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Lin Childhood Diabetes Center

from Blood glucose & Diabetes to Insulin & Metabolic Syndrome The changing face of childhood diabetes. Lin Childhood Diabetes Center. T1DM (childhood diabetes). Blood glucose regulation & Insulin (injections) DCCT. Lin Childhood Diabetes Center. T2DM Uncommon Undefined disease onset

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Lin Childhood Diabetes Center

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  1. fromBlood glucose & Diabetes toInsulin & Metabolic SyndromeThe changing face of childhood diabetes Lin Childhood Diabetes Center

  2. T1DM (childhood diabetes) Blood glucose regulation & Insulin (injections) DCCT Lin Childhood Diabetes Center

  3. T2DM Uncommon Undefined disease onset Usually Obese Dyslipidemia common Undefined role of hyperglycemia and hyperinsulinemia Overproduction of endogenous beta-cell hormones T1DM Common Defined disease onset Usually non-obese Dyslipidemia uncommon Major role of hyperglycemia No endogenous beta-cell hormone production Childhood Diabetes Lin Childhood Diabetes Center

  4. Distribution of BMI by Type of Diabetes Lin Childhood Diabetes Center

  5. Lin Childhood Diabetes Center

  6. Overweight and ObesityThe Millennium Epidemics Lin Childhood Diabetes Center

  7. The Epidemics Of Childhood Obesity USA Lin Childhood Diabetes Center

  8. Epidemics Of Childhood Obesity Europe

  9. Frequency of T2DM in USA

  10. Adult obesity & Health risk Lin Childhood Diabetes Center

  11. Hyperinsulinemia and Insulin resistance • Is a risk factor for the development of T2DM • Is also a risk factor for cardiovascular disease in persons with and without diabetes WHO committee on Diabetes and its complications (2005) Lin Childhood Diabetes Center

  12. Childhood Obesity & MTS • In Israel about 30% of adults are obese • In USA 1/5 children is obese • Childhood overweight predisposes to adult obesity, and its associated diseases • A world wide increase in the frequency of MTS is reported among children Lin Childhood Diabetes Center

  13. Components of MTS Central obesity CHO intolerance Hypertension Dyslipidemia Endothelial dysfunction/microalbuminuria Lin Childhood Diabetes Center

  14. The Metabolic Syndrome and Chronic Old Age Diseases Central/abdominal obesity Hyperinsulinemia Type 2 diabetes Insulin resistance syndrome Coronary heart disease Hypertension Dyslipidemia Microalbuminuria Groop et al. Front Horm Res 1997; 22:131–156.

  15. Childhood Obesity Is it a predisposing condition to development of old age disease ? or Is it a disease by itself ? Lin Childhood Diabetes Center

  16. Aims • To estimate the prevalence of IGT & T2DM among obese children with overweight. • To estimate the prevalence of MTS or its individual components in children with overweight. • To study the insulin response and sensitivity in obese children • To define predisposing factors for MTS development Lin Childhood Diabetes Center

  17. Study Group Study group 374 children (BMI>95ile) Sex F/M = 211/163 Age range = 1-17.8 yr. • =<10 yr. n= 132 (pre- pubertal group) • > 10 yr. n= 242 (adolescents group) Ethnicity • 83 = Ashkenazi • 90 = Non-Ashkenazi • 65 = Mixed • 72 = Arab and Druze • 64 = Undetermined Lin Childhood Diabetes Center

  18. Early Severe Metabolic Syndrome (ESMTS) n = 11 (age 13-16yrs.) f/m=8/3 Presented all components of MTS Lin Childhood Diabetes Center

  19. Control Groups a). Healthy, non-obese children No = 191 81= prepubertal, 110= adolescents F/M = 83/108 b). Children with T1DM No = 96 22 = prepubertal, 74 = adolescents F/M= 53/43

  20. Evaluation • Individual medical history. • Family history of obesity and T2DM • Daily activity (sedentary, physical) • Diet and nutrition • Physical examination focusing on Acanthosis Nigricans • Antrophometry: BMI; Bioimpedance; W/H ratio • Laboratory: Hematology; Biochemistry, Lipid and Hormones

  21. CHO intolerance by OGTT Inclusion criteria for OGTT • A family history of DM/MTS • Severe obesity • Severe acanthosis nigricans Subjects studied (OGTT) • 111 = obese children • 66 = control Parameters evaluated • Blood glucose, Insulin, and C-peptide Lin Childhood Diabetes Center

  22. Data Analysis • CHO intolerance ADA criteria • Insulin sensitivity and beta-cell function OGTT (2000, Diabetes Care) Homeostasis Model Assessment (HOMA) (1985, Diabetologia) Insulinogenic index, glucose predisposition index (2000, Diabetes Care) • Definitions of MTS TC, TG, LDL ( 95th), HDL (<5th) Hypertension (HTN) ( 95th), IGT/DM

  23. Results

  24. Results: Life Style Prepubertal (mean) Sedentary activity = 2.6 hr/day Physical activity = 1.6 hr/day Adolescents (mean) Sedentary activity = 4.6 hr/day Physical activity = 2.1 hr/day

