Research Article Relevance of Plasma Obestatin and Early ...adipokine (leptin, resistin, and adiponectin), ghrelin, and obestatin [ , ]. With the development of blood glucose-lowering

Hindawi Publishing CorporationJournal of Diabetes ResearchVolume 2013 Article ID 563919 6 pageshttpdxdoiorg1011552013563919

Research ArticleRelevance of Plasma Obestatin and Early Arteriosclerosis inPatients with Type 2 Diabetes Mellitus

Peng-ying Gu1 Dong-mei Kang1 Wei-dong Wang1 Yan Chen2 Zhi-hong Zhao3

Hui Zheng4 and Shan-dong Ye5

1 Department of Geriatric Medicine Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei Anhui 230001 China2Department of Endocrine Laboratory Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei Anhui 230001 China3Department of Ultrasonic Medicine Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei Anhui 230001 China4Department of Clinical Laboratory Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei Anhui 230001 China5 Department of Endocrinology Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei Anhui 230001 China

Correspondence should be addressed to Shan-dong Ye shandongyeeyhotmailcom

Received 22 May 2013 Revised 4 September 2013 Accepted 10 September 2013

Academic Editor Giuseppe Paolisso

Copyright copy 2013 Peng-ying Gu et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

We investigated the correlation between obestatin andmetabolic parameters and carotid intima-media thickness (IMT) in plasmaofpatients with type 2 diabetes mellitus (T2DM)We collected 103 patients aged from 60 to 83 years (6926 plusmn 583 years) form January2007 to May 2009 All patients were divided into normal glucose tolerance (NGT) impaired glucose tolerance (IGT) and T2DMaccording to the oral glucose tolerance test (OGTT) We found that higher levels of fasting insulin (Fins) fasting blood glucose2 h OGTT glucose homeostasis model assessment of insulin resistance (HOMA-IR) low density lipoprotein cholesterol glycatedhaemoglobin and C-reactive protein (CRP) as well as lower obestatin level and higher intima-media thickness level (IMT) existedin T2DM group compared with NGT group and IGT group (119875 lt 001) Also obestatin level was independently associated withHOMA-IR and CRP while IMT level was independently associated with HOMA-IR triglyceride Fins and obestatin (119875 lt 001)based on stepwise multiple regression analysis Therefore we deduced that the low level of plasma obestatin might be related toearly arteriosclerosis in patients with T2DM via increasing IMT level and elevated plasma obestatin levels might protect T2DMpatients against carotid atherosclerosis to some extent

1 Introduction

Type 2 diabetes mellitus (T2DM) is related to a significantincrease in the risk of atherosclerosis [1] In the past severalyears clinical studies have shown that high mortality inpatients with T2DM is due to cardiovascular disease [2]Besides T2DM often coexists with dyslipidemia coronarydisease hypertension and visceral obesity [3 4] As is wellknown cardiometabolic risk factors play important rolesin pathophysiology of arteriosclerosis and diabetes includ-ing hormones in the appetite and body weight regulationadipokine (leptin resistin and adiponectin) ghrelin andobestatin [5 6]

With the development of blood glucose-lowering medi-cations such as lifestyle-directed interventions insulin sul-fonylureas and metformin the number of treatment options

available for T2DM has increased recently [7] Besidesrosiglitazone maleate targets insulin resistance to enhancethe synthesis of glucose transporters and activate adipocytedifferentiation while metformin hydrochloride can promotethe lowering glucose by reducing hepatic glucose productionand enhance the gluconeogenesis by increasing peripheralglucose uptake the combination of two drugs is effective andsafe in reducing hyperglycemia in patients with T2DM [8]Although numerous reviews on the management of T2DMhave been published in recent years [9 10] a clear pathway oftherapy has not been confirmed

Obestatin a 23-amino acid peptide derived from theghrelin precursor protein is a risk factor for cardiovascu-lar disease [11] In previous studies obestatin was foundcorrelated with intima-media thickness (IMT) which is

2 Journal of Diabetes Research

regarded as a biomarker of early arteriosclerosis suggestingthat obestatin plays a positive role in inhibiting carotidatherosclerosis at the early stage [12] Obestatin also couldimprove myocardial function and decrease apoptosis ofcardiomyocytes in isolated rat heart which were regulated byspecific obestatin receptors on cardiac cells or via activationof reperfusion injury salvage kinase (RISK) pathways [13]Currently obestatin has been identified to be associated withinsulin resistance metabolic dysfunctions suppressing foodintake jejunal contraction and body weight gain [14] Forinstance obestatin inhibits secretion of pancreas polypep-tide and promotes generation of pancreatic juice enzymesthrough a vagal pathway [15 16] Furthermore the G protein-coupled orphan receptor (GPR39) which is regarded asreceptor of obestatin is decreased in adipose tissue of obesepatients with T2DM [17 18]

Although previous study have demonstrated that diabetespatients with fasting plasma glucose above 70mML havea higher risk of cardiovascular death [19] studies focus onthe relationship between obestatin and arteriosclerosis inpatients with T2DM are insufficient Therefore in our studywe examined the plasma level of obestatin and metabolicparameters to investigate the relationship among obestatinarteriosclerosis and T2DM

2 Materials and Methods

21 Subjects All persons have given their informed consentprior to their inclusion in the study and all human studieshave been approved by the China Ethics Committee andperformed in accordance with the ethical standards Onehundred and three patients aged which undergone physicalexamination and hospitalization from 60 to 83 years (6926 plusmn583 years) were selected from the Clinic for Retired VeteranCadres Anhui Provincial Hospital Affiliated to Anhui Medi-cal University from January 2007 to May 2009

After consulting the detail of medical history and physi-cal examination determining thyroid function biochemicalindicators and endocrine hormone subjects with stresshyperglycemia autoimmune diseases thyroid dysfunctionacromegaly hypercortisolism liver or renal insufficiencymalignant tumor or continuous use of glucocorticoiddiuretic niacin or indomethacin were excluded All patientswithout diabetic complications without factors of secondaryrise in blood sugar without diabetic vascular complica-tions and without administered drugs for gastrointestinalsystem within three months were included in this researchAmong patients 40 subjects had history of high bloodpressure the disease course was 3sim10 months and theperson who was given drugs with the effects on insulin-resistance was excluded totally 59 persons were diagnosedwith hyperlipemia the disease course was 0sim7 years therewas no long-term users of lipid-lowering drugs 10 subjectswere diagnosed with coronary heart disease with arteriog-raphy examination and 30 subjects represented myocardialischemia with electrocardiograph All subjects received oralglucose tolerance test (OGTT) and were divided into threegroups normal glucose tolerance (NGT) impaired glucosetolerance (IGT) and T2DM according to the diagnostic

criteria published by theWorldHealthOrganization (WHO)in 1999 The T2DM patients were newly diagnosed

22 Methods General information of the subjects wasrecorded including gender age height weight and bloodpressure (BP) Body mass index (BMI) was calculated asweight divided by height squared (kgm2) BP was measuredtwice (5min interval between the twomeasurements) with anaccuratemercury sphygmomanometer after a 5-min rest andthe average value was calculated Venous blood was collectedafter overnight fasting The contents of fasting insulin (Fins)were measured with an Abbott bichromatic analyzer (AbbottLabs USA) Fasting plasma insulin levels were measuredwith a commercial radioimmunoassay (Diagnostic ProductsUSA) Levels of Fins and FBGwere measured at 120min afterglucose load (OGTT-2 h) Homeostasis model assessmentof insulin resistance (HOMA-IR = Fins times FPG225) wasdetermined Glycosylated haemoglobin (HbA1c) was mea-sured by isoelectric focusing Fasting plasma lipid param-eters were detected with an automatic enzymatic analyzer(Hitachi 7600ISE-020 Japan) including total cholesterol(TC) triglyceride (TG) high-density lipoprotein cholesterol(HDL-c) and low-density lipoprotein cholesterol (HDL-c)Apolipoprotein (ApoA1 and ApoB) was measured by neph-elometric assay (Diasys German) C-reactive protein (CRP)was assayedwith ELISAObestatinwas assayed using enzymeimmunoassay kits (lot 09041254 RampDsystemsUSA) IMTofcarotid artery was blindly scanned three times by a B-modecolor Doppler ultrasound with a frequency of 75 to 10MHzIMT was electronically measured three times at the far wallof the distal common carotid arteries about 1 cm from thecarotid bifurcation The average values of bilateral arterieswere obtained

23 Statistical Analysis All statistical analyses were per-formed on SPSS 130 (SPSS Inc Chicago USA) Normaldistribution was assessed by independent sample 119905-testbetween the two groups Differences between multigroupswere compared using a one-way ANOVA Data expressedas mean plusmn SD Nonnormal distribution was performed withKruskal-Wallis test The relationships between two variableswere assessed with Pearson and rank correlation Stepwiseregression was used to explore the correlation of obestatinand IMT

