Prevention Of Diabetes

Prevention Of DiabetesType 2 Diabetes: Hyperglycemia

Insulin Resistance

Relative Impairment of Insulin Secretion

Pathogenesis: Poorly Understood

Genetic Factors Affecting Insulin Release and Responsiveness + Environmental Factors Such As Obesity Are Important.

Why PreventionType 2 diabetes One of the most common chronic diseases in the US and one of the fastest growing diseases in the world. In US, lifetime risk of developing Diabetes for individuals born in the year 2000 is 33% for males 39% for females.Diabetes has enormous human and financial costsA leading cause of heart disease, blindness, kidney failure, and amputationsCan be hard to treat once it developsThere are ways to improve glucose tolerance

Prediction Ability to predict and prevent type 2 diabetes in the

general population is limited.

However, we can identify hi risk groups of people such as:1) Close relatives with diabetes.2) Obesity and body fat distribution.3) Age and certain ethnic groups.4) Physical inactivity.5) Previous gestational diabetes.6) Elevated fasting glucose.7) Impaired glucose tolerance.

Family History and Risk of NIDDM

In the U.S. Positive family history imparts 2.7 fold risk of NIDDM after adjustment of other factors (Cowie, 1993).

Based on NHANES II , risk of NIDDM among Caucasians was 1.8 fold higher with one family member, 3.8 fold higher with two or more family members compared to persons with no known family history of NIDDM.

Obesity

Fat distribution

Birth Weight

There is an apparent inverse relationship between birth weight and risk of type 2 diabetes.

Subjects who had low birth weights have reduced beta cell function as adults, insulin resistance, and an increased incidence of type 2 diabetes.

Impaired Glucose Tolerance?

Risk factor for type 2 diabetes

– Increases risk of type 2 diabetes 5 - 8 fold

– 1- 9% per year develop type 2 diabetes

Major risk factor for heart disease

IGT may be the best time to intervene

– No symptoms

– May be reversible

– Diabetes complications have not developed

Gestational Diabetes The risk of type 2 diabetes is higher in women

who have gestational diabetes.

They have defects in both insulin secretion and insulin action.

2 studies have shown a five year incidence of 47-50 percent for type 2 diabetes in women with gestational diabetes.

The greatest increase in the risk was in the first five years.

Diabetes Prevention Program Clinics

..

.

..

.

.

. ..

. .

. ..

.

.... ..

.. ..27 clinics27 clinics3,819 participants3,819 participants

DPP Timeline

6/94 6/95 6/96 6/97 6/98 6/99 6/00 6/01 6/02

Planning Phase Began

Recruitment Began

Troglitazone stopped Recruitment

ended

DMBRecommendsEarly Termination

Volunteersunmasked

DPP Goals

PrimaryTo prevent or delay

type 2 diabetes in people with impaired glucose tolerance (IGT)

Secondary Reduce heart

disease and stroke Reduce risk factors

for heart disease and stroke

Who was eligible for the DPP? Individuals with IGT

– Fasting glucose 95-125 mg/dl – American Indians 125 mg/dl And– 2 hour glucose 140-199 mg/dl

Body mass index > 24 kg/m2 (Asians > 22 kg/m2 ) Age > 25 years Men and women All ethnic groups

Study InterventionsScreenScreen

RandomizeRandomize

Standard lifestyle teachingStandard lifestyle teaching

Intensive Intensive LifestyleLifestyle(n = 1079)(n = 1079)

MetforminMetformin(n = 1073)(n = 1073)

PlaceboPlacebo(n = 1082)(n = 1082)

TroglitazoneTroglitazonen= 585n= 585Until 6/98Until 6/98

Lifestyle Intervention

Intensive lifestyle goals

• Reduction of fat and calorie intakeReduction of fat and calorie intake

• Physical activity at least 150 minutes/week Physical activity at least 150 minutes/week

• Achieve and maintain at least 7% weight Achieve and maintain at least 7% weight lossloss

Metformin - 850 mg tablet once a day Metformin - 850 mg tablet once a day increasing after 4 weeks toincreasing after 4 weeks to

two a daytwo a day

Troglitazone - 400 mg per dayTroglitazone - 400 mg per day

Placebo- Placebo- Placebo tablets Placebo tablets

InterventionsInterventions

Medications

Average Weight ChangeAverage Weight Change

-8

-7

-6

-5

-4

-3

-2

-1

0

1

Wei

ght C

hang

e

( Kg

)

0 6 12 18 24 30 36 42

Months in study

Lifestyle

Metformin

+

Placebo

0 1 2 3 4

0

10

20

30

40

Placebo (n=1082)

Metformin (n=1073, p<0.001 vs. Plac)

Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )

Percent of all participants developing diabetes Percent of all participants developing diabetes

Years in study

Cu

mu

lati

ve i

nci

den

ce (

%)

Lifestyle

Metformin

Placebo

Development of Diabetes

Placebo Life-style Metformin

Percent developing 11.0% 4.8% 7.8%

diabetes each year

Reduction of diabetes ---- 58% 31% compared with placebo

Placebo, Lifestyle and Metformin

0

20

40

60

Lifestyle Metformin Placebo

Freq

uenc

y

(%)

Normal Diabetes

Percent of participants with normal glucose Percent of participants with normal glucose tolerance tolerance

or diabetes at 3 yearsor diabetes at 3 years

0

3

6

9

12

15

24-30 (n=1045) 30-36 (n=1174) > 36 (n=1015)

Cas

es

/

100

pers

on

- yrLifestyle Metformin Placebo

Diabetes incidence rates by BMI

Conclusions

• Intensive Lifestyle and Metformin Intensive Lifestyle and Metformin were accepted, well tolerated, and were accepted, well tolerated, and safesafe • Intensive lifestyle achieved weight Intensive lifestyle achieved weight loss and increased activityloss and increased activity

Conclusions

• Intensive lifestyle intervention reduced Intensive lifestyle intervention reduced the development of diabetes by 58%the development of diabetes by 58%

• Metformin reduced the development of Metformin reduced the development of diabetes by 31%diabetes by 31%

•Troglitazone reduced the development Troglitazone reduced the development of diabetes by 23% (used for only 10 of diabetes by 23% (used for only 10 months)months)

Conclusions

• Intensive Lifestyle was more Intensive Lifestyle was more effective than metformineffective than metformin

• Intensive Lifestyle and Metformin Intensive Lifestyle and Metformin were effective in both women and were effective in both women and men and all ethnic-racial groups men and all ethnic-racial groups

Conclusions

Diabetes can be delayed orDiabetes can be delayed orprevented for at least 3 years prevented for at least 3 years in people at high risk, such as in people at high risk, such as

those in the DPPthose in the DPP