Association of increased serum I-309 with renal function impairment and diabetic kidney disease in type 2 diabetes mellitus

Objective: The aim of this study was to determine serum I-309 levels in type 2 diabetes mellitus (T2DM) patients, as well as the association with clinical/laboratory phenotypes and disease complications. Methods: A total of 155 T2DM patients and 30 healthy controls (HC) were enrolled. The concentrations of serum I-309, interleukin-4 (IL-4), IL-6, IL-10, IL-12, IL-17, IL-23, tumor necrosis factor-α (TNF-α), and interferon (IFN)-γ were measured. The relationships between I-309 and various clinical and laboratory variables were analyzed. Results: The serum concentrations of I-309 were significantly higher in T2DM patients than in HC (P < 0.001). The serum I-309 levels were significantly elevated in T2DM patients with diabetic kidney disease (DKD), hypertension, coronary artery disease, peripheral neuropathy, peripheral artery disease, and diabetic ketosis (all P < 0.05), but reduced in drinkers (P = 0.018). The Spearman analysis showed that serum I-309 correlated positively with age, disease duration, CKD stages, urea, creatinine, urinary albumin-to-creatinine ratio, C-reactive protein, red blood cell distribution width, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, IL-6, IL-12, and IFN-γ, but negatively with estimated glomerular filtration rate (eGFR), fasting blood glucose, total bilirubin, albumin, lymphocyte count, red blood cell count, and hemoglobin. The multiple linear regression analysis indicated that serum I-309 was independently correlated only with eGFR and IFN-γ. The multivariate logistic regression analysis demonstrated that serum I-30 and IL-17A remained independently associated with DKD. Conclusion: Serum I-309 is markedly elevated in T2DM patients and is associated with increased DKD risk, suggesting its potential role as both a promising biomarker and a pathogenic mediator in the progression of T2DM, particularly DKD.