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

Abstract

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://ichgcp.net/clinical-trials-registry/NCT01554358.

Keywords: CDKAL1; Gene-lifestyle interaction; Gestational diabetes mellitus; Insulin resistance; Lifestyle intervention; MTNR1B.

Conflict of interest statement

Conflict of Interest Statement. No potential conflicts of interest relevant to this article were reported.

Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Figures

Figure 1.

Effects of the CDKAL1 and lifestyle intervention on 1-year changes in insulin and HOMA-IR in women with prior GDM. Values were means±SEs, adjusted for age, baseline BMI, weight loss at 1 year, baseline values of the respective outcomes, monthly income (<5000, 5000–8000, ≥8000), smoking (no, past, current), drinking (no, past, current), and family history of diabetes (no, yes) at baseline. Insulin and HOMA-IR was log-transformed before analysis. Panel A: changes in Insulin; panel B: changes in HOMA-IR.

Figure 2.

The effects of CDKAL1 genetic variants on changes in Insulin and HOMA-IR in response to lifestyle intervention. Generalized linear mixed models (GLMM) were used to test potential interactions between SNP rs7754840 with lifestyle interventions on the trajectory of changes in Insulin and HOMA-IR from baseline to 2 years. Values were means±SEs after adjustment for age, baseline BMI, weight change, baseline values for respective phenotypes, monthly income (<5000, 5000–8000, ≥8000), smoking (no, past, current), drinking (no, past, current), and family history of diabetes (no, yes). Insulin and HOMA-IR was log-transformed before analysis. Panel A: changes in Insulin in the lifestyle intervention group; panel B: changes in Insulin in the control group; panel C: changes in HOMA-IR in the lifestyle intervention group; panel D: changes in HOMA-IR in the control group.