P182	Complement factor B and sC5b-9 are elevated in first-degree relatives of South Asian subjects with type 2 diabetes mellitus.
R.Somani, P.Grant, A.Carter
University of Leeds, Leeds, GB.

Background: First-degree relatives of subjects with type 2 diabetes mellitus (T2DM) are recognised to be at increased risk of developing both T2DM and cardiovascular disease (CVD). Emerging data implicates inflammation, and specifically the complement cascade, in the pathogenesis of CVD and T2DM. Hypothesis: We assessed the hypothesis that levels of complement factors B, C3 and sC5b-9 are elevated in first-degree relatives of South Asian subjects with T2DM compared with healthy South Asian controls with no personal or family history of DM. Methods: We recruited 119 first-degree relatives of South Asian subjects with T2DM and 119 age and sex-matched South Asian controls. All subjects provided a full medical history, underwent a physical examination and provided a fasting blood sample for measurement of complement factors and standard biochemical risk factors. Data were analyzed with SPSS v12.0 and presented as mean (95% confidence intervals). Results: Levels of the complement activation marker sC5b-9 were significantly higher in the relatives [90.05 (83.29, 97.37) ng/ml] compared with the controls [75.31 (71.89, 78.89) ng/ml, P<0.001]. Complement factor B was also significantly higher in relatives [192.2 (184.1, 200.3) ug/ml] compared with controls [169.8 (162.2, 177.4) ug/ml, P=0.001]. However, there was no significant difference in C3 levels between relatives and controls nor was there a difference in C-reactive protein. For the biochemical variables, compared with controls the relatives had higher levels of total cholesterol [4.91 (4.71, 5.1) mmol/L Vs 4.58 (4.4, 4.76) mmol/L, P=0.016], higher LDL cholesterol [3.05 (2.89, 3.2) mmol/L Vs 2.78 (2.64, 2.92) mmol/L P=0.015] and higher triglyceride [1.25 (1.12, 1.39) mmol/L Vs 1.08 (0.97, 1.19) mmol/L, P=0.04]. No other differences were observed between the two study groups. Conclusions: There is increased complement activation in relatives of South Asian subjects with T2DM, in addition to increased factor B but not factor C3. These data therefore suggest that increased activity of the alternative complement cascade may be a risk factor for the development of T2DM and CVD.

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