We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Initial Insights into the Genetic Variation Associated with Metformin Treatment Failure in Youth with Type 2 Diabetes.
- Authors
Srinivasan, Shylaja; Chen, Ling; Udler, Miriam; Todd, Jennifer; Kelsey, Megan M.; Haymond, Morey W.; Arslanian, Silva; Zeitler, Philip; Gubitosi-Klug, Rose; Nadeau, Kristen J.; Kutney, Katherine; White, Neil H.; Li, Josephine H.; Perry, James A.; Kaur, Varinderpal; Brenner, Laura; Mercader, Josep M.; Dawed, Adem; Pearson, Ewan R.; Yee, Sook-Wah
- Abstract
Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10 − 6 ), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P = 0.06). A higher β-cell pPS was associated with a lower insulinogenic index (P = 0.02) and C-peptide (P = 0.047) at baseline and higher pPS related to two insulin resistance processes were associated with increased C-peptide at baseline (P = 0.04 , 0.02). Although pPS were not associated with changes in glycemic traits or metformin response, our results indicate a trend in the association of the β-cell pPS with reduced β-cell function over time. Our data show initial evidence for genetic variation associated with metformin response in youth with T2D.
- Subjects
STATISTICS; GLYCEMIC control; GENETIC variation; TYPE 2 diabetes; TREATMENT failure; INSULIN; DESCRIPTIVE statistics; GENOMES; RESEARCH funding; METFORMIN; DATA analysis; SECONDARY analysis; PANCREATIC beta cells; C-peptide; INSULIN resistance
- Publication
Pediatric Diabetes, 2023, p1
- ISSN
1399-543X
- Publication type
Article
- DOI
10.1155/2023/8883199