Presentation on theme: "Type 2 Diabetes in Youth Francine Ratner Kaufman, M.D."— Presentation transcript:
1Type 2 Diabetes in Youth Francine Ratner Kaufman, M.D. Distinguished Professor of PediatricsThe Keck School of Medicine of USCHead, Center for Diabetes and EndocrinologyChildrens Hospital Los Angeles
2What Do We Know About Type 2 Diabetes in Youth? QuestionWhat Do We Know About Type 2 Diabetes in Youth?
3Prevalence of Diabetes and IFG in US Adolescents – NHANES 1999-2002 Type 2 Diabetes0.5% of adolescents have diabetes71% type 1 and 29% type 2Determined by insulin use vs no insulin use39,005 US teens with T2DImpaired Fasting Glucose11% had IFG2,769,736 teens with IFGDiabetes Increased 41% from 4.9 to 6.9/1000 from 1997 to adultsDuncan, Arch Pediatr Adolesc Med 2006;160:523; Geiss, Am J Prevent Med 2006;30:371
4Is it an epidemic?The incidence is increasing and probably underestimatedPopulation based estimates indicate an ~10-fold increase in incident cases over the past years8% to 43% of all new cases of diabetes in the United States depending on ethnicityThe SEARCH TrialWhat about prevalence??Bloomgarden ZT. Diabetes Care. 2004;27: Centers for Disease Control. Diabetes Fact Sheet. 2005
5Controversies as to the Nature of this Epidemic Difficult to recruit for the TODAY trial13 centers across the countryPresence of antibodiesThe SEARCH Trial19,000 new patients with T1D4,100 new patients with T2DType 1a+ AbFCP < 0.8 ng/mlType 2- AbFCP > 2.9 ng/mlHybrid
6Diabetes Trends Among Adults in the US BRFSS 1990, 1995 and 2001
7Is Type 2 Diabetes An Epidemic? Little Rock, Cincinnati, San Antonio 35302520% with type 21510587888990919293949596Ten-fold increase 0.7 vs 7.2/1000008% to 43% of all new cases of diabetes in youth in US depending on ethnicityJ Pediatr 136: , 2000
8Question Is the Presentation the Same as in Adults? Does not appear to be preceded by long asymptomatic periodDo not find undiagnosed cases on screening
9Natural History of Type 2 Diabetes ComplicationsGenetic susceptibilityEnvironmental factorsOnset of diabetesDisabilityPREObesity Insulin resistanceOngoing hyperglycemiaDeathRisk forDiseaseMetabolicSyndromeBlindness Renal failure CHD AmputationAtherosclerosis Hyperglycemia HypertensionRetinopathy Nephropathy Neuropathy
10Pre-diabetes (IGT) and T2D Overweight SampleIGTT2DPaulsen et al, 196866 multi-ethnic youth (4-16 years)17%6%Weninger et al, 198015 subjects33%0%Sinha et al, 200255 multi-ethnic youth (>95th %ile)25%112 multi-ethnic teens (>95th %ile)21%4%Goran et al, 2004150 Hispanic +FH(8-13 years >85th %ile)28%IGT = Impaired Glucose Tolerance
13OGTT Feasibility Study Pre-diabetes and Diabetes by ADA Cut-offs Fasting glucose2-hour glucoseNormal(< 140)Pre-diabetes( )Diabetes( 200)(< 100)57.6%0.2%0.0%( )39.7%2.0%0.1%( 126)0.4%
14Type 2 Diabetes ? Curve for Youth B-cell Function (%) Progressive Pancreatic B-cell FailurePrevention and Early TreatmentUKPDS DataB-cell Function (%)? Curve for YouthYears from Clinical Diagnosis
15Occurs at the time of intense insulin resistance due to puberty QuestionIs the Pathophysiology the Same as in Adults?Associated with significant ß-cell failure as well as insulin resistanceOccurs at the time of intense insulin resistance due to puberty
18What distinguishes type 1 from type 2 diabetes in youth? QuestionWhat distinguishes type 1 from type 2 diabetes in youth?
