Pubertal metformin therapy to reduce total, visceral, and hepatic adiposity.
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.


METHODS
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.


CONCLUSIONS
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.
Ibáñez
Lourdes
L
Endocrinology, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, and CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain. libanez@hsjdbcn.org
Lopez-Bermejo
Abel
A
Diaz
Marta
M
Marcos
Maria Victoria
MV
de Zegher
Francis
F
D050154:Adiposity / Q000187:drug effects*; D000293:Adolescent; D001835:Body Weight / Q000187:drug effects; D002648:Child; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006946:Hyperinsulinism / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D050152:Intra-Abdominal Fat / Q000187:drug effects; D020738:Leptin / Q000097:blood; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D011629:Puberty, Precocious / Q000453:epidemiology / Q000503:physiopathology
D007004:Hypoglycemic Agents; D020738:Leptin; D008687:Metformin