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.

Keywords: UK Biobank; cohort; polygenic risk score; rest-activity rhythm; type 2 diabetes.