Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study.
ABSTRACT The objective of this pilot study was to evaluate the effects of exenatide on BMI (primary endpoint) and cardiometabolic risk factors in nondiabetic youth with extreme obesity. Twelve children and adolescents (age 9-16 years old) with extreme obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m(2)) were enrolled in a 6-month, randomized, open-label, crossover, clinical trial consisting of two, 3-month phases: (i) a control phase of lifestyle modification and (ii) a drug phase of lifestyle modification plus exenatide. Participants were equally randomized to phase-order (i.e., starting with control or drug therapy) then crossed-over to the other treatment. BMI, body fat percentage, blood pressure, lipids, oral glucose tolerance tests (OGTT), adipokines, plasma biomarkers of endothelial activation, and endothelial function were assessed at baseline, 3-, and 6-months. The mean change over each 3-month phase was compared between treatments. Compared to control, exenatide significantly reduced BMI (-1.7 kg/m(2), 95% confidence interval (CI) (-3.0, -0.4), P = 0.01), body weight (-3.9 kg, 95% CI (-7.11, -0.69), P = 0.02), and fasting insulin (-7.5 mU/l, 95% CI (-13.71, -1.37), P = 0.02). Significant improvements were observed for OGTT-derived insulin sensitivity (P = 0.02) and β-cell function (P = 0.03). Compliance with the injection regimen was excellent (≥94%) and exenatide was generally well-tolerated (the most common adverse event was mild nausea in 36%). These preliminary data suggest that exenatide should be evaluated in larger, well-controlled trials for its ability to reduce BMI and improve cardiometabolic risk factors in youth with extreme obesity.
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ABSTRACT: To test prospectively the reproducibility and feasibility of endothelial pulse amplitude testing (Endo-PAT), a novel Food and Drug Administration-approved technology, in healthy adolescents. We performed Endo-PAT testing on 2 different days separated by no more than 7 days in 30 healthy fasting adolescents, ages 13 to 19 years, to assess reproducibility and feasibility. The reported level of discomfort, as measured on a pain scale of 1 to 5, was documented. The mean difference in paired Endo-PAT indices was 0.12 (95% CI, -0.09-0.33; P = .24; intraclass correlation coefficient, 0.78), and the within-subject variation of Endo-PAT index was 0.16. The Endo-PAT index on test days 1 and 2 were 1.91 +/- 0.57 and 1.78 +/- 0.51 (mean plus or minus SD), respectively. All attempted studies (100%) were completed (95% CI, 88%-100%), and all completed studies (100%) could be analyzed (95% CI, 88%-100%). The median pain score was 1 on both days. In healthy adolescents, Endo-PAT is feasible and has excellent reproducibility. This technology may provide an easy and reliable means of assessing endothelial function in the pediatric population.The Journal of pediatrics 03/2009; 154(6):901-5. · 4.02 Impact Factor
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ABSTRACT: To explore the accuracy of various body mass index (BMI) cutpoints in identifying children who have excess adiposity (based on skinfold thicknesses), adverse levels of lipids, insulin, and blood pressures, and a high risk for severe adult obesity. Cross-sectional (n = 10,099) and longitudinal (n = 2392) analyses were performed among subjects who participated in the Bogalusa Heart Study. Of children with a BMI > or =95th percentile (P) of the Centers for Disease Control (CDC) growth charts, 39% had at least two risk factors, 65% had excess adiposity, and 65% had an adult BMI of > or =35 kg/m(2). Of those with a BMI > or =99th P, 59% had at least two risk factors, 94% had excess adiposity, and 88% had an adult BMI of > or =35 kg/m(2). About 4% of children in the US now have a BMI > or =99th P. The 99th P of BMI-for-age may be appropriate for identifying children who are at very high risk for biochemical abnormalities and severe adult obesity. More aggressive weight control strategies may be warranted for this subgroup.The Journal of pediatrics 01/2007; 150(1):12-17.e2. · 4.02 Impact Factor
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ABSTRACT: The worldwide increase in the prevalence of childhood obesity is reaching epidemic proportions and is associated with a dramatic rise in cases of type 2 diabetes. The prevalence of glucose intolerance and its determinants and the relation of cardiovascular risk factors with levels of glycemia and degree of obesity were studied in grossly obese children of European origin. A total of 710 grossly obese Italian children (SD score [SDS] of BMI 3.8 +/- 0.7) aged 6-18 years, including 345 male subjects, underwent an oral glucose tolerance test. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment for insulin resistance and the insulinogenic index, respectively. Fibrinogen, C-reactive protein, lipids, and uric acid were measured. The 2-h postload glucose and degree of obesity, calculated as the SDS of weight/height(2), were used as dependent variables. The prevalence of glucose intolerance was 4.5%. Insulin resistance (P < 0.0001), impaired insulin secretion (P < 0.0001), and diastolic blood pressure (BP) (P < 0.05) were significantly and independently related to 2-h postload glucose values. The degree of obesity did not relate to insulin resistance but was independently correlated with inflammatory proteins, uric acid, and systolic BP, variables that were often abnormal in this population. In these grossly obese children, both insulin resistance and impaired insulin secretion contribute to the elevation of glycemia, and the degree of obesity is related to cardiovascular risk factors independently of insulin resistance.Diabetes Care 01/2003; 26(1):118-24. · 7.74 Impact Factor