Clinical trial NCT03036592: MTNR1B SNP*Food Timing Interaction on Glucose Control
Official title: MTNR1B SNP*Food Timing Interaction on Glucose Control in a Late Eater Mediterranean Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Diabetic Disorder of Endocrine Pancreas
Keywords: Glucose tolerance test, MTNR1B, nutrigenomics, food timing
Lead sponsor: Universidad de Murcia
Sponsor class: OTHER
First posted: 2017-01-30
Enrollment: 889
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The purpose of this investigation is to assess the role of melatonin receptor 1B (MTNR1B) single nucleotide polymorphism (SNP)\*food timing interaction on glucose control in the deleterious effect in a vulnerable population with regular exposure to concurrent high melatonin and food intake as late night eaters (those having dinner within 2.5 h before their usual bed time). With the results from this study, we expect to advance our 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: 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 glucose oral tolerance test (OGTT) conditions: a) delayed OGTT or Late Eating (LE): starting1 hour before their usual bed time, b) advanced OGTT 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 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 (n=1000).

Eligibility criteria: Inclusion Criteria:

* Body Mass Index: \> 18.5 o \< 40 kg/m2
* Age: between 18 and 65 year of age
* European ancestry
* Day workers

Exclusion Criteria:

* Receiving treatment with thermogenic, lipogenic, or drugs
* Diabetes mellitus, chronic renal failure, hepatic diseases, or cancer diagnosis
* Bulimia diagnosis, prone to binge eating
* Undergoing treatment with Type 2 diabetes mellitus (high blood sugar) medications such as Metformin or other non-Metformin oral anti-diabetic drugs such as sulfonylureas, meglitinides, or glitazones
* Undergoing treatment with Corticosteroids/steroids, Growth hormone, Anticoagulant medicines, or blood thinners, Beta blockers for hypertension, Medications for sleep, Fluvoxamine, Opioids or Amphetamines, Tranquilizers, nonsteroidal anti-inflammatory drugs.
* Pregnant

Primary outcomes:
measure: Area Under the Curve (AUC) Glucose
timeFrame: Along 120 minutes in visits 1 and 2
measure: Disposition Index (DI)
timeFrame: Along 120 minutes in visits 1 and 2
Secondary outcomes:
measure: Corrected Insulin Response (CIR)
timeFrame: At minute 30 during the visit 1 and 2.
measure: Insulin Sensitivity Index (ISI)
timeFrame: Along 120min in visits 1 and 2
measure: Fasting Glucose
timeFrame: At minute 0 in visit 1 and 2.
measure: Fasting Insulin
timeFrame: At minute 0 in visit 1 and 2
measure: Serum Melatonin
timeFrame: At baseline and 120 minutes in visit 1 and 2
measure: Dim Light Melatonin Onset (DLMO) at Early Condition Only
timeFrame: Melatonin measured every half hour for 5 hours at Early condition in all participants
Other outcomes:
measure: Temperature Record (Mean Value 10hours Daytime)
timeFrame: For 1 week between visit 1 and 2
measure: Activity Record (Mean Value 10hours Daytime)
timeFrame: For 1 week between visit 1 and 2
measure: Light Exposure (Mean Value 10hours Daytime)
timeFrame: For 1 week between the visits 1 and 2
measure: Sleep Duration
timeFrame: For 1 week between visit 1 and 2
measure: Total Energy Intake
timeFrame: For 1 week between visit 1 and 2
measure: Dietary Composition
timeFrame: For 1 week between visit 1 and 2
measure: Dietary Intake Timing
timeFrame: For 1 week between visit 1 and 2
measure: Physical Activity
timeFrame: During the week of washout
measure: Chronotype
timeFrame: During the week of washout
measure: Emotional Eating
timeFrame: During the week of washout
measure: Sleep Quality
timeFrame: During the week of washout
measure: Insomnia
timeFrame: During the week of washout
measure: Depression
timeFrame: During the week of washout
Locations:
city: Murcia
country: Spain
facility: University of Murcia
Study officials:
affiliation: Universidad de Murcia
name: Purificación Gomez Abellan, PHD
role: STUDY_CHAIR
References:
citation: Garaulet M, Lopez-Minguez J, Dashti HS, Vetter C, Hernandez-Martinez AM, Perez-Ayala M, Baraza JC, Wang W, Florez JC, Scheer FAJL, Saxena R. Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial. Diabetes Care. 2022 Mar 1;45(3):512-519. doi: 10.2337/dc21-1314.