Quantitation of basal endogenous glucose production in Type II diabetes - Importance of the volume of distribution

The rate of endogenous glucose production (EGP) is important in understanding the pathophysiology of Type II (non-insulin-dependent) diabetes mellitus, the aetiology of its complications, and the identification of potential therapeutic targets. A great deal of effort has therefore been expended in its evaluation. Most measurements in humans have been made using tracers, or labelled analogues of glucose. Experimental strategies have included the injection and the infusion of such tracers which were often primed to achieve constant concentrations of the label more quickly. Primers have either been fixed or adjusted to the ambient glycaemia in each diabetic subject. Analyses were carried out using steady-state or non-steady-state calculations, the latter based on a one-compartment model or higher order systems. The principal finding of this review is that all approaches yield the same EGP when an appropriate model of the system is used. Under basal conditions, a single compartment model is sufficient to evaluate EGP, but the estimation of the volume of distribution, V, from individual data is critical in obtaining consistent results. Other sources of variation arose from the length of the fasting period and the patient population being studied. Overall, in Type II diabetes, EGP is frequently high in the morning and decreases gradually to rates comparable to healthy control subjects. This can be a very delayed response to a preceding meal, but more likely corresponds to an accentuated circadian rhythm in glucose production. Metabolic clearance of glucose, on the other hand, is decreased in diabetes, and remains so during the course of the day.