3 Results

31 Clinical and Biochemical Characteristics The metabolicindexes of the patients in three groups were listed in Table 1There were no differences of age diastolic blood pressure(DBP) systolic blood pressure (SBP) and BMI levels betweenthe three groups (119875 gt 005) Differences of concentrations ofbiochemical parameters in the three groups were significant(119875 lt 001) Increased levels of Fins FPG OGTT-2 h (2hPG)HOMA-IR HbA1c LDL-C and CRPwere detected in T2DMgroup compared with the other two groups (119875 lt 001)Compared to NGT group levels of TC TG and comparing

Journal of Diabetes Research 3

Table 1 Clinical and biochemical parameters of T2DM IGT and NGT groups

Variables NGT IGT T2DMNumber (menwomen) 42 (2913) 27 (207) 34 (2212)Age (y) 6850 plusmn 580 7022 plusmn 682 6944 plusmn 500

SBP (mmHg) 132 plusmn 14 138 plusmn 14 136 plusmn 16

DBP (mm Hg) 79 plusmn 9 81 plusmn 7 81 plusmn 10

BMI (kgm2) 2385 plusmn 224 2436 plusmn 295 2493 plusmn 259

Fins (mUL) 1055 plusmn 635 1280 plusmn 569 1863 plusmn 711lowastlowast998771998771

FBG (mmolL) 471 plusmn 065 512 plusmn 073lowast

614 plusmn 100lowastlowast998771998771

2hPG (mmolL) 644 plusmn 094 940 plusmn 134lowastlowast


HbA1c () 479 plusmn 050 502 plusmn 050lowastlowast


HOMA-IR 227 plusmn 150 331 plusmn 156lowast


TC (mmolL) 457 plusmn 100 537 plusmn 106lowastlowast

554 plusmn 100lowastlowast

TG (mmolL) 175 plusmn 154 208 plusmn 136 270 plusmn 096lowastlowast

HDL-C (mmolL) 135 plusmn 040 125 plusmn 052 110 plusmn 025lowastlowast

LDL-C (mmolL) 263 plusmn 074 311 plusmn 108lowastlowast


CRP (mgL) 0971 plusmn 0464 1340 plusmn 0894 2275 plusmn 0968lowastlowast998771998771

Data were expressed as mean plusmn SD lowastP lt 005 compared with NGT group lowastlowastP lt 001 compared with NGT group 998771P lt 005 compared with IGT group 998771998771Plt 005 compared with IGT group SBP systolic blood pressure DBP diastolic blood pressure BMI body mass index Fins fasting insulin FBG fasting bloodglucose 2hPG 2 h OGTT glucose HbA1c glycated haemoglobin HOMA-IR homeostasis model assessment-insulin resistance index TC total cholesterolTG total triglyceride HDL-C high density lipoprotein cholesterol LDL-C low density lipoprotein cholesterol CRP C-reactive protein

with NGT group higher levels of TC and TG were observedin T2DM group as well as lower level of HDL-C (119875 lt 001)

32 Levels of Obestatin and IMT Patients with T2DM hada lower level of obestatin by comparing with the NGT andIGT groups (119875 lt 001 Figure 1(a)) and the obestatin levelin patients of IGT group was lower than that in the NGTgroup (119875 lt 005) Increased levels of IMT were detected inT2DM group compared to NGT and IGT groups (119875 lt 001Figure 1(b)) However no significant difference of IMT levelswas observed between IGT group and NGT group

33 Correlations between Obestatin and IMT As shown inTable 2 the obestatin level was significantly correlated withBMI (119903 = minus0365 119875 = 0004) Fins (119903 = minus0269 119875 = 0036)HOMA-IR (119903 = minus0345 119875 = 0006) FBG (119903 = minus0286119875 = 0025) HbA1c (119903 = minus0310 119875 = 0015) TG (119903 = minus0345119875 = 0007) HDL-C (119903 = 0261 119875 = 0008) CRP (119903 = minus0524119875 = 0000) and IMT (119903 = minus0269 119875 = 0036) Throughstepwisemultiple regression analysis we found that obestatinlevel was independently associated with HOMA-IR and CRP(obestatin = 3926 minus 0053 times HOMA minus IR minus 0270 times CRP)residuals of values conformed to normal distribution

