Serum Soluble CD163 Predicts Risk of Type 2 Diabetes in the General Population

BACKGROUND: Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease has developed. METHODS: A prospective cohort study of 8849 study participants from the general population, the Copenhagen City Heart Study, was followed for 18 years for incidence of type 2 diabetes. Risk of disease was calculated according to age- and sex-adjusted percentile categories of serum sCD163 concentrations: 0%-33%, 34%-66%, 67%-90%, 91%-95%, and 96%-100%. RESULTS: A total of 568 participants developed type 2 diabetes. The cumulative incidence increased with increasing baseline sCD163 (trend P < 0.001), and sCD163 was strongly associated with known risk factors such as physical inactivity, body mass index, C-reactive protein, and triglycerides (all P < 0.001). Multifactorially adjusted hazard ratios for type 2 diabetes were 1.4 (95% CI, 1.0-1.9), 2.4 (1.8-3.2), 3.8 (2.6-5.5), and 5.2 (3.6-7.6) for categories 34%-66%, 67%-90%, 91%-95%, and 96%-100%, respectively, vs the 0%-33% category. In overweight men 50-70 and >70 years of age, serum sCD163 concentrations in the top 5% group predicted an absolute 10-year risk of type 2 diabetes of 29% and 36% vs 7% and 8% in the lowest percentile group. Equivalent values in women were 19% and 24% vs 4% and 5%. CONCLUSIONS: Increased concentrations of sCD163 predict increased risk of type 2 diabetes in the general population and may be useful for identification of high-risk overweight individuals.