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

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.