Increased Superoxide Production by Mononuclear Cells of Patients With Hypertriglyceridemia and Diabetes

Abstract

Diabetic patients with hypertriglyceridemia frequently develop atherosclerosis. Because superoxide (O−2) is suspected to play an important role in the initiation of atherosclerosis, we investigated whether an abnormal amount of O−2 was produced by circulating mononuclear cells of patients with both diabetes mellitus and hypertriglyceridemia. The rate of production of superoxide dismutase–inhibitable O−2 was measured when cells were stimulated by either 4β-phorbol 12β-myristate 13α-acetate (PMA) or by opsonized zymosan (OZ). In addition, the rates of O−2 production by mononuclear cells drawn from three other groups (normal, solely diabetic, and solely hypertriglyceridemic) were determined. We found that the rate of O−2 production by mononuclear cells from the diabetic hypertriglyceridemic group was significantly higher than that from normal, diabetic, and hypertriglyceridemic groups. When the rates of O−2 production by mononuclear cells were plotted against the levels of plasma triglyceride for all individuals tested, they correlated positively (r = .73 in PMA stimulation and r = .79 in OZ stimulation, P < .01). However, the rate of O−2 production did not relate to other parameters, i.e., plasma cholesterol level, hemoglobin A1 level in erythrocytes, and the molar ratio of free cholesterol to phospholipid in mononuclear cells. Thus, we concluded that the observed elevated rate of O−2 production in the diabetic hypertriglyceridemic mononuclear cells was a reflection of a hypertriglyceridemic condition and was not unique to the diabetic hypertriglyceridemic condition. Also, O−2 may be involved in the pathogenesis of atherosclerosis in diabetic hypertriglyceridemic patients when atherogenic factors specific to diabetes are concomitantly present.