The rest‐activity rhythm, genetic susceptibility and risk of type 2 diabetes: A prospective study in UK Biobank

Abstract Aims This study aims to examine the association between the rest‐activity rhythm (RAR) and the incidence of type 2 diabetes (T2D). Materials and Methods In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter‐daily stability, intra‐daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D‐PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D‐PRS on the occurrence of T2D. Results During 692 257 person‐years follow‐ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HR RA = 2.06, 95% CI: 1.76‐2.41; HR M10 = 1.33, 95% CI: 1.19‐1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55‐2.24). The joint analysis showed that the high T2D‐PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HR RA = 4.46, 95% CI: 3.36‐6.42; HR M10 = 3.15, 95% CI: 2.29‐4.32; HR L5 = 3.09, 95% CI: 2.40‐3.99). No modification effects of T2D‐PRS on the association between the RAR parameters and risk of T2D were observed ( p > .05). Conclusion The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D.