Youth versus adult-onset type 2 diabetic kidney disease: Insights into currently known structural differences and the potential underlying mechanisms.
Youth versus adult-onset type 2 diabetic kidney disease: Insights into currently known structural differences and the potential underlying mechanisms.
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DOI：
10.1042/cs20210627
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发表时间：
2022-11-11
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影响因子：
--
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文献类型：
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2型糖尿病（T2D）是一种全球性卫生大流行病，具有重大的人道主义、经济和社会影响，特别是对发病率呈指数级上升的青年和青壮年。青年发病的T2D比成年发病的T2D具有更强的侵袭性表型，这转化为糖尿病肾病（DKD）进展率的重要差异。我们假设，由T2D引起的青年发病DKD可能表现出与成人发病T2D不同的形态计量学、代谢和分子特征，并继发于肾脏能量消耗和底物代谢的固有差异，导致中枢代谢失衡。在青春期开始时，肾脏结构的变化很明显，这也加剧了器官的基本高能量消耗率。此外，青春期胰岛素抵抗的生理状态增加了患肾脏疾病的风险，并发糖尿病和肥胖会加剧这种风险。肾脏能量代谢失配可能是预防和治疗DKD的药物干预的新靶点。通过代谢组学和活检获得的肾组织RNA测序，进一步研究青年发病T2D中导致DKD的潜在分子机制，对于扩大我们对早期DKD和治疗干预的潜在靶点的理解是必要的。此外，需要进行大规模的临床试验，评估针对肾脏能量消耗代谢失配的药物干预对肾脏保护作用的持续时间，以帮助降低青年发病T2D的DKD风险。
Type 2 diabetes (T2D) is a global health pandemic with significant humanitarian, economic, and societal implications, particularly for youth and young adults who are experiencing an exponential rise in incident disease. Youth-onset T2D has a more aggressive phenotype than adult-onset T2D and this translates to important differences in rates of progression of diabetic kidney disease (DKD). We hypothesize that youth-onset DKD due to T2D may exhibit morphometric, metabolic, and molecular characteristics that are distinct from adult-onset T2D and develop secondary to inherent differences in renal energy expenditure and substrate metabolism, resulting in a central metabolic imbalance. Kidney structural changes that are evident at the onset of puberty also serve to exacerbate the organ’s baseline high rates of energy expenditure. Additionally, the physiologic state of insulin resistance seen during puberty increases the risk for kidney disease and is exacerbated by both concurrent diabetes and obesity. A metabolic mismatch in renal energetics may represent a novel target for pharmacologic intervention, both for prevention and treatment of DKD. Further investigation into the underlying molecular mechanisms resulting in DKD in youth-onset T2D using metabolomics and RNA sequencing of kidney tissue obtained at biopsy is necessary to expand our understanding of early DKD and potential targets for therapeutic intervention. Furthermore, large scale clinical trials evaluating the duration of kidney protective effects of pharmacologic interventions that target a metabolic mismatch in kidney energy expenditure are needed to help mitigate the risk of DKD in youth-onset T2D.
影响因子：
16.2
作者：
Pavkov ME;Hanson RL;Knowler WC;Sievers ML;Bennett PH;Nelson RG
通讯作者：
Nelson RG