A Research On The Relationship Between Complement And Vascular Diseases In Type 2 Diabetes Mellitus

Objective To investigate the expression changes of complement and complement regulatory proteins, and the relationship between them and vascular diseases in type 2 diabetes.Methods 40 patients with type 2 diabetes were selected in this study. 24 age-, sex-, body weight- matched healthy volunteers were served as controls. The levels of MBL and hsCRP in circulating serum was examined by ELISA, and serum complement C3 , C4 and Pf were tested by rate nephelometry. The expression of CD55, CD59 on circulating white blood cells was examined by flowcytometry. Urine albumin excretion rate (UAER), serum lipids, oxidized LDL and Lp(a) were also tested.Results MBL level which was positively correlated with HbA1c (r=0.431 P=0.009) and negatively correlated with triglyceride(TG)(r=-0.277 P=0.031) was not significantly changed in type 2 diabetes compared with healthy controls(2182.47 ± 1815.39 vs 2263.76 ± 1662.35 P=0.859). The levels of C3 and C4 in patients with type 2 diabetes were increased(1.25 ± 0.28 vs 1.44 ± 0.37, 0.30 ± 0.10 vs 0.37 ± 0.14 P=0.034, 0.047). C3 was positively correlated with TG, low density lipoprotein cholesterol(LDL-C), body mass index(BMI), waist circumference and waist-hip ratio( r=0.256 ~ 0.393 P=0.043 ~ 0.002 ) , C4 was positively correlated with total cholesterol(TC) and TG(r=0.395, 0.622 P=0.002, 0.000). The mean fluorescence intensity(MFI) of CD55 on lymphocytes, monocytes and granulocytes in patients with type 2 diabetes was down-regulated(2.31 ± 0.43 vs 1.95 ± 0.34,P 0.002, 4.35 ± 2.31 vs 3.28 ± 0.93,P 0.023 and 2.54 ± 0.74 vs 2.17 ± 0.50,P 0.046 respectively. ), so were percentages of CD55 positive lymphocytes,CD59 positive lymphocytes and CD59 positive granulocytes(43.10 ± 15.00 vs 34.50 ± 12.70,P 0.030, 68.20 ± 6.50 vs 65.20± 4.20,P 0.011 and 91.60 ± 6.00 vs 87.60 ± 6.90,P 0.025). The expression levels ofCD55, CD59 were negatively correlated with UAER. Multiple regression and partial correlation analysis revealed that diabetic course and mean fluorescence intensity of CD55 positive monocytes were independent predictors of UAER;TG, waist-hip ratio, fasting and 2h postprandial glucose were negatively correlated with percentages of CD55 positive cells (P 0.030-0.000) and /or mean fluorescence intensity (P 0.037-0.001). IL-6, hsCRP, LDL-C, ox-LDL and LP(a) were correlated with percentages of CD59 positive cells ( P 0.001-0.012 );HbAlc and TG were independent predictors of MBL;TG, BMI and LDL-C were the best for C3, TG was independent predictor of C4;Waist-hip ratio was the best predictor for the mean fluorescence of CD55 positive cells, TG was the best predictor for the percentages of CD55 positive cells, and IL-6 was the best predictor for the percentages of CD59 positive cells.Conclusion The levels of C3 and C4 but not MBL and Pf in patients with type 2 diabetes were increased compared with healthy controls. The expression of CD55, CD59 was down-regulated . The level of MBL was negatively correlated with TG and was positively correlated with HbAlc, C3 and C4 were related with obesity and dyslipidemia, and the expression levels of CD55, CD59 were negatively correlated with UAER in patients with type 2 diabetes. This findings indicated that the levels of C3 and C4 might be influenced by obesity and dyslipidemia and there were no direct relationship between MBL and nephritic complication in type 2 diabetes. The down-regulation of complement regulatory proteins was involved in the pathogenesis of chronic diabetic renal complication;The expression of CD55, CD59 might be influenced by obesity, dyslipidemia and inflammatory status in type 2 diabetes.