No evidence for isotope discrimination of tritiated glucose tracers in measurements of glucose turnover rates in man

Under non-steady-state conditions, glucose turnover rates determined with tritiated glucose tracers are often underestimated. To examine whether isotope discrimination or a tracer contaminant can contribute to this, we compared the turnover rates of unlabelled and tritiated glucose under isotopic steady-state conditions. The turnover rates were measured in 20 healthy subjects at two insulin concentrations (79±3 mU·l^-1 and 704±62 mU·l^-1). Euglycaemia was maintained by infusing unlabelled glucose mixed with (3³H)-or (6³H)-glucose. In both studies, the isotopically determined glucose disposal rate was virtually identical to the exogenous glucose infusion rate (low insulin 7.66±0.48 vs 7.58±0.44 mg·kg^-1·min^-1, high insulin 13.36±0.74 vs 13.55±0.98 mg·kg^-1·min^-1). The individual values were correlated in both the low (r = 0.85, p<0.001) and high dose insulin (r=0.81, p<0.001) studies. Tritiated glucose specific activities were also compared in arterialized and deep venous blood across forearm tissues during the high-dose insulin infusion. Glucose specific activities were similar in arterilized and deep venous blood when analysed with HPLC and conventional methods. In summary: (1) Under isotopic steady-state conditions the turnover rates of unlabelled and labelled glucoses are similar. (2) Unlabelled and labelled glucose are handled identically across forearm tissues. (3) We found no tracer impurity in our tritiated glucose preparations. We conclude that (3³H)- and (6³H)-glucose tracers can be used to reliably measure glucose turnover rates in man.