According to a study published in the peer-reviewed journal Metabolism, a “breathalyzer”-like technology, currently under development at the University of Wisconsin-Madison, may help diagnose diseases in the future. The study shows a simple, but sensitive technique, that can identify normal and disease-state glucose metabolism by a fast analysis of exhaled air or blood.

Several diseases, including infections, diabetes, and cancer, change the body’s metabolism in different ways. According to the researchers, these biochemical alterations can be identified considerably faster than usual symptoms would arise – even within a couple of hours – providing hope of early detection and diagnosis of disease.

Senior author Fariba Assadi-Porter, a UW-Madison biochemist and scientist at the Nuclear Magnetic Resonance Facility at Madison, explains:

“With this methodology, we have advanced methods for tracing metabolic pathways that are perturbed in disease. It’s a cheaper, faster, and more sensitive method of diagnosis.”

The team examined rodents with metabolic symptoms, comparable to those observed in women with polycystic ovary syndrome (PCOS). PCOS is one of the most prevalent female endocrine disorders, affecting around 1 in 10 women. The condition can cause metabolic dysfunction, infertility and ovarian cysts. At present, PCOS can only be diagnosed after puberty and by exclusion of all other likely diseases – a lengthy and frustrating process for both patients and doctors.

Assadi-Porter, explained:

“The goal is to find a better way of diagnosing these women early on, before puberty, when the disease can be controlled by medication or exercise and diet, and to prevent these women from getting metabolic syndromes like diabetes, obesity, and associated problems like heart disease.”

By measuring the isotopic signatures of carbon-containing metabolic byproducts in the blood or breath of mice, the team managed to identify distinct metabolic alterations. According to co-author Warren Porter, a UW-Madison professor zoology, the researchers injected glucose containing a single atom of the heavier isotope carbon-13 to track the most active metabolic pathways in healthy or sick rodents. Within minutes, the team was able to measure changes in the ratio of carbon-12 to carbon-13 in the carbon dioxide the mice exhaled.

One of the benefits of this strategy is that it monitors the functionality of the entire body with a single measure. Aside from simplifying diagnosis, it also offers a potential fast feedback of treatments efficacy.

Porter, said:

“The pattern of these ratios in blood or breath is different for different diseases – for example cancer, diabetes, or obesity – which makes this applicable to a wide range of diseases.”

The technology depends on the fact that the body uses various sources to generate energy under different conditions.

Porter explains:

“Your body changes its fuel source. When we’re healthy we use the food that we eat. When you get sick, the immune system takes over the body and starts tearing apart proteins to make antibodies and use them as an energy source.”

That change from sugars to proteins engages various biochemical pathways in the body, causing clear alterations in the carbon isotopes that appear in exhaled carbon dioxide. The alterations may indicate the earliest stages of disease, if detected quickly.

In addition, the team discovered similar patterns using two independent examinations – cavity ring-down spectroscopy on exhaled breath and nuclear magnetic resonance spectroscopy on blood serum. The researchers explain that the breath-based technique is particularly exciting, as it is considerably more sensitive than blood-based examinations and is non-invasive.

The methods used in the mice were sensitive enough to identify statistically considerable variations between even extremely small populations of sick and healthy mice.

Although the team imagined a small, hand-held “breathalyzer” that could be easily taken into remote or rural regions, the current cavity ring-down spectroscopy examinations uses a machine approximately the size of a shoebox.

The researches co-founded Isomark, LLC, in order to develop the technology and its applications. Their goal is to investigate the fundamental biology of disease and get a clearer picture as to whether the distinctive biochemical alterations they can observe are causative or adverse effects.

The National Institutes of Health, Wisconsin Institutes for Discovery, Rodale Foundation, and the Farmers Advocating for Organics fund, funded the study. The other co-authors are Julia Haviland, Marco Tonelli, and Dermot Haughey, all at UW-Madison.

Written by Grace Rattue