Inflammation, Oxidative Stress, and Antioxidant Micronutrients as Mediators of the Relationship Between Sleep, Insulin Sensitivity, and Glycosylated Hemoglobin

BACKGROUND: Sleep deprivation and poor sleep quality contribute to increases in oxidative stress, antioxidant imbalance, and a pro-inflammatory state which may predispose to a higher risk of diabetes. Our objective was to estimate the contributions of C-reactive protein (CRP), gamma glutamyl transferase (GGT), and micronutrient antioxidants (bilirubin, carotenoids, uric acid, vitamins A, C–E?) to the relationships between sleep-fasting insulin concentration and -glycosylated hemoglobin (HbA1c). METHODS: Data from the 2005/06 US National Health and Nutritional Examination Survey were used (N = 1,946; 20 y+). Sleep quality and quantity was assessed by the Sleep Disorders Questionnaire, and fasting blood was collected to quantify CRP, GGT, antioxidant micronutrients, insulin concentration, and HbA1c. The bootstrap method was used to estimate the amount of mediation or contribution of these mediators to the sleep–insulin concentration and -HbA1c relationships, which were quantified as large (≥0.25) or moderate (≥0.09). RESULTS: The sleep duration–fasting insulin relationship was mediated by GGT, carotenoids, uric acid, and vitamins C and D, whereas CRP and bilirubin were non-significant mediators of a moderate effect size. Similarly, the sleep quality–fasting insulin relationship was mediated by CRP, bilirubin and vitamin C, whereas GGT, carotenoids, uric acid, and vitamin D were non-significant large-to-moderate mediators. To a lesser degree, these micronutrients mediated for the relationship between sleep-HbA1c levels. CONCLUSION: Several factors related to inflammation, oxidative stress, and antioxidant status were found to lie on the pathway of the sleep–insulin and –glycemic control relationships. Sleep hygiene, reduced systemic inflammation/oxidative stress, and optimal antioxidants intake are potentially beneficial targets for managing diabetes risk.