This study developed an immune endotyping framework using routine blood immune cell counts in >1,500 adults with newly diagnosed type 2 diabetes (T2D) across three European cohorts, aiming to identify biologically distinct subgroups and their clinical trajectories.
Unsupervised clustering identified four stable immune endotypes (SIND, MIND, LYRD, LYDD); high-risk endotypes SIND and LYDD were independently associated with increased cardiovascular, renal, and mortality risk across cohorts, and immune endotyping improved cardiovascular risk prediction beyond SCORE2-Diabetes. The inflammatory profile of SIND was attenuated by IL-1β antagonism and bariatric surgery.
Cohorts are European only, limiting generalizability to other ancestries. As a clustering-based observational design, causal directionality between immune phenotype and clinical outcomes cannot be established. Long-term prospective validation of endotype-guided treatment strategies is not yet available.
Routine blood immune cell counts — already collected in most clinical settings — can stratify newly diagnosed T2D patients into risk groups with meaningfully different cardiovascular and renal outcomes. Clinicians should consider that patients resembling the high-inflammatory (SIND) profile may derive particular benefit from IL-1β antagonists or bariatric surgery.
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