Abstract
New strategies for an accurate and early detection of insulin resistance are important to delay or prevent the acute onset of type 2 diabetes (T2D). Currently, insulin sensitivity index (ISI0,120) is considered to be a viable invasive method of whole-body insulin resistance for use in clinical settings in comparison with other invasive sensitivity indexes like homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). To investigate how these sensitivity indexes link the 13C/12C-carbon isotopes of exhaled breath CO2 to pre-diabetes (PD) and type 2 diabetes in response to glucose ingestion, we studied excretion dynamics of 13C/12C-isotopic fractionations of breath CO2. Here, we show that 13C/12C-isotope ratios of breath CO2 were well correlated with blood glucose, insulin, glycosylated-hemoglobin as well as with HOMA-IR and 1/QUICKI. Conversely, the strongest correlation was observed between 1/ISI0,120 and breath CO2 isotopes. Consequently, we determined several optimal diagnostic cut-off points of 1/ISI0,120 and 13CO2/12CO2-isotope ratios to distinctively track the evolution of PD prior to the onset of T2D. Our findings suggest that isotopic breath CO2 is a novel method for accurate estimation of ISI0,120 and thus may open new perspectives into the isotope-specific non-invasive evaluation of insulin resistance for large-scale real-time diabetes screening purposes.
Highlights
Glucose concentrations, has been proposed to be a viable method of whole-body insulin sensitivity for use in clinical settings[8]
We initially investigated the time-dependent excretion kinetics of stable carbon-13 isotopes, expressed as δ DOB13C(t)‰ values, in exhaled breath samples by integrated cavity output spectroscopy (ICOS) method to investigate the distribution of 13CO2 isotopic abundance in breath samples associated with isotopically labelled glucose metabolism for Non-diabetic control (NDC)
These findings suggest that carbon isotopic fractionations of breath CO2 is capable of detecting marked differences in δ DOB13C(t)‰ values in exhaled breath samples within 90 min of a 5 h-oral glucose tolerance test (OGTT) among the groups with NDC, PD and Type 2 diabetes mellitus (T2D)
Summary
Glucose concentrations, has been proposed to be a viable method of whole-body insulin sensitivity for use in clinical settings[8]. The ability to non-invasively evaluate insulin sensitivity index (ISI0,120) for diagnosis of pre-diabetes and type 2 diabetes has a substantial clinical significance. There is a pressing need to evaluate the clinical efficacy of the carbon isotopic fractionations of breath CO2 during the glucose metabolism for large-scale screening of individuals with insulin resistance and type 2 diabetes. To find the association between the 13C/12C-isotope ratios of breath CO2 and the ISI0,120, we have analysed the exhaled breath carbon dioxide isotopes for the accurate and fast non-invasive assessment of insulin resistance in PD and T2D by means of a laser-based high-precision cavity-enhanced integrated cavity output spectroscopy (ICOS) system. We determined several diagnostic parameters of the breath isotope analysis including sensitivity, specificity, optimal diagnostic cut-off points along with positive and negative predictive values to accurately evaluate the insulin resistance as well as the precise metabolic transition from normal to PD and on to T2D
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