Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study
Research Design and Methods: This study triangulated evidence across multivariable regression (MVR), one-sample and two-sample Mendelian randomization (1SMR and 2SMR) including sensitivity analyses on the effects of 5 self-reported sleep traits (i.e., insomnia symptoms (difficulty initiating or maintaining sleep), sleep duration, daytime sleepiness, napping, chronotype) on HbA1c (in standard deviation (SD) units) in adults of European ancestry from the UK Biobank (for MVR and 1SMR analyses; n=336,999; mean (SD) age 57 (8) years, 54% female) and in the genome-wide association studies from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (for 2SMR analysis; n=46,368; 53 (11) years; 52% female).
Results: Across MV, 1SMR, 2SMR, and their sensitivity analyses we found a higher frequency of insomnia symptoms (usually vs sometimes or rarely/never) was associated with higher HbA1c (MVR: 0.05 SD units, 95% confidence interval (0.04 to 0.06), 1SMR: 0.52, (0.42 to 0.63), 2SMR: 0.24, (0.11 to 0.36)). Associations remained but point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency across, with some but not all, providing evidence of an effect.
Conclusions: Our results suggest that frequent insomnia symptoms causes higher HbA1c levels and by implication, that insomnia has a causal role in type 2 diabetes. These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycaemia and prevent diabetes.