Abstract

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 2-fold 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 one 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 (N=10, age 33±4y). All subjects participated on 4 different study days: a) OGTT, b) isoglycemic glucose infusion (Iso-IV), c) hyperglycemic clamp with oral glucose ingestion (clamp-OGTT), d) hyperglycemic clamp (clamp). With the classic OGTT/Iso-IV method the insulin response to glucose ingestion increased more than 2-fold 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 58-79% for insulin and 38-61% 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 timepoints 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.

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