Judith Fradkin, M.D.Director, Division of Diabetes,

Endocrinology, and Metabolic Diseases

National Institute ofDiabetes and

Digestive and Kidney Diseases

Diabetes and Obesity in WomenDiabetes and Obesity in Women

Diabetes: Diabetes: Scope of the ProblemScope of the Problem

• >17 million Americans

• Leading cause of:– Kidney failure, adult blindness, amputations

• Cardiovascular disease: main cause of death

• Estimated $132 billion health care costs

0

5

10

15

20

25

30

Peo

ple

(m

illi

on

s)

1960

1970

1980

1990

2000

2010

2020

2030

2040

2050

Diagnosed cases

Projected diagnosed cases

Prevalence of Diagnosed Diabetes in the United States

Diagnosed (1960-1998) and Projected Diagnosed (2000-2050) Cases

Data for 1960-1998 from the National Health Interview Survey, NCHS, CDC.

Projected data for 2000-2050 from Boyle JP, et al, Diabetes Care 24:1936-40, 2001.

Year

Estimated Growth in Type 2 Estimated Growth in Type 2 Diabetes and US Population Diabetes and US Population

From 2000-2050From 2000-2050

0

20

40

60

80

100

12020

00

2005

2010

2015

2020

2025

2030

2035

2040

2045

2050

Year

Per

cent

incr

ease

Type 2 DM

General population

Working age population (20-59)

Bagust A, et al. Diabetes 50, Suppl 2 A205, 2001

Prevalence of Diabetes by Race/Ethnicity and Sex

Gender Specific Effects of Diabetes

• Health risk to woman

• Health risk to offspring

• Prevention is possible

1 2 3 4 5 6 7Relative Risk

Adventist

Nurses

NHANES

Rancho

Framing

Chicago Ht

Cardiovascular Mortality: WomenDiabetes vs Nondiabetes

Diabetes and Atherosclerosis

• DM a CAD Risk Equivalent• Lose gender protection: equal age adjusted rates MI, stroke

claudication• Claudication increased 3.5-fold men and 8.6-fold women

(Framingham)• Mortality post MI double in diabetes• Mortality increased 1.4-fold for men and 1.9-fold women

(Italy) and 1.6-fold for men and 2.6-fold for women (Finland)

• CAD mortality decreasing in general population, steady in men with DM and increasing in women with DM (NHANES)

Source: National Health and Nutrition Examination Survey (NHANES), CDC, NCHS.

0

5

10

15

20

25

30

35

Black, not Hispanic

MalesFemalesMexicanAmerican

White, notHispanic

2010Target

Aspirin Therapy*: Persons with Diabetes, Age 40 years and Over, 1988-94

Age-adjusted percent

Total

*Took aspirin at least 15 times in past month. I 95% confidence interval.

The ABC’s of DiabetesThe ABC’s of DiabetesKnow Your NumbersKnow Your Numbers

AA is for A1C

BB is for Blood Pressure

CC is for Cholesterol

Gender Specific Effects on Acute Complications of T1D

• Adolescent girls had 2-3 fold increased risk DKA compared to boys or younger girls

• Adolescent girls had rates of hypoglycemia like DCCT conventional group while boys were similar to intensive group

• Hypothesis that girls skip insulin for fear of weight gain

Gestational Diabetes

• 14% of pregnancies• 135,000 women in U.S. annually• GDM has same risk factors as type 2 diabetes• Fetal macrosomia risk related to postprandial

glycemia• Increased diabetes in offspring• 60-90% risk of recurrence• risk of type 2 diabetes after pregnancy 30% over

10 years

Mother with Mother with DiabetesDiabetes

Woman with Woman with DiabetesDiabetes

Infant of Infant of Diabetic MotherDiabetic Mother

Diabetes in Pregnancy and Offspring: Diabetes in Pregnancy and Offspring: The Vicious CycleThe Vicious Cycle

Pettitt & Knowler, Pettitt & Knowler, J Obes Wt Reg J Obes Wt Reg 19881988

0

20

40

60

5-9 10-14 15-19 20-24 25-29

Age (years)

Prev

alen

ce (%

) nondiabeticprediabeticdiabetic

Diabetes in Offspring By Maternal Diabetes in Pregnancy

MotherMother

Birth Weight and Risk for Gestational Diabetes

• U shaped curve with increased risk at low birth weight and high birth weight

• Effect of high birth weight disappears with adjustment for maternal diabetes

• Susceptibility to diabetes and insulin resistance may be programmed in utero

0

10

20

30

10-19 20-29 30-39

Age (years)

Prev

alen

ce (%

)

>2 mo. Never

Prevalence of Diabetes Prevalence of Diabetes in Pima Indians by Infant Feedingin Pima Indians by Infant Feeding

Pettitt: Lancet, 1997Pettitt: Lancet, 1997

Breast FedBreast Fed

Adj. OR = 0.38 (0.16 – 0.89)Adj. OR = 0.38 (0.16 – 0.89)

0

5

15

25

10

20

30

Non-HispanicWhite

Non-HispanicBlack

Boys Aged 12-19 years

MexicanAmerican

P =<.001

P =<.001

P =.35

Non-HispanicWhite

Girls Aged 12-19 years

Non-HispanicBlack

MexicanAmerican

P =.10

P =.002

P =.08

Perc

enta

ge

Overweight Prevalence by Race/Ethnicity for Adolescent Boys and Girls

SOURCES: National Health and Nutrition Examination Survey,National Center for Health Statistics, CDC

NHANES III1988-1994NHANES1999-2000

Obesity and Women

• Major determinant of health related quality of life in women throughout the lifespan

• 34% of women vs 27.7% of men were obese in NHANES 1999-2000

• 6.3% of women vs 3.1% of men with class 3 obesity

• 15% of black women have class 3 obesity– 3-fold increase compared to non-Hispanic white women and Mexican American women

The Toll of Obesity

• Premature mortality: 280,000 deaths in U.S. annually

• Increased type 2 diabetes, CVD, arthritis, cancer• Strong correlation with low SES particularly in

women• Strong correlation with sedentary activities (TV

watching in women) and inverse correlation with physical activity

The Diabetes Prevention Program

A U.S. Randomized Clinical Trial to Prevent Type 2 Diabetes

in Persons at High Risk

Mean Weight Change from Baseline

-8

-7-6

-5

-4-3

-2

-10

1

Wei

gh

t C

han

ge

(Kg

)

0 6 12 18 24 30 36 42 48 Months

Lifestyle

Metformin

+Placebo

0 1 2 3 4

0

10

20

30

40

Placebo (n=1082)Metformin (n=1073, p<0.001 vs. Placebo)Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Placebo )

Percent Developing Diabetes Percent Developing Diabetes

All participants

Years from randomization

Cu

mu

lati

ve i

nci

den

ce (

%)

Small Steps. Big Small Steps. Big Rewards.Rewards.

What’s Your Game Plan?What’s Your Game Plan?