This review takes an inclusive approach to microvascular dysfunction in diabetes mellitus and cardiometabolic disease. In virtually every organ, dynamic interactions between the microvasculature and resident tissue elements normally modulate vascular and tissue function in a homeostatic fashion. This regulation is disordered by diabetes mellitus, by hypertension, by obesity, and by dyslipidemia individually (or combined in cardiometabolic disease), with dysfunction serving as an early marker of change. In particular, we suggest that the familiar retinal, renal, and neural complications of diabetes mellitus are late-stage manifestations of microvascular injury that begins years earlier and is often abetted by other cardiometabolic disease elements (eg, hypertension, obesity, dyslipidemia). We focus on evidence that microvascular dysfunction precedes anatomic microvascular disease in these organs as well as in heart, muscle, and brain. We suggest that early on, diabetes mellitus and/or cardiometabolic disease can each cause reversible microvascular injury with accompanying dysfunction, which in time may or may not become irreversible and anatomically identifiable disease (eg, vascular basement membrane thickening, capillary rarefaction, pericyte loss, etc.). Consequences can include the familiar vision loss, renal insufficiency, and neuropathy, but also heart failure, sarcopenia, cognitive impairment, and escalating metabolic dysfunction. Our understanding of normal microvascular function and early dysfunction is rapidly evolving, aided by innovative genetic and imaging tools. This is leading, in tissues like the retina, to testing novel preventive interventions at early, reversible stages of microvascular injury. Great hope lies in the possibility that some of these interventions may develop into effective therapies.

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糖尿病和心脏代谢疾病的微血管功能障碍

这篇综述对糖尿病和心脏代谢疾病的微血管功能障碍采取了包容性的方法。在几乎每个器官中，微血管系统和常驻组织元件之间的动态相互作用通常以稳态方式调节血管和组织功能。这种调节因糖尿病、高血压、肥胖症和血脂异常（或与心脏代谢疾病相结合）而紊乱，功能障碍是变化的早期标志。特别是，我们认为糖尿病常见的视网膜、肾脏和神经并发症是微血管损伤的晚期表现，多年前开始，通常由其他心脏代谢疾病因素（例如高血压、肥胖、血脂异常）助长。我们关注的证据表明，在这些器官以及心脏、肌肉和大脑中，微血管功能障碍先于解剖微血管疾病。我们建议早期，糖尿病和/或心脏代谢疾病均可导致可逆的微血管损伤并伴随功能障碍，随着时间的推移，这些损伤可能会或可能不会成为不可逆的和解剖学上可识别的疾病（例如，血管基底膜增厚、毛细血管稀疏、周细胞丢失、等等。）。后果可能包括常见的视力丧失、肾功能不全和神经病变，还有心力衰竭、肌肉减少症、认知障碍和不断升级的代谢功能障碍。在创新的遗传和成像工具的帮助下，我们对正常微血管功能和早期功能障碍的理解正在迅速发展。这导致，在像视网膜这样的组织中，在微血管损伤的早期可逆阶段测试新的预防干预措施。巨大的希望在于，其中一些干预措施有可能发展成为有效的疗法。