Thiols as markers of redox status in type 1 diabetes mellitus

Introduction: Type 1 diabetes mellitus (T1DM) is associated with inflammation and the production of reactive oxygen species (ROS). Systemically, free thiols (R-SH) can be oxidized by ROS and circulating R-SH concentrations may directly reflect the systemic redox status. In this study the association between R-SH and clinical parameters of T1DM, including glycated haemoglobin A1c (HbA1c), was investigated. This is of particular interest since thiols are amendable to therapeutic intervention. Methods: As part of a prospective cohort study, data from 216 patients with a mean age of 45 (12) years, 57% male, diabetes duration 22 (16, 30) years and HbA1c of 60 (11) mmol/mol were examined. Baseline data were collected in 2002 and follow-up data in 2018. Cox proportional hazards regression analysis, with age, sex, HbA1c and R-SH, was used to assess prognostic factors for the development of complications. Results: At baseline, the plasma concentration of R-SH was 281.8 +/- 34.0 mu M. In addition to a lower concentration of NT-proBNP in the highest R-SH quartile (305-379 mu M) there were no differences in baseline characteristics between the quartiles of R-SH. The Pearson correlation coefficient for R-SH and NT-proBNP was -0.290 (p < 0.001). No significant correlation between R-SH and baseline HbA1c (r = -0.024, p = 0.726) was present. During follow-up, 42 macrovascular and 92 microvascular complications occurred. In Cox regression, R-SH was not a prognostic factor for the development of microvascular [hazard ratio (HR) 0.999 (95% confidence interval (CI) 0.993, 1.005)] and macrovascular [HR 0.993 (95% CI 0.984, 1.002)] complications. Conclusions: In addition to a negative association with NT-proBNP, no relevant relationships between R-SH and parameters of T1DM, including HbA1c, were present in this study.