL, CARLY FLYNN, DEARBHAIL O’FLYNN, JAMES O’NEILL, TOMMY KYAW TUN, JOHN H. MCDERMOTT, SEAMUS SREENAN, Dub-lin, Ireland

The high prevalence of cardiovascular disease (CVD) and silent myocardial ischaemia in patients with diabetes has resulted in suggestions that this population should be screened for asymptomatic CVD. However, international guidelines vary on methods of patient selection and the most appropriate screening test. We examined the utility of an annual ECG in asymptomatic patients with diabetes in identifying those with underlying CVD.

A total of 312 consecutive patients with diabetes attending for routine, annual outpatient review over a 3 month period were studied retrospectively. All were asymptomatic for CVD, 206 (66.0%) were male and the mean age was 59.4 years. Of the total, 283 (91.0%) had type 2 diabetes, 27 (8.7%) type 1, 1 (0.32%) maturity onset diabetes of the young and 1 (0.32%) had diabetes secondary to pancreatitis. Each patient had a resting ECG completed by a cardiac technician and reviewed by the attending physician. Actions taken based on ECG fi ndings were identifi ed by chart analysis.

Abnormal fi ndings were noted on 71 (22.8%) ECGs: abnormal T-wave inver-sion was the most common. Of those with abnormal fi ndings 25 (35.2%) had a pre-existing diagnosis of CVD. The majority of abnormalities were estab-lished changes and intervention was not deemed necessary.

Further action was taken in 4 patients (1.3%): 2 were referred for exercise stress test and echocardiogram (1 patient didn’t attend further testing and 1 patient underwent coronary angiogram and stenting); 1 was commenced on

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warfarin for newly diagnosed atrial fi brillation; 1 non-compliant patient was reestablished on medications for ventricular bigeminy. In 2 of these 4 patients, the abnormality was identifi able by history and examination rendering the ECG unnecessary.

The low clinical yield in terms of undiagnosed CVD in this study does not support the practice of performing routine yearly ECGs on asymptomatic patients with diabetes.

2326-PODiabetic Foot and Endothelial Precursors Cells (EPC): Preliminary Results of an Italian AIL (Italian Leukemia Association Section of Treviso) Research ProjectMARIA SAMBATARO, ELENA SEGANFREDDO, AGOSTINO PACCAGNELLA, ANNA FURLAN, ANGELO PAOLO DEI TOS, Treviso, Italy

Introduction: Reduction of peripheral mononuclear cells (PMNC) with sur-face cluster differentiation CD34+, CD133+ common to endothelial precursor cells (EPC) characterize diabetic vascular complications. Myeloid calcifying cells (MCC) are involved in carotid placques in vitro but not in calcifi ed vas-cular diabetic lower limb arterial lesions in vivo. Indeed ex novo KDR+ vascu-logenesis and/or preexistent precursor cluster CD133+31+34- angiogenesis describe vascular homeostasis.

Aim and methods: we evaluate CD34+, CD133+, KDR+, CD31+, CD45- EPC by citofl uorimetry in non coronaropatic patients with acute (timing restitutio until 6 weeks) or remote III-IV TUC diabetic foot lesions and its relationship with coexistent critical vascular calcifi cation.

Subject: 9 C controls and 54 type 2 diabetic patients with peripheral somato-sensory neuropathy (positive DNI): 15 N without foot lesions; 16 N1 and 23 NV with foot lesions without or with endovascular or by vascular surgery revascularized critical limb ischemia (CLI: oximetric value < 30 mm Hg).

Results: CD34+ were related with age (p< 0.03; R2=.45) only in C+N and were reduced in NV (239±31 mean± SE for 106 cell counts) versus N1 and C (p< 0.001). CD133+ were reduced in N, N1 and NV versus C (1857±254 mean± SE p< 0.03). In acute lesions, CD34+KDR+ and CD133+31+ were respectively signifi cant reduced in NV and increased in N1 versus remote lesions and correlate with ABI ( ankle brachial oscillometric index).

Conclusions: CD34+ peripheral precursor cells are consumed by age and this correlation is lost in diabetes with advanced complications. Neuropatic and vascular foot lesions determine different vasculogenic or angiogenic homeostasis in terms of KDR or CD31+133+ surface cluster pattern. This phe-nomenon has a rule in worse prognosis of medial distal arterial calcifi cation. It remains to clarify if microvascular neuropathy precedes diabetic distal macroangiopathy.

2327-PO

2328-POAcute Hemodynamic Changes after a Cold Pressure Test in Healthy Subjects and in Type 2 Diabetic PatientsMARINOS FYSEKIDIS, KARIM TAKBOU, YAYA JABER, MINH TUAN NGUYEN, EMMANUEL COSSON, PAUL VALENSI, Bondy, France

Background and aims: Sympathetic activation during a cold pressure test (CPT) has been shown to induce an immediate increase in arterial stiffness and aortic systolic blood pressure (ASBP). This study aimed to examine the effects of CPT both in aorta and in peripheral arteries and to determine whether these effects are different in type 2 diabetic patients (T2D).

Subjects and methods: We recruited 41 subjects (16 females; mean age 42.4 ±12.5 years): 25 were healthy controls (HC) and 16 had T2D, 9 with normal blood pressure (T2D-NT) and 7 with hypertension (T2D-HT). After a 15-minute supine rest, radial and aortic systolic (SBP) and pulse (PP) pressure and the augmentation index (Aix) were measured by applanation tonometry (Sphyg-mocor®), twice at baseline (5 minutes and just before CPT: T-5,T0), and once for the next 2, 4 and 6 minutes (T2,T4,T6) after a two-minute left hand immer-sion in ice.

Results: The double product (DP: heart rate x systolic blood pressure) and AIx did not differ between HC, T2D-NT, T2D-HT at baseline nor at any other time. In the overall series DP and AIx increased from T0 to T2 (p=0.002) and then decreased 4 minutes after the beginning of the test (p< 0.001). The increase in SBP was greater in aorta than in radial artery (p=0.004). DP increase (%) was negatively correlated with the subendocardial viability ratio from T0 to T2 (p=0.006) and positively with the ASBP (p=0.001). The refl ection time of the incident wave was negatively correlated to DP, ASBP, aortic PP and to heart rate (p< 0.01) without signifi cant modifi cations after the CPT.

Conclusion: Sympathetic nervous system activation provokes a large increase in aortic systolic blood pressure. This effect may have important consequences in stressful situations in high cardiovascular risk patients.

2329-POEffect of Intensive Statin Therapy on the Instability of Carotid Artery Plaques in Diabetic Patients Determined by a Combination of Ultra-sonography and MR ImagingTAKAHIRO KAGEYAMA, HIROHUMI WATANABE, SHIGEKI IMAMURA, AIZAN HIRAI, Togane, Japan

Carotid-wall intima-media thickness (IMT) is a surrogate marker of athero-sclerosis associated with cardiovascular risk factors and with cardiovascular outcomes. MR imaging of carotid plaque has been shown to be superior to the diagnostic assessment of plaque instability at high risk of rupture, and to provide information useful to the choice of treatment. Regression of plaque has been reported by intensive statin therapy (IST). The effect of IST on the characteristics of carotid plaques, especially on the instability of plaques was determined using a combination of ultrasonography and MR imaging. In the present investigation, 35 patients with type 2 diabetes having max IMT over 1.5mm who were treated on IST for more than one year were studied. The black-blood method was used for the quantitative evaluation of the properties of carotid artery as described by Watanabe et al (J Magn Reson Imaging, 2008, 28:478-485). A horizontal cross-sectional image of plaque was taken with highlighting T1 and T2 mode under fat suppression. Finally, the ratio of the lesion and the submandibular gland was determined. Plaques having the ratio of T2 evaluation more than 1.25 were defi ned as unstable, while those below 1.25 were defi ned as stable. Patients were classifi ed into two groups; stable plaque group (group A, N=17) and unstable plaque group (group B, n=18). They were followed on IST additional one year. At the end of study, there were no signifi cant difference in max IMT and LDL-C between group A and B, while T2 contrast ratio after 1 year treatment of IST were 0.70 ± 0.17 and 1.74 ± 0.50 (p<0.0001). The present study showed that cervical plaques in diabetic patients can be stabilized by IST in the majority of patients, while a considerable number of patients exist whose plaques remain unstable even after IST. Novel therapeutic approach beyond statin therapy seems to be required.

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2330-PORestenosis after Percutaneous Transluminal Coronary Angioplasty in Patients With Different Categories of Glucose Tolerance: A 1-Year Follow-Up StudyLEI ZHANG, YAN GU, YANHU DONG, NINGNING HOU, DEYA SHANG, JAAKKO TUOMILEHTO, Qingdao, China, Jinan, China, Weifang, China, Helsinki, Finland

Patients with diabetes (DM) are at high risk for restenosis after coronary stenting. Information relating the outcome of percutaneous transluminal coronary angioplasty (PTCA) to prediabetes is, however, limited. The study objective was to investigate the relationship between restenosis after PTCA and baseline glucose categories. We retrospectively analyzed data of 1003 patients (mean age 58.5±4.2 yrs, 61.5% of men, mean history of coronary heart disease 9.5±1.1 yrs) who undertook PTCA at Emergency Department between Jan 2008 and Dec 2011. Baseline measures included blood pressure (BP), fasting plasma glucose, lipid profi le, A1c, C-reactive protein (C-RP), and 2-hour capillary glucose. All patients had follow-up coronary angiography 1 year after PTCA. Restenosis was defi ned as 50% stenosis in stent or within 5 mm adjacent to stent. The rate of restenosis was compared among patients with normal glucose tolerance (NGT, n=436), impaired glucose regulation (IGR, n=275), and DM (n=292) according to their baseline glucose levels or prior history of DM. Patients with DM had highest levels of body mass index (BMI), BP, triglycerides (TG), and C-RP, followed by those with IGR and NGT (P<0.01).The number of lesion was 1.6, 1.8, and 2.5 in patients with NGT, IGR, and DM, respectively (p<0.05). At year 1, the rate of restenosis were 4.2%, 5.3%, and 12.0% in patients with NGT, IGT, and DM, respectively (P<0.05). Among DM subgroup, compared with patients with A1c<8%, those with A1c>8% had increased rate of restenosis (14.6% vs. 11.2%, P<0.05). In the logistic regres-sion model, the odd ratio (OR) of having restenosis was 1.46 (95%CI: 1.05-1.87) for DM and 1.10 (95% CI: 1.01-1.25)for IGR, after adjusting for age, history of CHD, BMI, BP, LDL-C, TG, and C-RP. Restenosis is more frequent in patients with compared those without DM. Prediabetes is associated with increased risk of restenosis after PTCA during a follow-up period of 1 year.

2331-PODiabetes-Induced Reversal of Fortune? Contrasting Associations of the ACE Gene Insertion/Deletion Polymorphism With Cardiometa-bolic Risk Factors in Type 2 Diabetic Subjects and their First Degree RelativesNABILLA ABDELLA, OLUSEGUN A. MOJIMINIYI, FAHD AL MULLA, Safat, Kuwait

As several studies have shown associations between the DD genotype of ACE insertion/deletion (I/D) polymorphism with metabolic perturbations and complications of diabetes, the aim of this study was to investigate whether the associations of ACE gene I/D polymorphism with cardiometabolic risk factors is refl ected in fi rst degree relatives (FDR) of subjects with Type 2 diabetes (T2DM). Fasting glucose, lipids, insulin, adiponectin; HbA1c and plasma ACE were determined in 123 T2DM subjects and 219 non diabetic FDR-190 offspring (son/daughter) and 29 siblings. HOMA-IR and insulin sen-sitivity (%S) were calculated. In each group, plasma ACE was highest in DD and lowest in II genotype. Age, BMI and waist circumference did not differ by genotype. In T2DM, the ACE DD genotype compared to the II genotype was associated with CHD (regression odds ratio = 5.2), higher HbA1c (105 vs 88 mmol/mol), higher insulin (18.9 vs 13.5uU/ml), lower %S (64% vs 81%) higher HOMA-IR (8.9 vs 6.3), higher triglycerides (2.0 Vs 1.5 mmol/L), lower HDL-cholesterol (1.1 vs 1.28 mmol/L) and lower levels of the protective adi-pokine, adiponectin (6.1 vs 7.9 ug/ml). In contrast, II genotype compared to DD genotype in FDR was associated with higher HbA1c (45 vs 40 mmol/L), higher insulin (9.5 vs 7.9uU/ml), lower %S (87 vs 112), higher HOMA-IR (2.4 vs 1.7), higher triglycerides (1.5 vs 1.2 mmol/L), lower HDL-cholesterol.(1.01 vs 1.20mmol/L) and lower adiponectin (8.3 vs 9.5ug/ml). In T2DM, II genotype is protective in sharp contrast to FDR, where the DD genotype appears to be protective. As genetic predisposition to T2DM and complications is infl uenced by other factors, we postulate that these contrasting associations of ACE I/D genotypes may be due to effects of other genetic, environmental or metabolic factors that predispose the DD genotype to development of complications in the diabetic state.

Supported by: KFAS (2004-1302-03)

2332-POThe Effect of Vildagliptin on Arterial Stiffness in Drug Naïve Patients With Type 2 Diabetes MellitusIOANNA ZOGRAFOU, CHRISTOS SAMPANIS, ATHANASIOS PAPAGEORGIOU, BAR-BARA NIKOLAIDOU, PANAGIOTIS DOUKELIS, DESPINA PAPADOPOULOU, MICHAEL DOUMAS, STELLA DOUMA, Thessaloniki, Greece

Arterial Stiffness (AS) is a predictor of cardiovascular (CV) events and mor-tality in patients with Diabetes mellitus. We aimed to assess the effect of a DPP-4 inhibitor Vildagliptin (V) on AS in patients with type 2 diabetes mellitus (T2DM). This randomized open-label study investigated 64 drug naïve subjects with type T2DM (38 males, mean age 54, duration of diabetes<5years), with HbA1c 7-9%. Thirty-two patients received metformin (M) 1700 mg/d (M group) and 32 patients were given M 1700 mg/d plus Vildagliptin 100 mg/d (V group) for 6 months. AS (carotid femoral pulse wave velocity, cfPWV), body weight (BW), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), lipid profi le, Albumin/Creatinine ratio (A/C ratio), C-peptide were assessed at baseline and after 6 months. Homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were calculated. Results: cfPWV, SBP, DBP remained unchanged after 6 months in both groups (p=NS). BW and BMI improved in both groups but there were no differences between the two groups. V decreased HbA1c more effectively than M alone (V group: Δ (HbA1c) = -1.73 %, M group: Δ (HbA1c) = -1.22 %, p<0.05). Moreover C-peptide and HOMA-β signifi cantly increased in V group (V group Δ (C-peptide) = 1.32 ng/ml, M group Δ (C-peptide) = -0.23 ng/ml, p <0.05, V group Δ (HOMA-β) = 22.05 %, M group Δ (HOMA- β) = 8.07 %, p <0.05). There was no difference in lipid profi le, A/C ratio and HOMA-IR between the two groups (p =NS). Conclusions: The addition of V to M for a period of six months had no effect on AS in drug naïve T2DM patients but V treatment improved glycemic control (HbA1c) and β-cell function (C-peptide, HOMA-β).

2333-POAdditional Benefi ts of Pioglitazone to Lifestyle Modifi cation in Patients at Increased Risk for Diabetes and Newly Developed Dia-betesJI SUN NAM, JI WOON KIM, SHIN AE KANG, JONG SUK PARK, CHUL WOO AHN, BONG SOO CHA, KYUNG RAE KIM, HYUN CHUL KEE, Yongin, Republic of Korea, Seoul, Republic of Korea

Hyperglycemia-induced oxidative stress is known to mediate atheroscle-rosis and cardiovascular events in patients with prediabetes and diabetes, and thiazolidinediones have been shown to ameliorate oxidative stress. This study examines the effects of pioglitazone combined with lifestyle modifi ca-tion on oxidative stress, atherosclerosis, and cardiovascular risk factors in patients with prediabetes and newly developed diabetes.

Forty-six prediabetes or newly developed diabetes patients with HbA1c < 7.5% were randomized to lifestyle modifi cation only vs. pioglitazone 15 mg/day plus lifestyle modifi cation. Fasting plasma glucose, HbA1c, lipid profi le, insulin sensitivity index, and oxidative stress markers, and carotid intima-media thickness were measured at baseline and after 6 months.

At study end, patients taking pioglitazone had improved HOMA-IR, HbA1c, total cholesterol, LDL-cholesterol, gamma-GT levels (all P < 0.05), and it showed a regression of left maximal and mean carotid intima media thickness (0.70±0.17mm vs. 0.58±0.30, P=0.01 and 0.58±0.13mm vs. 0.52±0.11, P=0.068, respectively). Patients in lifestyle modifi cation group also showed a tendency toward improved glycemic control and lipid parameters, but they were with-out a statistical signifi cance. Postprandial isoprostane 8-epi prostaglandin F2-alpha level was decreased in both lifestyle modifi cation (138.69±3.5mg/mL vs. 101.28±43.32, P = 0.007) and pioglitazone group (137.44±3.90mg/ml vs. 111.49±45.32, P=0.093). Fasting and postprandial oxidized levels were also improved in pioglitazone group but without a statistical signifi cance (83.94±12.914U/L vs. 72.49±26.33 and 105.53±16.88U/L vs. 89.61±25.88, respectively)

Both pioglitazone and lifestyle modifi cation showed a tendency toward lowering oxidative stress markers, and pioglitazone was superior in improving glucose control, lipid parameters, and carotid artery intima medial thick-ness.

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2334-POComparison of the Antiplatelet Effect of Crushed Clopidogrel versus Whole Tablet in Diabetic Patients Presenting With an Acute Coronary SyndromeINES KHOCHTALI, FAOUZI ADDAD, CHAKER WESLATI, SYLVIA MAHJOUB, SALEM KACHBOURA, Monastir, Tunisia, Ariana, Tunisia

Dual anti-platelet therapy with aspirin and clopidogrel is the current ther-apeutic standard following acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). The response to clopidogrel shows wide popula-tion variability and high residual platelet reactivity (HRPR). It is actually known that patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. If clopidogrel given crushed provides faster absorption, it could allow earlier clopidogrel loading.

The aim of this study is to compare the antiplatelet action of 600 mg clopi-dogrel administered crushed versus whole tablets taken orally in diabetic patients with ACS

Methods: In a prospective, single-center, single-blind study, 30 (58.9 ± 8.4 years; 17 males). ACS diabetic patients were randomized to either 600 mg crushed clopidogrel (n = 15) or whole tablets (n = 15) and a maintenance dose of 150 mg respectively. Platelet function was assessed by VerifyNow P2Y12 assay at 24 h and 3 days post loading dose (LD). HRPR was defi ned as platelet reactivity units (PRU) > 230.

Results: The primary endpoint of platelet reactivity with crushed clopidogrel was lower at 24h post-LD PRU=199.73 ± 79.3 compared with whole tablets PRU=216.9 ± 70.1 but not signifi cant (p = 0, 53). However, the two groups had a similar PRU at 3 days (PRU = 164.3 ± 92.9 for crushed clopidogrel vs 160.5 ± 73.5 for whole tablet; p = 0, 9).

The secondary endpoint of HTPR rate was similar in the two groups, 40 % (p=1) at 24h. In both groups, HTPR rate diminished signifi cantly at 3 days to 20% of patients (p<0,001).

Conclusions: No greater platelet inhibition by VerifyNow P2Y12 was achieved by crushed clopidogrel at 24 h post-LD compared with whole tablets in diabetic patients. This study showed that the antiplatelet response to clopidogrel in this population of diabetics is delayed.

2335-PORelationships between Hyperglycemia and the Oxidative Stress in Type 2 or Type 1 DiabetesMITSUYASU ITOH, IZUMI HIRATSUKA, JUNKO HANASHITA, MIZUHO KONDO, KUMI YOSHIDA, YUKI NAKAMURA, TOMOYO NISHIDA, TAKESHI TAKAYANAGI, HIROYUKI HIRAI, MASAKI MAKINO, Toyoake, Japan

A continuous glucose monitoring (CGM) provides a good tool to investigate the infl uence of glucose fl uctuation on oxidative stress. The relationships between hyperglycemic excursion and the oxidative stress in type 2 diabetes (T2DM) have been disclosed, but such relationship remains unclear in T1DM. We measured various indexes for oxidative stress and compared with the glycemic factors. Methods: T2DM (n=29), T1DM (n=8), and healthy controls (n=17) were subjected to the CGM and their HbA1c, LDL, HDL, triglyceride, small dense (sd)- and oxidative (ox)-LDL, remnant-like particle lipoprotein (RLP), high-sensitivity (hs)-CRP, pentosidine, leptin, adiponectin, total free radical derived from reactive oxygen species (ROS), urinary output of 8-hydroxy-2’-deoxyguanosine (8-OHdG) and 15-isoprostane F2t (isoprostane) were mea-sured. The glucose instability was expressed as SD of the mean glucose and the combined percentages of hyper- plus hypoglycemia. Results: The LDL, sdLDL, oxLDL, and RLP values were higher, and total ROS values were slightly higher in T2DM than those in control, but no increase was observed in T1DM. The urinary output of 8-OHdG and isoprostane were not different between T2DM, T1DM, and control groups. The values of total ROS were correlated with those of average glucose (r2=0.235), average glucose plus SD (r2=0.276), combined percentages of hyper- and hypoglycemia, or hsCRP in T2DM, but no relationship was found in T1DM. The urinary output of 8-isoprostane were correlated with the values of average glucose, average glucose plus SD or total ROS in T2DM. Discussion and conclusion: Hyperglycemia and moreover, fl uctuation of blood glucose increased the production of oxidative stress detected by total ROS and urinary output of 8-isoprostane. These hypergly-cemic excursions also increase a risk factor, hsCRP in T2DM. Further studies are required to reveal the relationship between glycemic fl uctuation and other markers for oxidative stress in T1DM.

Supported by: Fujita Health University

2336-POThe Regulation of Autophagic Flux by Lipid Metabolism in Endothelial CellsHAE-SUK KIM, HYUN-JU JANG, JEONG-A KIM, Birmingham, AL

Obesity is associated with increased circulating fatty acids that cause infl ammation and lipotoxicity in various tissues. Autophagy is one of the pro-tective mechanisms by degrading organelles, lipids, and long-lived proteins. Inhibition of autophagy exacerbated lipotoxic cell death in pancreatic beta cells. In this study, we examined the role of lipid metabolism in autophagy and its association with formation of intracellular lipid droplets in vascular endothelial cells. We observed that treatment of primary bovine aortic endothelial cells (BAEC) with palmitate (200 µM)-induced LC3-II formation and intracellular lipid droplets which is due to the inhibition of autophagic fl ux (assessed by comparing the accumulation of LC3-II with and without lysosomal inhibitors). Inhibition of β-oxidation by etomoxir, an inhibitor of carnitin-palmitoyl transferase, exacerbated autophagic fl ux. Furthermore, pre-treat-ment with triacsin C (1 µM, an inhibitor of long fatty acyl-Co A synthetase) but not myriocin (10 µM, an inhibitor of de novo ceramide synthesis) facilitated autophagic fl ux. These suggest that there is an association between lipid metabolism and autophagy. Next, we examined whether activation of AMPK, a stimulator of β-oxidation, can alleviate palmitate-suppressed autophagic fl ux. Treatment with AMPK activator, 5-amino-1-β-D-ribofuranosyl-imidazole-4 carboxamide (AICAR) facilitated autophagic fl ux. Furthermore, treatment with green tea polyphenol, epigallocatechin gallate (an AMPK activator), reduced lipid droplets and facilitated autophagic fl ux in BAECs. These suggest that lipid metabolism in mitochondria is associated with autophagic fl ux, and vice versa. This suggests that mitochondrial functions may communicate with lysosomal degradation through autophagy. Thus, autophagy may play an important role in maintaining cellular homeostasis.

