Cardiovascular and Metabolic Risk Profile and Acylation-Stimulating Protein Levels in Children with Prader-Willi Syndrome and Effects of Growth Hormone Treatment

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 4; pp. 1758 - 1766
• Main Authors: de Lind van Wijngaarden, Roderick F. A, Cianflone, Katherine, Gao, Y, Leunissen, Ralph W. J, Hokken-Koelega, Anita C. S
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.04.2010
• Subjects: Absorptiometry, Photon; Aging - physiology; Anthropometry; Blood Pressure - physiology; Body Height - physiology; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Child; Child, Preschool; Chromosome Deletion; Complement C3; Dyslipidemias - blood; Dyslipidemias - complications; Female; Homeostasis; Human Growth Hormone - therapeutic use; Humans; Infant; Insulin Resistance - physiology; Intercellular Signaling Peptides and Proteins - blood; Male; Metabolic Diseases - blood; Metabolic Diseases - epidemiology; Metabolic Diseases - etiology; Netherlands; Prader-Willi Syndrome - blood; Prader-Willi Syndrome - complications; Prader-Willi Syndrome - epidemiology; Recombinant Proteins - therapeutic use; Risk Assessment; Netherlands
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-0656

Context: Reports on the cardiovascular and metabolic risk profile in children with Prader-Willi syndrome (PWS) and the effects of GH treatment are scarce. Acylation-stimulating protein (ASP) stimulates glucose uptake and triglyceride storage in adipose tissue. Objectives: The aim was to study the metabolic and cardiovascular risk profile and ASP levels and to investigate the effects of GH treatment. Design: We conducted a randomized controlled GH trial. Infants and prepubertal children were assigned to receive GH (1 mg/m2 · d) or to serve as controls for 12 and 24 months, respectively. Patients: Eighty-five children with PWS (mean ± sd age of 4.9 ± 3.0 yr) participated in the study. Main Outcome Measures: We measured fat percentage (fat%) with dual-energy x-ray absorptiometry, blood pressure, fasting insulin and glucose levels, serum lipids, and ASP levels. Results: Mean ± SD fat% was 28.4 ± 6.2 in infants and 36.9 ± 8.5 in prepubertal children. Fat% sd score (SDS) was above 2 SDS in 95% of prepubertal children. In addition, 63% of infants and 73% of prepubertal children demonstrated at least one cardiovascular risk factor, defined as hypertension or dyslipidemia. The metabolic syndrome was demonstrated in 5% of all children. Mean ± sd baseline ASP was 107 ± 45 nmol/liter (normal < 58 nmol/liter) and correlated with fat mass and TG levels. GH improved fat%SDS and the HDLc/LDLc ratio (P < 0.0001 and P = 0.04). GH had no effect on mean ASP levels in this population. Conclusions: Many children with PWS had dyslipidemia and high ASP levels. GH improved fat% and high-density lipoprotein cholesterol/low-density lipoprotein cholesterol, but not ASP. High ASP levels may prevent complete normalization of fat%SDS during GH treatment but may contribute in keeping glucose and insulin levels within normal range. In prepubertal children with Prader-Willi syndrome, the cardiovascular and metabolic risk profile is unfavorable and acylation stimulating protein levels are elevated.