title: Soluble CD163: a biomarker linking macrophages and insulin resistance.
abstract: OBJECTIVE
  Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance.
  
  
  METHODS
  This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance (IGT) and 104 with normal glucose tolerance (NGT), matched for sex and BMI. Glucose-lowering medication was paused for 1 week before plasma samples were obtained for determination of sCD163 and other inflammatory and metabolic variables. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR).
  
  
  RESULTS
  Concentrations of sCD163 were 1.95 mg/l (0.63-6.97) in individuals with type 2 diabetes, 1.64 mg/l (0.58-4.19) in those with IGT, and 1.48 mg/l (0.48-4.11) (median [range]) in those with NGT (p < 0.0001). In univariate analyses, sCD163 correlated significantly with HOMA-IR (R = 0.44), insulin (R = 0.41), glucose (R = 0.30), triacylglycerol (R = 0.29) and HDL-cholesterol (R = -0.34) (all p < 0.0001). All but glucose remained significant when adjusting for age, sex, BMI and glycaemic group. In univariate regression analyses, HOMA-IR was associated with sCD163, C-reactive protein (CRP), TNF-α and IL-6 (all p ≤ 0.0001). An increase of 50% in sCD163 resulted in an estimated increase in HOMA-IR of 36% (95% CI 26, 48; p < 0.0001). In multiple linear regression analyses, sCD163 (p = 0.001) and CRP (p = 0.01) remained independent predictors of HOMA-IR, whereas TNF-α and IL-6 did not.
  
  
  CONCLUSIONS
  Macrophage-specific sCD163 was strongly associated with insulin resistance independently of TNF-α and other predictors. Moreover, sCD163 was associated with well-known variables of the metabolic syndrome.
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Norrebrogade 44, 8000, Aarhus C, Denmark. tparkner@dadlnet.dk
authors.forename: T
authors.initials: T
authors.lastname: Parkner
authors.forename: L P
authors.initials: LP
authors.lastname: Sørensen
authors.forename: A R
authors.initials: AR
authors.lastname: Nielsen
authors.forename: C P
authors.initials: CP
authors.lastname: Fischer
authors.forename: B M
authors.initials: BM
authors.lastname: Bibby
authors.forename: S
authors.initials: S
authors.lastname: Nielsen
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: H J
authors.initials: HJ
authors.lastname: Møller
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000097:blood* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha