Role Of NGAL In The Gestational Diabetes Mellitus And Pre-eclampsia

Neutrophil gelatinase-associated lipocalin (NGAL), also known as Lipocalin-2and24p3, is a25-kDa secretory glycoprotein, which belongs to the lipocalin family. NGAL is expressed in many tissues and cells, including the neutrophil granules adipocytes, liver cells, kidney cells, epithelial cells and macrophages. NGAL was identified more than a decade ago, however, the physiologic functions of this protein remain poorly understood. Previous studies have focused on the role of this protein in the innate immune response to bacterial infection and in apoptosis. Recently, NGAL, as a member of adipokines, is highly expressed in adipocytes and that it induces insulin resistance. It has been demonstrated that NGAL may be involved in the developing of dyslipidemia, insulin resistance, chronic low-lever inflammation and type2diabetes mellitus. Furthermore, numerous studies confirm that NGAL is an early indicators of endothelial injury and renal failure. However, there is few data on NGAL and human pregnancy, and human pregnancy is exactly a condition characterized by increased insulin resistance.Gestational diabetes mellitus (GDM) and pre-eclampsia (PE) are the two major pregnancy complications which seriously endangers the safety of mother and fetal during pregnancy. Insulin resistance and systemic small vessel spasm are their physiopathologic basis, respectively. However, the pathogenesis of GDM and PE are not yet clear. Over the last few years’study, the discovery that some adipokines were key players in the regulation of insulin action suggested possible roles of the placenta and adipose tissue in understanding pregnancy-induced insulin resistance. Moreover, researchers have generally agreed that the systemic activation and injury of maternal endothelial cells which bring about a variety of clinical symptoms such as high pressure, protein urine, systemic inflammatory response is the central pathogenesis of PE. In the view of the relationship between NGAL、insulin resistance and endothelial injury, the aim of our study is1) To investigate second trimester serum NGAL concentrations in the pregnant women with glucose metabolism disorder and its relationship with insulin resistance, and the prediction values of NGAL for GDM.2) to explore the expression of NGAL in the second trimester of PE patients, and explore the relationship between NGAL and disease severity by combined with the clinical features. We also evaluate whether NGAL may be useful early maker in predicting PE.Section1The Correlation Study on NGAL and GDM Objective:To investigate second trimester serum NGAL concentrations in the pregnant women with glucose metabolism disorder and its relationship with insulin resistance and GDM.Methods:From a cohort of pregnant outpatients who participated in a screening program for Down’s syndrome at14-18weeks of gestation, we considered all84women with a singleton pregnancy, who developed gestational diabetes mellitus (GDM)(n=42) and impaired glucose tolerance (IGT)(n=42) respectively in the previous24months. Circulating NGAL, total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and insulin resistance by homeostasis model assessment ratio (HOMA-IR) were determined in the second trimester.Results:Serum NGAL concentrations were higher in the GDM [(45.83±6.93) ng/ml] and IGT [(28.55±6.30) ng/ml] groups compared with the control group [(19.72±5.77) ng/ml,(P<0.001)]. HOMA-IR was the only covariates that were independently and positively correlated with NGAL concentrations (beta=0.699, P<0.000; R2=0.625). The correlation coefficient of serum NGALand disease severity was0.851(P<0.000).Conclusions:Serum NGAL levels were significantly higher in the women with GDM than normal pregnant controls in the second trimester of pregnancy, which is the significant independent predictor of insulin resistance. There was a significant important correlation between the NGAL and severity of glucose metabolism disorder.Section2The Correlation Study on NGAL and Pre-eclampsiaObjective:To investigate second trimester serum NGAL concentrations in PE patients and the prediction values of NGAL for PE.Methods:From a cohort of pregnant outpatients who participated in a screening program for Down’s syndrome at14-18weeks of gestation, we considered all38women with a singleton pregnancy, who developed pre-eclampsia in the previous21months,and17women were severe pre-eclampsia. Circulating NGAL was determined by quantitative sandwich enzyme immunoassay in the second trimester. A receiver operating characteristics (ROC) curve was used to measure the prediction values of NGAL for PE.Results:Serum NGAL concentrations were significantly increased in the PE compared to the control women:[(41.81±14.21)ng/ml vs.(21.14±6.85) ng/ml, P<0.000], and were positively correlated to blood pressure and proteinuria (P=0.000). The correlation coefficient of serum NGALand disease severity was0.718(P<0.000). ROC curve analysis showed an AUC of0.912(P=0.000,95%CI:0.846-0.978) for NGAL in the prediction of GDM. A cut-off NGAL level of28.94ng/ml yielded a high sensitivity (81.6%) and a high specificity (89.5%).Conclusions:Compared with the normal pregnant women, the PE patients had a high level of serum NGAL, especially the severe PE patients. There was a significant important correlation between the NGAL and severity of the PE. NGAL is a good marker to predict the occurrence and development of the PE.