Serum interleukin-33 (IL-33) level and associated factors in patients with diabetic nephropathy

Objective: The aim of this study was to compare serum IL-33 levels among individuals with diabetic nephropathy (DN), those with type 2 diabetes mellitus (T2DM) without nephropathy, and a healthy control group. In addition, it aimed to evaluate the associations between IL-33 levels and clinical parameters such as glycemic control, kidney function, proteinuria, and medication usage. Methods: Between February 2024 and January 2025, a total of 184 individuals who presented to the Nephrology, Endocrinology and Metabolism, and Internal Medicine outpatient clinics of Selçuk University Faculty of Medicine Hospital were enrolled. Among them, 102 had DN, of which 52 were using SGLT-2 inhibitors. Additionally, 40 participants were diagnosed with T2DM without nephropathy, and 42 formed the healthy control group. Study conditions were explained, and written informed consent was obtained from participants. Individuals under 18 years of age, pregnant or lactating women, and those with chronic inflammatory diseases, asthma, malignancy, or local/systemic infection were excluded. Demographic data, medication use and duration, and comorbidities were recorded. Biochemistry, complete blood count, hormone panel, HbA1c, and serum IL-33 levels were assessed. Spot urine albumin/creatinine and protein/creatinine ratios were also calculated, and indices such as BMI, MHR, and HOMA-IR were generated. Results: Of the 184 participants, 54.9% were male and 45.1% female. The mean age was 59.13 ± 11.61 years. The average height was 165.52 ± 8.24 cm; the median weight was 80 (40–135) kg, and the median BMI was 28.7 (16.44–47.83) kg/m². Serum IL-33 levels differed significantly among groups (p=0.001), with the lowest levels in the DM group (169 ng/L), intermediate levels in the DN group (216.93 ng/L), and the highest in the control group (263.5 ng/L). IL-33 levels showed significant negative correlations with glucose (r=–0.311; p=0.004), HbA1c (r=–0.379; p<0.001), and spot urine protein/creatinine ratio (r=–0.244; p=0.014), while a significant positive correlation was found with GFR (r=0.276; p=0.012). In individuals using SGLT-2 inhibitors, glucose, HbA1c, creatinine, urea, and uric acid levels were lower, whereas GFR and calcium levels were higher. Additionally, IL-33 levels were lower in DN patients using glargine or calcium channel blockers and higher in those using statins. Conclusion: IL-33 appears to be associated with both glycemic control and renal function, and its levels vary according to disease stage. In this study, significant differences in IL-33 levels were observed among groups, with the highest levels detected in the healthy control group. ROC analysis showed that IL-33 may serve as a moderately predictive biomarker for identifying diabetes. Furthermore, higher IL-33 levels in statin users suggest a possible regulatory or enhancing effect of these medications. On the other hand, no statistically significant difference in IL-33 levels was found between SGLT-2 inhibitor users and non-users. These findings indicate that IL-33 may be a potential biomarker candidate in the evaluation of diabetic complications. Keywords: Type 2 Diabetes Mellitus, Diabetic Nephropathy, IL-33, Proteinuria, SGLT-2 Inhibitor, Glycemic Control, Biomarker.