1 / 42

Type 2 Diabetes in the Elderly: Lessons from the Diabetes Primary Prevention Program

Type 2 Diabetes in the Elderly: Lessons from the Diabetes Primary Prevention Program. Andrew P. Goldberg, MD Baltimore VA GRECC University of Maryland School of Medicine 410-605-7183 agoldber@grecc.umaryland.edu. Glucose Tolerance Categories.

amy
Download Presentation

Type 2 Diabetes in the Elderly: Lessons from the Diabetes Primary Prevention Program

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Type 2 Diabetes in the Elderly: Lessons from the Diabetes Primary Prevention Program • Andrew P. Goldberg, MD • Baltimore VA GRECC • University of Maryland School of Medicine • 410-605-7183 • agoldber@grecc.umaryland.edu

  2. Glucose Tolerance Categories Oral Glucose Tolerance TestFasting (2-Hour Glucose During OGTT)(mg/dL) (mg/dL) Normal<110<140 Impaired110-125140-199 Diabetes>125>199 Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-97.

  3. High Prevalence of Type 2 Diabetes Among Elderly People NHANES III Percentage of Population Harris MI, et al. Diab Care. 1998;21:518-524.Resnick HE, et al. Diab Care. 2000;23:176-180.

  4. Prevalenceof Diabesity by Age Percent Diabetic BMI (kg/m2) <22 >35 <22 >35 22-25 26-30 22-25 26-30 31-35 31-35 20 - 54 60 - 74 Age (years)

  5. Model for Age-Related Hyperglycemia Diabetes Risk Factors in Aging Decreased physical activity Increased adiposity Age effects on insulin action INSULIN RESISTANCE Impaired adaptation: No  insulin Progression to IGT and type 2 diabetes Medications Genetics DECREASED INSULIN SECRETION Coexisting illness Age effects on Muscle metabolism and  cells *Chang & Halter. AJP 284:E7-E12, 2003

  6. Normal Adaptation to Insulin Resistance Insulin resistance (of any cause) Compensatory hyperinsulinemia Maintenance of euglycemia Adaptation of -cell function

  7. Aging and Diabetes Comparison AgingDiabetes Inactivity/Deconditioning ++ Body Fat, Muscle++ Central Adiposity++ Atherosclerosis++ Renal failure++ Vision problems++ Cognitive problems++ Neuropathy++ Hypertension++ Insulin signaling/resistance++ Mortality ++ Response to CR++

  8. Atherosclerosis in Diabetes • ~80% of all diabetic mortality • 75% from coronary atherosclerosis • 25% from cerebral or peripheral vascular disease • >75% of all hospitalizations for diabetic complications • >50% of patients with newly diagnosed type 2 diabetes have CHD National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995.

  9. Mechanisms of Atherogenesis in Diabetes • Abnormal lipoproteins and apolipoproteins • Hypertension • Glucose toxicity • Protein glycosylation and glycation • Glycoxidation and oxidation • Insulin resistance and hyperinsulinemia • Procoagulant state • Hormone-, growth-factor–, and cytokine-enhanced SMC proliferation and foam cell formation SMC=smooth muscle cell. Adapted from Bierman EL. Arterioscler Thromb. 1992;12:647-656.

  10. Aging  Energy Flux Exercise  Energy Flux Hypocaloric Diet  Energy Expenditure  Energy Intake Exercise Weight Loss Maintain Muscle Mass  Body Fat Nutritional Balance “Health-Related Fitness” Age, Physical Inactivity, and Obesity

  11. Physical Characteristics of Subjects Dengel, DR. et al. Metabolism, 1998;47(9):1075-1082 Significantly different from Normal Lean men † P < 0.01, Significantly different from Baseline value: * P < 0.05; ** P < 0.01.