2337-PORosiglitazone Improves C-Reactive Protein and Liver Function in Impaired Glucose Tolerance but Not Coronary Artery Calcifi cation or Exercise FunctionJANE E.B. REUSCH, IRENE E. SCHAUER, CECILIA WANG, MARK BRIDENSTINE, ROY DURBIN, JUDY REGENSTEINER, Denver, CO, Aurora, CO

Type 2 diabetes (T2D) increases cardiovascular (CV) risk and decreases functional exercise capacity. We and others have reported that rosiglitazone (RO) improves functional exercise capacity and endothelial function in T2D and decreases coronary artery calcium (CAC), a CV disease surrogate. Impaired glucose tolerance (IGT) is associated with excess CV risk and progression to T2D. We tested the impact of RO on functional exercise capacity and CAC in 40 subjects with IGT randomized to RO or placebo (PL) for 18 months. VO2 peak, VO2 kinetics and CAC were assessed. Despite randomization, BMI and fasting insulin differed between groups at baseline, and a hemoglobin A1c (A1c) difference approached signifi cance. Paired analyses within each group demonstrated decreased 2 hr glucose on RO but not PL. Insulin increased and A1c trended up on PL but not RO. C-reactive protein (CRP) and liver function tests (LFTs) decreased in the RO group only. No change was observed in VO2 peak or VO2 kinetics in either group. CAC trended upward with no difference between groups but this study was limited by small sample size. In summary, RO resulted in benefi ts in glucose metabolism and improved CRP and LFTs. However, in contrast to effects in T2D, RO does not appear to improve exer-cise capacity or decrease CAC in IGT in this small cohort.

*p<0.05 vs. within-group baseline PL ROMean+SD Baseline 18 mo p Baseline 18 mo pBMI (kg/m2) 34.9±2.4 34.6±3.1 0.47 31.1±4.0 31.8±4.7 0.06OGTT 2 hr glucose (mg/dL) 169±22 164±64 0.78 167±19 143±31* 0.01A1c (%) 5.9±0.3 6.3±0.7 0.09 5.6±0.4 5.5±0.3 0.22Insulin (µIU/mL) 22±11 26±12* 0.009 15±7 14±6 0.43C-reactive protein (mg/L) 4.0±3.3 3.4±2.6 0.26 3.95±3.58 2.19±2.45* 0.008AST (U/L) 26±8 24±9 0.14 24±10 19±4* 0.04ALT (U/L) 37±16 32±14* 0.04 30±16 22±8* 0.03VO2peak (ml/kg/min) 19.9±4.5 20.7±4.2 0.08 19.7±4.5 19.1±4.9 0.77Tau1 (sec) 61±13 60±15 0.86 59±22 55±17 0.85CAC RCA (Agatston Score) 58.3±126.9 68.7±152.3 0.26 34.7±116.8 45.5±131.0 0.09CAC LAD ( Agatston Score) 44.0±94.2 51.8±105.3 0.10 114.0±248.6115.4±243.7 0.97

Supported by: NIH (UL1 TR000154), (P0IHL014985); GlaxoSmithKline; VA Medical Center

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2338-POAdipocytokines, Metabolic Syndrome and Cardiovascular Risk in Patients With Type 2 Diabetes and Chronic Hepatitis CRAMONA MARIA DRAGUT, EMILIA RUSU, CRISTINA PARPALA, RALUCA NAN, FLORIN RUSU, HORATIU POPESCU, GEORGIANA TOCACI, GABRIELA RADULIAN, Bucharest, Romania

Aims of the study were to evaluate the association between chronic hepatitis C (CHC), insulin resistance (IR), cytokines and cardiovascular risk, in patients with CHC and type 2 diabetes.

This transversal epidemiological, observational study, was held at the INDNBM”NC Paulescu”, Bucharest. 274 patients were divided in two: group A, 152 patients with type 2 diabetes and MetS and group B, 122 patients with type 2 diabetes without MetS. There were followed anthropometric indica-tors. Biochemical parameters followed were blood glucose, HbA1c, lipid profi le, liver profi le, complete blood count and cytokines. Cardiovascular risk was calculated for each patient using UKPDS software.

The average age of the evaluated patients was 51.2±8.6 years, 53.4% females (n=147), with type 2 diabetes for 7.5 years. Median serum concentra-tions of leptin, TNF-α, IL-6, resistin were higher in patients with UKPDS-CHD over 30 (all p<0.05). Using UKPDS score, 12.9% (n=36) and 45% (n=125) of the patients presented an high and moderat risk for CVD. In patients with MetS, UKPDS score was strongly correlated with, age (r=0.620, p=0.0001), CA (r=0.49, p=0.0001) with HbA1c (r=0.41, p=0.0001), GGT (r=0,31, p=0.0001), serum triglycerides (r=0.36, p=0.0001), HOMA-IR (r=0.44, p=0.0001), systolic blood pressure (SBP) (r=0.63, p=0.0001), leptin (r=0.30, p=0.0001), TNF-α (r=0.39, r=0.0001), resistin (r=0.27, p=0.001) and adverse with adiponectin (r=-0.38, p=0.0001) and HDL-C (r =-0.44, p=0.0001). In this population multiple regression models controlled by BMI indicated that adiponectin (R(2)=0.16, p=0.034), resistin (R(2)=0.18, p=0.045) and IL-6 (R(2)=0.112, p=0.048) were associated with SBP.

MetS is highly prevalent among patients with chronic hepatitis C, which associates type 2 diabetes, increasing the risk of CVD. UKPDS score identifi es more patients with high cardiovascular risk. Finding people with diabetes and increased cardiovascular risk is very important in medical practice.

2339-POEstimating the Role of Lowering Systolic Blood Pressure (SBP) in Prevention of Cardiovascular (CV) Outcomes: An Analysis in Patients With Type 2 Diabetes Mellitus (T2D) Using the Archimedes ModelSARAH WARD, BETH D. MITCHELL, BRAD CURTIS, DAVID R. NELSON, Indianapo-lis, IN

The ACCORD trial targeting SBP <120 mmHg in T2D patients at high risk for CV events found no reduction in rate of CV endpoints, except for stroke. This population was not broadly generalizable due to the inclusion criteria of the study (history of CV disease, 5 year follow-up). The aim of our analysis was to expand the patient population and follow-up using the Archimedes Model to simulate 10 years of treatment in a T2D population drawn from NHANES with SBP >140 mmHg. The Archimedes Model is a validated model of physiology, disease progression and healthcare delivery. Four simulations of 10,000 virtual patients were utilized to estimate reduction in risk of major acute coronary events (MACE), myocardial infarction (MI), and stroke. Within the simulations, pre-specifi ed subgroups that represent the Framingham risk factors were included to evaluate risk reduction. Output from each simulation included the number of cardiac events for individuals receiving standard of care (SOC) versus those with SOC plus SBP reduction to 120 mmHg, and rela-tive risks were calculated with 95% confi dence intervals. The overall popula-tion was 45% male with a mean age of 61.0 yrs, SBP of 152 mmHg, and HbA1c of 7.5 % at baseline. The Model projected a signifi cant reduction in CV events at 10 years consistently across subgroups. This hypothesis and understanding real world compliance requires further study.

Relative risk reduction (%) overall and within subgroupsMACE MI Stroke

All Subjects -31 -25 -40Age <65 yrs -34 -28 -43Age ≥65 yrs -30 -22 -39Male -31 -24 -43Smoker -31 -31 -32TC ≥200 mg/dL -29 -23 -39HDL <60 mg/dL -31 -23 -42

2340-POSignifi cance of IL-2 Concentration in Diabetic Foot Patients at Higher Risk of Coronary Artery DiseaseAWADHESH K. ARYA, SUNNY GARG, SANTOSH KUMAR YADAV, RICHIK TRIPATHI, KAMLAKAR TRIPATHI, Varanasi, India

Diabetic foot is characterised by a pronounced infl ammatory reaction which results in interaction of many pro infl ammatory cytokines involving migration of lymphocytes, laying of protein meshwork and endothelial cell proliferation to form the granulation tissue in a fi brin meshwork. Some of these cytokines (IL-2) and acute phase reactants (hsCRP) also activate coronary endothelial cells to predispose for acute coronary event and coronary artery disease. For the present study we recruited 90 type 2 diabetes mellitus patients having diabetic foot. These were divided into two groups of 45 each, one having hsCRP <3 mg/L (Group B) and other having hsCRP>3 mg/L (Group C). 35 healthy controls (Group A) were also recruited who did not have any clinical or bio-chemical evidence of diabetes or coronary artery disease. Plasma glucose, total cholesterol (TC), HDL cholesterol, LDL cholesterol and triglyceride (TG) levels were measured using autoanalyzer (Aeroset System Operations Man-ual, Abbott Laboratories, Abbott Park, IL). Concentrations of plasma hsCRP and IL-2 were determined by quantitative sandwich enzyme-linked immune-sorbent assay (ELISA) kit (R&D Systems, USA) as per manufacturer’s protocol.

We obtained signifi cantly higher concentration of IL-2 in group C as compare to group B and group A (p<0.001) whereas HDL value was signifi cantly reduced (p<0.001) in the same group. hsCRP, TC, TG and LDL values was also signifi -cantly higher in group C as compare to group B & A. There was signifi cant positive correlation was observed in between IL-2, hsCRP and lipid profi les.

Our study demonstrated that diabetic foot patients at higher risk of CAD showed higher IL-2 plasma level and positive correlation with hsCRP and lipid profi les. This observation supports that IL-2 production may potentially enhance the atherogenic process by promoting the recruitment of monocytes and T cells into the arterial intima.

2341-POTibial Arterial Calcifi cation, Cardiovascular Risk and Bone Mineral Density in Diabetes MellitusGAGIK GALSTYAN, NATALYA MOLITVOSLOVOVA, OKSANA MANCHENKO, MAR-IANNA YAROSLAVCEVA, TATYANA CHERNOVA, Moscow, Russian Federation

High cardiovascular mortality and morbidity are associated with diabetic neuropathy (DN) and diabetic foot (DF). Medial arterial calcifi cation is a com-mon feature of advanced stages in DN and DF. High coronary artery calcium index is a marker of a risk of serious cardiovascular events with high cardio-vascular and all-cause mortality. There is also evidence that arterial calcifi ca-tion and low bone mineral density (BMD) often co-exist.

The aim of the study is to assess the relationship between distal arterial calcifi cation, coronary artery disease and BMD in diabetic patients.

Sixty one patients with diabetes mellitus and DN (21 men, DM1-27, mean age -51,4±11,68 years) underwent multislice computed tomography and dual energy X ray absorptiometry (DEXA) scan. Coronary artery calcifi cation (CAC) and tibial arterial calcifi cation (TAC) scores were measured. BMD was mea-sured in lumbar spine, hip and foot using lunar DEXA scanner. Exclusion cri-teria were: peripheral artery disease, glomerular fi ltration rate <30 ml/min/1,73 m², DM1 duration<5 years. Calcium scores were determined accord-ing to the method described by Agatston et al. Individual calcium values for each artery in lower extremities were added together to get a single combined TAC score for each patient.

There was no correlation between BMD values and calcium scores. Foot BMD signifi cantly correlated with spine and hip BMD ( =0,52-0,63, <0,00001), diabetes duration (r=-0,3, p<0,005). Signifi cant correlation was found between TAC and CAC scores (r=0,4, p<0,0001), CAC score and age (r=0,37, p<0,005), inverse correlation between CAC and high-density lipoprotein level (r=-0,3, p<0,05). There was no correlation between CAC scores and HbA1c levels, diabetes duration and serum creatinine.

No association between arterial calcifi cation and BMD was found. Medial arterial calcifi cation is associated with coronary artery disease. These data may explain high rate of mortality in patients with DM and DPN and DF.

2342-POSerum Very Low Density Lipoprotein Levels and Cognitive Dysfunc-tion in Patients With Type 2 Diabetes and Metabolic SyndromeSARAH STRANJFORD, DIVYA YOGI-MORREN, LAURENCE KENNEDY, MARWAN HAMATY, JOHN GUNSTAD, SANGEETA R. KASHYAP, Cleveland, OH

Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction and demen-tia. The underlying mechanisms for this decline, however, are not understood. Studies have reported associations between different components of meta-

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bolic syndrome, including hyperlipidemia, and cognitive impairment. We aimed to determine the association of various metabolic syndrome components with cognitive function measures in T2D.

Methods: A prospective, longitudinal cohort study of 47 adults (59.6% female, age 58.0 ± 12.3 yrs, diab duration 11.9 yr) with T2D performed cogni-tive testing using the Webneuro computerized cognitive test battery. Data were compared to age and gender matched healthy subjects without medical conditions or medication use. Medical visits obtained historical (age, sex, race, diabetes duration, presence of co-morbid conditions, number of hypo-glycemic agents), physical (systolic and diastolic blood pressure, BMI), and biochemical (HbA1c, urine albumin, basic metabolic panel, lipid panel) data.

Results: Executive function at baseline was impaired in 35% (greater than 1 SD below control) of T2D. Avg cholesterol levels were 157± 150 mg/dL, with HDL, LDL and VLDL levels of 44.8 ±42 mg/dL, 84.3±22mg/dL, and 26.1 ± 12 mg/dL, with statin therapy. The association between serum VLDL levels and cognitive function was examined using partial correlations adjusted for esti-mated IQ, age, sex, race, BMI, HbA1c levels, and the presence of hypertension. Results showed that higher serum VLDL levels were correlated with poorer performance on tests of executive function, including set shifting (Switching of Attention, r = 0.47) and cognitive inhibition (Verbal Interference Color Word, r = -0.51) ( both P’s < 0.05). Conclusions: These data provide evidence that high serum VLDL levels may contribute to impaired executive function in individuals with T2D and future interventional studies targeting VLDL levels are indicated in this high risk group.

2343-POAsymptomatic Coronary Artery Disease in Diabetic Patients Diag-nosed With Carotid Wall Intima-Media Thickness as Surrogate Marker and Coronary CT AngiographyYUICHIRO YOSHIKAWA, SHIGEKI IMAMURA, KAZUO MISUMI, AIZAN HIRAI, Togane, Japan, Matsudo, Japan

Diabetes is associated with a marked increase in the risk of coronary artery disease (CAD). It is well known that patients with diabetes have often asymp-tomatic CAD. Carotid-wall intima-media thickness (IMT) is a surrogate marker of atherosclerosis associated with cardiovascular risk factors and with car-diovascular outcomes. In the present investigation, 506 diabetic patients without any episode of chest pain and having max IMT over 1.5mm were studied. Coronary computed tomography angiography(CCTA) using a 256 chan-nel MDCT scanner was performed. Then coronary angiography (CAG) was performed for the patients with positive fi ndings in CCTA. In the present study, 51.5% of the patients had coronary lesions with stenosis more than 25% in the CAG. Also, 38.1% of diabetic patients had coronary lesions with stenosis more than 75% in the CAG. False-positive rate of CCTA was 8.3% in the patients. Among various parameters, age and max IMT have positive correla-tion with the degree of coronary lesion. Chronic kidney disease(CKD) stage is closely correlated with the incidence of severe stenotic lesions more than 75%. Triple coronary vessel lesions with stenosis are increased with the progression of CKD in diabetic patients due to a signifi cant increase in RCA vessel lesions in G3a and G3b stage. Thus, max IMT of carotid artery over 1.5mm is a useful surrogate marker of asymptomatic CAD in diabetic patients.

2344-POThe Relationship between Plasma Glucose Levels and Neutrophil/Lymphocyte Ratio may Contribute to the Etiopathogenesis of the Impaired Fasting GlucoseSEVKET BALTA, MUSTAFA CAKAR, SAIT DEMIRKOL, MUHARREM AKHAN, HAKAN SARLAK, MURAT KARAMAN, SEYIT AHMET AY, OMER KURT, Ankara, Turkey

Neutrophil/lymphocyte(N/L) ratio is a novel, easy marker of systemic infl am-mation in clinical practice. Diabetic patients have higher levels of endothelial infl ammatory activity and damage. Upon which time the individuals with increasing plasma glucose levels get into an increased infl ammatory status that leads to potential vascular events is unknown. We aimed to investigate the endothelial infl ammation based on the relationship between fasting plasma glucose and N/L ratio in patients with impaired fasting glucose(IFG).

67 patients have been recruited in the study. 33 had IFG and 34 were controls. 14(45%) of the IFG and 18(55%) of the control groups subjects were female. The mean ages of the IFG and control groups were 49,45±9,6 and 45,95±11,3 years, respectively. The mean blood glucose levels of the patient and control groups were 112,1±6,9 and 88,9±8,2 mg/dl, respectively. N/L ratio were signifi cantly higher in patients with an IFG (2,31±0,76 vs 1,76±0,59 mU/mL, respectively; p<0,01). After adjustment for age and body mass indexes, N/L ratio was mildly correlated with serum CRP levels at the patient group (r=0,345).

In this study, we found that N/L ratio is increased in patients with an IFG. N/L ratio levels are also correlated with CRP levels, pointing towards the higher levels of endothelial infl ammation. The infl ammatory status starts with any increase in fasting plasma glucose levels. In reverse, besides endothelial dysfunction, we think that the relationship between increased fasting plasma glucose and higher N/L ratio may contribute to the etiopathogenesis of the IFG.

2345-POMicroalbuminuria Risk Factor for CV Disease also in Normotensive Type 2 Diabetics: A Primary Care Cross-Sectional StudyDAVIDE C. CARVALHO, LUIS MARTINS, PEDRO M. SILVA, JOSÉ NAZARÉ, CARLOS AGUIAR, M. CONCEIÇÃO MANSO, TERESA CARQUEJA, JORGE POLÓNIA, ON BEHALF OF RACE STUDY GROUP, Porto, Portugal, Santa Maria da Feira, Portugal, Lisbon, Portugal, Carnaxide, Portugal

Microalbuminuria (MA) is an independent risk factor for cardiovascular (CV) morbi-mortality. Aims: to evaluate the frequency of MA in a sample of con-secutive primary care (PC) attendees (pts) with diabetes and normal blood pressure (BP) and to correlate MA values with other risk factors and CV events.

Design: cross-sectional study in a nationwide sample of 500 PC physicians (PCP). Diabetes and co-morbidities were diagnosed by PCP. BP was the aver-age of 2 determinations and MA was measured in a spot urine MICRAL test. MA stages were grade 1 (G1) >20-<50; grade 2 (G2) >50-100 and grade 3 (G3)>100mg/L. The 432 normotensive type 2 diabetics (ND) 207 females (48.9%), mean BMI 27.7Kg/m2, were compared with 3100 hypertensive diabet-ics (HD) and 1906 controls (C). Estimated glomerular fi ltration rate (eGFR) was calculated by MDRD formula. Results: MA was present in 51.3% of ND: 37.6% G1, 9.5% G2 and 4.3% G3. Pts with MA were more frequently men (p=0.010) and had more coronary heart disease (CHD) (p=0.031) and eGRF decline (p=0.018).

ND with MA+ 60.2±12.1 years (y) were older vs MA- 57.9±12.1 (p<0.05), had a similar BMI and higher Systolic (SBP) and Diastolic BP (DBP) (p<0.001 and 0.012, respectively). In multivariate analysis, age>73y, male gender, SBP>130 and DBP>70mmHg were predictors of MA+ in ND. ND had median MA levels higher than C [ND 10 (5-24.3) vs C 5mg/L (2-11.2), p<0.001]. ND had higher MA+ frequency than C (ND n=217 - 51.3% vs C n=393 - 20.6%, p<0.001) which persisted in all MA grades (MA G1, DN 37.6 vs C 17.7; G2 DN 9.5 vs C 2.4 and G3 DN 4.3 vs C 0.5). ND had median MA levels lower than HD [ND 10 (5-24.3) vs DH 14.3 mg/L (6.4-33.0), p<0.001]. ND had lower MA+ frequency (DN - 51.3 vs DH n=1784 - 57.4% vs p<0.001). According to the grades of MA, ND had higher frequency of normal MA (DN 48.7 vs DH 42.5%) and MA G1 (DN 37.6 vs C 35.4) but lower frequencies of MA G2 (DN 9.5 vs DH 14.9) and G3 (DN 4.3 vs DH 7.3). We concluded that MA is increased in normotensive diabetics and is also a risk factor for CHD and renal failure.

Supported by: Novartis Pharmaceuticals Corporation

2346-POE-Selectin Levels are Signifi cantly Increased in Patients With a Newly Diagnosed Diabetes and may Point to Higher Risk for Future Vascular EventsSAIT DEMIRKOL, MUSTAFA CAKAR, SEVKET BALTA, HAKAN SARLAK, MUHAR-REM AKHAN, MURAT KARAMAN, TUNCER CAYCI, SEREF DEMIRBAS, Ankara, Turkey

Cellular adhesion molecules have been proposed to have roles in infl am-mation, tumour progression and metastasis. E-selectin is temporarily expressed on activated endothelial cells and mediates neutrophil, monocyte and memory T cell adhesion. In this study, we aimed to investigate the endothe-lial infl ammatory condition of patients with a newly diagnosed diabetes mel-litus (NDDM).

40 patients have been recruited in the study. 20 had a NDDM and 20 were controls. 4(20%) of the NDDM and 15(75%) of the control groups subjects were female. The mean ages of the NDDM and control groups were 48,45±20,8 and 39,95±11,3 years, respectively. The mean fasting plasma glucose levels of the patient and control groups were 223,8±148,4 and 88,8±8,24 mg/dl, respectively. E-selectin levels were signifi cantly higher in patients with a NDDM (139,84±75,9 vs 52,95±28,5 ng/ml, respectively; p=0,000). hsCRP levels of the patient and control groups were 3,1±3,84 and 1,19±0,93 mg/L, respectively(p=0,043). In the patient group, e-selectin levels were signifi cantly correlated with hsCRP (high sensitive CRP) levels (Pearson, r=0,293, p=0,008).

Our fi ndings show that e-selectin levels, as an infl ammatory marker, were increased in patients with a NDDM, who are on the zero point of the diagno-sis. E-selectin levels were signifi cantly correlated with hsCRP levels. These

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data represent that the endothelial infl ammation should start before the diagnosis of diabetes. Patients with higher e-selectin levels may be further candidates for future vascular events.

2347-POPrevalence of Extra-Coronary Artery Disease in Patients With Type 1 and 2 Diabetes Underwent Selective Coronary AngiographySVETLANA GRACHEVA, MARGARITA BIRAGOVA, ALEXANDRA GLAZUNOVA, INNA KLEFORTOVA, ALEXANDER IL’IN, TAT’YANA SOLDATOVA, MAYA DJAV-ELIDZE, MINARA SHAMKHALOVA, MARINA SHESTAKOVA, ELVINA TUGEEVA, KONSTANTIN MELKOZEROV, SIMON MATSKEPLISHVILI, YURIY BUZIASHVILI, Moscow, Russian Federation

To estimate prevalence of peripheral artery disease of lower extremities (PAD), brachiocephal arterial stenosis (BCAS), renal arterial stenosis (RAS) in type 1 and 2 diabetes patients (T1DP, T2DP) who were underwent selective coronary angiography (CA).

50 T2DP, 20 T1DP (mostly on a hemodialysis), 50 patients without diabetes (PWD) comparable age, have underwent CA, duplex ultrasonography (DU) of PAD, BCA, RA. The biomarkers of cardiac and kidney disease have been esti-mated (plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion mol-ecule (VCAM), soluble intercellular adhesion molecules-1 (sICAM), vascular endothelial growth factor (VEGF), asymmetric dimethylarginine (ADMA), homocystein (HCYST), transforming growth factor (TGF-β1), N-terminal frag-ment of pro-brain natriuretic peptide (NT-pro BNP), fi broblast growth factor 23 (FGF-23), regulated on activation normal T-cell expressed and secreted (RANTES), matrix metalloproteinase 9 (MMP9)).

