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      Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes

      research-article
      1 , 2 , 28 , 1 , 2 , 28 , 1 , 2 , 28 , 1 , 2 , 28 , 1 , 2 , 28 , 3 , 2 , 4 , 1 , 1 , 2 , 1 , 2 , 2 , 5 , 2 , 4 , 6 , 2 , 2 , 2 , 1 , 2 , 2 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 1 , 15 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 6 , 23 , 4 , 24 , , 25 , ∗∗ , 26 , ∗∗∗ , 1 , 2 , 5 , 27 , 29 , ∗∗∗∗
      Cell Metabolism
      Elsevier Inc.
      COVID-19, SARS-CoV-2, diabetes mellitus, blood glucose control, mortality

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          Summary

          Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.

          Graphical Abstract

          Highlights

          • A cohort of 7,337 COVID-19 patients with or without diabetes was retrospectively studied

          • Diabetes status increased the need for medical interventions during COVID-19

          • Diabetes status increased the mortality risk of patients with COVID-19

          • Well-controlled blood glucose correlated with improved outcomes in infected patients

          Abstract

          Type 2 diabetes (T2D) correlates with a worse outcome for COVID-19. Here, Zhu et al. show that among ∼7,300 cases of COVID-19, T2D is associated with a higher death rate, but diabetics with better controlled blood glucose die at a lower rate than diabetics with poorly controlled blood glucose.

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          Most cited references25

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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                Author and article information

                Contributors
                Journal
                Cell Metab
                Cell Metab
                Cell Metabolism
                Elsevier Inc.
                1550-4131
                1932-7420
                1 May 2020
                1 May 2020
                Affiliations
                [1 ]Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China
                [2 ]Institute of Model Animal, Wuhan University, Wuhan 430072, China
                [3 ]Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha 410000, China
                [4 ]Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
                [5 ]Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
                [6 ]Department of Cardiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430072, China
                [7 ]Wuhan Seventh Hospital, Wuhan 430072, China
                [8 ]The Ninth Hospital of Wuhan City, Wuhan 430072, China
                [9 ]Department of General Surgery, Huanggang Central Hospital, Huanggang 438000, China
                [10 ]Department of Pulmonary and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan 430072, China
                [11 ]Department of General Surgery, Ezhou Central Hospital, Ezhou 436000, China
                [12 ]Department of Neurology, Wuhan First Hospital/Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430072, China
                [13 ]Department of Urology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430072, China
                [14 ]Department of Stomatology, Xiantao First People’s Hospital, Xiantao 433000, China
                [15 ]The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, China
                [16 ]Department of Neurology, The First People’s Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen 448000, China
                [17 ]Department of Orthopedics, The First People’s Hospital of Jingmen affiliated to Hubei Minzu University, Jingmen 448000 China
                [18 ]Department of Hepatobiliary Surgery, The First Affiliated Hospital of Changjiang University, Jingzhou 434000, China
                [19 ]Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou 434000, China
                [20 ]Department of Hepatobiliary and Pancreatic Surgery, Xianning Central Hospital, Xianning 437000, China
                [21 ]Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China
                [22 ]Department of Hepatobiliary and Pancreatic Surgery, Suizhou Central Hospital Affiliated to Hubei Medical College, Suizhou 441300, China
                [23 ]Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University and Yichang Central People’s Hospital and Institute of Cardiovascular Diseases, China Three Gorges University, Yichang 443000, China
                [24 ]Department of Gastroenterology, Wuhan Third Hospital and Tongren Hospital of Wuhan University, Wuhan 430072, China
                [25 ]Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine & Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China and Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangzhou 510006, China
                [26 ]Department of Neonatology, Renmin Hospital of Wuhan University, Wuhan 430072, China
                [27 ]Basic Medical School, Wuhan University, Wuhan 430072, China
                Author notes
                []Corresponding author hxd19681031@ 123456whu.edu.cn
                [∗∗ ]Corresponding author guoj@ 123456gdpu.edu.cn
                [∗∗∗ ]Corresponding author rm001985@ 123456whu.edu.cn
                [∗∗∗∗ ]Corresponding author lihl@ 123456whu.edu.cn
                [28]

                These authors contributed equally

                [29]

                Lead Contact

                Article
                S1550-4131(20)30238-2
                10.1016/j.cmet.2020.04.021
                7252168
                32369736
                c774741a-772b-4bbb-a050-e91de1b0cea8
                © 2020 Elsevier Inc.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 20 April 2020
                : 26 April 2020
                : 28 April 2020
                Categories
                Article

                Cell biology
                covid-19,sars-cov-2,diabetes mellitus,blood glucose control,mortality
                Cell biology
                covid-19, sars-cov-2, diabetes mellitus, blood glucose control, mortality

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