Underestimation of glucose turnover determined using [6-3H]glucose tracer in non-steady state

Autor: Patrick M. Bell, C. N. Ennis, A. B. Atkinson, D. P. Rooney, Brian Sheridan, R. D. G. Neely, Elizabeth Trimble
Rok vydání: 1990
Předmět:
Zdroj: Diabetologia. 33:681-687
ISSN: 1432-0428
0012-186X
DOI: 10.1007/bf00400570
Popis: The use of tritiated glucose tracers may result in underestimation of glucose turnover during hyperinsulinaemic clamps giving paradoxical negative endogenous glucose production rates. While mathematical modelling errors in the analysis of tracer data are major determinants of this underestimate in the non-steady state, the relative importance of tracer contamination under these conditions remains in doubt. We have used high performance liquid chromatography to assess the possible contribution to this problem of a labelled tracer impurity found in [6-3H]glucose. In conventional 4 h hyperinsulinaemic clamps performed in six normal subjects, labelled impurity increased as a percentage of the neutral plasma radioactivity fraction from 5.3±0.9% after a 2 h equilibration period (0 min) to 13.5±2.2% at 120 min and 15.4±2.4% at 240 min, as plasma glucose specific activities fell following the infusion of insulin. Negative endogenous glucose production rates were observed both at 90–120 min (−8.8±1.6μmol·kg−1min−1) and at 210–240 min (−8.5±1.4 μmol·kg−1min−1) implying a persistent underestimate in isotopically determined glucose appearance rate. Using chromatography data to correct for impurity increased glucose appearance rates by 7.9±2.1% at 120 min and 11.0±2.5% at 240 min. Purified tracer was then used for a further six clamps. When the conventional protocol was used with unlabelled glucose infusion an obvious negative error persisted only at 90–120 min. In contrast, labelled infusions gave exclusively positive values for endogenous glucose production. We conclude that a labelled impurity of [6-3H]glucose may be an important source of error in measurement of glucose turnover and endogenous glucose production in the non-steady state. Use of chromatographically pure tritiated glucose tracers is recommended.
Databáze: OpenAIRE