Background <p>Diabetic retinopathy and diabetic nephropathy are major microvascular complications of type 2 diabetes mellitus and may progress silently before clinical detection. Plasma glycated CD59 has been proposed as a marker linked to complement-mediated endothelial injury. This study assessed plasma glycated CD59 levels in type 2 diabetic patients with retinopathy, nephropathy, and combined microvascular complications.</p> Methods <p>This cross-sectional observational study included 420 patients with type 2 diabetes mellitus. Participants were divided into four groups: diabetes without microvascular complications (<i>n</i> = 110), diabetic retinopathy alone (<i>n</i> = 105), diabetic nephropathy alone (<i>n</i> = 95), and combined diabetic retinopathy with nephropathy (<i>n</i> = 110). Clinical history, diabetes duration, fasting plasma glucose, glycated haemoglobin, serum creatinine, estimated glomerular filtration rate, urine albumin-creatinine ratio, and plasma glycated CD59 were assessed. Retinopathy was graded by fundus examination, and nephropathy was classified using albuminuria and renal function parameters.</p> Results <p>The mean age was 56.8 ± 9.4 years, and the mean diabetes duration was 8.9 ± 5.1 years. Plasma glycated CD59 was highest in patients with combined retinopathy and nephropathy (12.8 ± 3.6 AU/mL), followed by nephropathy alone (10.4 ± 2.9 AU/mL), retinopathy alone (9.6 ± 2.7 AU/mL), and diabetes without complications (6.2 ± 1.8 AU/mL). Plasma glycated CD59 correlated positively with glycated haemoglobin (<i>r</i> = 0.46, <i>p</i> &lt; 0.001) and urine albumin-creatinine ratio (<i>r</i> = 0.52, <i>p</i> &lt; 0.001), and negatively with estimated glomerular filtration rate (<i>r</i> = -0.41, <i>p</i> &lt; 0.001). Higher levels were observed in proliferative diabetic retinopathy and macroalbuminuria. On multivariate analysis, plasma glycated CD59 remained independently associated with combined microvascular complications.</p> Conclusion <p>Plasma glycated CD59 levels were higher in patients with type 2 diabetes who had microvascular complications, particularly in those with both diabetic retinopathy and diabetic nephropathy. These findings indicate that plasma glycated CD59 may be useful as an additional marker for assessing the burden of diabetic microvascular disease. However, as the study was cross-sectional, the results should not be interpreted as evidence of causation or prediction. Further prospective studies are needed to confirm its clinical usefulness.</p>