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



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-h, 75g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.



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 HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826±25 vs. 634±22μmol/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.



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.
Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, PR China; Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Jin
J
Lu
Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Ron T
RT
Varghese
Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Lianzhen
L
Zhou
Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Adrian
A
Vella
Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN. Electronic address: jensen@mayo.edu.
Michael D
MD
Jensen
D000328:Adult; D000368:Aged; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
D005230:Fatty Acids, Nonesterified; D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein
Fatty acids; Free fatty acids; Insulin action; Insulin secretion; Prediabetes