Late dinner impairs glucose tolerance in MTNR1B risk allele carriers: A randomized, cross-over study

Clin Nutr. 2018 Aug;37(4):1133-1140. doi: 10.1016/j.clnu.2017.04.003. Epub 2017 Apr 10.


Background & aims: Late-night dinner eating is associated with increased risk for type-2 diabetes. The underlying mechanism is unclear. One explanatory hypothesis is that the concurrence of elevated circulating melatonin and high glucose concentrations (characterizing late eating) leads to impaired glucose tolerance. However, to date no study has tested the influence of physiological melatonin concentrations on glucose-tolerance. The discovery of melatonin receptor MTNR1B as a diabetes risk gene provides evidence for a role of physiological levels of melatonin in glucose control. The aim of our study was to test the hypothesis that elevated endogenous melatonin concentrations worsen glucose control when eating late. Registered under Identifier no. NCT03003936.

Methods: We performed a randomized, cross-over trial to compare glucose tolerance in the presence (late dinner) or absence (early dinner) of elevated physiological melatonin concentrations and we compared the results between homozygous carriers and non-carriers of the MTNR1B risk allele.

Results: The concurrence of meal timing with elevated endogenous melatonin concentrations resulted in impaired glucose tolerance. This effect was stronger in MTNR1B risk-carriers than in non-carriers. Furthermore, eating late significantly impaired glucose tolerance only in risk-carriers and not in the non-risk carriers.

Conclusions: The interaction of dinner timing with MTNR1B supports a causal role of endogenous melatonin in the impairment of glucose tolerance. These results suggest that moving the dinner to an earlier time may result in better glucose tolerance specially in MTNR1B carriers.

Clinical trial registration:

Keywords: Diabetes; Glucose tolerance; MTNR1B; Meal timing; Melatonin.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose* / analysis
  • Blood Glucose* / metabolism
  • Blood Glucose* / physiology
  • Cross-Over Studies
  • Female
  • Glucose Tolerance Test
  • Humans
  • Meals / physiology*
  • Melatonin / analysis
  • Melatonin / metabolism
  • Middle Aged
  • Obesity
  • Polymorphism, Single Nucleotide
  • Receptor, Melatonin, MT2* / genetics
  • Receptor, Melatonin, MT2* / metabolism
  • Sleep
  • Time Factors


  • Blood Glucose
  • MTNR1B protein, human
  • Receptor, Melatonin, MT2
  • Melatonin

Associated data