Division of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Wynn Reader in Human Metabolism, Section of Metabolic Medicine, Faculty of Medicine, Imperial College London (St Mary's Campus), Room G1, Norfolk Place, London, W2 2NH, UK.
Sci Rep. 2024 Mar 28;14(1):7451. doi: 10.1038/s41598-024-54584-x.
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 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 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.
100 年来，静脉葡萄糖耐量试验（IVGTT）已广泛用于研究糖尿病的病理生理学，而 AIRg-即 IVGTT 引起的循环葡萄糖快速升高时的急性胰岛素反应-是胰岛素分泌能力的关键衡量指标。为了对 AIRg 进行有效评估，IVGTT 葡萄糖负荷应根据葡萄糖分布容积（gVOL）进行调整，以提供循环葡萄糖不变的、无趋势的瞬时升高（ΔG0）。基于体重的葡萄糖负荷已被广泛应用，但这些负荷是否能实现无趋势的 ΔG0 似乎尚未得到研究。通过分析一系列 IVGTT 负荷（包括观察到的和模拟的）下的 AIRg、ΔG0 和 gVOL 的变化，我们探讨了这样一个假设，即存在一种最佳的基于人体测量学的 IVGTT 负荷计算方法，通过实现无趋势的 ΔG0，不会影响 AIRg 作为β细胞功能指标的评估。数据来源于 3806 例 IVGTT 葡萄糖和胰岛素图谱的患者和研究志愿者记录。在非肥胖者中，随着 gVOL 的增加，体重增加的速度不成比例地加快。因此，为了实现不变的 ΔG0，所需的 IVGTT 葡萄糖负荷会被逐渐高估，这解释了 47%的 AIRg 变化。在肥胖者中，ΔG0 无趋势，但 AIRg 每单位体重指数增加 11.6%，这与 gVOL 下体重更成比例的增加以及肥胖相关的胰岛素抵抗的高胰岛素血症适应性一致。模拟进一步证实了我们的假设，即基于体表面积的 IVGTT 负荷计算可以提供更普遍不变的 IVGTT ΔG0。
