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Prevention Techniques for Diabetes Mellitus: Type 1 and 2

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

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  1. Prevention Techniques for Diabetes Mellitus: Type 1 and 2 Stephanie Pike Course: PAS 646 Advisor: Dennis Karounos, M.D.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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!

  10. 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

  11. 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

  12. 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!!!

  13. 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

  14. 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

  15. 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

  16. References: • 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: www.endotext.org, 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. • Greenbaum CJ, Cuthbertson D, Krischer JP, and the Diabetes Prevention Trial of Type 1 Diabetes Study group. Type 1 diabetes manifested solely by 2-h oral glucose tolerance test criteria. Diabetes 2001; 50: 470-476. • 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.

  17. More References… • Kibirige M, Renuka R, Metcalf B, Wilkin TJ. Testing the accelerator hypothesis. Diabetes Care 2003; 26: 2865-2870. • 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: http://ndep.nih.gov/, 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.

  18. More References… • Rayfield EJ, Kelly KJ, Yoon JW. Rubella virus-induced diabetes in the hamster. Diabetes. 1986; 35(11): 1278-1281. • 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: www.diabetestrialnet.org, 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.

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