Interaction of Melatonin and MTNR1B Genotype on Glucose Control - Study 1

Brigham and Women's Hospital23 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Glucose Circadian Rhythm Melatonin Genes

Interventions

melatoninDIETARY_SUPPLEMENT

5 mg of melatonin per os.

placeboDRUG

Eligibility

Sex: ALLMin age: 21 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Disposition Index

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.

Time frame: During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit

Secondary Outcomes

First-phase Beta-cell Responsivity

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.

Time frame: 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

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.

Time frame: During frequently sampled intravenous glucose tolerance test after melatonin/placebo administration on Day 2/4 (melatonin/placebo order randomized) in the laboratory visit

Glucose Tolerance

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.