title: Exhaled carbon monoxide levels elevated in diabetes and correlated with glucose concentration in blood: a new test for monitoring the disease?
abstract: OBJECTIVE
  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 (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.
  
  
  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 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.
  
  
  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.
authors.affiliation: Department of Thoracic Medicine , Imperial College, School of Medicine, National Heart and Lung Institute, London, England.
authors.forename: P
authors.initials: P
authors.lastname: Paredi
authors.forename: W
authors.initials: W
authors.lastname: Biernacki
authors.forename: G
authors.initials: G
authors.lastname: Invernizzi
authors.forename: S A
authors.initials: SA
authors.lastname: Kharitonov
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D001944:Breath Tests; D002248:Carbon Monoxide / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D018384:Oxidative Stress; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D002248:Carbon Monoxide