ABSTRACT
Background & objectives: Gestational or preexisting diabetes is one of the risk factors of pre-eclampsia. Both are responsible for higher maternal and fetal complications. The objective was to study clinical risk factors of pre-eclampsia and biochemical markers in early pregnancy of women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) for the development of pre-eclampsia. Methods: The study group comprised pregnant women diagnosed with GDM before the 20 wk of gestation and DM before pregnancy and the control group had age-, parity- and period of gestation-matched healthy women. Sex hormone-binding globulin (SHBG), insulin-like growth factor-I (IGF-I) and 25-hydroxy vitamin D [25(OH)D] levels and the polymorphism of these genes was evaluated at recruitment. Results: Out of 2050 pregnant women, 316 (15.41%) women (296 had GDM and 20 DM before pregnancy) were included in the study group. Of these, 96 women (30.38%) in the study group and 44 (13.92%) controls developed pre-eclampsia. Multivariate logistic regression analysis indicated those who belonged to the upper middle and upper class of socio-economic status (SES) were likely to be at 4.50 and 6.10 times higher risk of developing pre-eclampsia. The risk of getting pre-eclampsia among those who had DM before pregnancy and pre-eclampsia in their previous pregnancy was about 2.34 and 4.56 times higher compared to those who had no such events, respectively. The serum biomarkers [SHBG, IGF-I and 25(OH)D] were not found to be useful in predicting pre-eclampsia in women with GDM. To predict risk of development of pre-eclampsia, the fitted risk model by backward elimination procedure was used to calculate a risk score for each patient. Receiver operating characteristic (ROC) curve for pre-eclampsia showed that area under the curve was 0.68 (95% confidence interval: 0.63-0.73); P<0.001. Interpretation & conclusions: The findings of this study suggested that pregnant women with diabetes were at a higher risk for pre-eclampsia. SES, history of pre-eclampsia in previous pregnancy and pre-GDM were found to be the risk factors.
ABSTRACT
Reactive oxygen metabolites (ROMs), such as superoxide anions (O2*-) hydrogen peroxide (H2O2), and hydroxyl radical (*OH), malondialdehyde (MDA) and nitric oxide (NO) are directly or indirectly involved in multistage process of carcinogenesis. They are mainly involved in DNA damage leading sometimes to mutations in tumour suppressor genes. They also act as initiator and/or promotor in carcinogenesis. Some of them are mutagenic in mammalian systems. O2*-, H2O2 and *OH are reported to be involved in higher frequencies of sister chromatid exchanges (SCEs) and chromosome breaks and gaps (CBGs). MDA, a bi-product of lipid peroxidation (LPO), is said to be involved in DNA adduct formations, which are believed to be responsible for carcinogenesis. NO, on the other hand, plays a duel role in cancer. At high concentration it kills tumour cells, but at low concentration it promotes tumour growth and metastasis. It causes DNA single and double strand breaks. The metabolites of NO such as peroxynitrite (OONO-) is a potent mutagen that can induce transversion mutations. NO can stimulate O2*-/H2O2/*OH-induced LPO. These deleterious actions of oxidants can be countered by antioxidant defence system in humans. There are first line defense antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). SOD converts O2*- to H2O2, which is further converted to H2O with the help of GPx and CAT. SOD inhibits *OH production. SOD also act as antipoliferative agent, anticarcinogens, and inhibitor at initiation and promotion/transformation stage in carcinogenesis. GPx is another antioxidative enzyme which catalyses to convert H2O2, to H2O. The most potent enzyme is CAT. GPx and CAT are important in the inactivation of many environmental mutagens. CAT is also found to reduce the SCE levels and chromosomal aberrations. Antioxidative vitamins such as vitamin A, E, and C have a number of biological activities such as immune stimulation, inhibition of nitrosamine formation and an alteration of metabolic activations of carcinogens. They can prevent genetic changes by inhibiting DNA damage induced by the ROMs. Therefore, these antioxidants may be helpful in the treatment of human cancer. However, detailed studies are required to draw a definite conclusion.