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.

Objectives: 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.

Keywords: IGF-I; adipose tissue; body composition; catch-up; insulin; metformin; small-for-gestational-age; visceral fat.