Circadian Rhythm, Genes, Glucose, Melatonin
Conditions
Brief summary
This project aims to test the impact of melatonin and MTNR1B variation on regulation glucose regulation in a highly controlled in-laboratory setting and ex vivo in pancreatic islets.
Detailed description
The investigators' recent GWAS discovery of MTNR1B as a novel type 2 diabetes gene has sparked great interest into the role of melatonin in glycemic control, for which the mechanism is largely unknown. This research will determine the effect of melatonin and MTNR1B on glycemic control under highly-controlled, in-laboratory protocols while manipulating circulating melatonin concentrations (both up and down) and assessing glycemic control by frequently-sampled intravenous glucose tolerance tests, as well as in ex vivo human pancreatic islets. This research will provide mechanistic insights into the metabolic effects of melatonin and the MTNR1B risk variant and may help in evidence-based approaches and personalized recommendations to improve glycemic control in night shift workers and late-night eaters.
Interventions
DIETARY_SUPPLEMENTmelatonin
5 mg of melatonin per os.
DRUGplacebo
Sponsors
Brigham and Women's Hospital
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index: 20 and 35 kg/m2 * Age: 21-55 years of age * Caucasian * Non-smoking * With regular sleep-wake cycle * Passed medical and psychological screening tests
Exclusion criteria
* Acute, chronic or debilitating medical conditions * History of neurological or psychiatric disorder * History of sleep disorder or regular use of sleep-promoting medication * Current prescription, herbal, or over-the-counter medication use * Traveling across 2 or more time zones within past 3 months * Worked night or rotating shift work within past 1 year * Drug or alcohol dependency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disposition Index | During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit | Disposition index is determined by frequently sampled intravenous glucose tolerance test. It is a composite measure of β-cell function adjusted for insulin sensitivity-was calculated as the product of insulin sensitivity and insulin secretion indices. High value means stronger β-cell function. Theoretical minimum is 0, no theoretical maximum. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First-phase Beta-cell Responsivity | During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit | First-phase beta-cell responsivity to glucose is determined by frequently sampled intravenous glucose tolerance test. It likely represents exocytosis of previously primed and docked insulin secretory granules (commonly called the readily releasable pool). It is given by the ratio between the incremental amount of C-peptide secreted during the first phase and the maximum increment of the plasma glucose concentration.High value means stronger β-cell responsivity. Theoretical minimum is 0, no theoretical maximum. |
| Insulin Sensitivity | During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit | Insulin sensitivity is determined by frequently sampled intravenous glucose tolerance test. It is defined in quantitative terms as the effect of insulin to catalyse the disappearance of glucose from plasma.High value indicates better insulin sensitivity. Theoretical minimum is 0, no theoretical maximum. |
| Glucose Tolerance | During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit | glucose 3-hour incremental AUC during frequently sampled intravenous glucose tolerance test. High value indicates higher glucose level during the test, which is bad. Theoretical minimum is 0, no theoretical maximum. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORFrank AJL Scheer, PhD
Brigham and Women's Hospital
Participant flow
Pre-assignment details
Ambulatory phase (2/3 weeks), in which participants follow a self-selected Sleep-Wake cycle as well as eat pre-prepared, standardized meals for 3 days leading into the 5-day in-lab stay.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 30.1 years STANDARD_DEVIATION 10.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HbA1c | 5.2 % STANDARD_DEVIATION 0.28 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 2 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
None listed