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Adolescent Obesity

Adolescent Obesity. Objectives. Definition of overweight in youth Prevalence and trends Health implications Behavioral and pharmacological treatment. What Is BMI?. Body mass index (BMI) = weight (kg)/height (m 2 ) Or: BMI = [weight (pounds) X 703]/height (in 2 )

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Adolescent Obesity

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  1. Adolescent Obesity

  2. Objectives • Definition of overweight in youth • Prevalence and trends • Health implications • Behavioral and pharmacological treatment

  3. What Is BMI? • Body mass index (BMI) = weight (kg)/height (m2) • Or: BMI = [weight (pounds) X 703]/height (in2) • BMI is an effective screening tool; it is not a diagnostic tool • For children, BMI is age and gender specific, so BMI-for-age is the measure used for youth

  4. BMI-for-Age Cutoffs for Children and Adolescents

  5. BMI BMI BMI BMI For Children, BMI Changes with Age Boys: 2 to 20 years Example: 95th Percentile Tracking Age BMI 2 yrs 19.3 4 yrs 17.8 9 yrs 21.0 13 yrs 25.1

  6. Tracking BMI-for-Age from Birth to 18 Years with Percent of Overweight Children Who Are Obese at Age 25 Whitaker et al. NEJM.1997;337:869-873.

  7. Childhood Obesity: Risk for Disease Must A, et al. NEJM 1992;327:1350-1355. Example: Adults overweight as teens had an increased relative risk of all-cause morbidity and of coronary heart disease

  8. Metabolic Syndrome in Childhood • 439 obese children versus 51 overweight or non-obese (aged around 11-12 years) • 3 of following • BMI > 97th• Systolic BP > 95th • Triglyceride > 95th• HDL < 5th • Impaired glucose tolerance • Prevalence • 38.7% of moderately obese BMI SDS > +2 < +2.5 • 49.7% of severely obese BMI > +2.5 • Prevalence increases directly with degree of obesity Weiss R et al. NEJM:2004;350,23.

  9. Metabolic Syndrome Associated with Insulin Resistance Weiss et al 2004.

  10. BMI Is Associated with Metabolic Syndrome Risk Factors in Children and Adolescents Pearson Correlation Coefficients of Variables in the Analysis Weiss R et al. NEJM 2004 Weiss et al. JAMA. 2004

  11. Increasing Prevalence of Pediatric Type 2 Diabetes Mellitus in the US • 15 years ago Type 2 diabetes mellitus accounted for less than 3% of all new cases of diabetes in children and adolescents in the USA • The figure now stands at 45% • Estimated that Type 2 diabetes will exceed Type 1 in childhood within 10 years* * Report of American Academy of Pediatrics. 2003.112.

  12. Etiology of Obesity • Increased caloric consumption • Sedentary lifestyle • Genetic predisposition • Medications: psychotropics, steroids

  13. Long-Term Effects of Treating the Parent + Child (8 – 11 y/o) Epstein, Valoski, Wing & McCurley. Health Psychology. 1994;13:373-383.

  14. Previous Behavioral/Diet/Exercise Approaches to Weight Management in Adolescents • Few controlled studies on the treatment of adolescent obesity • Comprehensive family-based behavioral programs are the most studied interventions • Behavior therapy: self-monitoring, goal setting, positive reinforcement, stimulus control, contingency management focused upon changing eating and physical activity habits • The inclusion of parents in treatment is less clear than for the treatment of children; parents are usually included. • Most studies report weight losses of only 1 to 4 kg • Participants typically remain obese at the end of studies • New approaches are needed Berkowitz et al. JAMA 2003; 289: 1805-1812.

  15. Child Alone Mother-Child Alone Mother-Child Together Wadden TA, Stunkard AJ, Rich L, Rubin CJ, Sweidel G, McKinney S. Pediatrics. 1990; 85(3):345-52.

  16. Obesity Pharmacotherapy: NHLBI Adult Recommendations • “Appropriate weight-loss drugs can augment diet, physical activity, and behavior therapy in weight loss” • BMI  30 or  27 with co-morbidities • Pharmacotherapy should only be given in conjunction with lifestyle modification National Institutes of Health. Obes Res. 1998;6(suppl 2):51S–209S.

  17. Behavioral and Pharmacological Treatment Combined • Behavioral treatment helps the overweight person to develop skills to cope with an environment which promotes overeating and inactivity • Pharmacological treatment may minimize the effects of biological factors relating to weight gain • Behavioral and pharmacological treatments appear to be additive in adult studies Wadden TA. Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg C. Arch Gen Internal Med 2001;161:218-227.

