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

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.