The aim of our study was to elucidate whether serum thrombomodulin (S-TM) and urinary thrombomodulin (U-TM) levels would reflect the pathogenesis of diabetic complications. Studies were conducted in 188 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched healthy subjects. TM was measured by a newly developed enzyme immunoassay. Both S-TM and U-TM levels in NIDDM were much higher than those in healthy controls. S-TM values in NIDDM correlated significantly with age (P < 0.05), HbA1c (P < 0.05), serum 1.5 anhydroglucetol (AG) (P < 0.05) and urinary albumin concentration (UAC) (P < 0.01), respectively. On the other hand, fasting plasma glucose (FPG) (P < 0.001), HbA1c (P < 0 .01), serum fructosamine (P < 0.05) and serum 1.5 AG (P < 0.05) were closely correlated with U-TM values in NIDDM. Patients with clinical nephropathy showed obviously higher S-TM levels (P < 0.05) than patients with latent nephropathy. Furthermore, S-TM values in patients with diabetic proliferative retinopathy increased significantly compared with those in patients without diabetic retinopathy (P < 0.05). When all diabetic patients with normoalbuminuria were studied, no significant changes of S-TM were observed between the no diabetic retinopathy group and the proliferative diabetic retinopathy group.
Conclusions: The present data suggest that an increase in U-TM reflects the grade of glucose metabolism, whereas an increase in S-TM appears to reveal the advance of diabetic microangiopathy, including nephropathy.