CA revealed multivessel coronary artery disease in 94% T2DP, 90% in T1DP, 67% - in PWD. PAD was estimated in 42% T2DP, 25% T1DP, 10% PWD; hemo-dynamically signifi cant RAS - in 12%, 5% and 10% respectively, however BCAS - in 32% PWD, 28% in T2DP and 10% in T1DP. The co-existence athero-sclerosis in 3 and 4 vascular beds were identifi ed in 26% T2DP, 12%- in PWD (p=0.04). T1DP were found to have a signifi cant increase in NT-pro BNP, ADMA, RANTES, VICAM vs PWD; T2DP - in PAI-1, MMP9, sICAM vs PWD. NT-pro BNP and FGF-23 showed strongly negative correlation with glomerular fi ltration rate (GFR). Left ventricular hypertrophy was also associated with NT-pro BNP in T2DP. Patients with T1DP demonstrated negatively correlation NT-pro BNP and GFR, HDL and positively with TG.

Multivessel coronary artery disease was associated with hemodynamically signifi cant extra-coronary atherosclerosis in patients with diabetes, thus refl ecting elevation in biomarkers for cardiovascular and renal dysfunction.

2348-PODiastolic Arterial Wall Elasticity in Type 1 Diabetes is Inversely Related to Insulin ResistanceELEKTRA SZYMANSKA-GARBACZ, LESZEK CZUPRYNIAK, PIOTR GRZELAK, MICHAL PODGORSKI, MALGORZATA SARYUSZ-WOLSKA, MACIEJ PAWLOWSKI, JERZY LOBA, LUDOMIR STEFANCZYK, Lodz, Poland

Besides clear susceptibility to developing microvascular complications, Type 1 diabetes subjects are also at increased risk of cardiovascular and macrovascular complications. Recently, in 10 Type 1 diabetes subjects (mean [±SD] age 34.8±12.1 years, diabetes duration 10.9±6.0 years, BMI 23.5±1.4 kg/m2, HbA1c 9.5±2.1%) without any vascular complications, we have docu-mented the positive relationship between insulin resistance and QT interval. In the same group of subjects we conducted the study aiming at assessing arterial elasticity with the use of newly developed non- invasive two-dimen-sional strain imaging for estimation of vascular tissue motion and deformation (strain) during the cardiac cycle using speckle tracking. This technique enables angle-independent calculations of deformation arterial variables. Two-dimen-sional long- and short-axis grey-scale cine loops of the left and right common carotid arteries (CCA) were acquired in the study group and 10 healthy age-, gender- and BMI-matched controls. Circumferential strain (CS, %) and strain rate (CSr, strain per time unit, 1/s) were measured. Surprisingly, Type 1 dia-betes subjects presented with higher values of elasticity than the controls in left and right CCA (mean [±SD ] CS 7.62±2.58 vs 4.24±1.11; 6.5±2.31 vs 3.96±0.91%, p<0.01; CSr 1.47±0.9 vs 0.64±0.16; 1.01±0.28 vs 0.55±0.12 1/s, p<0.01; respectively) - even though no difference between the groups in carotid intima-media thickness was found. Interestingly, more insulin resistant diabetic subjects showed smaller diastolic strain (r=0.358; p<0.05). In conclu-sion, arterial wall elasticity in Type 1 diabetes might be increased in the early course of the disease, however insulin resistance is associated with decreased elastic properties of CCAs during diastole. These fi ndings might suggest that early signs of cardiovascular disease in Type 1 diabetes are associated with diastolic dysfunction of vasculature.

Supported by: Medical University of Lodz

2349-PODesign of the Empaglifl ozin Cardiovascular (CV) Outcome Event Trial in Type 2 Diabetes (T2D)BERNARD ZINMAN, SILVIO E. INZUCCHI, JOHN M. LACHIN, CHRISTOPH WANNER, ROBERTO FERRARI, ERICH BLUHMKI, STEFAN HANTEL, ODD ERIK JOHANSEN, HANS-JUERGEN WOERLE, ULI C. BROEDL, Toronto, ON, Canada, New Haven, CT, Rockville, MD, Würzburg, Germany, Ferrara, Italy, Ingelheim, Germany

The impact of different glucose-lowering therapies on CV disease remains unclear. The empaglifl ozin CV outcome event trial (NCT01131676) is an ongo-ing multi-center, randomized, double blind, placebo-controlled trial designed to assess the impact of the SGLT-2 inhibitor empaglifl ozin 10 or 25 mg, com-pared with placebo (1:1:1), on CV events. 7000 T2D patients being treatment naive or receiving any glucose lowering therapy (≥18 years, BMI≤45 kg/m2, eGFR≥30 mL/min/1.73m2) at elevated CV risk will be studied (TABLE). The primary outcome is time-to-fi rst occurrence of CV death, nonfatal myocardial infarction or nonfatal stroke. 691 events will be required to provide 90% power to yield the upper limit of the adjusted 95% CI for hazard ratio <1.3 at a one-sided α level of 0.025, assuming equal risks. Hierarchical testing for superior-ity will follow for the primary and those key secondary (primary + unstable angina hospitalization) outcomes where non-inferiority is achieved for the pooled doses vs. placebo. Other outcomes include a microvascular composite (laser therapy for retinopathy, vitreous hemorrhage, blindness, new/worsen-ing nephropathy [macroalbuminuria, doubling of serum-creatinine and eGFR ≤ 45, renal replacement therapy, death due to renal disease]) and effi cacy (glycaemia, weight, blood pressure). The empaglifl ozin CV outcome event trial is powered to show CV safety with the option to demonstrate CV superiority for the SGLT-2 inhibitor empaglifl ozin.

Supported by: Boehringer Ingelheim Pharmaceuticals, Inc.

2350-POFrequency of Macrovascular Complications in Patients With Micro-vascular Complications and Evaluation of Complication Related Risk Factors Type 2 Diabetic PatientsPELIN TÜTÜNCÜOGLU, ECE HARMAN, DEVRIM DÖLEK, NIHAN KAHYA, MITAT BAHCECI, Izmir, Turkey

Background and aim: We aimed to investigate frequency of macrovascular complications in patients with microvascular complications and evaluation of complication related risk factors type 2 dıabetıc patıents.

Subjects: A total of 262 type 2 diabetic patients were divided to 2 groups in according to presence of microvascular or macrovascular complications. We evaluated the relationship between frequency of microvascular and pres-ence of macrovascular complications.

Results: Mean age of patients with micro vascular complications (58,91±10,76) were higher than those of without micro-vascular complications (54,67±11,97) (p 0,009). There was no statistically signifi cant difference between in these groups in terms of gender, duration of diabetes, BMI and A1C levels. In patients with macro-vascular complications mean BMI were higher than those of without macro-vascular complications (p<0.04).

Relationship between frequency of microvascular and presence of macro-vascular complications: Two hundered patients (%76.3) had at least one micro-vascular complication. Of patients with at least 1 microvascular complication, 152 patients (%76) had additionally macro-vascular complication. While remaining 62 patients had no any microvascular complication, 35 patients (%56.5) had macro-vascular complication. Macrovascular complication ratio of patients with microvascular complication was higher than patients had no microvascular complication (p<0.001). We detected a signifi cant correlation

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between microvascular complication and coronary artery disease (p<0.05). Again the frequency of microvascular complication (2+) and macrovascular complication (p<0.05).

Our fi nding indicated that prevalence of micro and macro-vascular compli-cations are closely related each other. Frequency of micro-vascular complica-tions was related to occurrence of macro-vascular complication

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2352-POP-Selectin Levels may Not Refl ect Endothelial Infl ammation in Patients With Impaired Glucose ToleranceMUHARREM AKHAN, SAIT DEMIRKOL, SEVKET BALTA, MUSTAFA CAKAR, HAKAN SARLAK, MUSTAFA DINC, IRFAN SENER, SEREF DEMIRBAS, Ankara, Turkey

P-selectin is a cell adhesion molecule of stimulated platelets and endothe-lial cells, and mediates the interaction of these cells with neutrophils and monocytes. P-selectin is known to mediate the interaction of leukocytes with platelets in the area of tissue injury and a stimulated endothelium in infl am-mation and thrombosis. In this study, we aimed to investigate the endothelial infl ammation in patients with impaired glucose tolerance (IGT) through p-selectin levels.

We have recruited 40 subjects totally in the study. 20 patients had IGT and 20 were controls. The subjects were adults between the ages of 20 and 73. 12 (60%) of the patient group and 15 (75%) of the controls were female. The mean ages of the study group and controls were 53,25±12,8 and 39,9±11,3 years, respectively. The mean fasting/postpirandial plasma blood glucose levels of the IGT and control groups were 115,85±16,2/163,9±16,1 and 88,8±8,24/128,7±12,7 mg/dl, respectively. P-selectin levels were statistically similar in the IGT patients and control group (33,8±13,3 vs 35,8±15,6 ng/ml, respectively, p=0,914). However, high sensitive C-reactive protein (hsCRP) levels were signifi cantly higher in patients with IGT (4,5±4,32 vs 1,19±0,93 mg/L, p=0,003, respectively). The correlation was very weak between hsCRP and p-selectin levels (Pearson r=-0,038, p=0,874).

In our study, patients with an IGT had similar p-selectin levels compared to controls. P-selectin levels did not have any association with hsCRP levels. These fi ndings may represent that p-selectin levels may not refl ect endothe-lial infl ammation in patients with impaired glucose tolerance.

2353-POAssociation between Atherogenic CD14+CD16+ Monocytes and Indexes of Atherosclerosis in Type 2 Diabetic PatientsTAKASHI MISHIMA, KOKA MOTOYAMA, YUKO YAMAZAKI, TOMOAKI MORIOKA, KATSUHITO MORI, SHINYA FUKUMOTO, TETSUO SHOJI, MASANORI EMOTO, MASAAKI INABA, Osaka, Japan

Atherosclerosis is a crucial complication of diabetes. Recent studies have shown that circulating mononuclear cells are heterogeneous and are engaged

in chronic infl ammatory disease such as atherosclerosis. Since it is increas-ingly acknowledged that CD14+CD16+ monocytes were involved in cardio-vascular event, the association between CD14+CD16+ monocytes and indexes of atherosclerosis are to be elucidated. In this study, we investigated the association between monocyte subset CD14+CD16+ and atherosclerosis indexes in 149 type2 diabetes (age, 62 ± 14 (SD) years, duration 14 ± 12 (SD) years). Frequency of monocyte subsets (CD14++CD16- and CD14+CD16+) were analyzed by fl ow cytometry. As indexes of atherosclerosis,fl ow-mediated dilatation (FMD), pulse wave velocity (PWV) and intima-media thickness (IMT) were measured. In simple linear regression analysis, number of CD14+CD16+ monocytes was signifi cantly associated with PWV (r= 0.197, p=0.019) and exhibited weakly negative association with FMD (r= -0.185, p=0.034). On the other hand, number of CD14+CD16+ monocytes did not reach signifi cant cor-relation with IMT (r=0.152, p=0.067). Multiple regression analysis including age, gender, systolic blood pressure, LDL-C and CD14+CD16+ monocytes indi-cated that CD14+CD16+ monocyte (β= 0.133, p=0.019) were signifi cant inde-pendent contributor to PWV. In conclusion, CD14+CD16+ monocytes were associated with PWV in type2 diabetes.

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2355-POIncreased Arterial Stiffness Measurements in Newly Diagnosed Diabetic Patients: Should the Damage Start Long Before the Diabetes Diagnosis?HAKAN SARLAK, MUSTAFA CAKAR, SEVKET BALTA, MUHARREM AKHAN, SAIT DEMIRKOL, OMER KURT, ZEKERIYA ARSLAN, EROL ARSLAN, Ankara, Turkey

Recent clinical studies have shown that arterial stiffness is an independent predictor of cardiovascular mortality. Increased fasting plasma glucose (FPG) is a risk factor for arterial stiffness and cardiovascular disease. Arterial stiff-ness can be easily and noninvasively assessed by measuring the pulse wave velocity (PWV). The aim of the present study was to investigate the relation-ship between increased FPG and arterial stiffness in newly diagnosed diabetic patients.

Our study have been made on the total of 68 individuals; 34 newly diagnosed diabetic patients and 34 controls. The subjects were adults between 18 and 72 years of age, with mean ages of 43,12±16,1 and 38,0±9,6 years in patient and control groups, respectively. 10(29,4%) subjects of the patient group and 17(50%) subjects of the control group were female. Mean FPG of the patient and control groups were 236,8±137 mg/dl and 87,4±10,4 mg/dl, respectively.

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COMPLICATIONS—MACROVASCULAR—CELLULAR MECHANISMS OF ATHEROGENESIS IN DIABETES

The PWV measurements of the patients (8,3765±1,99 m/s) were higher than that of the control group (7,0059±1,02 m/s)(p=0,001). In the patient group, FPG was signifi cantly correlated with PWV measurements (Spearman’s rho, r=0,284, p=0,022).

An increase in FPG and a new diabetes diagnosis have been found associ-ated with aggravated arterial stiffness, as an indicator of increased cardio-vascular risk. Newly diagnosed diabetics should be evaluated in-depth from the fi rst increase in plasma glucose levels in terms of cardiovascular risks, indicating the need for good prediabetes follow up and awareness.

2356-POThe Prevalence of Severe Coronary Artery Disease in Patients With Diabetes Mellitus and Critical Limb IschemiaKONSTANTIN MELKOZEROV, VICTOR KALASHNIKOV, SERGEY TEREKHIN, Moscow, Russian Federation

The aim of the study was to examine the prevalence of severe coronary artery disease (CAD) and the necessity of myocardial revascularization (MR) prior to limb revascularization (LR) in patients with diabetes mellitus (DM) and critical limb ischemia (CLI). 118 diabetic patients (65 female, median of age ― 67,5 [59;73] years, median of DM duration ― 15 [9;21] years, type 2DM ― 107 patient (90,7%), median of HbA1c ― 8,2 [7,5;9,0]) with CLI were hospitalized in Endocrinology research center (Moscow, Russia) from October 2009 till December 2011. The electrocardiography, echocardiography, blood tests were performed in all patients. Moreover, all patients received optimal medical treatment and underwent balloon angioplasty/stenting of lower extremity arteries. Some patients underwent coronary angiography and per-cutaneous coronary intervention (PCI). At admission, 63 patient (53,4%) didn’t present any CAD, 27 patients (22,8%) had angina class I-II, 17 patients (14,4%) had angina class III-IV, 10 patients (8,4%) had non-ST elevation acute coronary syndrome (ACS), recent (within the period up to 3 month) myocardial infarction (MI) was revealed in 1 patient. 28 patients (23,7%) with ACS, angina class III-IV and resent MI underwent coronary angiography before LR: 4 patients (14,2 %) had one vessel disease, 11 (39,3%) - two vessel disease, 13 (46,4%) - multivessel disease, including 10 patients (35,7%) with left main disease. All patients suffered from DM type 2. The results didn’t show correlation between DM duration, HbA1c level, type of antidiabetic therapy and the risk of CAD development. 25 patients (21,2%) underwent PCI before LR. Drug eluting stents were used in 82% cases, each patient required 2,5 stents in average. The study shows that patients with DM and CLI frequently suffer from severe CAD and the necessity of coronary angiography and PCI before LR is about 25%. Also, multivessel coronary disease is typical for patients in this cohort.

2357-POSerum Uric Acid Levels Are Signifi cantly Correlated With Arterial Stiffness Parameters In Patients With Newly Diagnosed Diabetes MellitusSEVKET BALTA, HAKAN SARLAK, SAIT DEMIRKOL, MUHARREM AKHAN, MUS-TAFA DINC, MUSTAFA CAKAR, OMER KURT, KENAN SAGLAM, Ankara, Turkey

Uric acid had previously been known as an antioxidant agent, but recently, a growing body of data gives it a role indicating endothelial infl ammation and representing cardiovascular risks. Arterial stiffness is an easy and non-invasive way of determining the vascular health and endothelial dysfunction. Here we aimed to investigate the role of uric acid levels in determining the cardiovascular risk through arterial stiffness parameters in newly diagnosed diabetics.

The study has been made on 44 subjects, 24 of whom had a newly diagnosed diabetes mellitus (NDDM) and 20 were controls. 8(33%) of the NDDM and 15(75%) of the control groups subjects were female. The mean ages of the NDDM and control groups were 47,7±19,1 and 39,95±11,3 years, respectively. The mean fasting plasma glucose levels of the patient and control groups were 206,2±141,05 and 88,8±8,2 mg/dl, respectively. Serum uric acid levels of the patient and control groups were 4,98±1,67 and 4,02±1,25 mg/dl, respec-tively (p=0,071). The mean pulse wave velocity(PWV), central aortic pressure(CAP) and augmentation indexes(Ai) of the patients were 9,38±2,53 m/sec, 127,95±16,14 mmHg and 23,3±20,2 %, respectively. In the patient group, serum uric acid levels were signifi cantly correlated with arterial stiff-ness measurements (Spearman rho; r=0,513, p=0,05; r=0,677, p=0,006; r=0,729, p=0,002; for PWV, CAP and Ai, respectively).

Our patient group was relatively small, however, uric acid levels were higher in the NDDM group, though the difference was not statistically signifi cant. As an indicator of cardiovascular risk and endothelial infl ammation, determi-nation of serum uric acid levels should be held within the primary diagnostic work and follow up in NDDM patients.

2358-POBaseline Characteristics of Participants Enrolled in the CARdiovas-cular Outcome Study of LINAgliptin versus Glimepiride in Early Type 2 Diabetes (CAROLINA)NIKOLAUS MARX, JULIO ROSENSTOCK, STEVEN KAHN, BERNARD ZINMAN, JOHN J. KASTELEIN, JOHN M. LACHIN, ERICH BLUHMKI, MICHAELA MATTHEUS, SANJAY PATEL, ODD ERIK JOHANSEN, HANS-JUERGEN WOERLE, Aachen, Ger-many, Dallas, TX, Seattle, WA, Toronto, ON, Canada, Amsterdam, Netherlands, Rock-ville, MD, Ingelheim, Germany, Bracknell, United Kingdom

The intrinsic impact of different glucose-lowering therapies on cardiovas-cular (CV) burden remains unclear. In CAROLINA (NCT01243424) potential dif-fering effects on CV outcomes of linagliptin (5 mg/day) therapy versus glimepir-ide (up to 4 mg/day) will be determined in participants with early type 2 diabetes (T2D) at high CV risk or with CV complications. The study is a double-blind, double dummy, event driven (631 events) trial powered for CV non-inferiority and superiority. Between Dec 2010 and Dec 2012, 581 clinical sites globally randomized 6103 patients. At baseline, data on clinical history, symp-toms and medications along with centralized evaluations of ECGs and lab specimens were obtained. Most participants come from Europe (45.0%) or North-America (19.4%), 40.3% are women and 33.4% have previous CV com-plications. Diabetes duration was <5 years in 41%, 5-10 years in 28%. At base-line, HbA1c was 7.2% with 72.5% having HbA1c <7.5%. 67% were on 1 and 22% on 2 glucose-lowering agents, with the vast majority taking metformin (TABLE). The population was overweight/obese, with BMI ≥30 kg/m2 in 46% of participants. Baseline characteristics indicate that we have recruited an appropriate target population to address the study question of potential dif-fering effects of linagliptin and glimepiride on CV outcomes and thus will help inform clinical decision-making when selecting second line therapy in T2D.

Supported by: Boehringer Ingelheim Pharmaceuticals, Inc.


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2360-POGlucagon-Like Peptide-1 Protects Against High Glucose Induced Oxidative in Human Umbilical Vein Endothelial CellsYUE QIAO, LIXIN GUO, YAJUN LIN, LIN JIANG, JIANG LIU, LINA ZHANG, Beijing, China, Jiangxi, China

The aim of our study is to observe the change of oxidative stress, dysfunc-tion, apoptosis of human umbilical vein endothelial cells and the protection of glucagon-like peptide-1(GLP-1) to the injury of human umbilical vein endothe-lial cells induced by high concentration of glucose.

Human umbilical vein endothelial cells were divided into four groups includ-ing control group, glucose 19 mmol/L, 33 mmol/L and 47 mmol/L group which were treated with saline or different concentration of glucose for 48 hours. Cell viability was analyzed by MTT method; The change of reactive oxygen species (ROS) was invested by DCFH-DA fl uorescent probes and fl ow cytom-etry cell technology; Apoptosis of human umbilical vein endothelial cells was analyzed by Annexin v-PI staining combined with fl ow cytometry method. The expression levels of JNK, VCAM-1, ICAM-1, Bax and the phosphorylation of JNK were analyzed by Western blot.

Compared with the control group, cell viability in different GLP-1 (0.01, 0.1, 1, and 10 nmol/L) treated groups were signifi cantly increased Compared with high glucose group, 10 nmol/L GLP-1 can sigifi cantly increase the cell viability; GLP-1 treatment can signifi cantly reduce the ROS level of high glucose treat-ment group. Compared with the control group, the level of apoptosis in control group treated by GLP-1 was decreased, Early apoptosis were signifi cantly decreased in various concentrations of GLP-1 group, late apoptosis in the GLP-1 1 and 10nmol/L groups were signifi cantly decreased; The expression of VCAM-1 in high glucose group after intervention by GLP-1 was signifi cantly declined ,The phosphorylation of JNK and the expression of Bax was signifi -cantly decreased in high glucose group after intervention by GLP-1.

GLP-1 reduced the expression of endothelial cells ICAM-1 and VCAM-1 and inhibited cell apoptosis induced by high glucose by reducing ROS generation and the activation of JNK- Bax signal pathway.

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2362-POHyperinsulinemia may Contribute to Atherosclerosis through the Induction of microRNA33a/bMAKI YAMASHITA, YUUKI KIMURA, KOUKI MATSUMURA, HIROSHI MURAKAMI, KOUTA MATSUKI, JYUTAROU TANABE, HIROSHI MURAKAMI, JYUN MATSUI, NAOKI TAMASAWA, Hirosaki, Japan

Insulin resistance may induce atherosclerosis in type 2 diabetes, although the precise molecular mechanism has not been clarifi ed. Micro(Mi)RNAs are non-coding RNAs and recent studies have shown that miRNA33a and 33b have an important role in cholesterol homeostasis through ATP-binding cas-sette transporter(ABC)A1/G1 expressions. We studied effect of insulin on miRNA33a/b and ABCA1/G1 protein levels in macrophages.

Human monocyte-derived THP-1 cells were developed into macrophages. To investigate the mechanisms of the effect of insulin, the cells were treated with insulin (0, 20, 100 nM) for 24h. Then, the expressions of miRNA33a/b and ABCG1/A1 were analyzed. MiRNA was extracted using a mirVana miRNA isolation kit (Ambion). The TaqMan probes for miRNA33a/33b and GAPDH were purchased from Applied Biosystems. Protein levels of ABCG1/A1 were analyzed using western blotting.

20nM insulin signifi cantly increased expressions of both miRNA33a/b. However, 100 nM insulin did not increased miRNA33a nor 33b. As to protein levels of ABCA1 and ABCG1, Insulin (20 and 100nM) inhibited both proteins, in a concentration-dependent manner.

In human, miRNA-33a located in intron 16 of the sterol-regulatory elements binding protein (SREBP) 2 gene on chromosome 22, and miRNA-33b located in intron 17 of the SREBP1 gene on chromosome 17. Insulin has been reported to activate SREBP1c, which induce genes involved in fatty acid and triglycerid synthesis. Then, insulin enhances expression of miRNA33b, which decrease expression of ABCA1/G1 and cholesterol effl ux from macrophages. We had reported that super-physiological levels of insulin(100 and 500 nM) suppresses HDL-mediated cholesterol effl ux from macrophages through inhibition of neutral cholesteryl ester hydrolase and ABCG1 expressions.

In this study, we revealed that 20nM insulin increased expression of miRNA33a/b and inhibited both ABCA1/G1.

This fi nding is the important to clarify the mechanism of insulin resistance and atherosclerosis.

