Francis de Zegher1, Cristina García Beltrán2,3, Abel López-Bermejo4,5, Lourdes Ibáñez2,3. 1. Pediatric Endocrinology, University Hospital Gasthuisberg, Leuven, Belgium. 2. Pediatric Research Institute, Hospital Sant Joan de Déu, University of Barcelona, Esplugues, Spain. 3. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain. 4. Department of Pediatrics, Dr. Josep Trueta Hospital, Girona, Spain. 5. Girona Institute for Biomedical Research, Girona, Spain.
Abstract
BACKGROUND/AIMS: Girls with low-birth weight (LBW) and postnatal weight catch-up tend to develop visceral and hepatic fat excess, which may be accompanied by an upregulated adrenarche with precocious pubarche (PP) and by a rapidly progressive puberty with early menarche and shorter stature. A pilot study suggested that metformin treatment for 4 years reduces central adiposity in LBW-PP girls and normalizes puberty and adult height. In this cohort, we studied the relationship between metformin treatment, bone maturation, and body composition. METHODS: Longitudinal hand X-rays (0-4 years, analyzed by BoneXpert) were available from 34 LBW-PP girls (89% of the original cohort; n = 17 untreated, n = 17metformin-treated; age at the start of treatment 8 years) along with body composition (0-4 years, by DXA), hepatic fat, and abdominally subcutaneous and visceral fat (posttreatment, by MRI). RESULTS: The tempo of bone aging was accelerated in untreated girls (≈16% faster vs. chronological aging) and normal in metformin-treated girls (≈20% slower vs. untreated girls). Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat. The tempo of bone maturation was associated (R = 0.55; p < 0.001) with hepatic fat. CONCLUSION:Metformin treatment in rapidly maturing girls with central adiposity normalized bone maturation. This normalization was accompanied by less central fat and was related closely to hepatic fat.
RCT Entities:
BACKGROUND/AIMS: Girls with low-birth weight (LBW) and postnatal weight catch-up tend to develop visceral and hepatic fat excess, which may be accompanied by an upregulated adrenarche with precocious pubarche (PP) and by a rapidly progressive puberty with early menarche and shorter stature. A pilot study suggested that metformin treatment for 4 years reduces central adiposity in LBW-PP girls and normalizes puberty and adult height. In this cohort, we studied the relationship between metformin treatment, bone maturation, and body composition. METHODS: Longitudinal hand X-rays (0-4 years, analyzed by BoneXpert) were available from 34 LBW-PP girls (89% of the original cohort; n = 17 untreated, n = 17 metformin-treated; age at the start of treatment 8 years) along with body composition (0-4 years, by DXA), hepatic fat, and abdominally subcutaneous and visceral fat (posttreatment, by MRI). RESULTS: The tempo of bone aging was accelerated in untreated girls (≈16% faster vs. chronological aging) and normal in metformin-treated girls (≈20% slower vs. untreated girls). Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat. The tempo of bone maturation was associated (R = 0.55; p < 0.001) with hepatic fat. CONCLUSION:Metformin treatment in rapidly maturing girls with central adiposity normalized bone maturation. This normalization was accompanied by less central fat and was related closely to hepatic fat.