Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial
<strong>Objective: </strong>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 (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P<sub>int</sub></i><sub> </sub>AUCgluc=0.009, <i>P<sub>int</sub></i><sub> </sub>CIR=0.022, <i>P<sub>int </sub></i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>