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Fasting blood glucose predicts the occurrence of critical illness in COVID-19 patients: A multicenter retrospective cohort study

2020; Elsevier BV; Volume: 81; Issue: 3 Linguagem: Inglês

10.1016/j.jinf.2020.07.006

1532-2742

Qin Liu, Huai Chen, Jianyu Li, Xiaoyan Huang, Lihua Lai, Shenghao Li, Qingsi Zeng,

COVID-19 Clinical Research Studies

We read the recent published article by Lin and colleagues in journal of infection with great interest, which reported that serum ferritin as an independent risk factor for severity in COVID-19 patients.1Lin Z. Long F. Yang Y. et al.Serum ferritin as an independent risk factor for severity in COVID-19 patients.J Infect. 2020; https://doi.org/10.1016/j.jinf.2020.06.053Abstract Full Text Full Text PDF Scopus (99) Google Scholar Previous studies aimed to identification risk factors of critical or mortal condition of patients with COVID-19 from clinical, laboratory, and radiological characteristics at admission.2Zheng Z. Peng F. Xu B. et al.Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis.J Infect. 2020; https://doi.org/10.1016/j.jinf.2020.04.021Abstract Full Text Full Text PDF Scopus (1506) Google Scholar Early warning of patients who are most likely to develop critical disease will enable informed decisions, and facilitate the provision of timely supportive treatment in advance and thus reduce mortality. In this multicenter retrospective cohort study, we aimed to explore the value of admission fasting blood glucose (FBG) in predicting the occurrence of critical illness among patients hospitalized for COVID-19. We enrolled a total of 123 laboratory-confirmed COVID-19 patients from three designated hospitals of Wuhan and Guangzhou, China. We collected clinical and laboratory data at hospital admission from medical records. We defined the severity of COVID-19 according to the newest COVID-19 guidelines released by the National Health Commission of China3Guidelines for the diagnosis and treatment of novel coronavirus (2019-nCoV) infection (trial version 7) (in Chinese). National Health Commission of the People's Republic of China. March 04, 2020; doi:10.7661/j.cjim.20200202.064.Google Scholar and the guidelines of American Thoracic Society for community-acquired pneumonia.4Metlay J.P. Waterer G.W. Long A.C. et al.Diagnosis and Treatment of Adults with Community-acquired Pneumonia.Off. Clin. Pract. Guidel. Am. Thorac. Soc. Infect. Dis. Soc. Am.. Am J Respir Crit Care Med. 2019; 200: e45-e67Google Scholar We defined critical illness as a composite of admission to the intensive care unit (ICU), respiratory failure requiring mechanical ventilation, septic shock during hospitalization, or death. The optimal cutoff of FBG for discriminating COVID-19 patients with non-critical and critical illness was determined using receiver operating characteristic (ROC) curve and by maximizing the Youden index. To identify predictors for critical illness, baseline variables with p-value 6.1 mmol/L. The critical patients had significantly higher fasting blood glucose (FBG) level than the non-critical patients (p<0.001) (Fig. 1a). Multivariate logistic regression indicated that the FBG on admission was an independent risk factor for critical illness in patients with COVID-19 (Odds Ratio [OR] = 1.249, 95% confidence interval [CI]: 1.032–1.512). After adjusting for previous diabetes, the OR of FBG for predicting critical illness in COVID-19 patients was 1.245 (95% CI: 1.056–1.468). The optimal FBG level for predicting critical illness was ≥6.50 mmol/L, with an area under the curve (AUC) of 0.767 (95% CI: 0.677–0.857) (Fig. 1b). The FBG was positively correlated with white blood cells (WBC) (r = 0.300, p = 0.001), neutrophil (r = 0.360, p < 0.001), and lactic dehydrogenase (LDH) (r = 0.277, p = 0.002); while FBG was negatively correlated with lymphocyte (r = −0.310, p < 0.001), albumin (r = −0.265, p = 0.003), and indirect bilirubin (IBIL) (r = −0.193, p = 0.037) (Fig. 1c-h). After adjusting for WBC, neutrophil, LDH, lymphocyte, albumin and IBIL, the OR of FBG for predicting critical illness in COVID-19 patients was 1.307 (95% CI: 1.105–1.546).Table 1Comparison of baseline characteristics between critical and noncritical patients with COVID-19.CharacteristicsNoncritical (n = 84)Critical (n = 39)p-valueAge (years)58.5 (49.3–66.0)68.0 (61.0–78.0)0.001Sex, n (%) Male44 (52.4)26 (66.7)0.137 Female40 (47.6)13 (33.3)Comorbidities Hypertension, n(%)18 (21.4)15 (39.5)0.047 Coronary heart disease, n(%)9 (10.7)5 (12.8)0.765 Diabetes, n(%)10 (11.9)11 (28.2)0.025 Chronic liver diseases, n(%)5 (6.0)00.178 Chronic lung diseases, n(%)8 (9.5)4 (10.3)1.000 Others, n(%)22 (26.2)12 (30.8)0.597Laboratory findings WBC (× 109/L)5.6 (4.3–7.1)6.0 (4.4–9.4)0.127 Neutrophil (× 109/L)3.7 (2.7–5.5)5.1 (3.2–8.7)0.010 Lymphocyte (× 109/L)0.9 (0.7–1.4)0.7 (0.4–1.0)0.002 LDH (U/L)205.5 (161.8–279.8)395.5 (271.8–538.8)<0.001 Hemoglobin (g/L)127.0 (117.0–144.0)137.0 (122.0–146.0)0.245 Platelet (g/L)190.0 (139.0–274.5)164.0 (124.0–206.0)0.047 Albumin (g/L)36.7 (32.0–40.0)31.9 (29.3–36.2)0.001 AST (U/L)25.5 (18.0–36.0)40.0 (27.0–59.0)<0.001 ALT (U/L)23.0 (16.0–37.3)27.0 (20.0–41.0)0.186 DBIL (μmol/L)3.6 (2.8–5.0)4.2 (3.2–6.9)0.071 IBIL (μmol/L)7.2 (4.5–10.2)5.6 (4.5–7.4)0.126 TBIL (μmol/L)11.2 (7.9–14.9)9.8 (8.0–15.3)0.755 APTT (s)33.7 (31.2–36.6)35.4 (31.2–39.9)0.197 PT (s)13.3 (12.5–14.3)13.9 (12.9–15.1)0.061 d-dimer (μg/ml)0.3 (0.1–0.7)0.7 (0.2–7.2)0.003 Creatinine (μmol/L)70.0 (57.3–82.0)80.0 (67.0–100.0)0.002 hs-CRP (mg/L)12.0 (1.8–34.8)36.1 (32.1–36.9)<0.001 Procalcitonin (ng/ml)0.08 (0.05–0.12)0.2 (0.1–0.4)<0.001 FBG (mmol/L)5.7 (5.0–6.9)7.4 (6.5–11.9)<0.001 NTproBNP (pg/mL)97.3 (31.0–213.3)497.4 (127.0–843.8)<0.001Note: Data were number (percentage) or median (interquartile range).Abbreviations: WBC, white blood cells; LDH, lactate dehydrogenase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TBIL, Total Bilirubin; DBIL, Direct Bilirubin; IBIL, indirect bilirubin; APTT, activated partial thromboplastin time; PT, prothrombin time; hs-CRP, high-sensitivity C-reactive protein; FBG, fasting blood glucose; NTproBNP, N-terminal portion of proBNP. Open table in a new tab Table 2Risk factors associated with critical illness in univariable and multivariable logistic regression analysis.UnivariableMultivariableOR (95% CI)P valueOR (95% CI)P valueAge (years)1.047 (1.016–1.079)0.0031.029 (0.966–1.095)0.379Comorbidities Hypertension, n(%)2.292 (1.000–5.252)0.0501.331 (0.291–6.097)0.713 Diabetes, n(%)2.907 (1.113–7.596)0.0290.935 (0.151–5.782)0.942Laboratory findings WBC (× 109/L)1.126 (0.998–1.270)0.0530.866 (0.095–7.911)0.899 Neutrophil (× 109/L)1.168 (1.032–1.323)0.0141.253 (0.136–11.557)0.842 Lymphocyte (× 109/L)0.252 (0.099–0.644)0.0040.698 (0.055–8.868)0.782 LDH (U/L)1.007 (1.004–1.011)<0.0011.004 (0.997–1.010)0.265 Platelet (g/L)0.994 (0.988–0.999)0.0250.994 (0.983–1.006)0.314 Albumin (g/L)0.886 (0.820–0.957)0.0021.062 (0.862–1.308)0.571 AST (U/L)1.036 (1.014–1.058)0.0011.022 (0.985–1.060)0.251 PT (s)1.261 (1.041–1.528)0.0181.010 (0.697–1.466)0.956 d-dimer (μg/ml)1.226 (1.057–1.423)0.0071.016 (0.704–1.464)0.934 Creatinine (μmol/L)1.027 (1.009–1.045)0.0031.009 (0.975–1.045)0.601 hs-CRP (mg/L)1.018 (1.001–1.035)0.0350.990 (0.968–1.013)0.410 Procalcitonin (ng/ml)2.689 (1.016–7.118)0.0462.167 (0.289–16.253)0.452 FBG (mmol/L)1.317 (1.134–1.529)<0.0011.249 (1.032–1.512)0.022 NTproBNP (pg/mL)1.002 (1.001–1.003)0.0021.001 (1.000–1.002)0.211Note: Baseline variables with p-value <0.10 in univariable analysis were entered into multivariate logistic regression.Abbreviations: OR, Odds Ratio; WBC, white blood cells; LDH, lactate dehydrogenase; AST, aspartate aminotransferase; PT, prothrombin time; hs-CRP, high-sensitivity C-reactive protein; FBG, fasting blood glucose; NTproBNP, N-terminal portion of proBNP. Open table in a new tab Note: Data were number (percentage) or median (interquartile