2363-POClinical Study for Diagnostic Effi cacy of Diabetic Angiopathy Using Hemorheological Measurement System (RheoScan)JIYOON HA, MIN KYUNG KIM, CHANHEE KYUNG, SOHEE KIM, HAERI BAEK, TAE WOONG NOH, JIWOON KIM, JI SUN NAM, EUNJIN KWON, SEHYUN SHIN, SHI-NAE KANG, JONG SUK PARK, CHUL WOO AHN, KYUNG RAE KIM, Seoul, Republic of Korea

Several hemorheological parameters, such as erythrocyte deformability, erythrocyte aggregation are altered in patients with diabetes mellitus. These changes of erythrocyte in turn make whole blood more viscous and may play an important role on the pathogenesis of vascular complications of diabetes mellitus. So we intended to examine erythrocyte deformability and aggrega-tion in patients with type 2 diabetes, and assess the differences of these parameters compared with healthy controls.

81 subjects were enrolled. The erythrocyte deformability was measured in terms of elongation index (EI) with microfl uidic ektacytometer, RheoScan. The aggregation index (AI) was measured with RheoScan, too. All subjects were divided by 5 groups as follows: Healthy control (n=12), prediabetes (pre-DM, n=7), diabetes without vascular complications (DM-no Cx, n=24), diabetes with microvascular complications (DM-microCx, n=28) and diabetes with macrovascular complications (DM-macroCx, n=10).

A signifi cant reduction of erythrocyte deformability was observed in DM-microCx group and DM-macroCx compared with healthy control (0.325 & 0.325 vs. 0.344, p<0.05). Also, EI was signifi cantly decreased in the group of higher HbA1c level (a1c≥9%) compared with in the group of lower HbA1c level (a1c<7%, 0.328 vs. 0.339, p<0.05).

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COMPLICATIONS—NEPHROPATHY—BASIC AND EXPERIMENTAL SCIENCE

EI is a sensitive parameter to detect impairment of erythrocyte in diabetic process. The results in this study suggest that signifi cant reduction in the EI may have correlation with diabetic vascular complications, and furthermore could be one of the indicators of these complications.

2364-POEffects of Endoplasmic Reticulum Stress in Inducing Infl ammation in Vascular Endothelial CellYAWEI QIU, YAN-MING CHEN, QIUJU LV, XIAOFENG LI, WEI JIANG, LONGYI ZENG, Guangzhou, China

To explore the relationship between endoplasmic reticulum stress (ERS) and infl ammation in human umbilical vein endothelial cell lines (EAhy926) exposed to high glucose. The EAhy926 cells were incubated in normal glucose (NC,5.5mmol/L) or high glucose (HG, 25mmol/L ) for 0,2,4,8,12 hours, or exposed to ERS inducer thapsigargin (TG, 0.5µmol/L) for 24 hours. Western blot analysis was employed to assess the protein expression of infl ammatory factors, ERS markers, and phosphorylated signal transducer and activator of transcription 3(p-STAT3),total STAT3 (t-STAT3). The protein expression of infl ammatory factors, ERS markers and p-STAT3, were increased in a time-dependent manner after HG treatment. The level of GRP78 reach the peak at 8 hour, all the others were at 12 hour (P<0.05). Moreover,in EAhy926 cells exposured to TG, GRP78, p-eIF2α, ICAM-1, TNFα increased 5.55,1.63, 1.76 and 2.07 folds compared with NC group, respectively (all P<0.05), and p-STAT3 increased 2.15 folds compared with NC group (P<0.05), but t-STAT3 was not signifi cantly different between these two groups. Our data suggested high glucose could induce ERS and infl ammation in EAhy926 cells. ERS inducer also could induce infl ammation in EAhy926 cells. Phosphorylated STAT3 path-way may play an important role in bridging ERS and infl ammation.

Supported by: Guangdong Natural Science Foundation

2365-POHydrogen Sulfi de Protects H9c2 Cardiac Cells Against High Glucose-Induced Injury Through Inhibiting JNK PathwayXU WEN-MING, LIN JIAN-CONG, FENG JIAN-QIANG, Guangzhou, China

It has been shown that c-Jun N-terminal kinase(JNK) pathway plays a critical role in diabetes and that hydrogen sulfi de (H2S) is cardioprotective. The aim of this study is to explore whether exogenous H2S can protect against high glucose-induced injury by inhibiting JNK pathway in H9c2 cardiac cells. H9c2 cells were treated with high glucose to establish a model of cardiac cell injury. Here, we showed that treatment of H9c2 cells with 40mM glucose for 36h induced signifi cant injuries, as evidenced by a decrease in cell viability, an increase in reactive oxygen species (ROS) generation , and a loss of mito-chondrial membrane potential(MMP). In addition, the expression of phospho-rylated (p) JNK was upregulated by 40mM glucose treatment. However, pretreatment of H9c2 cells with 400µM NaHS ( a donor of H2S) for 30 min before glucose treatment attenuated not only the upregulation of p-JNK expression, but also the high glucose-induced injuries, leading to an increase in cell viability and decreases in ROS generation as well as MMP loss. More-over, pretreatment with either SP600125 (an inhibitor of JNK ) or N-acethl-L-cystein(NAC, a ROS scavenger) for 30 min markedly reduced high glucose-induced cytotoxicity. In summary, exogenous H2S protects against high glucose-induced-injury by inhibiting activation of JNK pathway and oxidative stress in H9c2 cardiac cells.

2366-POInhibition of P38 MAPK Pathway Contributes to the Protection of Edaravone Against High Glucose-Induced Insult in H9c2 Cardiac CellsXU WEN-MING, ZHANG CHANG-RAN, GUO RUN-MIN, FENG JIAN-QIANG, Guang-zhou, China

The P38 mitogen-activated protein kinase(MAPK)pathway has been reported to participate in diabetic cardionmyopthy and is activated by reactive Oxygen species(ROS).Edaravone(EDA), a novel free radical scavenger, is cardioprotec-tive. The present study tested the hypothesis that EDA could protect cardiac cells against high glucose-induced injury by inhibiting P38 MAPK pathway. H9c2 cardiac cells were treated with 40mM glucose for 36h to establish a model of cardiac cell injury. Our results showed that treatment with 40mM glucose induced signifi cant cardiomyocyte injury and oxidative stress, includ-ing decreases in cell viability and mitochondrial membrane potential(MMP),and increases in intracellular ROS generation, cleaved caspase-3 expression and number of apoptotic cells. These cardiomyocyte injuries were markedly attenuated by pretreatment of H9c2 cells with 40uM EDA for 60 min before exposure to high glucose. In addition, high glucose also upregulated the expression of phosphorylated(p) P38 MAPK which was reduced by the pretreat-ment with EDA. Moreover, pretreatment of H9c2 cells with 3uM SB203580( an inhibitor of P38 MAPK)obviously inhibited the high glucose-induced injuries, as evidenced by an increase in cell viability, decreases in ROS generation, cleaved capase-3 expression as well as loss of MMP. Taken together, we have demonstrated that EDA protects against high glucose-induced injury by inhib-iting P38 MAPK pathway and oxidative stress in H9c2 cardiac cells.


2367-POInsulin Treatment Downregulates Renal ADAM17 Protein Expression and ACE2 Shedding in Akita Diabetic MiceESAM SALEM, HARI K. SOMINENI, KHALID M. ELASED, Dayton, OH

Diabetic patients have a 40%-50% lifetime chance of developing chronic kidney disease which remains one of the leading causes of morbidity and mortality. Angiotensin converting enzyme 2 (ACE2) has a renoprotective role due to its ability to form Angiotensin (1-7) by degrading Angiotensin II. We have shown previously that hyperglycemia increased urinary ACE2 and albu-min excretion in db/db diabetic mice. The protease, a disintegrin and metal-loprotease (ADAM) 17, is involved in the ectodomain shedding of several transmembrane proteins, including ACE2 in vitro. Tissue inhibitor metallopro-teinase-3 (TIMP3) is known to be an endogenous inhibitor of ADAM17. We tested the hypothesis that normalizing hyperglycemia in Akita mice with insulin, will downregulate and upregulate renal ADAM17 and TIMP3 protein expression respectively. Metabolic parameters were monitored weekly. Urine was collected over 24 hours to measure urinary albumin and ACE2 activity. Western blot & immunostaining revealed upregulation of renal ADAM 17, ACE2, but no difference in TIMP3 protein expression in Akita mice compared to WT mice. Treatment of Akita mice with insulin implants (LinβitR) for 20 weeks signifi cantly decreased hyperglycemia, urinary ACE2 and albumin excretion. Insulin treatment also decreased renal ADAM17, ACE2, with no effect on TIMP3 protein expression. There was a positive linear correlation between urinary ACE2 excretion with albuminuria, blood glucose, plasma creatinine, plasma glucagon and triglycerides levels. In conclusion, in Akita diabetic mice there is upregulation of renal ADAM17, ACE2 protein expression which is associated with a signifi cant increase in urinary ACE2 excretion. It is tempting to speculate that renoprotection of insulin could be mediated via downregulation of renal ADAM17 protein expression and attenuation of renal ACE2 shedding. Urinary ACE2 could be an independent risk factor and a sen-sitive biomarker for early prediction of diabetic nephropathy.

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2370-POTherapeutic Effect of Zinc on Diabetic Nephropathy Is via Enhanced Akt/GSK3βWEIXIA SUN, YAOWEN FU, LU CAI, Changchun, China, Louisville, KY

Insulin resistance is a key pathogenic factor for diabetic nephropathy. We have shown the protective role of zinc supplement in the prevention of diabetic nephropathy in STZ-induced type 1 diabetic mice (J Nutr Biochem 2010, 21: 237-246). However, whether zinc have the protective effect on diabetic neph-ropathy in the transgenic OVE26 type 1 diabetic mice and Akt2-KO type 2 diabetic mice as well as the relationship between zinc and Akt/ GSK-3β insu-lin signaling pathway remains unknown. Here we used transgenic OVE26 type 1 diabetic mice and Akt2-KO type 2 diabetic mice and demonstrated that zinc have therapeutic effect on diabetes-induced renal structural disarrangements and remodeling, detected by fi brotic makers of CTGF and TGF-β1 expression and collagen deposition (Sirius-red staining). These pathological changes were accompanied by signifi cant increases in oxidative damage (3-NT and 4-HNE), and infl ammation (PAI-1 and TNF-α) in diabetic kidneys, which were partly prevented in zinc -treated diabetic kidneys. In the kidney of both type 1 and type 2 diabetic mice, we found the decreased phosphorylation of Akt and GSK-3β.Correspondingly, renal glycogen synthase phosphorylation, hexoki-

nase II and PGC-1α expression, which all involve in the regulation of glucose and lipid metabolisms, were signifi cantly altered. Diabetes also increased Akt negative regulators, tribbles (TRB)3 expression and phosphatase and tensin homolog (PTEN) phosphorylation . The above molecule’s changes were com-pletely prevented by zinc treatment for 3 months. These results suggest that zinc can increase Akt phosphorylation that inactivates GSK-3β function prob-ably via prevention of diabetic up-regulation of TRB3 and PTEN expression, resulting in a therapeutic effect on diabetic nephropathy.

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COMPLICATIONS—NEPHROPATHY—CLINICAL AND TRANSLATIONAL RESEARCH

2373-POVitamin D Receptor Infl uences LPS-Induced TGF-β and ATG Expres-sion in Podocytes Possibly via the NF-κB PathwayLIJUAN XU, ZHIMIN HUANG, HONGYU GUAN, DONGHONG FANG, XIAOYING HE, WEIWEI LIANG, WANPING DENG, YANBING LI, Guangzhou, China

Podocytes play an important part in the development and progression of diabetic nephropathy. We evaluated the effects of different activity status of vitamin D receptor (VDR) on the major infl ammatory cytokines in cultured murine podocytes with and without the presence of lipopolysaccharide (LPS) detected by RT-PCR and Western Blotting. For gene expression, we found that 1,25-Dihydroxyvitamin D3, which acted as an activator of VDR, signifi -cantly suppressed the elevated transforming growth factor-β(TGF-β) and angiotensinogen (ATG) mRNA for 90.00% and 99.99% respectively (P<0.05). On the contrary, levels of TGF-βand ATG were increased by 2.05 and 3.12 times in VDR siRNA transfected podocytes over the controls after the stimu-lation of LPS for 4 hours. For protein production, 1,25-Dihydroxyvitamin D3 reduced the increased levels of TGF-β, ATG, phosphorylated IκB (P-IκB) and phosphorylated IκB kinase (P-IKK) induced by LPS. While in the VDR siRNA transfected podocytes, TGF-βand ATG were inspected an excessive expres-sion after a 4-hour-stimulation of LPS (P<0.05). But differently, P-IKB and P-IKK were detected on the rise at the presence of LPS for 1 hour and 8 hours, which implied the NF-κB pathway might be repeatedly activated in this circle. In summary, we conclude that VDR infl uences the expression of TGF-βand ATG in LPS stimulated kidney podocytes. The NF-κB pathway might exert its cas-cade effects in this process.

2374-POOxoglutarate Receptor 1 Expressions in the Kidneys of Rats With DiabetesYONGXUE LIU, MING HU, XINKAI ZHU, CHUNGUANG HAN, CHANJUAN DI, MIN-GLI PENG, Beijing, China

Oxoglutarate (alpha-ketogrutarate) receptor 1 (OXGR1), also known as GPR80/99, is proven to be mainly distributed in kidneys. Very little is known about its biological functions. We investigated its expressions in the kidneys with diabetic progressing. Thirty male Wistar rats (180±20g) were randomly divided into normal (10 rats) and diabetic (20 rats) groups. To induce diabetes, Streptozotocin (65mg/kg) was singly intraperitoneal injected for every rat, and the blood glucose levels were measured in every week. In 16W and 32W of the diabetic induction, the rat kidneys were obtained and their pathological examinations were carried out. In the meantime, expressions of vimentin and OXGR1 in the kidneys were evaluated by immunofl uorescent method based on staining intensity and positive percentage (0-4+). In diabetic rats, their blood glucose kept sustained a range of high glucose levels (22.2~28.4 mmol/L). The rat kidneys demonstrated some pathological features of diabetic neph-ropathy (DN). We found that infl ammation, interstitial fi brosis and tubular atrophy lesions were predominantly peritubular, rather than glomerulus-centered, suggesting that the DN tubular lesions were primary. Results of double immunofl uorescence labeling indicated that, both OXGR1 and vimen-tin positive regions in the kidneys of diabetic rats were gradually increased with the process of diabetes (p<0.05, vs. normal rats), and OXGR1 and vimen-tin overlapping regions were also increased (p<0.05, vs. normal rats). In con-clusion, vimentin positive regions in the renal tubular epithelial cells usually indicate the epithelial-mesenchymal transdifferentiation of DN. The increased OXGR1 expression in renal tubular epithelial cells implies the receptor might be involved in the renal dysfunction during DN progress.

Supported by: NSFC


2375-POThe Role of Urine Storage on Urinary Alpha-1-Microglobulin in Type 2 Diabetes and Overt NephropathyNADAN GREGORIC, DRAZENKA BARLOVIC PONGRAC, ANDREJ JANEZ, Ljubljana, Slovenia

Urinary biomarkers are promising tool for detection and monitoring of kid-ney disease. Alpha-1-microglobulin (A1M) is associated with tubular damage in diabetic nephropathy. The 24-hour urine collection is still considered the gold standard for A1M measurement, but the requirement to store at low temperatures prior to analysis makes such method not always feasible. We aimed to determine if a more convenient storage of 24-hour urine samples at ambient temperature affects the reliability of measurements and if a spot urine sample could reliably replace it.

In patients with type 2 diabetes and overt nephropathy urinary A1M was determined by immunonephelometry from samples of three consecutive 24-hour collections stored at ambient temperatures and from a spot urine. We calculated a difference in urinary A1M/creatinine ratio between the fresh sample and samples stored for 1 or 2 days, respectively. A paired-sample T-test was used to test for a statistical signifi cance between the two groups. For comparison with the spot urine we used the Bland-Altman plot.

In included 24 patients (glycated hemoglobin 7,9+/-1,2 %; serum creatinine 176+/-67,9 µmol/L; blood pressure 153/81+/-19/11 mmHg; mean+/-SD; albu-minuria 156,4 (103,4; 264,4) g/mol; median (.25 .75)) the mean urinary A1M was 6,11+/-4,09 mg/mmol/l. The variability coeffi cient was higher in longer stored urine (2 days 19,5% vs. 1 day 8,1%) and in spot urine (32,2%). The absolute differences in urinary A1M among 24-hour urine samples that were stored for 1 or 2 days compared to fresh sample were not signifi cant (0,02+/-1,7 vs. 0,1+/-0,7 mg/mmol, p >0,05). There was also no signifi cant difference when comparing urinary A1M concentration of spot urine sample to fresh 24-hour sample (mean 6,11+/-4,09 vs. 6,07+/-5,73 mg/mmol, p >0,05).

Urine storage at ambient temperature for 2 days does not affect reliability of A1M measurement in patients with type 2 diabetes and overt nephropaty. The spot urine sample A1M measurement is reliable as well.

2376-PONon-Alcoholic Fatty Liver Disease (NAFLD) Is Associated With an Accelerated Rate of Decline of Kidney Function in Type 2 Diabetic PatientsMARIKO HIGA, AYANO DOI, EIKO YOSHIDA, AYUMU YOSHIFUJI, KAORU YAMASH-ITA, TAKAMASA ICHIJO, HIROMI OUCHI, Yokohama, Japan

[AIM]Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease (CVD) in type 2 diabetic patients. We conducted a 4-year follow-up study to investigate whether NAFLD might be associated with an accelerated rate of decline of kidney function in type 2 diabetic patients. [METHOD]The subjects of this study were 50 type 2 diabetic patients (age 63.2±12.1 years, 20 males and 30 females) with an urinary albu-min excretion rate (UAE) of less than 100mg/gCr. NAFLD was diagnosed based on the liver ultrasound fi ndings. Patients with a current/past history of alco-hol abuse or viral hepatitis were excluded. Among the 50 patients, 28 had NAFLD (FL group), while the remaining 22 did not have NAFLD (non FL group). The kidney function was determined by calculating the estimated GFR (eGFR) using MDRD. The rate of decline of eGFR over the 4 year follow-up period was compared between the groups with and without NAFLD. [RESULTS]In the FL group, west circumferences, BMI, and serum lipid and liver enzyme levels were signifi cantly higher than those in the non FL group. The UAE during the fi rst year was 23.7±31.7 mg/gCr in the FL group and 19.9±19.6 mg/gCr in the non FL group, with no signifi cant difference between the two groups. The FL group showed a signifi cantly higher rate of decline of the eGFR over the 4-year period than the non FL group (-3.2±2.6 vs -1.1±2.0 ml/min/1.73m2/year, p<0.05). The rate of decline of the eGFR over the 4-year period showed signifi cant negative correlations with the serum liver enzyme and triglyceride levels, and also the diastolic pressure. [CONCLUSION]Our fi ndings suggest that NAFLD is associated with an accelerated rate of decline of the kidney function in type 2 diabetic patients. These fi ndings may implicate NAFLD not only as a marker of the risk of CVD, but also as that of diabetic nephropathy, which might be mediated by infl ammatory cytokines release from steatotic liver.

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2377-POIncreased Normal-Range Albuminuria Predicts Peripheral Sensory Loss in Type 2 DiabetesDRAZENKA PONGRAC BARLOVIC, JELKA ZALETEL, VILMA URBANCIC ROVAN, Ljubljana, Slovenia

Diabetic microvascular disease affects nerves as well as glomeruli. How-ever, whether increased albuminuria still in normal range has a role in the progression of peripheral neuropathy in patients with Type 2 diabetes remains unknown.

After an 8-week washout period from the renin-angiotensin system inhib-itors we measured urinary albumin excretion rate (UAER) by radioimmunoas-say in three overnight urinary samples on two occasions in 71 patients with normoalbuminuria and microalbuminuria. A 10-g monofi lament test was per-formed at the study beginning and after a median of 4,3 (3,7; 4,7) years of follow-up. Independent samples t-test was used to delineate the differences between progressors and non-progressors of peripheral sensory loss. A p-value of below 0.05 was considered as statistically signifi cant.

From 71-patients enrolled (age 61±9 years, BMI 30±5, HbA1c 8,3±1,3, ambu-latory systolic RR 134±12 mmHg, UAER 3,95 (2,7, 12,4) ug/min), 53 completed the study. In the patients that developed peripheral sensory loss during the study follow-up (n=8), baseline albuminuria was signifi cantly higher compared to the patients with no change in sensory loss (lnUAER 2,3±0,8 ug/min vs. 1,5±1,4 ug/min, respectively; p<0.05).

Increased range albuminuria even in normal range is a signifi cant predictor of peripheral neuropathy progression in Type 2 diabetes.

2378-POTwo Potential Biomarkers, Urinary Posaposin and GM2AP, are Ele-vated in Children With Diabetes and Normal Albumin ExcretionVICTORIA MANWARING, WENDY HEYWOOD, ROBERT CLAYTON, SIMON HEALES, ROBIN H. LACHMANN, JOAN KEUTZER, BRYAN WINCHESTER, PETER C. HIND-MARSH, KEVIN MILLS, London, United Kingdom, Framingham, MA

Microalbuminuria is the traditional method for evaluating renal complica-tions of diabetes. Using label free quantative proteomics we have identifi ed 2 potential protein biomarkers that indicate presymptomatic kidney disease in the urine of paediatric patients with Type-I diabetes (n=10). Peptides were analysed in positive ion mode with the QTOF operated in v-mode with a typical resolving power of 10,000 FWHM. Protein identifi cation from the low/high collision spectra for each sample was processed using a hierarchical approach where more than three fragment ions per peptide, seven fragment ions per protein and more than two peptides per protein had to be matched. Prosaposin and GM2 activator protein (GM2AP) were observed to be elevated 1.4 fold (P=0.04) in the urine of the children with diabetes compared to age and sex matched controls. The presence of the biomarkers was independent of diabetes control and none of the children had evidence of microalbuminu-ria. These fi ndings were validated by development of a rapid MRM-based tandem mass spectrometry test.

These observations suggest that these biomarkers may be an earlier marker of renal involvement in diabetes.

2379-POPostprandial Responses of Incretins and Pancreatic Hormones in Nondiabetic Patients With End-Stage Renal DiseaseTHOMAS IDORN, FILIP K. KNOP, JENS J. HOLST, MADS HORNUM, BO FELDT-RASMUSSEN, Hellerup, Denmark, Copenhagen, Denmark

Patients with end-stage renal disease (ESRD) have a high prevalence of prediabetes. The underlying pathophysiology remains unclear, but may prove important for the strategies designed to prevent progression to overt diabe-tes. Meal-induced release of the insulinotropic gut incretin hormones and pancreatic glucagon plays a critical role in the maintenance of normal post-prandial glucose tolerance, however the postprandial responses of these hormones have never been examined in patients with ESRD. We evaluated plasma responses of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, glucagon and glucose during a stan-dardized 4h-liquid meal test in ESRD patients with normal (N=10) or impaired (N=10) glucose tolerance and in healthy control subjects (N=11). Glucose excur-sions were comparable between groups (P>0.59). Patients with ESRD exhib-ited higher fasting levels of GIP and GLP-1 compared with controls. Relative to fasting values, postprandial GIP responses in the two ESRD groups were lower (P=0.005), whereas absolute postprandial GLP-1 responses were higher compared with controls (P=0.002). Postprandial insulin responses were reduced (P=0.035) and glucagon responses were increased (P<0.001) in ESRD patients. None of these variables differed between the two ESRD subgroups. In conclusion, non-diabetic patients with ESRD are characterized by increased

absolute postprandial GLP-1 responses, reduced relative GIP responses, decreased insulin responses and exaggerated glucagon levels. These pertur-bations in the gut-pancreas axis may contribute to the disturbed glucose metabolism in ESRD patients.

