Rest-activity circadian rhythm and impaired glucose tolerance in adults:an analysis of NHANES 2011-2014

INTRODUCTION: Circadian rhythm disturbance occurs in type 2 diabetes, yet it is unknown whether it also exists in the prediagnostic phase of the disease. Thus, we examined the association of rest-activity circadian rhythm with 2-hour glucose levels and the risk of impaired glucose tolerance (IGT) in a nationally representative sample of adults without diabetes using a cross-sectional design. RESEARCH DESIGN AND METHODS: We analyzed data from 2760 adults without diabetes (age ≥20) with at least 4 days of validated accelerometer recordings and a valid oral glucose tolerance test from the National Health and Nutrition Examination Survey 2011-2014. Non-parametric rest-activity circadian rhythm parameters were derived from the accelerometer recordings. RESULTS: In the models adjusting for multiple covariates, a one-quantile increase in relative amplitude (ie, increased circadian rhythmicity) was associated with 2.66 mg/dL decrease in 2-hour glucose level (95% CI -3.94 to -1.38, p<0.001) and a decreased odds of IGT (OR 0.75, 95% CI 0.63 to 0.89, p=0.002). A one-quantile increase in intradaily variability (ie, increased rhythm fragmentation) was associated with 3.01 mg/dL increase in 2-hour glucose level (95% CI 1.52 to 4.49, p=0.001) and an increased odds of IGT (OR 1.37, 95% CI 1.19 to 1.58, p<0.001). CONCLUSIONS: Circadian disruption is significantly associated with impaired glucose homeostasis in a general population of adults without diabetes. The association of circadian rhythm abnormalities with indicators of the pre-diabetic state suggests that circadian dysfunction may contribute to early disease pathogenesis.