Improved predictive models for plasma glucose estimation from multi-linear regression analysis of exhaled volatile organic compounds

Abstract

Lee J, Ngo J, Blake DB, Meinardi S, Pontello AM, Newcomb R, Galassetti PR. Improved predictive models for plasma glucose estimation from multi-linear regression analysis of exhaled volatile organic compounds. J Appl Physiol 107: 155-160, 2009. First published May 7, 2009 doi:10.1152/japplphysiol.91657.2008.-Exhaled volatile organic compounds (VOCs) represent ideal biomarkers of endogenous metabolism and could be used to noninvasively measure circulating variables, including plasma glucose. We previously demonstrated that hyperglycemia in different metabolic settings (glucose ingestion in pediatric Type 1 diabetes) is paralleled by changes in exhaled ethanol, acetone, and methyl nitrate. In this study we integrated these gas changes along with three additional VOCs (2 forms of xylene and ethylbenzene) into multi-linear regression models to predict plasma glucose profiles in 10 healthy young adults, during the 2 h following an intravenous glucose bolus (matched samples of blood, exhaled and room air were collected at 12 separate time points). The four-gas model with highest predictive accuracy estimated plasma glucose in each subject with a mean R value of 0.91 (range 0.70 -0.98); increasing the number of VOCs in the model only marginally improved predictions (average R with best 5-gas model ϭ 0.93; with 6-gas model ϭ 0.95). While practical development of this methodology into clinically usable devices will require optimization of predictive algorithms on large-scale populations, our data prove the feasibility and potential accuracy of breath-based glucose testing. breath analysis; exhaled gases; hyperglycemia; intravenous glucose tolerance test VOLATILE ORGANIC COMPOUNDS (VOCs) present in human breath are potentially ideal biomarkers of endogenous metabolic processes, as human breath samples can be collected noninvasively and painlessly in virtually any condition. Many of these VOCs may be important by-products of physiological or altered endogenous metabolic pathways and can conceivably be developed into prognostic, diagnostic, and monitoring tools for a variety of biomedical fields. Only in recent years have advances in analytical technology drastically reduced prior measurement difficulties, allowing detection of hundreds, possibly thousands, of VOCs in human exhalates at extremely low concentrations (the best technology currently available allows measurements as low as 10 parts per quadrillion by volume). Most of the current studies applying this technology in a number of laboratories from various countries, however, are still at an exploratory stage (27), while concrete, practical applicability of this concept has been limited to a handful of gases present in exhaled breath at relatively high concentrations, such as exhaled acetone in diabetic ketoacidosis (20, 26) or exhaled urea in gastric H. pylori infection (16).An intriguing application of this technology is the identification and kinetic measurement of exhaled biomarkers of carbohydrate metabolism, with the downstream goal of developing portable devic...

Exhalation pattern changes during fasting and low dose glucose treatment in rats

“…As mentioned in the previous section, some studies found different correlations between blood glucose and exhaled breath, with a regression coefficient range from 0.08 to 0.98 [32][33][34][35][36][37][38][39][40]. Yet, in our study we found a negative correlation towards higher acetone concentrations when blood glucose concentrations declined, with a regression coefficient of only 0.52.…”

Gas Signatures from Cultured Neutrophils and Peripheral Blood Mononuclear Cells Obtained from Healthy Humans

“…These hydrocarbons have been detected in the exhaled human breath [19][20][21][22][23][24][25], and have been proposed as a means of assessing in vivo lipid peroxidation. Specifically, higher levels of exhaled acetone were observed in association with diabetes [22]. Additionally, increases in ethane concentration was observed from rat hepatocytes in the presence of oxidants [26].…”

Detection of Volatile Malodorous Compounds in Breath: Current Analytical Techniques and Implications in Human Disease

“…Nelson et al also reported no difference in isoprene levels between healthy controls and diabetes patients and no statistical difference between diabetes patients in the fasting and postinsulin state [178]. A few studies showed that methyl nitrate as well as ethanol, acetone and aromatic hydrocarbons have been correlated with blood glucose in patients with Type 1 diabetes [185][186][187]. Other compounds that can discriminate between healthy controls and patients with Type 2 diabetes include dimethyl sulfide, butanol and pyridine [188].…”