Genetic susceptibility, lifestyle intervention and glycemic changes among women with prior gestational diabetes

Summary Aims Women with prior gestational diabetes mellitus (GDM) or high genetic susceptibility are prone to development of type 2 diabetes. We examined whether a lifestyle intervention modified the genetic effect on changes in glycemic markers among women with prior GDM. Research design and methods This study included 560 women with prior GDM from a randomized controlled trial, the Tianjin Gestational Diabetes Mellitus Prevention Program, who were assigned into an intervention arm (improved physical activity and healthy dietary intakes) or a control arm. We assessed associations of GDM related genetic variants in/near the CDKAL1 (rs7754840) and MTNR1B (rs10830962) genes with changes in fasting levels of glucose and insulin, β-cell function (HOMA-B) and insulin resistance (HOMA-IR) at 1 year and 2 years after the baseline. Results We found significant interactions between CDKAL1 variant rs7754840 and lifestyle intervention on changes in fasting insulin and HOMA-IR at 1 year (P for interactions =0.008 and 0.006, respectively). The GDM-increasing C allele was associated with a 0.07-unit greater increase in fasting insulin (P=0.048) and HOMA-IR (P=0.045) in the control group, while opposite-directional associations were observed in the intervention group; women with the C allele seemed to decrease more in these glycemic markers than the non-C-carriers(both P≤0.06). The interactions between the CDKAL1 genetic variant and lifestyle intervention on changes in fasting insulin (P=0.035) and HOMA-IR (P=0.024) remained significant over the 2-year period, even though the effects of lifestyle intervention were attenuated at 2-year. The MTNR1B variant rs10830962 did not show interaction with lifestyle intervention on changes in the glycemic markers. Conclusions Healthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance. Trial registration number ClinicalTrials.gov NCT01554358. URL of registration https://clinicaltrials.gov/ct2/show/NCT01554358 .