IMT level was found to correlate positively with Fins (119903 =0269 119875 = 0036) FBG (119903 = 0238 119875 = 0048) 2hPG(119903 = 0278 119875 = 0030) HOMA-IR (119903 = 0288 119875 = 0024)TG (119903 = 0361 119875 = 0004) and CRP (119903 = 0289 119875 = 0024)as well as negatively with obestatin (119903 = 0269 119875 = 0036) insimple regression analysis in the pooled data (Table 3) Whilethe results of stepwise multiple regression analysis showedthat IMT level was independently associatedwithHOMA-IRTG Fins and obestatin (IMT = 1233+0044timesHOMAminusIR+0054 times TG minus 0010 times Fins minus 0095 times obestatin) Residuals ofvalues conformed to normal distribution

4 Discussion

In this study in T2DM IGT and NGT three groups signif-icantly higher plasma levels of Fins FBG 2hPG HOMA-IRTC TG LDL-C and CRP were detected in T2DM subjectscompared with NGT subjects (119875 lt 001) and only the levelof Fins FBG 2hPG HOMA-IR HbA1c CRP and LDL-Cin NGT patients were obviously different with IGT patientsSignificantly decreased obestatin level was also found inpatients with T2DM by comparing with NGT patients andIGT patients as well as IMT level comparing with NGTpatients Besides obestatin was independently correlatedwith IMT plasma levels in the diabetic patients Obestatinwas considered as a nutritional marker reflecting insulinresistance [20] body adiposity and a regulator of adipocytemetabolism [21 22] In previous studies plasma obestatinlevel that was indicated was lower in patients with T2DMand IGR than in controls and the multiple logistic regressionanalysis revealed obestatin to be independently associatedwith IGR and T2DM [23] Meanwhile the expression ofGPR39 which was identified as the receptor for obestatindisplayed significantly lower levels in obese T2DM patientsthan in lean and obese normoglycaemic subjects the mRNAexpression levels of GPR39 was also negatively related tofasting glucose concentrations but represented a positivecorrelation to adiponectin mRNA expression levels thissuggested an involvement of obestatin signal pathway inglucose homeostasis and T2DM development [24] while St-Pierre et al reported that normal and diabetic subjects displaysimilar levels of circulating obestatin in fasting condition[25] But in this study plasma level of obestatin was decreasedin diabetic patients Thus we supposed that lower level ofobestatin could be a predictor for patients with T2DM whilethe mechanisms of a reduction in obestatin levels in diabetic


0000

1000

2000

3000

4000

Obestatin (ngmL)

NGT IGT T2DM

998771

∙lowast

(a)

0000

050

1000

IMT (mm)

NGT IGT T2DM

∙lowast

(b)

Figure 1 Levels of obestatin (a) and IMT (b) in patients of NGT IGT and T2DM groups998771 119875 lt 005 compared with NGT group (the controlgroup) lowast 119875 lt 001 compared with NGT group ∙ 119875 lt 001 compared with IGT group and IMT intima-media thickness

Table 2 Correlation analysis of obestatin and various metabolicparameters

Variable Simple MultipleEstimate P value Estimate P value

Age minus0107 0412SBP 0220 0088DBP minus0097 0455BMI minus0365 0004FIns minus0269 0036FBG minus0286 00252hPG minus0243 0060HOMA-IR minus0345 0006 minus2056 0042HbA1c minus0310 0015TC minus0056 0671TG minus0345 0007HDL-C 0261 0008LDL-C minus0165 0203CRP minus0524 0000 minus4353 0000IMT minus0269 0036SBP systolic blood pressure DBP diastolic blood pressure BMI body massindex Fins fasting insulin FBG fasting blood glucose 2hPG 2 h OGTTglucose HOMA-IR homeostasismodel assessment-insulin resistance indexHbA1c glycated haemoglobin TC total cholesterol TG total triglycerideHDL-C high density lipoprotein cholesterol LDL-C low density lipoproteincholesterol CRP C-reactive protein IMT intima-media thickness

population are not quite clearWe supposed that the high levelof obestatin may be a defense of plasma hyperglycemia

Carotid arterial intima-media thickness was used as anoninvasive surrogate end point to measure progression of

