COVID-19 in Diabetics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Anahita Deylamsalehi, M.D.[2]
Overview
World Health Organization declared the COVID-19 outbreak a pandemic in 2020. Diabetes mellitus, specifically type 2 diabetes has been reported as one of the most common comorbidities of COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Numerous explanations have been developed for this Comorbidity, such as immune system impairment due to abnormal production of adipokines and cytokines (eg, Tumor necrosis factor-alpha and interferons), as well as decreased phagocytic activity and chemotaxis among diabetics. These explanations justify the higher prevalence of COVID-19 among diabetic patients. Old age, male sex and some ethnic minority groups, such as Hispanic, Latino and African American, are considered as risk factors and are also related to worse outcome. There are some confirmed risk factors for COVID-19 in diabetics such as glycemic instability, immune deficiency and related comorbidities, like obesity and cardiac and renal disease. There are also some hypothesized risk factors such as reduced ACE2, Increased furin and chronic inflammation. COVID-19 among diabetic patients has been related to higher rate of complications. Acute respiratory distress syndrome (ARDS), septic shock, acute kidney injury, acute heart injury and diabetic ketoacidosis are some of the frequently reported complications. Diabetic patients with COVID-19 have higher rate of hospitalization, intensive care unit admission and death, compared to non-diabetics. These patients are presented with fever, cough, dyspnea, fatigue, chest pain, headache and some gastrointestinal complains. Concurrent COVID-19 and diabetes have been related to lower levels of lymphocytes, red blood cells (RBC), albumin and hemoglobin. Conversely, higher levels of neutrophils, erythrocyte sedimentation rate (ESR), D-dimer, interleukin-6 (IL-6) and interleukin-10 (IL-10) have been reported in these patients. Bilateral consolidation and ground‐glass opacification have been reported based on chest X-ray and CT scan, respectively. Insulin is used for hospitalized patients in order to maintain a desirable glycemic control and higher insulin requirements have been reported among diabetic patients. There are numerous considerations regarding antidiabetics and Antihypertensive medications, their possible side effects and their effects on ACE2 expression. Hyperglycemia has been reported with Lopinavir, Ritonavir and Glucocorticoids use. Furthermore, antivirals such as Lopinavir and Ritonavir should be used with caution with statin therapy due to augmented risk of hepatic and muscle toxicity.
Historical Perspective
- On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
- Diabetes mellitus, specifically type 2 diabetes has been recognized as one of the most common comorbidities of COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has been estimated that 20-25% of patients with COVID-19 had diabetes.[1]
Classification
- There is no classification for COVID-19 in diabetes mellitus.
Pathophysiology
- COVID-19 is caused by a virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belong to the order nidovirale, family coronaviridae.
- Diabetes mellitus, specifically type 2 diabetes has been recognized as one of the most common comorbidities of COVID-19.[2]
- Abnormal production of adipokines and cytokines like Tumor necrosis factor-alpha and interferon in diabetic patients have been associated with impairment in immune system and increased susceptibility to infections.
- COVID-19 has been related to cytokine storm and beta cell damage. The latter effects added to the own nature of COVID-19 lead to the following conditions:[3]
- Hyperglycemia at the time of admission
- New onset diabetes
- Aggravated metabolic control in a diabetic patient
- The following factors have been demonstrated as responsible mechanisms which increase the risk of infections in diabetes:[4][5]
- Reduction of Interleukin production
- Decreased phagocytic activity and chemotaxis
- Immobilized granulocytes
- Poor circulation, especially with concurrent peripheral vascular disease (PVD)
Causes
- Coronavrus Disease 2019 (COVID-19) is caused by a virus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
- To browse the causes of Diabetes, click here.
Differentiating from other Diseases
- Two type of diabetes is better to be differentiated from each other in order to optimal approach.
- To browse the differential diagnosis of type 2 diabetes, click here.
- To browse the differential diagnosis of COVID-19, click here.
Epidemiology and Demographics
- It has been estimated that 20-25% of patients with COVID-19 had diabetes.[6]
- Based on a Meta-analysis, the prevalence of diabetes among Chinese population with COVID-19 was 9·7%.[7]
- A study done on 1317 participants reported that 88.5% of patients with COVID-19 had concurrent diabetes mellitus type 2.[8]
Age
- Diabetic patients of all age groups may develop COVID-19, although older age has higher prevalence and been related to higher mortality rate with exception of Korean population, which reported higher rate of COVID-19 among individuals aged 20–29 years.[9][10]
- Studies have been demonstrated an association between old age and worse outcome, furthermore this association has been speculated to be more strong in diabetic patients.[3]
- Individuals older than 80 years old have 12-times higher chance of worse outcome, compared to those aged 50-59 years old.[11]
Gender
- Male sex has been linked to higher prevalence of COVID-19.[3]
- Chance of worse outcome has been estimated twice in male sex, compared to females.[11]
Race
- There are some data supporting that non-white ethnic groups have higher chance of developing COVID-19.[11]
- An analysis reported that African Americans included 33% of individuals admitted to hospital with COVID-19 in the US.
