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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: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.

Project description:BACKGROUND:Physical activity might reduce the risk of developing dementia. However, it is still unclear whether the protective effect differs depending on the subtype of dementia. We aimed to investigate if midlife physical activity affects the development of vascular dementia (VaD) and Alzheimer's disease (AD) differently in two large study populations with different designs. METHODS:Using a prospective observational design, we studied whether long-distance skiers of the Swedish Vasaloppet (n?=?197,685) exhibited reduced incidence of VaD or AD compared to matched individuals from the general population (n?=?197,684) during 21?years of follow-up (median 10, interquartile range (IQR) 5-15?years). Next, we studied the association between self-reported physical activity, stated twice 5?years apart, and incident VaD and AD in 20,639 participants in the Swedish population-based Malmo Diet and Cancer Study during 18?years of follow-up (median 15, IQR 14-17?years). Finally, we used a mouse model of AD and studied brain levels of amyloid-?, synaptic proteins, and cognitive function following 6?months of voluntary wheel running. RESULTS:Vasaloppet skiers (median age 36.0?years [IQR 29.0-46.0], 38% women) had lower incidence of all-cause dementia (adjusted hazard ratio (HR) 0.63, 95% CI 0.52-0.75) and VaD (adjusted HR 0.49, 95% CI 0.33-0.73), but not AD, compared to non-skiers. Further, faster skiers exhibited a reduced incidence of VaD (adjusted HR 0.38, 95% CI 0.16-0.95), but not AD or all-cause dementia compared to slower skiers. In the Malmo Diet and Cancer Study (median age 57.5?years [IQR 51.0-63.8], 60% women), higher physical activity was associated with reduced incidence of VaD (adjusted HR 0.65, 95% CI 0.49-0.87), but not AD nor all-cause dementia. These findings were also independent of APOE-?4 genotype. In AD mice, voluntary running did not improve memory, amyloid-?, or synaptic proteins. CONCLUSIONS:Our results indicate that physical activity in midlife is associated with lower incidence of VaD. Using three different study designs, we found no significant association between physical activity and subsequent development of AD.

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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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