CLINICALLY meaningful subgroups in type 2 diabetes (T2D) can be identified through immune-based endotyping using routine blood counts, according to a new study presented at EASD 2026. The researchers reported that the approach enables robust risk stratification and capture of disease mechanisms.
Type 2 diabetes can be characterised as a highly heterogeneous disease. However, current classifications do not adequately reflect the biological diversity of T2D or guide precision care. As inflammation has a central role in T2D pathophysiology, the authors used routine blood parameters to develop a clinically scalable, immune-based stratification, enabling the identification of patient subgroups with different risk profiles and treatment potential.
Over 1,500 individuals with newly diagnosed T2D were included in an unsupervised clustering analysis of circulating neutrophil, lymphocyte, and monocyte counts. Individuals were from three independent longitudinal European cohorts from France, Italy, and Germany.
Endotypes were validated across multiple longitudinal cohorts containing up to 67,000 individuals and multi-omics approaches were used to characterise these endotypes. Cardiovascular, renal, and mortality outcomes were assessed over 5-12 years. Additionally, IL-1β antagonism and bariatric surgery were used to evaluate therapeutic modulation.
This study identified a total of four reproducible immune endotypes. These endotypes included severe inflammatory diabetes (SIND), mild inflammatory diabetes, lymphocyte-rich diabetes, and lymphocyte-deficient diabetes.
Significantly higher risks of cardiovascular events, renal decline, and mortality were associated with the endotypes SIND and lymphocyte-deficient diabetes while more favourable outcomes were found in mild inflammatory diabetes and lymphocyte-rich diabetes.
SIND had a strong pro-inflammatory signature revealed using multi-omic analyses. This signature was characterised by expansion of CCR2hi and CD39hi monocytes and activation of innate immune pathways.
Notably, the inflammatory profile appeared modifiable. IL-1β antagonism reduced proinflammatory monocytes and SIND classification, while bariatric surgery shifted patients towards lower-risk endotypes.
Overall, routine blood counts enabled immune-based endotyping. This resulted in the identification of four clinically meaningful and actionable T2D subgroups. Moreover, immune-based endotyping enables robust risk stratification, the capture of disease mechanisms, and, importantly, identifies a high-risk inflammatory endotype that is therapeutically modifiable. To conclude, the authors suggested that precision medicine strategies for T2D should include immune profiling.
Venteclef N et al. Immune endotypes define risk and trajectories in type 2 diabetes. Abstract OP05. EASD Congress, 28 September-2 October 2026.
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