PLASMA THROMBOMODULIN CONCENTRATION IN DIABETES-MELLITUS

Thrombomodulin is an endothelial cell membrane protein acting as a cofactor for the activation of plasma protein C. Recently, it was found that soluble forms of thrombomodulin exist in plasma. Although the physiological significance of circulating thrombomodulin is presently obscure, it may reflect injury of the endothelial cell. In the present study, we examined plasma thrombomodulin concentrations in 106 Type 2 (non-insulin-dependent) diabetic patients. Plasma thrombomodulin was determined by a sandwich ELISA employing monoclonal anti-thrombomodulin antibodies. The patients with proteinuria had higher plasma thrombomodulin concentrations (61.0 ± 36.0 ng/ml) compared to the patients without proteinuria (33.6 ± 9.5 ng/ml, P < 0.001) and control subjects (32.8 ± 6.5 ng/ml, P < 0.001). Plasma thrombomodulin concentrations were positively correlated with the level of serum creatine, blood urea nitrogen, urinary albumin and urinary β2-microglobulin (P < 0.001 for each), but not with fasting plasma glucose, hemoglobin A1c or fructosamine. Elevated plasma thrombomodulin was also observed in the patients with pre-proliferative (63.4 ± 28.9 ng/ml) or proliferative retinopathy (57.4 ± 34.7 ng/ml), but not in the patients with non-proliferative retinopathy (33.5 ± 12.9 ng/ml) or those without retinopathy (32.4 ± 8.9 ng/ml). Even in the 81 diabetic subjects without proteinuria as determined by a dip and read method, and whose serum creatinine was lower than 1.0 mg/dl, the plasma thrombomodulin concentration was significantly higher in the patients with pre-proliferative (41.5 ± 4.4 ng/ml) and proliferative retinopathy (41.0 ± 12.8 ng/ml) compared to the patients without retinopathy (32.2 ± 8.8 ng/ml) and those with non-proliferative retinopathy (31.9 ± 7.8 ng/ml). These results suggest that the plasma thrombomodulin concentration is increased in diabetic subjects with nephropathy and/or retinopathy and is affected by renal dysfunction. © 1990.