Glucose Tolerance, Meal Timing and MTNR1B

Study Overview
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Brief Summary
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The purpose of this investigation is to assess in a community-based cohort of late-night eaters the effect of coincident food intake and endogenous melatonin on glycemic control, and the putative interaction effect of melatonin receptor 1B (MTNR1B) genetic variation on this relationship. With the results from this study, the investigators expect to advance in the understanding of the role of endogenous melatonin on glucose metabolism in late night eaters and carriers of the MTNR1B risk allele, with potential implications on the guidelines to mitigate risk of type 2 diabetes in late night eaters and carriers of the MTNR1B risk allele.

Detailed Description
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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 the current study is to test the hypothesis that the concurrence of meal timing with elevated endogenous melatonin concentrations results in impaired glucose control and that this effect is stronger in homozygous MTNR1B risk carriers than in non-carriers. To do so we will test glucose tolerance using identical mixed meals under two dinner conditions: a) delayed dinner or Late Eating (LE): starting1 hour before usual bed time, b) advanced dinner or Early Eating (EE): starting 4 hours before habitual bed time, in a randomized, cross-over study design. These findings could support a clinical application for the screening of this single nucleotide polymorphism (SNP) and the possibility of implementing tailored and cost-effective behavioral interventions to prevent type 2 diabetes in vulnerable populations. These goals will be achieved through a specific approach: • Interventional (randomized, cross-over controlled trials) (Aim 1): To study the potential interaction between meal timing (dinner) and genetic variants MTNR1B for glucose tolerance.

Official Title
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Glucose Tolerance, Meal Timing and MTNR1B in a Mediterranean Population

Conditions
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Non-Diabetic Disorder of Endocrine Pancreas

Intervention / Treatment
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* Behavioral: Dinner timing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index: >19 kg/m2 Age: >18 years of age Caucasian Exclusion Criteria: Receiving treatment with thermogenic, lipogenic, or contraceptive drugs Diabetes mellitus, chronic renal failure, hepatic diseases, or cancer diagnosis Bulimia diagnosis, prone to binge eating Undergoing treatment with anxiolytic or antidepressant drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Dinner Timing<br>Test the lack of concurrence of meal timing with endogenous melatonin concentrations | Behavioral: Dinner timing<br>* Glucose tolerance after a late diner (1 hour before habitual bedtime) differs from early dinner (4 hours before habitual bedtime) due to the concurrence of meal timing with different levels of endogenous melatonin. This effect can be different among risk allele carriers (G) or non-rick allele carriers (C) of the MTNR1B.<br>|
| Experimental: Late Dinner Timing<br>Test the concurrence of meal timing with elevated endogenous melatonin concentrations | Behavioral: Dinner timing<br>* Glucose tolerance after a late diner (1 hour before habitual bedtime) differs from early dinner (4 hours before habitual bedtime) due to the concurrence of meal timing with different levels of endogenous melatonin. This effect can be different among risk allele carriers (G) or non-rick allele carriers (C) of the MTNR1B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) glucose | Investigators will measure glucose levels for 120 minutes at day time and night time visits, and compare the results by genotype at selected loci. | between 0-120 minutes, Visit 2 and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting glucose |  | between 0-120 minutes, Visit 2 and 3 | 
| Saliva Melatonin |  | between 0-120 minutes, Visit 2 and 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose tolerance, MTNR1B, nutrigenomics, Food timing