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Plasma C3d levels and ischemic heart disease in type II diabetes
A Figueredo1, J L Ibarra, J Bagazgoitia
1Department of Internal Medicine III, Hospital Universitario de San Carlos, Madrid, Spain.
Insights
The complement system, indicated by elevated plasma C3d levels, appears activated in type II diabetes patients with coronary artery disease (CAD). This suggests complement activation may contribute to macrovascular complications in diabetic individuals.
Area of Science:
- Immunology
- Endocrinology
- Cardiology
Background:
- Type II diabetes is associated with an increased risk of cardiovascular disease.
- The role of the complement system in diabetic macrovascular complications is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that the complement system is activated in type II diabetes patients with coronary artery disease (CAD).
Main Methods:
- Plasma C3d concentrations were measured in 106 type II diabetic patients and 25 controls using ELISA.
- Patients were stratified by albumin-excretion rate (AER): normoalbuminuria, microalbuminuria, and macroalbuminuria.
- Coronary disease presence was assessed via clinical examination, ECG, and coronary angiography.
Main Results:
- Plasma C3d levels were significantly higher in diabetic patients with ischemic heart disease (IHD) compared to those without IHD, across all AER subgroups.
- Patients with IHD consistently showed higher plasma C3d levels than control subjects.
- Multiple logistic regression revealed an association between plasma C3d concentration, IHD, and AER.
Conclusions:
- Complement system activation may play a role in the pathogenesis of macrovascular disease in type II diabetes.
- Elevated C3d levels are linked to both IHD and albuminuria in diabetic patients.
- These findings highlight a potential therapeutic target for preventing cardiovascular complications in 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.