title: Reduced circulating levels of TWEAK are associated with gestational diabetes mellitus.
abstract: BACKGROUND
  To evaluate the inflammatory axis mediated by tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its scavenger receptor CD163 during pregnancy and their influence on insulin sensitivity in normal pregnancy and in gestational diabetes mellitus (GDM).
  
  
  METHODS
  One hundred and thirty seven women with one singleton pregnancy, 71 with normal glucose tolerance (NGT) and 66 with GDM were studied. Glucose metabolism was assessed by oral glucose tolerance test. Serum concentrations of soluble TWEAK (sTWEAK) and CD163 (sCD163) and insulin resistance (HOMA-IR index) were determined in maternal blood drawn at recruitment, in the early third trimester. Offspring weight and height were assessed at birth.
  
  
  RESULTS
  Women with GDM had lower circulating sTWEAK concentrations than control NGT group (237·8 (192·1-301·0) pg/mL vs. 277·2 (206·4-355·7) pg/mL; P = 0·013). sTWEAK was negatively associated with the presence of GDM (r = -0·212; P = 0·013), HOMA-IR index (r = -0·197; P = 0·021) and ponderal index of the newborn (r = -0·196; P = 0·025), but positively with HDL cholesterol (r = 0·283; P = 0·001). In multiple regression analysis, sTWEAK concentration emerged as one of the main predictors of insulin resistance, along with BMI, triglycerides and low concentrations of HDL cholesterol (R(2)  = 0·486; P < 0·001). No relationship was found between HOMA-IR index and sCD163 or sCD163/sTWEAK ratio.
  
  
  CONCLUSIONS
  sTWEAK concentrations are lower in patients with GDM compared with healthy pregnant women, and low concentrations of sTWEAK are associated with insulin resistance. These findings suggest that insulin resistance during pregnancy is closely linked to inflammatory imbalance and sTWEAK may represent a new candidate associated with GDM.
authors.affiliation: Endocrinology, Diabetes and Nutrition Section, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili, Tarragona, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Simón-Muela
authors.forename: Gemma
authors.initials: G
authors.lastname: Llauradó
authors.forename: Matilde Rodriguez
authors.initials: MR
authors.lastname: Chacón
authors.forename: Montserrat
authors.initials: M
authors.lastname: Olona
authors.forename: Silvia
authors.initials: S
authors.lastname: Näf
authors.forename: Elsa
authors.initials: E
authors.lastname: Maymó-Masip
authors.forename: Pilar
authors.initials: P
authors.lastname: Gil
authors.forename: Miriam
authors.initials: M
authors.lastname: de la Flor
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Gonzalez Clemente
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Ana
authors.initials: A
authors.lastname: Megía
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D000074049:Cytokine TWEAK; D016640:Diabetes, Gestational / Q000209:etiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D011247:Pregnancy; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000378:metabolism; D012044:Regression Analysis; D048069:Tumor Necrosis Factors / Q000172:deficiency*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D000074049:Cytokine TWEAK; D011956:Receptors, Cell Surface; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors
keywords: Gestational diabetes mellitus; insulin resistance; low-grade inflammation; sTWEAK