Research articles

Corresponding Author Dr. SIMMI KHARB
Submitting Author Dr. Simmi Kharb

gestational diabetes, preeclampsia, diabetic preeclamptics, uric acid, ascorbic acid

KHARB S. Uric Acid And Ascorbic Acid Levels In Pregnancy With Preeclampsia And Diabetes. WebmedCentral BIOCHEMISTRY 2010;1(10):WMC00718
doi: 10.9754/journal.wmc.2010.00718
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Submitted on: 30 Oct 2010 04:53:02 PM GMT
Published on: 31 Oct 2010 12:20:18 AM GMT


Serum uric acid (SUA) and ascorbic acid levels were evaluated in 40 patients preclampsia [18-diabetic pre-eclamptic women (DM-PRW) & 22 without diabetes (PRW)]; 20 normotensive pregnant women [8 with gestational diabetes (G-DM) & rest 12 were healthy pregnant women (HPW)]; and control group consisting of 20 healthy non-pregnant women. SUA values were significantly increased in PRW & DM-PRW as compared to controls and were higher in PRW than DM-PRW (p >0.05). Also, SUA was significantly increased in G-DM as compared to HNPW (p<0.001). Serum ascorbic levels showed a significant fall in PRW and DM-PRW (p<0.01) with DM-PRW being still lower (p >0.05). Also, ascorbate levels were lowered in G-DM as compared to HNPW (p <0.001).

PRW showed a significant negative correlation between ascorbate and uric acid levels (p <0.01). Thus, the elevated circulating concentration of uric acid, a valuable marker of pre-eclampsia that we propose may be a marker of free radical generation, may also serve a protective role.


In men and in nonpregnant women there is a well-defined relationship between  essential hypertension and glucose intolerance, which has been termed the insulin-resistance syndrome syndrome X [1,2]. The relationship between hypertensive disorders of pregnancy and glucose intolerance, however, is less well established. High blood glucose levels induce oxidative stress and decrease antioxidant defences, thus leading to increased free radical formation [3]. Recently increased oxidative stress and formation of reactive oxygen species (ROS) have been proposed as another contributing source of hyperuricemia noted in preeclampia apart from renal dysfunction [4].

The most important physiological aqueous antioxidants are vitamin C (ascorbic acid) and uric acid, while bilirubin and thiol-containing molecules make a comparatively small contribution [5]. Hence, the present study was planned to evaluate uric acid and ascorbic acid levels in diabetic preeclamptic, non-diabetic preeclamptic and gestational diabetic women in relation to blood glucose levels.

Materials and Methods

The study was carried out in 80 women attending / admitted in Antenatal Clinics of Obstetrics and Gynecology Department at Pt. BDS PGIMS, Rohtak (India). Informed consent was taken. The diagnosis of preeclampsia was established in accordance with the definitions of the American College of Obstetrics and Gynaecologists [6]. Inclusion criteria was : age 18-35 years, primigravida, 28-40 weeks gestation, absence of labour contractions, absence of any other medical complications (such as renal disease, primary hypertension, cardiovascular disease, connective tisene disease) concurrent with preeclampsia.

Fasting samples were collected from three groups of women. The first group consisted of 40 patients of preeclampsia : 18 with diabetes (DM-PRW) and 22 without diabetes (PRW). The second group consisted of 20 normotensive pregnant women of which 8 were having gestational diabetes (G-DM) and rest 12 were healthy pregnant women (HPW). The control group consists of 20 healthy non-pregnant, volunteers (HNPW) in the age group 18-35 years.

Patients with family history of diabetes mellitus, hypertension and obesity were excluded from the study. None were taking any vitamin supplements or drugs. Oral glucose tolerance was carried according to criteria laid down by O’Sullivan and Mahan [7] by giving 100g glucose dissolved in water and estimating blood glucose at fasting, one, two and three hours by glucose oxidase perioxidase method [7]. Serum uric acid levels were measured by colorimetric assay [8] and ascorbic acid levels were estimated spectrophotometrically [9].


Table 1 shows the clinical data on the study and control groups. The mean fasting, one hour, 2 hours and 3 hours blood glucose levels in DM-PRW, PRW, G-DM are given in Table 2.

The mean  serum uric acid (SUA) values were significantly increased in both preeclamptic and diabetic preeclamptic women as compared to control (p < 0.01) SUA levels were higher in PRW as compared to DM – PRW (p > 0.05). Also, SUA was significantly increased in gestational diabetics as compared to HNPW (p < 0.001).

Significant fall in ascorbic acid levels were observed in both PRW as well as DM-PRW (p<0.01) Diabetic preeclamptic women showed a greater fall in ascorbic acid as compared to preeclamptics (p > 0.05). Aslo ascorbate levels were lower on G-DM as compared to HNPW (p<0.001).

