Reduced circulating levels of TWEAK are associated with Gestational Diabetes Mellitus

• Published in: European journal of clinical investigation Vol. 45; no. 1; pp. 27 - 35
• Main Authors: Simón-Muela, Inmaculada, Llauradó, Gemma, Chacón, Matilde Rodriguez, Olona, Montserrat, Näf, Silvia, Maymó-Masip, Elsa, Gil, Pilar, de la Flor, Miriam, Gonzalez Clemente, Jose Miguel, Vendrell, Joan, Megía, Ana
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2015
• Subjects: Adult; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Case-Control Studies; Cytokine TWEAK; Diabetes, Gestational - etiology; Female; Gestational diabetes mellitus; Humans; insulin resistance; Insulin Resistance - physiology; low-grade inflammation; Pregnancy; Prospective Studies; Receptors, Cell Surface - metabolism; Regression Analysis; sTWEAK; Tumor Necrosis Factors - deficiency; Gestational diabetes mellitus; low-grade inflammation; sTWEAK; insulin resistance
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.12375

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). Materials and 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 (R2 = 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.