title: Serum sTWEAK concentrations and risk of developing type 2 diabetes in a high cardiovascular risk population: a nested case-control study.
abstract: OBJECTIVE
  Because serum concentrations of soluble forms of TNF-like weak inducer of apoptosis (sTWEAK) and scavenger receptor CD163 (sCD163) have been associated with insulin resistance and type 2 diabetes mellitus (T2D), we tested the associations of sTWEAK and sCD163 with the future development of T2D in elderly subjects at high cardiovascular risk.
  
  
  METHODS
  A prospective, matched case-control study of 153 cases of newly diagnosed diabetic subjects and 306 individually matched controls who did not develop diabetes during a mean 5-year follow-up was conducted using data from the PREDIMED study. Conditional logistic regression was used to estimate the matched odds ratio (OR) for incident T2D according to categories of baseline sTWEAK and sCD163 concentrations measured by ELISA.
  
  
  RESULTS
  Baseline sTWEAK concentrations were lower in cases than controls. There were no case-control differences in sCD163 concentrations. In the conditional logistic model that took into account the matching factors, the ORs for T2D incidence in the highest vs the lowest quartile of sTWEAK and the sCD163/sTWEAK ratio were 0.49 (95% confidence interval [CI], 0.31-0.76; P for trend <.01) and 1.67 (95% CI, 1.06-2.63; P for trend = .05), respectively. Further adjustment for potential lifestyle confounding factors had little impact on these estimates, whereas adjustment for metabolic syndrome components and fasting insulin levels attenuated the magnitude of associations and only the sTWEAK remained statistically significant (OR = 0.63; 95% CI, 0.40-0.98; P for trend = .05).
  
  
  CONCLUSIONS
  These findings indicate that in a population at high cardiovascular risk, reduced circulating levels of sTWEAK are associated with an increased risk of diabetes incidence.
authors.affiliation: Human Nutrition Unit, Faculty of Medicine and Health Sciences, IISPV, Universitat Rovira i Virgili, 43201 Reus, Tarragona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Díaz-López
authors.forename: Matilde R
authors.initials: MR
authors.lastname: Chacón
authors.forename: Mònica
authors.initials: M
authors.lastname: Bulló
authors.forename: Elsa
authors.initials: E
authors.lastname: Maymó-Masip
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: Josep
authors.initials: J
authors.lastname: Basora
authors.forename: Javier
authors.initials: J
authors.lastname: Díez-Espino
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Covas
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D016022:Case-Control Studies; D000074049:Cytokine TWEAK; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood; D012306:Risk; D048069:Tumor Necrosis Factors / Q000097:blood*; 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