Evidence mapPaperPMID 42346809Full record

Trial reportDiabetes care2026

Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant.

Jingyi Qian, Darko Stefanovski, Phillip A K Andersen, Nina Vujovic, Lauren Kelly, Joshua Lepson, Hoa Nguyen, Sean Byrne, Wei Wang, Thomas Mandrup-Poulsen and 4 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Jingyi QianDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.ORCID 0000-0002-8793-9330
Darko StefanovskiDepartment of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA.
Phillip A K AndersenDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Nina VujovicDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Lauren KellyDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Joshua LepsonDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Hoa NguyenDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Sean ByrneDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Wei WangDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Thomas Mandrup-PoulsenDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Gail AdlerDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Mass General Brigham and Harvard Medical School, Boston, MA.
Marta GarauletDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.
Richa SaxenaDivision of Sleep Medicine, Harvard Medical School, Boston, MA.
Frank A J L ScheerDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.ORCID 0000-0002-2014-7582

Funding

Effect of high fat diet on the circadian system and on circadian rhythms in energy intake and expenditureR01HL167746 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$806k
Effect of temporal distribution of macronutrient intake on metabolismR01HL164454 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$805k
Food Timing to Mitigate Adverse Consequences of Night WorkR01HL153969 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$758k
ADA 1-17-PDF-103ADA K99 HL 148500CTSA UL1RR025758Harvard UniversityIndependent Research Fund Denmark 8020-00359BNHLBI NIH HHS R01 HL153969NHLBI NIH HHS R01 HL164454NHLBI NIH HHS R01 HL167746NIDDK NIH HHS R01 DK102696
6 · The paper itself

Abstract

objectiveMelatonin use quintupled in recent decades. The common melatonin receptor 1B gene (MTNR1B) variant increases risk of type 2 diabetes, raising concerns about melatonin's adverse metabolic effects and highlighting the need for a genotype-based personalized approach. We aimed to comprehensively characterize the actions of melatonin on glucose homeostasis, including first- and second-phase β-cell responsivity to glucose, β-cell negative feedback by exogeneous insulin, insulin sensitivity, and whether such effects are stronger in MTNR1B G-allele risk carriers compared with noncarriers. RESEARCH DESIGN AND

methodsTwenty-one healthy participants of European ancestry were studied in a randomized, double-blind, placebo-controlled, crossover trial, including 10 MTNR1B risk carriers and 11 noncarriers. Each participant underwent a highly controlled 5-day laboratory protocol, during which they received 5 mg oral melatonin or placebo in randomized order on two nonconsecutive days. Glycemic dynamics were assessed using insulin-modified intravenous glucose tolerance tests with minimal-model analysis.

resultsMelatonin worsened glucose tolerance and reduced early C-peptide responses in risk allele carriers (vs. placebo: 11.7% [95% CI 1.0-22.3] and -19.2% [-33.9 to -1.2], respectively; Padj < 0.05) but not in noncarriers. In carriers, impairments stemmed from a 40% (-52.4 to -24.3; Padj = 0.0003) suppression of glucose-stimulated first-phase β-cell responsivity, along with a slower insulin-induced decline in second-phase insulin secretion rate (64.3% [23.1-119.2]; Padj = 0.001). In carriers, melatonin also prevented exogenous insulin-induced hypoglycemia compared with placebo (zero vs. seven events, P = 0.001), but not in noncarriers.

conclusionsThese findings identify blunted β-cell responsivity to glucose and dysregulated insulin negative feedback as key mechanisms linking melatonin signaling to diabetes risk.

Indexed as

InsulinMelatoninReceptor, Melatonin, MT2AdultBlood GlucoseCross-Over StudiesDiabetes Mellitus, Type 2Double-Blind MethodFemaleGlucose Tolerance TestHumansInsulin-Secreting CellsInsulin SecretionMaleMiddle AgedBlood GlucoseInsulinMelatoninMTNR1B protein, humanReceptor, Melatonin, MT2

Identifiers

PMID42346809
PMCPMC13385946

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.