Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways, which are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of micro- and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.

中文翻译：

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糖尿病并发症的保护因素和发病机制。

糖尿病的慢性并发症是由多种代谢途径的多种紊乱引起的，这是与该疾病相关的大部分发病率和死亡率的原因。传统上，糖尿病并发症分为微血管起源的并发症和大血管起源的并发症。我们建议将这一过时的分类修改为血管、实质和混合（血管和实质）组织来源的糖尿病并发症，因为糖尿病并发症的范围从仅涉及血管组织的并发症到主要涉及实质器官的并发症。近年来，关于糖尿病并发症的发病机制发生了重大范式转变，其中重点已从风险研究转向风险与保护因素之间相互作用的研究。虽然危险因素对于糖尿病慢性并发症的发展显然很重要，但最近的研究表明，保护性因素在调节糖尿病并发症的发展和严重程度方面同样重要。这些保护性反应可能有助于解释某些组织中并发症的不同严重程度，甚至缺乏病理学。然而，尽管该领域的研究越来越多，但尚未对保护因素及其作用机制进行全面审查。因此，本综述重点关注支持内源性保护因子这一观点的临床、生化和分子机制，及其在糖尿病慢性并发症的发生和进展中的作用。此外，本次综述还旨在确定该领域未来研究的主要需求。