性别相关的糖尿病肾病差异：机制及潜在治疗意义的综述。
Sex-related differences in diabetic kidney disease: A review on the mechanisms and potential therapeutic implications.
机构信息
Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine and Surgery Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
出版信息
J Diabetes Complications. 2021 Apr;35(4):107841. doi: 10.1016/j.jdiacomp.2020.107841. Epub 2020 Dec 31.
Abstract
Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events.
摘要
性别二态性可能在糖尿病肾病（DKD）的发病机制中起关键作用，并解释了糖尿病男性和女性之间观察到的疾病表型、对干预措施的反应和疾病进展的差异。因此，忽略性别作为生物因素的考虑可能导致诊断延迟和治疗效果不佳。本文综述了性别二态性对 DKD 潜在代谢和分子机制的影响，以及这些差异对治疗干预的潜在影响。为了成功实施精准医学，我们需要更好地了解 DKD 病理生理进展中的性别二态性。这些见解可以揭示出潜在的治疗靶点，这些靶点具有在最大化疗效的同时最小化不良反应的潜力。
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2
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Diabetes Care. 2020 Jun;43(6):1227-1233. doi: 10.2337/dc19-2424. Epub 2020 Mar 31.
3
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