Enzymatic 2-Hydroxybutyrate Measurement for Dysglycemia Screening Beyond Conventional Fasting Measures

OBJECTIVE: We investigated whether fasting 2-hydroxybutyrate (2-HB), measured by a novel enzymatic assay (XpressGT), can provide incremental discrimination of dysglycemia beyond routine fasting measures. RESEARCH DESIGN AND METHODS: Associations of 2-HB with dysglycemia were assessed in the total Biomarkers of Personalized Medicine cohort and in the prespecified subcohort with fasting plasma glucose (FPG) <110 mg/dL and HbA1c <39 mmol/mol (5.7%). RESULTS: Among 772 individuals, 2-HB increased from normoglycemia (39.0 µmol/L) to prediabetes (51.9 µmol/L) and type 2 diabetes (57.0 µmol/L). In 534 individuals with normal FPG and HbA1c, 2-HB yielded the area under the receiver operating characteristic curve of 0.79 for postprandial dysglycemia (2-h glucose >140 mg/dL during oral glucose tolerance testing). A sensitivity of 90% was achieved at 39 µmol/L, with a negative predictive value of 98.9%. Each 1-SD increase in 2-HB was independently associated with dysglycemia (odds ratio 2.23; P < 0.001). CONCLUSIONS: Enzymatic 2-HB measurement may serve as a screening biomarker to rule out postprandial dysglycemia in individuals with normal FPG and HbA1c.