Association of Protein Z with Prediabetes and Type 2 Diabetes

Background: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease. Early detection of prediabetes is important to reduce the risk of T2DM. Some cytokines are known to be associated with T2DM. Therefore, we aimed to identify cytokines as novel biomarkers of glucose dysmetabolism. Methods: The fast stage of the study included 43 subjects (13 subjects with newly diagnosed T2DM, 13 with prediabetes. and 16 with normoglycemia) for cytokine microarray analysis. Blood samples of the subjects were assessed for 310 cytokines to identify potential indicators of prediabetes. The second stage included 142 subjects (36 subjects with T2DM, 35 with prediabetes, and 71 with normoglycemia) to validate the potential cytokines associated with prediabetes. Results: We identified 41 cytokines that differed by 1.5-fold or more in at least one out of the three comparisons (normoglycemia vs. prediabetes, normoglycemia vs. T2DM, and prediabetes vs. T2DM) among 310 cytokines. Finally, we selected protein Z (PROZ) and validated this finding to determine its association with prediabetes. Plasma PROZ levels were found to be decreased in patients with prediabetes (1,490.32 +/- 367.19 pg/mL) and T2DM (1,583.34 +/- 465.43 pg/mL) compared to those in subjects with normoglycemia (1,864.07 +/- 450.83 pg/mL) (P<0.001). There were significantly negative correlations between PROZ and fasting plasma glucose (P =0.001) and hemoglobin Alc (P=0.010). Conclusion: PROZ levels were associated with prediabetes and T2DM. We suggest that PROZ may be a promising biomarker for the early detection of prediabetes. Further large-scale studies are needed to evaluate the relationship and mechanism between PROZ and prediabetes and T2DM.