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Whole-Body Glycolysis Measured by the Deuterated-Glucose Disposal Test Correlates Highly With Insulin Resistance In Vivo

¹ KineMed, Inc., Emeryville, California
² San Francisco General Hospital, University of California at San Francisco, San Francisco, California
³ Stanford University, Palo Alto, California
⁴ Nutritional Sciences and Toxicology, University of California at Berkeley, California

Address correspondence and reprint requests to Marc Hellerstein, MD, PhD, Nutritional Sciences and Toxicology, 309 Morgan Hall, University of California at Berkeley, Berkeley, CA 94720. E-mail: march{at}nature.berkeley.edu

OBJECTIVE—The purpose of this study was to compare an in vivo test of whole-body glycolysis, the deuterated-glucose disposal test (²H-GDT), with insulin sensitivity measured by the euglycemic-hyperinsulinemic glucose clamp and the steady-state plasma glucose (SSPG) test.

RESEARCH DESIGN AND METHODS—The ²H-GDT consists of an oral glucose challenge containing deuterated glucose, followed by measurement of heavy water (²H₂O) production, which represents whole-body glycolytic disposal of the glucose load. ²H₂O production is corrected for ambient insulin concentration as an index of tissue insulin sensitivity. The ²H-GDT was compared with euglycemic-hyperinsulinemic glucose clamps in healthy lean subjects (n = 8) and subjects with the metabolic syndrome (n = 9) and with the SSPG test in overweight (n = 12) and obese (n = 6) subjects.

RESULTS—A strong correlation with the clamp was observed for the 75-g and 30-g ²H-GDT (r = 0.95, P < 0.0001 and r = 0.88, P < 0.0001, respectively). The ²H-GDT and clamp studies revealed marked insulin resistance in subjects with metabolic syndrome compared with lean control subjects. The correlation with the clamp was maintained in each group (lean, r = 0.86, P < 0.01; metabolic syndrome, r = 0.81, P < 0.01) for the 75-g test. The ²H-GDT also correlated strongly with the SSPG test (r = –0.87, P < 0.0001) in overweight and obese subjects.

CONCLUSIONS—The ²H-GDT, which measures whole-body glycolysis in humans in a quantitative manner, correlates highly with the euglycemic-hyperinsulinemic glucose clamp and the SSPG test. Impaired insulin-mediated whole-body glycolysis is a feature of insulin resistance, which provides a means of assessing insulin sensitivity in vivo.

Abbreviations: AUC, area under the curve • EGP, endogenous glucose production • ²H-GDT, deuterated-glucose disposal test • HOMA, homeostasis model assessment • IR-MS, isotope ratio-mass spectrometry • QUICKI, quantitative insulin sensitivity check index • SSPG, steady-state plasma glucose • TBW, total body water

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