Type 2 Diabetes in the Elderly: Options for Treatment David Kelley.
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Transcript of Type 2 Diabetes in the Elderly: Options for Treatment David Kelley.
1900 1930 1960 1990 2020 2050
Decade
Po
pu
lati
on
(m
illi
on
s)
US Population Aged 85+ Years (1900-2050)
Elderly 85 Years of Age Comprise Fastest-Growing Segment of Population
0
5
10
15
20
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-hrPost-75 g
Oral Glucose
Harris MI, et al. Diabetes Care. 1998;21:518-524.Resnick HE, et al. Diabetes Care. 2000;23:176-180.
Per
cen
tag
e o
f P
op
ula
tio
n
NHANES III
High Prevalence of Type 2 Diabetes Among Elderly People
0
5
10
15
20
40-49 50-59 60-74Age (years)
Previously diagnosed diabetes
Newly diagnosed diabetes by FPG
Newly diagnosed diabetes by OGTT (IPH)
Adapted from Resnick HE, et al. Diabetes Care. 2000;23:176-180.
NHANES III
Percentage of Newly Diagnosed Diabetes Missed
0
20
40
60
80
100
40-44 45-49 50-54 55-59 60-64 65-69 70-74Age (years)
Dia
gn
ose
s M
isse
d (
%)
Wahl PW, et al. Lancet. 1998;352:1012-1015.Rodriguez BL, et al. Diabetes Care. 1996;19:587-590.
Pre
vale
nce
(%
)
Age (years)
Diabetes Persists in Populations 70 Years of Age
0
5
10
15
20
25
30
35
40
70-74 75-79 80-84 85+
Cardiovascular Health Study
Honolulu Heart Study
Cardiovascular Health Study
Wahl PW, et al. Lancet. 1998;352:1012-1015.
Pre
vale
nce
(%
)
Normoglycemic IFG IGT New Diabetes
Identifying Diabetes Mellitus in Elderly People: OGTT vs. FPG
0
20
40
60
80
Classification
Based on FPGBased on OGTT
Isolated Postchallenge Hyperglycemia in Elderly Patients
IPH = FPG <126 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
Rancho Bernardo Study
Barrett-Connor E, et al. Diabetes Care. 1998;21:1236-1239.
Rel
ativ
e R
isk
*P=0.005**P=0.01
Clinical Importance of IPH in Elderly Patients
0
1
2
3
4
CVD Mortality IHD MortalityClassification
Men
Women* **
Weyer C, et al. J Clin Invest. 1999;104:787-794.
Inadequate -cell Compensation for Insulin Resistance
0
100
200
300
400
500
0 1 2 3 4 5
NGT
IGT
DIA
Nonprogressors (N = 31)
Progressors(N = 17)
-ce
ll F
unct
ion
Insulin Sensitivity
NGTNGTNGTNGT
NGTNGT
20g Glucose
Ward WK, et al. Diabetes Care. 1984;7:491-502.
Time (min) Time (min)
20g Glucose
Pla
sm
a IR
I (p
mo
l/L)
Pla
sm
a IR
I (p
mo
l/L)
Loss of First Phase Insulin Secretionin Type 2 Diabetes
0
200
400
600
800
-60 0 60 120 180
0
200
400
600
800
-60 0 60 120 180
Normal Type 2 Diabetes
Changes in Postprandial Glucose and Insulin Levels with Aging
Chen M, et al. J Am Geriatr Soc. 1987;35:417-424.
0
20
40
60
80
100
-30 0 30 60 90 120 150
Insu
lin
(m
cg/m
L)
Time (min)
80
100
120
140
160
180
-30 0 30 60 90 120 150
Glu
cose
(m
g/d
L)
Time (min)
Old Young
IGT, obese Normal, obese
IGT, nonobese Normal, nonobese
Link between Impaired Early Insulin Release and Excessive Prandial Glucose Excursions
Mitrakou A, et al. N Engl J Med. 1992;326:22-29.