Table 3 Correlation analysis of variables associated with IMT insubjects studied


Age minus0052 0693SBP 0085 0512DBP 0054 0681BMI 0007 0959FIns 0269 0036 minus2852 0006FBG 0238 00482hPG 0278 0030HOMA-IR 0288 0024 3822 0000HbA1c 0118 0367TC 0171 0186TG 0361 0004 3325 0002HDL-C minus0009 0945LDL-C 0064 0623CRP 0289 0024Obestatin minus0269 0036 minus2581 0012SBP systolic blood pressure DBP diastolic blood pressure BMI body massindex Fins fasting insulin FBG fasting blood glucose 2hPG 2 h OGTTglucose HOMA-IR homeostasismodel assessment-insulin resistance indexHbA1c glycated haemoglobin TC total cholesterol TG total triglycerideHDL-C high density lipoprotein cholesterol LDL-C low density lipoproteincholesterol CRP C-reactive protein

atherosclerosis and is increasingly used as a surrogate markerdue to its ability to predict future clinical cardiovascularend points [26 27] And increased IMT was considered notonly a biomarker of arteriosclerosis in the early phases but


also related with a clustering of risk factors for myocardialinfarction [4 28] Previously type 2 diabetes was associatedwith an 013mm increase in IMT compared with controlsubjects [29] And 6-month intensive lifestyle modificationintervention in T2DM patients showed enhanced glycemiccontrol and decreased progression of carotid IMT [30]Increased common carotid artery IMT and plaque scorewere also associated with acute ischemic stroke in T2DMpatients [31] Moreover the present study showed that IMTwas significantly increased in patients with T2DM and theplasma level of obestatin was correlated negatively to IMTthis suggested that high level obestatin might have a positiveeffect against carotid atherosclerosis

In addition obestatin administration had been demon-strated to exert a beneficial effect againstmyocardial dysfunc-tions and cardiomyocyte apoptosis in a rat model [32 33]Obestatin also displays protective effect in cardiac functionin humans both in physiological and pathological situationsIt is demonstrated that obestatin induces vascular relaxationby activating endothelium-dependent NO signaling [34]Obestatin together with TNF-120572 treatment even decreasedvascular cell adhesion molecule-1 expression and increasebinding of LDL to macrophages indicating the regulation ofobestatin in the early atherogenic processes [35] Hence theseevidences confirmed the effective protection of high levelobestatin against the complication such as atherosclerosisand myocardial infarction

5 Conclusion

In conclusion we have determined the levels of metabolicparameters in healthy people and patients with IGT orT2DM Inverse correlation between obestatin and IMT hasbeendemonstratedThe lower obestatin level in plasmamightbe an indicator of early arteriosclerosis The increasing ofplasma obestatin level might protect T2DM patients againstcarotid atherosclerosis complication to some extent How-ever the limitations of this study existed including the small-scale of subjects with T2DM and the elderly age of enrolledsubjects the mechanism of obestatin protecting T2DMpatients against arteriosclerosis in patients with T2DM needsto be investigated in long-term and large-scale studies

Conflict of Interests

The authors have no conflict of interests to state

References

[1] J A Beckman M A Creager and P Libby ldquoDiabetes andatherosclerosis epidemiology pathophysiology and manage-mentrdquo Journal of the AmericanMedical Association vol 287 no19 pp 2570ndash2581 2002

[2] D Kirpichnikov and J R Sowers ldquoDiabetes mellitus anddiabetes-associated vascular diseaserdquo Trends in Endocrinologyand Metabolism vol 12 no 5 pp 225ndash230 2001

[3] K Pyorala M Laakso and M Uusitupa ldquoDiabetes andatherosclerosis an epidemiologic viewrdquo DiabetesMetabolismReviews vol 3 no 2 pp 463ndash524 1987

[4] S M Haffner S Lehto T Ronnemaa K Pyorala and MLaakso ldquoMortality from coronary heart disease in subjectswith type 2 diabetes and in nondiabetic subjects with andwithout prior myocardial infarctionrdquoThe New England Journalof Medicine vol 339 no 4 pp 229ndash234 1998

[5] E Toussirot G Streit N U Nguyen et al ldquoAdipose tissueserum adipokines and ghrelin in patients with ankylosingspondylitisrdquoMetabolism vol 56 no 10 pp 1383ndash1389 2007

[6] J Vendrell M Broch N Vilarrasa et al ldquoResistin adiponectinghrelin leptin and proinflammatory cytokines relationships inobesityrdquo Obesity Research vol 12 no 6 pp 962ndash971 2004

[7] D M Nathan ldquoMedical management of hyperglycemia intype 2 diabetes a consensus algorithm for the initiation andadjustment of therapy a consensus statement of the americandiabetes association and the european association for the studyof diabetesrdquo Diabetes Care vol 32 no 3 pp e37ndashe38 2009

