The Circadian Rhythm–Related MTNR1B Genotype, Gestational Weight Gain, and Postpartum Glycemic Changes

Abstract

Context: Disturbed circadian rhythms and sleep quality during pregnancy have been related to gestational weight gain and gestational diabetes mellitus (GDM), which affect postpartum glucose metabolism and future risk of type 2 diabetes. Objective: We assessed whether the circadian rhythm-related melatonin receptor 1B (MTNR1B) genotype was associated with 1 to 5 years of postpartum glycemic changes among women with a history of GDM and whether gestational weight gain modified such associations. Design, Settings, and Participants: The established circadian rhythm-associated MTNR1B genetic variant (rs10830963) was genotyped in 1025 Chinese women with a history of GDM. Body weight and glycemic traits, during and after pregnancy, were longitudinally collected. Main Outcome Measures: The main outcome measure was postpartum glycemic changes. Results: We found that women carrying different MTNR1B genotypes showed distinct postpartum changes in 2-hour oral glucose tolerance test: 0.36, 0.20, and -0.19 mM per additional copy of the shorter sleep duration-related G allele in women with inadequate, adequate, and excessive gestational weight gain, respectively (for interaction, P = 0.028). The corresponding changes in fasting glucose were 0.14, 0.13, and 0.01 mM, although the modification effect of gestational weight gain on the genetic association was marginally significant (for interaction, P = 0.067). Conclusions: Our findings suggest that gestational weight gain may modify the circadian rhythm-related MTNR1B genetic variant on long-term glycemic changes, highlighting the significance of gestational weight management in diabetes prevention among women with GDM.