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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.)

TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity

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Ferreira, Mari Cassol [1, 2] ; Rossi da Silva, Maria Elizabeth [1] ; Fukui, Rosa Tsuneshiro [1] ; Arruda-Marques, Maria do Carmo [1] ; dos Santos, Rosa Ferreira [1]
Total Authors: 5
[1] Univ Sao Paulo, Sch Med, Div Endocrinol, Lab Med Invest LIM 18, Av Dr Arnaldo, 455 Room 3324, BR-01246903 Sao Paulo, SP - Brazil
[2] Unochapeco Univ, Sch Med, BR-89809900 Chapeco, SC - Brazil
Total Affiliations: 2
Document type: Journal article
Web of Science Citations: 2

Background: The TCF7L2 rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim of this study was to perform a metabolic characterization of T2DM patients with and without the TCF7L2 rs7903146 risk T allele and analyze some influences of the TCF7L2 genotype on glucose metabolism. Methods: Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism. Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C, 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. Additional secondary assessments included determination of insulinogenic index (IGI(30)), and insulin sensitivity (%S) and resistance (IR) by Homeostatic model assessment (HOMA). Results: Patients with the CT/TT genotype showed lower baseline plasma concentrations of C-peptide when compared with those with the CC genotype. Of the 56 individuals who participated in the mixed-meal test, 26 and 30 had the CC and CT/TT genotypes, respectively. CT/TT subjects, compared with CC individuals, had higher post prandial plasma levels of insulin and C-peptide at 30-120 min (p < 0.05) and proinsulin at 45-240 min (p < 0.05). Interestingly CT/TT individuals presented at baseline higher % S (p = 0.021), and lower IR (p = 0.020) than CC individuals. No significant differences in IGI(30) values were observed between groups. Conclusions: The T2DM individuals carrying the rs7903146 T allele of the TCF7L2 gene presented higher IR pattern in response to a mix-meal test, different of beta cell function at baseline assessed by C-peptide levels which was lower, and Homa-IR was lower when 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