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


RESULTS
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.


CONCLUSIONS
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.
Ibáñez
Lourdes
L
Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu 2, Esplugues, Barcelona, Spain. libanez@hsjdbcn.org
López-Bermejo
Abel
A
Díaz
Marta
M
Marcos
Maria Victoria
MV
de Zegher
Francis
F
D002648:Child; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D011629:Puberty, Precocious / Q000188:drug therapy* / Q000378:metabolism
D007004:Hypoglycemic Agents; D008055:Lipids; D007334:Insulin-Like Growth Factor I; D008687:Metformin