  25. Acanthosis Nigricans Lin Childhood Diabetes Center

  26. Frequency of Acanthosis Nigricans Was found in 34.5 % of obese children and adolescents

  27. Childhood Acanthosis Nigricans And Ethnicity In Israel Lin Childhood Diabetes Center

  28. BMI Distribution by Groups Lin Childhood Diabetes Center

  29. Aims • To estimate the prevalence of IGT & T2DM among children with overweight. • To estimate the prevalence of metabolic syndrome or its individual components in children with overweight. • To study the insulin response and sensitivity in obese children and their controls • To define predisposing factors for MTS development Lin Childhood Diabetes Center

  30. CHO intolerance by OGTT • 3% (3/101) = Silent diabetes • 8% (8/101) = IGT No pathology among prepubertal obese children Lin Childhood Diabetes Center

  31. Family History STUDY FAM. FAM. GROUP T2DM OBESITY • Obese 18.7% 62% • IGT+T2DM 33%) 90% • ESMTS 75%) 44% • Normal 3.5% 22% Lin Childhood Diabetes Center

  32. Aims • To estimate the prevalence of IGT & type 2 diabetes among children with overweight. • To estimate the prevalence of MTS or its individual components in children with overweight. • To study the insulin response and sensitivity in obese children and their controls • To define predisposing factors for MTS development Lin Childhood Diabetes Center

  33. Mean Level Of Dyslipidemia (adolescents)

  34. Frequency of Dyslipidemia (adolescents) **=P<.0001 *=p<.05 ** ** * ** ** ** * ** Lin Childhood Diabetes Center

  35. Mean Level of Dyslipidemia (prepubertal)

  36. Frequency of Dyslipidemia (prepubertal) **=P<.0001 *=p<.05 ** ** ** ** ** Lin Childhood Diabetes Center

  37. Mean Level of Blood Pressure (adolescents)

  38. **=P<.0001 *=p<.05 ** ** ** ** ** ** Lin Childhood Diabetes Center

  39. Mean Level of Blood Pressure (prepubertal)

  40. **=P<.0001 *=p<.05 ** ** ** ** Lin Childhood Diabetes Center

  41. AIMS • To estimate the prevalence of IGT & type 2 diabetes among children with overweight. • To estimate the prevalence of metabolic syndrome or its individual components in children with overweight. • To study the insulin response and sensitivity in obese children and their controls • To define predisposing factors for MTS development Lin Childhood Diabetes Center

  42. Blood Glucose And Insulin Response In Obese Adolescents Mean BG Insulin Iinsulin C-pep C-pep fasting fasting AUC fasting AUC (mg/dl) (pmol/l) U x hr (pmol/l) (U x hr) Obese 84±8 125±78 1290 ±545 1200 ±445 5734 ±1493 IGT 90±14 184 ±129 1793 ± 863 1643 ± 482 6831 ±2165 & DM ESMTS 145 ±22 217±132 ND 1429 ± 568 ND Normal 84 ± 9 84 ± 22 734 ± 88 617 ±249 ND P <0.0001 0.0001 <0.0001 <0.0001 0.06 Lin Childhood Diabetes Center

  43. Insulin Sensitivity & Beta-cell Function In Obese Adolescents HOMA ISI Ins. Glu. I phase II phase index predis. index Obese 3.6 ±2.4 0.06 ±.03 16 ±14 16,109 2426 ±1046 597 ±245 IGT 6.1 ±6 -0.02 ±.02 12 ±11 8,120 2211 ±980 557 ±225 & DM ESMTS 11.5 ±9 ND ND ND ND ND Normal 2.6 ±8 .8 0.13 ±.00 8 ±1.8 15,388 1460 ±170 378 ±38 P<0.0001 <0.0001 0.02 0.0008 0.0002 <0.0001 Lin Childhood Diabetes Center

  44. AIMS • To estimate the prevalence of IGT & type 2 diabetes among children with overweight. • To estimate the prevalence of metabolic syndrome or its individual components in children with overweight. • To study the insulin response and sensitivity in obese children and their controls • To define predisposing factors for MTS development Lin Childhood Diabetes Center

  45. Predisposing Factors Obese Obese ESMTS simple silent DM n 90 11 9 ---------------------------------------------------------------------------------------------- Age (y) 13.9 ± 2 15.5 ± 1.3 15 ± 2.2 BMI 32.6 ± 6.8 40.4 ± 3.8 32.7 ± 6.7 F/M 44/46 8/37/2 Fam. DM (%) 17 3371 Fam .Obes (%) 71 90 38 Fast. Ins. (pmol/l) 125±78 184 ±129 217±132 HOMA 3.6 ±2.4 6.1 ±6 11.5 ±9

  46. MTS Predictors Adolescents BMI > 38 Females Acanthosis Nigricans Family History of T2DM/obesity Fasting Hyperinsulinemia (>180) Insulin Resistance (Homa > 4 ) Lin Childhood Diabetes Center

  47. Summary • Above 10% of obese children in Israel have either IGT or T2DM. • About 50% of obese prepubertal children and adolescents have dyslipidemia and HTN • Acantosis Nigricans was found in 34% of obese children and adolescents, more frequent among children of Arab and non-Ashkenazi origin. Lin Childhood Diabetes Center

  48. The good news Weight loss and physical activity reverse most of the pathologies in children and adolescents (data not shown) Lin Childhood Diabetes Center

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