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Division of Pediatric Endocrinology and Diabetes (P.G.B., M.F.), Duke University Medical Center, Durham, North Carolina 27710; Advanced Analytics (M.B.), SAS Institute Inc., Cary, North Carolina 27513; Duke Molecular Physiology Institute (M.J.M., M.F.), Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina 27710; Knight Cardiovascular Institute (J.Q.P.), Oregon Health & Science University, Portland, Oregon 97239; and Department of Medicine (D.B.) and Division of Pediatric Endocrinology and Diabetes (A.M.H.), University of Alberta, Edmonton, AB T6G 2R3 Canada.
Published: October 2015
AI Article Synopsis
Article Abstract
Background: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood.
Objective: We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) -matched obese controls (OCs).
Methods: In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z.
Results: Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable.
Conclusion: Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive.
