ESTIMATION OF INSULIN-SECRETION RATES FROM C-PEPTIDE LEVELS - COMPARISON OF INDIVIDUAL AND STANDARD KINETIC-PARAMETERS FOR C-PEPTIDE CLEARANCE
ESTIMATION OF INSULIN-SECRETION RATES FROM C-PEPTIDE LEVELS - COMPARISON OF INDIVIDUAL AND STANDARD KINETIC-PARAMETERS FOR C-PEPTIDE CLEARANCE
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DOI：
10.2337/diabetes.41.3.368
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发表时间：
1992-03-01
期刊：
影响因子：
7.7
通讯作者：
POLONSKY, KS
中科院分区：
文献类型：
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作者：
VANCAUTER, E;MESTREZ, F;POLONSKY, KS
使用c肽分布和降解的双室模型，可以从血浆c肽水平准确估计胰岛素分泌率。在以往的研究中，c肽清除的动力学参数是根据每个受试者静脉注射生物合成的人c肽后观察到的衰减曲线得出的。为了确定是否可以定义c肽清除的标准参数，并在不获得每个受试者的衰减曲线的情况下用于计算胰岛素分泌，我们分析了在我们实验室研究的正常、肥胖和非胰岛素依赖性糖尿病受试者中获得的200条生物合成人c肽衰减曲线。该分析表明，在年龄、性别、肥胖程度和糖耐量高度异质性的人群中，c肽分布的体积分布和代谢的动力学参数变化< 30%。分布的体积与肥胖程度相关，由体表面积（BSA）量化。c肽分布体积对BSA的依赖性在男性中比在女性中更为明显。老年受试者的半衰期比年轻人稍长。当考虑到BSA、性别和年龄的影响时，c肽动力学参数在正常、肥胖和糖尿病受试者中非常相似。基于这些发现，定义了一种简单的程序，以获得考虑肥胖程度、性别和年龄的c肽清除率的标准参数。这些标准参数得出了平均胰岛素分泌率的估计值，每个受试者的平均胰岛素分泌率与单独参数的估计值仅相差10-12%。使用标准参数而不是个体参数的方法没有系统地低估或高估胰岛素分泌，因此使用标准参数获得的空腹分泌率、平均24小时分泌率以及分泌脉冲的数量和幅度的组值与使用个体参数获得的值仅相差1-2%。此外，基于标准参数的测量准确度与在同一受试者中重复测定c肽清除参数的准确度没有区别。我们的结论是，用c肽清除率的标准参数，而不是单独获得的参数，从血浆c肽水平估计胰岛素分泌率是可能的，而不会有明显的准确性损失。
Insulin secretion rates can be accurately estimated from plasma C-peptide levels with a two-compartment model for C-peptide distribution and degradation. In previous studies, the kinetic parameters of C-peptide clearance were derived in each subject from the decay curve observed after bolus intravenous injection of biosynthetic human C-peptide. To determine whether standard parameters for C-peptide clearance could be defined and used to calculate insulin secretion without obtaining a decay curve in each subject, we analyzed 200 decay curves of biosynthetic human C-peptide obtained in normal, obese, and non-insulin-dependent diabetes mellitus subjects studied in our laboratory. This analysis showed that the volume of distribution and kinetic parameters of C-peptide distribution and metabolism vary by < 30% in a population highly heterogenous in terms of age, sex, degree of obesity, and degree of glucose tolerance. The volume of distribution correlated with the degree of obesity as quantified by body surface area (BSA). This dependence of C-peptide distribution volume on BSA was more marked in men than in women. The long half-life was slightly longer in elderly subjects than in younger adults. When effects of BSA, sex, and age were taken into account, the parameters of C-peptide kinetics were very similar in normal, obese, and diabetic subjects. Based on these findings, a simple procedure to derive standard parameters for C-peptide clearance taking into account degree of obesity, sex, and age was defined. These standard parameters resulted in estimations of mean insulin secretion rates, which differed in each subject by only 10-12% from those obtained with individual parameters. The approach of using standard rather than individual parameters did not systematically underestimate or overestimate insulin secretion so that group values for the fasting secretion rate, the mean 24-h secretion rate, and the number and the amplitude of secretory pulses obtained with standard parameters differed by only 1-2% from the values obtained with individual parameters. Furthermore, the accuracy of measurements based on standard parameters was not different from that associated with replicate determinations of the parameters of C-peptide clearance in the same subject. We conclude that it is possible to estimate insulin secretion rates from plasma C-peptide levels with standard parameters for C-peptide clearance rather than individually derived parameters without significant loss of accuracy.