Polygenic subtype identified in ACCORD trial displays a favorable type 2 diabetes phenotype in the UKBiobank population

TL;DR

A genetic subtype of type 2 diabetes is associated with a milder disease course and better outcomes in a large population study.

Contribution

Identification of a polygenic subtype of T2D with favorable clinical characteristics in the UKBiobank.

Findings

C4 individuals were less likely to develop T2D and had lower HbA1c values.

C4 individuals were less likely to be prescribed T2D medications.

Genetic variants in MAS1 and IGF2R were linked to fewer T2D prescriptions.

Abstract

We previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort.

Using our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications.

C4 individuals were less likely to develop T2D, were slightly older at T2D diagnosis, had lower HbA1c values, and were less likely to be prescribed T2D medications (P < .05). Genetic variants in MAS1 and IGF2R, major components of the C4 PS, were associated with fewer overall T2D prescriptions.

We have confirmed C4 individuals are a lower risk subpopulation of patients with T2D.

The online version contains supplementary material available at 10.1186/s40246-024-00639-z.

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