Experimental And Clinical Study About Gestational Diabetes Induced Maternal And Neonatal Complications

Background Gestational diabetes mellitus (GDM) is associated with long-term cardiovascular and metabolic diseases in offspring. However, the mechanisms are not well understood. It is hypothesized that impaired endothelial function may play a role. Vitamin D3deficiency is common in pregnant women and it is associated with an increased risk for GDM. In vitro study has found that vitamin D3stimulates endothelial colony forming cell (ECFC) angiogenic function. Thus, we explored whether fetal exposure to a gestational diabetic environment is associated with its ECFCs dysfunction, and whether vitamin D can reverse the impairment.Methods Nineteen women with uncomplicated pregnancies (NP) and18women with GDM were recruited before delivery. ECFCs were isolated from cord blood. Time to first appearance of ECFCs colonies and number of ECFC colonies formed from culture of cord peripheral blood mononuclear cells were determined.25-OH vitamin D3in maternal and cord blood and HbAlc in maternal blood were detected. In vitro experiments with hyperglycemia were performed with ECFCs obtained from NP. A mild hyperglycemic environment was created by incubation with7,11and15mM glucose for7days compared to5.5mM glucose as control. Functions of endothelial cells, e.g. population doubling time, migration and tubule formation were tested in ECFCs with the presence or absence of10nM vitamin D3. Comparisons were performed between GDM and NP or between hyperglycemic treatment and control in NP. Vitamin D receptor silencing (VDR siRNA), blocking (P5P) and VEGF inhibition (SU5416) were also performed in ECFCs from NP and GDM pregnancies.Results Neonatal ECFCs from GDM pregnancies formed fewer colonies in culture (P=0.04) and displayed reduced proliferation (P=0.02), migration (P=0.04) and tubule formation (P=0.03) compared to uncomplicated pregnancies. Neonatal ECFCs exposed to hyperglycemia in vitro exhibited less migration (P<0.05) and less tubule formation (P<0.05) than normoglycemic control. This effect was concentration dependent (P<0.05). Vitamin D significantly improved the dysfunction of neonatal ECFCs from pregnancies complicated by GDM or after exposure of healthy ECFCs to hyperglycemia (P<0.05). There was no significant difference between hyperglycemia and control except15mM glucose treated group. After treatment with VDR siRNA, P5P and SU5416, both GDM-and NP-ECFCs showed reduced migration and tubule formation (P<0.05). Addition of vitamin D3reversed the inhibitory effect, except the tubule formation in GDM-ECFCs treated with SU5416.Conclusions Neonatal ECFCs from GDM pregnancies or NP-ECFCs exposed to hyperglycemia in vitro exhibit impaired quantity and angiogenesis-related functions. Even mild hyperglycemia can adversely affect endothelial cell function and might therefore lead to cardiovascular complications in mothers and offspring of women with pregnancies complicated by GDM. The results of VDR-silencing and-blocking suggest that non-VDR-mediated signals are also involved in the functional responses of endothelial cells. The beneficial effect of vitamin D3seems more valid in milder hyperglycemic conditions prevalent in many GDM pregnancies, as vitamin D3could not rescue ECFC function at15.0mmol/L glucose. Given that vitamin D3deficiency is common during pregnancy we propose that avoidance of hypovitaminosis D would favorably impact ECFC function, maternal and fetal outcomes and possibly long-term endothelial health. Background Diabetes and gestational diabetes are associated with various adverse maternal and fetal outcomes. The purposes of this study were to explore whether the maternal-fetal outcomes differed among various types of hyperglycemia during pregnancy and whether the values of glycemic screening in the middle phase of pregnancy could predict maternal-fetal outcomes.Methods A retrospective study was conducted to study the incidence of maternal-fetal outcomes in383singleton pregnant women with diabetes or gestational diabetes admitted to our hospital from November2007to March2013. Patients were divided into three groups:prepregnant DM (pDM, Type1and Type2diabetes mellitus) group, GDM (gestational diabetes mellitus) group and DM (diabetes mellitus detected during pregnancy) group. Maternal basic clinical characteristics, results of oral glucose tolerance test (OGTT), antenatal random glycemia and maternal-fetal outcomes were collected. Binary logistic regression was used to estimate the association of blood glucose with the maternal-fetal outcomes. Predictive accuracy was assessed by calculating the areas under the receiver operating characteristic curves.Results The maternal basic clinical characteristics, maternal complications and neonatal complications did not differ significantly between pDM group and DM group, except neonatal intensive care units (NICU) admission. Incidences of preterm, NICU and preeclampsia were significantly lower in the GDM group than in the pDM and DM groups (P<0.05). After adjusted by confounding factors, the value of OGTT0h could predict gestational hypertension (OR=1.24,95%CI [1.04to1.46], P=0.015), preterm birth (OR=1.23,95%CI [1.03to1.47], P=0.025) and stillbirth (OR=1.55,95%CI [1.14to2.10], P=0.005); antenatal random glycemia could predict preterm birth (OR=1.19,95%CI [1.08to1.31], P<0.001) and stillbirth (OR=1.41,95%CI [1.17to1.71], P<0.001).Conclusions Pregnant women in the GDM group have better outcomes than those in the pDM and DM groups. The outcomes in pDM and DM groups are similar. The values of OGTT in the middle phase of pregnancy and antenatal random glycemia could predict gestational hypertension, preterm birth or stillbirth to some extent.