title: Circulating milk fat globule-epidermal growth factor 8 levels are increased in pregnancy and gestational diabetes mellitus.
abstract: OBJECTIVE
  Milk fat globule-epidermal growth factor 8 (MFG-E8) is the key mediator in anti-inflammatory responses that facilitate phagocytosis of apoptotic cells, and play an essential role in type 2 diabetes and pregnancy, both of which are under a low-grade inflammatory state. However, the action of MFG-E8 in gestational diabetes mellitus (GDM) is unclear. We measured plasma MFG-E8 levels in pregnancy and GDM for the first time, and elucidated possible relationships between its plasma levels and various metabolic parameters.
  
  
  METHODS
  Plasma MFG-E8 levels were quantified by enzyme-linked immunosorbent assay in 66 women with GDM, 70 with normal pregnancy (p-NGT) and 44 healthy non-pregnant controls (CON), who were matched for age and body mass index. Inflammatory factors tumor necrosis factor-α (TNF-α) and C-reactive protein levels were measured, oral glucose tolerance test was carried out and β-cell function was evaluated.
  
  
  RESULTS
  Plasma MFG-E8 levels were remarkably higher in p-NGT than in CON (P = 0.024), and were further elevated in GDM vs p-NGT (P = 0.016). MFG-E8 concentrations correlated positively with hemoglobin A1c, glucose levels and insulin resistance (homeostasis model assessment for insulin resistance), and correlated inversely with TNF-α and insulin secretion evaluated by disposition indices in pregnancies. Fasting glucose levels, disposition index of first phase insulin secretion and TNF-α were independent predictors of MFG-E8 levels in pregnancies. Logistic regression analyses showed that women in the third tertile of MFG-E8 levels had a markedly elevated risk of GDM.
  
  
  CONCLUSIONS
  Circulating MFG-E8 levels are dramatically elevated in pregnancy, and are significantly higher in GDM vs p-NGT. MFG-E8 concentrations are significantly associated with TNF-α, fasting glucose levels, homeostasis model assessment for insulin resistance and disposition indices. However, further studies are required to elucidate the regulation mechanism of MFG-E8 during pregnancy and GDM.
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Wenzhuo
authors.initials: W
authors.lastname: Ran
authors.affiliation: Department of Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Luo
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000097:blood*; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D016015:Logistic Models; D008894:Milk Proteins / Q000097:blood*; D011247:Pregnancy
chemical_list: D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins
keywords: Gestational diabetes mellitus; Inflammation; Milk-fat globule-epidermal growth factor 8