P147	Altered clot formation and lysis in first-degree relatives of South Asian subjects with type 2 diabetes mellitus.
R.Somani, A.Carter, C.Cymbalista, P.Grant
University of Leeds, Leeds, GB.

Background: First-degree relatives of South Asian (SA) subjects with type 2 diabetes mellitus (T2DM) are recognised to be at increased risk of developing both T2DM and cardiovascular disease (CVD). Hypothesis: We assessed the hypothesis that first-degree relatives of SA subjects with T2DM have altered clot formation and function, which contributes to the increased risk of CVD. Methods: We recruited 119 first-degree relatives of SA subjects with T2DM (mean age 35.4 years; 32M, 87 F) and 119 age and sex-matched SA controls (mean age 35.2 years; 32M, 87 F). All subjects provided a full medical history, underwent a physical examination and gave a fasting blood sample for measurement of standard biochemical risk factors, fibrinogen, clot turbidity (lag time and maximum absorbency [max Abs, a measure of clot density]) and clot lysis (time to 50% lysis). Data were analysed with SPSS v12.0 and presented as mean (95% confidence intervals). Results: Turbidity analysis demonstrated that plasma from SA relatives formed clots more quickly than SA controls as assessed by the lag time (SA relatives: 260 [255, 266] seconds; SA controls: 291 [281, 302] seconds, p<0.001). There was no difference in clot max Abs between relatives (0.445 [0.427, 0.463]) and controls (0.426 [0.408, 0.443], p=0.13). Clot lysis was significantly prolonged in the relatives (3774 [3111, 4579] seconds) compared with controls (1719 [1542, 1915] seconds, p]<0.001. Fibrinogen levels were also significantly higher in the relatives (2.45 [2.35, 2.55] g/L) compared with controls (2.30 [2.20, 2.40] g/L, p=0.037). After adjusting for age, sex, smoking and fibrinogen, the differences in lag time and clot lysis between SA relatives and controls remained (adjusted lag: relatives 266 [259, 273] seconds, controls 291 [284, 298] seconds, P<0.001; adjusted lysis: relatives 3683 [3115, 4356] seconds, controls 1758 [1485, 2080] seconds, p<0.001). Conclusion: The relatives of South Asian subjects with T2DM show altered clot formation and lysis, forming clots which polymerise more quickly and lyse more slowly. These data suggest that abnormalities in clot formation and lysis are familial and contribute to the increased risk for CVD in SA relatives of subjects with T2DM.

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