Background: Low birth weight (LBW) followed by a rapid postnatal catch-up in weight predisposes individuals to a central distribution of body fat, which is reverted by metformin. Growth-and-differentiation-factor-15 (GDF15) plays an important role in the regulation of energy homeostasis, reducing food intake and lowering body weight. We aimed to assess whether GDF15 concentrations are raised by long-term metformin treatment in LBW/catch-up girls with precocious pubarche (PP, pubic hair before age 8 years), and whether they relate to changes in endocrine-metabolic variables, body composition and abdominal fat partitioning.
Methods: Circulating GDF15 was determined in 32 LBW/catch-up girls with PP randomly assigned to receive metformin for 4 years (n=16; 425 mg/d for 2 years, then 850 mg/d for 2 years) or to remain untreated (n=16). Thirty patients were included in the final analysis (n=15 in each study arm), after excluding basal outliers. Endocrine-metabolic variables, body composition (by absorptiometry) and abdominal fat partitioning (by MRI) were assessed at start and yearly during the follow-up.
Results: Circulating GDF15 concentrations increased significantly in LBW-PP girls only after 3 and 4 years on metformin. GDF15 levels associated negatively with insulin, HOMA-IR, androgens, body fat and visceral fat.
Conclusion: Prepubertal intervention with metformin reduces central adiposity and insulin resistance in girls with reduced prenatal growth. GDF15 could be among the mediators of such metformin effects, especially over the long term.
15 Sep 2022 - 17 Sep 2022