Total radical-trapping antioxidant potential in gestational diabetes

High blood glucose levels induce oxidative stress and decrease antioxidant defenses, leading to increased free radical production [1]. Low insulin sensitivity has also been suggested as a cause of oxidative stress in diabetes [2]; and there is considerable evidence that antioxidant defense systems are depleted and antioxidant enzyme activity is reduced in those with the condition [3]. A test has been developed to measure the total radical-trapping antioxidant potential (TRAP) in plasma [3]. Gestational diabetes is associated with oxidative stress and the antioxidant status in this condition is complex. The present study was conducted to measure the serum antioxidants urate, ascorbate, and tocopherol, and to calculate TRAP in women with gestational diabetes.

The study group consisted of 25 women with gestational diabetes who attended the outpatient department of the Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, India. The participants were between 18 and 36 years old, between 32 and 37 weeks of pregnancy, and primigravid. The first control group comprised 25 age- and gestation-matched healthy pregnant women who attended for routine prenatal check-ups, while the second control group comprised 25 age-matched healthy, nonpregnant women who were either students or paramedic staff at PGIMS. Gestational diabetes was diagnosed following an oral glucose tolerance test using 100 g of glucose [4], according to WHO criteria. None of the participants had a family history of diabetes mellitus, hypertension, or obesity.

Study samples of uric acid, vitamins C and E, malonaldehyde, and total plasma sulfhydryl concentration were drawn after overnight fasting and before the women began any hypoglycemic treatment [3]. TRAP was calculated stoichiometrically using the experimentally-determined efficiency of each mol of an antioxidant to trap a peroxyl radical [5]. TRAP (μmol/L)=1.3 uric acid+1.7 vitamin C+2.0 vitamin E+0.2 total plasma sulphydryl. The data were analyzed using analysis of variance (ANOVA).

Serum uric acid levels were significantly raised in the study group compared with the control groups (P<0.001; Table 1), while levels of vitamins C and E, and total thiols were lower in the study group compared with the control groups. Levels of malonaldehyde, a product of lipid peroxidation, were higher in the study group compared with nonpregnant women (control group 2), but lower has compared with healthy pregnant women (control group 1). TRAP was significantly lower in the study group compared with healthy pregnant women (P<0.05), but higher has compared with nonpregnant women (P<0.05). Compared with the control groups, no differences were observed in gestational age at delivery or birth weight.

Table 1. Total radical-trapping antioxidant potential seen in the three groupsa

		Women with gestational diabetes	Healthy pregnant women (control 1)	Nonpregnant women (control 2)
	Malonaldehyde, μmol/L	1.54±0.26c,e	1.68±0.12b	1.14±0.07
	Vitamin E, μmol/L	21.21±1.38f,g	23.62±0.97d	25.75±0.89
	Vitamin C, μmol/L	45.69±5.58c,e	62.18±12.27b	113.56±10.22
	Thiols, μmol/L	380.0±109.0c,e	393.0±112.0b	449.0±37.0
	Uric acid, μmol/L	308.57±19.47c,e	295.0±14.75	175.23±32.45
	TRAP	590.16±59.36f,g	611.67±83.08	562.14±228.0

Abbreviations: TRAP, total radical-trapping antioxidant potential.

a Values are given as mean ± SD. b P<0.001 compared with nonpregnant women. c P<0.001 compared with healthy pregnant women. d P<0.05 compared with nonpregnant women. e P<0.001 compared with nonpregnant women. f P<0.05 compared with nonpregnant women. g P<0.05 compared with healthy pregnant women.

Uric acid possesses antioxidant properties and contributes approximately 60% of free scavenging activity in human serum [4]. Protein thiols have the highest plasma concentration, but act as relatively ineffective antioxidants. In contrast, antioxidant vitamins C and E contribute 13%–17% and 2%–8%, respectively. In the present study, serum vitamin E level was significantly lower in women with gestational diabetes compared with healthy pregnant women, which is consistent with other studies [6]. Vitamin C levels were lower in the study group compared with both control groups, which is also consistent with other reports [5]. Increased oxidative stress and the formation of free radicals have been proposed as a contributing source of hyperuricemia seen in pre-eclampsia.

Ascorbic acid can regenerate vitamin E from alpha tocopheroxyl radicals. Urate and sulfhydryl groups, unlike vitamin C, are unable to regenerate vitamin E and both act more by sparing vitamin E than by recycling [3].

In the present study, lower TRAP values were observed in women with gestational diabetes compared with healthy pregnant women, but higher values were observed compared with nonpregnant women. This could be explained by the higher serum urate concentrations found in the women with gestational diabetes and healthy pregnant women. Previous studies have reported differences in urate concentration observed in pre-eclampsia, normal pregnancy, and gestational diabetes [5], [6], [7]. The observed urate elevation may be a protective response, capable of opposing the harmful effects of free radical activity and oxidative stress. Several studies have found evidence of involvement of oxidative stress or antioxidant depletion in diabetic mothers, and increased lipid peroxidation is involved in the pathogenesis of gestational diabetes [1], [7]. Decreased TRAP in gestational diabetes indicates decreased detoxification or free radical scavenging capacity in pregnancies complicated by diabetes. Monitoring of TRAP and antioxidant supplementation in women with gestational diabetes may help achieve effective glycemic control and improve perinatal outcome.