TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: DIABETOLOGY & METABOLIC SYNDROME; v. 10, APR 26 2018.
• Web of Science Citations: 2

Abstract

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 Opportunities: Regular Research Grants