Zhaoxia Liang1, Leishen Wang2, Huikun Liu2, Yuhang Chen3, Tao Zhou4, Yoriko Heianza4, Junhong Leng2, Weiqin Li2, Xilin Yang5, Yun Shen6, Ru Gao7, Gang Hu7, Lu Qi8. 1. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA; Department of Obstetrical, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. 2. Tianjin Women's and Children's Health Center, Tianjin, China. 3. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA; Department of Public Health Laboratory Sciences, West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China. 4. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA. 5. Department of Epidemiology, School of Public Health, Tianjin Medical University, Tianjin, China. 6. Pennington Biomedical Research Center, Baton Rouge, LA, USA; Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China. 7. Pennington Biomedical Research Center, Baton Rouge, LA, USA. 8. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: lqi1@tulane.edu.
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://clinicaltrials.gov/ct2/show/NCT01554358.
RCT Entities:
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.
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