Decrease in ascorbate levels and rise in uric acid levels showed a significant negative correlation (r = —0.41, p<0.01) in case of PRW, but not statistically significant in case of DM-PRW and G-DM (r = 0.18 p > 0.05 and  r = 0.21, p > 0.05 respectively).


Consistent with previous reports [4,10], mean serum uric acid levels are significantly higher in preeclampsia than in normal pregnant in the present study. The most commonly accepted explanation is increased reabsorption and decreased excretion of uric acid in proximal tubules, similar to the physiologic response to hypovolemia.     

Uric acid possesses antioxidant properties, and contributes about 60% of free radical scavenging activity in human serum [5]. The observed uric acid elevation may be a protective response, capable of opposing harmful effects of free radical activity and oxidative stress. 

The relationship between hypertensive disorders of pregnancy and glucose intolerance is not established. Earlier reports had shown attenuated glucose response to intravenous insulin in preeclampsia suggesting an association between preeclampsia and insulin resistance [11,12]. In contrast, a recent study has reported a reduced insulin resistance during preeclampsia together with lack of correlation between mean arterial blood pressure and insulin sensitivity thereby suggesting that insulin resistance is not involved in the pathophysiology of raised blood pressure in preeclampsia [13].

Elevated serum uric acid is a consistant feature of insulin resistance syndromes [14], though no reports are available in literature regards uric acid levels in diabetic preeclamptics and gestational diabetes. Insulin has a physiological action on renal tubules causing reduced sodium and uric acid clearance [15]. Because plasma insulin is characteristically elevated, hyperuricemia may arise as a consequence of enhanced renal insulin activity. Elevated serum uric acid concentrations predict development of diabetes mellitus [16] and hypertension [17], even in the presence of normal creatinine clearance and plasma glucose concentration, and therefore may be a subtle, early marker of peripheral insulin resistance syndromes.

In addition, an elevated SUA concentration may reflect impaired endothelial integrity, in which endothelial dependent vascular relaxation produced by nitric oxide (NO) is reduced [18]. In diabetic subjects, the problem is not a failure of generate NO; instead NO is removed through the scavenging action of oxygen free radicals. SUA may, therefore, be linked to cardiovascular disease because it reflects increased xanthine oxidase activity [19], which is present in endothelial cells and is a powerful generator of oxygen free radicals. The observed SUA elevation may be a protective response, capable of opposing the harmful effects of free-radical activity and oxidative stress.

There is further evidence that hydrophilic antioxidants play a pivotal role in cardiovascular system by preventing lipid peroxidation. Several reports implicate role of lipid peroxidation in preeclampsia and gestational diabetes [20-23].

Substantial evidence from animal models suggests that oxidative stress in diabetic pregnancy might contribute to risk of fetal abnormality and this can be prevented by antioxidants [24].

In the present study, we observed low ascorbic levels in PRW and DM-PRW as compared to controls (Table 3, p <0.01). Also, ascorbic acid levels were lower in G-DM as compared to controls (p<0.01). Although preeclamptic women showed the lower levels as compared to diabetic preeclamptic, the difference is not statistically significant (p >0.05). Little information is available with regard to antioxidant defenses and diabetic preeclamptics and gestational diabetes. However, reports are available regarding antioxidant defenses in preeclampsia [20,23,25]

Short term administration of vitamin C in diabetic subjects, hypertensive subjects and those who use tobacco regularly with low circulating vitamin C concentration, leads to restoration of normal vascular function [26] and offering further evidence that endothelial dysfunction may be consequence of oxidative stress. A recent randomized study of effects of systemic uric acid administration, 1000mg), in healthy volunteers, compared with vitamin C (1000 mg) has shown a significant increase in serum antioxidants scavenging capacity [27].

Both ascorbic acid and uric acid are most important physiological aqueous antioxidants and uric acid is found significantly in higher concentrations than ascorbic acid. As a result of higher concentration uric acid provides most abundant source of scavenging activity in human serum (as much as 60%). High blood glucose levels, ischaemia reperfusion, hypoxia, induce oxidative stress and decrease antioxidant defences, thus leading to impaired oxidative metabolism. The resulting free radicals may damage not only the organ in which they are formed but if released into circulation also remote organs. Fetus is a potential source of substrate for xanthine dehydrogenase/oxidase and hypoxanthine on crossing placenta provides substrate for maternal xanthine dehydrogenase/oxidase, would amplify reactive oxygen species generation distant site.

Thus, the elevated circulating concentration of uric acid, a valuable marker of preeclampsia may be a marker of free radical generation in these conditions.


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