Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood: A New Test for Monitoring the Disease?

Abstract

In diabetes, the interaction of glycated proteins with their cell-surface binding sites leads to oxidative stress and induction of the stress protein heme oxygenase (HO)-1. Considering that carbon monoxide (CO) is a product of HO activity, we studied the level of exhaled CO as a marker of oxidative stress in diabetes. Eight patients with insulin-dependent diabetes mellitus (type 1) (4 men, 4 women; [mean +/- SEM] age, 50 +/- 8 years) were studied, of whom 2 had peripheral neuropathy and 1 had renal failure. Sixteen patients with non-insulin-dependent diabetes mellitus (type 2) (5 men, 11 women; age 63 +/- 8 years) were studied, of whom 2 had peripheral neuropathy. Glycosylated hemoglobin (HbA(1)c) levels were higher (7.4 +/- 0.3%) in patients with type 1 (mean duration of the disease, 20 +/- 5 years) than in type 2 (4.9 +/- 0.4%; p < 0.05; mean duration of the disease, 11 +/- 2 years). All of the patients were lifelong nonsmokers. Levels of exhaled CO were higher in patients with diabetes (type 1, 4.0 +/- 0.7 ppm; type 2, 5.0 +/- 0.4 ppm) when compared to 37 nonsmoking healthy subjects (20 men, 17 women; age, 33 +/- 3 years) (2.9 +/- 0.2 ppm; p < 0.05). There was a positive correlation between exhaled CO levels and the incidence of glycemia in all subjects (r = 0.52, p < 0.05) and the duration of diabetes (r = 0.48, p < 0.05), but there was not a strong correlation with concentrations of HbA(1)c (r = 0.06, p = 0.8). In addition, an oral glucose tolerance test was performed in five healthy nonsmoking volunteers (three men; age, 33 +/- 4 years). The maximal glucose increase (from 3.9 +/- 0.2 to 5.5 +/- 0.1 mmol/L at 15 min; p < 0.05) was associated with a significant increase in exhaled CO concentration (from 3.0 +/- 0.5 to 6.3 +/- 1.0 ppm; p < 0. 05). Both parameters returned to the baseline at 40 min after glucose administration. Elevated levels of exhaled CO in diabetes may reflect HO-1 induction and oxidative stress. The measurement of CO may be a new tool for disease monitoring.