Lu Jin, Varghese Ron T, Zhou Lianzhen, Vella Adrian, Jensen Michael D
Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, PR China; Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN.
Metabolism. 2017 Mar;68:55-63. doi: 10.1016/j.metabol.2016.11.018. Epub 2016 Dec 9.
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.
TCF7L2基因变体rs7903146与2型糖尿病风险增加相关。我们研究了TCF7L2基因变体rs7903146及糖耐量对游离脂肪酸（FFA）代谢的影响。
我们招募了120名个体，其中一半在rs7903146位点为主要CC等位基因的纯合子，另一半为次要TT等位基因的纯合子；每人都接受了2小时、75克口服葡萄糖耐量试验（OGTT）。在OGTT之前及期间采集的血液中测量血浆葡萄糖、胰岛素和游离脂肪酸浓度。
当将男性和女性一起考虑时，CC和TT携带者在OGTT期间的总FFA浓度及脂肪酸种类百分比并无差异。然而，在OGTT期间，TT女性的单不饱和脂肪酸（MUFA）浓度及百分比高于CC女性。高胰岛素抵抗稳态模型评估（HOMA-IR）的TT携带者比高HOMA-IR的CC携带者有显著更高的空腹FFA浓度、更低的处置指数（DI）及更大的葡萄糖曲线下面积（AUC），而在低HOMA-IR组中未观察到此类差异。我们发现，与糖耐量正常（NGT）受试者相比，糖耐量受损（IGT）受试者的空腹（826±25对634±22μmol/L，P<0.0001）及OGTT血浆FFA浓度更高，在调整性别、年龄、体重指数（BMI）和基因型后该差异仍然存在。最后，在OGTT期间，IGT受试者的MUFA浓度及百分比高于NGT受试者。
尽管空腹胰岛素和葡萄糖水平相似，但IGT成年人的空腹血浆FFA高于NGT成年人。胰岛素抵抗和性别影响TCF7L2 rs7903146次要T等位基因携带者的血浆FFA反应。
