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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes

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Ferreira, Mari Cassol [1, 2] ; Rossi da Silva, Maria Elizabeth [1] ; Fukui, Rosa Tsuneshiro [3] ; Arruda-Marques, Maria do Carmo [3] ; Azhar, Salman [4] ; dos Santos, Rosa Ferreira [1]
Total Authors: 6
[1] Univ Sao Paulo, Sch Med, Sao Paulo - Brazil
[2] Unochapeco Univ, Sch Med, Chapeco, SC - Brazil
[3] Univ Sao Paulo, Sch Med, LIM 18, Sao Paulo - Brazil
[4] Stanford Sch Med, Palo Alto, CA - USA
Total Affiliations: 4
Document type: Journal article
Web of Science Citations: 1

BackgroundGlucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity.ObjectivesTo evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the TCF7L2 variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide.MethodsIntervention study. Patients with T2DM (n=162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8weeks.ResultsPatients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0-180min before treatment and a similar decrease after treatment (p<0.001). Before exenatide, insulin levels at 30-120min were higher in CT/TT versus CC subjects (p<0.05). After treatment with exenatide, only CT/TT individuals demonstrated insulin reduction at 30-180 min during the meal test (p<0.05). Patients with the CC genotype presented no differences in insulin concentrations before and after treatment. The areas under the glucagon curve between 0 and 180min were similar before treatment and reduced after treatment in both groups (p<0.001).ConclusionsThe presence of the TCF7L2 rs7903146 T allele in patients with T2DM was associated with increased secretion of insulin response to a mixed-meal test. Furthermore, after treatment with exenatide, only the carriers of the T allele showed significantly decreased postprandial plasma insulin peak levels comparing with non carriers. (AU)

FAPESP's process: 10/17943-7 - Assessment of diabete treatment of individuals with diabetes type 2, with GLP-1 mimetic, exenatide, response to GLP1 mimetic of GLP-1 treatment, in patients with type 2 diabetes, related to the SNPs rs12255372 (G / T) and rs7903146 (C / T) of TCF7L2 gene
Grantee:Rosa Ferreira dos Santos
Support type: Regular Research Grants