Plasma C3d Levels and Ischemic Heart Disease in Type II Diabetes

Abstract

OBJECTIVE--To test the hypothesis that the complement system may be activated in patients with type II diabetes and CAD. RESEARCH DESIGN AND METHODS--The plasma C3d concentration was measured in 106 type II diabetic patients and 25 nondiabetic control subjects. The patient group was subdivided according to AER, and the groups were adjusted for age, sex, and known duration of diabetes. For the assignment to a given subgroup, normoalbuminuria was defined as AER < 15 microns/min, microalbuminuria as AER 16-250 micrograms/min, and macroalbuminuria as AER > 250 micrograms/min. The presence or absence of coronary disease was assessed through clinical examination, ECG, and coronary angiography. An RIA system was used for measurement of urinary albumin levels, and the plasma C3d concentrations were measured by ELISA. RESULTS--Within each of the AER-defined subgroups, the plasma C3d levels were significantly higher in patients with IHD than in those without. Thus, in the normoalbuminuric group, plasma C3d levels were 16.3 AU/ml (95% CI 13.9-19) in patients with IHD vs. 11.6 AU/ml (95% CI 10.5-12.7) in those without (P < 0.001). The corresponding data for the microalbuminuric and macroalbuminuric groups were 21.8 (95% CI 18.1-26.3) vs. 13.6 (95% CI 12.3-15.1) and 31.6 (95% CI 24.9-40) vs. 17.5 (13.6-22.6) AU/ml (P < 0.01), respectively. Patients with IHD also had significantly higher plasma C3d levels than normal control subjects, regardless of AER subgroup. A multiple logistic regression analysis demonstrated an association between the plasma C3d concentration and IHD and AER. CONCLUSIONS--Activation of the complement system may play a role in the development of macrovascular disease in type II diabetes.

Levels of C3 in patients with severe, morbid and extreme obesity: its relationship to insulin resistance and different cardiovascular risk factors

“…6 There is a correlation between C3 and the majority of conventional risk factors, both in the general population 4 as well as in patients with cardiovascular disease. 5 Increases in C3 were observed in patients with type 2 diabetes, 21,22 hypertension 22 and dyslipidemia, 27 even in the absence of obesity. Our study revealed an additive effect of these diseases on C3.…”

“…19 A positive correlation has been shown between C3 and ASP, although the latter is not correlated with the insulin levels in a baseline situation. 20 There are various lines of evidence where there seems to be an increase in C3 in situations of insulin resistance 20 and in ischemic cardiopathy; 4,21,22 furthermore, the presence of C3 was also verified on the arteriosclerotic plaque. 23 These findings indicate a hypothesis that one of the pathways by which the situation of insulin resistance could bring about an atherosclerotic process would be by means of an immunologic reaction in which C3 would be a very important factor.…”

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

“…Elevated C3 concentration levels have been reported in individuals with obesity, 51 type 2 diabetes, 52 hypertension, 53 dyslipidemia, 25 and coronary artery disease, 54 all of Pearson's coefficients (R) were calculated for all data and the four groups individually. Non-normally distributed parameters were log-transformed prior to analysis.…”

Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes

“…Its cleavage product acylation stimulating protein [23] has a pivotal function in triglyceride synthesis within adipocytes [23]. Its other split product C3 d is raised in Type II diabetic patients with ischaemic heart disease or increased albumin excretion rate but normal in patients without these complications [30]. Concentrations of C3 and C3 d are not correlated in patients with inflammatory diseases [31].…”