The relationship between chronic glycaemic control and oxidative stress in type 2 diabetes mellitus

Abstract

This study compares the lipid peroxidation marker urinary thiobarbituric acid reactive substances (TBARS) and antioxidants including plasma alpha-tocopherol (vitamin E), plasma (P-GSH-Px) and erythrocyte glutathione peroxidase (E-GSH-Px) activities, and plasma selenium levels in two groups of type 2 diabetic subjects (both n=20) with a disease duration of < or =2 (GP1) and 4-6 years (GP2), and non-diabetic age and gender-matched control subjects (CG, n=20). The mean (standard deviation [SD]) age of the groups was similar at 41(10) years. Fasting blood and midstream urine samples were obtained from diabetic and non-diabetic subjects attending the diabetic clinic and HbAlc, fructosamine, urine TBARS, total antioxidant (TAS) levels, P-GSH-Px, E-GSHPx and plasma selenium and vitamin E concentrations were measured. HbA1c (%) and fructosamine levels in the GP1 and GP2 diabetic subjects and the controls were 5.75 (0.67), 11.43 (2.01) and 4.33 (0.47), and 3.09 (0.57), 6.09 (1.15) and 1.67 (0.31), respectively (GP1 vs. GP2, GP1 vs. GC and GP2 vs. CG, all P < 0.001). Elevated urinary TBARS (micromol/mmol urinary creatinine) in the GP1, GP2 and GC groups were 2.47 (0.37), 3.73 (0.93) and 1.18 (0.24), respectively (GP1 vs. GP2, GP1 vs. GC and GP2 vs. CG, all P < 0.001). A significant correlation between HbA1c and TBARS was also noted (r2 = 0.894, P < 0.001) but only in the GP2 subjects. TAS levels were only decreased in the GP2 group compared to control values (0.59 [0.18] vs. 1.74 [0.21], P < 0.001). Plasma vitamin E concentrations (micromol/L) of 34.11 (3.31), 9.57 (2.20) and 39.01 (2.91) were observed in the GP1, GP2 and GC groups, respectively (GP1 vs. CG, P < 0.05 and GP1 vs. GP2 and GP vs. CG, both P < 0.001). E-GSH-Px (U/g Hb) and P-GSH-Px (U/L) activities in GP1, GP2 and CG groups were also decreased at 57.04 (4.31), 24.0 (8.94) and 67.6 (4.29), and 6.16 (1.56), 2.67 (0.47) and 8.72 (0.31), respectively (E-GSH-Px: CG vs. GP1, P < 0.01, CG vs. GP2 and GP1 vs. GP2, both P < 0.001; P-GSH-Px: CG vs. GP1, CG vs. GP2 and GP1 vs. GP2, all P < 0.001). Plasma selenium levels (miromol/L) were only significantly decreased in GP2 compared to both GP1 and CG values (0.49 [0.29] vs. 1.67 [0.80] vs. 1.79 [0.26], both P < 0.001). These observations support the suggestion that chronic hyperglycaemia can influence the generation of free radicals, which may lead ultimately to increased lipid peroxidation and depletion of antioxidants, and thereby enhanced oxidative stress in subjects with type 2 diabetes mellitus.

Associations of FPG, A1C and disease duration with protein markers of oxidative damage and antioxidative defense in type 2 diabetes and diabetic retinopathy

“…Our findings are in accordance with previous studies in DM [17][18][19][20][21] and DR patients. 11 However, we could not find reports on both IMA and GSH simultaneously in DM and DR patients.…”

“…20,21 The mechanisms underlying decreased GSH in diabetes are hyperglycemia-associated metabolic disturbances, abnormal protein balance, and inadequate GSH synthesis leading to OS. 7,20 In line with this, we observed a negative association between FPG and GSH, as hyperglycemia could per se influence oxidant-antioxidant homeostasis. 12 Moreover, GSH may be utilized as an antioxidant to neutralize excess FR generated in diabetes.…”

“…Although decreased levels of GSH were reported in diabetes, the cause of GSH deficiency is still unclear. 20,21 Moreover, to the best of our knowledge, there are no reports that have evaluated IMA and GSH in relation to hyperglycemia, glycated hemoglobin (A1C), and disease duration in both diabetes and DR (literature was mined by PubMed search using MeSH terms diabetes, diabetic retinopathy, free radicals, reactive oxygen species, oxidative stress, albumin, ischemia modified albumin, and glutathione).…”

Selenium and diabetes - evidence from animal studies

“…Data from earlier epidemiologic investigations showed correlations between abnormal glucose or lipid metabolism and decreased plasma Se concentrations or selenoperoxidase activity in diabetic subjects [41][42][43][44][45][46][47][48]. Likewise, there were also similar correlations or associations in animals.…”

Selenium biochemistry and its role for human health

“…239,240 Finally, in some cases the difference in Se status was limited to specific sub-groups such as males 241 or patients with a disease duration r2 years. 234 The latest results from randomized trials confirmed such conflicting data, showing that Se supplementation could either increase the risk of type 2 diabetes or be ineffective. 242,243 As a whole, the association between Se and type 2 diabetes appears to follow a U-shape, so that it may show variable effects depending on the position of the population baseline level of Se intake.…”