Phenotypic heterogeneity of type 2 diabetes and risks of all-cause and cause-specific mortality

Type 2 diabetes (T2D) is a heterogeneous condition, but its phenotypic variation and links with mortality are unclear. We apply the discriminative dimensionality reduction with trees (DDRTree) algorithm to seven clinical variables in 10,091 adults with newly diagnosed T2D from a nationally representative Chinese cohort. Distinct mortality patterns are observed across phenotypes. Cardiovascular mortality is highest in the most hypertensive and obese individuals, while diabetic ketoacidosis/coma mortality is largely driven by the combination of hyperglycemia and dyslipidemia. Additionally, chronic obstructive pulmonary disease mortality is higher in those with elevated high-density lipoprotein (HDL) and total cholesterol levels. These patterns are similar in UK Biobank, though cardiovascular mortality is highest in those with dyslipidemia and obesity. Predictive models incorporating these variables show good performance and an online tool is provided for individual risk prediction. Overall, this study visualizes phenotypic variation in T2D and its impact on mortality, underscoring the need for personalized treatment strategies.

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Publication Details

Journal
Cell Reports Medicine
Published
2025-09-23
DOI
https://doi.org/10.1016/j.xcrm.2025.102367
Citations
1
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
1.82
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Phenotypic heterogeneity of type 2 diabetes and risks of all-cause and cause-specific mortality

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Phenotypic heterogeneity of type 2 diabetes and risks of all-cause and cause-specific mortality

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article en
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Abstract

Type 2 diabetes (T2D) is a heterogeneous condition, but its phenotypic variation and links with mortality are unclear. We apply the discriminative dimensionality reduction with trees (DDRTree) algorithm to seven clinical variables in 10,091 adults with newly diagnosed T2D from a nationally representative Chinese cohort. Distinct mortality patterns are observed across phenotypes. Cardiovascular mortality is highest in the most hypertensive and obese individuals, while diabetic ketoacidosis/coma mortality is largely driven by the combination of hyperglycemia and dyslipidemia. Additionally, chronic obstructive pulmonary disease mortality is higher in those with elevated high-density lipoprotein (HDL) and total cholesterol levels. These patterns are similar in UK Biobank, though cardiovascular mortality is highest in those with dyslipidemia and obesity. Predictive models incorporating these variables show good performance and an online tool is provided for individual risk prediction. Overall, this study visualizes phenotypic variation in T2D and its impact on mortality, underscoring the need for personalized treatment strategies.

Cell Reports MedicineVol. 6(11)
Boston University (US), Boston Medical Center (US), Union Hospital (HK), Utrecht University (NL), University Medical Center Utrecht (NL), University of Oxford (GB), National Center for Chronic and Noncommunicable Disease Control and Prevention (CN), Wuhan Union Hospital (CN), Tongji Hospital (CN), Union Hospital (CN), Huazhong University of Science and Technology (CN)
Openalex Percentile: Top 12%
Genetic Associations and Epidemiology
1.82
DOIOpen Access PDFOpenAlex
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