Gestational diabetes mellitus (GDM) is characterized by glucose intolerance that is caused by metabolic changes during pregnancy, and is considered a risk factor for the occurrence of DM in future. There are studies that reported changes in the cytokine in women with GDM. The concentration of serum IFN-γ and adiponectin decreased, while serum leptin, IL-6, IL-10, and TNF-α increased in GDM women when compared to that in healthy pregnant women. 16 17 Placenta and adipose tissues from patients with GDM released higher amounts of TNF-α in response to high glucose than that from normal pregnant women.18 Plasma TNF-α were reported to be low during the first and second trimester, but it increased during late pregnancy, and was inversely correlated with the insulin sensitivity. 19, 20 However, the relationship between GDM and the functions of NK cells in pregnant women has not been clarified so far. The purpose of this study was to evaluate the expression of peripheral blood NK (pNK) cell surface markers (CD16, NKp46, and NKp30) and the percentage of cytokine (IFN-γ, TNF-α, TGF-β, and VEGF) producing pNK cells in women with / without GDM at 12 weeks of pregnancy.
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Materials and Methods
Study SubjectsWe designed a prospective study and patients from Hirosaki University Hospital were recruited for this study between July 2014 and March 2015. This study was approved by the local ethics committee, and signed informed consent forms were obtained from all study subjects. Blood samples were collected during routine blood tests for prenatal check-up at 12weeks of gestation.Thirty-four Japanese women (GDM (n=7), non-GDM (n=27)) with singleton pregnancy were included. All GDM patients were diagnosed at 12 to 16 weeks of gestation. Pregnant women with multi-fetal gestations, pre-gestational diabetes, and overt diabetes were excluded, while pregnant women with impaired glucose tolerance before the onset of pregnancy were included in this study. Maternal and neonatal characteristics are shown in Table 1. Two-hour-glucose level of 75-g OGTT in GDM group was significantly higher than that in the non-GDM group.There were no complications reported in the newborn infants (such as macrosomia, shoulder dystocia, and hypoglycemia) in both the GDM and non-GDM groups and there were no pregnant women suffering from PE in both the GDM and non-GDM groups.
Screening of GDMAll pregnant women were subjected to a two-step screening method for GDM. This screening method is based on the Guideline for Obstetrical Practice in Japan 2014. 21 Briefly, women who had a random plasma glucose level of ≥95mg/dl at 12 weeks of gestation were subjected to 75-g OGTT after fasting overnight. Diagnosis of GDM was based on the criteria of one or more abnormal values [fasting ≥92mg/dl (5.1mmol/l), such as 1 hour ≥180mg/dl (10.0mmol/l) or 2 hour ≥153mg / dl (8.5mmol/l)] reported for the subjects. Pregnant women, not diagnosed as GDM at 12 weeks of screening, were again subjected to random blood glucose measurement at 3 28 weeks of gestation. Women with random...
