Rouskas Konstantinos, Cauchi Stephane, Raverdy Violeta, Yengo Loic, Froguel Philippe, Pattou François
INSERM, UMR 859 Biotherapies for Diabetes, Lille, France; CHRU, Lille, France; European Genetic Institute for Diabetes, Lille, France.
European Genetic Institute for Diabetes, Lille, France; University of Lille-Nord de France, Lille, France; CNRS UMR 8199, Institut Pasteur de Lille, France.
Surg Obes Relat Dis. 2014 Jul-Aug;10(4):679-83. doi: 10.1016/j.soard.2013.12.016. Epub 2014 Jan 9.
Roux-en-Y gastric bypass (RYGB) surgery improves glucose control in most but not all patients with type 2 diabetes mellitus (T2 DM). Transcription factor 7-like 2 (TCF7 L2) gene variation (rs7903146, C: wild-type allele, T: risk-allele) is the strongest contributor to T2 DM risk. Until now, there are no studies investigating gene interactions with changes of glycemia in obese patients with T2 DM after RYGB. The objective of this study was to assess the effect of TCF7 L2 genotype on RYGB-induced changes in glucose homeostasis in 99 obese patients with T2 DM at 1-year follow-up.
Body mass index (BMI) and fasting blood glucose (FBG) were measured before and 1, 3, 6, and 12 months after RYGB. Genotyping was performed with TaqMan technology. The effect of the interaction between TCF7 L2 genotype and postoperative time on BMI and FBG changes was analyzed with a linear mixed model.
Preoperatively, there was no difference in BMI, FBG, and other diabetes associated traits between homozygous (CC) (n = 49) and heterozygous (CT) or homozygous (TT) T risk-allele carriers (n = 50). One year after RYGB, 48 out of 99 patients had glycosylated hemoglobin (HbA1 c) lower than 6.5% in absence of any antidiabetic medication. BMI decreased similarly in both groups (P = .769, genotype-time interaction), however, the decrease in FBG over time was lower in T risk-allele carriers (P = .016, genotype-time interaction). At 1 year, FBG was 6.42 ± 2.98 mmol/L in CT/TT versus 5.36 ± 0.98 mmol/L in CC (P = .022, t test).
TCF7 L2 gene variation affected the decrease of FBG after RYGB in obese patients with T2 DM, independently of weight loss.
Roux-en-Y胃旁路术（RYGB）可改善大多数但并非所有2型糖尿病（T2 DM）患者的血糖控制。转录因子7样2（TCF7L2）基因变异（rs7903146，C：野生型等位基因，T：风险等位基因）是T2 DM风险的最强影响因素。到目前为止，尚无研究调查肥胖T2 DM患者RYGB术后基因与血糖变化之间的相互作用。本研究的目的是评估在99例肥胖T2 DM患者1年随访期内，TCF7L2基因型对RYGB诱导的葡萄糖稳态变化的影响。
在RYGB术前及术后1、3、6和12个月测量体重指数（BMI）和空腹血糖（FBG）。采用TaqMan技术进行基因分型。用线性混合模型分析TCF7L2基因型与术后时间之间的相互作用对BMI和FBG变化的影响。
术前，纯合子（CC）（n = 49）与杂合子（CT）或纯合子（TT）T风险等位基因携带者（n = 50）之间的BMI、FBG及其他糖尿病相关特征无差异。RYGB术后1年，99例患者中有48例在未使用任何抗糖尿病药物的情况下糖化血红蛋白（HbA1c）低于6.5%。两组的BMI下降情况相似（P = 0.769，基因型-时间相互作用），然而，T风险等位基因携带者的FBG随时间的下降幅度较小（P = 0.016，基因型-时间相互作用）。1年时，CT/TT组的FBG为6.42±2.98 mmol/L，而CC组为5.36±0.98 mmol/L（P = 0.022，t检验）。
TCF7L2基因变异影响肥胖T2 DM患者RYGB术后FBG的下降，与体重减轻无关。