[8] V Fonseca J Rosenstock R Patwardhan and A SalzmanldquoEffect of metformin and rosiglitazone combination therapy inpatients with type 2 diabetes mellitus a randomized controlledtrialrdquo Journal of the American Medical Association vol 283 no13 pp 1695ndash1702 2000

[9] D M Nathan ldquoInitial management of glycemia in type 2diabetes mellitusrdquo The New England Journal of Medicine vol347 no 17 pp 1342ndash1349 2002

[10] S E Inzucchi ldquoOral antihyperglycemic therapy for type 2diabetes scientific reviewrdquo Journal of the American MedicalAssociation vol 287 no 3 pp 360ndash372 2002

[11] D C Klonoff J B Buse L L Nielsen et al ldquoExenatide effectson diabetes obesity cardiovascular risk factors and hepaticbiomarkers in patients with type 2 diabetes treated for at least 3yearsrdquo Current Medical Research and Opinion vol 24 no 1 pp275ndash286 2008

[12] A-D Cui N-N Gai X-H Zhang et al ldquoDecreased serumobestatin consequent upon TRIB3 Q84R polymorphism exac-erbates carotid atherosclerosis in subjects with metabolic syn-dromerdquo Diabetology and Metabolic Syndrome vol 4 no 1 pp1ndash5 2012

[13] G Alloatti E Arnoletti E Bassino et al ldquoObestatin affordscardioprotection to the ischemic-reperfused isolated rat heartand inhibits apoptosis in cultures of similarly stressed car-diomyocytesrdquo American Journal of Physiology vol 299 no 2pp H470ndashH481 2010

[14] J V Zhang P-G Ren O Avsian-Kretchmer et al ldquoMedicineobestatin a peptide encoded by the ghrelin gene opposesghrelinrsquos effects on food intakerdquo Science vol 310 no 5750 pp996ndash999 2005

[15] S S Qader R Hakanson J F Rehfeld I Lundquist and ASalehi ldquoProghrelin-derived peptides influence the secretionof insulin glucagon pancreatic polypeptide and somatostatina study on isolated islets from mouse and rat pancreasrdquoRegulatory Peptides vol 146 no 1ndash3 pp 230ndash237 2008

[16] M Kapica M Zabielska I Puzio et al ldquoObestatin stimulatesthe secretion of pancreatic juice enzymes through a vagalpathway in anaesthetized ratsmdashpreliminary resultsrdquo Journal ofPhysiology and Pharmacology vol 58 no 3 pp 123ndash130 2007

[17] J V Zhang P-G Ren O Avsian-Kretchmer et al ldquoMedicineObestatin a peptide encoded by the ghrelin gene opposesghrelinrsquos effects on food intakerdquo Science vol 310 no 5750 pp996ndash999 2005

[18] V Catalan J Gomez-Ambrosi F Rotellar et al ldquoThe obestatinreceptor (GPR39) is expressed in human adipose tissue and is


down-regulated in obesity-associated type 2 diabetes mellitusrdquoClinical Endocrinology vol 66 no 4 pp 598ndash601 2007

[19] S Mohr-Kahaly ldquoNew diagnostic criteria for diabetes andcoronary artery disease insights from an angiographic studyrdquoJournal of the American College of Cardiology vol 37 no 6 pp1543ndash1550 2001

[20] T Nakahara T Harada D Yasuhara et al ldquoPlasma obestatinconcentrations are negatively correlated with body mass indexinsulin resistance index and plasma leptin concentrations inobesity and anorexia nervosardquo Biological Psychiatry vol 64 no3 pp 252ndash255 2008

[21] U Gurriaran-Rodrıguez O Al-Massadi A Roca-Rivada etal ldquoObestatin as a regulator of adipocyte metabolism andadipogenesisrdquo Journal of Cellular and Molecular Medicine vol15 no 9 pp 1927ndash1940 2011

[22] R Granata D Gallo R M Luque et al ldquoObestatin regulatesadipocyte function and protects against diet-induced insulinresistance and inflammationrdquo The FASEB Journal vol 26 no8 pp 3393ndash3411 2012

[23] XQi L Li G Yang et al ldquoCirculating obestatin levels in normalsubjects and in patients with impaired glucose regulation andtype 2 diabetes mellitusrdquo Clinical Endocrinology vol 66 no 4pp 593ndash597 2007

[24] V Catalan J Gomez-Ambrosi F Rotellar et al ldquoThe obestatinreceptor (GPR39) is expressed in human adipose tissue and isdown-regulated in obesity-associated type 2 diabetes mellitusrdquoClinical Endocrinology vol 66 no 4 pp 598ndash601 2007

[25] D H St-Pierre F Settanni I Olivetti et al ldquoCirculatingobestatin levels in normal and Type 2 diabetic subjectsrdquo Journalof Endocrinological Investigation vol 33 no 4 pp 211ndash214 2010

[26] H N Hodis W J Mack L LaBree et al ldquoThe role of carotidarterial intimamdashmedia thickness in predicting clinical coronaryeventsrdquoAnnals of Internal Medicine vol 128 no 4 pp 262ndash2691998

[27] M W Lorenz H S Markus M L Bots M Rosvall andM Sitzer ldquoPrediction of clinical cardiovascular events withcarotid intima-media thickness a systematic review and meta-analysisrdquo Circulation vol 115 no 4 pp 459ndash467 2007

[28] T Temelkova-Kurktschiev C Koehler E Henkel and MHanefeld ldquoLeukocyte count and fibrinogen are associated withcarotid and femoral intima-media thickness in a risk populationfor diabetesrdquo Cardiovascular Research vol 56 no 2 pp 277ndash283 2002

[29] G Brohall A Oden and B Fagerberg ldquoCarotid artery intima-media thickness in patients with Type 2 diabetes mellitusand impaired glucose tolerance a systematic reviewrdquo DiabeticMedicine vol 23 no 6 pp 609ndash616 2006

[30] S H Kim S J Lee E S Kang et al ldquoEffects of lifestylemodification on metabolic parameters and carotid intima-media thickness in patients with type 2 diabetes mellitusrdquoMetabolism vol 55 no 8 pp 1053ndash1059 2006

[31] E J Lee H J Kim J M Bae et al ldquoRelevance of commoncarotid intima-media thickness and carotid plaque as riskfactors for ischemic stroke in patients with type 2 diabetesmellitusrdquoAmerican Journal of Neuroradiology vol 28 no 5 pp916ndash919 2007

[32] E Kellokoski A KunnariM Jokela SMakela Y A Kesaniemiand S Horkko ldquoGhrelin and obestatin modulate early athero-genic processes on cells enhancement of monocyte adhesionand oxidized low-density lipoprotein bindingrdquoMetabolism vol58 no 11 pp 1572ndash1580 2009


[34] A J Agnew E Robinson C M McVicar et al ldquoThe gas-trointestinal peptide obestatin induces vascular relaxation viaspecific activation of endothelium-dependent NO signallingrdquoBritish Journal of Pharmacology vol 166 no 1 pp 327ndash3382012


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Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


regarded as a biomarker of early arteriosclerosis suggestingthat obestatin plays a positive role in inhibiting carotidatherosclerosis at the early stage [12] Obestatin also couldimprove myocardial function and decrease apoptosis ofcardiomyocytes in isolated rat heart which were regulated byspecific obestatin receptors on cardiac cells or via activationof reperfusion injury salvage kinase (RISK) pathways [13]Currently obestatin has been identified to be associated withinsulin resistance metabolic dysfunctions suppressing foodintake jejunal contraction and body weight gain [14] Forinstance obestatin inhibits secretion of pancreas polypep-tide and promotes generation of pancreatic juice enzymesthrough a vagal pathway [15 16] Furthermore the G protein-coupled orphan receptor (GPR39) which is regarded asreceptor of obestatin is decreased in adipose tissue of obesepatients with T2DM [17 18]

Although previous study have demonstrated that diabetespatients with fasting plasma glucose above 70mML havea higher risk of cardiovascular death [19] studies focus onthe relationship between obestatin and arteriosclerosis inpatients with T2DM are insufficient Therefore in our studywe examined the plasma level of obestatin and metabolicparameters to investigate the relationship among obestatinarteriosclerosis and T2DM

2 Materials and Methods

21 Subjects All persons have given their informed consentprior to their inclusion in the study and all human studieshave been approved by the China Ethics Committee andperformed in accordance with the ethical standards Onehundred and three patients aged which undergone physicalexamination and hospitalization from 60 to 83 years (6926 plusmn583 years) were selected from the Clinic for Retired VeteranCadres Anhui Provincial Hospital Affiliated to Anhui Medi-cal University from January 2007 to May 2009

