ONTIME-MT: MTNR1B SNP*Food Timing Interaction on Glucose Control
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 in obese women (n=1000).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MTNR1B CC Test glucose tolerance in homozygous non-carriers (CC) for MTNR1B rs10830963 in Early OGTT and Late OGTT |
Behavioral: Early OGTT
Test glucose tolerance using identical mixed 75 gr of glucose under early condition (4 hours before habitual bedtime)
Behavioral: Late OGTT
Test glucose tolerance using identical mixed 75 gr of glucose under late condition (1 hour before habitual bedtime)
|
| Experimental: MTNR1B GG Test glucose tolerance in homozygous (GG) risk allele carriers for MTNR1B rs10830963 in Early OGTT and Late OGTT |
Behavioral: Early OGTT
Test glucose tolerance using identical mixed 75 gr of glucose under early condition (4 hours before habitual bedtime)
Behavioral: Late OGTT
Test glucose tolerance using identical mixed 75 gr of glucose under late condition (1 hour before habitual bedtime)
|
| Experimental: MTNR1B CG Test glucose tolerance in heterozygous (CG) risk allele carriers for MTNR1B rs10830963 in Early OGTT and Late OGTT |
Behavioral: Early OGTT
Test glucose tolerance using identical mixed 75 gr of glucose under early condition (4 hours before habitual bedtime)
Behavioral: Late OGTT
Test glucose tolerance using identical mixed 75 gr of glucose under late condition (1 hour before habitual bedtime)
|
Outcome Measures
Primary Outcome Measures
- Area Under the Curve (AUC) glucose [between 0-120 minutes, Visit 2 and 3]
Investigators will measure insulin and glucose levels for 120 minutes at day time and night time visits, and compare them by genotype at selected loci.
- Disposition index [between 0-120 minutes, Visit 2 and 3]
Disposition index will be determined by frequently sampled oral glucose tolerance test
Secondary Outcome Measures
- Corrected Insulin Response [between 0-120 minutes, Visit 2 and 3]
Corrected Insulin Response
- Insulin Sensitivity Index [between 0-120 minutes, Visit 2 and 3]
Insulin Sensitivity Index
- Fasting glucose [between 0-120 minutes, Visit 2 and 3]
Fasting glucose
- Fasting insulin [0-120 minutes, Visit 2 and 3]
Fasting insulin
- Serum Melatonin [at baseline and 120 minutes, Visit 2 and 3]
Serum Melatonin
- DLMO [between 0-5 hours, Visit 3]
Dim Light Melatonin Onset
Other Outcome Measures
- Temperature record [total of 1 week between Visit 1 and 2]
Measured using temperature sensor
- Activity record [total of 1 week between Visit 1 and 2]
Measured using Acceleration Data Logger
- Light Exposure [total of 1 week between Visit 1 and 2]
Measured using a light sensor
- Sleep Duration [total of 1 week between Visit 1 and 2]
Sleep duration will be computed from self-reported
- Total Energy Intake [total of 1 week between Visit 1 and 2]
Total energy intake in kcal/day will be computed from 7-day 24-hr dietary recalls
- Dietary Composition [total of 1 week between Visit 1 and 2]
Macronutrient and micronutrient intake will be computed from 7-days of self-reported 24-hr dietary recalls
- Dietary Intake Timing [total of 1 week between Visit 1 and 2]
Food timing will be self-reported and averaged across 7-days of 24-hr dietary recalls
- Physical activity [at baseline]
Assessed using the International Physical Activity Questionnaire (IPAQ)
- Chronotype [at baseline]
Assessed using the Morningness-Eveningness Questionnaire (MEQ).
- Emotional eating [at baseline]
Assessed using the Emotional Eating Questionnaire (EEQ)
- Sleep quality [at baseline]
Assessed using the Pittsburgh Sleep Quality Index (PSQI)
- Insomnia [at baseline]
Assessed using the Insomnia Severity Index (ISI)
- Depression [at baseline]
Assessed using the Patient Health Questionnaire (PHQ-9)
Eligibility Criteria
Criteria
IInclusion Criteria:
-
Body Mass Index: > 18.5 o < 40 kg/m2
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Age: between 18 and 65 year of age
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Caucasian
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Day workers
Exclusion Criteria:
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Receiving treatment with thermogenic, lipogenic, or drugs
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Diabetes mellitus, chronic renal failure, hepatic diseases, or cancer diagnosis
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Bulimia diagnosis, prone to binge eating
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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
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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.
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Pregnant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Murcia | Murcia | Spain | 30100 |
Sponsors and Collaborators
- Universidad de Murcia
Investigators
- Study Chair: Purificación Gomez Abellan, PHD, Universidad de Murcia
Study Documents (Full-Text)
More Information
Publications
None provided.- 2017ES00001