OBJECTIVE Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

中文翻译：

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因 COVID-19 住院的糖尿病患者的炎症、高血糖和不良结果

目的 糖尿病 (DM) 是 2019 年严重冠状病毒病 (COVID-19) 的主要危险因素，原因尚不清楚。研究设计和方法 我们利用 COVID-19 国际炎症研究 (ISIC)，这是一项对 2,044 名因 COVID-19 住院的患者进行的多中心观察研究，以描述 DM 对住院结果的影响并评估炎症和高血糖归因于 DM 的风险。我们测量了入院时收集的炎症生物标志物，并收集了整个住院期间的葡萄糖水平和胰岛素数据。主要结局是院内死亡、需要机械通气和需要肾脏替代治疗的复合结果。结果 在参与者（平均年龄 60 岁，58.2% 为男性）中，DM 患者（n = 686、33. 5%）的主要结局累积发生率（37.8% 对 28.6%）和炎症生物标志物水平明显高于没有 DM 的人群。在生物标志物中，DM 仅与多变量分析中较高的可溶性尿激酶纤溶酶原激活物受体 (suPAR) 水平相关。调整 suPAR 水平消除了 DM 与主要结果之间的关联（调整后的比值比 1.23 [95% CI 0.78, 1.37]）。在中介分析中，我们估计 DM 对 suPAR 介导的主要结果的影响比例为 84.2%。高血糖和更高的胰岛素剂量是主要结局的独立预测因子，效应大小不受调整 suPAR 水平的影响。