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Andrea M. Haqq1,2, Michael Muehlbauer2, Laura P. Svetkey2,3 , Christopher B. Newgard2, Jonathan Q. Purnell4, Steven C. Grambow5,6 and Michael S. Freemark1 1Department of Pediatrics, Division of Pediatric Endocrinology, and 2 Sarah W. Stedman Nutrition and Metabolism Center, and 3Department of Medicine, Division of Nephrology, Duke University Medical Center, Durham, NC 27710 and 4 Center for the Study of Weight Regulation and the Department of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA and 5 Center for Health Services Research in Primary Care, Durham Veterans Affairs Medical Center, Durham, NC 27705, USA and 6 Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA Objective: Prader-Willi Syndrome (PWS) is a genetic syndrome characterized by relative hypoinsulinemia and normal or increased insulin sensitivity despite profound obesity. We hypothesized that this increased insulin sensitivity is mediated by increased levels of total and high molecular weight adiponectin and examine the relationship to other known satiety peptide hormones. Design, Patients and Measurements: We measured total adiponectin and its isoforms (high molecular weight (HMW), middle-molecular weight (MMW) or low molecular weight (LMW)) in 14 children with PWS (median age and body mass index (BMI)-Z score: 11.35 yr and 2.15) and 14 BMI-matched controls (median age and BMI-Z score: 11.97 yr and 2.34). Results: Despite comparable BMI-Z score and leptin levels, the PWS children exhibited lower fasting insulin and HOMA-IR compared to obese controls. For any given BMI-Z score, the PWS children showed higher concentrations of fasting total, HMW and HMW/total adiponectin ratios. The HMW/total adioponectin ratio was preserved in children with PWS at high degrees of obesity. In PWS children, fasting plasma total adiponectin, HMW adiponectin and HMW/total adiponectin ratio correlated negatively with age (p<0.05), HOMA-IR (p<0.01), BMI-Z score (p<0.05), insulin (p<0.01) and leptin (p<0.05). In addition to higher fasting ghrelin concentrations, the PWS children showed significantly higher fasting levels of total PYY and GIP compared to obese controls. Conclusions: Relative to obese controls of similar age and BMI-Z score, the PWS children had significantly higher levels of total and HMW adiponectin and increased ratios of HMW/total adiponectin. These findings suggest a physiological link whereby some PWS children might be relatively protected from developing as severe of obesity-related insulin resistance as similarly obese children without PWS.
edited: 02/09/2012 |