2380-PO

2381-POThe Value of Urinary L-FABP,KIM-1,NGAL and Serrum Cystatin C in Predicting the Early Diabetic NephropathyYONG XU, MAOJUN YANG, XUEQIN ZHOU, WEI HUANG, FEI XIE, CHENLIN GAO, Luzhou, China

Nowadays early diagnosis of diabetic nephropathy(DN) is based primarily on urinary microalbumin.However,the early kidney damage with normal range urinary microalbumin is existed.It is necessary to seek a specifi c new marker for predicting early DN.Recent studies showed urinary L-FABP (liver-type fatty acid-binding protein), KIM-1 (kidney injury molecule-1) and NGAL (neutrophil gelatinase-associated lipocalin) were expressed in the proximal tubule and were increased signifi cantly in a variety of acute and chronic renal disease, positively correlated with the degree of renal injury.Serum cystatin C is more sensitive than serum creatinine for the detection of glomerular fi ltration rate.The purpose of this study is to investigate the levels of four biomarkers in type 2 diabetes patients(DM) with different degree of albuminuria and to explore the value of these biomarkers in predicting the early DN. 118 patients with type 2 diabetes and 41 control subjects were recruited. The diabetic patients were categorized into 3 groups according to their urinary albumin-to-creatinine ratio(UACR).Enzyme-linked immunosorbent assay were used to measure the levels of urinary L-FABP, KIM-1 and NGAL.Compared with the control group,urinary L-FABP,KIM-1,NGAL and serum cystatin C were signifi -cantly increased in the microalbuminuria group(P<0.05).All the four tubular biomarkers were increased in macroalbuminuria group whereas only urinary L-FABP and serum cystatin C were signifi cantly different among the three DM groups with different degree of albuminuria.After adjusting for several clini-cal parameters, urinary L-FABP and serum cystatin C were strong positively correlated with albuminuria (R = 0.719, 0.726,repectively P<0.01).Our study indicate that urinary L-FABP,KIM-1,NGAL and serum cystatin C were elevated in early DN whereas only urinary L-FABP and serum cystatin C can predict the severity of diabetic nephropathy.

Supported by: Affi liated Hospital of Luzhou Medical College

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2382-POSerum Fetuin-A Levels are Decreased in Type 2 Diabetes Patients With Overt NephropathyHYEONGKYU PARK, SUNGWAAN JEON, YEOJOO KIM, DONGWON BYUN, KYOIL SUH, MYUNGHI YOO, Seoul, Republic of Korea

Fetuin-A, a potent calcifi cation inhibitor, is a liver-synthesized protein that is secreted into serum. Fetuin-A can bind the insulin receptor and inhibit insulin signaling. Higher fetuin-A levels are related to obesity and insulin resistance, future risk of type 2 diabetes(T2DM), myocardial infarction, and ischemic stroke in the general population. In contrast, low levels of fetuin-A are associated with cardiovascular mortality in patients on dialysis. Therefore, the role of fetuin-A on vascular disease seems to be complex and not well defi ned. In this study, we assessed serum fetuin-A levels of 137 T2DM patients to investigate the relationships between fetuin-A and metabolic parameters and vascular markers such as pulse-wave velocity(PWV) and carotid intima-media thickness(IMT). Fetuin-A is signifi cantly associated with age(r=0.28, P < 0.05), body mass index(BMI; r=0.39, P < 0.001), estimated glomerular fi ltra-tion rate(GFR; r=0.18, P < 0.05), CRP(r= -0.21, P < 0.05), adiponectin(r= -0.34, P < 0.005), and resistin(r= -0.23, P < 0.05), while there were no associations with PWV, or carotid IMT. Fetuin A levels did not differ between patients with known cardiovascular disease(CVD) and those without known CVD. Serum levels of fetuin-A were signifi cantly lower in patients with overt proteinu-ria(158 ± 42 ug/ml), compared to those with normoalbuminuria(196 ± 43 ug/ml), or microalbuminuria(192 ± 56 ug/ml). When we analyzed the patients without known CVD, fetuin-A is associated with age, BMI, estimated GFR, PWV(r= -0.19, P < 0.05), adiponectin, and resistin. Multiple linear regression analysis showed that there is no signifi cant association between PWV and fetuin-A levels. In summary, our data suggest that lower fetuin-A levels are related to overt nephropathy, while there are no associations of fetuin-A with markers for macrovascular complications in T2DM patients.

2383-PO

2384-POIncidence of Chronic Kidney Disease by Hypertension Statusin a Community-Based Endocrinology Practice: Real World Impact of the 2013 Clinical Practice Recommendations for Blood PressureGRETCHEN A. PIATT, SWARNA VARMA, Ann Arbor, MI, Bridgeville, PA

Increased blood pressure (BP) is predictive of microvascular complications, including chronic kidney disease (CKD). Based on data from large, randomized controlled trials (RCT), the ADA 2013 Standards of Medical Care includes a modifi cation to the BP recommendations from a BP goal of < 130/80 mmHg to < 140/80 mmHg. We therefore aimed to determine the implication of the new BP standards compared to the previous standards on incident CKD in a

community-based endocrinology practice (CBEP) over 10 years. 301 consecu-tive patients seen in consultation for diabetes management in a CBEP com-prised the analysis cohort. To be included, a patient had ≥ 2 BP measurements without prevalent CKD. CKD was defi ned as eGFR < 60 mL/min/1.73 m2. All patients were 18 years or older with a diagnosis of diabetes before or during calendar year 2000. Average age was 56.8 years, 92.4% were Non-Hispanic white, 57.1% were female, and 16.9% had type 1 diabetes. At baseline, 42.2% had BP < 130/80 mmHg compared to 55.5% with BP < 140/80 mmHg. Over time, 85.4% of patients improved BP to < 130/80 mmHg compared to 84.7% who improved to 140/80 mmHg. 42.9% of patients developed incident CKD over 10 years. In determining the BP effect on CKD, 52.1% of patients who improved their BP control to < 130/80 mmHg remained free of CKD over the 10 year period (p<0.0001). Similarly, 51.4% of patients who improved their BP to < 140/80 mmHg remained free of CKD during the 10 year period (p<0.0001). These results highlight the feasibility of attaining high levels BP control and the impact on CKD in clinical practice. Additionally, the results confi rm the fi ndings of large RCTs that demonstrate little benefi t between BP cut points. Models of care that incorporate the 2013 clinical practice recommendations for BP and focus on secondary prevention of complications may lead to decreased morbidity for patients with diabetes.

2385-POAssociation between Arg913Gln Variation in SLC12A3 Gene and Type 2 Diabetic Nephropathy in ChineseLIMEI LIU, WEIJING ZHAO, CAN LI, MINGMING ZHAO, LANGEN ZHUANG, RONG ZHANG, TAISHAN ZHENG, MING LI, NIANSONG WANG, FENG WANG, KUNSAN XIANG, YUQIAN BAO, WEIPING JIA, Shanghai, China

Whether Arg913Gln variation in SLC12A3 gene contributes to the develop-ment of diabetic nephropathy remains controversial among different ethnic groups, such as Korean, Japanese and Caucasians. To explore the relationship between Arg913Gln variation(G→A)of SLC12A3 (solute carrier family 12 mem-ber 3) gene and diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) in Chinese. Two hundred and fi fty-eight Shanghai Han ethnic people with T2DM and eighty-two non-DM controls with normal OGTT detection were enrolled.According to albuminuric excretion rate (AER),T2DM subjects were sub-divided into three groups:non-DN group (DN0 group),microalbuminuria group (DN1 group) and macroalbuminuria group (DN2 group). PCR-sequencing was used to detect genotypes of Arg913Gln variation of SLC12A3 gene for groups. Genotypic and allelic frequencies and clinical characteristics were compared among the groups. Three genotypes were detected, i.e.GG, GA and AA genotype. In comparison with control groups,frequencies of GA+AA genotype and A allele in T2DM group showed elevated tendency (p>0.05 for each). There were no signifi cant differences in genotypic or allelic frequencies among DN0,DN1 and DN2 groups. The T2DM with GA+AA genotypic group exhibited increased TG, AER, FINS and HOMA-IR (P values were 0.047, 0.048, 0.001 and 0.002, respectively) when compared with GG genotypic group. Our data suggested that Arg913Gln(G→A)variation of SLC12A3 gene was not signifi cantly associated with T2DM and DN in Chinese. T2DM with GA+AA genotype showed signifi cant elevation in AER when compared with GG genotype, suggesting that the Arg913Gln(G→A) variation of SLC12A3 gene may predict the increase of albuminuria in T2DM patients in Chinese.

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2387-POUsefulness of Estimated GFR by Cystatin C from the Survey of the Relationship between Dipstick Proteinuria and Urine Albumin-Cre-atinine Ratios in Type 2 Diabetic PatientsATSUKO ABIKO, KENTARO SAKAI, YOSHINARI ARAI, YUKI NAGASHIMA, KEN TSUJI, HIDEMITSU SAKAGAMI, KANAKI ISHIZEKI, YUKIHIRO FUJITA, YUMI TAKIYAMA, MASAKAZU HANEDA, Asahikawa, Japan

We examine the urine dipstick test for the routine urinalysis of the diabetic patients, because direct measurement of urinary albumin is not readily avail-able for them every visit. We conducted a cross-sectional survey to examine the relationship between dipstick proteinuria (UP) and urine albumin-creati-nine ratios (UACR) in diabetic patients. We also characterized the patients who have negative UP with micro or macroalbuminuria. Single-spot urine specimens were collected from 855 (436M/419F) outpatients with type 2 diabetes between Sep. 2111 and Dec. 2111. To evaluate renal function, esti-mated GFR were calculated by serum creatinine (eGFRcre) and cystatin C (eGFRcys). The mean age was 64±13 years and the mean HbA1c was 7.1±1.1%. The prevalence of each UP (-),(±), (1+) and (2+) or more were 63.3, 17.8, 10.7 and 8.2%, respectively. The median UACR of each UP were 8.0, 49.9, 318.9 and 2287.1 mg/g Cr, and the mean eGFRcre/eGFRcys of each UP were 83.1/89.6, 79.1/82.5, 68.6/71.8 and 50.4/54.2 ml/min/1.73m2, respectively. In UP(-) patients, the prevalence of A1 (UACR<30mg/gCr) , A2 (UACR 30~299mg/gCr) and A3 (UACR>300mg/gCr) were 76, 23.3 and 0.7%. In UP(±) patients, the prevalence of A1, A2 and A3 were 35.3, 54.6 and 9.9%.

We compared the UP (-) patients with A1 (n= 411) and A2/3 (n=130). The mean age and HbA1c were signifi cantly higher in A2/3 than in A1 (p<0.01, respectively). eGFRcre were not signifi cant between A1 and A2/3, but eGFRcys were signifi cantly lower in A2/3 than in A1 (92.1±28.6vs. 82.1±28.0 ml/min/1.73m2, p<0.01). One hundred eleven patients in A2/3 could evaluate UP and UACR next year. The mean eGFRcys signifi cant declined 4.4ml/min/1.73m2/year in UP (-) A2/3 patients. In summary, our survey demonstrates that about a quarter of UP negative patients show micro or macroalbuminuria and the eGFRcys may be able to evaluate the early renal dysfunction for such a patients.

2388-PO

2389-POPrimary Study of Related Risk Factor about Adult Renal Post-Trans-plantation Diabetes MellitusWANG YING JI, CHEN PING, CHEN SHU, YANG HONG JI, Chengdu, China

Objective: To understand the incidence of renal post-transplantation dia-betes mellitus (PTDM)and screen related risk factors possibly of it to formu-late individual therapy after transplantation. Methods: We investigate 128 patients according to the diagnosis standards of PTDM (88 men, 40 women) which experienced allogeneic renal transplant surgery. The patients were divided into two groups (PTDM 51 patients,N-PTDM 77 patients. Age, body mass index (BMI), history, cholesterol, triglyceride, blood pressure, uric acid, dialysis, and postoperative immunosuppressive programs and the postop-erative acute rejection reaction were invegisted. The unconditional logistic regression mode for simple factors or multi-factors, chi-square test and t test were used. Results: Among 128 cases, average age (36.22±9.76y). The PTDM incidence of renal transplantation was 39.84% in our hospital.There were no statistical differences between the two groups in age, sex, BMI, blood pres-sure, blood lipids, blood uric acid and other basic treatment before operation (P>0.05). Single factor and many factors logistic regression analysis showed that the immunosuppression protocols using FK506 primarily and the acute rejection occurs were signifi cantly associated with PTDM (P<0.05).Conclusion: The incidence of PTDM was 39.84%in our hospital. The result was similar with other correlated studies in domestic and foreign. The immunosuppression protocols using FK506 primarily and the acute rejection occurred was inde-pendent risk factors of PTDM while dialysis and the dialysis time had no correlation with PTDM.

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2391-PODemographic and Clinical Factors Associated With Early Mortality Risk in ESRD Patients With Diabetes Mellitus Starting DialysisCRISTIAN SERAFINCEANU, VIVIANA IULIA ELIAN, ANNE MARIE CRACIUN, CRIS-TIAN NECULAESCU, DAN CIMPONERIU, DAN CHETA, Bucharest, Romania

Early mortality (EM), defi ned as all deaths registered in the fi rst three months after dialysis initiation, is frequently associated to patient’s characteristics at the moment of dialysis initiation. The aim of this study is to identify pos-sible demographic or clinical risk factors for early mortality in Romanian patients with diabetes mellitus (DM) and end stage renal disease (ESRD) initiated on dialysis.

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We have enrolled in an observational cohort study 788 DM patients (453 males), that started dialysis between 1996 and 2005 and have been followed up in our unit for at least three months or till their death. Demographic and clinical data were collected. The study population was analyzed using sub-groups based on gender, dialysis method and 3 months survival status.

The factors associated with a higher relative risk (RR) for EM in our cohort were: female gender (RR = 1.29; p= 0.02), late initiation of dialysis (RR=1.77; p< 0.0001), older age at initiation (RR=4.77; p< 0.0001) and hemodialysis as the initiation method (RR = 2.89; p< 0.0001). The relationship between female gender and early mortality was confi rmed for type 2 diabetes mellitus patients initiated on both hemodialysis (RR = 1.36; p= 0.013) and peritoneal dialysis (RR = 2.61; p= 0.001). Hemodialysis as fi rst method was associated with higher RR in males (RR = 4.54; p < 0.0001) than in females (RR = 1.89; p < 0.001). The RR related to late initiation was also higher in males (RR = 2.27; p< 0.0001) than in females (RR = 1.52; p = 0.01).

Besides age and late initiation, previously accepted as risk factors for EM, the present study show, for the patients with diabetes mellitus, the infl uence of gender (females are overall more prone to EM, especially for T2DM patients) and initiation method on EM rates.

2392-POEffects of Ramipril, Telmisartan and Amlodipine Medications on the Development of Diabetic Nephropathy and Advanced Glycation End Products in Patients With Type 2 Diabetes Mellitus and Hyperten-sionYAVUZ YALCIN, FUNDA YALCIN, GULAY KOCAK, ALPER AZAK, TURKAN METE, SERDAR GULER, MURAT DURANAY, Ankara, Turkey

Advanced glycation end-products and their receptors are thought to have an impact on the development and the progresssion of diabetic nephropathy. We aimed to evaluate the impact of ramipril, telmisartan and amlodipine medications on soluble RAGE (sRAGE) the subform of RAGE in patients with diabetes mellitus and hypertension without nephropathy.

This study is performed in Ankara Education and Research Hospital, Depart-ment of Nephrology out-patient clinic, patients with diabetes mellitus and hypertension and without nephropathy who are receiving ramipril and telm-isartan and amlodipine (n=20) medications at least for 6 months are enrolled, also 20 control patients diagnosed with diabetes mellitus but not hypertension are included as controls, in total 80 individuals are analyzed.

There was no statistically signifi cant difference between ramipril and telmisartan groups in terms of serum sRAGE levels (p>0,05). But in these two groups the results were signifi cantly lower than amlodipine and control groups (p<0,001). Serum sRAGE levels were similar in amlodipin and control groups (p>0,05).

By the end of two years, the data of 69 patients have been evaluated. Microal-buminuria has been diagnosed in total 9 patients which are; 2 patients in ramipril group, 3 patients in telmisartan group and 4 patients in amlodipine group. We did not reveal any signifi cant relationship between serum sRAGE and GFR, urinary albumin levels in microalbuminuric patients (R=0,249, p>0,05).

In hypertensive type 2 diabetic patients ramipril and telmisartan theraphies signifi cantly reduces sRAGE levels when compared to amlodipine treatment. Our results did not suppport any relationship between serum sRAGE and development of microalbuminuria. Our results comfi rms that different anti-hypertensive agents alternate serum sRAGE levels, but useing as a marker in development of nephropathy is still not clear.

2393-POFasting and Post Prandial C-peptide Index(CPI) are Predictive Indica-tors of Insulin Requirement for Diabetic End-Stage Renal DiseaseTERUKI KONDO, Nagano, Japan

Previously, insulin and limited oral hypoglycemic agents (glinides,αGIs) have been able to use for glycemic control of diabetic end-stage renal disease (ESRD) in Japan. With recent introduction of DPP-4 inhibitors (DPP4i) and GLP-1 R agonists for these patients, it is more diffi cult to identify the indica-tion of insulin therapy and other hypoglycemic agents.

Goto and Saisho reported fasting and post prandial C-peptide index (CPI= serum C-peptide/ plasma glucose×100) are predictors of insulin requirement for diabetic patients with normal renal function. Usually, serum C-peptide seemed to be poorly associated with insulin secretion and clinical phenotype of diabetic ESRD. We found distinction of CPI between insulin and other hypolycemic agent group of diabetic ESRD.

We evaluate the usefulness of fasting (f) and post prandial (pp) CPI for deciding insulin requirement of diabetic ESRD.

A total of 101 patients receiving regular hemodialysis in Nagano Chuo Hospital in 2011 were investigated. All patients were divided into nondiabetic

patients (34) and diabetic dietary (28), Glinide (11), DPP4i (12) and insulin (15) treatment groups. We mesured fasting and post prandial glucose, C-peptide, HbA1c and Glycoalbumin (GA). After calculation of f- and pp-CPI, we investi-gated the usefulness of CPI for deciding insulin requirement.

The mean age of the subjects are 69.4 y/o, male/female 62/39, mean dura-tion of hemodialysis 5.0year, fasting plasma glucose (FPG) 115.8mg/dl, f-C-peptide 7.3ng/ml, f-CPI 6.8, pp C-peptide 11.1ng/ml, pp-CPI9.1. Although both f- and pp-CPI have good relation to HbA1c and GA, pp-CPI and GA have better relation than f-CPI and GA.

From the investigation of relationship of CPI between various diabetic treat-ment, we assume that f-CPI<3 and/or pp-CPI<5 may be cut off for insulin requirement of japanese diabetc ESRD.

2394-POThe Change of Type 2 Diabetes With Diabetic Nephropathy on Plasma Brain Natriuretic Peptide Levels after Treatment by IrbesartanQI-YA HUANG, CAI-XIAN YANG, ZHI-MING MAI, DA-LI LIANG, JIE-FENG GUO, JUN-XING LIANG, SHAO-QING LI, WEN-JUNG JIA, LI YAN, Qingyuan, China, Guang-zhou, China

Objective: To investigate the possibility of brain natriuretic peptide as early new markers to diagnose diabetic nephropathy. Methods: 114 type 2 diabetes with diabetic nephropathy and 53 type 2 diabetes with normal urine protein were studied. According to urinary albumin creatinine ratio (ACR), the 114 type 2 diabetes with diabetic nephropathy were divided into two groups, 54 cases with macroalbuminuric (ACR≥300ug/mg) and the other 60 cases with microalbuminuria (30≤ACR<300 ug/mg). All patients were given Irbesartan 150 mg every day, continuous 24 weeks. The plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), Creatinine (Cr), glycated hemoglo-bin (HbA1c) and ACR were measured before and after treatment.The change before and after treatment of plasma NT - proBNP level and the relationship between NT - proBNP and Cr,ACR was compared. Results: After treatment, NT - proBNP of diabetic nephropathy declined obviously [macroalbuminuric group (180.01±168.79) vs (671.75±223.11) pg/ml, microalbuminuria group (61.08±43.11) vs (170.45±133.42) pg/ml, P<O.01].NT - proBNP has signifi cant correlation with ACR (r = 0.628, P = 0.000) and Cr (r = 0.551, P = 0.000). Conclu-sion: Irbesartan reduce urine protein of diabetic nephropathy, at the same time the NT - proBNP level fall subsequently. So the decline of kidney function lead to the raise of brain natriuretic peptide. brain natriuretic peptide may be becomes an early new markers to diagnose diabetic nephropathy and turn into supplementary means of estimate diabetic nephropathy.


2395-POMean QTc Interval in Patients With Type 2 Diabetes Is Associated With Heart Rate Variability During Night-Time but Not During Day-Time Continuous ECG RecordingSTAVROS LIATIS, PETROS THOMAKOS, STAVROULA KALOPITA, NICHOLAS KATSI-LAMBROS, KONSTANTINOS MAKRILAKIS, Athens, Greece

Type 2 diabetes (T2D) is a well identifi ed risk factor for cardiovascular disease and sudden death, while QTC interval is repeatedly found increased in T2D, often in association with cardiac autonomic neuropathy (CAN).

Aim of the present study was to investigate possible associations between QTC interval and cardiac autonomic nervous system function in patients with T2D, of relatively short duration, measured by continuous 24-hour ECG monitor-ing and examine these associations for possible effect of circadian rhythm.

A total of 116 T2D patients (67 men, aged 59.5±9.6 years, median T2D duration 6 years) underwent continuous 24-h ECG monitoring. The presence of CAN was assessed via the Ewing tests. Autonomic function was also assessed by measuring the spontaneous barorefl ex sensitivity (BRS) and heart rate variability (HRV) by frequency and time domain analysis. HRV and mean QTc interval were calculated during the 24-h ECG recording and analyzed for day and night separately.

24-hour mean QTc interval showed a weak but statistically signifi cant asso-ciation only with total power and low-frequency (LF) power of HRV (r=-0.216, P=0.02 and r=-0.201, P=0.03 respectively). During the day, no signifi cant asso-ciations were revealed between QTc and autonomic function parameters. During the night, QTc correlated signifi cantly to all HRV parameters both in frequency (total power, LF and HF) and time (PNN30, PNN50, rMSSD, SDANN) domain analysis, the strongest association being with total power (r=-0.315, P=0.001). No association was found between mean QTc and BRS. The mean QTc did not differ between day and night, while the LF/HF ratio (a measure of sympathovagal balance) decreased during the night.

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Mean QTc interval and HRV, both obtained by 24-h ECG monitoring, are inversely associated during the night but not during the day. This fi nding is possibly due to withdrawal of sympathetic activation during sleep and needs further investigation.

2396-POValidation of Neuropathy Symptoms Score (NSS) & Neuropathy Dis-ability Score (NDS) For Bed Side Diagnosis of Peripheral Neuropathy in Diabetic PatientsAASTHA CHAWLA, RAJEEV CHAWLA, AASTIK CHAWLA, GIRISH KUMAR BHASIN, Delhi, India

The symptoms of neuropathy & the conventional assessment of it with Cotton wool, Vibrating tuning fork, pin prick and hot and cold sensation can give only a qualitative diagnosis Biothesiometer (VPT) can quantify & pick up early cases of Diabetic Peripheral Neuropathy(DPN) & is considered a gold standard diagnostic tool. There are not much studies validating use of Neu-ropathy Symptoms Score (NSS) & Neuropathy Disability Score (NDS ) for Bed Side Diagnosis of DPN comparing it with VPT.

This study was carried out to Validate NSS & NDS usefulness as simple bed side screening modalities for DPN as per “Young et al” criterion & then to study DPN co-association with other diabetic complications.

855 Type 2 diabetes patients between July 2011-June 2012 were evaluated by NDS & NSS DPN was diagnosed clinically if NDS + NSS was > 10.

