What question did this study set out to answer?

The study aims to identify data-driven subtypes of type 2 diabetes and their associations with dementia, stroke, and brain structural changes.

May 11, 2026Open Access

Data-driven subtypes of type 2 diabetes and risk of dementia, stroke, and brain structural changes in the UK Biobank

Key Points

The study aims to identify data-driven subtypes of type 2 diabetes and their associations with dementia, stroke, and brain structural changes.
Analyzed data from 14,353 UK Biobank participants with type 2 diabetes.
Applied k-means clustering using various metabolic and physiological measures.
Utilized Cox models to estimate hazard ratios for dementia, stroke, and mortality risks.
Severe obesity-related inflammatory diabetes was associated with greater risks of all-cause dementia (HR 1.24, 95% CI 1.01-1.52), vascular dementia (HR 1.42, 95% CI 1.01-1.99), and stroke (HR 1.38, 95% CI 1.14-1.68).
Mild age-related hypertension-predominant diabetes showed modest relative but highest absolute risks.
SOID subtype exhibited lower gray matter and higher white matter hyperintensity.

Abstract

AimsType 2 diabetes (T2D) is associated with increased risks of dementia and stroke with heterogeneity.We aimed to identify data-driven T2D subtypes and examine associations with dementia, stroke, mortality, and brain structure. MethodsIn 14,353 UK Biobank participants with T2D (mean age 59.8 years), k-means clustering was applied using age at diagnosis, body mass index, glycated hemoglobin, insulin resistance, systolic blood pressure, and C-reactive protein.Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).Brain structural measures were analyzed in a subset. ResultsThree subtypes emerged: severe obesity-related inflammatory diabetes (SOID), mild metabolic diabetes (MMD, reference), and mild age-related hypertension-predominant diabetes (MARD-H).Versus MMD, SOID showed higher risks of all-cause dementia (HR 1.24, 95% CI 1.01-1.52),vascular dementia (HR 1.42, 95% CI 1.01-1.99),stroke (HR 1.38, 95% CI 1.14-1.68),ischemic stroke (HR 1.48, 95% CI 1.21-1.82),all-cause mortality (HR 1.59, 95% CI 1.45-1.74),and cardiovascular death (HR 1.88, 95% CI 1.59-2.23).MARD-H showed modest relative but highest absolute risks.SOID showed lower gray matter and greater white matter hyperintensity. ConclusionsT2D subtypes show distinct vascular and neurological risks.The obesity-inflammation subtype carries elevated risks of dementia, stroke, mortality, and adverse brain changes.

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