Revisão sistemática sobre a relação entre estado inflamatório e metabolismo de ferro em população adulta com obesidade
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Data
2023-12-12
Autores
Alves, July do Nascimento [UNIFESP]
Orientadores
Lee, Kil Sun [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: A obesidade é uma doença de alta incidência mundial que acarreta sérios riscos metabólicos, como síndrome metabólica, hipertensão arterial, doenças cardíacas, problemas hepáticos, diabetes, dislipidemia, câncer, prejuízos na função cognitiva, inflamação e possíveis impacto no metabolismo de ferro. Estudos sugerem que a inflamação advinda da obesidade seria possivelmente uma das razões para a deficiência de ferro nessa população. Objetivos: Avaliar a associação entre a inflamação e a deficiência de ferro em população adulta com obesidade. Métodos: foi desenvolvido uma revisão sistemática/ metanálise com protocolo registrado no PROSPERO - CRD42020205546. Os estudos foram selecionados de modo sistematizado, por dois revisores independentes, com base nos resultados obtidos em PubMed, Cocharane, Lilacas, Scopus, Embase, Open Grey, Google Scholar e MedRxiv. Os critérios de inclusão utilizados foram adultos com o Índice de Massa Corporal maior que 30Kg/m², presença de valores absolutos de marcadores de inflamação (Proteína C-reativa, Interleucina-6, Interleucina-12 ou Fator de Necrose Tumoral alfa) e de marcadores de ferro (ferro, ferritina, saturação de transferrina, transferrina, capacidade total de ligação do ferro, receptor de transferrina solúvel ou hepcidina). Estudos apresentados sob a forma de revisão, com população com obesidade mesclada a sobrepeso, população envolvendo idosos e/ou crianças, dados de cultura celular ou animais e indivíduos com hemocromatose foram excluídos. Após a extração dos dados de interesse, realizou-se a análise qualitativa (metassíntese) e quantitativa (metanálise) por meio de testes de diferença de médias padronizada segundo o modelo randômico de Hedge, funnel e forest plot, análise de heterogeneidade e viés de publicação. Foi considerado um valor de p<0,05 como estatisticamente significante. Resultados: Dos 2883 artigos identificados na triagem, apenas 45 foram selecionados para análise qualitativa. Ainda, dos 45 estudos, apenas 18 estratificavam a população com obesidade em grupos, e desses apenas um estudo estratificava por grau de inflamação, não sendo possível analisar diretamente a influência da inflamação no status de ferro. As demais estratificações foram decorrentes de sexo, ausência ou presença de diabetes mellitus, grau de obesidade, hepatopatias, ausência ou presença de diabetes mellitus associada a anemia e intervenções. Limitações relacionados ao desenho do estudo e ausência de normalidade dos valores dos exames resultou em metanálise com poucos artigos. Dessa forma, verificou-se que não há diferença estatística significante de ferro na amostra presente ou ausente de diabetes mellitus (p=0,453) e que o índice de massa corporal e CRP não se difere entre os grupos deficientes de ferro e suficientes de ferro (p=0,415 e 0,365, respectivamente). Contudo, o alto grau de heterogeneidade encontrado nos estudos e de viés de publicação limitam os resultados encontrados. Conclusões: Apesar de não haver evidências fortes para verificar se a obesidade ocasiona deficiência de ferro, percebe-se que essa relação é complexa, envolvendo múltiplas vias orgânicas e limitações advindas não somente da busca em literatura, mas da fisiologia humana, tais quais grupos étnicos, gênero e status reprodutivos e demais fatores de confusão.
