The Clinical Signanficancs Of Advanced Oxidation Protein Products At Different Gestational Stages In Patients With And Without Gestational Diabetes Mellitus

BcakgroundsGestational diabetes mellitus(GDM)is a common obstetric disease.Recently, There is an upward trend about the incidence of GDM in the global.GDM is asssociated with increased risk of adverse outcome for mother and infant,in both short-and long-term. Early detection,early diagnosis, early treatment of GDM is particularly important.so far,the pathogenesis of GDM is not clear. The factors for GDM include genetics, nutritional factors, inflammatory, adipocytokines and so on. It is well established that GDM and type2diabetes share commom pathogenesis. Insulin resistance (IR) and β-cell dysfunction may be the key factors in the pathogenesis of GDM. Studies showed that oxidative stress plays an important role in IR and β-cell dysfunction, which result in impaired glucose regulation and increased glycation.Considerable attention has been focused on the relationship between oxidative stress and GDM.Normal pregnancy is considered a state of enhanced oxidative stress. When maternal-fetal blood circulation just set up, the of concentration of oxygen increases rapidly in the placenta, this phenomenon,which is similar to the ischemia-reperfusion process,can produce a large number of ROS. Studies showed that lipid peroxidation enhanced in normal pregnant women. Lipid peroxidation is the result of peroxidation caused by excess free radicals, which can reflect the degree of lipid peroxidation, and also the level of oxidative damage. Ciragil et al. found that pregnant women in vivo LPO (lipid peroxides) and superoxide dismutase (SOD), catalase (CAT) levels were significantly higher than that of non-pregnant women, and in pregnant women without urinary tract infection, the levels of CAT, SOD, LPO increased gradually from early pregnancy to late pregnancy. Corresponding enhanced antioxidant defenses, normal pregnancy can be maintained, due to the balance between oxidation and antioxidation system. Some schlars thought that oxidative stress played an important role in placental development,fluff formation and fetal development. However, it is a matter of debate about the presence of oxidative stress in middle-late pregnancy. Some scholars believed that there was no oxidative stress during middle-late pregnancy in pregnant women, or oxidative stress was decreased.The excessive generation of ROS results in an imbalance between oxidation and antioxidant system, and total balance tend to oxidative stress. Excessive ROC can directly or indirectly cause tissue or cell damage.At present, the link of oxidative stress and type2diabetes has been clear. Excessive ROS,which can be used as functional signal molecules to activate the stress sensitivity signaling pathways in the cell, in order to interfere with insulin signaling,and cause insulin resistance, can directly or indirectly damage pancreatic beta cell,and promote p-cell apoptosis, resulting in a decrease of insulin secretion, cause glucose metabolic disorders. In the condition of hyperglycemia, superoxide dismutase, catalase and glutathione peroxidase activities are reduced by glycosylation,and ROS is increased.Diabetes and its complication may be closely associated with imbalance between oxidation and antioxidant system. Studies found that oxidative stress might occur prior to hyperglycemia. Brownlee et al. reported diabetic vascular (such as cardiovascular, cerebrovascular, and lower limb blood vessel) and microvascular complications (such as god, nerve blood vessels) have a common pathogenesis, namely oxidative stress. Ceriello et al. discribed a "common soil" hypothesis that oxidative stress is the common pathogenesis of insulin resistance,diabetes and cardiovascular disease.but there are limited data about the correlation between oxidative stress and GDM. The pathophysiology of GDM is similar to type2diabetes. Research has shown increased the oxidation products in patients with GDM (lipid peroxide, nucleic acid, protein oxidation products), and reduced antioxidant capacity. We hypothesize that oxidative stress may be closely associated with GDM.But there are limited data ahout the correlation between oxidative stress and GDM.Advanced oxidation protein product (AOPP) is a new type of protein oxidatiion markers, is the final product of various proteins oxidation formed by oxidative stress. It is firstly found in the plasma of patients with chronic renal failure by Witko-Sarsat in1996, is a protein cross-linking protduct containing a pair of tyrosine.Its main component is the product of serum albumin reacting with free radicals and reactive oxygen system (mainly neutrophils myeloperoxidase chloride oxide). AOPP levels are increased in