Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 08 24 1 11 Linfeng Jin Department of Science and Education, Jiangsu Medical College Jianhu Clinical College, Yancheng, China Jinjiang He Department of Pharmacy, Jianhu County Shuanghu Hospital of Traditional Chinese Medicine, Yancheng, China Jian Zhang Department of Pharmacy, Jianhu County People's Hospital, Yancheng, China 2026 04 02 2026 05 05 This study evaluates the association between 24-hour urinary glucose excretion (UGE) and urogenital tract infection (UGTI) risk in patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter 2 inhibitor-containing therapy and explores potential immune-metabolic mechanisms. This prospective single-center cohort enrolled adults initiating SGLT2 inhibitor-containing therapy between February 2024 and June 2025. Of 412 enrolled patients, 380 were included in the final analysis and followed for up to 12 months. Patients were categorized into quartiles according to 24-hour UGE measured 3 months after treatment initiation. Urinary immune-cell subsets, soluble immune factors, antimicrobial peptides, and glucose-related metabolites were assessed. Time-to-event, restricted cubic spline, mediation, and sensitivity analyses were performed. Each UGE quartile included 95 patients. The cumulative incidence of pathogen-confirmed UGTI was 10.26% and increased progressively from Q1 to Q4 (3.16%, 7.37%, 12.63%, and 17.89%, respectively). Higher UGE remained independently associated with increased UGTI risk after multivariable adjustment, with a nonlinear positive exposure-response relationship. UGE statistically mediated part of the association between glycemic improvement and infection risk. Higher UGE was also associated with a lower urinary macrophage M1/M2 ratio, reduced interleukin-8 and β-defensin 2 levels, and lower pyruvate, lactate, and citrate levels. Higher UGE was independently associated with greater UGTI risk and unfavorable urinary immune-metabolic profiles. These observational findings support UGE as a potential clinical mediator but do not establish causality. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4782 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4782/2394