Background <p>Albumin is an abundant plasma protein which gets modified with advanced glycation end products (AGEs) predominantly in diabetic condition. AGE modification induces immune response and autoantibodies are generated which play an important role in disease pathology.</p> Objective <p>This study aimed to illustrate the role of autoantibodies against Nε-carboxymethyl lysine (CML) and methylglyoxal (MG) modified albumin in diabetic cardiovascular complications.</p> Methods <p>Type-2 diabetes subjects were enrolled and further grouped into stress test positive or stress test negative based on treadmill stress test (TMT). Autoantibody titer was quantified by ELISA assay for CML-modified albumin (stress test positive, n = 40; stress test negative, n = 59) and MG-modified albumin (stress test positive, n = 35; stress test negative, n = 58). An optimal cutoff values for both autoantibodies were determined by ROC analysis. These cutoff values were used to calculate the predictive scores.</p> Results <p>It is observed that autoantibody titer for CML-modified albumin and MG-modified albumin were elevated along with AGE fluorescence in the diabetic stress test-positive group. In ROC analysis, CML-modified albumin showed a greater area (AUC 0.742, p &lt; 0.001) than AGE fluorescence and MG-modified albumin (AUC 0.711, p &lt; 0.001 and AUC 0.605). The cutoff values were determined as AGE fluorescence &gt; 6.98 AU (Se 72.5, Sp 62.71), CML-modified albumin autoantibodies &gt; 36.17 ng/ml (Se 87.5, Sp 57.63) and MG-modified albumin autoantibodies &gt; 59.24 ng/ml (Se 51.43. Sp 70.69). Negative predictive score for CML-modified albumin autoantibodies (86.84%) was higher than AGE fluorescence (76.60%)and for MG-modified albumin (70.69%).</p> Conclusions <p>This study concluded that CML-modified albumin autoantibodies exhibited high negative predictive scores which has a promising role in early diagnosis of cardiovascular risk in type-2 diabetes.</p>