0
200
400
600
800
1000
5 6 7 8 9 10 11 12 13
2-hour Plasma Glucose (mmol/L)
Insu
lin
Co
nce
ntr
atio
n
at 2
Ho
urs
(p
mo
l/L
) r = 0.52P < 0.01
0
100
200
300
400
500
600
5 6 7 8 9 10 11 12 13
2-hour Plasma Glucose (mmol/L)
Insu
lin
Co
nce
ntr
atio
n
at 3
0 M
inu
tes
(pm
ol/
L) r = -0.75
P < 0.0001
0
4
8
12
16
20
-60 0 60 120 180 240 300 360
Kelley D, et al. Metabolism. 1994;43:1549-1557.
Mechanism of Postprandial Hyperglycemia: Glucose Production
-4
0
4
8
12
16
-60 0 60 120 180 240 300 360
Time (min) Time (min)
Type 2 Diabetes Control
En
do
ge
no
us
Glu
cos
e (µ
mo
l/min
/kg
)
Ing
este
d G
luco
se
(µm
ol/
min
/kg
)
Adapted from Halter JB. In: Masoro EJ (ed). Handbook of Physiology, Volume on Aging. 1995.
Insulin Resistance
Mild Hyperglycemia
-cell Function
Normal
Hyperinsulinemia
Euglycemia
Abnormal
Impaired Insulin Secretion
Hyperglycemia
Adaptation Maladaptation
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
CoexistingIllness
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
CoexistingIllness
Adiposity
*BMI 30
1991 1995
2000
Mokdad A H, et al. JAMA. 1999;282:1519-1522, 2001;286:1195-2000.
Obesity* Trends Among U.S. Adults
BRFSS, 1991, 1995 and 2000BRFSS, 1991, 1995 and 2000
No DataNo Data
<10%<10%
10-14%10-14%
15-19%15-19%
20%20%
*Diagnosed diabetes including women with a history of GDM
1990 1995
2000
Diabetes* Trends Among U.S. Adults
BRFSS, 1990, 1995 and 2000BRFSS, 1990, 1995 and 2000
No DataNo Data
<4%<4%
4-6%4-6%
>6%>6%
BMI and Risk of Type 2 Diabetes Mellitus in Women
Colditz GA. Ann Intern Med. 1995;122:481-486.
0
10
20
30
40
50
60
70
80
90
100
<22 23 24 25 25-27 27-29 29-31 31-33 33-35 >35
BMI (kg/m2)
Rel
ativ
e R
isk
(Age
adj
uste
d)
Correlation Between BMI and Body Fat Percentage
Jackson A.S. et al Int. J. Obesity 2002;26:789-796.
0
10
20
30
40
50
60
15 20 25 30 35 40 45 50
Body Mass Index (wt/kg2)
Per
cen
t B
od
y F
at (
%)
Men
Women
0
5
10
15
20
25
III II I
I
II
III
Probability of Developing Diabetes:BMI and WHR
WHR = waist to hip ratio.Ohlson LO et al, Diabetes. 34:1055-8, 1985
Rel
ativ
e R
isk
BMI Tertile
WHR T
ertile
Relationship Between Visceral Adipose Tissue and Insulin Action
Banerji, M et al Am J Physiol 1997; 273:E425-E432
0
2
4
6
8
10
12
14
16
18
1 2 3 4 5Glu
co
se
Dis
po
sal (
mg
/kg
LB
M/m
in)
Visceral adipose tissue volume perunit surface area (L/m2)
Women Men
Healthy Aging and and Body Composition(HEALTH ABC)
Epidemiology, Demography and Biometry Program, NIAObjective: 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
We Lose Muscle as We Age“Sarcopenia”
60
80
100
120
140
160
180
60
80
100
120
140
160
180
Mid
-thi
gh C
SA
(cm
2)
<71 71-72 73-74 75-76 77-78 79-80
Age (y)
Men
Women