Objectively-Defined Sleep Regularity Is Associated with Macrovascular and Microvascular Complications among Individuals with Type 2 Diabetes Mellitus: A Cohort Study

Background: To assess the association of accelerometer-measured sleep regularity with macrovascular and microvascular complications among individuals with type 2 diabetes mellitus (T2DM). Methods: A total of 3,862 participants with T2DM at baseline participated. The sleep regularity metrics measured by wrist-worn accelerometers include sleep regularity index (SRI) and standard deviation (SD) of sleep duration. Incident macrovascular complications including coronary heart disease (CHD) and stroke, microvascular complications including diabetic neuropathy, diabetic kidney disease, and diabetic retinopathy were recorded. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for macrovascular and microvascular complications. Results: During a median follow-up of 7.2 years, 410 composite macrovascular and 615 composite microvascular events occurred. Compared to regular sleepers (the highest tertile of SRI), irregular sleepers were at higher risk of composite macrovascular complications (HR, 1.29; 95% CI, 1.01 to 1.66) and stroke (HR, 1.97; 95% CI, 1.08 to 3.58). Compared to regular sleepers (the lowest tertile of sleep duration SD), irregular sleepers were at higher risk of composite macrovascular complications (HR, 1.44; 95% CI, 1.12 to 1.84), CHD (HR, 1.40; 95% CI, 1.07 to 1.82), and stroke (HR, 2.07; 95% CI, 1.13 to 3.81). For microvascular complications, no significant association of sleep regularity metrics was found (all P>0.05). However, the dose-response analysis suggested a potential nonlinear association between SRI and diabetic neuropathy, with lower SRI consistently associated with higher risk of diabetic neuropathy (HR, 1.92; 95% CI, 1.28 to 2.88; 5th percentile vs. 50th percentile). Conclusion: An irregular sleep pattern across days is clinically relevant for increasing the risk of macrovascular complications and diabetic neuropathy among individuals with T2DM.