Whole-body glycolysis measured by the deuterated-glucose disposal test correlates highly with insulin resistance in vivo.
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.


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.
Beysen
Carine
C
KineMed, Inc., Emeryville, California, USA.
Murphy
Elizabeth J
EJ
McLaughlin
Tracey
T
Riiff
Timothy
T
Lamendola
Cindy
C
Turner
Holly C
HC
Awada
Mohamad
M
Turner
Scott M
SM
Reaven
Gerald
G
Hellerstein
Marc K
MK
D000284:Administration, Oral; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003903:Deuterium; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D007333:Insulin Resistance; D007553:Isotope Labeling / Q000379:methods; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology; D008954:Models, Biological; D012680:Sensitivity and Specificity
D001786:Blood Glucose; D007328:Insulin; D003903:Deuterium; D005947:Glucose