α-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Abstract:
      Background: Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression. Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects. Methods: Using mass spectrometry, non-targeted biochemical profiling was conducted in a cohort of 399 nondiabetic subjects representing a broad spectrum of insulin sensitivity and glucose tolerance (based on the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing, respectively). Results: Random forest statistical analysis selected α-hydroxybutyrate (α-HB) as the top-ranked biochemical for separating insulin resistant (lower third of the clamp-derived MFFM = 33 [12] μmol·min-1·kgFFM -1, median [interquartile range], n = 140) from insulin sensitive subjects (MFFM = 66 [23] mmol·min-1·kgFFM -1) with a 76% accuracy. By targeted isotope dilution assay, plasma α-HB concentrations were reciprocally related to MFFM; and by partition analysis, an α-HB value of 5 mg/ml was found to best separate insulin resistant from insulin sensitive subjects. α-HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of, and in an additive fashion to, insulin resistance. These associations were also independent of sex, age and BMI. Other metabolites from this global analysis that significantly correlated to insulin sensitivity included certain organic acid, amino acid, lysophospholipid, acylcarnitine and fatty acid species. Several metabolites are intermediates related to α-HB metabolism and biosynthesis. Conclusions: a-hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation. The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)