Abstract
Background: Offspring of mothers with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic diseases. Adipokines such as adiponectin and leptin may be involved in the underlying mechanisms. Fibroblast growth factor 21 (FGF-21) has recently been identified as a potent metabolic regulator. Therefore, we investigated the impact of fetal exposure to GDM on adiponectin, leptin and FGF-21 levels and their associations with metabolic and adiposity traits during adolescence. Methods: A prospective study comparing 502 offspring of GDM exposed mothers and 535 offspring of non-exposed mothers. During a clinical exam of offspring, aged 9-16 years old, metabolic traits were measured and fasting blood samples collected and assayed for serum concentrations of leptin, adiponectin and FGF-21. Results: GDM exposed offspring had 34% (95% CI: 18-51%) higher leptin levels, and 34% (95% CI: -48, -15%) lower FGF-21 concentrations than non-exposed offspring (p<0.05), but no significant differences in adiponectin concentrations were found. These differences remained significant after adjusting for major confounders, including maternal pre-pregnancy BMI. Offspring leptin concentrations correlated positively with insulin and HOMA-IR, whereas adiponectin concentrations were inversely correlated (p<0.05). Elevated leptin and decreased adiponectin concentrations correlated with all measures of adiposity, whereas FGF-21 correlated with total fat percentage only. In analyses stratified by offspring BMI z-score categories, GDM exposure had no significant effect on leptin and adiponectin concentrations. Conclusion: GDM exposed offspring had higher leptin and lower FGF-21 concentrations than non-exposed controls, but this was driven by higher prevalence of adiposity among GDM offspring. The differential adipokine concentration does not seem to be the major driver behind the dysmetabolic phenotype among GDM offspring. Disclosure F.B. Kampmann: None. A. Thuesen: None. L. Hjort: None. M. Bjerre: None. J. Frystyk: None. I. Tetens: None. A.A. Bjerregaard: None. J.E. Chavarro: None. S.F. Olsen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. A.A. Vaag: Employee; Self; AstraZeneca. L. Grunnet: None. Funding Danish Council for Strategic Research; Innovation Fund, Denmark (09-067124, 11-115923); Novo Nordisk Foundation (NNF160C0022518); Danish Diabetes Academy
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