Whole-Body Glycolysis Measured by the Deuterated-Glucose Disposal Test Correlates Highly With Insulin Resistance In Vivo
- Carine Beysen, DPHIL1,
- Elizabeth J. Murphy, MD, DPHIL12,
- Tracey McLaughlin, MD3,
- Timothy Riiff, BS, MSE1,
- Cindy Lamendola, BA3,
- Holly C. Turner, BS1,
- Mohamad Awada, PHD1,
- Scott M. Turner, PHD1,
- Gerald Reaven, MD3 and
- Marc K. Hellerstein, MD, PHD24
- 1KineMed, Inc., Emeryville, California
- 2San Francisco General Hospital, University of California at San Francisco, San Francisco, California
- 3Stanford University, Palo Alto, California
- 4Nutritional 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
Abstract
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.
- 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
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 26 January 2007. DOI: 10.2337/dc06-1809.
M.K.H. is on the Board of Directors for, serves as Chair of the Scientific Advisory Board of, and holds stock in KineMed.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted January 17, 2007.
- Received August 29, 2006.
- DIABETES CARE
