RESUMO Objetivo: identificar na literatura os fatores que estão associados ao desenvolvimento de disfunções vestibulares em indivíduos com diabetes mellitus tipo 2 (DM2). Métodos: trata-se de uma revisão integrativa da literatura, cuja busca foi realizada nas bases de dados ISI, Scielo, LILACS e PubMed, sendo utilizados os descritores: “type 2 diabetes mellitus”, “vertigo”, “dizziness” e “vestibular diseases”. Foram incluídos artigos publicados nos últimos dez anos e que respondessem a seguinte questão: quais fatores estão associados ao desenvolvimento de disfunções vestibulares em indivíduos com DM2? Resultados: a busca resultou em 426 artigos, sendo que 10 atenderam aos critérios de elegibilidade. A maioria dos participantes dos estudos selecionados que apresentaram disfunções vestibulares eram do sexo feminino, idade superior a 40 anos e possuíam mais de uma comorbidade associada a DM2, sendo a principal, a hipertensão arterial sistêmica (HAS). De acordo com a literatura, a fisiologia da orelha interna permite que pequenas alterações de glicose influenciem seu funcionamento normal, o que torna os indivíduos diabéticos mais suscetíveis a desenvolverem disfunções vestibulares. Conclusão: o presente estudo constatou que a DM2 pode desencadear ou contribuir para a manifestação da disfunção vestibular, tendo como principais fatores associados a idade avançada, o sexo feminino e comorbidades diversas, tais como dislipidemia, HAS e síndrome metabólica.

ABSTRACT Purpose: to identify, in the literature, the factors associated with the development of vestibular dysfunctions in individuals with type 2 diabetes mellitus (DM2). Methods: an integrative review of the literature, whose survey was conducted in the databases ISI, SciELO, LILACS and PubMed, using the following descriptors: “type 2 diabetes mellitus”, “vertigo”, “dizziness”, and “vestibular diseases". Articles published in the last 10 years that answered the research question (“What factors are associated with the development of vestibular disorders in individuals with DM2?”) were included in the study. Results: the search returned 426 articles, 10 of which met the eligibility criteria. Most of the participants of the selected studies who had vestibular dysfunctions were women over 40 years old and had more than one comorbidity related to DM2, the main one being the systemic arterial hypertension (SAH). According to the literature, the physiology of the inner ear allows small glucose alterations to influence its normal functioning, which makes diabetic individuals more susceptible to developing vestibular dysfunctions. Conclusion: according to this study, DM2 can trigger or contribute to the manifestation of vestibular dysfunction, whose main associated factors are advanced age, female gender, and various comorbidities, as dyslipidemia, SAH and metabolic syndrome.

The TK6 lymphoblastoid cell line is known to be mismatch repair (MMR) and p53 proficient. Deficiency in MMR results in a mutator phenotype characterized by microsatellite instability (MSI) and increased hprt mutant frequency (MF). Increased hprt MF is also a biomarker of effect for exposure to ionizing radiation. In order to test if a mutator phenotype could be induced by low doses of gamma ionizing radiation, an hprt cloning assay and a MSI investigation were performed after radiation exposure. The spontaneous MF was 1.6 x 10-6. The groups exposed to 0.2, 0.5 and 1.0 Gy had hprt MFs of 2.3, 3.3 and 2.2 x 10-6, respectively. The spontaneous MSI frequency per allele in non-selected cells was 5.4 x 10-3, as evidenced at the loci D11S35, nm23-H1, D8S135 and p53. MSI frequencies in the groups exposed to 0.2, 0.5 and 1.0 Gy were found to be < 4.7, < 7.7 and < 12 x 10-3, respectively. The frequencies of hprt mutants and MSI found in this study suggest that low doses of ionizing radiation increase hprt mutant frequency without triggering the mutator phenotype pathway.

The multisteps of tumorigenesis involve the classic chromosomal instability and the mutator phenotype pathways featured by a predisposition to acquire mutations in tumor suppressor genes and oncogenes. Expansion and contraction of microsatellite sequences due to a deficient mismatch repair system are a marker of the mutator phenotype. Controversial results regarding the extent of microsatellite instability (MSI) have been reported in the development and progression of myeloid malignancies. Here, we investigated MSI and loss of heterozygosity (LOH) frequencies at the microsatellite loci BAT-26, D7S486, D8S135, ANK1, IFNA, TP53 and bcr of 19 Brazilian patients with acute (AML) and chronic myeloid leukemia (CML). One AML patient and one CML patient were categorized as having a high degree of microsatellite instability (MSI-H), corresponding to 10.5% (2/19) of all patients. LOH at loci BAT-26 and TP53 was present in 30% of the patients with AML alone. Despite the small sample size, our results suggest that the mutator phenotype, as verified by MSI frequency, could play a role in the leukemogenesis of a small subset of patients with myeloid leukemia.