Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

Abstract

Objective TCF7L2 variant rs7903146 is associated with increased risk for Type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism. Research design and methods We recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-hour, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT. Results Total FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMAIR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 µmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT. Conclusions Despite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.

Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu

“…1,2,15,16 Mechanistic studies addressing the presence and association of these polymorphisms in the risk of incidence of T2DM highlight that carriers of the SNPs exhibit modulations in glucagon and insulin secretion, oral glucose tolerance, leptin regulation and adipose tissue metabolism. 1,8,9,17 In order to understand the risk of incidence of T2DM in the non-diabetic controls (mean age 26.15±1.4) of the present study we carried out an OGTT and similar to other earlier reports, the present data also indicates that the risk allele carriers exhibited relatively higher plasma glucose levels, thus indicating that proper counseling, dietary interventions and physical exercise could play a vital role in the preventive management of T2DM.…”

“…[2][3][4][5][6][7] The rs7903146, rs12255372 intronic variants of the TCF7L2 gene are reported to functionally impair glucagon, insulin, incretin secretions; impair glucose regulation, tolerance and modulate body mass index (BMI). 8,9 While population specific studies on the association of TCF7L2 with T2DM in regions of North India, Chennai and Hyderabad exists, the prevalence and distribution of these allelic variants in south Tamil Nadu has been obscure. [10][11][12][13] Hence the present study aims in determining the incidence and prevalence of the TCF7L2 polymorphisms rs7903146, rs12255372 in the regional south Tamil Nadu population, and understand their influence in the risk of incidence of T2DM.…”

The Type 2 Diabetes Susceptibility PROX1 Gene Variants Are Associated with Postprandial Plasma Metabolites Profile in Non-Diabetic Men

“…This trial was registered at as NCT03792685. Only males were enrolled into the meal-challenge-tests because of the possible sexual dimorphism of investigated factors [20]. The study participants ( n = 28) were divided into 2 groups dependent on the PROX1 rs340874 genotypes: the homozygous carriers of high-risk (HR) allele C (CC genotype, n = 12) and carriers of low-risk (LR) allele T (both CT and TT genotypes, n = 16).…”

A Preliminary Study Showing the Impact of Genetic and Dietary Factors on GC–MS-Based Plasma Metabolome of Patients with and without PROX1-Genetic Predisposition to T2DM up to 5 Years Prior to Prediabetes Appearance

“…This trial was registered at www.clinicaltrials.gov (accessed on 15 April 2021) as NCT03792685. Taking into consideration the fact that investigated factors can be characterised by sexual dimorphism [23], only male participants were included in the study group. Participants (n = 18) were divided into 2 groups based on the PROX1 rs340874 genotypes: the homozygous carriers of high-risk (HR) allele C (CC genotype, n = 12) and carriers of low-risk (LR) allele T (TT genotypes, n = 6).…”