α-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic populationα-hydroxybutyrate是胰岛素抵抗和葡萄糖耐受不良的早期生物标志物在非糖尿病的人口.pdf

a-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population 1 1 1 1 1 Walter E. Gall *, Kirk Beebe , Kay A. Lawton , Klaus-Peter Adam , Matthew W. Mitchell , Pamela J. 1 1 1 2 2 2 Nakhle , John A. Ryals , Michael V. Milburn , Monica Nannipieri , Stefania Camastra , Andrea Natali , Ele Ferrannini2 for the the RISC Study Group¤ 1 Metabolon, Inc., Research Triangle Park, North Carolina, United States of America, 2 RISC (Relationship of Insulin Sensitivity to Cardiovascular Disease) Coordinating Office, Department of Internal Medicine, University of Pisa School of Medicine, Pisa, Italy 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 a-hydroxybutyrate (a–HB) as the top-ranked biochemical for separating insulin resistant (lower third of the clamp-derived MFFM = 33 [12] mmol?min21?kgFFM21, median [interquartile range], n = 140) from insulin sensitive subjects (MFFM = 66 [23] mmol?min21?kgFFM21) with a 76% accu