Soluble CD163: a biomarker linking macrophages and insulin resistance

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. 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). 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 ( < 0.0001). In univariate analyses, sCD163 correlated significantly with HOMA-IR ( = 0.44), insulin ( = 0.41), glucose ( = 0.30), triacylglycerol ( = 0.29) and HDL-cholesterol ( = -0.34) (all < 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-alpha and IL-6 (all a parts per thousand currency signaEuro parts per thousand 0.0001). An increase of 50% in sCD163 resulted in an estimated increase in HOMA-IR of 36% (95% CI 26, 48; < 0.0001). In multiple linear regression analyses, sCD163 ( = 0.001) and CRP ( = 0.01) remained independent predictors of HOMA-IR, whereas TNF-alpha and IL-6 did not. Macrophage-specific sCD163 was strongly associated with insulin resistance independently of TNF-alpha and other predictors. Moreover, sCD163 was associated with well-known variables of the metabolic syndrome.