title: Metformin treatment to reduce central adiposity after prenatal growth restraint: a placebo-controlled pilot study in prepubertal children.
abstract: BACKGROUND
  Children born small-for-gestational-age (SGA) who experience rapid postnatal catch-up in weight are at risk for central adiposity and hyperinsulinemia.
  
  
  OBJECTIVE
  To study the effects of prepubertal metformin intervention over 24 months on the body composition and endocrine-metabolic profile of catch-up SGA children.
  
  
  METHODS
  Double-blind, placebo-controlled, pilot study including 23 post-catch-up non-obese prepubertal SGA children [age, 7.7 yr; body mass index standard deviation score (BMI SDS) >50th and <97th centile for age] with increased visceral fat [by magnetic resonance imaging (MRI) and insulin-like growth factor-I (IGF-I) both p > 75th for age]. Patients were randomized to receive either placebo or metformin (425 mg/d) for 24 months. Clinical, biochemical [IGF-I, glucose, insulin, lipids, androgens, sex-hormone-binding globulin (SHBG) and high-molecular-weight (HMW)-adiponectin] and imaging [body composition (absorptiometry and MRI; carotid intima-media thickness (ultrasonography)] variables were assessed at baseline, and at 6, 12, and 24 months.
  
  
  RESULTS
  After 24 months, metformin-treated children were leaner, had higher SHBG levels, and less total and abdominal fat than placebo-treated children (all p ≤ 0.05). Longitudinal analyses showed that metformin had a significant effect on anthropometric (weight, BMI, and waist) and biochemical variables [glucose, homeostasis model assessment-insulin resistance (HOMA-IR), and triglycerides] (all p ≤ 0.05); and in total and abdominal fat (p = 0.01 and p = 0.02).
  
  
  CONCLUSIONS
  Prepubertal intervention with metformin reduces central adiposity and improves insulin sensitivity in non-obese catch-up SGA children.
authors.affiliation: Hospital Sant Joan de Déu, University of Barcelona, Esplugues, 08950, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Department of Pediatrics, Dr Josep Trueta Hospital, Girona Institute for Biomedical Research, Girona, 17007, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Bassols
authors.affiliation: Department of Pediatrics, Dr Josep Trueta Hospital, Girona Institute for Biomedical Research, Girona, 17007, Spain.
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.affiliation: Pediatric Endocrinology, University Hospital Gasthuisberg, Leuven, 3000, Belgium.
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.affiliation: Hospital Sant Joan de Déu, University of Barcelona, Esplugues, 08950, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D050153:Abdominal Fat / Q000187:drug effects / Q000473:pathology; D050154:Adiposity / Q000187:drug effects*; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002648:Child; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D056128:Obesity, Abdominal / Q000209:etiology / Q000517:prevention & control*; D063766:Pediatric Obesity / Q000209:etiology / Q000517:prevention & control*; D010865:Pilot Projects; D055105:Waist Circumference / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D015415:Biomarkers; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: IGF-I; adipose tissue; body composition; catch-up; insulin; metformin; small-for-gestational-age; visceral fat