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Data-driven subtypes of type 2 diabetes and risk of dementia, stroke, and brain structural changes in the UK Biobank
Si Han1, Yingying Zhou2, Miriam Sturkenboom1
1Department of Data Science and Biostatistics, Julius Global Health, University Medical Centre Utrecht, Utrecht, the Netherlands.
Aims:
Type 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.
Methods:
In 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.
Results:
Three 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.
Conclusions:
T2D 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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