Abstract

The purpose of this study was to investigate the heterogeneity of the association between glycemic variability and oxidative stress markers in T1DM patients under daily life insulin treatment. We studied, in a cross-sectional analysis, 76 T1DM patients without clinical chronic diabetes complications and 22 healthy individuals. Were evaluated the short-term glycemic variability (STGV), long-term glycemic variability (LTGV), oxidative stress markers [8-isoprostaglandin-F2α (Ur-8-iso-PGF2α), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and erythrocytes reduced/oxidized glutathione (GSH/GSSG)] and biochemical dosages (glycaemia, HbA1c, lipidogram, albuminuria). Plasmatic NO was positively associated with LTGV (last year average of HbA1c) (8.7 ± 1.6% or 71 ± 18 mmol) (rS: 0.278; p: 0.042). Plasmatic TBARS, erythrocytes GSH/GSSH and Ur-8-iso-PGF-2α didn't show correlation with glycemic variability. GSH/GSSG was inversely correlated with LDL-cholesterol (rS: - 0.417; p: 0.047) and triglycerides (rS: -0.521; p: 0.013). Albuminuria was positive correlated with age (rS: 0.340; p: 0.002), plasmatic NO (rS: 0.267; p 0.049) and TBARS (rS: 0.327; p: 0.015). In daily life insulin treatment, young T1DM patients have higher plasmatic NO than healthy subjects. However, the correlation between glycemic variability and oxidative stress markers is heterogeneous. Lipid profile and albuminuria are associated with different oxidative stress markers. These data collaborate to explain the controversial results in this issue.

Highlights

  • Large randomized studies have established that early and persistent glycemic control during diabetes mellitus natural history, reduces the risk to develop both micro and macrovascular chronic complications of this disease [1]

  • body mass index (BMI), shortterm glycemic variability (STGV), long-term glycemic variability (LTGV), albuminuria, serum C-reactive protein (CRP) and plasmatic nitric oxide (NO) were significantly different between controls and type 1 diabetes mellitus (T1DM) patients

  • There were no significant differences between the groups for gender distribution, serum lipid profile, ferritin, urinary 8-iso-PGF-2α, plasmatic thiobarbituric acid reactive substances (TBARS) and GSH/GSSG

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Summary

Introduction

Large randomized studies have established that early and persistent glycemic control during diabetes mellitus natural history, reduces the risk to develop both micro and macrovascular chronic complications of this disease [1]. The initial and prolonged effect of overall glycemic control in this process is part of the “metabolic memory”. This concept supports the adoption of a precocious, aggressive and continuous treatment approach, at least, since the clinical diabetes diagnosis [2]. Recent evidence suggests that acute glucose fluctuations may accelerate the development of diabetes chronic complications [4] more than chronic hyperglycemia [5], by triggering oxidative stress [6]. Majority of studies are based on the 7-point glucose profiles, that may not capture the full degree of variability that is observed in the CGMS [8]

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