PreventionTechniquesforDiabetesMellitusType1and2

1、Prevention Techniques for Diabetes Mellitus: Type 1 and 2Stephanie PikeCourse: PAS 646Advisor: Dennis Karounos, M.D.1Types of Diabetes:TYPE 1 DIABETES (T1DM)5-10% casesAutoimmune diseaseRequires insulinSpontaneous?Genetic predispositionTYPE 2 DIABETES (T2DM)90-95% casesInsulin resistance and beta ce

2、ll dysfunctionGenetic predisposition- StrongOTHERS2Prevention of T1DM:RUBELLA AVOIDANCECongenital Rubella Syndrome (CRS)Viral infection that correlates with T1DMSTUDY- Infected rabbits with CRResult: Changes in rabbit beta cells similar to those in diabetic miceDirect infection vs. IndirectIndirect-

3、 Induces an immune responseStudy- molecular mimicry3Prevention of T1DM:RUBELLA AVOIDANCEClinically:MMR vaccine prevents infection!Children: 12-15 mo; again 4-6 yrsQuestion women of childbearing ageVaccinate; avoid pregnancy for 28 daysTiter: family planningSusceptible pregnant women: vaccinate after

4、 delivery before hospital discharge4Prevention of T1DM:BREAST MILK VS. COWS MILKBreastfeeding- independent protective factorCase controlled datasetT1DM decreased as Breastfeeding increasedSO breastfeeding helps protect from T1DMDuration unclear5Prevention of T1DM:BREAST MILK VS. COWS MILKParallel ef

5、fect: Avoiding cows milkBovine insulin-binding antibodiesCross reacting to induce T1DMProspective study 200 infantsCows milk associated with T1DMClinically:Breastfeed and avoid cows milk for as long as possible up to 12 mo.6Prevention of T1DM:HONEYMOON STAGEHoneymoon stageFunctional recovery of beta

6、 cell functionNeed for exogenous insulin lowContinue insulinLow dose basal insulinEndogenous insulin secretionBetter metabolic controlAfter honeymoon stageLong honeymoon = Better metabolic control after remissionStudy 178 diabetic children and adolsecents7Prevention of T1DM:ACCELERATOR HYPOTHESISLif

7、estyle factors overlooked in T1DMAutoimmune diseaseIs this appropriate?T2DM and ObesityWell known correlationPast 35 yearsObesity- doubledT2DM- doubledT1DM- doubled8Prevention of T1DM:ACCELERATOR HYPOTHESISStudy- retrospective; 94 children in UKGreater BMI at diagnosis T1DM earlier ageOverlap of pre

8、vention measuresSame intense lifestyle changesDont believe?Prevent CV disease!9Prevention of T1DM:CLINICAL TRIALSDPT-1Large, multicenterInsulin as antigen specific immune therapyUnsuccessful, BUTAccurate predictionsID Asymptomatic ptsInsulin- does not accelerate disease processMorePreclinical trials

9、Successful in mouse modelDosing?Metabolically inactive insulin analog10Prevention of T1DM:CLINICAL TRIALSNIH TrialnetMulti-center, internationalNatural history studiesDiabetes prevention studiesDiabetes intervention studiesActively recruiting New onset diabetesFirst degree relatives11Prevention of T

10、2DM:LIFESTYLE CHANGESDefinitive dataEating healthy + regular exerciseSTUDY 3234 overweight, non-diabetic individualsPlaceboMedication-31%Intense lifestyle changes 58%ClinicallyNEDP suggests30 min physical activity 5 days each weekEating healthierLosing small amt weightTHIS IS NOT EASY!12Prevention o

11、f T2DM:STOP SMOKINGInsulin Resistance Atherosclerosis Study906 subjectsCurrent smokers- 25% T2DM w/in 5 yearsNever smokers- 14% T2DM w/in 5 yearsPhysicians Health StudyProspective studySmokers- age adjusted relative risk 2:1 for T2DMPregnant womenDecreased glucose toleranceInc risk gestational diabe

12、tesChildren- Second hand smoke2273 subjectsIndependently associated with metabolic syndrome13CLINICAL APPLICATION-CONCLUSION:First or second degree T1DM relativeRubellaVaccinate children with MMRQuestion and Retest titer in women of childbearing age; Vaccinate women if necessaryBreast feed 3-12 mo.H

13、oneymoon stage- continue insulin therapyLifestyle changes- diet and exerciseClinical trials14CLINICAL APPLICATION-CONCLUSION:T2DM in family Hx; sedentary lifestyle; overweightIntense lifestyle changesExercise 30 min 5 days/weekEat healthier Goal: BMI 24.9Stop smokingNo smoking during pregnancyAvoid

14、exposing children to second hand smokeWill also reduce risk of cardiovascular disease15References: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 o

15、f 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

16、 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

17、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 diabet

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20、l antibody to rubella virus capsid protein recognizes a -cell antigen. J Immunol 1993; 150: 3080- 3085.16More ReferencesKibirige 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 Essential

21、s 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 childrenan analysis of 178 cases. Acta Paediatr Scand. 1982; 71: 90-98.Knowler WC, Barrett-Conner E, Fowler SE, Hamman RF, Lachin JM

22、, 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 cell

23、s 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 increasi

24、ng 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

25、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: 89-98.17

26、More ReferencesRayfield EJ, Kelly KJ, Yoon JW. Rubella virus-induced diabetes in the hamster. Diabetes. 1986; 35(11): 1278-1281.Sadauskaite-Kuehne V, Ludvigsson J, Padaiga , Jainskinen E, Samuelsson U. Longer breastfeeding in an independent protective factor against development of type 1 diabetes me

27、llitus 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.