Fas and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Are Closely Linked to the Levels of Glycated and Fetal Hemoglobin in Patients with Diabetes Mellitus

Background: The aim of this study was to investigate the relationships between apoptotic markers and the levels of glycated and fetal hemoglobin (HbA1c and HbF) in diabetes. Methods: The levels of Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), HbF, and HbA1c were measured in 112 patients with type 2 diabetes. Results: Diabetic patients with microalbuminuria had an elevated Fas level and a decreased TRAIL level, compared to healthy controls. Elevated HbF level was more often observed in patients with decreased TRAIL level than in those with increased TRAIL level (33.9% versus 12.5%, p < 0.05). Fas was positively correlated with HbA1c (r = 0.31, p < 0.001), but TRAIL was inversely correlated with HbA1c and HbF (r = -0.30 and r = -0.32, respectively; p < 0.001). In a multivariate logistic regression analysis, decreased TRAIL level was significantly associated with enhanced HbF production after adjusting for potential confounders [odds ratio, 1.35 (95% CI, 1.09 - 2.87), p = 0.004]. The diagnostic ability of TRAIL to identify an elevated HbF > 1.0% was significantly higher than that of the Fas [0.760 (95% CI, 0.638 -0.882) versus 0.589 (95% CI, 0.457 - 0.721), p < 0.001]. Conclusions: Fas is closely associated with long-term hyperglycemia, while TRAIL plays certain roles in enhancing HbF production in type 2 diabetes.