135 out of 855 patients who had NSS + NDS > 10 were evaluated by Bio-thesiometer to validate this score . VPT> 15 volts as mild & VPT >25 volts was considered as signifi cant DPN.

These patients were also evaluated for Microabluminuria, Retinopathy, PVD and Dyslipidaemia.

NSS+NDS > 10 N=135

Study Group

NSS+NDS < 10 N=720

Comparison Group

TotalN=855

No. of patients 135 720Age (Years) 57.6 + 9.2 55.6 + 7.8PVD by Hand Doppler 4.2% 3.9%Duration of Diabetes(Mean) Yrs 13.5 Yrs 11.8 YrsMicroalbumin uria 61.3% 38 %Dyslipidaemia 36.4 % 28 %Retinopathy 44.1 % 19.2%VPT > 15 volts 26.6% (N=36) 4.8%VPT > 25 volts 44.4% (N=60) 5.2%Prevalence of P-Neuropathy(Baye’s Theorem)

15.4%

VPT +ve 96 72 168VPT -ve 39 648 687

135 720 855Sensitivity 96/135 = 71.1%Specifi city 648/720 = 90%+ve Predictive Value 57.14%-ve Predictive Value 94.32%

Neurological examination like NSS & NDS is an important bed side tool for early diagnosis of DPN with a sensitivity of 71.1% & specifi city of 90%.

It is simple, acceptable, reproducible & validated as per our study.DPN has a strong co-association with other complications like DR (44.1%

vs 19.2%) and Microalbuminuria 61.3 % vs 38%.

2397-POAssociation between Chronic Kidney Disease and Cardiac Auto-nomic Neuropathy in Adults With Type 2 DiabetesYING-CHUEN LAI, LEE-MING CHUANG, Douliu City, Taiwan, Taipei, Taiwan

Cardiac autonomic neuropathy (CAN) is associated silent myocardial isch-emia and mortality. Diabetic nephropathy is considered to be an important risk factor of CAN. The aim of our study is to examine the relationship between the severities of kidney damage and CAN in adults with type 2 diabetes.

60 normal controls aged 47 ± 11 years and 193 patients with type 2 diabe-tes aged 61 ± 12 years were included. The glomerular fi ltration rate (GFR) was estimated. Chronic kidney disease (CKD) stages were defi ned according to the suggestions of the National Kidney Foundation. Heart rate variation (HRV) of one-minute deep breathing test was measured by a portable EKG recorder. Normal cardiac autonomic function was defi ned if maximal heart rate minus

minimal heart rate (HR Max-Min) > 15 beats/min. CAN was defi ned if HR Max-Min< 10 beats/min.

Compared with normal control, diabetic patients had a higher prevalence of albuminuria (35.8 % vs. 10.0 %) and CAN (27.5 % vs.3.3 %). An association between CKD stages and heart rate variability was observed in subjects with type 2 diabetes (ptrend = 0.007). Odds ratios (95%CIs) for CAN were 1 (refer-ence), 0.57 (0.25-1.30), and 2.67 (1.04-6.83) for CKD stage 1, stage 2, and stage 3 respectively. After adjustment for serum levels of HbA1c, total cholesterol and triglyceride, CKD stage 3 is still independently associated with the odds of CAN.

In subjects with type 2 diabetes, estimated GFR < 60 mL/min per 1.73 m2 was independently associated with impaired cardiac autonomic function, as assessed by heart rate variability. CKD is an important risk factor for CAN, which may require screening for cardiovascular disease.

2398-PO

2399-POCross Sectional Study to Evaluate the Effect of Duration of Type 2 Diabetes Mellitus on the Nerve Conduction Velocity in Diabetic Peripheral NeuropathyGAUGAR HUSSAIN, S. AIJAZ ABBAS RIZVI, SANGEETA SINGHAL, MOHAMMAD ZUBAIR, JAMAL AHMAD, Aligarh, India

To study the nerve conduction velocity in clinically undetectable and detect-able peripheral neuropathy in type 2 diabetes mellitus with variable duration. This cross sectional study was conducted in diagnosed type 2 diabetes mel-litus patients. They were divided in groups; Group I ( n= 37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n= 27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with T2DM patients (n=22) without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study. The comparisons were done between nerve conduction velocities of motor and sensory nerves in patients of clinically detectable neuropathy and patients without neuropathy in type 2 diabetes mellitus population. This study showed signifi cant electrophysiological changes with duration of disease. Nerve conduction velocities in lower limbs were signifi cantly reduced even in patients of shorter duration with normal upper limb nerve conduction velocities. Diabetic neuropathy symptom score (NSS) and Neuropathy dis-ability score (NDS) can help in evaluation of diabetic sensorimotor polyneu-

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ropathy though nerve conduction study is more powerful test and can help in diagnosing cases of neuropathy.

2400-POAssessment of Small Fiber Neuropathy through a Quick, Simple and Non-Invasive Method in a Diabetes Outpatient ClinicJEAN-HENRI CALVET, PETER SCHWARZ, Paris, France, Dresden, Germany

Sudomotor dysfunction is one of the earliest neurophysiologic abnormalities to manifest in distal small fi ber neuropathy. SUDOSCAN was developed to provide a non invasive, quick, simple and quantitative measurement of sweat function. This observational study aimed to assess the feasibility and useful-ness of sweat function assessment in a diabetes outpatient consult clinic.

The study was conducted on patients from a diabetes outpatient clinic in Germany with type 1 and type 2 diabetes. Sweat function was evaluated by measuring the electrochemical sweat conductance (ESC, expressed in micro-Siemens, µS) of the hands and feet. Patients were required to place their palms and soles - where sweat gland density is the highest - on two large stainless-steel electrodes on which a small current (<4V, direct current, DC) was applied, and then to stand still for 2 minutes. ESC is the ratio between current generated and the constant DC stimulus applied on the electrodes. A 1-year follow-up of ESC according to insulin administration was also assessed.

52 patients with type 1 diabetes and 115 patients with type 2 diabetes (69 receiving insulin) were involved in this observational study. Hand and foot ESC were lower in patients with type 2 diabetes when compared to patients with type 1 diabetes. During the 1-year follow-up, a slight decrease in hand and foot ESC was observed in patients with type 2 diabetes not receiving insulin, while an increase was observed in patients receiving insulin (-3.8±9.7 vs 1.0±9.7 µS, p =0.02 for the hands and -2.2±7.5 vs 4.1±8.8 µS, p<0.001 for the feet). No subject experienced discomfort during the tests.

This study shows that assessment of small C fi ber neuropathy through a quick, non invasive and quantitative measurement of sweat function can be performed in standard diabetes outpatient practice. The observation that ESC improves with insulin treatment must be confi rmed in a clinical study per-formed on a larger population.

2401-POCan You Hear Me? The Link between Diabetes and Hearing LossJOANNE K. RINKER, KATHY DOWD, Badin, NC, Charlotte, NC

Common complications of diabetes include kidney, eye, heart and nerve damage. An estimated 36 million people have some type of hearing loss (17%). NIH has found that hearing loss is twice as common in people with diabetes. Of the 79 million adults thought to have pre-diabetes, the rate of hearing loss is 30% higher than in those with normal blood sugar. The research suggests that diabetes may lead to hearing loss by damaging the nerves and blood vessels of the inner ear. Autopsy studies of diabetes patients have shown evidence of such damage. Additionally, 54% of people with diabetes had at least mild hearing loss in their ability to hear high-frequency tones, compared with 32% of those with no history of diabetes. 21% of participants with diabetes had at least mild hearing loss in their ability to hear low-to-mid frequency tones, compared with 9% of those without diabetes.

Diabetes patients need to be screened routinely for hearing loss, just as they are for eye and kidney problems. Patients need to then have more intense screening and treatment based on the results of a routine screening that can be done with an educator or at a provider offi ce. Treatment may include hear-ing aids or medications and the results can lead to improved job performance, improved memory, improved mood, less loneliness, increased alertness and ability to learn new things, decreased risk for personal safety, increased social activity, less fatigue, tension, stress, negativism, anger, better relationships with their families, better feelings about themselves, improved mental health, greater independence and security, better relationships with their families, better feelings about themselves, improved mental health and greater inde-pendence and security and overall decrease in depression. It is important for diabetes educators to add this screening to their curriculum, and have a pro-cess to refer patients from a DSME program to an audiologist who can do more extensive screenings and treatment, to improve the patients overall quality of life.

2402-POComparing Clinical Autonomic Neuropathy Grading With Newer Device ANSiscopeTMSHRIKANT S. SOMANI, ASHA N. SHAH, DHAVAL DOSHI, PATHIK M. PARIKH, ABHINAV JAIN, PINAKIN PATEL, Ahmedabad, India

Heart rate variability(HRV) is recommended test for detecting cardiovas-cular autonomic neuropathy(CAN) in diabetes. Fifty patients of Type 2 diabe-tes were classifi ed separately using Ewing’s and Bellavere’s criteria using heart rate response to expiration-inspiration, standing(30:15 ratio), Valsalva and blood pressure response to standing, isometric exercise and tested by ANSiscope and comparison was drawn.

On comparison of Bellavere’s and Ewing’s with ANSiscope grades, we got p value of 0.0007 and 0.01 respectively. Ewing’s can’t classify(30%) those patients who show abnormal blood pressure tests but only borderline dysfunc-tion in heart rate tests. Also as Bellavere’s criteria involve only heart rate tests, patients with dominant sympathetic neuropathy are likely to be missed.

Thus, ANSiscopeTM is a quick (5 to 7 minutes) and simple way (supine position without involvement of manoeuvres) for diagnosing early CAN and can become a standard measurement.

Correlation of ANSiscope autonomic dysfunction grades with those of Bella-vere’s classifi cationANS Grade Bellavere’s Grade Total

No CAN Early CAN Defi nite CAN Can’t classifyEarly 10 2 0 0 12(24%)Late 1 9 4 2 16(32%)Advanced 1 1 16 4 22(44%)Total (%) 12(24%) 12(24%) 20(40%) 6(12%) 50

Correlation of ANSiscope autonomic dysfunction grades with those of Ewing’s classifi cationANS Grade Ewing’s Grade Total

Normal Early Defi nite Severe Can’t classifyEarly 10 1 0 0 1 12(24%)Late 1 4 2 1 8 16(32%)Advanced 1 1 3 11 6 22(44%)Total(%) 12(24%) 6(12%) 5(10%) 12(24%) 15(30%) 50


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2404-POThe Levels of PEDF and TNF-α and NF-κB Increased in PBMCs in Diabetic RetinopathyYAN-MING CHEN, QIU-JU LV, PAN-WEI MU, XI-XIANG TANG, MAN-MAN WANG, LONG-YI ZENG, Guangzhou, China

Pigment epithelium derived factor (PEDF) has been widely implicated in chronic infl ammatory diseases, such as diabetes and its complications. How-ever, it remains unknown whether PEDF expresses in the peripheral blood mononuclear cells (PBMCs). This study aimed to investigate the role of infl am-atory factors such as PEDF, TNF-α and NF-κB in PBMCs in diabetes retinopathy(DR). Thirty-six healthy persons (control group), forty-one type 2 diabetes patients without retinopathy(DM group) and forty-two type 2 dia-betes patients with retinopathy (DR group) were enrolled. The levels of PEDF, TNF-α and NF-κB were measured by western blot in PBMCs. The levels of PEDF, TNF-α and NF-κB were statistically higher in DR or DM group than those in control group (P<0.05). The levels of TNF-α and NF-κB increased signifi cantly in DR group, as compared with those in DM group (P<0.05). The level of PEDF increased slightly but not signifi cantly in DR group than that of in DM group (P>0.05). Our data indicated PBMCs could express PEDF, which was markedly increased, accompanied with the elevation of NF-κB and TNF-α in type 2 diabetes patients especially in DR. These results suggested PEDF might contribute to DR via chronic infl ammation pathway.

Supported by: Science and Technology Development Program of Guangdong (2011B031800155)

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2407-POBaseline GAD Auto-Antibody Levels Do Not Predict Diabetic Retin-opathy in Youth With Type 1 DiabetesHEIDI HARO, GEORGEANNA KLINGENSMITH, BRIAN BUCCA, KIM MCFANN, CHIEN LAI, Aurora, CO

Studies on the relationship between GAD auto-antibodies (GADA) and diabetic retinopathy (DR) in those with type 1 diabetes (T1D) are inconclusive. We investigated the relationship between GADA and DR in subjects 12-25 years of age with T1D duration of > 5 years and an A1C <10%. Additional risk factors assessed include age, duration, sex, A1C, LDL, HDL, Triglycerides and BMI z-score.

Baseline GADAs 3-6m after diagnosis were available in 48 cases with DR (age 18.1+2.9 years, T1D duration 11.8+3.9 years, 37.7% male) and 54 controls without DR (mean age 14.6+2.9 years, T1D duration 8.4+2.3 years, 66.7% male). Retinopathy (>1 microaneurysms) was assessed by a single observer using 60 degree 2-fi eld fundus photography. Cases consisted of those with DR in either eye on two consecutive exams and controls were those without DR. Univariate logistic regression was used to examine whether GADA levels or other risk factors were associated with the presence of retinopathy. Step-wise logistic regression was used to see which variables were associated with retinopathy in a full model including age, duration, sex, A1c, LDL, HDL, triglycerides, and BMI Z-score. Log transformed variables were used in all analyses due to their skewed distributions. The Wilcoxon rank sum test was used to compare continuous variables between those with DR and those without.

Those with DR were older, had a longer duration of diabetes, higher trig-lycerides, higher diastolic blood pressure and higher weight. There was no association between GADA and DR, OR = 1.05 (0.83-1.33), p = 0.66. In a step-wise logistical regression, only age, OR = 1.35 (1.12-1.63), p = 0.002, duration, OR = 1.27 (1.05-1.54), p = 0.016, and female sex, OR = 6.07 (2.07-17.82), p = 0.001, were associated with DR.

Overall, we found no correlation between baseline GADA and the presence of DR (p=0.66). After adjustment for age, duration, sex, A1C, HDL and BMI z-score, only increased age (p<0.0001) and female sex (p=0.002) correlated with DR.

2408-PORelationship of Glucose Fluctuation, Microvascular Complications and Serum VEGF, PDGF-BB in Type 2 Diabetic PatientsLIJUAN XU, YUZHI YANG, KUN FENG, Harbin, China

To observe the correlation of glucose fl uctuation and diabetic microvascu-lar complications (diabetic retinopathy), and the relationship of glucose fl uc-tuation and serum vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB) in type 2 diabetic patients with HBA1c lower than 7.0%. 110 type 2 diabetic patients with HbA1c low than 7% were enrolled in Heilongjiang Provincial Hospital, divided into diabetic retinopathy (DR) group (n=57), and non-diabetic retinopathy (NDR) group (n=53) according to the results of Fluorescence fundus angiography and health control group (n=45). Indicators refl ecting blood glucose fl uctuation such as SDBG,MAGE, LAGE and MODD were recorded and calculated by CGMS. Levels of serum VEGF, PDGF-BB were measured by ELISA. (1) VEGF and PDGF were signifi cantly higher than DR group than in NDR group(P<0. 05). (2) There were signifi cant increases inSDBG, MAGE, LAGE and MODD in DR group compared with NDR group(P<0.05).(3) There was a signifi cant linear correlation between serum levels of VEGF and PDGF-BB and the glucose fl uctuation indexes of SDBG and MODD(P<0.05).(4) Pearson correlation analysis revealed that there was a positive relationship between serum VEGF, PDGF-BB and PPG, SDBG, MAGE and LAGE (P<0.05).

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DIABETIC DYSLIPIDEMIA

There was a signifi cant correlation between diabetic microvascular com-plications and blood glucose fl uctuation. Blood glucose fl uctuation might induce the increases of serum VEGF and PDGF-BB, involved into the develop-ment diabetic retinopathy.

2409-POUp-Regulation of VEGF mRNA by Advanced Glycation Endproducts in Hydroquinone-Treated Human Retinal Pigment Epithelial CellsHIROKI TSUJINAKA, ASAKO ITAYA-HIRONAKA, AKIYO YAMAUCHI, SUMIYO SAKURAMOTO-TSUCHIDA, HIROYO OTA, TAKANORI FUJIMURA, KATSUNORI NOCHIOKA, KIMIE SHIMOYAMA, NAHOKO OGATA, SHIN TAKASAWA, Sakurai, Japan, Kashihara, Japan

Age-related macular degeneration (AMD) is one of most important causes of blindness in the elderly population. AMD is generally divided into 2 main subtypes: the dry and exudative AMD. The dry form AMD was defi ned as progressive destruction of retinal pigment epithelial (RPE) cells. Exudative form AMD is characterized by choroidal neovascularization. In the present study, we examined the effects of advanced glycation endproducts (AGE) in hydroquinone (HQ)-treated human RPE cells. ARPE-19 cells, human RPE cells, were treated with HQ (20 µM) and/or AGE-BSA (0-300 µg/ml) for 12 hours. After the treatment, the viable cell numbers were measured by WST-8 method. The viable cell numbers were markedly reduced by HQ treatment, and the addition of AGE-BSA but not BSA increased the HQ-treated ARPE-19 cell numbers (P=0.0001) in a dose-dependent manner. We next examined apop-tosis of ARPE-19 cells by TUNEL method and found that HQ increased apop-tosis (P=0.0002 vs control) and that the AGE-BSA addition did not reduce the apoptosis of HQ-treated cells (P=0.6112). We then measured replicative DNA synthesis of ARPE-19 cells by 5’-iodo-2’-deoxyuridine (IdU) incorporation and found that the addition of AGE-BSA increased the IdU incorporation of HQ-treated ARPE-19 cells (P=0.0001), indicating that AGE increases ARPE-19 cell number by activating HQ-treated ARPE-19 cell replication. To verify what gene is activated for cell proliferation in HQ+AGE-BSA treated ARPE-19 cells, we performed real-time RT-PCR and found that VEGF mRNA was induced by HQ treatment and that the combined addition of AGE-BSA resulted in a further enhancement of VEGF mRNA (P=0.0025). These results suggest that dry form AMD may be induced by smoking (HQ) via apoptosis of RPE cells. While the accumulation of AGE by diabetes or aging enhances VEGF expression, it may cause proliferation of RPE and/or vascular cells by autocrine/paracrine mech-anism, resulting in exudative form AMD.

2410-POFree Mydriatic Fundus Photography for Diabetic Retinopathy Screen-ing and Risk Factors AnalysisPENGQIU LI, Chengdu, China

Objective: Use free mydriatic fundus photography to screen diabetic retin-opathy (DR) in type 2 diabetes mellitus (T2DM) patients and Investigate its risk factors.

Methods: 768 T2DM patients from department of endocrinology in our hospital were enrolled in this study. Weight, height, blood pressure and medical history were recorded. Serum levels of glucose, insulin, lipids, gly-cated hemoglobin and uric acid were measured. All patients underwent free mydriatic fundus photography, and were divided into two groups: non-diabetic retinopathy group (NC group) and DR group, in accordance with the 2002 DR international clinical staging.

Result: 317 out of 768 T2DM patients were suffered DR, total detection rate was 41.28%. compared with controls, DR group was older, and had higher lev-els of duration, systolic blood pressure (SBP), glycated hemoglobin and uric acid. Two logistic regression analysis showed that duration, sex, SBP and glycated hemoglobin were independent determinants of DR in T2DM patients.

Conclusion: DR in T2DM patients is quite common and closely associated with duration, sex, SBP and glycated hemoglobin .

Supported by: Project of Science and Technology Bureau of Sichuan Province

2411-POStudy of Risk Factors Associated With Type 2 Diabetes Patients With Diabetic RetinopathyKUN FENG, YU LIU, YU-ZHI YANG, Harbin, China

To determine the prevalence of diabetic retinopathy grading and related risk factors in patientswith type 2 diabetes. Questionnaires, laboratory tests, and non-madriatic photography were performed for 365 patients with type 2 diabetes. The prevalence of diabetic retinopathy classifi cation and the related risk factors including duration, glycated hemoglobin, 24h albumin, blood pressure, blood lipids were analysed. The overall incidence of the inci-dence of diabetic retinopathy was 71.52%, and 61.22% with Non-proliferative diabetic retinopathy VS 10.30% with proliferative diabetic retinopathy. There was a signifi cant difference between duration of disease in the two groups. 24h albumin and Systolic blood pressure of the proliferative diabetic retin-opathy group were signifi cantly higher than other groups(p<0.01). The inci-dence of diabetic retinopathy is high in patients with type 2 diabetes.

Multiple risk factors involved in its progression, positive and appropriate control of these risk factors may play an instructive role in prevention and treatment of diabetic retinopathy.


2412-POHow Successful the Statin Therapy Is Among Patients With Type 2 Diabetes? Results of the MULTI GAP Study (2009, 2010, and 2011)GYÖRGY JERMENDY, ISTVÁN KARÁDI, LÁSZLÓ MÁRK, GYULA PADOS, GYÖRGY PARAGH, ISTVÁN REIBER, ZOLTÁN KISS, Budapest, Hungary, Gyula, Hungary, Debre-cen, Hungary, Székesfehérvár, Hungary

The statin therapy is of great importance among patients with type 2 dia-betes (target value of serum LDL-cholesterol [LDL-C] <2.5 mmol/L or total cholesterol [TC] <4.5 mmol/L, with co-existing cardiovascular diseases <1.8 mmol/L or <3.5 mmol/L, respectively). The aim of our study was to evaluate the attainment of serum cholesterol target values in patients with type 2 diabetes treated with statins. As a part of the MULTI GAP (MULTI Goal Attain-ment Problem) survey, structured questionnaires were used in 2009 (1582 patients, 55.0% men), in 2010 (1159 patients, 58.4% men) and in 2011 (668 patients, 59.1% men). The main clinical fi ndings were as follows: age 64.1±9.9 - 65.4±9.2 - 66.2±9.8 year; weight 87.7±15.7 - 87.8±15.7 - 86.6±16,4 kg; BMI: 30.2±5.6 - 30.6±5.2 - 30.6±5.1 kg/m2), values in 2009, 2010 and 2011, respec-tively. The mean HbA1c values remained nearly unchanged (7.3 - 7.2%). In 2011, atorvastatin was used most frequently (46.0%; daily dose 32.9 mg) followed by rosuvastatin (29.2%; daily dose 19.5 mg) and simvastatin (18.3%; daily dose 19.8 mg). The TC values in 2009, in 2010 and in 2011 were 5.27±1.23 mmol/L, 4.90±1.30 mmol/L, and 4.88±1.29 mmol/L, respectively (p>0.05). The proportion of patients at TC target value of <4.5 mmol/L was 24.3%, 38.4%, and 40.4% while that of <3.5 mmol/L was 6.0%, 11.5%, and 12.0% (p<0.01; 2011 vs 2009). The LDL-C values were 2.94±1.04 mmol/L, 2.73±0.95 mmol/L, and 2.69±1.03 mmol/L, respectively (p>0.05). The proportion of patients at LDL-C target value of <2.5 mmol/L was 35.2%, 42.8%, and 47.8% while that of <1.8 mmol/L was 10.6%, 15.9%, and 16.8%, respectively (p<0.01; 2011 vs 2009). In 2009-2011, a slight improvement in serum cholesterol levels and a signifi cant increase of patients at target TC or LDL-C values were documented among patients with type 2 diabetes and cardiovascular diseases. More effec-tive treatment strategy is still needed in order to increase the proportion of patients with serum cholesterol values at target.

2413-POEvaluation of Residual Cardiovascular Risk in Patients With Type 2 Diabetes MellitusJASON S. REINGOLD, KHURRAM NASIR, NEEL R. PATEL, RAY POURFARZIB, DEBORAH WINEGAR, Atlanta, GA, Miami, FL, Maitland, FL, Raleigh, NC

Patients with Type 2 Diabetes Mellitus (T2D) are at increased risk of devel-oping cardiovascular disease (CVD). Current guidelines recommend treatment with lipid-lowering drugs to reduce LDL-cholesterol (LDL-C) to a goal of <100 mg/dL. Despite screening and LDL lowering therapy, diabetics continue to experience CVD events. In some cases, this residual risk may be explained by elevated LDL particle concentrations (LDL-P) however, low HDL particle (HDL-P) number may also contribute. Our goal was to assess variations in LDL-P and HDL-P concentrations in patients with T2D that may contribute to resid-ual CVD risk.

