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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: DIABETOLOGY & METABOLIC SYNDROME; v. 11, JAN 25 2019.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 10/17943-7 - Avaliação da resposta ao uso de análogo do GLP-1 em função dos SNPs rs12255372 (G/T) e rs7903146 (C/T) do gene TCF7L2 em indivíduos com diabete melito tipo 2
• Beneficiário: Rosa Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular