2240-P: Enzymatic Quantification of 2-Hydroxybutyrate: A Dynamic Biomarker for Predicting Glycemic Dysfunction

Introduction and Objective: Routine tests such as fasting plasma glucose (FPG) and HbA1c miss up to 40% of dysglycemic subjects while the oral glucose tolerance test (OGTT) as gold-standard is not routinely performed. Fasting plasma 2-hydroxybutyrate (2-HB) is an established marker of insulin resistance, but clinical utility has been limited by mass spectrometry dependence. We assessed whether 2-HB measured by a new enzymatic test (XpressGT®) provides information comparable to OGTT-derived glucose status. Methods: We analyzed adults with at least one CV risk factor or known T2D (BioPersMed cohort) who had 2 completed OGTTs. Data collection occurred at 2-year intervals over a median observation period of 9 years. Logistic regression models adjusted for age, sex, body mass index, FPG, and HbA1c evaluated associations with dysglycemia (preDM and T2D) and glycemic progression during follow-up. Diagnostic performance was assessed using classification tables and ROC curves. Results: A total of 772 individuals (median age 56.7 years, IQR 11.8; 45.5% male) were included. In cross-sectional analyses, 2-HB increased stepwise from normoglycemia (n=632; median 39.0 µmol/L) to preDM (n=67; 51.9 µmol/L) and T2D (n=73; 57.0 µmol/L) and correlated with OGTT glucose AUCi (ρ=0.44), FPG (ρ=0.39) and dysglycemia status (ρ=0.34; all p<0.001). Each SD increase in 2-HB was associated with higher odds of dysglycemia and remained independent after adjustment (OR 1.51, 95% CI 1.14 to 2.01). In the univariate model, 2-HB identified normoglycemia with a specificity of 98%. A model including age, sex, BMI, HbA1c, FPG and OGTT glucose AUCi achieved an AUC of 0.969. Replacing OGTT AUCi with 2-HB yielded an AUC of 0.919. During follow-up of normoglycemic participants, 2-HB independently predicted progression to preDM or T2D (OR 1.45 per SD, 95% CI 1.08 to 1.93). Conclusion: Using an enzymatic assay, fasting plasma 2-HB provides clinically highly relevant information on glycemic status. It discriminates dysglycemia with high specificity and predicts future glycemic deterioration. Disclosure C. Strohhofer: None. K. Eberhard: None. B.M. Obermayer-Pietsch: None. D. Stadler: Employee; Current; DirectSens GmbH. P. Herzog: Employee; Current; DirectSens GmbH. N. Verheyen: None. T.R. Pieber: Other - Speaker, Board member, Advisory panel; Current; Arecor. Research Support; Current; AstraZeneca. Other - Research support, Speaker, Board member, Advisory panel; Current; Eli Lilly and Company, Novo Nordisk, Sanofi. Employee; Current; CBmed – Center for Biomarker Research in Medicine. Funding Austrian Science Fund (FWF) for excellence cluster 10.55776/COE14