Is the type of diabetes treatment relevant to outcome of COVID‐19?

It has long been recognized that inflammation is strongly related to insulin resistance1, 2 and plays an important role in driving complications of diabetes. ³ The acceleration of atherosclerosis in type 2 diabetes has been considered to reflect this process, ⁴ involving vascular macrophage infiltration associated both with profibrotic changes and with thrombosis. ⁵ Similar acceleration of inflammation is related to diabetic nephropathy ⁶ and to the progression from nonalcoholic fatty liver to steatohepatitis. ⁷ A number of treatments of type 2 diabetes are associated with improvement in cardiovascular outcome. In the case of thiazolidinediones, such benefits appear linked both to insulin sensitization and to anti‐inflammatory effects. ⁸

An important aspect of the pathophysiology of the 2019 novel coronavirus infectious disease (COVID‐19) involves the development of diffuse pulmonary alveolar damage with extensive macrocyte infiltration. ⁹ Based on this observation, the use of anti‐inflammatory treatments has been proposed for COVID‐19, with some recommendation for chloroquine and hydroxychloroquine, 10, 11 although two preliminary reports failed to show benefit.12, 13 In addition, these can lead to QT interval prolongation with risk of ventricular arrhythmia, particularly when administered with azithromycin. ¹⁴ The recent US National Institutes of Health treatment guidelines statement suggested that prophylactic use of hydroxychloroquine has no evidence of efficacy and recommended that the combination with azithromycin not be used. ¹⁵ Recently, the observation that severity of COVID‐19 tracks with elevation in circulating inflammatory mediators ¹⁶ has led to the proposal that anti‐inflammatory agents, corticosteroids, and immune suppressant treatments might be of benefit, ¹⁷ although others argue against such approaches. ¹⁸ Similarly, use of nonsteroidal anti‐inflammatory agents has been recommended by some authors, ¹⁹ whereas others suggest these drugs may worsen outcome of respiratory infections and hence be inadvisable in COVID‐19, ²⁰ leaving at least some degree of doubt. ²¹

The use of existing treatments for type 2 diabetes with recognized anti‐inflammatory effects may have benefits both in early and in advanced COVID‐19, without the potential harms of existing anti‐inflammatory agents. Furthermore, there is reason to think that the degree of glycemic control may influence outcome of COVID‐19. ²² Existing data sets give minimal information as to drivers of outcome among persons with diabetes, at best noting the presence or absence of diabetes. ²³ We need to know much more about the characteristics of people with diabetes with COVID‐19, at all levels of severity, including their diabetes treatment regimen, measures of glycemic control, and measures associated with insulin resistance including body mass index, waist circumference, and triglyceride and high‐density lipoprotein cholesterol levels, to ascertain factors that may be associated with differing prognosis of the infection, both in earlier/milder and later/more severe cases, and, ultimately, to design appropriate diabetes treatment approaches that may play a role in optimizing outcome.

长期以来, 炎症与胰岛素抵抗密切相关, 且在糖尿病并发症中起重要作用, 2型糖尿病动脉粥样硬化的加速被认为反映了这一过程, 包括与纤维化改变和血栓形成相关的血管巨噬细胞浸润。类似的炎症加速还与糖尿病肾病以及非酒精性脂肪肝到脂肪性肝炎的进展有关。一些2型糖尿病的治疗与心血管预后的改善有关。在噻唑烷二酮类药物中, 这种益处似乎与胰岛素增敏和抗炎作用有关。

COVID‐19病理生理学的一个重要方面包括弥漫性肺泡损伤的形成, 并伴有广泛的巨幼红细胞浸润。基于这一观察, 抗炎治疗已经被建议应用于COVID‐19, 有些建议推荐使用氯喹和羟氯喹, 尽管有两个初步报告表明这两个药物没有体现出期望的疗效。此外, 这些药物可能导致QT间期延长, 有室性心律失常的风险, 特别是在联合服用阿奇霉素时。美国国立卫生研究院最近发表的治疗指南指出, 预防性使用羟基氯喹没有疗效, 并建议不要与阿奇霉素联合使用。最近, 观察到COVID‐19的严重程度与循环炎症介质的升高有关, 因此使用抗炎药、皮质类固醇和免疫抑制剂可能是有益的建议, 尽管也有人反对这些方法。同样, 一些作者建议使用非甾体抗炎药, 而另一些人则认为这些药物可能会恶化呼吸道感染, 因此对COVID‐19来说是不适宜的, 至少引起一定程度的怀疑和争议。

使用现有公认具抗炎作用治疗2型糖尿病的药物可能会对早期和晚期COVID‐19有好处, 而不会产生现有抗炎药的潜在危害。此外, 有理由认为血糖控制的程度可能会影响COVID‐19的预后。现有的数据集很少提供关于糖尿病患者预后驱动因素的信息, 充其量也就是注意到了糖尿病的存在或不存在。我们需要更多地了解COVID‐19糖尿病患者在各个方面的特征, 在所有严重程度上, 包括糖尿病治疗方案, 血糖控制的措施, 以及与胰岛素抵抗相关的指标, 包括体重指数, 腰围, 甘油三酯和高密度脂蛋白胆固醇水平, 以确定可能与早期(轻度)和晚期(重度)感染的不同预后相关的因素, 最终设计可能对优化预后起作用的糖尿病治疗方法。