This analytical cross-sectional study aimed to investigate and compare serum and salivary fructosamine and sestrin-2 levels in type 2 diabetic mellitus (T2DM) patients and controls. Methods: Ninety eight participants were enrolled in this study and subdivided into 2 subgroups, the first group (G2), which represented the control group, consisted of (49) individuals, and the forty-eight patients with DM represented the second group (G1). Serum and saliva samples collected from fasting subjects. Sestrin-2 and Fructosamine were measured from serum and saliva samples using ELISA technique. Results: The serum and salivary fructosamine and sestrin-2 levels were high in diabetic patients, and the difference between the salivary fructosamine and sestrin-2 levels of diabetic and healthy individuals was found to be statistically significant. Serum and saliva C-peptide and HbA1c levels were higher in the uncontrolled T1DM than in the controlled T1DM. Serum and saliva sestrin-2 (≥1.970 and ≥0.640, respectively), a sensitivity of 100.0%, a specificity of 100.0%, and an AUC of 1.000 and 0.996, respectively, were observed for predicting DM. At the cut-off value ≥308.3 and ≥2.032 for serum and saliva fructosamine, a sensitivity of 69.4 and 93.9, respectively, a specificity of 89.8 and 73.5, respectively, and an AUC of 0.787 and 0.911, respectively, were observed for predicting DM. Conclusions: Fructosamine and sestrin-2 can be used as novel biomarkers in people with diabetes in serum and saliva.
