4 Importance of Glycemic Control, The Potential Benefits of New Technologies

8/9/2019 4 Importance of Glycemic Control, The Potential Benefits of New Technologies

1/22

1

The Importance of Glycemic Control, the Potential

Benefits of New Technologies, and the Need for

Additional Research in Medicare Populations

Presentation to the Medicare Coverage Advisory Committee

Aaron Kowalski Ph.D.

Director, Strategic Research Projects

Juvenile Diabetes Research Foundation (JDRF)

August 30, 2006


2/22

2

About JDRF

JDRFs mission: to find a cure for diabetes and itscomplications through research

JDRF is the leading charitable funder of type 1diabetes research worldwide ($140 million a year)

JDRF was founded in 1970 by the parents ofchildren with type 1 diabetes, and JDRF'svolunteers -- who have a personal connection to thedisease -- are the driving force behind JDRF's

commitment


3/22

3

Tight Glycemic Control is the

Recommended Standard of Care

American Diabetes Association (ADA)(ADA, 2006.)

Glycemic control is fundamental to the management of diabetes

The HbA1c (A1c) goal for patients in general is an A1c goal of


4/22

4

Hemoglobin A1c Levels are Elevated in the

United States and Appear to Have Plateaued

Reported at Diabetes Mellitus Interagency

Coordinating Committee (DMICC) (DMICC, 2005)

CDC: NHANES III Mean A1c 7.7%, NHANES II MeanA

1c 7.6%, 60% >7.0% Kaiser: TRIAD A1cs have stayed the same or declined

slightly over the past 10 years

VA : 59% of people with diabetes above A1c 7.0%

Summary: Many factors, but tools may besuboptimal for reducing A1c below 7.0%


5/22

5

Hyperglycemia Causes Complications

in Type 1 and Type 2 Diabetes

LowerA1c confers significantly reduced risk ofmicrovascular and macrovascular complications:

Diabetes Control and Complications Trial (DCCT) Type1 (Diabetes Control and Complications Trial Research Group, 1993)

Epidemiology of Diabetes Interventions and Complications(EDIC) Type 1 (DCCT/EDIC Research Group, 2000, Nathan et al., 2005)

UK Prospective Diabetes Trial (UKPDS) Type 2 (UKPDSGroup, 1998)

Benefits were realized in as soon as three years


6/22

6

There are Common Pathways in

Diabetes Complications

Oxidative

Stress

Cellular

Dysfunction

AGE Formation

Cell

Damage

Hexosamine

Pathway

ROS

ROS

Glucose Peripheral & Autonomic Neuropathy

Nephropathy

Retinopathy

Vascular

Damage

Different complications (eye, kidney, nerve, blood vessels)arise from limited number of triggers perturbing a limitednumber of metabolic pathway(s) (Brownlee, 2001)


7/22

7

Hypoglycemia Remains a Significant Burden

Hypoglycemia

Is a real obstacle to tight glycemic control (Reportfrom the American Diabetes Association Workgroup on Hypoglycemia,2005, Cryer et al., 2003)

Is a source of significant morbidity in older adultswith diabetes (Kennedy et al., 2002)

Elderly are at increased risk for hypoglycemiccoma (Ben-ami et al., 1999)

Elderly have reduced awareness of theautonomoic symptoms of hypoglycemia (Meneilly etal., 1994)


8/22

8

Significant Glycemic Variability is Found

in both Type 1 and Type 2 Diabetes

Type 1 Patients (Bode et al., 2005):

9.6% (2.3 hours) hypoglycemic

30% (7.2 hours) hyperglycemic

Type 2 Patients (Bode et al., 2005):

4.2% (1.0 hours) hypoglycemic

28.7% (6.9 hours) hyperglycemic


9/22

9

Variability May Exacerbate Complications Pathways

Intensive management may reduce risk ofdeveloping complications by both reducingA1c and by reducing variability (Brownlee and Hirsch,2006)

Monnier et al.(2006):

Type 2 Patients Mean Age 63.6

MeanA

1c 9.6% Acute Glucose Swings Activate Oxidative Stress

Pathways


10/22

10

Tight Glycemic Control Improves Outcomes for all

People with Diabetes the Young and the Elderly

LowerA1c equals:

Less blindness, less renal failure, fewer amputations,fewer strokes, fewer heart attacks

And continues to be critical in the elderly Increased survival for those on dialysis (Oomichi et al., 2006)

Decreased post-operative morbidity (Ben Ami et al., 1999)

Prevents progression of retinopathy (Morisaki et al., 1994)

Prolonged hospitalization with exacerbated congestiveheart failure (Bhatia et al., 2004)