Data were derived from the LipoScience clinical database on subjects with complete lipid and NMR lipoprotein profi le data obtained from Jan 2010 to April 2012. Cases were patients with ICD 9 codes for T2D as reported by the

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ordering physician. Total cholesterol, triglycerides and HDL-C were measured using standard automated methods and LDL-C was calculated using the Frie-dewald equation. The NMR lipoprotein profi le was determined using a 400-MHz proton NMR analyzer.

The study population (n = 704) consisted of equal numbers of men and women (mean age 76 years). Mean lipid and lipoprotein levels were LDL-C: 92 + 37 mg/dL; LDL-P: 1190 + 437 nmol/L; HDL-C: 49 + 11 mg/dL and HDL-P: 35 + 6 umol/L. Most patients (67%) achieved LDL-C goals of <100 mg/dL whereas only 35% achieved comparable LDL-P goals of <1000 nmol/L. HDL-C and HDL-P levels were more closely correlated (r= 0.5691) but below recom-mended goals. Among patients meeting LDL-P goals of <1000 nmol/L, 21% had low HDL-P levels as did 24% of those with LDL-P levels >1600 nmol/L. Also, levels of both HDL-C and HDL- P varied little across a range of LDL-P concentrations.

In conclusion, the majority of patients in this cohort of T2D achieved primary LDL-C target goals but a signifi cant number failed to achieve LDL-P goals and had low HDL-P levels. This discordance may lead to increased residual CVD events and therefore warrant more aggressive lipid lowering treatment.

2414-POGlycemic Control Is Associated With Liver Enzymes in Patients With Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD)BARBARA IDZIOR-WALUS, ALEKSANDRA TROJAK, MALGORZATA WALUS-MIARKA, EWA WOZNIAKIEWICZ, MACIEJ T. MALECKI, Kraków, Poland

Non-alcoholic fatty liver disease is frequently found in patients with type 2 diabetes. NAFLD is associated with dyslipidemia, central obesity and insu-lin resistance.

The aim of this study was to assess the factors associated with glycemic control in patients with type 2 diabetes and NAFLD.

Material included 101 consecutive patients with type 2 diabetes, 72 with and 29 without NAFLD. In all patients standardized questionnaire, anthropo-metric measurements and laboratory tests were performed. Glycated hemo-globin A1c was analyzed by HLPC, serum lipid concetrations and enzymes by enzymatic methods. NAFLD was diagnosed by ultrasonography.

Mean age of patients was 53.1 ± 10.4 years in NAFLD group and 44.9 ± 10.9 years in patients without NAFLD (p<0.001). Mean duration of diabetes was 10 ± 6.3 years in patients with and 15.1 ± 7.8 years in those without NAFLD (p<0.001). Mean values of glycated hemoglobin A1c were similar in both com-pared groups with and without NAFLD: 9.1 ± 2.0% vs 8.4 ± 2.0% respectively. 86.2% of patients without NAFLD and 72.2% of patients with NAFLD were treated with insulin. NAFLD patients were characterized by signifi cantly higher values of alanine aminotransferase (p=0.033), and lower serum concentrations of HDL-cholesterol (p< 0.001) and creatinine (p=0.034).

In a group of patients with NAFLD signifi cant correlations between glycated hemoglobin and waist circumference (r=0.03188, p=0.1), LDL-C (r=0.2479, p=.048), HDL-C (r=-0.2602, p=0.038), gamma glutamyl transferase (r=0.3275, p=0.032) and alkaline phosphatase (r=0.5882, p<001) were observed. In patients without NAFLD the only signifi cant correlation between A1c and triglyceride level was observed (r=0.5122, p<0.009). No correlation between alanine aminotransferase and A1c was found.

The results of the study indicate that glycemic control in type 2 diabetes is associated with fatty liver disease as indicated by association with liver enzymes and with unfavorable lipid profi le.

2415-POSignifi cance of HDL Functionality (PON1) in Dysglycemic Young and Old AdultsTRUDY R. GAILLARD, KWAME OSEI, Columbus, OH

Introduction: Paraoxonase enzyme (PON1) has been implicated as a measure of the oxidative and antiproinfl ammatory indicators of HDL functionality. However, the role of dysglycemia (DYS) in PON1 in young (DYSY) and old (DYSO) individuals remains uncertain. Therefore, we examined PON1 and other CVD risk factors in DYSY and DYSO subjects.

Subjects and Methods: We studied traditional and nontraditional CVD risk factors in 118 nondiabetic adults categorized according to age ({DYSY, N=66} <50 years (38±7.1 yrs) and {DYSO, N=52} ≥ 50 years (56.3±4.4 yrs, p=0.0001). DYS was defi ned as either (fasting plasma glucose, >100-125mg/dl, 2 Hr glu-cose, 140-199mg/dl and/or A1C, 5.7-6.5%). Each subject completed standard OGTT with fasting and 2 hour serum glucose (GLU), insulin (INS) and c-peptide (C-PEP). Fasting blood samples were obtained for lipids/ lipoproteins, Apoli-poprotein A1 (Apo A1) and Apo B and HDL functionality (PON1) and hsCRP. Anthropometric parameters were obtained in each subject. Insulin resistance was calculated using HOMA-IR.

Results: DYSY had signifi cantly lower fasting GLU and AlC vs DYSO (92.5±10.9 vs 100.9±12mg/dl, p=0.0001 and 5.7±0.43 vs 6.0±0.45%, p=0.0001). There were no signifi cant differences in the fasting INS and C-PEP, nor the 2 hour GLU, INS, C-PEP and HOMA-IR among DYSY vs DYSO. We found statis-tically signifi cant lower SBP, total cholesterol, LDL-C, Apo A1 and Apo B in our DYSY vs DYSO. However, we found no differences in triglycerides, HDL-C and BMI among our groups. PON1 was signifi cantly lower in DYSY vs DYSO (0.48±0.26 vs 0.64±0.35ng/dl, p=0.004). In contrast, hsCRP was signifi cantly higher in DYSY vs DYSO (9.0±9.7 vs 5.9±6.5mg/dl, p=0.05).

Conclusion: We found DYSY appear to have alterations in nontraditional CVD risks factors that refl ect HDL functionality (PON1 and hsCRP). Therefore, screening for CVD risk factors in DYSY should include not only traditional but nontraditional CVD risk factors. Hence, DYSY should be targeted for appropri-ate CVD intervention.

Supported by: National Center for Advancing Translational Sciences (UL-1TR000090)

2416-POThe Prevalence of Vitamin D Defi ciency and its Association With Glucose and Insulin Resistance in Chinese Diabetes PatientsHUI SHENG, XUEFEI RUI, CHUNPING PAN, JUNLEI SU, CHENYU ZHAN, PENG YANG, CHUNJUN SHENG, WENJUN LI, HONG LI, SHEN QU, Shanghai, China

To evaluate the status of 25-hydroxyvitamin D [25(OH)D] and its association with glucose metabolism in the type two diabetes Chinese patients.

Plasma 25(OH)D was measured in a cross-sectional sample of 592 men and 543 women aged 30-80 years from Shanghai Chinese patients, who have been diagnosed with type two diabetes mellitus. Fasting plasma glucose, insulin, A1C were measured. Homeostasis model assessment of β cell function (HOMA-β) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated based on the above parameters.

The geometric mean of plasma 25(OH)D was 52 nmol/l, and percentages of vitamin D defi ciency [25(OH)D <50 nmol/l] and insuffi ciency [50 ≤ 25(OH)D <75 nmol/l] were 53.1% and 25.8%, respectively. Signifi cant inverse associa-tions existed between 25(OH)D with A1C and fasting plasma glucose and HOMA-IR(r=-0.066,p<0.05; r=-0.122, p<0.01; r=-0.091, p<0.01).

Vitamin D defi ciency is common in diabetic Chinese population. 25(OH)D level is signifi cantly negatively associated with plasma glucose and HOMA-IR, implying 25(OH)D might lower glucose through improve insulin resistance. Prospective randomized clinical trials are warranted to determine the role of 25(OH)D in regulating glucose metabolism.

Supported by: NSFC (30900698); Doctoral Fund of Ministry of Education (20090072120020)

2417-POA Comparison of Spontaneous and Two Different High Fat Diet Induced Metabolic Disease Models in Cynomolgus Monkeys and Characterization of Diabetic ProgressionXIAOYUN ZHU, LIANGZHI XU, Kunming, China

Cynomolgus monkeys serve as best animal model for human diabetics as the monkeys develop diabetes naturally with changes in plasma lipids and lipoprotein and pancreatic islet lesions similar to those that occur in human diabetics. Therefore, development of metabolic disease cynomolgus monkey models will be interested in both research community and pharmaceutical industry.

In this study, 327 aged cynomolgus monkeys (age: 13.05 ± 2.81 years; body weight: 7.39 ± 1.61 kg) were screened for the incidence of diabetes. The monkeys in the study were classifi ed into the following three stages: (A) normoglycemic monkeys, (N, FPG < 80 mg/dl), (B) prediabetic monkeys (PreDM, FPG: 80-125mg/dl), and (C) monkeys with type 2 diabetes (T2DM, FPG ≥ 126 mg/dl). To develop a robust metabolic disease model, two groups of monkeys (31 each group) containing similar N, PreDM, or T2DM animals were fed separately with two different high fat diets: HFD1 (21.50% protein, 20.9% fat and 42.40% carbohydrate) or HFD2 (11.80% protein, 24.50% fat and 42.70% carbohydrate). After 4 months on HFD, the monkeys were evaluated for the diabetic progress and lipid profi le. Among monkeys on HFD1, 25% N advanced into PreDM with increase of FPG/FPI (13.39%/486.58%) and 28% PreDM became T2DM with increase of FPG/FPI (87.78%/79.23%); triglycerides (TG) increased 169.57%, HDL, LDL, and total cholesterol (TC) did not change sig-nifi cantly. Among those fed with HFD2, 78% N became PreDM with increase of FPG/FPI (18.69%/66.86%), 10% N advanced into T2DM with increase of FPG/FPI (72.26%/-7.23%), and 40% PreDM progressed to T2DM with increase of FPG/FPI (49.74%/133.14%); TG increased 103.60%, HDL increased 67.47%, LDL increased 242.37%, and TC increased 140.15%.

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In conclusion, the spontaneous and HFDs induced cynomolgus monkey models in a range of metabolic disease stages will promote our understand-ing of metabolic disease and facilitate drug discovery.

2418-POF-2 Is a Natural PPARα/γ Dual Agonist for the Treatment of DiabetesLI FENG, Shanghai, China

The nuclear receptor transcription factor Peroxisome proliferator-activated receptor gamma (PPARγ) plays a central role in glucose metabolism, while PPARα mainly regulates lipoprotein metabolism. Targeting PPARα/γ is a strategy for the treatment of dyslipidemia and hyperglycemia. However, cur-rent PPARα/γ-targeting drugs are characterized by undesirable side effects. Natural products may provide a structurally diverse resource to alleviate the complex metabolic disorders. We used chimeric PPARα/γ reporter assays to screen natural compounds. To test the effects on lipid metabolism, 3T3-L1 pre-adipocytes were treated with the compounds (0-25µmol/L). Adipocytes differentiation/lipid accumulation was evaluated by oil red O staining. To elucidate the mechanism of compounds on the metabolism of 3T3-L1 and HepG2 cells, gene expression assay was performed with a real time RT-PCR. The db/db mice were treated with F-2 by intragastric administration and the fasting blood glucose, glucose tolerance test, serum lipid profi le and the liver lipid contents were analyzed to determine therapeutic effects in vivo. We found that compound F-2 activated the full-length PPARα and γ transcription activities and stimulated the differentiation of 3T3-L1 pre-adipose cell lines potently. In db/db mice, F-2 lowered signifi cantly fasting blood glucose, improved glucose tolerance test and lowed serum triglyceride content. Using real-time RT-PCR assay, gene expression analysis revealed that F-2 upregu-lated the expression of PPARα/γ target genes in 3T3-L1 and HepG2 cells, indicateing that F-2 lowers blood glucose levels and improves serum lipid profi les through the enhancement of PPARγ and PPARα transactivities. Our data suggest that the natural PPARα/γ dual agonist may be developed as a promising approach to combat metabolic disease.

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2420-POOne Undescribed Compound, Isolated from Crotalari, Inhibits Adipo-cyte Differentiation via Inhibition of PPAR-gammaYU ZHANG, Shanghai, China

Genus Crotalaria, belonging to Fabaceae family, is known to be a rich source of pyrrolizidine alkaloids (PAs). We found one undescribed compound (Com-pound 1), belongings to isofl avones from Genus Crotalaria. To test its effects on lipid metabolism, 3T3-L1 adipocyte were treated with Compound 1 (0-50µmol/L). Adipocyte differentiation/lipid uptake was evaluated by oil red O staining. We mimicked hyperglycemia by exposing HepG2 cells to high glucose and the cells were treaded with Compound 1. The hepatic lipid con-tents were measured. To elucidate the mechanism of Compound 1 on the metabolism of 3T3-L1 and HepG2 cell, we used reporter assay and gene expression analysis.

We found that the Compound 1 was able to inhibit the 3T3-L1 differentia-tion and reduced the hepatic lipid contents in HepG2 cell. In reporter assay and gene expression analysis, we found Compound 1 inhibited peroxisome proliferator-activated receptor γ (PPARγ) transactivity signifi cantly and the expression of its target genes. The results indicated that Compound 1could inhibit 3T3-L1 adipocyte differentiation and decreased the hepatic lipid accu-mulation in HepG2 cell via the inhibition of PPAR-γsignaling.

Our data suggest that Compound 1 is a PPARγ antagonist and it may be used for treatment of obesity and hepatic steatosis.

2421-POHigher Hepatic Fat Content in Type II Diabetics Compared to Hyper-lipidaemic Male Subjects With NGTLANA KOSI, YVONNE WINHOFER, MIRIAM LEITNER, GIOVANNI PACINI, ANTON LUGER, ALEXANDRA KAUTZKY-WILLER, Vienna, Austria, Padova, Italy

Background: Elevated hepatic fat is common in type 2 diabetes (T2DM)and hyperlipidaemia and associated with an increased risc for liver fi brosis/cir-rhosis and cardiovascular events. The aim of this study was to compare the extent of hepatic fat content in T2DM with NGT (normal glucose tolerance) subjects.

Methods: 20 T2DM and 20 hyperlipidaemic NGT male patients treated at our outpatient clinic of the Medical University of Vienna were included in the study. All underwent magnetic resonance spectroscopy which was performed with 3 Tesla Siemens MRT. The non-diabetic subjects recevied a 3-hour 75g oral glucose tolerance test.

Results: The mean age in the diabetic group was 55,9±7,2, weight 88,3±17, BMI 31,6± 5,1kg/m2 and duration of diabetes 6±4 years. In the NGT group the mean age: 46.6±10a, BMI: 28.7±3.9kg/m². All patients recieved statin therapy, the NGT group fi brates.

The hepatic lipid content was signifi cantly higher in type 2 diabetics than in the NGT group (9,75±7,3 % vs 3,25±7,3 %, p=0.001).

Plasma lipids were similar in both groups (T2DM: 260,3 ±130 mg/dl vs 295,3±160,0, p=n.s.) and correlated positively with the hepatic fat content especially in the diabetic group (rS=0.35; p=0.009).

To conclude type 2 diabetes is associated with elevated hepatic content, signifi cantly higher than in the NGT group. In both groups the plasma lipids strongly correlated with hepatic fat content, especially in the NGT group. Type 2 diabetes per se is a risc for developing fatty liver as well as hyper-lipidaemia although in a smaller extent when compared to T2DM. Further bigger studies are needed to confi rm our fi ndings. hence regular performance of an OGTT in men at increased cardiovascular (CV)-risk should avoid delayed diagnosis of diabetes in this young population because with the onset of diabetes the hepatic fat content and CV risk increase enormly and should be diagnosed and treated as soon as possible to prevent CV events.

2422-POApolipoprotein B/A1 Ratio Is Independently Associated With Insulin Resistance and Adiponectin in Metabolic SyndromeMIN KYUNG KIM, JIYOON HA, CHANHEE KYUNG, SOHEE KIM, HAERI BAEK, JIWOON KIM, JI SUN NAM, TAE WOONG NOH, SHINAE KANG, JONG SUK PARK, CHUL WOO AHN, KYUNG RAE KIM, Seoul, Republic of Korea

Recent studies indicate that apolipoprotein B to A-1 ratio (apo B/A-1) is a predictor of atherosclerotic vascular disease. The aim of this study was to assess the association of apolipoprotein B/A1 ratio with insulin resistance and adiponectin in metabolic syndrome.

Metabolic syndrome was defi ned according to the updated National Cho-lesterol Education Program Adult Treatment Panel III criteria applying the Asia-Pacifi c World Health Organization guidelines for WC. Total 1653 meta-bolic patients were enrolled in this study. BMI, WC, and serum concentration of apolipoprotein B, apolipoprotein A1, glucose, lipids (triglycerides, HDL cho-

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lesterol, and total cholesterol) and adiponectin were measured. Insulin resis-tance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). PWV was evaluated to assess arterial stiffness.

Apolipoprotein B/A1 ratio signifi cantly correlated with total cholesterol (γ=0.349, P<0.01), TG (γ=0.191, P<0.01), LDL-C (γ=0.271, P<0.01), HDL-C (γ= -0.309, P<0.01), adiponectin (γ= -0.142, P<0.01), HOMA-IR (γ=0.048, P=0.049), insulin (γ=0.065, P=0.048), and peripheral PWV (γ=0.043, P=0.083). Multple regression analysis showed that Apolipoprotein B/A1 ratio was signifi cantly associated with total cholesterol (β=0.360, P<0.01), TG (β=0.175, P<0.01), HDL-C (β= -0.325, P<0.01), HOMA-IR (β=0.057, P=0.04) and adiponectin (β= -0.160, P<0.01).

Adiponectin and insulin resistance are important independent factors asso-ciated with Apolipoprotein B/A1 ratio in metabolic syndrome.

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2426-POEvaluation of LDL and HDL Particle Concentrations Following Roux-en-Y Gastric Bypass in Obese DiabeticsG. LYNIS DOHM, WALTER J. PORIES, JOHN R. PENDER, WILLIAM H. CHAPMAN, MELISSA A. REED, ED TAPSCOTT, ALLAN SMITH, RITA BOWDEN, RAY POURFAR-ZIB, DEBORAH WINEGAR, Greenville, NC, Raleigh, NC

Obesity and type 2 diabetes (T2D) are associated with increased risk of CVD and CVD risk correlates with lipoprotein particle concentrations: high LDL-P is predictive of high CVD risk while high HDL-P is protective. Roux-en-Y gastric bypass (RYGB) has been shown to reduce CVD morbidity and mortal-ity and to improve LDL and HDL cholesterol levels but effects on LDL-P and HDL-P have not been studied.

We aimed to test the hypothesis that RYGB will lead to lower LDL-P and and/or higher HDL-P concentrations in obese T2D patients.

Nine morbidly obese diabetic women were studied before and after RYGB compared to a non-surgery control group of 9 lean females. Fasting plasma obtained 1 week prior to surgery and 1 week and 3 months post surgery was analyzed for lipoprotein particle concentrations by NMR spectroscopy.

Prior to surgery, LDL-P concentrations tended to be higher and HDL-P con-centrations lower in obese T2D patients compared to lean controls but the differences were not statistically signifi cant (Table). Following RYGB, both BMI and fasting glucose signifi cantly improved but there was little change in LDL-P levels, even after 3 months post-surgery. In contrast, HDL-P levels were signifi cantly reduced within 1 week of RYGB.

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FOOT CARE—LOWER EXTREMITIES

These early changes in LDL-P and HDL-P after RYGB do not predict a reduc-tion in CVD risk. Changes in other risk factors such as infl ammation and dia-betes status may better explain the improved CVD risk profi le following bariatric surgery.

2427-PO

2428-POEffect of Fenofi brate on Renal Function in Korean Type 2 Diabetic PatientsCHANHEE KYUNG, SOHEE KIM, HAERI BAEK, JIYOON HA, MIN KYUNG KIM, JIWOON KIM, JI SUN NAM, TAE WOONG NOH, SHINAE KANG, JONG SUK PARK, CHUL WOO AHN, KYUNG RAE KIM, HYUNJEONG LEE, Seoul, Republic of Korea

It is known that fenofi brate may affect the renal function through several studies. But the exact mechanism is not understood and it has not been studied that fenofi brate affect the renal function in especially in Korean elderly type 2 diabetic (T2DM) patients. Therefore we attempt to study the effect of

fenofi brate in Korean T2DM patients over the age of 60 through the various factors that refl ect the renal function.

From January 2007 to October 2012, We retrospectively evaluated the effect of fenofi brate (160mg/day) in 142 patients (30-60 years; 70 patients, 61-80 years; 72 patients) with T2DM and dyslipidemia. In this study, we moni-tered renal function through serum creatinine, cystatin C and estimated glomerular fi ltration ratio (e GFR) before fi brate treatment and 3 months after fi brate treatment. Patients who were started a new medication after fi brate add-on treatment or had a serum creatinine concentration greater than 2.0 mg/dL, or chronic liver disease, were excluded from the study.

Serum creatinine (1.09 ± 0.28 vs. 1.19 ± 0.33 mg/dL, P <0.001) were increased signifi cantly in total patients after 3 months fenofi brate treatment while e GFR decreased. (71.8 ± 21 vs. 65.9 ± 19 ml/min/1.73m2, P <0.001).

Serum cystatin C increased in total patients, but was not statistically sig-nifi cant. (1.01 ± 0.32 vs. 1.04 ± 0.36 mg/L, P=0.066). Cystatin C increased signifi cantly in elderly (age; 61-80 years) patients. (1.11 ± 0.30 vs. 1.17 ± 0.36mg/L, P=0.007) and decreased in young (age; 30-60 years) patients but was not signifi cant (0.92 ± 0.30 vs. 0.91 ± 0.31mg/L, P=0.671)

Increased concentration of serum cystatin C, an independent marker of renal function accompanied by the increases in serum creatinine and the decreases in e GFR observed in elderly patients. These suggest that fenofi -brate may impair renal function especially in elderly patients. Therefore, we suggest that renal function should be closely monitored in elderly T2DM patients when they are started with fi brates treatment.

2429-POEvaluation of PTS CardioChek Meters to Measure Blood Lipid Levels in RodentsQINGYUN YAN, YIMIN ZHU, SASWATA TALUKDAR, MARTIN B. BRENNER, MYLENE PERREAULT, Cambridge, MA

Type 2 diabetes is a metabolic disorder characterized by peripheral insulin resistance and hyperglycemia that is associated with multiple comorbidities, including obesity and dyslipidemia. Measurement of circulating lipid levels in animal models of obesity and type 2 diabetes is often hindered by the fact that most commercially available assays are designed for humans and/or require large amounts of blood. The PTS (Polymer Technology System) Car-dioChek is a simple and convenient way to measure total cholesterol (Chol), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C) and triglycerides (TG) in real time and has been FDA cleared for its use in humans. However, given the simplicity and relative accuracy of this approach in man, it is noteworthy that the applicability of this system has not been investigated in rodent research. To this end, we evaluated the CardioChek strips using capillary, venous and arterial blood from different rodent strains, and compared the results against a clinical analyzer and other commercially available kits to obtain a clear indication of the accuracy and correlation between these methods. In fed ob/ob mice, we observed a very high degree of correlation between the Car-diochek strips and data obtained from a clinical analyzer, with correlation factors of 0.885 for TG and 0.850 for Chol. After a 4 hour fast, the correlation factors were 0.7684 and 0.7527 for TG and Chol, respectively. Overall, we found that the simplicity, portability, speed and relative ease of operation are benefi cial to researchers for lipid prescreen and longitudinal studies in mod-els where small amounts of blood are available. However, the system in its current design limits its use to few strains because of signifi cant differences in lipid levels between rodents and humans.