  12. ATPIII Criteria for Metabolic Syndrome Metabolic Syndrome if 3 or More: Abdominal Obesity: Waist >102 cm (men), > 88cm (women)  Triglyceride: >150 mg/dl  HDL-C: < 40 mg/dl (men), < 50 mg/dl (women)  BP: >135/85 mm Hg  Fasting Glucose: >100 mg/dl

  13. AEX + WL in Metabolic SyndromeImproves Oral Glucose Tolerance

  14. AE + WL in Metabolic Syndrome Improves Lipid Profiles Data are Mean ± SEM, mg/dl; *p < 0.05; **p < 0.01 vs Baseline

  15. 170 110 160 100 150 Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg) 140 90 130 80 120 110 70 AEX+WL in Metabolic Syndrome Reduces Blood Pressure  = -8%  = -10%

  16. Effects of Exercise and Weight Loss on Components of Metabolic Syndrome Metabolic Abnormality Baseline AEX+WL Central Obesity 17 10 Hypertension 17 6 ­ 17 10 Insulin Glucose Intolerance 10 5 Low HDL-C 17 10 ­ 6 3 TG Totals 84 44

  17. Diabetes Prevention Trials There are now a large number of prevention trials—some limited to life-style intervention, some limited to anti-diabetic drug trials; however, only rarely do studies include both types of potential prevention. • Da Qing IGT and Diabetes Study (Pan et al. Diabetes Care 1997). Randomized 577 IGT subjects (283M/247F) mean age 45yrs –diabetes incidence: control (15.7%) v diet (10%) v exercise (8.3%) v diet + exercise (9.6%). • Finnish Diabetes Prevention Trial (Tuomilehto et al., NEJM 2001). Randomized 422 IGT subjects age 40-64 ( 350F/172M, mean 55 yrs ) to diet counseling and circuit-type weight training vs. control. F/U 3.2 yrs. Diabetes incidence: 58% reduction (19.8% control vs. 8.3% intervention. Of importance to this talk, the Diabetes Prevention Program (NEJM, 2002) is the only one that includes old subjects (60–85 yr).

  18. Diabetes Prevention Program (DPP) A Randomized Clinical Trialat 27 sites to Prevent Type 2 Diabetes in Persons at High Risk

  19. DPP Primary Goal To prevent or delay the development of type 2 diabetes in persons with impaired glucose tolerance (IGT).

  20. Eligibility Criteria • Age > 25 years • Plasma glucose • 2 hour glucose 140-199 mg/dl (7.8- <11.1 mmol/L) and • Fasting glucose 95-125 mg/dl (5.3- <7.0 mmol/L) • Body mass index >24 kg/m2 • All ethnic groups • Goal of up to 50% subjects from high riskpopulations – old, African American, American Indian, Hispanic, Asian NEJM 346:393-403, 2002

  21. Study Interventions Eligible Participants Randomized Standard Lifestyle Recommendations Intensive Metformin Placebo Lifestyle (n = 1079) (n = 1073) (n = 1082)

  22. Sex Distribution Age Distribution DPP Population > 60 20% Men 32% 25-44 31% 45-59 49% Women 68% The DPP Research Group, Diabetes Care 23:1619-29, 2000

  23. Base-Line Characteristics of the Study Participants N Engl J Med, 2002; 346(6):393-403 *Values are means ± SD ¶Data are based on responses to the Modifiable Activity Questionnaire

  24. Lifestyle Intervention Structure • 16 session core curriculum • Long-term maintenance program • Supervised by a case manager & lifestyle support staff • Dietician • Behavioral specialist • Exercise physiologist / trainer

  25. Lifestyle Intervention Exercise Component • Moderate intensity aerobic exercise • Structured classes offered 1-2 x per week • Tool box strategies • Pedometers, exercise videos, health club memberships • Activity assessed by self-report • LoPAR (habitual physical activity) • MAQ (leisure activity)

  26. Mean Change in Leisure Physical Activity Lifestyle Metformin Placebo The DPP Research Group, NEJM 346:393-403, 2002

  27. Incidence of Diabetes Placebo (n=1082) Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Metformin , p<0.001 vs. Placebo) Risk reduction 31% by metformin 58% by lifestyle The DPP Research Group, NEJM 346:393-403, 2002

