title: Serum α-hydroxybutyrate (α-HB) predicts elevated 1 h glucose levels and early-phase β-cell dysfunction during OGTT.
abstract: 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).
  
  
  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% (p<0.0001).
  
  
  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.
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Varvel
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA ; Department of Internal Medicine , Sanford School of Medicine, University of South Dakota , Sioux Falls, South Dakota , USA.
authors.forename: James V
authors.initials: JV
authors.lastname: Pottala
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Thiselton
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Caffrey
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Dall
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Maciek
authors.initials: M
authors.lastname: Sasinowski
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McConnell
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: G Russell
authors.initials: GR
authors.lastname: Warnick
authors.affiliation: Health Diagnostic Laboratory, Inc. , Richmond, Virginia , USA.
authors.forename: Szilard
authors.initials: S
authors.lastname: Voros
authors.affiliation: Department of Medicine, Biochemistry and Nutrition , University of Utah , Salt Lake City, Utah , USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Graham
keywords: Biomarkers; Insulin Resistance; Oral Glucose Tolerance Test; Pancreatice Insulin Secretion