In:
Pediatric Diabetes, Hindawi Limited, Vol. 2023 ( 2023-5-24), p. 1-6
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.
Type of Medium:
Online Resource
ISSN:
1399-5448
,
1399-543X
DOI:
10.1155/2023/8883199
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2023
detail.hit.zdb_id:
2025536-6
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