Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study

Objective: To examine the effects of sleep traits on glycated haemoglobin (HbA1c). Design: Observational multivariable regression (MVR), one-sample Mendelian randomization (1SMR), and two-sample summary data Mendelian randomization (2SMR). Setting: UK Biobank (UKB) prospective cohort study and genome-wide association studies from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). Participants: In MVR and 1SMR, participants were adults (mean (SD) age 57 (8) years; 54% female) from the UKB (n=336,999); in 2SMR, participants were adults (53 (11) years; 52% female) from MAGIC (n=46,368). All participants were adults of European ancestry. Exposures: Self-reported insomnia frequency (usually vs sometimes or rarely/never); sleep duration: 24-hour sleep duration (hours/day); short sleep ([≤]6 hours vs 7-8 hours) and long sleep ([≥]9 hours vs 7-8 hours); daytime sleepiness and daytime napping (each consisting of 3 categories: never/rarely, sometimes, usually); chronotype (5 categories from definite morning to definite evening preference). Main outcome measure: HbA1c in standard deviation (SD) units. Results: Across MV, 1SMR, 2SMR, and their sensitivity analyses we found a higher frequency of insomnia (usually vs sometimes or rarely/never) was associated with higher HbA1c (MVR: 0.053 SD units, 95% confidence interval (0.046 to 0.061), 1SMR: 0.52, (0.42 to 0.63), 2SMR: 0.22, (0.10 to 0.35)). Results remained significant but point estimates were somewhat attenuated after excluding people with diagnosed diabetes. For other sleep traits, there was less consistency with significant associations when using some, but not all methods. Conclusions: This study suggests that insomnia increases HbA1c levels. These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycaemia and prevent diabetes.