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The genetic variants near the Melanocortin-4 receptor gene ( MC4R ), a key protein regulating energy balance and adiposity, have been related to obesity and glucose metabolism. We aimed to assess whether the  MC4R  genotype affected longitudinal changes in body weight and glucose metabolism biomarkers among women with prior gestational diabetes mellitus (GDM). The  MC4R  genotype, postpartum weight reduction, and glycemic changes between after delivery and pregnancy were assessed in a cohort of 1208 Chinese women who had experienced GDM. The adiposity-increasing allele (C) of the  MC4R  variant rs6567160 was associated with greater postpartum increase of HbA1c (β = 0.08%;  P  = 0.03) and 2-hour OGTT glucose concentrations (β = 0.25 mmol/L;  P  = 0.02). In addition, we found an interaction between the  MC4R  genotype and postpartum weight reduction on changes in fasting plasma glucose ( P -interaction = 0.03). We found that the  MC4R  genotype was associated with postpartum glycemic changes; and the association with fasting glucose were significantly modified by postpartum weight reduction in women who had experienced GDM.

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The MC4R genotype is associated with postpartum weight reduction and glycemic changes among women with prior gestational diabetes: longitudinal analysis