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

Identification of non-invasive biomarkers reflecting glycaemic status and microvascular risk remains a priority in type 2 Diabetes Mellitus (T2DM). α₂-Macroglobulin (α₂MG), 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 α₂MG with glycaemic control and Diabetic Retinopathy (DR).

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 α₂MG 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.

Salivary α₂MG concentrations were significantly higher in uncontrolled T2DM than in controlled T2DM and controls (P < 0.001). α₂MG correlated positively with fasting glucose, postprandial glucose, glycated haemoglobin (HbA1c), triglycerides, insulin levels, and HOMA-IR. Participants with DR had significantly higher α₂MG 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%).

These findings suggest salivary α₂MG 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.

Salivary α₂MG 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.