Introduction: Obesity is a world incident disease which results in serious metabolic risks, such as metabolic syndrome, arterial hypertension, cardiac disease, hepatic injuries, diabetes, dyslipidemia, cancer, cognitive functional damage, inflammation and possible impact on iron metabolism. Studies suggest that obesity inflammation would be the cause of iron deficiency in this population. Objective: To evaluate the association between inflammation and iron deficiency in the obese population. Methods: A systematic review/meta-analysis was developed, under PROSPERO registration - CRD42020205546. The studies were systematically analyzed by two independent reviewers, based on results from PubMed, Cocharane, Lilacas, Scopus, Embase, Open Grey, Google Scholar and MedRxiv. Inclusion criteria: adults with obesity, defined as Body Mass Index≥30lg/m², absolute values of inflammation markers (C-reactive protein, Interleukin-6, Interleukin-12 or Tumor necrosis factor-alpha) and iron markers (iron, ferritin, transferrin saturation, transferrin, total iron binding capacity, soluble transferrin receptor or hepcidin). Review, studies with obese and overweight sample mixed or with elderly and/or children, as well cell culture or animals data and hemochromatosis disease were excluded. After extracting the data from the variables of interest, qualitative (metasynthesis) and quantitative (meta-analysis) analysis was carried out, using standardized mean difference tests according to Hedge's random model, funnel and forest plot, heterogeneity and bias analysis of publication. A value of p<0.05 was considered statistically significant. Results: Of the 2883 articles identified in the screening, only 45 were selected for qualitative analysis. Furthermore, of the 45 studies, only 18 stratified the obese population into groups, and only one study stratified by degree of inflammation, do not allowing the directly analyze of the inflammation influence on iron status. The other stratifications were due to sex, absence or presence of diabetes mellitus, degree of obesity, liver disease, absence or presence of diabetes mellitus associated with anemia and future interventions. Limitations related to study design and variables normality absence resulted in a meta-analysis with few articles. Thus, it was verified that there is no statistically significant difference in iron in the present or absent of diabetes mellitus (p=0.453) and that the body mass index and C-reactive protein do not differ between iron sufficient and iron deficient groups (p= 0.415 and 0.365, respectively). However, this analysis showed a high degree of heterogeneity and publication bias, limiting the overall results. Conclusion: Although there is no strong evidence to verify whether obesity causes iron deficiency, it is clear the complexity of this relationship, since involving multiple pathways, as well limitations factor not only from literature searches, but from human physiology, due to ethnicity, gender and reproductive status and others confounding factors.
Introduction: Obesity is a world incident disease which results in serious metabolic risks, such as metabolic syndrome, arterial hypertension, cardiac disease, hepatic injuries, diabetes, dyslipidemia, cancer, cognitive functional damage, inflammation and possible impact on iron metabolism. Studies suggest that obesity inflammation would be the cause of iron deficiency in this population. Objective: To evaluate the association between inflammation and iron deficiency in the obese population. Methods: A systematic review/meta-analysis was developed, under PROSPERO registration - CRD42020205546. The studies were systematically analyzed by two independent reviewers, based on results from PubMed, Cocharane, Lilacas, Scopus, Embase, Open Grey, Google Scholar and MedRxiv. Inclusion criteria: adults with obesity, defined as Body Mass Index≥30lg/m², absolute values of inflammation markers (C-reactive protein, Interleukin-6, Interleukin-12 or Tumor necrosis factor-alpha) and iron markers (iron, ferritin, transferrin saturation, transferrin, total iron binding capacity, soluble transferrin receptor or hepcidin). Review, studies with obese and overweight sample mixed or with elderly and/or children, as well cell culture or animals data and hemochromatosis disease were excluded. After extracting the data from the variables of interest, qualitative (metasynthesis) and quantitative (meta-analysis) analysis was carried out, using standardized mean difference tests according to Hedge's random model, funnel and forest plot, heterogeneity and bias analysis of publication. A value of p<0.05 was considered statistically significant. Results: Of the 2883 articles identified in the screening, only 45 were selected for qualitative analysis. Furthermore, of the 45 studies, only 18 stratified the obese population into groups, and only one study stratified by degree of inflammation, do not allowing the directly analyze of the inflammation influence on iron status. The other stratifications were due to sex, absence or presence of diabetes mellitus, degree of obesity, liver disease, absence or presence of diabetes mellitus associated with anemia and future interventions. Limitations related to study design and variables normality absence resulted in a meta-analysis with few articles. Thus, it was verified that there is no statistically significant difference in iron in the present or absent of diabetes mellitus (p=0.453) and that the body mass index and C-reactive protein do not differ between iron sufficient and iron deficient groups (p= 0.415 and 0.365, respectively). However, this analysis showed a high degree of heterogeneity and publication bias, limiting the overall results. Conclusion: Although there is no strong evidence to verify whether obesity causes iron deficiency, it is clear the complexity of this relationship, since involving multiple pathways, as well limitations factor not only from literature searches, but from human physiology, due to ethnicity, gender and reproductive status and others confounding factors.
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Citação
ALVES, July do Nascimento. Revisão sistemática sobre a relação entre estado inflamatório e metabolismo de ferro em população adulta com obesidade. Dissertação (Mestrado em Biologia Molecular) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2023.