Metformin treatment for four years to reduce total and visceral fat in low birth weight girls with precocious pubarche

J Clin Endocrinol Metab. 2008 May;93(5):1841-5. doi: 10.1210/jc.2008-0013. Epub 2008 Mar 4.

Abstract

Context and objective: A low birth weight (LBW) tends to be followed by overweight due to an excess of fat, including visceral fat. LBW girls with precocious pubarche (PP) (pubic hair < 8 yr) are at high risk for developing an adipose state of hyperinsulinemic androgen excess that leads toward early menarche. We explored the effects of insulin sensitization with metformin in LBW-PP girls. SETTING, DESIGN, PATIENTS, INTERVENTION: Prepubertal LBW girls with PP (mean body weight 2.4 kg; age 7.9 yr; body mass index 18.4 kg/m(2)) were studied. Girls were randomly assigned to remain untreated (n=19) or receive metformin for 4 yr (n = 19; 425 mg/d for 2 yr, then 850 mg/d for 2 yr).

Main outcomes: At the start and after 4 yr, height, weight, fasting insulin, glucose, IGF-I, testosterone, lipids, leptin, high molecular weight adiponectin, body composition by absorptiometry, abdominal fat partitioning (only 4 yr) by magnetic resonance imaging, and menarcheal status were determined.

Results: Metformin-treated girls gained on average 5.5 kg (or approximately 50%) less fat, after 4 yr were less insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less atherogenic lipid profile, and were less likely to be post-menarcheal than untreated girls, whereas their gain in height, lean mass, and bone mineral density were similar. After 4 yr, untreated girls had more visceral fat, a higher ratio of visceral-to-sc fat, and a higher leptin-to-high molecular weight adiponectin ratio (all approximately 50% higher) than metformin-treated girls.

Conclusion: Long-term metformin treatment appears to reduce total and visceral fat in LBW-PP girls, and to delay menarche without attenuating linear growth, thereby opening the perspective that adult height may be increased.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Infant, Low Birth Weight*
  • Infant, Newborn
  • Insulin-Like Growth Factor I / analysis
  • Intra-Abdominal Fat / metabolism*
  • Lipids / blood
  • Metformin / therapeutic use*
  • Puberty, Precocious / drug therapy*
  • Puberty, Precocious / metabolism

Substances

  • Hypoglycemic Agents
  • Lipids
  • Insulin-Like Growth Factor I
  • Metformin