Fasting serum α‑hydroxybutyrate and pyroglutamic acid as important metabolites for detecting isolated post-challenge diabetes based on organic acid profiles

The aim of this study was to develop a method to detect serum organic acid profiles in patients with isolated post-challenge diabetes (IPD) and to compare the metabolites between IPD patients, type 2 diabetes mellitus (T2DM) and healthy controls. We developed a gas chromatography-mass spectrometry method to detect serum organic acids and validated it using serum from 40 patients with IPD, 47 with newly diagnosed T2DM, and 48 healthy controls. We then analyzed the organic acid profiles by multivariate analysis to identify potential metabolites. This method allowed the fast and accurate measurement of 27 organic acids in serum. Serum organic acid profiles differed significantly among IPD patients, T2DM patients, and healthy controls. IPD samples had significantly higher concentrations of α‑hydroxybutyrate and β‑hydroxybutyrate (P < 0.05) and lower pyroglutamic acid concentration (P < 0.05) compared with the healthy controls, and the area under the curve for the combination of α‑hydroxybutyrate and pyroglutamic acid was 0.863 for the IPD group. These results provide useful information regarding the changes in organic acid metabolism associated with IPD. Measurement of these metabolites in fasting serum from IPD patients may provide useful diagnostic and/or prognostic biomarkers, as well as helpful markers for the therapeutic monitoring of IPD patients.