Circadian meal timing is heritable and associated with insulin sensitivity

Abstract Background Although the contribution of the circadian clock to metabolic regulation is widely recognized, the role of meal timing in glucose metabolism and diabetes risk remains insufficiently studied. This study aimed (i) to investigate the link between individual circadian meal timing pattern and glucose homeostasis and (ii) to explore the contribution of genetic and environmental factors to meal timing parameters. Methods In the German NUtriGenomic Analysis in Twins (NUGAT) cohort, which includes 92 adult twins, glucose metabolism parameters were assessed using fasting samples and the oral glucose tolerance test (OGTT). Parameters of meal timing pattern (meal timing itself, daily calorie distribution, and meal number) were extracted from five-day food records. Circadian eating timing was determined relative to the individual’s chronotype (MSFsc) assessed by the Munich chronotype questionnaire. The heritability of meal timing components was estimated using the ACE model. Results Multiple meal timing components showed associations with glucose metabolism parameters. Most associations were found for the calorie midpoint defined as the time point at which 50% of daily calories were consumed. Indices of insulin sensitivity, ISI Stumvoll (β = 0.334, p = 2.9 x 10 -4 ) and HOMA-IR (β = -0.276, p = 0.007), as well as fasting insulin levels were significantly associated with the circadian caloric midpoint even after the model adjustment for gender, age, energy intake, and sleep duration. BMI and waist circumference also demonstrated robust associations with circadian caloric midpoint. High or moderate heritability was shown for all meal timing components. Meal timing pattern was also strongly related to individual sleep timing and chronotype, both of which also showed a marked genetic impact. Conclusion Circadian meal timing is associated with insulin sensitivity and shows significant genetic influences, sharing a common genetic architecture with sleep behaviour. Shifting the main calorie intake to earlier circadian time might protect against diabetes, although this could be challenging due to the high heritability of meal timing components. Graphical abstract Highlights Circadian caloric midpoint shows a robust association with insulin sensitivity It remains significant after the adjustment for energy intake and other cofounders Meal timing, daily calorie distribution, and meal number show a high or moderate heritability Meal timing strongly relates to the sleeping behaviour and chronotype