Persistent Complement Activation is Associated with Insulin Resistance and Chronic Inflammation in Overweight Patients with Type 2 Diabetes with Dyslipidemia

Insulin resistance is a major player in the pathogenesis of type 2 diabetes. C3 converts to C3a and acylation stimulating protein (ASP) by complement activation. ASP activates adipose tissue macrophages and accelerates continuous inflammation. Tissuebound C3a is known to induce insulin resistance. We examined the relationship between insulin resistance and complement activation by the in vivo alteration of ASP. The levels of ASP and parameters of insulin resistance and inflammation were measured in plasma from 25 patients with type 2 diabetes. A selective peroxisome proliferator-activated receptor gamma (PPAR) agonist was administered to these 25 patients for three months, and then ASP and the parameters were measured again. The alterations of ASP and the parameters were examined in the pathophysiological state. Plasma levels of ASP and complement activation products were significantly higher in diabetes. Parameters of insulin resistance were also significantly increased. The ASP level significantly improved after PPAR agonist administration. The improvement in ASP level correlated with improvements in parameters of insulin resistance and inflammation. The levels of other relevant adipocytokines by insulin resistance correlated with the degree of inflammation. ASP and complement activation were associated with insulin resistance and chronic inflammation in diabetes.