International Journal of General Medicine (Jul 2021)
Defective Allele of the Neuronal Nitric Oxide Synthase Gene Increases Insulin Resistance During Acute Phase of Myocardial Infarction
Abstract
Otávio T Nóbrega,1 Alessandra M Campos-Staffico,2 Elayne Kelen Oliveira,3 Daniel B Munhoz,3 Filipe A Moura,3 Luis Sérgio F Carvalho,4 Alexandre Anderson SM Soares,1,5 Ciro M Gomes,1,6 Audrey C Tonet-Furioso,7 Andrei C Sposito1,3 On behalf of Brasilia Heart Study and the Brasilia Heart Study Group1Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, Brazil; 2Departamento de Farmácia, Faculdade de Ciências da Saúde, Universidade de Brasília (UnB), Brasília, DF, Brazil; 3Departamento de Cardiologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil; 4Centro de Inovação, Ensino e Pesquisa, Instituto de Gestão Estratégica em Saúde do Distrito Federal, Brasília, DF, Brazil; 5Serviço de Cardiologia, Instituto Biocárdios, Brasília, DF, Brazil; 6Laboratório de Dermatomicologia, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, Brazil; 7Programa de Pós-Graduação em Gerontologia, Universidade Católica de Brasília (UCB-DF), Taguatinga, DF, BrazilCorrespondence: Andrei C SpositoLaboratório de Biologia Vascular e Aterosclerose (AteroLab), Departamento de Cardiologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), 126 Rua Tessália Vieira de Camargo, Campinas, 13083-887, SP, BrazilTel +55 19 3521 9590Fax +55 19 3289 4107Email [email protected]: Glycemic disorders are strong predictors of mortality in ST-elevation myocardial infarction (STEMI) patients, and disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether a defective allele of the neuronal nitric oxide synthase (nNOS) gene (NOS1) might influence insulin response and blood-glucose balance during the acute phase of STEMI and if post-infarction total plasma-NO levels and vasodilation scores varied across nNOS genotypes.Methods: Consecutive patients with STEMI (n=354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. In-hospital clinical and blood evaluations were performed at admission and five days after STEMI, with glycemic, insulinemic, and disposition indices assessed at the same times. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day.Results: Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity on day 1 while showing the highest β-cell function and no changes in the circulating NO pool, which is compatible with hyperresponsive β cells counteracting the inherent glucose-resistant state of AA patients. At day 5, glycemic scores had shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a significant yet poor increase in NO bioavailability compared to that among G carriers. All in all, defective homozygotes showed greater insulin resistance at admission that had reversed by 5 days after STEMI. Even so, A carriers developed lower FMD scores compared to G homozygotes after the acute phase.Conclusion: A defective nNOS allele (and due decline in NO production) seemed to elicit a hyperinsulinemia response to compensate for an insulin-resistant state during the acute phase of STEMI and to be associated with poor endothelial function after the acute phase.Keywords: nitric oxide, insulin, blood glucose, vasodilation, polymorphism, myocardial infarction
