Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes

Abstract

Objective: Fetal exposure to gestational diabetes mellitus (GDM) increase s the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 ( FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposur e to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposit y and metabolic traits during childhood/adolescence. Design and methods: The follow-up study included 504 GDM and 540 control offspring aged 9-16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concen trations of leptin, adiponectin, and FGF21 were measured by validated immune assays. Results: GDM offspring had 38% (95% CI: 22-55%) higher leptin, 0.6 mg/L (95% CI: -1.2, -0.04 mg/L) lower adiponectin, and 32% (95% CI: -47%, -12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concen trations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated wit h fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage. Conclusions: GDM offspring had higher leptin, lower adiponectin and FGF21 co ncentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.