range). Abbreviations: WBC, white blood cells; LDH, lactate dehydrogenase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; TBIL, Total Bilirubin; DBIL, Direct Bilirubin; IBIL, indirect bilirubin; APTT, activated partial thromboplastin time; PT, prothrombin time; hs-CRP, high-sensitivity C-reactive protein; FBG, fasting blood glucose; NTproBNP, N-terminal portion of proBNP. Note: Baseline variables with p-value <0.10 in univariable analysis were entered into multivariate logistic regression. Abbreviations: OR, Odds Ratio; WBC, white blood cells; LDH, lactate dehydrogenase; AST, aspartate aminotransferase; PT, prothrombin time; hs-CRP, high-sensitivity C-reactive protein; FBG, fasting blood glucose; NTproBNP, N-terminal portion of proBNP. Our study suggested that elevated FBG at admission is a crucial risk factor for critical illness in COVID-19 patients, although most patients (82.9%) had no previous diabetes, which was consistent with previous studies.5Deng M., Qi Y., Deng L., et al. Obesity as a potential predictor of disease severity in young COVID-19 patients: a retrospective study. obesity (Silver Spring)2020. doi: 10.1002/oby.22943.Google Scholar,6Iacobellis G. Penaherrera C.A. Bermudez L.E. Bernal Mizrachi E Admission hyperglycemia and radiological findings of SARS-CoV2 in patients with and without diabetes.Diabetes Res Clin Pract. 2020; 164108185Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar After adjusting for previous diabetes, the OR of FBG level was not significantly changed. The proportion of hyperglycemia was higher than a previous report of 47.2%.7Wu J. Huang J. Zhu G. et al.Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study.BMJ Open Diabetes Res Care. 2020; https://doi.org/10.1136/bmjdrc-2020-001476Crossref Scopus (97) Google Scholar which may be due to the higher rate of critically ill patients we included. Except for well-known diabetes, elevation of FBG level at admission could also due to stress hyperglycemia. Stress hyperglycemia has been often found in patients without diabetes, which is more concerning in clinical practice. Stress hyperglycemia may be induced by a decrease of both insulin secretion and the worsening of insulin resistance.8Ceriello A. De Nigris V. Prattichizzo F Why is hyperglycaemia worsening COVID-19 and its prognosis?.Diabetes Obes Metab. 2020; https://doi.org/10.1111/dom.14098Crossref Scopus (63) Google Scholar it may produce organ damage by inducing endothelial dysfunction and thrombosis through the glycation process and oxidative stress generation.8Ceriello A. De Nigris V. Prattichizzo F Why is hyperglycaemia worsening COVID-19 and its prognosis?.Diabetes Obes Metab. 2020; https://doi.org/10.1111/dom.14098Crossref Scopus (63) Google Scholar Evidences have showed that critical COVID-19 cases exhibit characteristics of severely impaired immune system, systemic inflammatory reactions and cytokine storm. Our study indicated that admission FBG level was positively correlated with inflammatory biomarkers, such as WBC and neutrophil and negatively correlated with immune state biomarker—lymphocyte. In conclusion, this present study demonstrated that a high level of admission FBG was an independent risk factor for developing critical illness of COVID-19 patients. Admission FBG was associated with systemic inflammatory reactions and immune state. As a convenient and easy-to-detect marker, blood glucose level can be obtained and monitored in clinical settings. Continuous glucose monitoring is particularly necessary in COVID-19 patients with elevated admission FBG. Glucose control helps prevent and control infections and their complications.9Zhu L. She Z.G. Cheng X. et al.Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.Cell Metab. 2020; 31 (1068-1077.e3.)Abstract Full Text Full Text PDF Scopus (1078) Google Scholar Therefore, well-controlled blood glucose may lead to an improved outcomes of patients with COVID-19. The authors declare no competing interests.