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Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program.

ABSTRACT: BACKGROUND:A history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM. OBJECTIVE:The objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM. METHODS:We genotyped MC4R rs6567160 and measured glucose and insulin in fasting plasma samples at baseline and during the first 2 follow-up visits in 1128 women with prior GDM. They were randomly assigned to either a 4-y lifestyle intervention involving both diet and physical activity or a control group from a randomized clinical trial, the Tianjin Gestational Diabetes Mellitus Prevention Program. We analyzed the interaction between the MC4R genotype and lifestyle intervention on changes in insulin resistance. RESULTS:From baseline to 1.28 y, the MC4R genotype was related to changes in fasting insulin, HOMA-IR, and homeostasis model assessment of ? cell function (HOMA-B) in the intervention group. Each risk allele (C) of rs6567160 was associated with a 0.08-unit greater decrease in log(insulin), log(HOMA-IR), and log(HOMA-B) (P = 0.02, 0.04, and 0.04, respectively), whereas in the control group, each C allele tended to be associated with a greater increase in HOMA-IR (P = 0.09). We found significant interactions between the MC4R genotype and lifestyle intervention on 1.28-y changes in fasting insulin and HOMA-IR (P = 0.006 and 0.008, respectively), and such interaction remained significant when we analyzed the trajectory of changes in insulin and HOMA-IR from baseline to 2.55 y (both P = 0.03). CONCLUSIONS:The exploratory results from the first 2 follow-up visits indicate that women with prior GDM carrying a diabetes-increasing MC4R genotype (CC or TC) may obtain better improvement than the TT genotype in insulin resistance through lifestyle intervention. This trial was registered at clinicaltrials.gov as NCT01554358.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6736191 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program.

Chen Yuhang Y Liu Huikun H Wang Leishen L Zhou Tao T Liang Zhaoxia Z Li Weiqin W Shang Xiaoyun X Leng Junhong J Shen Yun Y Hu Gang G Qi Lu L

The American journal of clinical nutrition 20190901 3

<h4>Background</h4>A history of gestational diabetes mellitus (GDM) has been related to an elevated risk of type 2 diabetes. The melanocortin-4 receptor (MC4R) genotype has been related to glycemic changes in women with prior GDM.<h4>Objective</h4>The objective of this study was to analyze whether lifestyle intervention modified the association between the MC4R genotype and changes in insulin sensitivity among women with prior GDM.<h4>Methods</h4>We genotyped MC4R rs6567160 and measured glucose ...[more]

PMID: 31271198

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Project description:AimsWomen 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 methodsThis 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.ResultsWe 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.ConclusionsHealthy lifestyle intervention may be beneficial for women with the GDM predisposing CDKAL1 genetic variant in improvement of insulin resistance.Trial registration numberClinicalTrials.gov NCT01554358. URL OF REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01554358.

Project description:Self-administered eHealth interventions provide a potential low-cost solution for reducing diabetes risk. The aim of this pilot randomised controlled trial (RCT) was to evaluate the feasibility, including recruitment, retention, preliminary efficacy (primary outcome) and acceptability (secondary outcome) of the "Body Balance Beyond" eHealth intervention in women with previous gestational diabetes mellitus (GDM). Women with overweight/obesity who had recent GDM (previous 24 months) were randomised into one of three groups: 1) high personalisation (access to "Body Balance Beyond" website, individual telehealth coaching via video call by a dietitian and exercise physiologist, and text message support); 2) low personalisation (website only); or 3) waitlist control. To evaluate preliminary efficacy, weight (kg), glycosylated hemoglobin, type A1C (HbA1c), cholesterol (total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)), diet quality and moderate-vigorous physical activity were analysed at baseline and at 3 and 6 months using generalised linear mixed models. To investigate acceptability, process evaluation was conducted at 3 and 6 months. Of the 327 potential participants screened, 42 women (mean age 33.5 ± 4.0 years and BMI 32.4 ± 4.3 kg/m2) were randomised, with 30 (71%) completing the study. Retention at 6 months was 80%, 54% and 79% for high personalisation, low personalisation and waitlist control, respectively (reasons: personal/work commitments, n = 4; started weight-loss diet, n = 1; pregnant, n = 1; resources not useful, n = 1; and not contactable, n = 5). No significant group-by-time interactions were observed for preliminary efficacy outcomes, with the exception of HDL cholesterol, where a difference favoured the low personalisation group relative to the control (p = 0.028). The majority (91%) of women accessed the website in the first 3 months and 57% from 4-6 months. The website provided useful information for 95% and 92% of women at 3 and 6 months, respectively, although only a third of women found it motivating (30% and 25% at 3 and 6 months, respectively). Most women agreed that the telehealth coaching increased their confidence for improving diet (85%) and physical activity (92%) behaviours, although fewer women regarded the text messages as positive (22% and 31% for improving diet and physical activity, respectively). The majority of women (82% at 3 months and 87% at 6 months) in the high personalisation group would recommend the program to other women with GDM. Recruiting and retaining women with a recent diagnosis of GDM is challenging. The "Body Balance Beyond" website combined with telehealth coaching via video call is largely acceptable and useful for women with recent GDM. Further analysis of the effect on diabetes risk reduction in a larger study is needed.

Project description:ObjectiveTo quantify the association between a combination of healthy lifestyle factors before pregnancy (healthy body weight, healthy diet, regular exercise, and not smoking) and the risk of gestational diabetes.DesignProspective cohort study.SettingNurses' Health Study II, United States.Participants20,136 singleton live births in 14,437 women without chronic disease.Main outcome measureSelf reported incident gestational diabetes diagnosed by a physician, validated by medical records in a previous study.ResultsIncident first time gestational diabetes was reported in 823 pregnancies. Each lifestyle factor measured was independently and significantly associated with risk of gestational diabetes. The combination of three low risk factors (non-smoker, ≥ 150 minutes a week of moderate to vigorous physical activity, and healthy eating (top two fifths of Alternate Healthy Eating Index-2010 adherence score)) was associated with a 41% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.59, 95% confidence interval 0.48 to 0.71). Addition of body mass index (BMI) <25 before pregnancy (giving a combination of four low risk factors) was associated with a 52% lower risk of gestational diabetes compared with all other pregnancies (relative risk 0.48, 0.38 to 0.61). Compared with pregnancies in women who did not meet any of the low risk lifestyle factors, those meeting all four criteria had an 83% lower risk of gestational diabetes (relative risk 0.17, 0.12 to 0.25). The population attributable risk percentage of the four risk factors in combination (smoking, inactivity, overweight, and poor diet) was 47.5% (95% confidence interval 35.6% to 56.6%). A similar population attributable risk percentage (49.2%) was observed when the distributions of the four low risk factors from the US National Health and Nutrition Examination Survey (2007-10) data were applied to the calculation.ConclusionsAdherence to a low risk lifestyle before pregnancy is associated with a low risk of gestational diabetes and could be an effective strategy for the prevention of gestational diabetes.

Dataset Information

Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program.

Publications

Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program.

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