Fountoulakis Nikolaos, Miyamoto Yoshihisa, Pavkov Meda E, Karalliedde Janaka, Maltese Giuseppe
School of Cardiovascular, Metabolic Medicine and Sciences, King's College London, London, UK.
Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Diabet Med. 2025 Feb;42(2):e15464. doi: 10.1111/dme.15464. Epub 2024 Nov 5.
Among people with diabetes those with chronic kidney disease (CKD) have a reduced life expectancy with increased risk of cardiovascular disease (CVD) a major contributor to morbidity and mortality. CKD related to diabetes is growing worldwide and is one of the leading causes of kidney failure globally. Diabetes is associated with accelerated vascular ageing and the related mechanisms and mediators that drive the progression of CKD and CVD disease in people with diabetes may help provide insights into the pathophysiology of cardio-renal complications and guide treatment interventions in people with diabetes.
We conducted a narrative review of the literature using PubMed for English language articles that contained keywords that related to diabetes, chronic or diabetic kidney disease, ageing, cellular senescence, arterial stiffness, Klotho and sirtuins, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, renin angiotensin aldosterone system (RAAS) and glucagon-like peptide-1 (GLP-1) receptor agonists.
Progressive kidney disease in diabetes is associated with accelerated ageing driven in part by multiple processes such as cellular senescence, inflammation, oxidative stress and circulating uremic toxins. This accelerated ageing phenotype contributes to increased arterial stiffness, endothelial dysfunction, cognitive decline and muscle wasting, thereby elevating morbidity and mortality in individuals with diabetes and CKD. Deficiency of the kidney-derived anti-ageing hormone Klotho and reduced sirtuin levels play pivotal roles in these ageing pathways. Dietary, lifestyle and pharmacological interventions targeting vascular ageing may help reduce the progression of CKD and associated CVD in people with diabetes. The current standard of care and pillars of treatment for kidney disease such as RAAS inhibitors, SGLT-2 inhibitors and GLP-1 receptor agonists all influence pathways involved in vascular ageing.
A multifactorial intervention to prevent the development of CKD by targeting traditional risk factors as well as treatment with novel agents with cardio-renal beneficial effects can prevent accelerated ageing and extend lifespan in people with diabetes.
在糖尿病患者中，患有慢性肾脏病（CKD）的患者预期寿命缩短，心血管疾病（CVD）风险增加，而心血管疾病是发病和死亡的主要原因。与糖尿病相关的慢性肾脏病在全球范围内呈上升趋势，是全球肾衰竭的主要原因之一。糖尿病与血管加速老化有关，驱动糖尿病患者慢性肾脏病和心血管疾病进展的相关机制和介质可能有助于深入了解心肾并发症的病理生理学，并指导糖尿病患者的治疗干预。
我们使用PubMed对文献进行了叙述性综述，检索了包含与糖尿病、慢性或糖尿病肾病、衰老、细胞衰老、动脉僵硬度、klotho和sirtuins、钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂、肾素-血管紧张素-醛固酮系统（RAAS）和胰高血糖素样肽-1（GLP-1）受体激动剂相关关键词的英文文章。
糖尿病中的进行性肾病与加速衰老有关，这部分是由细胞衰老、炎症、氧化应激和循环尿毒症毒素等多种过程驱动的。这种加速衰老的表型导致动脉僵硬度增加、内皮功能障碍、认知衰退和肌肉萎缩，从而提高了糖尿病和慢性肾脏病患者的发病率和死亡率。肾脏来源的抗衰老激素klotho缺乏和sirtuin水平降低在这些衰老途径中起关键作用。针对血管老化的饮食、生活方式和药物干预可能有助于减少糖尿病患者慢性肾脏病和相关心血管疾病的进展。目前治疗肾病的标准护理和治疗支柱，如RAAS抑制剂、SGLT-2抑制剂和GLP-1受体激动剂，都影响参与血管老化的途径。
通过针对传统危险因素进行多因素干预以预防慢性肾脏病的发生，以及使用具有心肾有益作用的新型药物进行治疗，可以预防加速衰老并延长糖尿病患者的寿命。
