DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes
Authors' conclusion
Metformin-associated alterations in DNA methylation partially mediates metformin's antidiabetic effects on HbA1c in newly-diagnosed individuals with type 2 diabetes.
Study context
- Population
- Newly-diagnosed individuals with T2D, Scandinavian discovery and replication cohorts; blood DNA methylation
- Comparison
- Metformin vs no diabetes medication
- Outcome
- Metformin-associated alterations in DNA methylation
- Follow-up
- ∼ 3 months
Methodological detailsdiscovery and replication cohorts, MethylationEPIC arrays, causal mediation analysis
- Discovery and replication cohorts
- MethylationEPIC arrays
- Causal mediation analysis
Main finding
As reported in the abstract
DNA methylation in blood
- Methylation sites altered with metformin therapy (FDR < 0.05)
- 26
- Share of the 26 sites hypermethylated with metformin vs controls
- 88%
- Blood-based methylation markers mirroring the pattern in muscle and adipose tissue (FDR < 0.05)
- 2
- T2D-associated SNPs annotated to differentially methylated genes (e.g., GRB10, RPTOR, SLC22A18AS, TH2LCRR)
- 4
- Genes with methylation correlating with expression in human islets
- 2
Further findings
- Metformin-associated methylation sites (PKNOX2, WDTC1, MICB) partially mediating effects on follow-up HbA1c
- 3
- Proportion of metformin's effect on HbA1c mediated by combined methylation score (up to)
- 32%
- Causal mediation analysis
Original publication
DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes. Diabetes Res Clin Pract. Published 24 June 2023. doi:10.
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