After consulting the detail of medical history and physi-cal examination determining thyroid function biochemicalindicators and endocrine hormone subjects with stresshyperglycemia autoimmune diseases thyroid dysfunctionacromegaly hypercortisolism liver or renal insufficiencymalignant tumor or continuous use of glucocorticoiddiuretic niacin or indomethacin were excluded All patientswithout diabetic complications without factors of secondaryrise in blood sugar without diabetic vascular complica-tions and without administered drugs for gastrointestinalsystem within three months were included in this researchAmong patients 40 subjects had history of high bloodpressure the disease course was 3sim10 months and theperson who was given drugs with the effects on insulin-resistance was excluded totally 59 persons were diagnosedwith hyperlipemia the disease course was 0sim7 years therewas no long-term users of lipid-lowering drugs 10 subjectswere diagnosed with coronary heart disease with arteriog-raphy examination and 30 subjects represented myocardialischemia with electrocardiograph All subjects received oralglucose tolerance test (OGTT) and were divided into threegroups normal glucose tolerance (NGT) impaired glucosetolerance (IGT) and T2DM according to the diagnostic

criteria published by theWorldHealthOrganization (WHO)in 1999 The T2DM patients were newly diagnosed

22 Methods General information of the subjects wasrecorded including gender age height weight and bloodpressure (BP) Body mass index (BMI) was calculated asweight divided by height squared (kgm2) BP was measuredtwice (5min interval between the twomeasurements) with anaccuratemercury sphygmomanometer after a 5-min rest andthe average value was calculated Venous blood was collectedafter overnight fasting The contents of fasting insulin (Fins)were measured with an Abbott bichromatic analyzer (AbbottLabs USA) Fasting plasma insulin levels were measuredwith a commercial radioimmunoassay (Diagnostic ProductsUSA) Levels of Fins and FBGwere measured at 120min afterglucose load (OGTT-2 h) Homeostasis model assessmentof insulin resistance (HOMA-IR = Fins times FPG225) wasdetermined Glycosylated haemoglobin (HbA1c) was mea-sured by isoelectric focusing Fasting plasma lipid param-eters were detected with an automatic enzymatic analyzer(Hitachi 7600ISE-020 Japan) including total cholesterol(TC) triglyceride (TG) high-density lipoprotein cholesterol(HDL-c) and low-density lipoprotein cholesterol (HDL-c)Apolipoprotein (ApoA1 and ApoB) was measured by neph-elometric assay (Diasys German) C-reactive protein (CRP)was assayedwith ELISAObestatinwas assayed using enzymeimmunoassay kits (lot 09041254 RampDsystemsUSA) IMTofcarotid artery was blindly scanned three times by a B-modecolor Doppler ultrasound with a frequency of 75 to 10MHzIMT was electronically measured three times at the far wallof the distal common carotid arteries about 1 cm from thecarotid bifurcation The average values of bilateral arterieswere obtained

23 Statistical Analysis All statistical analyses were per-formed on SPSS 130 (SPSS Inc Chicago USA) Normaldistribution was assessed by independent sample 119905-testbetween the two groups Differences between multigroupswere compared using a one-way ANOVA Data expressedas mean plusmn SD Nonnormal distribution was performed withKruskal-Wallis test The relationships between two variableswere assessed with Pearson and rank correlation Stepwiseregression was used to explore the correlation of obestatinand IMT

3 Results

31 Clinical and Biochemical Characteristics The metabolicindexes of the patients in three groups were listed in Table 1There were no differences of age diastolic blood pressure(DBP) systolic blood pressure (SBP) and BMI levels betweenthe three groups (119875 gt 005) Differences of concentrations ofbiochemical parameters in the three groups were significant(119875 lt 001) Increased levels of Fins FPG OGTT-2 h (2hPG)HOMA-IR HbA1c LDL-C and CRPwere detected in T2DMgroup compared with the other two groups (119875 lt 001)Compared to NGT group levels of TC TG and comparing




























4 Discussion



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5 Conclusion




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4 Discussion



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5 Conclusion




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0000

1000

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5 Conclusion




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of






Disease Markers



OncologyJournal of





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5 Conclusion




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OncologyJournal of





PPAR Research



Journal of

ObesityJournal of








































of






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OncologyJournal of





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OncologyJournal of





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Documents

Research Article Relevance of Plasma Obestatin and Early ...adipokine (leptin, resistin, and adiponectin), ghrelin, and obestatin [ , ]. With the development of blood glucose-lowering