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Case #1
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  1. Case #1 • 15 yo white male • Referred for evaluation and treatment of obesity and hyperlipidemia detected on routine screening • Otherwise healthy • Past medical history is unremarkable • No current medications

  2. Trend in Overweight Prevalence for Youths 6-17 yrs Troiano et. al (Pediatrics 1998)

  3. Case #1 • Activity • Watching TV, playing video games • Diet • Frequent high-fat fast foods, high-sugar snacks • Skips breakfast • Analysis of 3-day food diary • Average 3360 kcal/day • Diet composition (% of total calories) • Protein 18% • Fat 36% • Carbohydrate 46%

  4. Effect of Television Watching on US Children: 8-16 years old Andersen et. al. (JAMA 1998)

  5. 62 yo hypertension stroke 53 yo diabetes MI 72 yo hypertension 69 yo healthy 38 yo obese CH 204 TG 204 HDL 42 48 yo stroke 39 yo obese hypertension CH 236 TG 499 HDL 28 9 yo healthy CH ? 12 yo obese CH 210 TG 201 HDL 38 15 yo obese Hypertension Type II diabetes CH 226 TG 320 HDL 30 Case #1

  6. Case #1 • Social • Freshman in high school. Described as “average” student. • Smokes 2-3 cigarettes/day • Denies alcohol/substance abuse • Mother accompanies patient to clinic. Parents are separated. Lives with mother, who works two jobs. • Has few friends

  7. Case #1 • Physical exam • BP 142/90 right arm sitting (normal 135/85) • Ht 178 cm (90th percentile) • Wt 96 kg (> 95th percentile) • BMI (wt/ht2) 30.3 (> 95th percentile) • Hyperpigmented, rough plaques on neck, groin, inner thigh (acanthosis nigricans) • Mild hepatomegaly

  8. Acanthosis Nigricans • Occurs in skin fold areas, especially neck and arm pits • Associated with hyperinsulinemia

  9. Case #1 • Fasting serum lipid profile • Total cholesterol 220 mg/dl, repeat 226 mg/dl (normal < 200 mg/dL) • Triglycerides 320 mg/dL (normal < 200 mg/dL) • HDL cholesterol 30 mg/dL (normal > 35 mg/dL) • LDL cholesterol 131 mg/dl (normal < 130 mg/dL)

  10. Case #1 • Other lab • Normal thyroid profile • 8 AM serum cortisol 19 µg/dL (normal 5-23 µg/dL) • Fasting glucose 190 mg/dL (diabetic >115 mg/dL) • Glucose tolerance test • 60 min 223 mg/dL (diabetic > 200 mg/dL) • 90 min 233 mg/dL (diabetic > 200 mg/dL) • 120 min 188 mg/dL (diabetic > 140 mg/dL) • Fasting insulin 48 mU/L (normal 7-24 mU/L) • Serum/urine ketones negative • Serum transaminases • ALT 119 U/L (normal 5-45 U/L) • AST 98 U/L (normal 5-45 U/L)

  11. Risk Factors for Premature Atherosclerotic Heart Disease • Dyslipidemia (high LDL, low HDL) • Diabetes • Hypertension • Obesity • Sedentary lifestyle • Smoking • Male sex

  12. BP Systolic Cholesterol HDL-C Diabetes Cigarettes LHV by ECG 120 220 50 - - - 160 220 50 - - - 160 260 50 - - - 160 260 35 - - - 160 260 35 + - - 160 260 35 + + - 160 260 35 + + + Coronary Heart Disease Wilson, AmJHypertens, 1994)

  13. Effect of Multiple Risk Factors on Atherosclerosis in the Aorta and Coronary Arteries in Children and Young Adults 3 2 3 2 1 1 0 0 Aorta Coronary Arteries Number of Risk Factors Berenson et. al (NEJM 1998)

  14. Obesity and Inflammation • N-HANES III • 3512 kids (age 8-16) • Kids with elevated CRP (>.22mg/dL) or WBC > 10,000 • Overweight (>85%) vs < 85% • Odds Ratio (OR) of 3.7 (M) and 3.1 for correlation of CRP with overweight • Also elevated risk for WBC M Visser et al Pediatrics e13, January 2001

  15. % of High School Students Not Enrolled in Physical Education Class, 1997 Data missing 8 From 1997 Youth Risk Behavior Survey

  16. Syndrome X • Metabolic syndrome associated with greatly increased risk for premature cardiovascular disease • Syndrome • Obesity • Hypertension • Insulin resistance • Dyslipidemia • Increased triglycerides • Low HDL cholesterol

  17. Insulin Resistance • Associated with Type II diabetes • Closely linked with obesity (direction?) • Decreased insulin-stimulated glucose transport and metabolism in adipocytes and skeletal muscle • Impaired suppression of hepatic glucose output • Tissue specific signaling abnormalities • “Dose” of body fat affects resistance, especially central fat

  18. Complications of Obesity • Cardiovascular-hypertension, heart disease • Insulin resistance/Type II diabetes mellitus • Hyperlipidemia • Growth-advanced bone age, increased height, early menarche • Psychosocial • Hepatobiliary-non-alcoholic steatohepatitis, cholelithiasis • Pulmonary-sleep apnea, Pickwickian syndrome • Orthopedic-slipped capital femoral epiphysis, Blount disease • Cancer-endometrial, breast, prostate, colon • CNS-pseudotumor cerebri

  19. Obesity and Diabetes Risk Knowler WC, et al. Am J Epidemiol. 1981;113:144-156.

  20. Complications of Diabetes • Retinopathy • Nephropathy • Neuropathy • Atherosclerosis

  21. Non-Alcoholic Steatohepatitis(NASH) • Associated with obesity and insulin resistance • Presents with hepatomegaly and mild serum transaminase elevation • Lipid accumulation within hepatocytes with inflammation and fibrosis/cirrhosis • Pathogenesis: “two hit” hypothesis • 1st hit: triglyceride accumulation • 2nd hit: generation of reactive oxygen species and lipid peroxidation

  22. Goals for Therapy for Type II Diabetes • Focus on glucose and lipid goals • Modify fat intake • Improve food choices • Space meals throughout the day • If obese, reduce calories for moderate weight loss • Increase physical activity • Monitor blood glucose, glycohemoglobin, lipids, blood pressure • Add diabetes medication, if needed American Diabetes Assoc.

  23. Beneficial Effects of Exercise in Type II Diabetes exercise increased insulin sensitivity decreased counter- regulatory hormones increased glucose utilization decreased hepatic gluconeogenesis improved blood glucose control