title: Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans.
abstract: Elevated plasma IL-18 is present in several conditions sharing insulin-resistance as common trait, but the association with insulin-resistance per se is not established. Plasma/serum IL-6, IL-18, TNF-alpha, soluble TNF receptor II (sTNFR2), and C-reactive protein (CRP) were measured in 97 patients with type 2 diabetes (DM) and 84 non-diabetic controls (CON). The association with insulin-resistance-estimated using the homeostasis model assessment (HOMA-IR)-was analyzed using multivariate linear and logistic regression. Compared to CON, DM demonstrated higher plasma levels of IL-18 (P = 0.001), IL-6 (P < 0.001), sTNFR2 (P = 0.005), and CRP (P < 0.001), while TNF-alpha was lower (P = 0.017). Plasma IL-18 increased across HOMA-IR quartiles in both DM and CON, both with and without adjustment for confounders (all P < 0.05). In contrast, neither IL-6, TNF-alpha, sTNFR2, nor CRP was associated with HOMA-IR in CON when adjusting for confounders. Accordingly, 50% increase of IL-18 corresponded to a marked increase of HOMA-IR in both DM and CON (DM: 26%, P = 0.014; CON: 25%, P = 0.003) after adjustment for confounders. Our results show that plasma IL-18 was associated with HOMA-IR independent of obesity and type 2 diabetes.
authors.affiliation: Centre of Inflammation and Metabolism, The Department of Infectious Diseases and The Copenhagen Muscle Research Centre, Rigshospitalet and The Faculty of Health Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark. cfischer@dadlnet.dk
authors.forename: Christian P
authors.initials: CP
authors.lastname: Fischer
authors.forename: Lisbeth B
authors.initials: LB
authors.lastname: Perstrup
authors.forename: Annika
authors.initials: A
authors.lastname: Berntsen
authors.forename: Peter
authors.initials: P
authors.lastname: Eskildsen
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D020382:Interleukin-18 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D020382:Interleukin-18; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein