Type 2 Diabetes in the Elderly: Options for Treatment David Kelley

Decade Population (millions) US Population Aged 85+ Years ( ) Elderly  85 Years of Age Comprise Fastest-Growing Segment of Population

Diagnosing Type 2 Diabetes Type 2 Diabetes*  126 mg/dL  200 mg/dL (7.0 mmol/L)(11.1 mmol/L) Impaired Glucose  126 mg/dL  140 mg/dL (7.8 mmol/L), Tolerance (IGT)(7.0 mmol/L)but  200 mg/dL (11.1 mmol/L) Impaired Fasting  110 mg/dL--- Glucose (IFG)(6.1 mmol/L) but  126 mg/dL *Either of these criteria can establish a diagnosis. Confirmation on a separate day is recommended. Fasting Plasma Glucose (FPG) 2-hr Post-75 g Oral Glucose

Harris MI, et al. Diabetes Care. 1998;21: Resnick HE, et al. Diabetes Care. 2000;23: Percentage of Population NHANES III High Prevalence of Type 2 Diabetes Among Elderly People Age (years) Previously diagnosed diabetes Newly diagnosed diabetes by FPG Newly diagnosed diabetes by OGTT (IPH)

Adapted from Resnick HE, et al. Diabetes Care. 2000;23: NHANES III Percentage of Newly Diagnosed Diabetes Missed Age (years) Diagnoses Missed (%)

Wahl PW, et al. Lancet. 1998;352: Rodriguez BL, et al. Diabetes Care. 1996;19: Prevalence (%) Age (years) Diabetes Persists in Populations  70 Years of Age Cardiovascular Health Study Honolulu Heart Study

Cardiovascular Health Study Wahl PW, et al. Lancet. 1998;352: Prevalence (%) NormoglycemicIFGIGTNew Diabetes Identifying Diabetes Mellitus in Elderly People: OGTT vs. FPG Classification Based on FPG Based on OGTT

Isolated Postchallenge Hyperglycemia in Elderly Patients l IPH = FPG <126 mg/dL (7.0 mmol/L) + 2-hr postchallenge PG  200 mg/dL (11.1 mmol/L) l Prevalence of IPH increases with age l Clinicians who rely solely on FPG may miss the diagnosis in many elderly patients

Rancho Bernardo Study Barrett-Connor E, et al. Diabetes Care. 1998;21: Relative Risk *P=0.005 **P=0.01 Clinical Importance of IPH in Elderly Patients CVD MortalityIHD Mortality Classification Men Women * **

Weyer C, et al. J Clin Invest. 1999;104: Inadequate  -cell Compensation for Insulin Resistance NGT IGT DIA Nonprogressors (N = 31) Progressors (N = 17)  -cell Function Insulin Sensitivity NGT

20g Glucose Ward WK, et al. Diabetes Care. 1984;7: Time (min) 20g Glucose Plasma IRI (pmol/L) Loss of First Phase Insulin Secretion in Type 2 Diabetes Normal Type 2 Diabetes

Changes in Postprandial Glucose and Insulin Levels with Aging Chen M, et al. J Am Geriatr Soc. 1987;35: Insulin (mcg/mL) Time (min) Glucose (mg/dL) Time (min) OldYoung

IGT, obeseNormal, obese IGT, nonobeseNormal, nonobese Link between Impaired Early Insulin Release and Excessive Prandial Glucose Excursions Mitrakou A, et al. N Engl J Med. 1992;326: hour Plasma Glucose (mmol/L) Insulin Concentration at 2 Hours (pmol/L) r = 0.52 P < hour Plasma Glucose (mmol/L) Insulin Concentration at 30 Minutes (pmol/L) r = P <

Kelley D, et al. Metabolism. 1994;43: Mechanism of Postprandial Hyperglycemia: Glucose Production Time (min) Type 2 DiabetesControl Endogenous Glucose (µmol/min/kg) Ingested Glucose (µmol/min/kg)

Adapted from Halter JB. In: Masoro EJ (ed). Handbook of Physiology, Volume on Aging Insulin Resistance Mild Hyperglycemia  -cell Function Normal Hyperinsulinemia Euglycemia Abnormal Impaired Insulin Secretion Hyperglycemia AdaptationMaladaptation Interaction Between Impaired Insulin Secretion and Insulin Resistance in Type 2 Diabetes

Pathophysiology of Type 2 Diabetes in Elderly People: Impaired Insulin Secretion Factors Predisposing the Elderly to Diabetes Age-related Decreased Insulin Secretion Age-related Insulin Resistance Decreased Physical Activity Drugs Genetics Coexisting Illness Adiposity

Pathophysiology of Type 2 Diabetes in Elderly People: Impaired Insulin Sensitivity Factors Predisposing the Elderly to Diabetes Age-related Decreased Insulin Secretion Age-related Insulin Resistance Decreased Physical Activity Drugs Genetics Coexisting Illness Adiposity

*BMI  Mokdad A H, et al. JAMA. 1999;282: , 2001;286: Obesity* Trends Among U.S. Adults BRFSS, 1991, 1995 and 2000 No Data <10%10-14%15-19%  20%

* Diagnosed diabetes including women with a history of GDM Diabetes* Trends Among U.S. Adults BRFSS, 1990, 1995 and 2000 No Data <4%4-6%>6%

BMI and Risk of Type 2 Diabetes Mellitus in Women Colditz GA. Ann Intern Med. 1995;122: BMI (kg/m 2 ) Relative Risk (Age adjusted)

Correlation Between BMI and Body Fat Percentage Jackson A.S. et al Int. J. Obesity 2002;26: Body Mass Index (wt/kg 2 ) Percent Body Fat (%) Men Women

Abdominal CT Visceral Adipose Tissue Subcutaneous Adipose Tissue

Probability of Developing Diabetes: BMI and WHR WHR = waist to hip ratio. Ohlson LO et al, Diabetes. 34:1055-8, 1985 Relative Risk BMI Tertile WHR Tertile

Relationship Between Visceral Adipose Tissue and Insulin Action Banerji, M et al Am J Physiol 1997; 273:E425-E432 Glucose Disposal (mg/kg LBM/min) Visceral adipose tissue volume per unit surface area (L/m 2 ) Women Men

Skeletal Muscle fat LessMore Most

Loci of IR in Skeletal Muscle:

Healthy Aging and and Body Composition (HEALTH ABC) Epidemiology, Demography and Biometry Program, NIA Objective: To relate changes in body composition in old age, particularly increases in body fat and decline in lean mass and bone mineral, to disease and disability. 3,075 men and women age y high proportion of African-Americans free from disability and free of functional limitations Major outcome variables to be examined yearly over 7 years: Self-reported disability Measures of physical function, eg. Rising from a chair, balance Measures of muscle strength Walking endurance

We Lose Muscle as We Age “Sarcopenia” Men Women

BMI (kgm -2 ) Muscle attenuation is associated with obesity in Health ABC