Experimental studies have shown that reducing sleep duration or disrupting sleep results in increased insulin resistance and higher plasma glucose levels. Systematic reviews and meta-analyses of prospective studies have consistently found that both shorter and longer sleep durations are associated with an increased risk of type 2 diabetes (T2D).
Observational studies have also shown that insomnia, daytime napping, and chronotype (night preference) are associated with an increased risk of T2D. However, causal relationships are unclear from these data due to potential biases from residual confounding (e.g., from physical activity and diet) and reverse causality (e.g., from nocturia and neuropathic pain).
Mendelian randomization (MR) analysis, which uses genetic variants as instrumental variables to assess the causal effects of exposures on outcomes, is less prone to confounding or reverse causality than conventional multivariable observational regression (MVR). MR has different sources of bias relative to MVR; therefore, consistency in the results of these two methods increases confidence in assessing causality.
Recently published two-sample MRI (2SMR) studies found little consistent evidence for causal effects of sleep duration on T2D and/or related glycemic traits. Previous MR studies suggested that insomnia could causally increase the risk of T2D, but did not evaluate whether insomnia influences glycemic levels in the general population. These previous studies had limited statistical power and potential for weak instrument bias. Understanding the impact of sleep traits on glycemic levels in the general population could have profound public health implications for diabetes prevention.
Aim
To examine the effects of sleep traits on glycated hemoglobin (HbA1c).
Our objective was to explore the effects of sleep traits (e.g., insomnia, sleep duration, daytime sleepiness, daytime napping, and chronotype) on average glycemic levels as assessed by glycated hemoglobin (HbA1c) (main outcome) and glucose. (secondary outcome) in the general population.
Methodology
This study triangulated the evidence through multivariable regression (MVR) and one-sample (1SMR) and two-sample (2SMR) Mendelian randomization, including sensitivity analyzes on the effects of five self-reported sleep traits (i.e., sleep symptoms). insomnia [difficulty initiating or maintaining sleep], sleep duration, daytime sleepiness, napping and chronotype) in HbA1c (in SD units) in adults of European ancestry from the UK Biobank (for MVR and 1SMR analyses) (n = 336 999; mean [SD] age 57 years; 54% female) and in the Glucose and Insulin Related Traits Consortium (MAGIC) genome-wide association studies (for 2SMR analyses) (n = 46,368; 53 [11] years; 52% women).
Results
Through MVR, 1SMR, 2SMR, and their sensitivity analyses, we found that a higher frequency of insomnia symptoms (usually vs. sometimes or rarely/never) was associated with higher HbA1c (MVR 0.05 SD units [95% CI 0.04–0.06]; 1SMR 0.52 [0.42-0.63]; 2SMR 0.24 [0.11-0.36]).
The associations remained, but the point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency between methods, and some, but not all, provided evidence of an effect.
Conclusions Our results suggest that frequent insomnia symptoms cause higher levels of HbA1c 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 hyperglycemia and prevent diabetes. |
