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基于最小模型的胰岛素敏感性和葡萄糖清除率估计:标记静脉葡萄糖耐量试验的新见解

Estimation of insulin sensitivity and glucose clearance from minimal model: new insights from labeled IVGTT.

作者信息

Cobelli C, Pacini G, Toffolo G, Saccà L

出版信息

Am J Physiol. 1986 May;250(5 Pt 1):E591-8. doi: 10.1152/ajpendo.1986.250.5.E591.

DOI:10.1152/ajpendo.1986.250.5.E591
PMID:3518490
Abstract

The "minimal model" of glucose disappearance provides noninvasive estimates of insulin sensitivity and glucose effectiveness from an intravenous glucose tolerance test (IVGTT). However, this model does not allow the separation of glucose production from utilization. To overcome this limitation, labeled glucose was injected along with cold glucose in six normal dogs, and both cold and labeled glucose time courses were monitored along with insulin concentration. A revised minimal model was fitted to tracer data to obtain new measures of insulin sensitivity (SI* = 6.41 +/- 0.91 10(-4) min-1 X microU-1 X ml-1) and fractional glucose clearance (SG* = 0.0092 +/- 0.0009 min-1). SG* was compared with a direct measure obtained by a hepatic arterial-venous difference technique, which yielded a value of 0.0097 +/- 0.0002, virtually identical to SG*, thereby validating the model estimate. When the original minimal model was identified from cold data, we obtained S1 = 4.52 +/- 1.39 and SG = 0.042 +/- 0.009. SI* and SG* were different from SI and SG, respectively. In particular SG overestimates fractional glucose clearance by approximately five times. The revised minimal model yields glucose disposal parameters SI* and SG* that are not affected by the confounding effect of insulin and glucose inhibition of glucose production. Limitations inherent in cold IVGTT and original minimal model are overcome by labeled IVGTT and the revised minimal model, while test simplicity remains.

摘要

葡萄糖消失的“最小模型”通过静脉葡萄糖耐量试验(IVGTT)提供胰岛素敏感性和葡萄糖效能的非侵入性估计。然而,该模型无法区分葡萄糖生成与利用。为克服这一局限性,在6只正常犬中同时注射标记葡萄糖和冷葡萄糖,并监测冷葡萄糖和标记葡萄糖的时程以及胰岛素浓度。将修正后的最小模型拟合至示踪剂数据,以获得胰岛素敏感性(SI* = 6.41 +/- 0.91×10⁻⁴ min⁻¹×μU⁻¹×ml⁻¹)和葡萄糖清除分数(SG* = 0.0092 +/- 0.0009 min⁻¹)的新测量值。将SG与通过肝动静脉差值技术获得的直接测量值进行比较,后者得出的值为0.0097 +/- 0.0002,与SG几乎相同,从而验证了模型估计值。当从冷数据确定原始最小模型时,我们得到S1 = 4.52 +/- 1.39和SG = 0.042 +/- 0.009。SI和SG分别与SI和SG不同。特别是SG将葡萄糖清除分数高估了约5倍。修正后的最小模型产生的葡萄糖处置参数SI和SG不受胰岛素和葡萄糖对葡萄糖生成抑制的混杂效应影响。标记IVGTT和修正后的最小模型克服了冷IVGTT和原始最小模型固有的局限性,同时保持了测试的简便性。

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