Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes
Abstract Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG < 70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to i...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-00284-z |
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| author | Mark Woollam Paula Angarita-Rivera Sanskar Thakur Ali Daneshkhah Amanda P. Siegel Dana S. Hardin Mangilal Agarwal |
| author_facet | Mark Woollam Paula Angarita-Rivera Sanskar Thakur Ali Daneshkhah Amanda P. Siegel Dana S. Hardin Mangilal Agarwal |
| author_sort | Mark Woollam |
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| description | Abstract Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG < 70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D. |
| format | Article |
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| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-8cabb45c76d2430ab73ac98e1a40ffb72025-08-20T02:03:31ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-00284-zSteps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetesMark Woollam0Paula Angarita-Rivera1Sanskar Thakur2Ali Daneshkhah3Amanda P. Siegel4Dana S. Hardin5Mangilal Agarwal6Integrated Nanosystems Development Institute, Indiana University IndianapolisIntegrated Nanosystems Development Institute, Indiana University IndianapolisIntegrated Nanosystems Development Institute, Indiana University IndianapolisIntegrated Nanosystems Development Institute, Indiana University IndianapolisDepartment of Chemistry and Chemical Biology, Indiana University IndianapolisOhioHealth Physician GroupIntegrated Nanosystems Development Institute, Indiana University IndianapolisAbstract Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG < 70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.https://doi.org/10.1038/s41598-025-00284-zType 1 diabetesHypoglycemiaVolatile organic compoundsExhaled breathGas chromatographyMass spectrometry |
| spellingShingle | Mark Woollam Paula Angarita-Rivera Sanskar Thakur Ali Daneshkhah Amanda P. Siegel Dana S. Hardin Mangilal Agarwal Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes Scientific Reports Type 1 diabetes Hypoglycemia Volatile organic compounds Exhaled breath Gas chromatography Mass spectrometry |
| title | Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes |
| title_full | Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes |
| title_fullStr | Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes |
| title_full_unstemmed | Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes |
| title_short | Steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes |
| title_sort | steps toward clinical validation of exhaled volatile organic compound biomarkers for hypoglycemia in persons with type 1 diabetes |
| topic | Type 1 diabetes Hypoglycemia Volatile organic compounds Exhaled breath Gas chromatography Mass spectrometry |
| url | https://doi.org/10.1038/s41598-025-00284-z |
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