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

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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. 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. 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. The main outcome measure was postpartum glycemic changes. 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). 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.