MTNR1B SNP*Food Timing Interaction on Glucose Control

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.

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.

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.

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.

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.

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.

Measurement of serum melatonin is made at time 0 and at time 120 in both the early and late conditions of everyone.

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).

Measured using a temperature sensor which records the temperature during 7 days. We only determined it during the washout period (neither early nor late conditions).

During the seven days of the study, individuals wore a wristwatch in their non-dominant hand, that integrates two sensors: a temperature sensor, and an accelerometer sensor that records physical activity and body position data (G Acceleration Data Logger UA-004-64; Onset Computer, Bourne, MA, USA). Activity was expressed as the change in degrees per minute (Δ°/min). We calculated the average activity value during the 10 consecutive hours of maximum values. We only determined it during the washout period (neither early nor late conditions).

Measured using a light sensor during 7 days. We only determined it during the washout period (neither early nor late conditions).

Sleep duration will be computed from self-reported. We only determined it during the washout period (neither early nor late conditions).

Total energy intake in kcal/day will be computed with a 7-day dietary log. We only determined it during the washout period (neither early nor late conditions).

Macronutrient and micronutrient intake will be computed from 7-days of self-reported 24-hr dietary recalls.

Percentage Kcal respect to the Total Energy Intake. We only determined it during the washout period (neither early nor late conditions).

Food timing will be self-reported and averaged across 7-days of 24-hour dietary recalls. We only determined it during the washout period (neither early nor late conditions).

Assessed using the International Physical Activity Questionnaire (IPAQ). This international questionnaire measures physical activity through the amount of energy expended carrying out physical activity i.e., Metabolic Units (MET) minutes a week. The higher the MET, the more amount of physical activity the individual performs. This allows us to classify low, moderate, or vigorous activity. 7 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 3000 MET minutes a week. We only determined it during the washout period (neither early nor late conditions).

Formula for computation of Met-minutes:

• Walking MET-minutes/week = 3.3 * walking minutes * walking "days"
• Moderate MET-minutes/week = 4.0 * moderate-intensity activity minutes * moderate days
• Vigorous MET-minutes/week = 8.0 * vigorous-intensity activity minutes * vigorous-intensity days

Assessed using the Morningness-Eveningness Questionnaire (MEQ). Its main purpose is to measure whether a person's circadian rhythm produces peak alertness in the morning, in the evening, or in between. It is a score that indicates the degree to which the individual favors the morning over the night. We only determined it during the washout period (neither early nor late conditions).

Values:

Min: 17 Max: 86

Explanation:

17-30: extreme eveningness 31-41: eveningness 42-58: neither 59-69: morningness 70-86: extreme morningness

Assessed using the Emotional Eating Questionnaire (EEQ). This questionnaire classifies individuals based on the relationship between food intake and emotions.

Score between 0 and 30. We only determined it during the washout period (neither early nor late conditions).

Explanation:

0-5: nothing emotional 5-10: less emotional 10-20: emotional 20-30: Very emotional

Assessed using the Pittsburgh Sleep Quality Index (PSQI). This questionnaire is used to quantitatively assess the quality of sleep. 7 scores are obtained that inform us about various aspects of sleep quality. We only determined it during the washout period (neither early nor late conditions).

Score between 0 and 21. Total score of the questionnaire is divided into 7 items. Those items have a score from 0 (no problem) to 3 (severe problem).

0-5: sleep quality optimum 6-21: sleep disorders

Assessed using the Insomnia Severity Index (ISI). This questionnaire has 5 items and is used to assess the possible existence of sleep problems. According to the score obtained, a classification is made from no insomnia to severe clinical insomnia. We only determined it during the washout period (neither early nor late conditions).

Score ranges between 0 and 28

Explanation:

0-7: no insomnia 8-14: subclinical insomnia 15-21: moderate insomnia 22-28: severe insomnia The higher the score, the more harmful

Assessed using the Patient Health Questionnaire (PHQ-9). This instrument aims to help the diagnosis of depression through the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and to determine the severity of the disorder. It is made up of 9 items that refer to the last two weeks. The score ranges between 0 and 27. We only determined it during the washout period (neither early nor late conditions).

0-4: no depression 5-9: mild depression 10-14: moderate depression 15-19: moderate-severe depression 20-27: severe depression

Explanation:

0-4: no depression 5-9: mild depression 10-14: moderate depression 15-19: moderate-severe depression 20-27: severe depression The higher the score, the more harmful