Association between allelic variants in the glucagon-like peptide 1 and cholecystokinin receptor genes with gastric emptying and glucose tolerance

Bradley Anderson, Paula Carlson, Marcello Laurenti, Adrian Vella, Michael Camilleri, Anshuman Desai, Kelly Feuerhak, Adil E. Bharucha

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Abstract

Background: Nutrient-mediated release of cholecystokinin and glucagon-like peptide-1 (GLP-1) regulates gastric emptying (GE) via duodenogastric feedback mechanisms; GLP-1 also regulates postprandial insulin secretion. Some patients with functional upper gastrointestinal symptoms have impaired glucose tolerance during enteral dextrose infusion. Our hypothesis was that variants in CCK, GLP-1, and TCF7L2 (transcription factor 7-like 2 locus), which is associated with greatest genetic risk for development of type 2 diabetes mellitus, are associated with GE and independently with glucose tolerance. Our aims were to evaluate the associations between these GE, glucose tolerance, and these single nucleotide polymorphisms (SNPs). Methods: Genetic variants, scintigraphic GE of solids, plasma glucose, insulin, and GLP-1 during enteral dextrose infusion (75gm over 2 hours) were measured. GE and enteral dextrose infusion were, respectively, evaluated in 44 (27 controls and 17 patients with functional dyspepsia or nausea) and 42 (28 controls, 14 patients) participants; of these, 51 participants consented to assessment of SNPs. Four functional SNPs were studied: rs6923761 and rs1042044 at GLP-1 receptor, rs7903146 (TCF7L2), and rs1800857 (CCK receptor). Key Results: Gastric emptying was normal in 38, rapid in 4, and delayed in two participants; 38 had normal, and four had impaired glucose tolerance. The T allele at rs7903146 (TCF7L2) was non-significantly associated (P =.14) with faster GE. The associations between SNPs and demographic variables, GE thalf, glucose tolerance and plasma GLP1 levels were not significant. Conclusions & Inferences: There is a trend toward an association between faster GE and the diabetes-associated allele at rs7903146 in TCF7L2. However, these SNPs were not associated with plasma glucose or GLP1 concentrations during enteral dextrose infusion.

Original languageEnglish (US)
Article numbere13724
JournalNeurogastroenterology and Motility
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2020

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Keywords

  • dumping
  • functional dyspepsia
  • glucose tolerance
  • insulin secretion

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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