Abstract
Background/ObjectivesThe changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.Subjects/MethodsThe study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water.ResultsMain outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects.ConclusionsIt seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance.Trial RegistrationClinicalTrials.gov NCT01875575
Highlights
In the lean, the insulin response to an oral glucose challenge or to meal ingestion is largely influenced by the rate of gastric emptying and by the concomitant secretion of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) [1,2,3,4]
Rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance
The insulin response to an oral glucose challenge or to meal ingestion is largely influenced by the rate of gastric emptying and by the concomitant secretion of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) [1,2,3,4]
Summary
The insulin response to an oral glucose challenge or to meal ingestion is largely influenced by the rate of gastric emptying and by the concomitant secretion of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) [1,2,3,4]. Gastric emptying accounts roughly for one-third of the variance in the glycemic response, as determined with a standard 75 g glucose tolerance test in healthy controls [2]. In response to oral glucose, the incretin hormones increase with the size of the glucose load, resulting in similar glucose excursions, independent of the glucose load [1,6]. This regulatory adaption was explained as dose-dependent responses by both GLP-1 and GIP [1,6]. According to Nauck and coworkers [1], the incretin effect accounts for up to 70% of the insulin response to a standard 75 g oral glucose tolerance test
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