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

Courtney Hershberger; Arshiya Mariam; Kevin M Pantalone; John B Buse; Alison A Motsinger-Reif; Daniel M Rotroff

doi:10.1186/s40246-024-00639-z

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

Hum Genomics. 2024 Jun 22;18(1):70. doi: 10.1186/s40246-024-00639-z.

Authors

Courtney Hershberger^{1

2}, Arshiya Mariam^{1

2}, Kevin M Pantalone^{1

2

3}, John B Buse⁴, Alison A Motsinger-Reif⁵, Daniel M Rotroff^{6

7

8}

Affiliations

¹ Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
² Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH, 44195, USA.
³ Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
⁴ Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institute of Health, Durham, NC, USA.
⁶ Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. [email protected].
⁷ Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH, 44195, USA. [email protected].
⁸ Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. [email protected].

Abstract

Introduction: 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.

Research design and methods: 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.

Results: 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.

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

Keywords: A1c level; Genomics; Polygenic score; Precision medicine; Prescribing trends; Single-nucleotide polymorphism (SNP); Subtypes; Type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural

MeSH terms

Aged
Biological Specimen Banks
Cardiovascular Diseases / drug therapy
Cardiovascular Diseases / epidemiology
Cardiovascular Diseases / genetics
Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / epidemiology
Diabetes Mellitus, Type 2* / genetics
Diabetes Mellitus, Type 2* / pathology
Female
Genetic Predisposition to Disease
Glycated Hemoglobin / genetics
Glycated Hemoglobin / metabolism
Humans
Male
Middle Aged
Multifactorial Inheritance* / genetics
Phenotype
Polymorphism, Single Nucleotide / genetics
United Kingdom / epidemiology

Substances

Glycated Hemoglobin

Abstract

Publication types

MeSH terms

Substances

Grants and funding