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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 a-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 £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 HbA1c, 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 (μmol/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 (μmol/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 (μmol/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.