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Wednesday, April 17, 2024
Glucose Mouse CO2

UW spotlight: Diagnosis by breathalyzer

SCIENCE

The breathalyzer test may soon become commonplace in more than just roadside drunk-driving tests. Researchers at the University of Wisconsin-Madison are using breathalyzers to provide early disease diagnosis.

In the study, published by the journal Metabolism in February, Dr. Fariba Assadi-Porter and her team were able to diagnose polycystic ovary syndrome (PCOS) using only breathalyzer and blood tests.

PCOS is a disease characterized by an imbalance in female sex hormones, which can cause ovarian cysts, infertility, skin problems and metabolic dysfunction. As many as one in 10 women have PCOS, however many are diagnosed well after puberty when they experience difficulty conceiving.

“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,” Assadi-Porter said.

Assadi-Porter, a UW-Madison biochemist and scientist at the Nuclear Magnetic Resonance Facility at Madison identified differences in lipid metabolism in women with PCOS versus women without the disease.

Notably, PCOS leads to a higher generation of certain lipids. This change in metabolism can be monitored by using glucose labeled with the heavier carbon isotope, known as carbon-13. Glucose, a precursor in the lipid-producing pentose cycle, contains six carbons, each of which is known to have distinct fates based on the metabolic pathways it is shuttled through.

Using this knowledge, Assadi-Porter and coworkers injected carbon-13 labeled glucose into mice. While the carbon at position 6 in the glucose molecule is retained regardless of metabolic pathway, carbon 1 is lost as carbon dioxide (CO2) in the pentose cycle, but retained by an alternative metabolic pathway. Therefore, the ratios of carbon-12 to carbon-13 exhaled serve as a readout of how the body is metabolizing the glucose.  

A specialized breathalyzer uses a laser to detect changes in the ratio of carbon-12 to carbon-13 in CO2 exhaled by the mice soon after the injection with labeled glucose. This information, paired with a blood test analyzed by nuclear magnetic resonance (NMR) spectroscopy, provides detailed information on carbon-12 to carbon-13 ratios. Both techniques can differentiate between healthy and sick mice.  

This new method of detecting PCOS is a major advancement in disease diagnosis. PCOS diagnosis today usually occurs after puberty, and often only after excluding all other likely diseases. Using this new technology, PCOS could be diagnosed earlier, allowing for more preventative measures including weight loss, and medication to balance hormone levels in the earlier stages of disease.

The ability to diagnose a disease using breath is very appealing. Not only is the technology rapid and less invasive than traditional methods, but more sensitive than the comparable blood testing.

The breathalyzer device is approximately the size of a shoebox, but could be developed into a smaller, hand held device that could make testing in any setting easy. A major challenge to medicine today is to deliver diagnostics and treatment in a cost-effective manner to rural or remote regions.

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“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,” Assadi-Porter said.

Changes in metabolism associated with disease often occur far earlier than symptoms arise. Monitoring changes in metabolism can therefore provide a way to diagnose many diseases earlier, and to begin treatments before a disease advances.

Assadi-Porter further explained that by varying the selective labeling in the molecule source, the changes in the way the body uses the fuel can be monitored, leading to disease diagnosis.

The technology developed in this study, combined with ever-increasing knowledge about metabolism and disease states may make it possible to diagnose diseases through a puff into a breathalyzer in the future.

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