AimsTo assess the validity of the C-13-glucose breath test (C-13-GBT) to identify insulin resistance (IR) in non-diabetic individuals, using hyperinsulinemic-euglycemic clamps as gold standard. This validity was compared with that of other IR surrogates.MethodologyNon-diabetic adults were studied in a cross-sectional design. In a first appointment, oral glucose tolerance tests were conducted simultaneously with C-13-GBTs. Oral 75g glucose dissolved in 150ml water, followed by 1.5mg/Kg body weight U-C-13-glucose dissolved in 50ml water, was administered. Breath and blood samples were collected at baseline and at 30-min intervals. The percentages of glucose-oxidized dose at given periods were calculated. Clamps were conducted a week later. A clamp-derived M value6.0mg/kg*min was used as cut-off. ROC curves were constructed for C-13-GBT, fasting insulin, HOMA, and ISI-composite.ResultsThirty-eight subjects completed the study protocol. The correlation coefficient between the C-13-GBT derived glucose-oxidized dose at 180min and M values was 0.524 (p=0.001). The optimal value to identify IR with the C-13-GBT was 4.23% (AUC 0.81; 95CI 0.66, 0.96; accuracy 0.82, 95CI 0.66, 0.92). The C-13-GBT sensitivity (0.88) was higher than HOMA and fasting insulin sensitivities (0.83 and 0.75 respectively), while their specificities were comparable (0.71, 0.71, and 0.79, respectively). The sensitivity of ISI-C was higher (0.92) than that of the C-13-GBT, but its specificity was poor (0.36). The accuracy of the C-13-GBT was superior to that of the other studied surrogates.ConclusionsThe C-13-GBT is a valid and accurate method to detect IR in non-diabetic adults. Therefore, it is potentially useful in clinical and community settings.