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

Abstract

A new method to replace commercially prepared C-labelled glucose with naturally availableC-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 C enrichment in the diet taken by subjects. Here, we formulated a new test meal comprising naturally availableC-enriched foods and subsequently administered it to non-diabetic control (NDC) subjects and those with T2D. We found that the new test meal-derived C enrichment of breath CO was significantly lower in T2D compared with NDC. Furthermore, from our observations T2D exhibited higher isotopic enrichment of oxygen-18 (O) in breath CO compared with NDC following ingestion of the new meal. We determined the optimal diagnostic cut-off values of C (i.e. δC‰ = 7.5‰) and O (i.e. δO‰ = 3.5‰) isotopes in breath CO for precise classification of T2D and NDC. Our new method involving the administration of naturally C-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 commercialC-enriched glucose which thus may serve as an alternative diagnostic tool for routine clinical applications.

Stable Isotope Abundance and Fractionation in Human Diseases

“…Bone apatite δ 18 O of sick mice were significantly lower than those of healthy mice, and the sickest mice exhibited the lowest δ 18 O [64]. These results were confirmed in the enamel apatite samples of suspected anaemics, which had significantly lower δ 18 O values relative to their lesion-free counterparts [33].…”

“…Still, there is no specific δ 13 C signature of exhaled breath CO 2 in (pre)diabetic patients [18,43]. It has been suggested that (pre)diabetic patients have an altered carbonic anhydrase activity, causing a change in CO 2 -water oxygen equilibration in tissues and thus a specific δ 18 O value in exhaled CO 2 [18]. This remains controversial since no highly significant difference was found in another study [43].…”

“…Aa metabolism 13 C, 15 N Collagen [12] Chronic malnutrition and potential growth retardation (stunted children) Aa metabolism 13 C, 15 N Hair [13] Patients with metabolic syndrome Glycaemia Aa metabolism 13 C, 15 N Hair [14] Diabetic patients Sugar metabolism 13 C, 15 N Hair [15][16][17][18]…”

“…Fe deficiency 56 Fe Whole blood [27] Multiple myeloma Bone formation (apatite deposition) 44 Ca Serum and urine [31] Chronic kidney disease or diabetes Bone formation (apatite deposition) 44 Ca Serum [32] Anaemia in skeleton fragments Respiratory biochemistry 18 O Bone and enamel apatite [33] Osteopenia and osteoporosis in female skeleton Urea excretion and/or renal function 15 N Bone collagen [34] Cealiac disease in skeleton Aa metabolism 13 C, 15 N Bone collagen [35]…”

“…Noteworthy, isotopic variations also likely come from differences in country-specific food intake behaviour and thus how patients with diabetes and metabolic syndrome readjust their diet. Still, there is no specific δ 13 C signature of exhaled breath CO 2 in (pre)diabetic patients [18,43]. It has been suggested that (pre)diabetic patients have an altered carbonic anhydrase activity, causing a change in CO 2 -water oxygen equilibration in tissues and thus a specific δ 18 O value in exhaled CO 2 [18].…”