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 (ΔG0). Body weight-based glucose loads have been
widely used but whether these achieve a trend-free ΔG0 does not appear to have been
investigated. By analysing variation in AIRg, ΔG0 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 ΔG0, would not
compromise evaluation of AIRg as an index of beta cell function. Data derived from patient
and research volunteer records for 3,806 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 ΔG0 was progressively overestimated,
accounting for 47% of variation in AIRg. Among the obese, ΔG0 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 ΔG0.