Rare MTNR1B variants causing diminished MT2 signalling associate with elevated HbA1c levels but not with type 2 diabetes
Main finding · HbA1c (UK Biobank)Result — go to the resultβ 0.087 SD 95% CI 0.039–0.135Authors' conclusion
The higher type 2 diabetes prevalence previously observed in carriers of missense MTNR1B variants causing impairment in MT2 signalling was not replicated in the UK Biobank, yet carriers had elevated HbA1c levels.
Study context
- Population
- UK Biobank participants (glycaemic phenotypes without diabetes; other cardiometabolic phenotypes; T2D case-control); Danish Inter99 participants without diabetes; DD2 cohort cases; recall-by-genotype study of individuals without diabetes
- Exposure
- Carriers of MTNR1B variants vs non-carriers
- Outcome
- HbA1c (UK Biobank)
Methodological detailsvariant burden testing, case-control study, recall-by-genotype study
- Variant burden testing
- Case-control study
- Recall-by-genotype study
Main finding
As reported in the abstract
β
0.087 SD
95% CI 0.039–0.135
Observational data: associations, not effects.
Further findings
| Outcome | Estimate |
|---|---|
| Glucose-stimulated insulin response, carriers of variants impairing MT2 signallingNominally significant lower response | β −0.47 SD (95% CI −0.82 to −0.11) |
| Insulin response after melatonin treatment (recall-by-genotype)Carriers vs Non-carriers | β −476.0 (95% CI −928.6 to −24.4) |
| Insulin response after melatonin treatment (recall-by-genotype)rs10830963 carriers vs Non-carriers · reduced response | β −390.8 (95% CI −740.1 to −41.6) |
- Insulin response after melatonin treatment (recall-by-genotype): reduced response in carriers of variants impairing MT2 signalling
Glycaemic phenotypes (Inter99)
- No significant associations with glycaemic phenotypes in Inter99
Original publication
Rare MTNR1B variants causing diminished MT2 signalling associate with elevated HbA1c levels but not with type 2 diabetes. Diabetologia. Published 10 March 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →