Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial.
Level 2 - randomized trial
Individual randomized crossover trial
PubMed 35015083 · doi:10.2337/dc21-1314
What was done
A randomized crossover trial in 845 participants from a Spanish natural late-eating population evaluated how dinner timing interacts with endogenous melatonin levels and the MTNR1B type 2 diabetes risk variant. Following an 8-hour fast, each participant completed two 2-hour 75-g oral glucose tolerance tests (OGTT): an early condition 4 hours before habitual bedtime and a late condition 1 hour before habitual bedtime. Postprandial glucose and insulin incremental area under the curve (AUC) were measured and analyzed by MTNR1B genotype.
What was found
Serum melatonin levels were 3.5-fold higher in the late versus early dinner condition. Late dinner timing led to an 8.3% higher glucose AUC and a 6.7% lower insulin AUC overall. The impairment in glucose tolerance from late eating was significantly stronger among carriers of the MTNR1B G allele compared to noncarriers, driven by impaired beta-cell function (interaction p-values: glucose AUC Pint = 0.009, corrected insulin response Pint = 0.022, disposition index Pint = 0.018).
Why it matters
This demonstrates a mechanistic link between late-night carbohydrate intake, elevated endogenous melatonin, and impaired glycemic control, identifying MTNR1B risk allele carriers as particularly susceptible to metabolic disruption from late meals.
Limits
The study was conducted in a single Spanish population with late-eating habits, which may limit generalizability to other chronotypes, eating patterns, or ancestries. Glycemia was tested using an acute 75-g oral glucose load after an 8-hour daytime fast rather than a typical mixed evening meal, and long-term metabolic outcomes were not evaluated.
Cited by
- supports Melatonin reduces the responsiveness of pancreatic beta-islet cells to glucose, decreasing insulin secretion.