Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial.

Abstract

OBJECTIVE:

We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin receptor-1B gene (MTNR1B).

RESEARCH DESIGN AND METHODS:

In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime ("early dinner timing") and a late condition scheduled 1 h prior to habitual bedtime ("late dinner timing"), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method.

RESULTS:

Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. The effect of late eating impairing glucose tolerance was stronger in the MTNR1B G-allele carriers than in noncarriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint disposition index = 0.018).

CONCLUSIONS:

Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.

• Authors: Marta Garaulet, Jesus Lopez-Minguez, Hassan S Dashti, Céline Vetter, Antonio Miguel Hernández-Martínez, Millán Pérez-Ayala, Juan Carlos Baraza, Wei Wang, Jose C Florez, Frank A J L Scheer, Richa Saxena
• Journal: Diabetes care (Diabetes Care) Vol. 45 Issue 3 Pg. 512-519 (03 01 2022) ISSN: 1935-5548 [Electronic] United States
• PMID: 35015083 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by the American Diabetes Association.

Chemical References

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

Topics

• Blood Glucose
• Cross-Over Studies
• Diabetes Mellitus, Type 2 (genetics)
• Eating
• Genotype
• Glucose (administration & dosage, metabolism)
• Humans
• Insulin (metabolism)
• Insulin Secretion (genetics)
• Meals (physiology)
• Melatonin (blood)
• Receptor, Melatonin, MT2 (genetics)
• Risk Factors
• Spain
• Time Factors