the oxidative stress related desorders. Studies have shown that plasma AOPP leves in the patients without dialysis would increase with the deterioration of renal function, AOPP leves in patients with end-stage renal disease are three times as much as normal people. AOPPs deposit in vessel wall existing pathological changes of atherosclerosis.Intravenous repeatedly, AOPPs can accelerate the formation of atherosclerotic plaque in the high cholesterol diet feeding rabbits. Studies suggest that AOPP may be an independent risk factor for atherosclerosis cardiovascular disease. AOPPs leves significantly higher in type2diabetes, some scholars found it is probably a useful indicator of protein oxidatiion in diabetes patient. Some scholars examined plasma AOPP leves in the patients with coronary heart disease diagnosed by coronary angiography,with HD and healthy volunteers, found that plasma AOPP leves in the patients with coronary heart disease diagnosed by coronary angiography,with HD are increased, and stay low in healthy volunteers. Also studies have shown that plasma AOPPs content is closely related with the severity of coronary heart disease, suggesting AOPPs may be involved in development and incidence of coronary heart disease (CHD). AOPPs are the product of oxidative stress, also can cause respiratory burst of neutrophil and monocyte, inducing mononuclear cells to product many more ROS, positively feedbacking oxidative stress, so that the body shows a continuous state of oxidative stress. Experiments in vitro showed AOPP can lead to endothelial cell damage, produce a large number of cytokines, increased oxidative stress.At present, limited data are available regarding AOPP levels in the normal pregnant women and patients with GDM both in domestic and forein. In this paper,through the Compare of AOPP leves in different weeks of pregnancy in normal pregnant women and patients with GDM, discussed the changing law of AOPP during normal pregnancy, and its correlation with GDM.ObjectiveTo analyze the variational law of AOPP at different gestational stages by investigating the leves of plasma AOPP during the second and third trimester of pregancy in normal pregnant women;to explore the assosiation between gestational diabetes mellitus (GDM) and AOPP by investigating the levels of AOPP in patiens with GDM,and further explore the role of AOPP in the process of GDM.MethodsA retrospective cohort study was conducted.From March to Novanber2012,400singleton pregnancy cases who accepted regular prenatal healthcare were enrolled. Among them,24incident GDM cases and168normal pregnant women were ascertained.The levels of AOPP at16-20gestational weeks,24-28gestational weeks,32-36gestational weeks were measured by spectroPhotometric.The levels of AOPP at different gestational stages were campared in normal pregnant women. The levels of AOPP were campared between GDM group and normal pregnanies group. Logistic regression was performed to demonstrate whether AOPP level is an independent factor for the prevelence of GDM. Bivariate correlation analysis was used to clear the association between plasma AOPP level and blood glucose level, glycosylated hemoglobin (HbAlc).The predictie values of sensitivity and specificity of AOPP were calculated by receiver operating characteristic curve.ResultsIn normal pregnant women, The plasmal AOPP level at24-28gestational weeks were significantly higher than those at16-20gestational weeks (P<0.05),the plasma AOPP level at32-36gestational weeks were significantly higher than those at16-20gestational weeks,24-28gestational weeks(P<0.05);(2)Compared with normal pregnancies,the levels of AOPP at16-20gestational weeks,24-28gestational weeks,32-36gestational weeks were all significantly incresced(P<0.05);(3)Logistic regression analysis showed that AOPP level is an independent factor for the prevelence of GDM; Bivariate correlation analysis showed that there were significant positive correlation between AOPP level and2-h plasma glucose, HbA1c levels in patient with GDM(P=0.000,P=0.000);The analysis of receiver operating characteristic curve demonstrated that the area under the curve for AOPP level was0.894(95%CI:0.832～0.957, P=0.000);0.826,(95%CI:0.728～0.925,P=0.000,respectively.ConclusionsAt second and third trimester, plasma AOPP levels were increased with the increase of gestational week in normal pregnant women, showed the imbalance between oxidation and antioxidant system may be enchanced gradually in middle-late pregnancy. The AOPP levels in patients with GDM were significantly higher than those in normal pregnant women, suggested AOPP may be assiosiated with GDM. The AOPP levels at16-20gestational weeks positively correlate with GDM, AOPP may be an independent risk factor for GDM, and has certain predictive value.