19Type 1 Versus type 2 Diabetes in youth? T1DMT2DMWeight20% may be overweight / obeseVirtually all BMI > 85%th percentileCourseRapidFrom DPT-1 can be indolentIndolentVirtually none found on screeningDKA35%-40%Ketonuria (33%)Mild DKA (5%-25%)Relative with DM5% with T1DMUp to 30% may have with T2DMFH of T2 2-3Xs in person with T174%-100% - 1st –2nd degree with T2DMComorbidThyroid, adrenal, vitiligo, celiacIncrease in polycystic ovary syndromeAcanthosis nigricansC-peptideC-peptide can be preserved at DXNormal or increasedAntibodyEthnicity85%Whites predominate15% (reported as high as 30%)NA, AA, HA, Asian, Pacific IslanderKaufman,Endocrinol Meta Clinics N Am, 34; : 2005
20Differentiation Between Type 1 and 2 48 with type 2 vs 39 with type 1Type 2Ethnicity, 1st degree relative, BMI>24, +C-peptide, acanthosisType 2Type 1DKA33%53%C-peptideug/lug/lAbs8.1% ICA30% GAD 35%IAA85% have islet autoimmunityHathout et al Pediatrics 107e102,June,2001
21Question How Does Type 2 Present in Youth? Is it asymptomatic or symptomatic in youth?
22Diagnosis with Type 2 Fagot-Campagna et al J Pediatr 2000 Mean Age yearsGirls > Boys :1Obese BMI >85th %Minority Groups 94%Strong Family History %Acanthosis Nigricans %Diagnosis made by Symptoms, not ScreeningHbA1c %Weight loss %Glucose in urine 95%Ketosis %DKA %
23Question What Are Treatment Targets in Youth with Type 2 Diabetes? Are they the same as in adults?
24TREATMENT GOALS Glucose control, HbA1c <7% Goals (Diabetes Care, 2000)FGPPBedA1c <7.0TREATMENT GOALSGlucose control, HbA1c <7%Eliminate symptoms of hyperglycemiaMaintenance of reasonable body weightImprove cardiovascular risk factorsReduce microvascular complicationsImprovement in physical and emotional well-being
25Treatment Issues Self-monitoring of blood glucose Fasting and postprandialFrequency depends on regimenMedical Nutrition TherapyDiabetes EducationInvolves familyDirect family supervision produces better glycemic control outcomes1Lifestyle CoachingPreconception counselingImmunizationsDental careSmoking and alcohol counseling1. Bradshaw, J Pediatr Endocrinol Meta 15, 20022. Pediatrics 112:2003 Prevention and treatment of type 2 diabetes in children with special emphasis on Native American Youth
26What are the Treatment Regimens for Youth? QuestionWhat are the Treatment Regimens for Youth?
28Start with insulin and diet, exercise DiagnosisBG 250 mg/dL or 12 mmol/LAsymptomaticStart with insulin and diet, exerciseDiet and exercise<7%<7%Monthly review, A1C q3moAdd metforminAttempt towean insulin>7%Add metformin>7%Add insulin, TZD, sulfonylurea>7%Add 3rd agentTZD = thiazolidinedioneSilverstein JH, Rosenbloom AL.J Pediatr Endcrinol Metab. 2000;13 Suppl 6:
29LWPES Survey 130 Clinical Practices 48% treated with insulin alone2 injections44% with oral agents71% metformin46% sulfonylurea9% TZD4% meglitinide8% lifestyle
30A1c at CHLA 2005 Diabetes Type Type 1 n=1534 Type 2 n=276 A1c % AgeyearsDuration yearsVisit Number
31T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus. Intensive Therapy for Diabetes: Reduction in Incidence of ComplicationsT1DMDCCTT2DMKumamotoUKPDSA1C9% 7%8% 7%Retinopathy63%69%17%–21%Nephropathy54%70%24%–33%Neuropathy60%58%–Cardiovascular disease41%*52*16%*Review DataT1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.*Not statistically significant due to small number of events.†Showed statistical significance in subsequent epidemiologic analysis.DCCT Research Group. N Engl J Med. 1993;329: ; Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28: ; UKPDS 33: Lancet. 1998;352: ; Stratton IM, et al. Brit Med J. 2000;321:
32Long term outcome Pima Indians - diagnosed < 20 years of age 22% had microalbuminuria at diagnosisIncreased to 60% at years of ageIndigenous Canadians- mean age 23 yrs, 9 yrs duration of diabetesHbA1c 10.9%67% poor glycemic control45% hypertension requiring treatment35% microalbuminuria (6% required dialysis)38% pregnancy loss9% mortalityArslanian S. Hormone Res 2002; 57 Suppl 1: Dean., Diabetes 2002;51(Suppl 2):A24.
