¹³C isotopic abundances in natural nutrients: A newly formulated test meal for non-invasive diagnosis of type 2 diabetes

A new method to replace commercially prepared ¹³C-labelled glucose with naturally available ¹³C-enriched substrates could result in promotion of the clinical applicability of the isotopic breath test for detection of type 2 diabetes (T2D). Variation of the carbon-13 isotope in human breath depends on the ¹³C enrichment in the diet taken by subjects. Here, we formulated a new test meal comprising naturally available ¹³C-enriched foods and subsequently administered it to non-diabetic control (NDC) subjects and those with T2D. We found that the new test meal-derived ¹³C enrichment of breath CO₂ was significantly lower in T2D compared with NDC. Furthermore, from our observations T2D exhibited higher isotopic enrichment of oxygen-18 (¹⁸O) in breath CO₂ compared with NDC following ingestion of the new meal. We determined the optimal diagnostic cut-off values of ¹³C (i.e. δ¹³C‰ = 7.5‰) and ¹⁸O (i.e. δ¹⁸O‰ = 3.5‰) isotopes in breath CO₂ for precise classification of T2D and NDC. Our new method involving the administration of naturally ¹³C-abundant nutrients showed a typical diagnostic sensitivity and specificity of about 95%, suggesting a valid and potentially robust global method devoid of any synthetically manufactured commercial ¹³C-enriched glucose which thus may serve as an alternative diagnostic tool for routine clinical applications.