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

30
Type 2 Diabetes in the Elderly: Options for Treatment David Kelley

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

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

Abdominal CT

Visceral Adipose Tissue

Subcutaneous Adipose Tissue

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

Skeletal Muscle fat Less More Most

02468

1012141618

25 30 35 40 45 50

Rd

(mg/

min

/kg

FF

M)

Muscle Attenuation (HU)

r- 0.48, p<0.01

Loci of IR in Skeletal Muscle:

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

25

30

35

40

45

50

25

30

35

40

45

50

Mid

-thi

gh a

tten

uati

on (

HU

)

<24.1 24.1-26.9 26.9-30.1 >30.1BMI (kg•m-2)

Muscle attenuation is associated with obesity in Health ABC