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Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk.

ABSTRACT: We examined whether or not the association of physical activity with type 2 diabetes incidence differs according to several types of genetic susceptibility.In a large prospective cohort with 821 incident cases of type 2 diabetes, we examined interactions of physical activity with: (1) each of 65 type 2 diabetes-associated single nucleotide polymorphisms (SNPs); (2) a genetic risk score (GRS) comprising all 65 SNPs; (3) two GRSs comprised of SNPs implicated in insulin resistance (IR) and insulin secretion; (4) GRSs for fasting insulin (FI) and fasting glucose.We found a significant interaction of physical activity and the type 2 diabetes GRS (p interaction?=?0.016), suggesting a weaker protective effect of physical activity in those at high genetic risk. Based on the interactions observed with the IR GRS (p interaction?=?0.046) and the FI GRS (p interaction?=?0.042), it appears that the overall type 2 diabetes GRS interaction most likely occurs through genetic susceptibility to IR as opposed to insulin secretion. Furthermore, this interaction was more pronounced in women (p interaction?=?0.0025) than in men (p interaction?=?0.46). No single SNP stood out as displaying a strong interaction with physical activity.We conclude that although physical activity appears to have an overall protective effect on type 2 diabetes, this putative effect is weakest among individuals with high genetic risk for type 2 diabetes and IR.

SUBMITTER: Klimentidis YC

PROVIDER: S-EPMC4221563 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk.

Klimentidis Yann C YC Chen Zhao Z Arora Amit A Hsu Chiu-Hsieh CH

Diabetologia 20141002 12

<h4>Aims/hypothesis</h4>We examined whether or not the association of physical activity with type 2 diabetes incidence differs according to several types of genetic susceptibility.<h4>Methods</h4>In a large prospective cohort with 821 incident cases of type 2 diabetes, we examined interactions of physical activity with: (1) each of 65 type 2 diabetes-associated single nucleotide polymorphisms (SNPs); (2) a genetic risk score (GRS) comprising all 65 SNPs; (3) two GRSs comprised of SNPs implicated ...[more]

PMID: 25273344

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Project description:ImportancePolygenic risk scores (PRS) for type 2 diabetes (T2D) can improve risk prediction for gestational diabetes (GD), yet the strength of the association between genetic and lifestyle risk factors has not been quantified.ObjectiveTo assess the association of PRS and physical activity in existing GD risk models and identify patient subgroups who may receive the most benefits from a PRS or physical activity intervention.Design, settings, and participantsThe Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort was established to study individuals without previous pregnancy lasting at least 20 weeks (nulliparous) and to elucidate factors associated with adverse pregnancy outcomes. A subcohort of 3533 participants with European ancestry was used for risk assessment and performance evaluation. Participants were enrolled from October 5, 2010, to December 3, 2013, and underwent genotyping between February 19, 2019, and February 28, 2020. Data were analyzed from September 15, 2020, to November 10, 2021.ExposuresSelf-reported total physical activity in early pregnancy was quantified as metabolic equivalents of task (METs). Polygenic risk scores were calculated for T2D using contributions of 84 single nucleotide variants, weighted by their association in the Diabetes Genetics Replication and Meta-analysis Consortium data.Main outcomes and measuresEstimation of the development of GD from clinical, genetic, and environmental variables collected in early pregnancy, assessed using measures of model discrimination. Odds ratios and positive likelihood ratios were used to evaluate the association of PRS and physical activity with GD risk.ResultsA total of 3533 women were included in this analysis (mean [SD] age, 28.6 [4.9] years). In high-risk population subgroups (body mass index ≥25 or aged ≥35 years), individuals with high PRS (top 25th percentile) or low activity levels (METs <450) had increased odds of a GD diagnosis of 25% to 75%. Compared with the general population, participants with both high PRS and low activity levels had higher odds of a GD diagnosis (odds ratio, 3.4 [95% CI, 2.3-5.3]), whereas participants with low PRS and high METs had significantly reduced risk of a GD diagnosis (odds ratio, 0.5 [95% CI, 0.3-0.9]; P = .01).Conclusions and relevanceIn this cohort study, the addition of PRS was associated with the stratified risk of GD diagnosis among high-risk patient subgroups, suggesting the benefits of targeted PRS ascertainment to encourage early intervention.

Project description:Aims/hypothesisThis work examined the role of physical activity in the course of diabetes using data spanning nearly three decades. Our first aim was to examine the long-term association of moderate and vigorous physical activity with incidence of type 2 diabetes. Our second aim was to investigate the association of moderate-to-vigorous physical activity post-diabetes diagnosis with subsequent risk of all-cause and cardiovascular disease mortality.MethodsA total of 9987 participants from the Whitehall II cohort study free of type 2 diabetes at baseline (1985-1988) were followed for incidence of type 2 diabetes, based on clinical assessments between 1985 and 2016 and linkage to electronic health records up to 31 March 2017. We first examined the association of moderate and vigorous physical activity measured by questionnaire in 1985-1988 (mean age 44.9 [SD 6.0] years; women, 32.7%) with incident type 2 diabetes, using the interval-censored, illness-death model, a competing risk analysis that takes into account both competing risk of death and intermittent ascertainment of diabetes due to reliance on data collection cycles (interval-censored). The second analysis was based on individuals with type 2 diabetes over the follow-up period where we used Cox regression with inverse probability weighting to examine the association of moderate-to-vigorous physical activity after diagnosis of type 2 diabetes with risk of all-cause and cardiovascular disease mortality.ResultsOf the 9987 participants, 1553 developed type 2 diabetes during a mean follow-up of 27.1 (SD 6.3) years. Compared with participants who were inactive in 1985-1988, those who undertook any duration of moderate-to-vigorous physical activity had a lower risk of type 2 diabetes (HR 0.85 [95% CI 0.75, 0.97], p = 0.02; analysis adjusted for sociodemographic, behavioural and health-related factors). In 1026 participants with a diagnosis of type 2 diabetes over the follow-up period, data on moderate-to-vigorous physical activity after diabetes diagnosis were available; 165 all-cause deaths and 55 cardiovascular disease-related deaths were recorded during a mean follow-up of 8.8 (SD 6.1) years. In these participants with diabetes, any duration of moderate-to-vigorous physical activity was associated with lower all-cause mortality (HR 0.61 [95% CI 0.41, 0.93], p = 0.02) while the association with cardiovascular mortality was evident only for physical activity undertaken at or above recommendations (≥2.5 h per week of moderate-to-vigorous physical activity or ≥1.25 h per week of vigorous physical activity; HR 0.40 [95% CI 0.16, 0.96], p = 0.04) in fully adjusted models.Conclusions/interpretationModerate-to-vigorous physical activity plays an important role in diabetes, influencing both its incidence and prognosis. A protective effect on incidence was seen for durations of activity below recommendations and a marginal additional benefit was observed at higher durations. Among individuals with type 2 diabetes, any duration of moderate-to-vigorous physical activity was associated with reduced all-cause mortality while recommended durations of physical activity were required for protection against cardiovascular disease-related mortality.Data availabilityWhitehall II data, protocols and other metadata are available to the scientific community. Please refer to the Whitehall II data sharing policy at https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii/data-sharing.

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Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk.

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Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk.

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