The Findings Of A Study Of Iron Metabolism And Gestational Diabetes

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with outset or first recognition during pregnancy. GDM is a frequent complication of pregnancy and is one of the leading causes of maternal and neonatal mortality and morbidity. Considering the classical views, insulin resistance may play an important role in pathogenesis and development of GDM. However, the pathogenic mechanism of further enhanced normal pregnancy-induced insulin resistance in GDM is not fully understood. Recently, increasing evidences suggest that iron, a transitional metal and a strong prooxidant, influence glucose metabolism. Increased serum ferritin (SF) concentration is independent risk factor for GDM. Since that, whether iron supplementation during pregnancy could increase the incidence of GDM? SF is the chief form in which iron is stored in the body. Whether SF could be considered as an effective indicator for the prediction and diagnosis of GDM? In this study, on the one hand, we examined the early second-trimester SF levels in women with GDM and healthy pregnancy controls to evaluate the value of SF in predicting GDM; on the other hand, we detected changes in glucose metabolism and expression of GLUT4, which could reflect the situation of whole-body insulin resistance, in adipose tissue and skeletal muscle of pregnant rats with iron supplementation, to investigate the role of iron supplementation during pregnancy in the occurrence of GDM.Section1The value of early second-trimester serum ferritin level in predicting gestational diabetes mellitusObjective To estimate the ability of maternal serum ferritin (SF) in the early second trimester to predict the occurrence of gestational diabetes mellitus (GDM).Methods From January2008to July2009,41GDM patients (experimental group) and42non-GDM patients (control group) who underwent screening for Down’s syndrome and were delivered in Obstetrics and Gynecology Hospital of Fudan University, were studied retrospectively. The basic clinical characteristics, SF levels during15-20gestational weeks and fasting plasma glucose (FPG) during24-28gestational weeks, were analyzed. The value of early second-trimester SF levels in predicting GDM was evaluated by receiver operating characteristic (ROC) curve.Results (1) The mean level of SF in the early second trimester and concentration of FPG during24-28gestational weeks were (230.59±97.93)μg/L and (5.77±0.92)mmol/L respectively in GDM group, which were significantly higher than the levels found in the control group [(108.05±34.54)μg/L and (4.02±0.35)mmol/L, t=-7.566and t=-11.369, P=0.000].(2) The correlation analysis revealed that SF levels in the GDM pregnancies were positively associated with the levels of FPG during24-28gestational weeks (γ=0.390,P=0.012) and the weight of neonates (r=0.434, P=0.005).(3) Multiple stepwise regression analysis showed that SF level was still positively associated with FPG and neonatal birth weight (BW)(FPG=0.312+0.131SF+0.006Hb; BW=0.508+0.542SF) in GDM group.(4) Receiver operating characteristic curve analysis showed that the area under the curve (AUC) was0.921(P=0.000). When the cut-off value of SF was=148.94μg/L, the sensitivity and specificity in assessing the incidence of GDM were80%and90%, respectively.Conclusions SF level in the early second trimester has predictive value for the diagnosis of GDM.Section2Effect of Iron Supplementation on Glucose Transporter4Expression in Adipose Tissue and Skeletal Muscle of Pregnant RatsObjective To evaluate the glucose metabolism profiles and the expression of GLUT4in adipose tissue and skeletal muscle from pregnant rats with iron supplementation and basic diet controls in order to investigate the relationship between iron supplementation during pregnancy and GDM.Methods The pregnant rats were allotted randomly to either an iron supplementation group (n=12) with high-iron diet (700mg/kg) or a control group (n=12) with basic diet (150mg/kg). Feed intake, body weight gain and information of neonatal rats were recorded. Intraperitoneal glucose tolerance test was performed after overnight (12-14h) fasting on gestational day (GD)20. The samples for measurement were obtained after general anesthesia on GD21. Levels of SI、TIBC, expression of GLUT4mRNA and protein were examined using ELISA、RT-PCR and western blot, respectively.Results There were no significant differences of feed intakes and the number of pups born per litter between iron supplementation and control group (P>0.05), but the body weight gain is lower in iron supplementation rats (P=0.003) and the neonatal weight is higher in iron supplementation group (P=0.000). The glucose utilization was significantly lower in iron supplementation group than that in control group. In iron supplementation group, the SI level is significantly higher (P=0.000) and the TIBC level is significantly lower (P=0.006). The expression of GLUT4mRNAand protein in adipose tissue of pregnant rats were lower with iron supplementation (P=0.000, P=0.000). But in skeletal muscle, we found this decreasing only in the expression of GLUT4mRNA (P=0.000), not in the GLUT4protein (P>0.05)Conclusions Iron supplementation during pregnancy may cause a disturbance in glucose metabolism. It could lead to or alleviate insulin resistance and play a role in the occurrence and development of GDM.