Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes
Authors' conclusion
Our data show initial evidence for genetic variation associated with metformin response in youth with T2D.
Study context
- Population
- Youth with T2D treated with metformin in the TODAY studyTODAY study
- Participants
- 506 participants
- Outcome
- Metformin response (common genetic variants associated with it)
Methodological detailsgenome-wide approach, replication in three cohorts, partitioned polygenic scores
- Genome-wide approach
- Replication in three cohorts
- Partitioned polygenic scores
Main finding
As reported in the abstract
Genome-wide variants associated with metformin response
- Several variants met a suggestive threshold; none, incl. published adult variants, reached genome-wide significance
- P < 1 × 10-6
Further findings
Replication of top nine variants: rs76195229 in ATRNL1 and metformin response, Metformin Genetics Consortium (n = 7,812)
- rs76195229 associated with worse metformin response; not significant after Bonferroni correction
- P = 0.06
β-cell partitioned polygenic scores (pPS) and baseline β-cell function
- Higher β-cell pPS associated with lower insulinogenic index
- P = 0.02
- Higher β-cell pPS associated with lower C-peptide
- P = 0.047
Insulin resistance pPS and baseline C-peptide
- Higher pPS of two insulin resistance processes associated with increased C-peptide
- P = 0.04,0.02
pPS and changes in glycemic traits or metformin response
- pPS not associated with changes in glycemic traits or metformin response; trend for β-cell pPS with reduced β-cell function over time
Original publication
Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes. Pediatr Diabetes. Published 24 May 2023. doi:10.
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