Cintra Riobaldo, Moura Filipe A, Carvalho Luiz S F, Daher Mauricio, Santos Simone N, Costa Ana P R, Figueiredo Valeria N, Andrade Joalbo M, Neves Francisco A R, Silva Jose C Quinaglia E, Sposito Andrei C
Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), Campinas, SP, Brazil.
Health Science School, University of Brasília (UnB), Brasília, DF, Brazil.
BBA Clin. 2016 Apr 2;5:159-65. doi: 10.1016/j.bbacli.2016.03.010. eCollection 2016 Jun.
The favorable effects of insulin during myocardial infarction (MI) remain unclear due to the divergence between mechanistic studies and clinical trials of exogenous insulin administration. The rs7903146 polymorphism of the transcription factor 7-like 2 (TCF7L2) gene is associated with attenuated insulin secretion.
In non-diabetic patients with ST-elevation MI (STEMI), using such a model of genetically determined down-regulation of endogenous insulin secretion we investigated the change in plasma insulin, C-peptide, interleukin-2 (IL-2), C-reactive protein (CRP), and nitric oxide (NOx) levels between admission (D1) and the fifth day after MI (D5). Coronary angiography and flow-mediated dilation (FMD) were performed at admission and 30 days after MI, respectively. Homeostasis Model Assessment estimated insulin secretion (HOMA2%β) and insulin sensitivity (HOMA2%S).
Although glycemia did not differ between genotypes, carriers of the T-allele had lower HOMA2%β and higher HOMA2%S at both D1 and D5. As compared with non-carriers, T-allele carriers had higher plasma IL-2 and CRP at D5, higher intracoronary thrombus grade, lower FMD and NOx change between D1 and D5 and higher 30-day mortality.
In non-diabetic STEMI patients, the rs7903146 TCF7L2 gene polymorphism is associated with lower insulin secretion, worse endothelial function, higher coronary thrombotic burden, and higher short-term mortality.
During the acute phase of MI, a lower capacity of insulin secretion may influence clinical outcome.
由于外源性胰岛素给药的机制研究与临床试验结果存在差异，胰岛素在心肌梗死（MI）期间的有益作用仍不明确。转录因子7样2（TCF7L2）基因的rs7903146多态性与胰岛素分泌减弱有关。
在非糖尿病ST段抬高型心肌梗死（STEMI）患者中，利用这种内源性胰岛素分泌基因决定下调的模型，我们研究了入院时（D1）和心肌梗死后第5天（D5）血浆胰岛素、C肽、白细胞介素-2（IL-2）、C反应蛋白（CRP）和一氧化氮（NOx）水平的变化。分别在入院时和心肌梗死后30天进行冠状动脉造影和血流介导的血管舒张（FMD）。稳态模型评估估计胰岛素分泌（HOMA2%β）和胰岛素敏感性（HOMA2%S）。
尽管不同基因型之间血糖无差异，但T等位基因携带者在D1和D5时的HOMA2%β较低，HOMA2%S较高。与非携带者相比，T等位基因携带者在D5时血浆IL-2和CRP较高，冠状动脉内血栓分级较高，D1和D5之间FMD和NOx变化较低，30天死亡率较高。
在非糖尿病STEMI患者中，rs7903146 TCF7L2基因多态性与胰岛素分泌降低、内皮功能较差、冠状动脉血栓负荷较高和短期死亡率较高有关。
在心肌梗死急性期，较低的胰岛素分泌能力可能影响临床结局。
