A Novel Multi-Biomarker Approach For The Diagnosis Of Type 2 Diabetes Mellitus: Combined Evaluation Of Beta Trace Protein, Beta-2 Microglobulin, And Trefoil Factor-3

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with persistent hyperglycemia, chronic inflammation, endothelial dysfunction, and progressive renal impairment. Early identification of biomarkers reflecting these pathological changes is essential for improving diagnosis and preventing diabetes-related complications. Aim: This study aimed to evaluate the diagnostic value of Beta Trace Protein (BTP), Beta-2 Microglobulin (β2M), and Trefoil Factor 3 (TFF3) as potential biomarkers for Type 2 Diabetes Mellitus using receiver operating characteristic (ROC) curve analysis. Methodology: A case-control study was conducted on 120 participants recruited from hospitals affiliated with the Baghdad Health Directorate/Al-Karkh between January and June 2025. The study included 90 patients diagnosed with T2DM and 30 age- and sex-matched healthy controls. Serum concentrations of BTP, β2M, and TFF3 were measured and compared between groups. Diagnostic performance was evaluated using ROC curve analysis, including the area under the curve (AUC), sensitivity, specificity, and optimal cut-off values. Results: Serum levels of BTP, β2M, and TFF3 were significantly higher in patients with Type 2 Diabetes Mellitus (T2DM) than in healthy controls (1072 ± 281.3 vs. 683.6 ± 153.5 μg/dL for BTP, 21.42 ± 3.672 vs. 8.142 ± 1.814 μg/mL for β2M, and 42.59 ± 16.81 vs. 16.86 ± 4.631 ng/mL for TFF3; P < 0.0001 for all comparisons). ROC curve analysis demonstrated excellent diagnostic performance for all three biomarkers. β2M showed the highest diagnostic accuracy (AUC = 0.9959), with 98.89% sensitivity and 100% specificity at a cut-off value >11.66 μg/mL. TFF3 also demonstrated excellent performance (AUC = 0.9578) with 90% sensitivity and 90% specificity, whereas BTP showed good diagnostic accuracy (AUC = 0.8844), with 82% sensitivity and 90% specificity. These findings indicate that β2M is the most accurate biomarker among those evaluated, while the combined assessment of BTP, β2M, and TFF3 may further enhance the early diagnosis of T2DM and improve the identification of patients at increased risk of renal and vascular complications. Conclusion: BTP, β2M, and TFF3 are promising biomarkers for the diagnosis of T2DM, as demonstrated by ROC curve analysis. Among them, β2M exhibited the highest diagnostic performance. Combined assessment of these biomarkers may improve the early detection of diabetes and facilitate the identification of patients at increased risk of renal and vascular complications.