The importance of intravenous glucose tolerance test glucose stimulus for the evaluation of insulin secretion

For 100 years, the Intravenous glucose tolerance test (IVGTT) has been used extensively in researching the pathophysiology of diabetes mellitus and AIRg-the IVGTT-induced acute insulin response to the rapid rise in circulating glucose-is a key measure of insulin secretory capacity. For an effective evaluation of AIRg, IVGTT glucose loading should be adjusted for glucose distribution volume (gVOL) to provide an invariant, trend-free immediate rise in circulating glucose (Delta G0). Body weight-based glucose loads have been widely used but whether these achieve a trend-free Delta G0 does not appear to have been investigated. By analysing variation in AIRg, Delta G0 and gVOL with a range of IVGTT loads, both observed and simulated, we explored the hypothesis that there would be an optimum anthropometry-based IVGTT load calculation that, by achieving a trend-free Delta G0, would not compromise evaluation of AIRg as an index of beta cell function. Data derived from patient and research volunteer records for 3806 IVGTT glucose and insulin profiles. Among the non-obese, as gVOL rose, weight increased disproportionately rapidly. Consequently, the IVGTT glucose load needed for an invariant Delta G0 was progressively overestimated, accounting for 47% of variation in AIRg. Among the obese, Delta G0 was trend-free yet AIRg increased by 11.6% per unit body mass index, consistent with a more proportionate increase in weight with gVOL and a hyperinsulinaemic adaptation to adiposity-associated insulin resistance. Simulations further confirmed our hypothesis by demonstrating that a body surface area-based IVGTT load calculation could provide for a more generally invariant IVGTT Delta G0.