Glycation of the Complement Regulatory Protein CD59 Is a Novel Biomarker for Glucose Handling in Humans

Context: Human CD59, an inhibitor of the membrane attack complex of complement, is inactivated by glycation. Glycation inactivation of CD59 enhances complement-mediated injury in target organs of diabetes complications. Objective: We hypothesized that circulating soluble glycated CD59 (GCD59) represents a novel biomarker of blood glucose handling and aimed to conduct human study protocols to test this hypothesis. Design, Setting, Participants, and Outcome Measures: Using a newly developed ELISA, we measured circulating soluble GCD59 in samples from 3 separate human studies evaluating acute and chronic glucose handling and glucose responses to insulin therapy. Study 1 (normal vs diabetic subjects) evaluated the cross-sectional association between GCD59 and glycated hemoglobin (HbA1c) in 400 subjects with and without type 2 diabetes. Study 2 (oral glucose tolerance test [OGTT] in nondiabetics) evaluated whether fasting GCD59 independently predicted the 2-hour glucose response to an OGTT in 109 subjects with...