Prevention Techniques for Diabetes Mellitus:

Type 1 and 2

Stephanie Pike

Course: PAS 646

Advisor:

Dennis Karounos, M.D.

Types of Diabetes: TYPE 1 DIABETES (T1DM)

5-10% cases Autoimmune disease Requires insulin Spontaneous? Genetic predisposition

TYPE 2 DIABETES (T2DM) 90-95% cases Insulin resistance and beta cell dysfunction Genetic predisposition- Strong

OTHERS

Prevention of T1DM:RUBELLA AVOIDANCE

Congenital Rubella Syndrome (CRS) Viral infection that correlates with T1DM

STUDY- Infected rabbits with CR Result: Changes in rabbit beta cells similar to

those in diabetic mice Direct infection vs. Indirect

Indirect- Induces an immune response Study- molecular mimicry

Prevention of T1DM:RUBELLA AVOIDANCE

Clinically: MMR vaccine prevents infection!

Children: 12-15 mo; again 4-6 yrs Question women of childbearing age

Vaccinate; avoid pregnancy for 28 days Titer: family planning Susceptible pregnant women: vaccinate after delivery

before hospital discharge

Prevention of T1DM:BREAST MILK VS. COW’S MILK

Breastfeeding- independent protective factor Case controlled dataset T1DM decreased as Breastfeeding increased SO… breastfeeding helps protect from T1DM

Duration unclear

Prevention of T1DM:BREAST MILK VS. COW’S MILK

Parallel effect: Avoiding cow’s milk Bovine insulin-binding antibodies Cross reacting to induce T1DM Prospective study 200 infants

Cow’s milk associated with T1DM

Clinically: Breastfeed and avoid cow’s milk for as long as

possible up to 12 mo.

Prevention of T1DM:HONEYMOON STAGE

Honeymoon stage Functional recovery of beta cell function Need for exogenous insulin low

Continue insulin Low dose basal insulin Endogenous insulin secretion Better metabolic control

After honeymoon stage Long honeymoon = Better metabolic control after remission Study 178 diabetic children and adolsecents

Prevention of T1DM:ACCELERATOR HYPOTHESIS

Lifestyle factors overlooked in T1DM Autoimmune disease Is this appropriate?

T2DM and Obesity Well known correlation

Past 35 years… Obesity- doubled T2DM- doubled T1DM- doubled

Prevention of T1DM:ACCELERATOR HYPOTHESIS

Study- retrospective; 94 children in UK Greater BMI at diagnosis T1DM earlier age

Overlap of prevention measures Same intense lifestyle changes

Don’t believe? Prevent CV disease!

Prevention of T1DM:CLINICAL TRIALS

DPT-1 Large, multicenter

Insulin as antigen specific immune therapy Unsuccessful, BUT…

Accurate predictions ID Asymptomatic pts Insulin- does not accelerate disease process

More… Preclinical trials

Successful in mouse model Dosing? Metabolically inactive insulin analog

Prevention of T1DM:CLINICAL TRIALS

NIH Trialnet Multi-center, international

Natural history studies Diabetes prevention studies Diabetes intervention studies

Actively recruiting New onset diabetes First degree relatives www.diabetestrailnet.org

Prevention of T2DM:LIFESTYLE CHANGES

Definitive data Eating healthy + regular exercise STUDY 3234 overweight, non-diabetic individuals

Placebo Medication-31% Intense lifestyle changes– 58%

Clinically NEDP suggests

30 min physical activity 5 days each week Eating healthier Losing small amt weight

THIS IS NOT EASY!!!

Prevention of T2DM:STOP SMOKINGInsulin Resistance Atherosclerosis Study

906 subjects Current smokers- 25% T2DM w/in 5 years Never smokers- 14% T2DM w/in 5 years

Physician’s Health Study Prospective study Smokers- age adjusted relative risk 2:1 for T2DM

Pregnant women Decreased glucose tolerance Inc risk gestational diabetes

Children- Second hand smoke 2273 subjects Independently associated with metabolic syndrome

CLINICAL APPLICATION--CONCLUSION:

First or second degree T1DM relative Rubella

Vaccinate children with MMR Question and Retest titer in women of childbearing

age; Vaccinate women if necessary Breast feed 3-12 mo. Honeymoon stage- continue insulin therapy Lifestyle changes- diet and exercise Clinical trials

www.diabetestrialnet.org

CLINICAL APPLICATION--CONCLUSION:

T2DM in family Hx; sedentary lifestyle; overweight Intense lifestyle changes

Exercise 30 min 5 days/week Eat healthier Goal: BMI < 24.9

Stop smoking No smoking during pregnancy Avoid exposing children to second hand smoke Will also reduce risk of cardiovascular disease

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