ROSA FERREIRA DOS SANTOS

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LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 19 Citação(ões) na Scopus
    Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes
    (2019) FERREIRA, Mari Cassol; SILVA, Maria Elizabeth Rossi da; FUKUI, Rosa Tsuneshiro; ARRUDA-MARQUES, Maria do Carmo; AZHAR, Salman; SANTOS, Rosa Ferreira dos
    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.