  18. Obesity Pharmacotherapy There have been no comparative safety and efficacy trials between orlistat and sibutramine or phentermine. Refer to Physicians’ Desk Reference for other products.

  19. S S Reuptake S S Serotonin S S Reuptake S S Norepinephrine Mechanisms of Action Sibutramine’s Active Metabolites Block Serotonin and Norepinephrine Reuptake S = sibutramine= norepinephrine = serotonin Ryan DH et al. Obes Res. 1995;3(suppl 4):553S.

  20. Behavior Therapy and Sibutramine for the Treatment of Adolescent Obesity: A Randomized Controlled Trial Robert I Berkowitz, MD, Thomas A Wadden, PhD, Andrew M Tershakovec, MD, Joanna L Cronquist, BA JAMA 2003; 289:1805-1812 Support: NIH, Abbott Laboratories

  21. Behavior Therapy and Sibutramine for the Treatment of Adolescent Obesity: A Randomized Controlled Trial • 6 month randomized, double-blind, placebo-controlled evaluation of efficacy and safety of sibutramine (final dose 15 mg) when added to a comprehensive family-based behavioral program • Open label sibutramine months 7 – 12 • Objectives: Percent change in BMI, hunger and disinhibition of eating (Stunkard Messick Eating Inventory), adherence to self-monitoring, lipids, insulin, HOMA, BP, pulse, adverse events Berkowitz et al, JAMA 2003; 289: 1805-1812.

  22. Sibutramine Dosage Titration • Week 1: placebo • Week 2: sibutramine 5 mg or placebo • Week 3: sibutramine 10 mg or placebo • Week 7: sibutramine 15 mg or placebo • If systolic or diastolic BP increased from baseline by ≥ 10 mm Hg or pulse increased by 15%, dose decreased by 5 mg decrements Berkowitz et al, JAMA 2003; 289: 1805-1812.

  23. Family-Based Bbehavioral Therapy Program • Phase 1 • 13 weekly group sessions followed by • 6 biweekly group sessions • Phase 2 • Biweekly group sessions months 7 – 9 • Monthly group sessions months 10 – 12 • Behavior therapy: self-monitoring, goal setting, positive reinforcement, stimulus control, slowing eating rate, parents involved • Dietary recommendation: 1200 – 1500 kcal/day, 30% fat, 15% protein • Physical activity target of 120 minutes per week (e.g. walking) Berkowitz et al, JAMA 2003; 289: 1805-1812.

  24. Characteristics of Aadolescents at Baseline Berkowitz et al, JAMA 2003; 289: 1805-1812.

  25. Mean Percentage Change in Initial BMI (Intention-to-Treat Analysis) 0 Placebo + BT (n = 39) -1 -2 -3 -4 -5 % change in BMI *** *** P = 0 .001 -6 -7 Sibutramine + BT (n = 43) -8 *** -9 -10 0 3 6 Month of Treatment Berkowitz et al, JAMA 2003; 289: 1805-1812.

  26. Placebo + BT, months 1-6 Sibutramine + BT, months 1-6 70 63* 60 * P = 0.02 50 40* 40 36 % change in BMI 30 19* 20 15 10 3 0 > 5% > 10% > 15% Percentage of Adolescents Achieving 5%, 10%, and 15% Rreductions in BMI at Mmonth 6 Berkowitz et al, JAMA 2003; 289: 1805-1812.

  27. Self-Monitoring and PercentageChange in BMI at Month 6 High self-monitoring Low self-monitoring 0 -2 (n = 16) -4 -6 (n = 23) -8 % change in BMI (n = 25) -10 -12 -14 (n = 18) -16 Placebo + BT Sibutramine + BT Berkowitz et al, JAMA 2003; 289: 1805-1812.

  28. Mean Percentage Change in Initial BMI (Intention-to-Treat Analysis) 0 Placebo + BT group receivedsibutramine during months 7 – 12 Placebo + BT (n = 39) -1 -2 -3 -4 -5 *** -6 % change in BMI *** P = 0 .001 -7 Sibutramine + BT (n = 43) -8 *** -9 -10 0 3 6 9 12 Placebo controlled All subjects received sibutramine Month of Treatment Berkowitz et al, JAMA 2003; 289: 1805-1812.