  28. Mean Weight Change Placebo Metformin Lifestyle The DPP Research Group, NEJM 346:393-403, 2002

  29. Intensive Lifestyle (ILS) Activities by Age Age in years

  30. Changes in Body Fat Distribution ● Placebo; ▲ Metformin; ■ Lifestyle Intervention Diabetes. 2007 Jun;56(6):1680-5.

  31. Hazard Rate for Development of Diabetes in Relation to Weight Change

  32. Diabetes Incidence Rates by Age p = 0.007 ILS by age p= 0.067 metformin by age Age (years) NEJM 346:393-403, 2002

  33. Diabetes Risk Reduction by Age ILS Metformin Percent Risk Reduction * Age in Years * p< 0.05 ILS v. Metformin NEJM 346:393-403, 2002

  34. Percent Achieving Normal Glucose Tolerance by Age ILS Metformin Placebo Percent with NGT Age in Years p=0.01 Metformin by age

  35. Better success in achieving exercise goals Better success in achieving weight loss goals More likely to complete self-monitoring records Achieved greatest reduction in diabetes risk This suggests there are benefits from including older subjects in clinical trials to prevent diabetes DPP : Age 60+ Intensive Lifestyle Group

  36. Change in CVD Risk Factors LifestyleMetforminPlacebo Lipids Blood pressure * mm Hg * mg/dl * * p<0.001 ILS v P, M * p<0.001 ILS v P, M Diabetes 2003; Suppl 1:A169

  37. Change in Non-traditional CVD Risk Markers LifestyleMetforminPlacebo Percent Change at 1 year p< 0.01 Met v Placebo p<0.001 ILS v Placebo Diabetes 2003; Suppl 1:A169

  38. Weight Loss vs. Exercise in Diabetes Prevention • Weight loss was strongest variable associated with reduced diabetes and CVD risk. • For every kg lost, 16% reduction in diabetes risk. • Increased activity, in the absence of weight loss, had minimal effect on diabetes prevention in DPP. • In contrast, Finnish DPS reported those who met physical activity goal, but not wt loss goal, had 70% reduction in DM risk. NEJM 2001;344:1343-50; Cox, et al. Am J Clin Nutr 2004:80:308-16

  39. Summary - DPP • Lifestyle modification can prevent diabetes in high risk older adults • The robust effect in 60+ older subjects was due to greater ILS participation (intensity too low in young and middle-age?) • ILS program preferred over medication in older individuals • Additional benefits of ILS – lower CVD risk factors

  40. Progression to Diabetes Distinct Phenotypes? IGT Older, more sedentary Younger, fitter ? Post-challenge Hyperglycemia Fasting Hyperglycemia >intensity? + + ILS Metformin DIABETES

  41. Prevention of Diabetes • Weight Loss and Exercise : • Increase Aerobic Capacity • Reduce Obesity (central) • Decrease Hyperglycemia • Lower Blood Pressure • Benefit Dyslipidemia • Increase Insulin Sensitivity But also, • Stop Cigarette smoking • Insulin Sensitizers – TZDs, Metformin

  42. Treatment of Type 2 Diabetes OrganGoalLong-Term EffectAction EyesAnnual ExamPrevent RetinopathyLaser Heart, BrainSemiannual CVA, CAD, PADEx+WL Blood Pressure,MI, DeathsACE-I, Lipid Rx Lipids KidneyAnnual Microalbumin ESRDACE-I  DialysisLipid Rx  Transplant LegsCheck Feet Charcot JointFootcare, Pulses, Doppler Revascularize Exercise, Sensory Exam AmputationStents, Bypass Whole BodyQuarterly HbA1c Vascular, Cardiac,Exercise/WL, NeuropathicIntensive ComplicationsGlucose Control

More Related