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首页> 外文期刊>Computer Methods and Programs in Biomedicine: An International Journal Devoted to the Development, Implementation and Exchange of Computing Methodology and Software Systems in Biomedical Research and Medical Practice >Model-based assessment of insulin sensitivity of glucose disposal and endogenous glucose production from double-tracer oral glucose tolerance test.
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Model-based assessment of insulin sensitivity of glucose disposal and endogenous glucose production from double-tracer oral glucose tolerance test.

机译：通过基于双示踪剂的口服葡萄糖耐量试验对葡萄糖处置和内源性葡萄糖产生的胰岛素敏感性进行基于模型的评估。

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A new mathematical model of short-term glucose regulation by insulin is proposed to exploit the oral glucose tolerance test (OGTT), which is commonly used for clinical diagnosis of glucose intolerance and diabetes. Contributions of endogenous and exogenous sources to measured plasma glucose concentrations have been separated by means of additional oral administration and constant intravenous infusion of glucose labeled with two different tracers. Twelve type 2 diabetic patients (7 males and 5 females) and 10 control subjects (5 males and 5 females) with normal glucose tolerance and matched body mass index (BMI) participated in this study. Blood samples for measurement of concentrations/activity of unlabeled and double-tracer glucose and insulin were collected every 15min for 3h following the oral glucose load. A minimal model combined with non-linear mixed-effects population parameter estimation has been devised to characterize group-average and between-patient variability of: (i) gastrointestinal glucose absorption; (ii) endogenous glucose production (EGP), and (iii) glucose disposal rate. Results indicate that insulin-independent glucose clearance does not vary significantly with gender or diabetic state and that the latter strongly affects, as expected, insulin-dependent clearance (insulin sensitivity). Inhibition of EGP, interpreted in terms of variations from basal of insulin concentrations, does not appear to be affected by diabetes but rather by BMI, i.e. by the degree of obesity. This study supports the utility of a minimal modelling approach, combined with population parameter estimation, to characterize glucose absorption, production and disposition during double-tracer OGTT experiments. The model provides a means for planning further experiments to validate the new hypothesis on the influence of individual factors, such as BMI and diabetes, on glucose appearance and disappearance, and for designing new simplified clinical tests.
机译：提出了一种利用胰岛素短期调节葡萄糖的新数学模型，以利用口服葡萄糖耐量试验（OGTT），该试验通常用于临床对葡萄糖耐量和糖尿病的诊断。内源性和外源性来源对测量的血浆葡萄糖浓度的贡献已通过额外的口服给药和持续静脉内输注两种不同示踪剂标记的葡萄糖而得以分离。十二名2型糖尿病患者（男7例，女5例）和10例葡萄糖耐量正常且体重指数匹配（BMI）的对照组（男5例，女5例）参加了这项研究。口服葡萄糖负荷后3小时，每15分钟收集一次血样，用于测量未标记的和双示踪葡萄糖和胰岛素的浓度/活性。设计了一个结合非线性混合效应总体参数估计的最小模型，以表征以下人群的群体平均和患者之间的差异：（i）胃肠道葡萄糖吸收; （ii）内源性葡萄糖生产（EGP），以及（iii）葡萄糖处置率。结果表明，不依赖胰岛素​​的葡萄糖清除率不会随性别或糖尿病状态而发生显着变化，并且正如预期的那样，后者会严重影响依赖胰岛素​​的清除率（胰岛素敏感性）。用胰岛素基础浓度的变化来解释EGP的抑制作用似乎不受糖尿病的影响，而受BMI的影响，即受肥胖程度的影响。这项研究支持最小建模方法和总体参数估计相结合来表征双示踪OGTT实验中葡萄糖的吸收，产生和处置。该模型为规划进一步的实验提供了一种手段，以验证有关个体因素（例如BMI和糖尿病）对葡萄糖出现和消失的影响的新假设，以及设计新的简化的临床试验。

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