Does increased leukotriene B4 in type 1 diabetes result from elevated cholesteryl ester transfer protein activity?

Elevated cholesteryl ester transfer protein (CETP) activity has been reported in type 1 diabetic subjects and may be one cause of the high incidence of macrovascular complications in these patients. LDL delivers arachidonic acid (AA), in the form of cholesteryl ester (CE), to cells such as monocytes and fibroblasts, as precursor for eicosanoid synthesis. We discovered that AA content in LDL CE was significantly correlated with CETP activity, even after controlling for CETP concentration, in type 1 diabetic children. The production of LTB(4), a potent chemotactic and pro-inflammatory factor which plays a role in atherogenesis, has been shown to be increased in type 1 diabetic patients. We hypothesized that in these subjects, increased AA content in LDL CE, resulting from increased CETP activity and transient hyperinsulinemia, may lead to enhanced synthesis of LTB(4) and subsequently the higher incidence of cardiovascular disease.