Department of Medicine II, University Hospital, LMU Munich, Munich, Germany.
Clinical Research Unit, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, United States.
Am J Physiol Endocrinol Metab. 2023 Oct 1;325(4):E412-E420. doi: 10.1152/ajpendo.00104.2022. Epub 2023 Sep 13.
The incretin effect describes the insulin response to nutrient ingestion that exceeds the response to glycemia per se. It is mediated by gastrointestinal factors and is necessary to maintain postprandial glucose homeostasis. The incretin effect results in a more than twofold increase of the insulin response to a meal in healthy people and two different techniques have been used in the past to measure its magnitude. Most studies employ an OGTT on 1 day, followed by a matching glucose infusion on a separate day. Another study design employs a hyperglycemic glucose clamp that is maintained after oral ingestion of glucose. Both protocols allow quantification of the incretin effect by comparing the insulin response to an identical glycemic stimulus. Here we performed a within-subject comparison of both techniques to quantify the incretin effect and suggest different calculation methods to interpret the results derived from the clamp experiment in a cohort of healthy young adults ( = 10, age 33 ± 4 yr). All subjects participated on four different study days: ) OGTT, ) isoglycemic glucose infusion (Iso-IV), ) hyperglycemic clamp with oral glucose ingestion (clamp-OGTT), and ) hyperglycemic clamp (clamp). With the classic OGTT/Iso-IV method, the insulin response to glucose ingestion increased more than twofold and was 60 ± 6% and 49 ± 5% for insulin and c-peptide. Different estimates of the incretin effect based on the clamp method ranged from 58% to 79% for insulin and 38% to 61% for c-peptide, both significantly higher than values derived from the OGTT/isoglycemic infusion method. However, when the effect of continuous hyperglycemia on insulin secretion was accounted for, using extrapolation from early time points of the clamp, good agreement was noted between the two methods. Based on these results, both techniques seem to be equally suited to measure the incretin effect and should be employed according to the scientific questions, experimental contingencies, and investigator experience. This proof-of-concept study shows that the incretin effect can be reliably assessed by two different methods with similar quantitative results. A single-day hyperglycemic clamp with oral glucose ingestion allows the determination of the incretin effect with fewer study days and less day-to-day variability.
肠促胰岛素效应描述了摄入营养物质后胰岛素的反应超过了血糖本身的反应。它是由胃肠道因素介导的，是维持餐后血糖稳态所必需的。在健康人群中，肠促胰岛素效应使进餐时的胰岛素反应增加了两倍以上，过去曾使用两种不同的技术来测量其幅度。大多数研究在 1 天内进行口服葡萄糖耐量试验（OGTT），然后在另一天进行匹配的葡萄糖输注。另一种研究设计采用高血糖葡萄糖钳夹，在口服葡萄糖后维持。这两种方案都通过比较相同血糖刺激下的胰岛素反应来定量肠促胰岛素效应。在这里，我们在一组健康年轻成年人（= 10，年龄 33±4 岁）中进行了这两种技术的个体内比较，以定量肠促胰岛素效应，并提出了不同的计算方法来解释来自钳夹实验的结果。所有受试者在 4 个不同的研究日参加：) OGTT，) 等血糖葡萄糖输注（Iso-IV），) 口服葡萄糖摄入的高血糖钳夹（clamp-OGTT），和) 高血糖钳夹（clamp）。使用经典的 OGTT/Iso-IV 方法，葡萄糖摄入后的胰岛素反应增加了两倍以上，胰岛素和 C 肽分别增加了 60±6%和 49±5%。基于钳夹方法的不同肠促胰岛素效应估计值在胰岛素为 58%至 79%之间，C 肽为 38%至 61%，均明显高于 OGTT/等血糖输注方法得出的值。然而，当考虑到持续高血糖对胰岛素分泌的影响时，使用钳夹的早期时间点进行外推，两种方法之间存在良好的一致性。基于这些结果，两种技术似乎都同样适合测量肠促胰岛素效应，应根据科学问题、实验情况和研究者经验选择使用。这项概念验证研究表明，两种不同的方法都可以可靠地评估肠促胰岛素效应，并且可以获得相似的定量结果。一天一次的口服葡萄糖高血糖钳夹可以在较少的研究天数和更少的日常变异性下确定肠促胰岛素效应。
