Leukocyte Counts and T Cell Frequencies Differ Between Novel Subgroups of Diabetes and Associate with Metabolic Parameters and Biomarkers of Inflammation

Frequencies of circulating immune cells are altered in type 1 and type 2 diabetes compared with healthy individuals and associate with insulin sensitivity, glycemic control and lipid levels. This study aimed to determine whether specific immune cell types are associated with novel diabetes subgroups. We analyzed automated white blood cell counts (n=669) and flow cytometry data (n=201) of participants of the German Diabetes Study with recent-onset (<1 year) diabetes, who were allocated to five subgroups based on data-driven analysis of clinical variables. Leukocyte numbers were highest in severe insulin-resistant diabetes (SIRD) and moderate obesity-related diabetes (MOD) and lowest in severe autoimmune diabetes (SAID). CD4⁺ T cell frequencies were higher in SIRD vs. SAID, MOD and mild age-related diabetes (MARD), and frequencies of CCR4⁺ regulatory T cells were higher in SIRD vs. SAID and MOD and MARD vs. SAID. Pairwise differences between subgroups were partially explained by differences in clustering variables. Frequencies of CD4⁺ T cells were positively associated with age, BMI, HOMA2-B and HOMA2-IR, and frequencies of CCR4⁺ regulatory T cells with age, HOMA2-B and HOMA2-IR. In conclusion, different leukocyte profiles exist between novel diabetes subgroups and suggest distinct inflammatory processes in these diabetes subgroups.