Serum α-hydroxybutyrate (α-HB) predicts elevated 1?h glucose levels and early-phase β-cell dysfunction during OGTT

摘要

Objective Serum α-hydroxybutyrate (α-HB) is elevated in insulin resistance and diabetes. We tested the hypothesis that the α-HB level predicts abnormal 1?h glucose levels and β-cell dysfunction inferred from plasma insulin kinetics during a 75?g oral glucose tolerance test (OGTT). Research design and methods This cross-sectional study included 217 patients at increased risk for diabetes. 75?g OGTTs were performed with multiple postload glucose and insulin measurements over a 30–120?min period. OGTT responses were analyzed by repeated measures analysis of variance (ANOVA). Multivariable logistic regression was used to predict 1?h glucose ≥155?mg/dL with α-HB added to traditional risk factors. Results Mean±SD age was 51±15?years (44% male, 25% with impaired glucose tolerance). Fasting glucose and insulin levels, but not age or body mass index (BMI), were significantly higher in the second/third α-HB tertiles (3.9?μg/mL) than in the first tertile. Patients in the second/third α-HB tertiles exhibited a higher glucose area under the receiver operating characteristics curve (AUC) and reduced initial slope of insulin response during OGTT. The AUC for predicting 1?h glucose ≥155?mg/dL was 0.82 for a base model that included age, gender, BMI, fasting glucose, glycated hemoglobin (HbA1c), and insulin, and increased to 0.86 with α-HB added (p=0.015), with a net reclassification index of 52% (p0.0001). Conclusions Fasting serum α-HB levels predicted elevated 1?h glucose during OGTT, potentially due to impaired insulin secretion kinetics. This association persisted even in patients with an otherwise normal insulin–glucose homeostasis. Measuring serum α-HB could thus provide a rapid, inexpensive screening tool for detecting early subclinical hyperglycemia, β-cell dysfunction, and increased risk for diabetes.