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

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posted on 11.01.2022, 18:52 by 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 AJL Scheer, Richa Saxena
Objective: We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (MTNR1B).

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

Results: Melatonin serum levels were 3.5-fold higher in the late vs. early condition, with late dinner-timing resulting in 6.7% lower insulin area-under-the-curve (AUC) and 8.3% higher glucose AUC. In the late condition MTNR1B G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (Pint AUCgluc=0.009, Pint CIR=0.022, Pint DI=0.018).

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

Funding

ONTIME-MT was funded by the NIH R01 grant R01DK105072. Marta Garaulet is supported by the Spanish Government of Investigation, Development and Innovation (SAF2017-84135-R) including FEDER co-funding; Séneca Foundation (20795/PI/18) and NIDDK R01DK105072. Hassan S Dashti and Richa Saxena are supported by NIH R01DK107859. Richa Saxena and Frank AJL Scheer are supported by NIH R01DK102696 and R01DK105072. Céline Vetter is supported by R01DK105072. Frank AJL Scheer is further supported by R01DK099512, R01HL118601, and R01HL140574. Jose C. Florez and Richa Saxena are Massachusetts General Hospital Research Scholars. Jose C. Florez is supported by NIDDK K24 DK110550. The funding sources had no influence on study design, data analyses, or interpretation of the findings.

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