2430-POFrequency of Risk Foot among Type 2 Diabetic Patients With Appar-ent Healthy FootPAULA BALDERRAMO GIL, MARIA EUGENIA LOZANO, SUSANA CAROLINA BER-TOLA, JORGE WAITMAN, Córdoba, Argentina

Lower limb amputation is perhaps the most feared complication among DM patients. At diagnosis, 8% of T2DM patients present diabetic neuropathy and 7.8% of neuropathic patients develop foot lesions each year. However, risk foot frequency has not yet been established.

A cross-sectional study was conducted to determine risk foot frequency among asymptomatic T2DM patients without foot lesions, and assisted at the multidisciplinary healthcare unit between July 2011 and November 2012. An educational activity with audiovisual support, graphic material delivery and neurological (Neuropathy Symptom Score, modifi ed Neurological Dis-ability Score), vascular (symptoms evaluation, peripheral pulses and ankle-brachial index), orthopedic and infectious assessment (Infectious Diseases

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Society of America guidelines) was conducted. Risk foot was defi ned as the presence of peripheral vasculopathy, neuropathy associated or not to ortho-pedic disorders or mixed pathology.

Patients: 256 (63% oral antidiabetics, 35% insulin, 2% lifestyle modifi ca-tions) 56% male, age 56±7 yrs, 55% <5 yrs from diagnosis. HBP 69.5%, dys-lipidemia (DLP) 48%, smoking 24 %, micro/macrovascular complications 21.4% /26%. Risk foot rate: 74% (39% neuropathy + orthopedic alterations, 17% neuropathy, 15% mixed condition, 3% vasculopathy). Frequency was higher in those with longer diagnosis periods (<5 yrs vs >15 yrs p=0.04). Around 85% never received education on foot care, and from these 71% presented risk foot (p=0.04). A statistically signifi cant relationship between vasculo-pathic risk foot and either DLP (p=0.01) or macrovascular complications (p<0.0001) was found.

A high risk foot frequency was found among patients with apparent healthy foot. Those T2 diabetic patients with longer time from diagnosis and no pre-vious education on foot care were the most affected. We consider that an early education focused on the incorporation of foot care habits and intensi-fi ed multifactorial treatment is priority to prevent future lesions.

2431-POThe Role of Collagen Neoepitopes Generated by Oxidative Stress in the Pathogenesis of Charcot NeuroarthropathyPAOLA RIZZO, DARIO PITOCCO, GIUSEPPE SCAVONE, ENRICO DI STASIO, FED-ERICA COSTANTINI, ROCKY STROLLO, MARCO GALLI, PAOLO POZZILLI, GIOVANNI GHIRLANDA, AHUVA NISSIM, Rome, Italy, London, United Kingdom

A feature of Charcot neuroarthopathy (CN) is the presence of an acute infl ammation which might cause an high consumption of oxygen and the for-mation of highly reactive oxygen species (ROS). ROS together with Advanced Glycation End-products (AGE) oxidize extracellular proteins altering theirs structure and antigenic characteristics that may affect antigen recognition in immune response.

Aim of this is to establish a potential relationship between CN and oxida-tive modifi cations of collagen type I and II.

Sera from patients with Charcot neuroarthropathy (CN), diabetic neuropa-thy (DN), only type 2 diabetes without complications (D) and healthy controls (H) were tested for the presence of autoantibodies against native collagen type I and II (CI and CII), and post-translationally modifi ed CI and CII using reactive oxygen species (HOCl, H2O2, ONOO-).

We show a signifi cant increase in binding of Charcot serum samples to native and ROS modifi ed CII, as follows: CII native: Ch vs D (p=0.011); CII gly-cated: Ch vs H, Ch vs D (p=0.000); CII HOCl: Ch vs H, Ch vs DN, Ch vs D (p=0.000); CII H2O2: Ch vs H, Ch vs DN, Ch vs D (p=0.000); CII ONOO-: Ch vs H (p=0.007). We also show reactivity against CI: CI native: Ch vs D (p=0.000); CI HOCl: Ch vs D, Ch vs H (p=0.000); CI H2O2: Ch vs D, Ch vs H (p=0.000); CI ONOO-: Ch vs DN, Ch vs D, Ch vs H (p=0.01).

We demonstrate for the fi rst time that the exposure to free radicals in Charcot foot can elicit autoimmunity leading to the formation of post-trans-lationally neoantigenic epitopes on the extracellular matrix components, directly affecting the bones and joints of the foot.

2432-POLimb Salvage With Transmetatarsal Amputations (TMA) at the Carl T. Hayden VA Medical CenterJAMINELLI BANKS, ROBERT FRYKBERG, ROBERT GIFFORD, EDWARD TIERNEY, Phoenix, AZ

Purpose: The value of the TMA in the diabetic population is often debated. There have been few studies analyzing outcomes when comparing various risk factors. This study aims to assist physicians in predicting outcomes of a TMA in the presence of various risk factors and correlate its effects on surgi-cal results and healing rates when dealing with limb salvage in the diabetic population.

Methods: A retrospective cohort study design was used. Twenty patients with a TMA at Carl T. Hayden VAMC were included in this analysis. Risk fac-tors including smoking, diabetic status, peripheral arterial disease (PAD), chronic kidney disease (CKD), presence of infection, HgbA1C, elevated fi brin-ogen and homocysteine were recorded as well as healing rates, time to heal, and post-operative complications.

Results: Average age of patients (all male with type II DM) was 63 years. Overall healing rate was 63%. There was a 60% post-operative complication rate overall. Overall healing rate in those with PAD was 54% vs. 83% in those without PAD. 100% of those with WBC >12.0 had post operative complications. Average time to heal in smokers was 172 days vs. 134 among non-smokers. Healing rate was 54% among smokers and 71% among non-smokers. Post operative complication rate in those with CKD was 86% vs. 54% in those

without. Healing rate of those with elevated fi brinogen levels at time of sur-gery was 44%.

Conclusions: Risk factors of PAD, smoking and elevated plasma fi brinogen levels all correlated with lower healing rates. Those who were more likely to experience post-operative complications were those with PAD, WBC> 12.0, CKD, smokers, elevated fi brinogen levels. We are currently performing sta-tistical analysis to assess the strength of our data as well as increasing the sample size to provide more defi nitive information. These preliminary fi ndings are somewhat helpful in shedding more light on which risk factors may infl u-ence healing rates and with which risk factors one can expect more complica-tions post-operatively.

2433-POInfl uence of Blood Glucose Fluctuation on Diabetic Foot in Patients With Diabetes MellitusLU ZUQIAN, CHI JIANCHANG, ZHANG XINGZHE, LI XIANG, JIANG YUFENG, XU ZHANGRONG, Beijing, China

To identify the risk factors for the occurrence and development of diabetic foot (DF) in patients with type 2 diabetes, and especially blood glucose fl uc-tuations on DF. 192 cases of non-diabetic foot (NDF) and 575 cases of DF patients were enrolled in the study. 575 cases of DF patients are not only divided into DF three groups (Wagner 1 and 2 grade, Wagner 3 grade, and Wagner 4 and 5 grade), according to the severity of DF; but also divided into DF with amputation and without amputation groups. Retrospective analysis study general factors, biochemical parameters, blood glucose levels, the standard deviation of blood glucose (SDBG), the coeffi cient of variation (CV-FPG), and large amplitude of glycemic excursions (LAGE). Each group was compared blood glucose fl uctuations differences. Data shown that the DF patients had more increased age, diabetic course, serum creatinine, uric acid, hyper-sensitivity C reaction protein (hsCRP), urinary albumin creatinine ratio (Alb/Cr),SDBG,CV-FPG, and LAGE compared to the NDF patients. However, total protein, serum albumin, total cholesterol, triglyceride and low density lipoprotein cholesterol decreased in DF group. Moreover, only the hsCRP, SDBG and CV-FPG (P<0.05) was statistically different between the DF and NDF groups. Compared with NDF group, the DF with amputation group had signifi cantly increased SDBG, CV-FPG and LAGE (P<0.05).in addition, SDBG also showed statistically signifi cant different between DF with amputation and without amputation groups (P<0.05).Logistic regression analysis showed that hsCRP, Alb/Cr, serum albumin, SDBG and CV-FPG were the independent risk factors for diabetic foot; and also SDBG was the independent risk factor for amputation in DF patients. Our results indicate that serum hsCRP, albumin, urinary Alb/Cr, SDBG and CV-FPG may be associated with diabetes foot closely related to the occurrence and development.

2434-PONotch-1 Signaling Is Activated in Diabetes and Contributes to Defec-tive Wound HealingVIVEKANANDA GUPTA SUNKARI, ILEANA RUXANDRA BOTUSAN, JACOB GRÜN-LER, ANCA IRINEL CATRINA, XIAOWEI ZHENG, KERSTIN BRISMAR, SERGIU-BOGDAN CATRINA, Stockholm, Sweden

Diabetic wounds are characterized by impaired coordination of several mechanisms essential for healing as cell proliferation, cell differentiation and angiogenesis.

We have proposed to study the modulation of the Notch system in diabetes and its potential relevance for defective diabetic wound healing since Notch signaling plays a major role in cell differentiation and angiogenesis. It is a cell-cell signaling system that activates after proteolytic cleavage (by γ-secretase complex) of the intracellular domain of one of its receptors (Notch 1-4).

The modulation of Notch system by hyperglycemia was studied both in vitro and in vivo using the corresponding technique (WB, reporter gene assay or RT-PCR). The functional consequence of the notch system modulation was studied in vitro by assessment of the cell migration and angiogenesis and in vivo by the effect on wound healing rate in diabetic mice (db/db or streptozo-cine-induced). Notch signaling was blocked either nonspecifi c by γ-secretase inhibitors (GSI) or specifi c by siRNA silencing of the Notch receptors (1-4) or by using “cre-lox” system.

We could show that hyperglycemia activates Notch pathway at multiple levels. The overactivation of Notch signaling had pathogenic consequences since the repressive effect of high glucose on migration (fi broblasts) and angiogenesis (endothelial cells) was cancelled after blocking the notch signal-ing either with GSI or by specifi c silencing of Notch 1. Moreover local treatment with GSI improved the wound healing in diabetic mice followed by an increase in granulation, epidermal formation and blood vessel formation.

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The central role of Notch-1 signaling was confi rmed by a better wound healing rate in diabetic animals in which Notch-1 signaling was specifi cally knock out in skin.

In conclusion hyperglycemia activates Notch1 signaling that impairs wound healing rate in diabetic animals.

2435-PO

2436-POPatients With Diabetes Attending a Tertiary Centre Multidisciplinary Foot Clinic Undergoing Lower Limb Angiography: One Year Out-comesYISU GU, CATHERINE GOODAY, DARREN MORROW, KETAN K. DHATARIYA, Nor-wich, United Kingdom

We wanted to assess the outcomes of vascular patients attending our multidisciplinary regional foot service where physicians and surgeons jointly assess patients.

We reviewed the foot disease history, current presentation, & 1 year out-come of all patients with diabetes who underwent a lower limb angiogram between 01/01/09 to 12/31/10.

Baseline Characteristics: 80 patients were included, 54M:26F; mean age of 75.8yrs. 94% had T2DM, with 43% on insulin. 45% had had previous lower limb surgical intervention - 36% more than once. 62 patients had CVD. 43 were current or ex-smokers. For the index admission, 29 patients had foot ulcers, 21 claudication, 13 gangrene, 9 critical ischaemia, 5 rest pain, & 3 had other presentations requiring angiogram. 31 patients (39%) progressed to angioplasty. For the other 49 patients, 27 were treated conservatively, 12 had amputations, 6 underwent bypass, 4 patients had other interventions. Out-comes: At one year, 52% of patients were symptom-free or discharged from vascular follow up in the conservatively-treated arm, compared to 55% treated with revascularisation & 45% treated with an amputation. Conversely, 15% of patients treated conservatively had progressed to amputation, compared to 14% in the revascularisation group. Of patients who had prior surgical intervention of the lower limb, 36% were symptom free, compared to 55% who did not have previous surgery. 46% of patients admitted with gangrene underwent amputation either at presentation or at one year follow up, com-pared to only 27% admitted with other symptoms.

In contrast to previous studies our results show that patients who become symptom free at follow up had similar outcomes in the surgical intervention & aggressively medically treated groups. Our data is similar to previous work showing that patients presenting with gangrene are more likely to progress to amputation whilst those without previous surgical treatment were more likely to be symptom free at follow up.

2437-POThe Precipitating Factors of Amputation as Initial Treatment in Dia-betic FootSANGBONG KO, SUNGHWAN BYUN, Cherry Hill, NJ, Voorhees, NJ

Purpose: To evaluate the precipitating factors of amputation as initial treat-ment in diabetic foot patients.

Materials and Methods: Between March, 1994 and February 2010, 41 cases (37 patients) diabetic foot patients who had diabetic ulcer, pyogenic infl am-mation and gangrene and followed up over 1 year were collected. Among them, We evaluate the precipitating factors of amputation for average 39.6 months (12-118months).

Results: Among many factors, Wagner classifi cation, pulse volume record-ing of toes, Ankle-Brachial Index and Albumin level are statistically signifi cant in amputation patients.

Conclusions: In determining the amputation of diabetic foot as initial treat-ment, the trauma history, circulation of foot and serum albumin level are important precipitating factors. So the education about preventing even minor trauma and maintaining good nutrition state decrease the amputation rate in diabetic foot patients.

Supported by: Sangbong Ko

2438-POInfection of the Diabetic Foot: Does Osteomyelitis Always Lead to Amputation?DIMITRIOS SKOUTAS, IOANNIS KATSANOS, CHRYSANTHI NTASIOPOULOU, CHRISTOS MYLOPOULOS, STAMATIA GEORGA, ATHANASIOS NIKOLAIDIS, LOU-KAS DOUKAS, EIRINI MOUZA, MOUSLECH ZADALA, IOANNIS TSITOURIDIS, CHRISTOS MANES, Thessaloniki, Greece

Background: Infection of the diabetic foot is the main cause of amputation in 25-50% of diabetic patients.Osteomyelitis occurs in 20% of diabetics with infection in the lower extremities and can go up to 60% when the infection is serious. The purpose of this study is to identify whether there are patients with osteomyelitis that heal their ulcers and avoid amputation.

Method: Over 3 year observational study in the participating centers with follow-up period at least 12 months in the patients with diabetic foot. Age, sex, previous hospitalization, type of diabetes, HbA1c, Charcot arthropathy, ulcer site and duration, presence of neuropathy and/or PAD, infl ammatory markers, history of previous infection were recorded. Patients were treated with surgical debridement, cultures and radiologic assessment for the sug-gestion of DFO.Healing was complete epithelization without amputation and absence of relapse.

Results: From the 80 patients enrolled with diabetic foot and osteomyelitis, 60 completed the follow-up period: 44 had successful conventional therapy, 10 were amputated and 6 failed to heal. In 7 patients vascular surgery was necessary. Peripheral neuropathy was present in all patients, and in 30 of them there was also peripheral arterial disease. Staphylococus aureus was the most common pathogen isolated. Prior hospitalization p=0,01 history of previous infection p=0,04 and empirical treatment without cultures p=0,01 were correlated with the failure of conventional treatment of osteomyelitis in diabetic patients.

Conclusions: Suspicion of osteomyelitis in diabetic foot should arise when an infected ulcer doesn’t improve with antimicrobial treatment even in the cases that the bone is not exposed or does not have radiologic lesion of osteomyelitis. Antibiotic treatment according to results of cultures (mainly from bone biopsy), seems to help to the successful treatment of the diabetic foot osteomyelitis, avoiding amputation. Surgery should be reserved only for cases that fail to respond.

2439-POClinical Characteristics and Medical Costs in the Patients With Dia-betic Amputation and the Non-Diabetic Patients With Non-Traumatic Amputation in China Central Urban HospitalsAIHONG WANG, ZHANGRONG XU, LINONG JI, Beijing, China

Objective: To analyze the clinical characteristics, amputation level, fi nal outcome of amputation and medical cost between the diabetic amputation and nontraumatic amputation in China central urban hospitals.

Method: The amputation data in the year 2010 from the 19 central munic-ipal general hospitals located in the different big cities in China were retro-spectively analyzed according to the standardized protocol, including clinical characteristics, level and prognosis of the amputation, and medical cost in the hospitals. The patients were divided into diabetic amputation group and non-traumatic amputation group. A total of 419 amputation patients were recruited.

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CATEGORY

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DIABETES EDUCATION

Results: 27.3 % of the all amputated patients or 41.5% of the non-traumatic patients were diabetic patients. Compared with non-traumatic amputation, patients with diabetic amputation were older (65.4±11.6 vs 50.1±20.4 yrs, p=0.000), with higher systolic blood pressure (136.7±19.7 vs 128.0±19.2mmHg, p=0.000) and fasting blood glucose level (8.3±3.7 vs 5.6±1.9mmol/L, p=0.000), lower triglycerides (1.3±0.7 vs 1.5±1.0 mmol/L, p=0.028) and high density lipoprotein cholesterol (HDL-C) (1.0±0.4 vs

1.2±0.4 mmol/L, p= 0.000) level. Minor amputation was more common in the patients with diabetic foot disease (55.7%) than those with nontraumatic foot disease (18.3%) (x2=63.450, p =0.000). There were signifi cant differences in days of hospital stay (33.5 vs 22.0 d) and medical cost (36392 vs 25337 Yuan RMB) between the two groups. Conclusion: The 42.2% of non-tramatic amputation were caused by diabetic foot diseases The patients with diabetic amputation were older with higher blood glucose, blood pressure and lower TG and HDL-C level. Most of them required minor amputation. Their hospital stay was longer with signifi cantly higher medical costs.

2440-POManagement of Osteomyelitis in a Multidisciplinary Foot ClinicEDWARD B. JUDE, CHRISTINA ARAPOSTATHI, NIKOLAOS TENTOLOURIS, Ashton-under-Lyne, United Kingdom, Athens, Greece

Diabetic foot infections and osteomyelitis are associated with substantial morbidity and mortality. The aim of this study was to look at the fi nal outcome in patients with osteomyelitis.

In a retrospective study patients attending a diabetic foot clinic and diag-nosed with osteomyelitis, were selected. All patients are followed up for fi ve years after diagnosis of osteomyelitis. Diagnosis was based on a positive probe to bone test and an abnormal foot x-ray. Demographic, clinical, bio-chemical, treatment and outcome data were obtained from the computer records of the patients.

A total of 59 patients (51 with Type 2 diabetes, mean HbA1c: 7.9±1.9% and age: 67±14 years) were entered into the study. The most frequent site of osteomyelitis was the forefoot (62.5%). 12 patients underwent amputation (75%), the majority of whom had osteomyelitis in the forefoot (p=0.001). 31 patients died during follow up and were older than those who survived (mean age: 71±13 vs 62 ±14 years, p=0.009). Risk factors such as neuropathy, ischemic heart disease, peripheral arterial disease and hyperlipidemia were more com-mon among the amputated compared to the not amputated patients (p<0.05). Patients who were younger healed more frequently compared to elderly patients (mean age: 61±15 vs 70±13 years, p<0.005).

Age plays an important role in healing and mortality but site of osteomy-elitis has a predictive role in amputations. Modifying the risk factors may help in reducing amputations and also more intensive management of the elderly patients might result in better outcomes in this age group.

DIABETES EDUCATION

2441-POCompliance With Lifestyle Recommendations and Achievement of Therapeutic Goals in Type 2 Diabetic Married CouplesIOANNIS IOANNIDIS, FOTINI ARTEMAKI, ATHANASIOS NIKOLOPOULOS, DANAI TSALTA, DIMITRA TASIOPOULOU, NIKOLAOS KOMITOPOULOS, Athens, Greece

Introduction: The treatment of diabetes is based on lifestyle changes (diet and physical activity) and in compliance to medication in order to achieve the goals of good glucose control, lipids and blood pressure.

Aim: Was to examine the achievement of goals and lifestyle changes in diabetic couples and the degree of coincidence patterns among individuals in each pair.

Subjects: We studied 50 married couples of diabetic patients in reaching treatment goals and compliance in lifestyle changes and the degree of agree-ment between them.

Results: 64% of couples had HbA1c <7%, 8% had> 7% and the remaining 28% had one of the two HbA1c <7%.

68% of couples had SBP <140 mmHg, 14% had> 140 mmHg and 18% had SBP <140 mmHg one of the two.

As far as LDL cholesterol is concerned only 28% of couples had a value <100. 20% had> 100 while in 52% of couples only one of the two achieved target value.

68% of couples do not smoke, 8% smoke and in 26% of couples one of the two spouses smokes.

80% of couples do not drink alcohol while in the remaining 20% one of the two spouses drink alcohol (low to moderate consumption).

52% of couples do mild physical activity, 12% do not exercise at all and the

remaining 36% reported physical activity of different intensity between the pair.

In 84% of couples referred daily consumption of more than 2 servings of vegetables, while only 8% do not eat any vegetables. Finally, 92% of couples consume at least 2 fruits daily and only 4% of couples do not eat fruit.

Conclusions: With a high degree of identity, people of couples with type 2 diabetes show good compliance in lifestyle change (mainly vegetables and fruit consumption and secondarily on physical activity and smoking habit). Highly identity between spouse recorded in good glycemic control and good blood pressure. The lowest degree of both achieving the goal and coincidence between the members recorded in LDL cholesterol.

2442-POWait-List Control Study of a Diabetes (DM) Education ProgramMATTHEW BERGER, SARAH G. IMERSHEIN, RICHARD A. JACKSON, Boston, MA

A wait-list control study (n=89) was used to assess biomarker change result-ing from the use of On the Road (OTR), a low-literacy DM education and outreach program in Pennsylvania. OTR was a collaboration between Joslin Diabetes Center and Extension educators of the National Institute for Food and Agriculture, a division of the USDA. Programs were delivered to small groups in non-medical settings, and included point-of-care A1C and blood pressure (BP) testing, emphasizing the importance of BP control in reducing DM-related complications.

Participants were randomized so that 46 completed OTR in February 2012 (“Intervention”), while 43 waited until June 2012 (“Control”). Spouse or com-panion pairs were allowed to randomize together as one unit, leading to some unevenly distributed characteristics, including systolic blood pressure (SBP). Follow-up rates were 87% for the Intervention group and 90% for the Control group.

Figure 1 shows mean SBP (average of 2 readings) and 95% confi dence intervals (CI) for Intervention and Control participants at key study points.

At baseline, mean SBP was 6.3 higher for Control participants than for Intervention participants (95% CI=-2.0 - 14.6). However, mean SPB improve-ment was greater for the Intervention group than Controls (decrease of 7.9 versus 5.7, respectively, difference of difference 2.2, 95% CI -4.1 - 8.5).

Low-cost DM outreach education may lead to improved blood pressure control in low-literacy populations compared to those who do not receive education.

Supported by: U.S. Dept. of Agriculture

2443-POImprovement in Outcomes Following the Implementation of a Com-prehensive Diabetes Management ProgramSHELLEY WILLIAMS, MARGARET RIEDL, KENNETH IZUORA, Las Vegas, NV

The implementation of a comprehensive diabetes management program has been shown to improve outcomes in diabetes care. The establishment of a comprehensive diabetes education program in our center led to the introduc-tion of diabetes self management education program and medical nutrition therapy taught through CDEs according to AADE 7 standards. Also, strategies for identifi cation and correction of shortfalls in core measures in diabetes care were instituted. Point of care A1c testing and onsite retinal screening were initiated. There was also closer patient follow up between visits with more frequent contacts for review of home glucose logs and pump downloads. We have analyzed hemoglobin A1c, LDL-C goals, BMI and compliance to dia-

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