Association of Salivary α2-Macroglobulin Levels with Glycaemic Status and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus

Introduction Identification of non-invasive biomarkers reflecting glycaemic status and microvascular risk remains a priority in type 2 Diabetes Mellitus (T2DM). α 2 -Macroglobulin (α 2 MG), a high-molecular-weight acute-phase glycoprotein involved in inflammatory regulation, increases in hyperglycaemic states and may be detectable in saliva. This study evaluated the association of salivary α 2 MG with glycaemic control and Diabetic Retinopathy (DR). Methods In this cross-sectional study (January–October 2025), 130 adults were categorised as healthy controls (n=26), controlled T2DM (n=52), and uncontrolled T2DM (n=52). Unstimulated saliva was collected and α 2 MG quantified by enzyme-linked immunosorbent assay. Glycaemic indices, lipid parameters, insulin levels, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and DR status were assessed. Correlation, multivariable regression, and Receiver Operating Characteristic (ROC) analyses were performed. Results Salivary α 2 MG concentrations were significantly higher in uncontrolled T2DM than in controlled T2DM and controls ( P < 0.001). α 2 MG correlated positively with fasting glucose, postprandial glucose, glycated haemoglobin (HbA1c), triglycerides, insulin levels, and HOMA-IR. Participants with DR had significantly higher α 2 MG concentrations than those without retinopathy ( P < 0.001). ROC analysis showed modest discrimination for identifying uncontrolled T2DM, with an optimal cut-off of 764 ng/mL (sensitivity 76.15%; specificity 70%). Discussion These findings suggest salivary α 2 MG reflects both metabolic dysregulation and microvascular injury, supporting its potential relevance as a non-invasive adjunct biomarker in diabetes monitoring, complication risk assessment, and microvascular risk stratification in T2DM. Conclusion Salivary α 2 MG was associated with glycaemic dysregulation and DR in T2DM, supporting its potential as a non-invasive adjunct biomarker. Its ease of collection may facilitate metabolic assessment, particularly in resource-limited settings, pending longitudinal validation.