Clinical Significance of Serum CCR2 and IDO1 in Diabetic Peripheral Neuropathy

Yubin Liu, Qiaoe Yang Department of Endocrinology and Diabetes, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Qiaoe Yang, Department of Endocrinology and Diabetes, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei, No. 31 Huanghe West Road, Cangzhou, Hebei, 061000, People’s Republic of China, Email [email protected]: To quantify circulating levels of C-C chemokine receptor-2 (CCR2) and indoleamine-2,3-dioxygenase-1 (IDO1) in patients with type 2 diabetes mellitus (T2DM) complicated by diabetic peripheral neuropathy (DPN) and to evaluate their potential as early biomarkers for DPN detection.Methods: In this retrospective observational study, 367 patients with T2DM admitted to Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei between January 2021 and November 2024 were consecutively enrolled. Participants were stratified into a DPN group (n = 108) and a non-DPN group (n = 259) based on the presence or absence of DPN. Clinical baseline data were collected, and serum CCR2 and IDO1 levels were determined by enzyme-linked immunosorbent assays (ELISA). Their associations with DPN and predictive performance were evaluated using Spearman correlation, multivariate logistic regression, random-forest modeling, and receiver operating characteristic (ROC) curve analyses.Results: Median serum CCR2 (7.32 ng/mL) and IDO1 (9.77 ng/mL) concentrations were both significantly higher in the DPN cohort than in the non-DPN group (P < 0.05 for each) and were positively correlated (r = 0.384, P < 0.001). Multivariable logistic regression identified elevated CCR2 (OR 1.460, 95% CI 1.047– 2.035) and IDO1 (OR 1.317, 95% CI 1.220– 1.421) as independent risk factors for DPN. In a random forest model, CCR2 and IDO1 ranked as the third and fourth most important predictors, respectively. ROC analysis yielded areas under the curve (AUCs) of 0.728 for CCR2 and 0.749 for IDO1 individually; combining the two biomarkers increased the AUC to 0.786 (95% CI 0.729– 0.844), with 62.0% sensitivity and 89.6% specificity.Conclusion: Serum CCR2 and IDO1 are significantly up-regulated in patients with DPN and represent independent risk factors for its development. Their combined measurement enhances early detection accuracy, offering a clinically useful biomarker panel for DPN. Keywords: C-C chemokine receptor-2, indoleamine-2,3-dioxygenase-1, diabetic peripheral neuropathy, biomarkers, clinical utility