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Genetic Susceptibility to Diabetes Subtypes and Risk of Developing Coronary Artery Disease

Pan, Mengyu LU orcid ; Al-Sharify, Dania LU orcid ; Engström, Gunnar LU ; Ahlqvist, Emma LU ; Lotta, Luca ; Nilsson, Jan LU ; Goncalves, Isabel LU orcid ; Sun, Jiangming LU orcid and Edsfeldt, Andreas LU orcid (2026) In Diabetes Care 49(5).
Abstract

OBJECTIVE: Diabetes significantly increases the risk for atherosclerotic complications, including coronary artery disease (CAD). Previous studies have suggested that adult-onset diabetes can be classified into five different clinical subtypes, including moderate obesity-related diabetes (MOD). The aim of this study was to investigate the genetic associations between the five diabetes subtypes and the risk of developing CAD and diabetes in the general population.

RESEARCH DESIGN AND METHODS: The Malmö Diet and Cancer cohort (N = 24,025) was used to assess whether polygenic risk scores (PRSs) for the five diabetes subtypes could predict future diabetes and CAD. Genetic correlations and causal effects of the MOD subtype on CAD were... (More)

OBJECTIVE: Diabetes significantly increases the risk for atherosclerotic complications, including coronary artery disease (CAD). Previous studies have suggested that adult-onset diabetes can be classified into five different clinical subtypes, including moderate obesity-related diabetes (MOD). The aim of this study was to investigate the genetic associations between the five diabetes subtypes and the risk of developing CAD and diabetes in the general population.

RESEARCH DESIGN AND METHODS: The Malmö Diet and Cancer cohort (N = 24,025) was used to assess whether polygenic risk scores (PRSs) for the five diabetes subtypes could predict future diabetes and CAD. Genetic correlations and causal effects of the MOD subtype on CAD were investigated using data from large genome-wide association studies of the MOD subtype (N = 4,116) and CAD (N = 296,525).

RESULTS: During follow-up, 4,105 participants (17.1%) developed diabetes (median follow-up 24.0 years) and 3,841 (16.0%) developed CAD (median follow-up 24.6 years). PRS for MOD (PRSMOD) was associated with incident diabetes and CAD. In addition, participants in the third tertile of PRSMOD had a 1.10-fold higher risk of developing CAD compared with those in the first tertile. A positive genetic correlation between MOD and CAD was observed, and Mendelian randomization analyses suggested a causal effect of MOD on CAD.

CONCLUSIONS: The current study showed that the genetic susceptibilities for all five diabetes subtypes were associated with incident diabetes. However, only the MOD subtype was associated with incident CAD. These findings underscore the significance of a high genetic risk for MOD as an early marker for CAD.

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Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Diabetes Care
volume
49
issue
5
pages
10 pages
publisher
American Diabetes Association
external identifiers
  • pmid:41912451
ISSN
1935-5548
DOI
10.2337/dc25-1711
language
English
LU publication?
yes
additional info
© 2026 by the American Diabetes Association.
id
00710c33-da5e-444c-a8ea-b0e480123deb
date added to LUP
2026-03-31 14:15:02
date last changed
2026-03-31 14:15:02
@article{00710c33-da5e-444c-a8ea-b0e480123deb,
  abstract     = {{<p>OBJECTIVE: Diabetes significantly increases the risk for atherosclerotic complications, including coronary artery disease (CAD). Previous studies have suggested that adult-onset diabetes can be classified into five different clinical subtypes, including moderate obesity-related diabetes (MOD). The aim of this study was to investigate the genetic associations between the five diabetes subtypes and the risk of developing CAD and diabetes in the general population.</p><p>RESEARCH DESIGN AND METHODS: The Malmö Diet and Cancer cohort (N = 24,025) was used to assess whether polygenic risk scores (PRSs) for the five diabetes subtypes could predict future diabetes and CAD. Genetic correlations and causal effects of the MOD subtype on CAD were investigated using data from large genome-wide association studies of the MOD subtype (N = 4,116) and CAD (N = 296,525).</p><p>RESULTS: During follow-up, 4,105 participants (17.1%) developed diabetes (median follow-up 24.0 years) and 3,841 (16.0%) developed CAD (median follow-up 24.6 years). PRS for MOD (PRSMOD) was associated with incident diabetes and CAD. In addition, participants in the third tertile of PRSMOD had a 1.10-fold higher risk of developing CAD compared with those in the first tertile. A positive genetic correlation between MOD and CAD was observed, and Mendelian randomization analyses suggested a causal effect of MOD on CAD.</p><p>CONCLUSIONS: The current study showed that the genetic susceptibilities for all five diabetes subtypes were associated with incident diabetes. However, only the MOD subtype was associated with incident CAD. These findings underscore the significance of a high genetic risk for MOD as an early marker for CAD.</p>}},
  author       = {{Pan, Mengyu and Al-Sharify, Dania and Engström, Gunnar and Ahlqvist, Emma and Lotta, Luca and Nilsson, Jan and Goncalves, Isabel and Sun, Jiangming and Edsfeldt, Andreas}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{5}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Genetic Susceptibility to Diabetes Subtypes and Risk of Developing Coronary Artery Disease}},
  url          = {{http://dx.doi.org/10.2337/dc25-1711}},
  doi          = {{10.2337/dc25-1711}},
  volume       = {{49}},
  year         = {{2026}},
}