Oxidative stress is associated with diabetes mellitus: a role of vascular NADPH oxidase as a source of superoxide has been demonstrated. We determined whether in type 2 diabetes mononuclear cells, NADPH oxidase and the inducible hemeoxygenase (HO-1) gene expressions are activated. In monocytes from 25 outpatients with type 2 diabetes, p22 phox gene expression was higher (0.71 ؎ 0.09 p22 phox /␤-actin gene expression ratio) than that observed in 19 controls (0.56 ؎ 0.09, P < 0.001). Similarly,

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... -1 gene expression was significantly higher in diabetic patients (0.77 ؎ 0.12 HO-1/␤-actin gene expression ratio) than in controls (0.41 ؎ 0.14, P < 0.001). The p22 phox and HO-1 gene expressions were also determined during (plasma glucose 363 ؎ 40 mg/dl) and after (125 ؎ 11 mg/dl) metabolic decompensation in 10 type 2 diabetic patients. The correction of the metabolic milieu was associated with a 19% ؎ 3% (P < 0.01) and 30% ؎ 3% (P < 0.01) decrease in the p22 phox and HO-1 gene expressions, respectively. In a multivariate analysis, age was independently associated to p22 phox gene expression in circulating monocytes in type 2 diabetics [13% (adjusted R 2 ), P < 0.05]. Decompensated type 2 diabetes is associated with increased p22 phox and HO-1 gene expressions in circulating monocytes; the metabolic normalization reduces but does not normalize this activation. These findings suggest that these cells, which play a crucial role in the earliest events of atherosclerotic lesion, are subjected to an increased oxidative stress