Melatonin impairs glucose tolerance and first-phase insulin secretion in MTNR1B diabetes risk variant carriers
In a randomized, double-blind, placebo-controlled crossover trial, 5 mg oral melatonin worsened glucose tolerance (11.7% increase) and reduced early C-peptide responses (19.2% decrease) in MTNR1B G-allele risk carriers, but not in noncarriers. The impairments were driven by a 40% suppression of glucose-stimulated first-phase β-cell responsivity and dysregulated insulin negative feedback.
This article is automatically generated from the structured evidence profile behind the claim above. Scores reflect the quality and quantity of available research, not clinical advice.
Melatonin impairs glucose tolerance and first-phase insulin secretion in MTNR1B diabetes risk variant carriers The current body of evidence comprises 1 study, including 1 randomized controlled trial. EvidenceHub rates the overall confidence at 44/100 (low).
The Claim
Melatonin impairs glucose tolerance and first-phase insulin secretion in MTNR1B diabetes risk variant carriers
This conclusion is most relevant to: 21 healthy participants of European ancestry (10 MTNR1B risk carriers, 11 noncarriers).
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant. (Diabetes care, 2026) —
How It Works
The proposed biological pathway:
- ▸Melatonin binds to MTNR1B receptors on pancreatic β-cells
- ▸Suppresses glucose-stimulated first-phase insulin secretion
- ▸Slows insulin-induced decline in second-phase insulin secretion rate
- ▸Results in worsened glucose tolerance and impaired glycemic control
Who Might Benefit
Evidence fit by population:
- ▸21 healthy participants of European ancestry (10 MTNR1B risk carriers, 11 noncarriers)
Recommended Dose
5 mg
Limitations & Caveats
Important context when interpreting this evidence:
- ▸Small sample size (n=21) limits generalizability
- ▸Single dose (5 mg) and short-term exposure may not reflect long-term melatonin use
Frequently Asked Questions
Does melatonin affect blood sugar in everyone?▼
No, the study found that melatonin impaired glucose tolerance only in individuals carrying the MTNR1B diabetes risk variant (G-allele), not in noncarriers.
What dose of melatonin was used in this study?▼
Participants received 5 mg of oral melatonin, which is a common over-the-counter dose.
How was glucose tolerance measured in this trial?▼
Glycemic dynamics were assessed using insulin-modified intravenous glucose tolerance tests with minimal-model analysis.
What is the MTNR1B gene variant?▼
The MTNR1B gene encodes the melatonin receptor 1B; a common variant (G-allele) increases the risk of type 2 diabetes and may make carriers more susceptible to melatonin's adverse metabolic effects.
References
- 1.Qian J, Stefanovski D, Andersen PAK, Vujovic N, Kelly L, Lepson J, Nguyen H, Byrne S, Wang W, Mandrup-Poulsen T, Adler G, Garaulet M, Saxena R, Scheer FAJL. “Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant..” Diabetes care, 2026. PMID: 42346809 DOI: 10.2337/dc26-0164