Better cognitive function (Meneilly et al., 1993, Gradman et al., 1993)


11/22

11

Better Glycemic Control Increases Survival for

People with Diabetes on Dialysis

(Oomichi et al., 2006)


12/22

12

Better Glycemic Control Reduces Post-Operative

Morbidity in Elderly People with Diabetes

Dronge et al., 2006

Median age = 71 years

Primary outcomes = infectious complications,

including pneumonia, wound infection, urinarytract infection, or sepsis

CONCLUSION: Good preoperative glycemiccontrol (A1c levels


13/22

13

Better Glycemic Control Reduces Hospitalization

Time for Elderly People with Diabetes and CHF

Bhatia et al., 2004

Patients with diabetes admitted to a tertiary care center withexacerbation of Congestive Heart Failure (CHF)

Mean Age = 76.5

In-hospital glycemic control strongly correlated positively with thenumber of days of hospitalization

Admission blood glucose level also showed a strong positivecorrelation with the days of hospitalization

Mean hemoglobin A1c correlated positively with the number ofdays in the hospital

51 patients with uncontrolled diabetes (A1c >7%) werehospitalized for a mean period of 6.3 +/- 3.2 days, in comparisonwith a mean duration of3.2 +/- 1.9 days for the 49 patients withgood outpatient glycemic control (A1c < or =7%)


14/22

14

Better Glycemic Control Prevents the Progression

of Retinopathy in Elderly People with Diabetes

Morisaki et al., 1994

Non-insulin-dependent patients with diabetes 60 years ofage

The progression rates of retinopathy as a function of themean A1c during the follow-up were as follows: lower than7%, 2%; 7-8%, 20%; 8-9%, 40%; more than 9%, 61%

Only A1c was a significant risk factor for progression ofretinopathy

CONCLUSIONS: Control of diabetes mellitus is themost important factor associated with prevention of

progression of retinopathy in elderly patients


15/22

15

Better Glycemic Control Improves Cognitive

Function in Elderly People with Diabetes

Meneilly et al.,1993: Improved glycemic controlin the elderly patient with NIDDM may havebeneficial effects on selective areas of cognition

Gradman et al., 1993: Verbal learning andmemory may improve with improved glycemiccontrol


16/22

16

New Technologies Hold Potential to

Improve Control

Continuous Glucose Sensors Show ConsiderablePromise in Preliminary Studies(Presentations 2005 and 2005,Garg et al. 2006, Bailey et al., 2006)

Preliminary Studies have shown:

Statistically significant reductions in A1c (Presentations 2005 and2005, and Bailey et al., 2006)

Statistically significant reductions in hypoglycemia (Garg et al.,2006)

Statistically significant increase in time spent in targetrange (Garg et al., 2006A-B)

Benefits in both type 1 and type 2 patients young andadults (Garg et al. 2006A-B, Bailey et al. 2006)


17/22

17

New Technologies Provide Additional Information

Provide both point-in-time and glucosetrends

Alarm at hyper and hypoglycemic thresholds

Tells people with diabetes whether theirglucose level is trending upwards ordownwards, allowing them to adjust their

insulin, diet and exercise to prevent highsand lows


18/22

18

JDRF Plans Prospective Studies in Elderly

The JDRF Artificial Pancreas Project

Aims to close the loop tying insulin delivery tocontinuous glucose sensing

Aims to bring new technologies to people withdiabetes that will improve glycemic control anddiabetes outcomes

Plans to fund outcome-based continuous sensortrial in over 65 patients with IDDM

Would like feedback on outcome prioritization


19/22

19

Potential JDRF Studies will Examine

Diabetes Outcomes in Over 65 patients

Randomized controlled trial

Primary outcomes ofA1c and Hypoglycemia

Secondary outcomes of quality of life,glycemic variability, time in target

Economic analysis i.e. fewerhospitalizations, reduced morbidity

JDRF-funded: Independent


20/22

20

References

American Diabetes Association. Standards of medical care in diabetes -2006. Diabetes Care. 2006; 29Suppl 1:S4-42.

Bailey T., Kaplan R., Schwartz S. Reduction in A1c with Real-Time Continuous Glucose Monitoring:Interim Results from a 12-Week Clinical Study. ADA Late breaking Abstract 1-LB. 2006 AnnualScientific Sessions.

Ben-Ami H, Nagachandran P, Mendelson A et al. Drug-induced hypoglycemic coma in 102 diabeticpatients. Arch Intern Med 1999; 159: 281284.

