Glucose Tolerance, Meal Timing and MTNR1B (ONTIME-DINE)

Glucose Tolerance, Meal Timing and MTNR1B in a Mediterranean Population

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.

Study Overview

• Status: Completed
• Conditions: Non-Diabetic Disorder of Endocrine Pancreas
• Intervention / Treatment: Behavioral: Dinner timing

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30100
    • University of Murcia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early Dinner Timing; Test the lack of concurrence of meal timing with endogenous melatonin concentrations	Behavioral: Dinner timing; 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.
Experimental: Late Dinner Timing; Test the concurrence of meal timing with elevated endogenous melatonin concentrations	Behavioral: Dinner timing; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Duration	Sleep duration will be computed from self-reported.	total of 2 weeks between Visit 1 and 3
Light Exposure	Measured using Pendant G Acceleration Data Logger.	total of 2 weeks between Visit 1 and 3
Total Energy Intake	Total energy intake in kcal/day will be computed from 14-day 24-hr dietary record.	total of 2 weeks between Visit 1 and 3
Dietary Composition	Macronutrient and micronutrient intake will be computed from 14-days of self-reported 24-hr dietary record.	total of 2 weeks between Visit 1 and 3
Dietary Intake Timing	Food timing will be self-reported and averaged across 14-days of 24-hr dietary record.	total of 2 weeks between Visit 1 and 3
Chronotype	Assessed using the Morningness-Eveningness Questionnaire (MEQ).	at baseline

Collaborators and Investigators

• Sponsor: Universidad de Murcia
• Investigators: Study Director: Marta Garaulet, PHD, Universidad de Murcia

Publications and helpful links

General Publications

• Lopez-Minguez J, Saxena R, Bandin C, Scheer FA, Garaulet M. 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: December 16, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimate): December 28, 2016

Study Record Updates

• Last Update Posted (Actual): October 27, 2017
• Last Update Submitted That Met QC Criteria: October 26, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Glucose tolerance; nutrigenomics; Food timing; MTNR1B
• Other Study ID Numbers: 15123/PI/10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO