Basu Rita, Di Camillo Barbara, Toffolo Gianna, Basu Ananda, Shah Pankaj, Vella Adrian, Rizza Robert, Cobelli Claudio
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol Endocrinol Metab. 2003 Jan;284(1):E55-69. doi: 10.1152/ajpendo.00190.2001.
Numerous studies have used the dual-tracer method to assess postprandial glucose metabolism. The present experiments were undertaken to determine whether the marked tracer nonsteady state that occurs with the dual-tracer approach after food ingestion introduces error when it is used to simultaneously measure both meal glucose appearance (R(a meal)) and endogenous glucose production (EGP). To do so, a novel triple-tracer approach was designed: 12 subjects ingested a mixed meal containing [1-(13)C]glucose while [6-(3)H]glucose and [6,6-(2)H(2)]glucose were infused intravenously in patterns that minimized the change in the plasma ratios of [6-(3)H]glucose to [1-(13)C]glucose and of [6,6-(2)H(2)]glucose to endogenous glucose, respectively. R(a meal) and EGP measured with this approach were essentially model independent, since non-steady-state error was minimized by the protocol. Initial splanchnic glucose extraction (ISE) was 12.9% +/- 3.4%, and suppression of EGP (EGPS) was 40.3% +/- 4.1%. In contrast, when calculated with the dual-tracer one-compartment model, ISE was higher (P < 0.05) and EGPS was lower (P < 0.005) than observed with the triple-tracer approach. These errors could only be prevented by using time-varying volumes different for R(a meal) and EGP. Analysis of the dual-tracer data with a two-compartment model reduced but did not totally avoid the problems associated with marked postprandial changes in the tracer-to-tracee ratios. We conclude that results from previous studies that have used the dual-tracer one-compartment model to measure postprandial carbohydrate metabolism need to be reevaluated and that the triple-tracer technique may provide a useful approach for doing so.
众多研究已采用双示踪剂法来评估餐后葡萄糖代谢。本实验旨在确定食物摄入后双示踪剂法出现的显著示踪剂非稳态在用于同时测量餐时葡萄糖出现率（R(a餐)）和内源性葡萄糖生成（EGP）时是否会引入误差。为此，设计了一种新型的三示踪剂法：12名受试者摄入含[1-(13)C]葡萄糖的混合餐，同时以能使[6-(3)H]葡萄糖与[1-(13)C]葡萄糖的血浆比值以及[6,6-(2)H(2)]葡萄糖与内源性葡萄糖的血浆比值变化最小化的模式静脉输注[6-(3)H]葡萄糖和[6,6-(2)H(2)]葡萄糖。用这种方法测量的R(a餐)和EGP基本与模型无关，因为该方案将非稳态误差最小化了。初始内脏葡萄糖提取率（ISE）为12.9%±3.4%，内源性葡萄糖生成抑制率（EGPS）为40.3%±4.1%。相比之下，用双示踪剂单室模型计算时，ISE比用三示踪剂法观察到的更高（P<0.05），EGPS更低（P<0.005）。这些误差只能通过对R(a餐)和EGP使用不同的随时间变化的容积来防止。用双室模型分析双示踪剂数据减少了但并未完全避免与餐后示踪剂与被示踪物比值显著变化相关的问题。我们得出结论，之前使用双示踪剂单室模型测量餐后碳水化合物代谢的研究结果需要重新评估，并且三示踪剂技术可能为此提供一种有用的方法。
