Exhaled Breath Analysis for Diabetes Diagnosis and Monitoring: Relevance, Challenges and Possibilities

With the global population prevalence of diabetes surpassing 463 million cases in 2019 and diabetes leading to millions of deaths each year, there is a critical need for feasible, rapid, and non-invasive methodologies for continuous blood glucose monitoring in contrast to the current procedures that are either invasive, complicated, or expensive. Breath analysis is a viable methodology for non-invasive diabetes management owing to its potential for multiple disease diagnoses, the nominal requirement of sample processing, and immense sample accessibility; however, the development of functional commercial sensors is challenging due to the low concentration of volatile organic compounds (VOCs) present in exhaled breath and the confounding factors influencing the exhaled breath profile. Given the complexity of the topic and the skyrocketing spread of diabetes, a multifarious review of exhaled breath analysis for diabetes monitoring is essential to track the technological progress in the field and comprehend the obstacles in developing a breath analysis-based diabetes management system. In this review, we consolidate the relevance of exhaled breath analysis through a critical assessment of current technologies and recent advancements in sensing methods to address the shortcomings associated with blood glucose monitoring. We provide a detailed assessment of the intricacies involved in the development of non-invasive diabetes monitoring devices. In addition, we spotlight the need to consider breath biomarker clusters as opposed to standalone biomarkers for the clinical applicability of exhaled breath monitoring. We present potential VOC clusters suitable for diabetes management and highlight the recent buildout of breath sensing methodologies, focusing on novel sensing materials and transduction mechanisms. Finally, we portray a multifaceted comparison of exhaled breath analysis for diabetes monitoring and highlight remaining challenges on the path to realizing breath analysis as a non-invasive healthcare approach.