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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

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Prevention techniques for diabetes mellitus type 1 and 2 l.jpg

Prevention Techniques for Diabetes Mellitus: Type 1 and 2

Stephanie Pike

Course: PAS 646


Dennis Karounos, M.D.

Types of diabetes l.jpg
Types of Diabetes:


    • 5-10% cases

    • Autoimmune disease

    • Requires insulin

    • Spontaneous?

    • Genetic predisposition


    • 90-95% cases

    • Insulin resistance and beta cell dysfunction

    • Genetic predisposition- Strong


Prevention of t1dm rubella avoidance l.jpg

  • 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 avoidance4 l.jpg

  • 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 l.jpg

  • Breastfeeding- independent protective factor

    • Case controlled dataset

    • T1DM decreased as Breastfeeding increased

    • SO… breastfeeding helps protect from T1DM

      • Duration unclear

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  • 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 l.jpg

  • 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 l.jpg

  • 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

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  • 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 l.jpg

  • 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

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  • NIH Trialnet

    • Multi-center, international

      • Natural history studies

      • Diabetes prevention studies

      • Diabetes intervention studies

    • Actively recruiting

      • New onset diabetes

      • First degree relatives


Prevention of t2dm lifestyle changes l.jpg

  • 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


Prevention of t2dm stop smoking l.jpg
Prevention of T2DM:STOP SMOKING

Insulin 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 l.jpg

    • 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


    Clinical application conclusion15 l.jpg

    • 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

    References l.jpg

    • American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 2006; 29 (Suppl. 1): S43-S48.

    • Andreoli TE, Carpenter CC, Griggs RC, Loscalzo J, editors. Cecil Essentials of Medicine. 6th Ed.Philadelphia: W. B. Saunders Company; 2004.

    • Endotext, Current Strategies for the Prevention of Type 1 and 2 Diabetes Mellitus- Chapter 41. Available at:, Accessed on October 30, 2005.

    • England LJ, Levine RJ, Qian C, Soule LM, Schisterman EF, Yu KF, et al. Glucose tolerance and risk of gestational diabetes mellitus in nulliparous women who smoke during pregnancy. Am J Epidemiol 2004; 160: 1205-1213.

    • Foy CG, Bell RA, Farmer DF, Goff DC, Wagenknecht. Smoking and incidence of diabetes among U.S. adults. Diabetes Care 2005; 28: 2501-7.

    • Francis BH, Thomas AK, McCarthy CA. The impact of rubella immunization on the serological status of women of childbearing age: a retrospective longitudinal study in Melbourne, Australia. Am J Public Health 2003; 93: 1274-1276.

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    • Hanson RL, Imperatore G, Bennett PH, Knowler WC. Components of the “metabolic syndrome” and incidence of type 2 diabetes. Diabetes 2002; 51: 3120–3127.

    • Karounos DG. Convergence of genetic and environmental factors in the immunopathogenesis of type 1 diabetes mellitus. J Clin Ligand Assay 1998; 3: 262-271.

    • Karounos DG, Bryson JS, Cohen DA. Metabolically inactive insulin analog prevents type 1 diabetes in prediabetic NOD mice. J Clin Invest 1997; 100: 1344-1348.

    • Karounos DG, Wolinsky JS, Thomas JW. Monoclonal antibody to rubella virus capsid protein recognizes a β-cell antigen. J Immunol 1993; 150: 3080- 3085.

    More references l.jpg
    More References…

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    • Kliegman RM, Jenson HB, Marcdante KJ, Behrman RE. Nelson Essentials of Pediatrics.5th Ed. Philadelphia: Elsevier Saunders; 2006.

    • Knip M, Sakkinen A, Huttunen NP, Kaar ML, Lankela S, Mustonen A, et al. Postinitial remission in diabetic children—an analysis of 178 cases. Acta Paediatr Scand. 1982; 71: 90-98.

    • Knowler WC, Barrett-Conner E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. The Diabetes Program Prevention Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403.

    • Kobayashi T, Maruyama T, Shimada A, Kasuga A, Kanatsuka A, Takei I, et al. Insulin intervention to preserve β cells in slowly progressive insulin-dependent (type 1) diabetes mellitus. Ann NY Acad Sci 2002; 958: 117-130.

    • Malcova H, Sumnik Z, Drevinek P, Venhacova J, Lebi J, Cinek O. Absence of breast-feeding is associated with the risk of type 1 diabetes: a case-control study in a population with rapidly increasing incidence. Eur J Pediatr 2006; 165: 114-119.

    • Manson JE, Ajani UA, Liu S, Nathan DM, Hennekens CH. A prospective study of cigarette smoking and the incidence of diabetes mellitus among US male physicians. Am J Med 2000; 109: 538-542.

    • Menser MA, Forrest JM, Bransby RD. Rubella infection and diabetes mellitus. Lancet. 1978; 1: 57-60.

    • National Institutes of Health, National Diabetes Education Program. Available at:, Accessed on October 30, 2005.

    • Palmer JP. Beta cell rest and recovery-does it bring patients with latent autoimmune diabetes in adults to euglycemia? Ann NY Acad Sci 2002; 958: 89-98.

    More references18 l.jpg
    More References…

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    • Sadauskaite-Kuehne V, Ludvigsson J, Padaiga Ž, Jašinskinenė E, Samuelsson U. Longer breastfeeding in an independent protective factor against development of type 1 diabetes mellitus in childhood. Diabetes Metab Res Rev 2004; 20: 150-157.

    • Schoenhoff DD, Lane TW, Hansen CJ. Primary prevention and rubella immunity: overlooked issues in the outpatient obstetric setting. Infect Control Hosp Epidemiol 1997; 18: 633-636.

    • Sklyer JS, Brown D, Chase HP, Collier E, Cowie C, Eisenbarth GS, et al. Diabetes Prevention Trial- Type 1 (DPT-1) Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 2002; 346: 1685-1691B.

    • The Diabetes Control and Complications Trial (DCCT) Research Group. Effect of intensive therapy on residual β-cell function in patients with type 1 diabetes in the diabetes control and complications trail. Ann Intern Med 1998; 128: 517-523.

    • Trialnet. Available at:, Accessed on February 3, 2006.

    • Vaarala O, Knip M, Paronen J, Hämäläinen A, Muona P, Väätäinen M, et al. Cow’s milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 1999; 48: 1389-1394.

    • Waston JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Reccom Rep 1998; 47: 1-57.

    • Weitzman M, Cook S, Auinger P, Florin TA, Daniels S, Nguyen M, et al. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 2005; 112; 862-869.