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Although epinephrine is known to induce HO activity, steroids are the only nonmetalloporphyrin compounds known to inhibit the induction of HO-1. The effect of different medications on HO activity has not been systematically investigated. Furthermore, the treatment of diabetes by modifying the levels of glucose and the production of AGEs may modulate the level of oxidative stress and indirectly change HO-1 activity and CO produc-tion. Therefore, the effect of treatment on CO levels should also be investigated in future studies.

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Competitive inhibitors of HO such as Sn-meso-porphyrin and zinc protoporphyrin effectively reduce hyperbilirubinemia and CO production in newborns, but their effects have not been evaluated in adults. HO activators in asthmatic patients have been investigated in a previous study where the inhalation of hemin was shown to increase the levels of exhaled CO, whereas such levels were reduced in steroid-treated patients. Furthermore, in the same study we showed that the high levels of exhaled CO found in asthmatic patients were associated with an increased expression of HO-1. Taken together, these data indicate that the exhaled CO concentration may reflect HO activity. Source

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Exhaled CO Concentration During OGTT Maximal increase in glucose concentration (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 the level of exhaled CO (from 3.0 ± 0.5 to 6.3 ± 1.0 ppm; p < 0.05). Both parameters returned to the baseline 40 min after glucose administration (Fig 2). Discussion Exhaled CO levels are elevated in patients with diabetes, correlate with blood glucose levels and duration of the disease, and may reflect the amount of HO-1 induction caused by increased oxidative stress.

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Blood Glucose Level Measurement Blood glucose levels were measured with a portable blood glucose meter (Reflolux S; Boehringer Mannheim; Mannheim, Germany), which was previously shown to provide glucose levels comparable to those of the hexokinase method and to have a low coefficient of variation. The device was calibrated before every series of measurements. OGTT An OGTT was performed in the morning in five fasting healthy volunteers, with the administration of75 g glucose. Monitoring of glucose levels was performed every 10 min for 2 h after glucose administration. The concentration of exhaled CO was monitored at the same time points. The OGTT response was normal (exhaled CO, < 200 mg [11.1 mmol] over 2 h) in all subjects evaluated.

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Subjects We have compared exhaled CO levels in 8 patients with type 1 disease (4 men, 4 women; [mean ± SEM] age, 50 ± 8 years), in 16 patients with type 2 disease (5 men, 11 women; age, 63 ± 8 years), and in 37 healthy subjects (20 men, 17 women; age, 33 ± 3 years). All subjects were lifelong nonsmokers. The mean duration of disease for patients with type 1 diabetes was 20 ± 5 years and, for type 2 patients,11 ± 2 years.

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A New Test for Monitoring the Disease? In diabetes, the interaction of glycated proteins with their cell-surface binding sites leads to oxidative stress, manifested by the appearance of mal-ondialdehyde determinants in the vessel wall, thio-barbituric acid-reactive substances in the tissues, and induction of the transcription factor nuclear fac-tor-KB and of heme oxygenase (HO)-1. This may explain the previously reported finding of elevated exhaled carbon monoxide (CO) levels. Oxidative stress also plays an important role in the development of diabetes-related complications; superoxide anions and elevated levels of plasma peroxide have been implicated in retinal damage, and lipid peroxides in the severity of coronary atherosclerosis in patients with type 1 and type 2 diabetes.

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