Abstract 4940: Inflammatory Thrombotic Interactions in Young Type 1 Diabetes Subjects: Effects of Glycaemic Control

Abstract

The inflammatory and thrombotic pathways have a crucial role in the development of coronary artery disease, and inflammatory thrombotic markers predict cardiovascular events. Although the atherosclerotic process in type 1 diabetes (T1DM) starts at an early age, little is known about inflammatory markers and clot structure in this population. The aims of this study were to investigate C-reactive protein (CRP), complement C3 (C3) and fibrin clot structure/fibrinolysis in children and young adults with T1DM, the effects of improving glycaemic control on these parameters and complement/fibrin interactions affecting clot structure/function. In 47 children (14±3yrs) C3 levels were higher in T1DM than controls (1.13±0.24 versus 0.83±0.24mg/ml respectively; p<0.001), whereas CRP levels were no different. Clot final turbidity (FT), an indicator of clot density, was higher in diabetes children compared with controls, and lysis time longer (599±18 and 516±17 secs, respectively, p=0.02). In 18 young adults with T1DM (23±5yrs) a 1.3% reduction in HbA1c was associated with a decrease in C3 levels from 1.09±0.05 to 0.96±0.05mg/ml (p<0.05), with no effect on CRP levels. Improving glycaemic control reduced FT and shortened lysis time from 601±21 to 550±19 secs (p=0.02). Clot FT and lysis correlated positively with C3 plasma levels (r=0.39 and r= 0.585, respectively; p<0.01). C3 incorporation into the plasma clot was 26% and 19% in T1DM and controls respectively, a difference that failed to reach statistical significance. However, clots made from plasma-purified fibrinogen diabetes patients exhibited a 71% increase in lysis time in the presence of purified C3, whereas this increase was only 41% using fibrinogen purified from controls (p=0.03). These results demonstrate that young children with T1DM already have evidence of inflammatory thrombotic processes as indicated by elevated C3 levels, a denser clot structure and prolonged clot lysis times. Interactions between C3 and fibrin occur in non-diabetic subjects, but are significantly enhanced in the presence of diabetes. Improving glycaemic control is associated with reduction in C3 levels and favourable changes in clot structure/function, which is potentially due to a direct effect of C3 on clot lysis.