一种基于模型的口服葡萄糖耐量试验评估胰岛素敏感性的方法。

A model-based method for assessing insulin sensitivity from the oral glucose tolerance test.

作者信息

Mari A, Pacini G, Murphy E, Ludvik B, Nolan J J

机构信息

Institute of Systems Science and Biomedical Engineering, National Research Council, Padova, Italy.

出版信息

Diabetes Care. 2001 Mar;24(3):539-48. doi: 10.2337/diacare.24.3.539.

DOI:10.2337/diacare.24.3.539

PMID:11289482

Abstract

OBJECTIVE

Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data.

RESEARCH DESIGN AND METHODS

OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT).

RESULTS

OGIS and Cl CLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/- 11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239 +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P < 0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar.

CONCLUSIONS

OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.

摘要

目的

基于口服葡萄糖耐量试验（OGTT）的现有胰岛素敏感性（IS）方法是经验性的。我们使用葡萄糖 - 胰岛素模型推导了一种基于OGTT的IS（口服葡萄糖胰岛素敏感性[OGIS]）指数，该指数可预测葡萄糖钳夹试验中的葡萄糖清除率。我们根据钳夹试验数据对OGIS进行了验证。

研究设计与方法

OGIS需要0、2和3小时（3小时OGTT）或0、1.5和2小时（2小时OGTT）的75克OGTT中的葡萄糖和胰岛素浓度。该公式包含六个经过优化以匹配钳夹试验结果的常数。为此，15名体重正常的非糖尿病受试者（体重指数<25kg/m²）、38名肥胖非糖尿病受试者（体重指数>25kg/m²）和38名2型糖尿病受试者随机接受了OGTT和120mU·min⁻¹·m⁻²胰岛素输注的正常血糖钳夹试验。将钳夹试验最后一小时期间葡萄糖输注与浓度之比计算得出的葡萄糖清除率（Cl CLAMP）与OGIS进行比较。OGIS还在一组13名糖耐量受损（IGT）的独立受试者中进行了测试。

结果

OGIS与Cl CLAMP在整个组（R = 0.77，P < 0.0001）、亚组（体重正常：R = 0.59；肥胖：R = 0.73；2型糖尿病：R = 0.49；P < 0.02）以及独立的IGT组（R = 0.65，P < 0.02）中均具有相关性。OGIS和Cl CLAMP的可重复性相似（变异系数：OGIS为7.1%，Cl CLAMP为6.4%）。OGIS在区分不同组方面与Cl CLAMP同样有效（对于OGIS，体重正常与肥胖：440±16 vs. 362±11ml·min⁻¹·m⁻²，p < 0.001；体重正常与2型糖尿病：440±16 vs. 239±7，P < 0.0001；肥胖与2型糖尿病：362±11 vs. 239±7，P < 0.0001；Cl CLAMP的结果相似）。研究了IS与体重指数、空腹血浆胰岛素和胰岛素分泌（根据OGTT胰岛素浓度计算）之间的关系。OGIS得出的结果与Cl CLAMP相似，且完全符合既定的生理原则。3小时和2小时OGTT指数的表现相似。