The Relationship of the Plasma Glycated CD59 Level with Microvascular Complications in Diabetic Patients and Its Evaluation as a Predictive Marker.

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease characterized by chronic hyperglycemia and progressive microvascular complications, including retinopathy, nephropathy, and neuropathy. While traditional markers like HbA1c capture average glycemic control, they often fail to predict microvascular damage risk. Glycated CD59 (GCD59), a complement regulatory protein modified under hyperglycemic conditions, has emerged as a promising biomarker reflecting complement dysregulation and endothelial injury. This study aimed to examine the relationship between plasma GCD59 levels and the presence of microvascular complications in patients with type 2 diabetes mellitus and to evaluate whether GCD59 shows potential for future use as a predictive biomarker, pending prospective validation. In this single-center, prospective case-control study, 246 participants were enrolled: 82 healthy controls, 82 T2DM patients without microvascular complications (DM - MC), and 82 T2DM patients with microvascular complications (DM + MC). Microvascular complications were defined based on standardized criteria for retinopathy, nephropathy, and neuropathy. Plasma GCD59 levels were measured using validated ELISA methods. Receiver operating characteristic (ROC) analyses, forest plots, and odds ratio calculations were employed to assess the discriminatory performance of GCD59. Statistical significance was set at < 0.05. Plasma GCD59 levels were significantly elevated across all diabetic groups compared to healthy controls ( < 0.001), with the highest levels in the DM + MC group (median 4.5 ng/mL) versus DM - MC (median 1.9 ng/mL) and controls (median 1.2 ng/mL). ROC analysis demonstrated excellent diagnostic performance for distinguishing DM + MC from healthy controls (AUC = 0.946, sensitivity 89%, specificity 97.6%) and good performance for distinguishing DM + MC from DM - MC (AUC = 0.849, sensitivity 72%, specificity 87.8%). Forest plot analyses confirmed significantly elevated odds ratios for GCD59 across all microvascular subgroups. Importantly, GCD59 levels correlated positively with inflammatory markers (CRP, ESR, leukocyte count), suggesting a combined role of complement dysregulation and chronic inflammation in diabetic microangiopathy. Plasma GCD59 may be a promising biomarker for identifying T2DM patients who may be at increased risk for microvascular complications, independent of conventional glycemic markers. Given the cross-sectional design of this study, causal inference is not possible; prospective validation is required. The observed strong discriminatory performance highlights potential future clinical utility, pending further validation of diagnostic thresholds, assay standardization, and feasibility in routine care settings.