Pubertal Metformin Therapy to Reduce Total, Visceral, and Hepatic Adiposity
Received 1 March 2009; received in revised form 10 June 2009; accepted 6 July 2009. published online 23 September 2009.
Objective
Puberty is part of a critical window in which adiposity and its correlates can be fine-tuned toward reproduction, which implies that puberty provides an opportunity to reprogram a misprogramming that occurred in early life. We tested this hypothesis in low-birthweight (LBW) girls with precocious pubarche (PP), who are at risk for hyperinsulinemic body adiposity during and beyond puberty.
Study design
LBW girls with PP (n = 38; mean age 8 years) were randomized to remain untreated or to receive metformin across puberty (425 mg/d for 2 years, then 850 mg/d for 2 years); subsequently, all girls were monitored for 1 year without intervention. Here we report on the latter year.
Results
The benefits of metformin were mostly maintained during the posttreatment year so that, after 5 years, metformin therapy was associated with more lean mass; with less total, visceral, and hepatic fat; with lower circulating levels of androgens and leptin; and with elevated levels of high-molecular-weight adiponectin and undercarboxylated osteocalcin.
Conclusion
In LBW girls with PP, pubertal metformin therapy was followed by a favorable adipokine profile and by a reduction of total, visceral, and hepatic adiposity beyond puberty.
aEndocrinology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, and CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain
bPediatric Endocrinology, Dr. Trueta Hospital, Girona, Spain
cEndocrinology Unit, Hospital de Terrassa, Terrassa, Spain
dDepartment of Woman & Child, University of Leuven, Leuven, Belgium
Reprint requests: Lourdes Ibáñez, MD, PhD, Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain.
L.I., M.D., and M.V.M. are Clinical Investigators of CIBERDEM (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain). A.L.B. is an Investigator of the Fund for Scientific Research I3 (Ministry of Education and Science, Spain). F.dZ. is a Clinical Investigator of the Fund for Scientific Research (Flanders, Belgium).
ABSTRACT