Vitamin D receptor methylation attenuates the association between physical activity and type 2 diabetes mellitus: a case-control study.

Background Physical activity and vitamin D receptor (VDR) were associated with Type 2 Diabetes Mellitus (T2DM). However, the associations of VDR methylation with T2DM and physical activity remain unknown. We aimed to investigate whether VDR methylation was a link between physical activity and T2DM. Methods A 1:1 matching case-control study was designed based on the Henan Rural Cohort Study, including 272 pairs of T2DM patients and non-patients. Physical activity level was assessed using the International Physical Activity Questionnaire. High resolution melt (HRM) method was applied to determine the methylation level of the promoter region of VDR. Association between physical activity and T2DM was analyzed with conditional logistic regression model. The effect modification of VDR methylation levels on the association between physical activity and T2DM was conducted. Multivariate correlation analysis model was applied to investigate correlations of VDR methylation with insulin sensitivity. Results Physical activity level was associated with T2DM risk (crude model: OR: 0.611, 95% CI: 0.416-0.897; adjusted model: OR: 0.619, 95% CI: 0.418-0.917). In effect modification analysis, the effects of physical activity on T2DM were stronger for low VDR methylation level than high (P=0.025). Besides, VDR methylation levels was associated with insulin (r=-0.089, P=0.039), as well as HOMA-IR (r=-0.098, P=0.022). Conclusions Methylation status of VDR promoter is associated with the secretion and sensitivity of insulin. VDR methylation attenuates the association between physical activity and T2DM, indicating that proactively physical activity may reduce the risk of T2DM, especially in people with low VDR methylation level.