Indiana University School of Medicine, Indianapolis, USA.
Am J Physiol Endocrinol Metab. 2010 Feb;298(2):E229-36. doi: 10.1152/ajpendo.00603.2009. Epub 2009 Nov 17.
After a constant insulin infusion is initiated, determination of steady-state conditions for glucose infusion rates (GIR) typically requires >or=3 h. The glucose infusion follows a simple time-dependent rise, reaching a plateau at steady state. We hypothesized that nonlinear fitting of abbreviated data sets consisting of only the early portion of the clamp study can provide accurate estimates of steady-state GIR. Data sets from two independent laboratories were used to develop and validate this approach. Accuracy of the predicted steady-state GDR was assessed using regression analysis and Altman-Bland plots, and precision was compared by applying a calibration model. In the development data set (n = 88 glucose clamp studies), fitting the full data set with a simple monoexponential model predicted reference GDR values with good accuracy (difference between the 2 methods -0.37 mg x kg(-1) x min(-1)) and precision [root mean square error (RMSE) = 1.11], validating the modeling procedure. Fitting data from the first 180 or 120 min predicted final GDRs with comparable accuracy but with progressively reduced precision [fitGDR-180 RMSE = 1.27 (P = NS vs. fitGDR-full); fitGDR-120 RMSE = 1.56 (P < 0.001)]. Similar results were obtained with the validation data set (n = 183 glucose clamp studies), confirming the generalizability of this approach. The modeling approach also derives kinetic parameters that are not available from standard approaches to clamp data analysis. We conclude that fitting a monoexponential curve to abbreviated clamp data produces steady-state GDR values that accurately predict the GDR values obtained from the full data sets, albeit with reduced precision. This approach may help reduce the resources required for undertaking clamp studies.
在开始持续胰岛素输注后,通常需要 >or=3 h 来确定葡萄糖输注率 (GIR) 的稳态条件。葡萄糖输注遵循简单的时间依赖性上升,在稳态时达到平台期。我们假设,对仅包括钳夹研究早期部分的缩短数据集进行非线性拟合,可以提供稳态 GIR 的准确估计。使用来自两个独立实验室的数据来开发和验证这种方法。使用回归分析和 Altman-Bland 图评估预测稳态 GDR 的准确性,并通过应用校准模型比较精度。在开发数据集(n = 88 项葡萄糖钳夹研究)中,用简单的单指数模型拟合全数据集可以很好地预测参考 GDR 值(两种方法之间的差异为-0.37 mg x kg(-1) x min(-1)),并且精度较高[均方根误差 (RMSE) = 1.11],验证了模型构建过程。拟合最初 180 或 120 分钟的数据可以预测最终 GDR,具有相当的准确性,但精度逐渐降低[fitGDR-180 RMSE = 1.27 (P = NS 与 fitGDR-full 相比);fitGDR-120 RMSE = 1.56 (P < 0.001)]。使用验证数据集(n = 183 项葡萄糖钳夹研究)获得了类似的结果,证实了这种方法的普遍性。该建模方法还可以得出标准钳夹数据分析方法无法获得的动力学参数。我们得出结论,用单指数曲线拟合缩短的钳夹数据可以产生与从完整数据集获得的 GDR 值准确预测的稳态 GDR 值,尽管精度降低。这种方法可能有助于减少进行钳夹研究所需的资源。