  29. 6 months 12 months Change (%) in Lipids at Month 6 (n = 74) and Month 12 (n = 62)† Total cholesterol HDL cholesterol LDL cholesterol Triglyceride 10 7.6 8 **** Baseline values (mg/dL) 6 4 2.3 2 (101.7) (165.5) (99.8) 0 % change (45.4) -2 *** -2.5 -2.3 ** -4 -3.2 * P = 0.02 **P = 0.05***P = 0.01****P = 0.001 -4.6 -6 ** -8 * -10 -9.3 -9.0 † Pooled data (no significant difference between placebo + BT and sibutramine + BT groups) -12 Berkowitz et al, JAMA 2003; 289: 1805-1812.

  30. Change (%) in Insulin, Glucose and HOMA at Months 6 (n = 74) & 12 (n = 62)† Insulin(27 U/mL) Serum glucose(90.3 mg/dL) HOMA(6.1) (Baseline values) 0 -1.9 -2.6 -5 -10 6 months % change * 12 months -12.8 ** -15 -14.8 * P = 0.02** P = 0.01***P < 0.001 *** -20 -20.2 *** † Pooled data (no significant difference between placebo + BT and sibutramine + BT groups) -22.8 -25 Berkowitz et al, JAMA 2003; 289: 1805-1812.

  31. BT + placebo Sibutramine added to placebo group BT + sibutramine Blood Pressure (Mean mm Hg) 140 P = 0.02 P = 0.06 120 Systolic 100 80 Mean BP (mmHg) 60 Diastolic 40 20 0 Baseline Month 3 Month 6 Month 12 Berkowitz et al, JAMA 2003; 289: 1805-1812.

  32. BT + placebo Sibutramine added to placebo group BT + sibutramine Pulse Rate (mean beats/min) 90 85 80 P < 0.001 P = 0.007 P < 0.001 75 70 Pulse rate (beats/min) 65 60 55 50 Baseline Month 3 Month 6 Month 12 Berkowitz et al, JAMA 2003; 289: 1805-1812.

  33. Reasons for Discontinuation (Entire Study) Berkowitz et al, JAMA 2003; 289: 1805-1812.

  34. Mechanism of Action: Orlistat1,2 • Inhibition of lipases by orlistat blocks systemic absorption of dietary fat2 • Unabsorbed fat is excreted into feces (up to one-third of ingested fat)2 • Zhi et al. J Clin Pharmacol. 1995;35:1103-1108. • Zhi et al. Clin Pharmacol Ther. 1994;56:82-85.

  35. Three-Month Tolerability of Orlistat in Adolescents with Obesity-Related Comorbid Conditions McDuffie JR, Calis KA, Uwaifo GI, Sebring NG, Fallon EM, Hubbard, Yanovski JA. Obesity Research. 2002;10:642-650

  36. Objective • Study safety, tolerability, and potential efficacy of orlistat in adolescents with obesity and its comorbid conditions Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

  37. Research Methods and Procedures • 20 adolescents • Age: 14.6 ± 2.0 yrs • BMI: 44.1 ± 12.6 kg/m2 • Subjects took orlistat (120 mg 3 times daily) and a multivitamin for 3 months • Subjects were simultaneously enrolled in a 12-week lifestyle modification program, with emphasis on: • Diet • Exercise • Behavior modification Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

  38. Results • 85% completed treatment • Took 80% of prescribed medication • Adverse effects generally mild • Limited to GI effects observed in adults Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

  39. Results (cont.) Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

  40. Results (cont.) Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

  41. Summary • Comorbid conditions associated with obesity in this patient sample included:  • Hyperinsulinemia: 100% • Hyperlipidemia: 20% • Hypertension: 10% • Type 2 diabetes: 5% • Impaired glucose tolerance: 5% • In adolescents, short-term treatment with orlistat in the context of a behavioral program is well-tolerated and has a side effect profile similar to that observed in adults • True benefit versus conventional therapy remains to be determined in placebo-controlled trials Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

  42. Conclusions • Overweight is defined by BMI ≥ 95th percentile for age and gender • Increased co-morbidities, including metabolic syndrome and type 2 diabetes mellitus with increasing BMI • Increasing prevalence of overweight among youth • Overweight tracks from childhood to adulthood

  43. Conclusions • Additive effects of behavior + sibutramine in adolescents for weight loss by month 6 in teens • Continuation of sibutramine resulted in maintenance of weight loss by month 12 • Blood pressure and pulse effects (n = 19), similar to those in adults, resolved through dose reduction (n = 15) in BT + sibutramine group • Significant improvements in lipids, insulin and HOMA • Orlistat: Promising initial uncontrolled study of weight loss with orlistat • Orlistat: improvements in lipids, insulin

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