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Exhaled Carbon Monoxide Levels Elevated in Diabetes and Correlated With Glucose Concentration in Blood^*

A New Test for Monitoring the Disease?

^* From the Department of Thoracic Medicine (Drs. Barnes, Paredi, Biernacki, and Kharitonov), Imperial College, School of Medicine, National Heart and Lung Institute, London, England; and General Practice (Dr. Invernizzi), Chiavenna, Italy. Supported by grants from University of Milan and the British Lung Foundation (UK).

Correspondence to: P. J. Barnes, MA, DM, DSc, Department of Thoracic Medicine, National heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK; e-mail: p.j.barnes{at}ic.ac.uk

Purpose: 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.

Methods: 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 (HbA₁c) 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.

Results: 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 HbA₁c (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.

Conclusions: 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.

Key Words: carbon monoxide • glucose tolerance test • oxidative stress

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