Bhatia V, Wilding GE, Dhindsa G, Bhatia R, Garg RK, Bonner AJ, Dhindsa S. Association of poor

glycemic control with prolonged hospital stay in patients with diabetes admitted withexacerbation of congestive heart failure. Endocr Pract. 2004; 10: 467-71.

Bode BW, Schwartz S, Stubbs HA, Block JE. Glycemic characteristics in continuously monitoredpatients with type 1 and type 2 diabetes: normative values. Diabetes Care. 2005; 28: 2361-6.

Brown AF, Mangione CM, Saliba D, Sarkisian CA; California Healthcare Foundation/AmericanGeriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improvingthe care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003; 51(5 SupplGuidelines): S265-80.

Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414:813-20.

Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabeticComplications. JAMA. 2006; 295: 1707-8.

Cryer P, Davis SN, and Shamoon, H.,. Hypoglycemia in Diabetes, Diabetes Care. 2003; 26: 1902-12.


21/22

21

References

Diabetes Control and Complications Trial Research Group. The effect of intensive treatment ofdiabetes on the development and progression of long-term complications in insulin-dependentdiabetes mellitus. N Engl J Med 1993; 329: 977-986.

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and ComplicationsResearch Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after atrial of intensive therapy. N Engl J Med 2000; 342: 381-389.

DMICCHbA1c, Diabetes and Public Health December 12, 2005 Summary Minutes.http://www.niddk.nih.gov/federal/dmicc/2005/12-12-05/summary.pdf

Dronge AS, Perkal MF, Kancir S, Concato J, Aslan M, Rosenthal RA. Long-term glycemic control andpostoperative infectious complications. Arch Surg. 2006; 141: 375-80.

Garg S., ZisserH., Jovanovic L. Improvement in Glucose Excursions Using a Seven-Day ContinuousGlucose Sensor: Managing the Extremes. Abstract Number: 393-P. ADA Annual ScientificSessions. 2006.

Garg S, ZisserH, Schwartz S, et. al. Improvement in Glycemic Excursions With a Transcutaneous,Real-Time Continuous Glucose Sensor: A randomized controlled trial, Diabetes Care. 2006; 29:44-50.

Gradman TJ, Laws A, Thompson LW, Reaven GM: Verbal learning and/or memory improves withglycemic control in older subjects with non-insulin dependent diabetes mellitus. J Am Geriatr

Soc. 1993; 41: 1305-12.Kennedy RL et al. Accidents in patients with insulin-treated diabetes: increased risk of low-impact

falls but not motor vehicle crashes- a prospective register-based study. J Trauma. 2002; 52:660-6.

Meneilly GS, Cheung E, Tessier D, Yakura C, Tuokko H: The effect of improved glycemic control oncognitive functions in the elderly patient with diabetes. J Gerontol. 1993; 48: M117-21.

Meneilly GS, Cheung E, Tuokko H. Altered responses to hypoglycemia of healthy elderly people. JClin Endocrinol Metab. 1994; 78: 1341-8.


22/22

22

References

Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress byacute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type2 diabetes. JAMA. 2006; 295: 1681-7.

Morisaki N, Watanabe S, Kobayashi J, Kanzaki T, Takahashi K, Yokote K, Tezuka M, Tashiro J,Inadera H, Saito Y, et al. Diabetic control and progression of retinopathy in elderly patients: five-year follow-up study. J Am Geriatr Soc. 1994; 42: 142-5.

Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B;Diabetes Control and Complications Trial/Epidemiology of Diabetes. Interventions andComplications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and

cardiovascular disease in patients with type 1 diabetes N Engl J Med. 2005; 353: 2643-53.Oomichi T, Emoto M, Tabata T, Morioka T, Tsujimoto Y, Tahara H, Shoji T, Nishizawa Y. Impact of

glycemic control on survival of diabetic patients on chronic regular hemodialysis: a 7-yearobservational study. Diabetes Care. 2006; 29: 1496-500.

Presentations at the 9-05 EASD meeting in Athens, Greece and the 11-05 Diabetes TechnologyMeeting in San Francisco.

Report from the American Diabetes Association Workgroup on Hypoglycemia, 2005. Diabetes Care28: 1245-9.

The American Association of Clinical Endocrinologists Medical Guidelines for the Management of

Diabetes Mellitus:The AACE System of Intensive Diabetes Self-Management2002 Update.Endocrine Practice. 2002; Vol. 8 (Suppl. 1).

UKPDS Group. Intensive blood glucose control with sulphonylureas or insulin compared withconventional treatment and risk for complications in patients with type 2 diabetes. Lancet. 1998;352: 837-853.

Documents

4 Importance of Glycemic Control, The Potential Benefits of New Technologies