RESUMO
Adipose tissue undergoes significant changes in structure, composition, and function with age including altered adipokine secretion, decreased adipogenesis, altered immune cell profile and increased inflammation. Considering the role of adipose tissue in whole-body energy homeostasis, age-related dysfunction in adipose metabolism could potentially contribute to an increased risk for metabolic diseases and accelerate the onset of other age-related diseases. Increasing cellular energy expenditure in adipose tissue, also referred to as thermogenesis, has emerged as a promising strategy to improve adipose metabolism and treat obesity-related metabolic disorders. However, translating this strategy to the aged population comes with several challenges such as decreased thermogenic response and the paucity of safe pharmacological agents to activate thermogenesis. This mini-review aims to discuss the current body of knowledge on aging and thermogenesis and highlight the unexplored opportunities (cellular mechanisms and secreted factors) to target thermogenic mechanisms for delaying aging and age-related diseases. Finally, we also discuss the emerging role of thermogenic adipocytes in healthspan and lifespan extension.
Assuntos
Tecido Adiposo Marrom , Obesidade , Humanos , Idoso , Tecido Adiposo Marrom/metabolismo , Obesidade/metabolismo , Metabolismo Energético/fisiologia , Envelhecimento , Termogênese/fisiologiaRESUMO
Objetivo: Avaliar a relação de custo-efetividade de mirabegrona como tratamento de primeira escolha de pacientes adultos com síndrome da bexiga hiperativa (SBH) comparada a antimuscarínicos orais comumente prescritos no manejo dessa condição. Métodos: O modelo de Markov foi utilizado, com ciclos mensais e horizonte temporal de um ano, para analisar a relação de custo-efetividade de mirabegrona em comparação a tolterodina, oxibutinina, darifenacina e solifenacina. Os pacientes iniciaram o modelo em tratamento com mirabegrona ou um dos comparadores, sendo distribuídos em cinco níveis de gravidade da doença, de acordo com a frequência miccional e número de episódios de incontinência, e a cada ciclo mensal poderiam melhorar, piorar ou permanecer no mesmo nível de severidade do ciclo anterior. Os resultados foram apresentados por meio de uma razão de custo-efetividade incremental. Resultados: Considerando a perspectiva do sistema de saúde suplementar, o custo total do tratamento com mirabegrona foi de R$ 2.455,26 e os parâmetros de efetividade em 0,491 e 0,498 (melhora na gravidade da incontinência e frequência miccional, respectivamente), sendo mais efetivo que os comparadores. Com relação à perspectiva pública, foi estimado um custo com o tratamento de R$ 1.396,01, com características similares de efetividade. De maneira geral, o tratamento com mirabegrona foi dominante quando comparado à tolterodina e custo-efetivo na comparação com os demais antimuscarínicos, em ambas as perspectivas analisadas. Conclusão: Mirabegrona demonstrou ser a melhor opção para tratamento de primeira escolha da SBH com potencial de redução de custos ao longo do tempo, tanto para o sistema público quanto para o sistema de saúde suplementar brasileiro.
Objective: To assess the cost-effectiveness of mirabegron as first-choice treatment in adult patients with of overactive bladder (OAB) compared to oral antimuscarinics, usually prescribed for this condition. Methods: A Markov model has been adopted, with monthly cycles and a one-year time horizon, to analyze the cost-effectiveness of mirabegron compared to antimuscarinic agents: tolterodine; oxybutynin; darifenacin; and solifenacin. The model started with patients receiving treatment with mirabegron or one of the comparators and then, they were assigned to five disease severity levels according to micturition frequency and number of incontinence episodes, and within each monthly cycle they could improve, worsen or remain at the same symptom severity level. Results were presented using an incremental cost-effectiveness ratio. Results: Considering the Brazilian private perspective, treatment with mirabegron resulted in a total cost of R$ 2,455.26 and effectiveness parameters at 0.491 and 0.498 (improvement in incontinence severity and micturition, respectively), being more effective than the comparators. Regarding the Brazilian public perspective, treatment with mirabegron resulted in a total cost of R$ 1,396.01 with similar effectiveness estimation. In general, a dominance was observed when mirabegron was compared to tolterodine and a cost-effectiveness profile against the other muscarinic antagonists, considering both health perspectives. Conclusion: Mirabegron has proven to be the best option for OAB first-line treatment with potential cost savings over time for both the public and private health care systems in Brazil.
