Division of Endocrinology, Department of Medicine, Woodlands Health Campus Singapore, Singapore, Singapore.
Clinical Research Unit, Khoo Teck Puat Hospital Singapore, Singapore, Singapore.
J Med Virol. 2021 May;93(5):3023-3032. doi: 10.1002/jmv.26837. Epub 2021 Feb 9.
Diabetes is a risk factor for developing severe COVID-19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID-19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID-19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%-6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID-19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID-19 outcome was analyzed by cox regression. Adjusted mediation analysis of C-reactive protein (CRP) on the relationship between diabetes and severe COVID-19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID-19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID-19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54-17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92-8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22-4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID-19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID-19 infection, confirming that inflammation is important in the pathogenesis of severe COVID-19 in diabetes.
糖尿病是发生严重 COVID-19 的一个危险因素，但发病机制尚不清楚。我们研究了糖尿病与 COVID-19 严重程度之间的关联是否可能与炎症有关。我们还假设这种风险增加可能扩展到糖尿病前期。在新加坡进行的一项回顾性队列研究中，将住院的 COVID-19 患者分为三组：血糖正常组（HbA1c：≤5.6%）、糖尿病前期组（HbA1c：5.7%-6.4%）和糖尿病组（HbA1c：≥6.5%）。严重 COVID-19 的主要结局定义为呼吸频率≥30 次/分、SpO2≤93%或入住重症监护病房。采用 Cox 回归分析临床因素与严重 COVID-19 结局的关系。对 C 反应蛋白（CRP）在糖尿病与严重 COVID-19 之间的关系进行了调整中介分析。在 1042 名住院患者中，平均年龄 39±11 岁，13%患有糖尿病，9%患有糖尿病前期，78%血糖正常。4.9%的患者发生严重 COVID-19。与血糖正常组相比，糖尿病前期组和糖尿病组在单变量（危险比[HR]：9.94；95%置信区间[CI]：5.54-17.84；p<0.001）和多变量分析（HR：3.99；95% CI：1.92-8.31；p<0.001）中均与严重 COVID-19 显著相关，而糖尿病前期不是危险因素（HR：0.94；95% CI：0.22-4.03；p=0.929）。CRP 是炎症的生物标志物，介导了糖尿病与严重 COVID-19 结局之间总关联的 32.7%。总之，CRP 是糖尿病与严重 COVID-19 感染之间关联的部分中介物，证实了炎症在糖尿病严重 COVID-19 的发病机制中很重要。
