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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
889
Oral glucose tolerance test using identical mixed 75 gr of glucose under early condition (4 hours before habitual bedtime)
Oral glucose tolerance test using identical mixed 75 gr of glucose under late condition (1 hour before habitual bedtime)
University of Murcia
Murcia, Spain
Area Under the Curve (AUC) Glucose
Glucose levels are measured along 120 minutes corresponding to at early and late condition in each visit. The Area Under the Curve was calculated as the sum of the area of several trapezoids. This trapezoids was obtained at times 0-30 min, 30-60 min, 60-90 min, 90-120 min. The values are the difference between the late and the early condition.
Time frame: Along 120 minutes in visits 1 and 2
Disposition Index (DI)
Disposition Index (DI) is the product of insulin sensitivity times by the amount of insulin secreted in response to blood glucose levels. Disposition index is used as a measure of beta cell function and the ability of the body to dispose of a glucose load. This index was determined by this formula: DI= CIR × ISI, where CIR is the measure Corrected Insulin Response, and ISI is Insulin Sensitivity Index. The values are the difference between the late and the early condition. Higher DI indicates an increased beta cell function and increased ability of the body to dispose of a glucose load.
Time frame: Along 120 minutes in visits 1 and 2
Corrected Insulin Response (CIR)
The measure of Corrected Insulin Response (CIR) uses the insulin and glucose levels at minute 30, integrating these values in the formula: CIR= l30/(G30 × (G30 - 70)).The values are the difference between the late and the early conditions. CIR is an index that assesses the insulin secretion capacity of B cells. A low CIR implies hyposecretion in response to glucose levels.
Time frame: At minute 30 during the visit 1 and 2.
Insulin Sensitivity Index (ISI)
Insulin Sensitivity Index is a measurement which integrates fasting glucose and insulin concentrations (0 min) and the mean of the glucose and insulin levels from 0 to 120 minutes (0, 30, 60, 90 and 120 min), from an OGTT, to measure insulin sensitivity. This formula allows its use in clinical settings as well as in large epidemiological studies. The values are the difference between the late and the early condition. Elevated ISI values typically indicate a favorable outcome. This index reflects the body's responsiveness to insulin, a hormone crucial for regulating blood sugar levels. Higher sensitivity to insulin suggests that cells efficiently utilize insulin's signals, promoting better blood sugar management. Lower ISI may lead to challenges in maintaining stable blood glucose levels and is often associated with conditions such as type 2 diabetes and metabolic syndrome.
Time frame: Along 120min in visits 1 and 2
Fasting Glucose
Fasting glucose (or basal glucose) is a simple measurement of glucose concentrations at minute 0 to see how glucose levels rise immediately after an OGTT. The values are the difference between the late and the early condition.
Time frame: At minute 0 in visit 1 and 2.
Fasting Insulin
Fasting insulin (or basal insulin) is a simple measurement of insulin concentrations at minute 0 to see how insulin levels rise immediately after an OGTT.The values are the difference between the late and the early condition.
Time frame: At minute 0 in visit 1 and 2
Serum Melatonin
Measurement of serum melatonin is made at time 0 and at time 120 in both the early and late conditions of everyone.
Time frame: At baseline and 120 minutes in visit 1 and 2
Dim Light Melatonin Onset (DLMO) at Early Condition Only
This measurement shows the decimal time of the onset of melatonin in dim light conditions. In the case of DLMO, we only performed this measure at the early condition in order to get the analysis of melatonin during 5 hours (4 hours before the habitual bedtime and 1 hour later), as it is described in literature (DOI: 10.1002/oby.23749).
Time frame: Melatonin measured every half hour for 5 hours at Early condition in all participants
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