Type 2 diabetes mellitus (T2DM) is associated with increased risks of dementia and stroke, although vascular and neurological risk may vary across biologically distinct metabolic subtypes. A UK Biobank analysis published in Diabetes Research and Clinical Practice identified data-driven T2DM subtypes and evaluated their associations with dementia, stroke, mortality, and brain structural measures.

The analysis included 14,353 participants with T2DM with a mean age of 59.8 years. K-means clustering was performed using age at diagnosis, body mass index (BMI), glycated hemoglobin (HbA1c), insulin resistance, systolic blood pressure, and C-reactive protein levels. Three subtypes were identified: severe obesity-related inflammatory diabetes (SOID), mild metabolic diabetes (MMD), and mild age-related hypertension-predominant diabetes (MARD-H).

Compared with MMD, SOID was associated with 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). The MARD-H subtype showed comparatively modest relative risks but the highest absolute risks across outcomes.

In brain imaging analyses, SOID was associated with lower gray matter volume and greater white matter hyperintensity burden. Overall, the obesity-related inflammatory T2DM subtype was associated with higher vascular, neurological, and mortality risks.