Association between serum adenosine deaminase activity and insulin resistance in adults with type 2 diabetes

Purpose Routine markers such as HbA1c incompletely reflect metabolic dysfunction in type 2 diabetes mellitus (T2DM) patients. Adenosine deaminase (ADA) is a purine metabolism enzyme that depletes adenosine and promotes inflammation; however, its role in insulin resistance in T2DM patients is poorly characterized. This study evaluated the serum ADA concentration and its association with insulin resistance in T2DM patients and controls. Methods This cross-sectional case‒control study involved 90 adults with type 2 diabetes mellitus (T2DM) and 40 age- and sex-matched controls. Serum ADA, insulin, fasting glucose, HbA1c, and uric acid were measured in overnight fasting blood samples. Insulin resistance was quantified via the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Spearman's rank correlation, log-linear regression adjusted for age, sex and body mass index (BMI), and receiver operating characteristic (ROC) curve analysis were performed. Results Serum ADA was significantly greater in T2DM patients than in controls (median 28.3vs8.2 U/L; p < 0.001; r = 0.79). ADA was strongly correlated with HOMA-IR (ρ = 0.799; 95%CI 0.71–0.87), HbA1c (ρ = 0.606) and fasting glucose (ρ = 0.735). Regression identified ADA as the strongest independent predictor of HOMA-IR (β = 0.735; p < 0.001; R²=0.576). ROC analysis yielded an AUC = 0.887; an optimal cutoff of ≥ 13.1 U/L provided 87.0% sensitivity and 81.6% specificity. Conclusion Serum ADA is markedly elevated in T2DM patients and shows a strong, independent association with insulin resistance alongside promising discriminatory ability. These findings are consistent with the role of ADA in adenosine depletion and impaired glucose disposal, supporting its potential as a cost-effective surrogate biomarker following prospective external validation.