The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study

Study Objectives Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar results observed in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other sleep traits, on glycated haemoglobin (HbA1c). Our aims were a) to explore potential effects of accelerometer-derived sleep traits on HbA1c and glucose levels and b) to determine genetic correlations across accelerometer-derived and self-reported sleep traits. Methods We used MR methods to explore effects of accelerometer-derived sleep traits (duration, mid-point least active 5-hours, mid-point most active 10-hours, sleep fragmentation, and efficiency) on HbA1c in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 149,054). Cross-trait linkage disequilibrium score regression was also applied to determine genetic correlations across all accelerometer-derived and self-reported sleep traits and HbA1c/glucose. Results Main and sensitivity MR analyses showed no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. Conclusions Taken together, these findings suggested accelerometer-derived sleep traits do not causally affect HbA1c levels, and accelerometer-derived measures of sleep duration and sleep quality might not simply be ‘objective’ measures of self-reported sleep duration and insomnia, but rather captured different underlying sleep characteristics. Statement of Significance Self-reported and accelerometer-derived sleep disturbance is associated with increased risk of hyperglycaemia and type 2 diabetes in observational analyses. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not other self-reported sleep traits, on glycated haemoglobin (HbA1c). This MR study showed little evidence supporting an effect of any accelerometer-derived sleep trait on HbA1c or glucose, but a potential non-linear (e.g., U-shaped) effect cannot be ruled out. The genetic correlation suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different exposures.