33Uncontrolled diabetes AmputationsLoss of SensationsHeart diseaseand strokesBlindnessUncontrolled diabetescan lead to…DeathKidney failure
35Studies to Treat Or Prevent Pediatric Type 2 Diabetes STOPP-T2D Funded byNational Institute of Diabetes and Digestiveand Kidney DiseasesNational Institutes of Health
36STOPP-T2 TREATMENT PRIMARY AIM To compare the efficacy of 3 treatment regimensMetforminMetformin + lifestyleMetformin + TZDOn Time to Treatment Failure and on Glycemic ControlTODAY
37Primary Outcomes Treatment goal Treatment failure HbA1c < 6% (glycemic control)Treatment failureHbA1c 8.0% over 6 consecutive monthsORInability to wean from temporary insulin therapy due to metabolic decompensation
38Outcome Measures Glycemia Insulin sensitivity and secretion HbA1c, fasting and postprandial glucose by home monitoringInsulin sensitivity and secretionOGTT, HOMA, QUICKI, proinsulin, C-peptideBody compositionBMI, DEXA, waist circumference, abdominal heightFitness and physical activityPDPAR, PWC 170, accelerometer
39Outcome Measures (continued) Nutritionfood frequency questionnaireCardiovascular disease riskBP, lipids, inflammatory markers, coagulation factorsMicrovascular complicationsmicroalbuminuria, neuropathyQuality of lifeCost
40Inclusion Criteria Age 10 to 17 years Duration of diabetes < 2 yearsBMI 85th percentileAdult involved in the daily activities of the child agrees to participate in the interventionAbsence of pancreatic autoimmunityFasting C-peptide > 0.6 mmol/LFluency in English or Spanish
41National Diabetes Education Program’s Tip Sheets for Kids with Type 2 In terms of publications, these colorful tip sheets provide basic information about type 2 diabetes and encourage young people to take steps to manage the disease for a long and healthy life.Written in simple language, the tip sheets are helpful for anyone who has type 2 diabetes and their loved ones. Topics include:What is Diabetes?Be Active.Stay at a Healthy Weight.Eat Healthy Foods.These tip sheets also are available online on the NDEP website.Additional tip sheets are in development covering dealing with diabetes and diabetes prevention.What is Diabetes?Be ActiveStay at a Healthy WeightEat Healthy Foods
42Helping the Student with Diabetes Succeed The school guide is called Helping the Student with Diabetes Succeed. A Guide for School Personnel.NDEP took on this project because of reports from NDEP partner organizations and their constituents of the lack of awareness and knowledge on how to manage kids with diabetes during the school day and the discrimination against children with diabetes in the school setting.Numerous NDEP partners joined NDEP to create and pretest the school guide.
43Conclusion Increased incidence Difficult to distinguish from type 1 Occurs at the time of intense insulin resistance due to pubertyDoes not appear to be preceded by long asymptomatic periodMore insulin deficiency and requirement for exogenous insulin earlySafety and efficacy of therapeutic agentsRapid progression of co-morbidities and complications