Joon Ha, Stephanie T Chung, Max Springer, Joon Young Kim, Phil Chen, Aaryan Chhabra, Melanie G Cree, Cecilia Diniz Behn, Anne E Sumner, Silva A Arslanian, Arthur S Sherman
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However, current analytical methods for OGTT-derived <i>S</i><sub>I</sub> and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. 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引用次数: 0
摘要
高效准确地估算胰岛素敏感性(SI)和β细胞功能(BCF)的方法对于研究 2 型糖尿病的发病机制和治疗效果非常重要。现有的方法在灵敏度、输入数据和技术要求方面各不相同。口服葡萄糖耐量试验(OGTT)比静脉注射法更简单、更符合生理学原理,因此更受青睐。然而,目前针对 OGTT 得出的 SI 和 BCF 的分析方法也有不同的复杂程度;口服最小模型需要数学专业知识进行解卷积和微分方程拟合,而简单的代数代用指数(如松田指数、胰岛素生成指数)可能会产生非生理值。我们为临床研究开发了一种新的 ISS(胰岛素分泌和敏感性)模型,该模型可通过标准 OGTT 精确估算 SI 和 BCF,并注重有效性、易实施性和实用性。该模型是通过对葡萄糖和胰岛素进行一对微分方程拟合而开发的,无需解旋或 C 肽数据。该模型源于已发表的 T2D 进展纵向模拟模型,该模型表示葡萄糖-胰岛素平衡,包括挑战后肝糖生成抑制以及第一和第二阶段胰岛素分泌。ISS 模型在三个不同的队列中对整个生命周期进行了评估。新模型与静脉葡萄糖耐量试验和胰岛素钳夹的黄金标准估计值具有很强的相关性。ISS 模型在性能、保真度和复杂性之间取得了平衡,可提供可靠的 T2D 风险表型,因此在不同人群中具有广泛的适用性。
Estimating insulin sensitivity and β-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.
Efficient and accurate methods to estimate insulin sensitivity (SI) and β-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity (SI) and β-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.
期刊介绍:
The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.