Efeitos da suplementação com selênio em marcadores do controle glicêmico em roedores saudáveis: uma revisão sistemática e metanálise

Abstract

In vivo and in vitro studies have shown that selenium supplementation has insulinmimetic action related to the antioxidant activity of this micronutrient. Otherwise, other studies suggest the ingestion of high doses of selenium interferes with insulin signaling, leading to insulin resistance and hyperglycemia. In view of these controversies, this systematic review aimed to answer the following question: “Does Se supplementation affect glycemic control markers in healthy rodents?” The review registered at PROSPERO (CRD42021212011) will be developed based on Preferred Reporting Items for Systematic Review and Metanalysis (PRISMA). Experimental, randomized or non-randomized trials of healthy animal models (rodents) of both sexes, only supplemented with selenium (inorganic, organic or synthetic compounds), regardless of dose, frequency or route of administration, will be included. Fasting blood glucose (FBG) will be considered as the primary outcome and insulin concentration, insulin resistance (HOMA-IR), selenium concentration and GPx expression as secondary outcomes. The process of search, selection, extraction and quality analysis will be carried out independently, by two reviewers. Divergences will be resolved by a third reviewer. Searches will be conducted in the databases Embase, Scopus, Medline-Pubmed, Web of Science and CINAHL. The analysis of risk of bias and methodological quality of the included studies will be performed by SYRCLE and CAMARADES tools, respectively. Stata software version 15.1 was used to conduct the meta-analysis. Continuous variables represented as standard mean differences (DMP) with 95% confidence intervals (CIs). Heterogeneity between studies was verified by the I² test. The search strategy resulted in 1389 articles reported, with 13 studies remaining at the end of the selection. Among the selected articles, 38% (5 articles) had adverse effects on fasting blood glucose, insulin or glycated hemoglobin, after treatment with doses between 5 µmol/kg/day and 4000 µg/kg/day sodium selenite, for 28-30 days. Another five studies did not report significant changes in fasting glucose after treatment with sodium selenite, as well as two studies conducted with selenium nanoparticles (SeNPS). The meta-analysis indicated a significant increase in fasting glucose in healthy rodents after supplementation with sodium selenite (DMP (95% CI)=5,10 (2,19-8,01) and I²=95.4% (p<0.001)), effect confirmed in the analysis of subgroups according to intervention doses. In turn, Hb1Ac and GPX concentration did not showed significant effects after the intervention. In total, 23.1% of the studies were classified as high quality, with a high risk of selection bias, with no biased reporting of results. Due to the low methodological quality and heterogeneity of studies observed in this review, judicious standardization of doses and forms of selenium supplementation in preclinical studies is suggested, in order to safely guide extrapolation for clinical studies.