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Whole-Body Glycolysis Measured by the Deuterated-Glucose Disposal Test Correlates Highly with Insulin Resistance in vivo

¹KineMed, Inc., Emeryville, CA
²SF General Hospital, University of California at San Francisco, San Francisco, CA 94110
³Stanford University, Palo Alto, CA 94305
⁴Nutritional Sciences and Toxicology, University of California at Berkeley, CA 94720

march{at}nature.Berkeley.edu

ABSTRACT

OBJECTIVE 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 to euglycemic-hyperinsulinemic glucose clamps in healthy lean subjects (n=8) and subjects diagnosed with the metabolic syndrome (n=9), and to the SSPG in overweight (n=12) and obese (n=6) subjects.

RESULTS A strong correlation with the clamp was observed for the 75g and 30g 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 metabolic syndrome subjects compared to lean controls. 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 75g test. The ²H-GDT also correlated strongly with the SSPG (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. Impaired insulin-mediated whole-body glycolysis is a feature of insulin resistance, providing a means of assessing insulin sensitivity in vivo.

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