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The insulin resistance syndrome, pre diabetes and obesity Shlomit Shalitin

The insulin resistance syndrome, pre diabetes and obesity Shlomit Shalitin Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel; Petah Tiqva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Prevalence of Childhood Obesity.

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The insulin resistance syndrome, pre diabetes and obesity Shlomit Shalitin

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  1. The insulin resistance syndrome, pre diabetes and obesity Shlomit Shalitin Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel; Petah Tiqva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

  2. Prevalence of Childhood Obesity • The prevalence of obesity in adolescence in the USA is 10-25% • Obesity prevalence in the USA among adolescents increased by 20% in the last decade

  3. Risks of Obesity “Sudden death is more common in those who are naturally fat than in the lean” Hipocrates • BMI’s in excess of 28 kg/m² are associated with a 3- 4-fold increase in risk of hypertension, dyslipidemia, insulin resistance (IR) and type 2 diabetes.

  4. Global Projections for the DiabetesEpidemic: 2003-2025 (millions) 38.2 44.2 16% Europe North America Asia 25.0 39.7 59% 81.8 156.1 91% Middle East 18.2 35.9 97% Africa 13.6 26.9 98% South &Central America 10.4 19.7 88% Oceania 1.1 1.7 59% WORLD 2003 = 189 million 2025 = 324 million Increase 72%

  5. Type 2 diabetes mellitus in the young population • The prevalence of type 2 diabetes in the young population is increasing throughout the world wherever childhood obesity is becoming more prevalent • The risk of type 2 diabetes increases with the degree and duration of obesity and with a more central distribution of body fat.

  6. Genetics and Environment in obesity IR and type 2 diabetes

  7. Insulin resistance (IR) • IR is defined as an impaired ability of plasma insulin at usual concentrations to adequately promote peripheral glucose disposal, suppress hepatic glucose, and inhibit VLDL output. • IR can be inferred on clinical evidence and confirmed by insulin and glucose measurements made by fasting insulin/glucose screening, OGTT, and insulin/glucose clamp studies.

  8. “The metabolic syndrome” • Diagnosis is made if ≥ 3 of the following criteria are met: • Obesity(BMI z score ≥2, adjusted for age & gender). • Hypertension(values >95th percentile for age & gender). • Dyslipidemia(triglyceride >95th percentile, HDL • cholesterol< 5th percentile, adjusted for age & gender). • Insulin resistance, IGT or type 2 diabetes. • Hepatic steatosis • Hyperandrogenism /PCO • Acanthosis nigricans, striae • Pseudoacromegaly, low IGFBP-1 • Increased CRP, TNFαlevels

  9. NEJMJune 3 2004

  10. CLINICAL STUDY: Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity-a problem that is no longer restricted to minority groupsWiegand S et al,Paediatric Endocrinology, Charitי Children's Hospital; Humboldt University Berlin; Germany Eur J Endocrinol 2004

  11. Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary care center in IsraelS Shalitin, M Abrahami, P Lilos, M Phillip Aim To establish the prevalence of IR and IGT and their determinants in obese children and adolescents. Methods The group study included 234 patients (BMI ≥ 95thpercentile for age & sex)& 22 patients (BMI 85th-95thpercentilefor age & sex)aged 5-22 ys who had been referred between 1997-2003. Fasting blood samples were obtained for evaluation of glucose, insulin and lipid profile. Estimates of insulin resistance (HOMA-IR), insulin sensitivity (QUICKI, GF/IF) and β- cell function (HOMA%B) were derived from fasting measurements. An OGTT was performed in 192 patients to determine the presence of IGT.

  12. Clinical characteristics of obese children and adolescents

  13. Clinical & laboratory characteristics of obese children and adolescents

  14. Clinical & laboratory characteristics of obese children and adolescents (cont.)

  15. Characteristics of obese children and adolescents with normal or impaired glucose tolerance

  16. Characteristics of obese children and adolescents with normal or impaired glucose tolerance

  17. Results • Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. • GF/IF & QUICKI decreased significantly during puberty(p<0.005). • Insulin resistance & insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or type 2 diabetes in family. • Only 2 patients with IGT also had impaired fasting glucose.

  18. Conclusions: • Insulin resistance is highlyprevalent in obese children and adolescents. • Neither fasting blood glucose or insulin levels nor HOMA-IR or HOMA-%B are effective in the screening of IGT. • As there are no predictive cut-point values of insulin resistance or insulin sensitivity indexes for IGT, an OGTT is required in all subjects at high risk. • Improving insulin resistance may be crucial in the prevention of both type 2 diabetes and premature cardiovascular disease in this at-risk population.

  19. ADA recommendations for screening for type 2 diabetes in youth • BMI> 85th percentile for age and gender • Any 2 or more of the following risk factors: • Family history of type 2 diabetes in first or second-degree relative • Member of a high risk ethnicity • Signs of insulin resistance: acanthosis nigricans, hypertension, dyslipidemia, or PCOs. Screening should include a fasting plasma glucose (Begin testing at 10 years old or at onset of puberty).

  20. As IR is the precursor of type 2 diabetes, and IR begins in childhood, then the earlier an intervention can be initiated in the natural history of the disease, the more effective it will be to prevent or delay progression to diabetes. • Modest weight reductions of 5-10% significantly decrease the risk of complications of IR.

  21. Prevention and treatment • Family based behavioral interventions for obese children have been associated with reductions in cholesterol, increases in HDL, and reductions in IR. Pasquali R, JCEM 1989. • There are reports that with appropriate changes in lifestyle (diet & physical activity) and weight reduction progression from IGT to diabetes can be delayed or prevented. Tuomilehro J et al. N Engl J Med, 2001.

  22. Prevention and treatment The STOP-NIDDM trial has shown that pharmacological intervention with Acarbose in adult patients with IGT can reduce the progression to type 2 diabetes by 25%. This trial also demonstrated that Acarbose increases the probability that IGT will revert to normal glucose tolerance over time.Chiasson-JL et al. Lancet, 2002.

  23. Prevention and treatment

  24. Thank you

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