Harry Shamoon

1
Type 2 Diabetes in the Elderly Options for
Treatment
David Kelley
2
Elderly ?85 Years of Age Comprise
Fastest-Growing Segment of Population
US Population Aged 85 Years (1900-2050)
20
15
Population (millions)
10
5
0
1900
1930
1960
1990
2020
2050
Decade
3
Diagnosing Type 2 Diabetes
2-hrPost-75 gOral Glucose
Fasting Plasma Glucose(FPG)

• 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.
4
High Prevalence of Type 2 Diabetes Among Elderly
People
NHANES III
20
Previously diagnosed diabetes
Newly diagnosed diabetes by FPG
15
Newly diagnosed diabetes by OGTT (IPH)
Percentage of Population
10
5
0
50-59
40-49
60-74
Age (years)
Harris MI, et al. Diabetes Care.
199821518-524.Resnick HE, et al. Diabetes
Care. 200023176-180.
5
Percentage of Newly Diagnosed Diabetes Missed
NHANES III
100
80
60
Diagnoses Missed ()
40
20
0
40-44
45-49
50-54
55-59
60-64
65-69
70-74
Age (years)
Adapted from Resnick HE, et al. Diabetes Care.
200023176-180.
6
Diabetes Persists in Populations ?70 Years of Age
40
Cardiovascular Health Study
35
Honolulu Heart Study
30
25
Prevalence ()
20
15
10
5
0
75-79
80-84
70-74
85
Age (years)
Wahl PW, et al. Lancet. 19983521012-1015.Rodrig
uez BL, et al. Diabetes Care. 199619587-590.
7
Identifying Diabetes Mellitus in Elderly People
OGTT vs. FPG
Cardiovascular Health Study
80
Based on FPG Based on OGTT
60
Prevalence ()
40
20
0
Normoglycemic
IFG
IGT
New Diabetes
Classification
Wahl PW, et al. Lancet. 19983521012-1015.
8
Isolated Postchallenge Hyperglycemia in Elderly
Patients

• IPH FPG lt126 mg/dL (7.0 mmol/L) 2-hr
  postchallenge PG ?200 mg/dL (11.1 mmol/L)
• Prevalence of IPH increases with age
• Clinicians who rely solely on FPG may miss the
  diagnosis in many elderly patients

9
Clinical Importance of IPH in Elderly Patients
Rancho Bernardo Study
4
Men

Women

3
Relative Risk
2
1
0
CVD Mortality
IHD Mortality
Classification
P0.005 P0.01
Barrett-Connor E, et al. Diabetes Care.
1998211236-1239.
10
Inadequate ?-cell Compensation for Insulin
Resistance
500
Nonprogressors (N 31)

400
NGT
300
?-cell Function
NGT
NGT
NGT
200
IGT
Progressors(N 17)
100
DIA
0
0
1
2
3
4
5
Insulin Sensitivity
Weyer C, et al. J Clin Invest. 1999104787-794.
11
Loss of First Phase Insulin Secretionin Type 2
Diabetes
20g Glucose
20g Glucose
Plasma IRI (pmol/L)
Plasma IRI (pmol/L)
Time (min)
Time (min)
Normal Type 2
Diabetes
Ward WK, et al. Diabetes Care. 19847491-502.
12
Changes in Postprandial Glucose and Insulin
Levels with Aging
Insulin (mcg/mL)
Glucose (mg/dL)
Time (min)
Time (min)
Old Young
Chen M, et al. J Am Geriatr Soc. 198735417-424.
13
Link between Impaired Early Insulin Release and
Excessive Prandial Glucose Excursions
r 0.52 P lt 0.01
r -0.75 P lt 0.0001
Insulin Concentration at 2 Hours (pmol/L)
Insulin Concentration at 30 Minutes (pmol/L)
2-hour Plasma Glucose (mmol/L)
2-hour Plasma Glucose (mmol/L)
IGT, obese Normal, obese IGT, nonobese Normal,
nonobese
Mitrakou A, et al. N Engl J Med. 199232622-29.
14
Mechanism of Postprandial Hyperglycemia Glucose
Production
Endogenous Glucose (µmol/min/kg)
Ingested Glucose (µmol/min/kg)
Time (min)
Time (min)
Type 2 Diabetes Control
Kelley D, et al. Metabolism. 1994431549-1557.
15
Interaction Between Impaired Insulin Secretion
and Insulin Resistance in Type 2 Diabetes
Insulin Resistance Mild Hyperglycemia ?-cell
Function
Normal Hyperinsulinemia Euglycemia
Abnormal Impaired Insulin Secretion Hyperglycemia
Adaptation
Maladaptation
Adapted from Halter JB. In Masoro EJ (ed).
Handbook of Physiology, Volume on Aging. 1995.
16
Pathophysiology of Type 2 Diabetes in Elderly
People Impaired Insulin Secretion
Age-related Decreased Insulin Secretion
Coexisting Illness
Factors Predisposing the Elderly to Diabetes
Genetics
Age-related Insulin Resistance
Drugs
Adiposity
Decreased Physical Activity
17
Pathophysiology of Type 2 Diabetes in Elderly
People Impaired Insulin Sensitivity
Age-related Decreased Insulin Secretion
Coexisting Illness
Factors Predisposing the Elderly to Diabetes
Genetics
Age-related Insulin Resistance
Drugs
Adiposity
Decreased Physical Activity
18
Obesity Trends Among U.S. Adults
BRFSS, 1991, 1995 and 2000
2000
No Data lt10 10-14 15-19 ? 20
BMI ? 30
Mokdad A H, et al. JAMA. 19992821519-1522,
20012861195-2000.
19
Diabetes Trends Among U.S. Adults
BRFSS, 1990, 1995 and 2000
2000
No Data lt4 4-6 gt6
Diagnosed diabetes including women with a
history of GDM
20
BMI and Risk of Type 2 Diabetes Mellitus in Women
Relative Risk (Age adjusted)
BMI (kg/m2)
Colditz GA. Ann Intern Med. 1995122481-486.
21
Correlation Between BMI and Body Fat Percentage
Percent Body Fat ()
Body Mass Index (wt/kg2)
Jackson A.S. et al Int. J. Obesity
200226789-796.
22
Abdominal CT
Visceral Adipose Tissue
Subcutaneous Adipose Tissue
23
Probability of Developing DiabetesBMI and WHR
Relative Risk
WHR Tertile
BMI Tertile
WHR waist to hip ratio. Ohlson LO et al,
Diabetes. 341055-8, 1985
24
Relationship Between Visceral Adipose Tissue and
Insulin Action
Women Men
Glucose Disposal (mg/kg LBM/min)
Visceral adipose tissue volume perunit surface
area (L/m2)
Banerji, M et al Am J Physiol 1997 273E425-E432
25
Skeletal Muscle fat
Less More Most
26
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27
Loci of IR in Skeletal Muscle
28

• 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 70-79 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

29
We Lose Muscle as We AgeSarcopenia
30
Muscle attenuation is associated with obesity in
Health ABC
BMI (kgm-2)