Associations of hs-CRP and interleukin-6 with diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study from Uzbekistan

Abstract

Diabetic nephropathy is a major microvascular complication of type 2 diabetes mellitus (T2DM) and a leading cause of chronic kidney disease worldwide. Chronic low-grade inflammation has been implicated in diabetic nephropathy, but evidence from Central Asian populations remains limited. This study investigated the associations of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) with diabetic nephropathy among patients with T2DM in Uzbekistan. This cross-sectional study included 227 patients with T2DM, comprising 95 patients without microvascular complications and 132 patients with diabetic nephropathy. Demographic, clinical, laboratory, and medication data were collected. Group comparisons were performed using the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. Five multivariable logistic regression models were constructed to evaluate the associations of hs-CRP and IL-6 with diabetic nephropathy. Model discrimination was assessed using ROC curve analysis and pairwise AUC comparisons, while calibration was evaluated using calibration plots, Brier scores, and the Hosmer–Lemeshow test. Internal validation was performed using 1,000 bootstrap resamples. Statistical significance was defined as P  < 0.05. Patients with diabetic nephropathy were older, had a longer duration of diabetes, and more frequently had hypertension. Patients with diabetic nephropathy had significantly higher hs-CRP and IL-6 concentrations than those without microvascular complications (7.50 [5.40–8.60] vs. 4.54 [3.40–6.38] mg/L and 13.30 [11.28–16.20] vs. 8.40 [5.55–10.60] pg/mL, respectively; both P  < 0.001). In the fully adjusted model, hs-CRP (AOR 1.31, 95% CI 1.07–1.59) and IL-6 (AOR 1.50, 95% CI 1.31–1.72) remained independently associated with diabetic nephropathy. Adding inflammatory biomarkers improved model discrimination from an AUC of 0.814 for the clinical model to 0.943 for the combined model; the optimism-corrected AUC was 0.921. Elevated hs-CRP and IL-6 levels were independently associated with diabetic nephropathy among patients with T2DM in Uzbekistan. Longer diabetes duration, hypertension, and higher fasting plasma glucose levels were also independently associated with diabetic nephropathy. These findings are consistent with a potential role of chronic low-grade inflammation in diabetic nephropathy. However, prospective and externally validated studies are needed to determine the clinical utility of hs-CRP and IL-6 before they can be considered for routine clinical risk assessment. Not applicable.