Normalisation of Tissue Factor Pathway Inhibitor Activity after Glycaemic Control Optimisation in Type 1 Diabetic Patients

Abstract

Increased plasma concentrations of various markers of endothelial damage have been observed in type I diabetic patients, particularly in those with microangiopathy. To evaluate the effect of near-normalisation of glycaemic control on different markers of endothelial injury involved in haemostasis in poorly-controlled type 1 diabetic patients. TFPI, thrombomodulin (TM), plasminogen activator inhibitor, tissue-type plasminogen activator and von Willebrand factor were measured in 14 poorly-controlled type 1 diabetic patients free of diabetes-related complications (8 men, 6 women; mean age 29.8 +/- 9.9 years) before (baseline) and after 3 months of intensive therapy and in 14 sex-, age- and BMI-matched control subjects. After a mean follow-up of 107 +/- 49 days (56-210), HbA1c decreased from 11.2 +/- 2.3 to 6.7 +/- 0.7% (p <0.0001). TFPI activity at baseline was higher than in the control group (126.9 +/- 34 vs 92.0 +/- 13%, p <0.005) and decreased after good glycaemic control was achieved (p <0.005), becoming similar to that in the control group (91.0 +/- 16.5%). The TFPI descent correlated with the variations observed in HbA1c (p <0.05; r = 0.54). TM levels at baseline were significantly higher than in the control group (42.3 +/- 9.1 vs 29.00 +/- 10.9; p <0.005) and did not change. The remaining parameters studied were similar between patients and controls and did not change after glycaemic optimisation. Optimisation of glycaemic control normalises the increased activity of TFPI but not the higher TM levels observed in poorly-controlled type I diabetic patients without chronic complications.