- Even though only 28% of New York city population consisted of Hispanic or Latin individuals, 34% of COVID-19 deaths of New York were consisted of the aforementioned minorities.[12]
- The higher chance of COVID-19 in these ethnic minority groups has been speculated to be due to both biological and environmental circumstances, as well as socioeconomic and life style related factors.[3]
Risk Factors
- Some possible factors that lead to more severe COVID-19 in diabetic patient have been summarized in the table below:[13]
| Confirmed factors | hypothesized factors |
|---|---|
| 1- Glycemic instability
2- Immune deficiency (specially T-cell response) 3- Related comorbidities, like obesity and cardiac and renal disease |
1- Chronic inflammation (elevated interleukin-6)
2- Elevated plasmin 3- Reduced ACE2 |
- HbA1C more than 86 mmol/mol (10%) has been related to worst outcome and higher chance of death, compared to HbA1C less than 48 mmol/mol (6·5%), which further confirms the importance of desirable glycemic control.[14]
Natural History, Complications and Prognosis
Complications
- Diabetic patients with SARS-CoV-2 infection had higher rate of the following complications: [15][16][17]
- Acute Respiratory Distress Syndrome (ARDS)
- Septic Shock
- Acute kidney injury
- Acute heart injury
- Requirement of oxygen inhalation
- Multi-organ failure
- Both non-invasive and invasive ventilation (eg, extracorporeal membrane oxygenation (ECMO))
- Diabetic ketoacidosis:
- Associate to higher mortality rate
- Associate to higher mortality rate
- Hyperosmolar hyperglycemic state
- Optimal metabolic control reduces the chance of complications in concurrent diabetes mellitus and COVID-19 in outpatients.
- COVID-19 has been related to high coagulation activity, probably due to hypoxia related endothelial dysfunction. The latter COVID-19 consequence will be more augmented by the prothrombotic state in diabetic patients, which can lead to more unwanted complications.[18]
Prognosis
- SARS-CoV-2 infection has been linked with higher rate of hospitalization and mortality in diabetic patients compared to non-diabetics.
- Records from the Centers for Disease Control and Prevention (CDC) and other national health centers and hospitals state that diabetic patients with COVID-19 have up to 50% higher chance of death compared to non diabetics with this infection.[19]]]
- Another study done in the US reports more than fourfold mortality rate elevation in COVID-19 in diabetic patients.[20]
- Study on COVID-19 patients in intensive care unit showed a twofold increase in incidence of diabetes, compared to non-intensive care patients.
- Another study done among 1561 patients with COVID-19 in Wuhan demonstrated that diabetic patients had higher rate of intensive care unit (ICU) admission and death, compared to nondiabetics.[21]
- A cohort study done on 5693 patients in England demonstrated higher chance of death among patients with uncontrolled diabetes.[11]
- Complications of diabetes and higher prevalence of comorbidities such as hypertension, cardiovascular disease, cerebrovascular disease, Pulmonology and chronic kidney disease.[3]
- Estimated GFR less than 60 mL/min per 1·73 m2 at the time of admission is correlated to higher rate of early death in diabetic patients with COVID-19.[22]
Diagnosis
History and Symptoms
- Symptoms of [COVID-19] may include the following:[23]
- ever]
- Cough
- Shortness of breath
- Fatigue
- Chest pain
- Chest tightness
- Headache
- Mild gastrointestinal disease (diarrhea, nausea and vomiting)
- For explore further about symptoms of COVID-19, click here
- To browse the Symptoms of type 2 diabetes, click here.
Physical Examination
- To browse the physical examination of COVID-19, click here.
- To browse the physical examination of type 2 diabetes, click here.
Laboratory Findings
- Diabetic patients with SARS-CoV-2 infection have lower levels of the following, compared to non-diabetics:[24][25]
- Diabetic patients with SARS-CoV-2 infection have higher levels of the following, compared to non-diabetics:[25][24][3][26][27]
- Neutrophils
- Erythrocyte sedimentation rate (ESR)
- D-dimer
- A-hydroxybutyrate dehydrogenase
- Lactic dehydrogenase
- Alanine aminotransferase (ALT)
- Fibrinogen
- C reactive protein
- Ferritin
- Interleukin-6 (IL-6)
- Interleukin-10 (IL-10)
- γ-glutamyl transferase
- Procalcitonin
- High C-reactive protein (CPR) level is one of the risk factors that increase mortality rate in diabetic patients who become infected with SARS-CoV-2. Therefore, A study suggests usage of C-reactive protein (CRP) as a tool to identify patients with higher chance of dying during hospitalization.[28] Based on a prospective cohort study, C-reactive protein higher than 200 mg/L and Ferritin more than 2500 ng/mL at the time of admission have been related to more severe COVID-19.[29]
- Sever COVID-19 in diabetic patients were related to higher levels of serum amyloid A (SAA) and low CD4+ T lymphocyte counts.[30]
- There is a J-curve association between HbA1c and risk of infections in general, particularly respiratory tract infections.[3]
Electrocardiogram
There are no ECG findings associated with COVID-19 in diabetics.
X-ray
- could be normal in early stages of COVID-19 or in mild disease
- Bilateral consolidation or airspace opacities
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with COVID-19 in diabetics.
CT scan
MRI
Other Imaging Findings
- There are no other imaging findings associated with COVID-19 in diabetics.
Other Diagnostic Studies
- There are no other diagnostic studies associated with COVID-19 in diabetics.
Treatment
Medical Therapy
- Even though some studies reported that insulin was associated with poor prognosis in diabetic patients with COVID-19[31], Insulin is still the choice agent to control blood glucose in hospitalized diabetic patients with COVID-19.
- Possible β cell damage caused by SARS-CoV-2 can cause to insulin deficiency, which explain increased insulin requirement in these patients. Due to elevated insulin consumption, intravenous infusion must be considered.[32]
- Although angiotensin-converting enzyme II (ACE) expression has been reduced in COVID-19, treatment with ACE inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) in diabetic patient with hypertension had no significant difference compared to other anti-hypertensive treatments based on one study.[33] On the other hand, another study done on diabetic patients showed higher risk of SARS-CoV-2 infection with ACE2-increasing drugs. Elevated ACE2 level can ease the entry of virus. Therefore It is hypothesized that medications like, Angiotensin-converting-enzyme inhibitors (ACEI), angiotensin II type-I receptor blockers (ARB), thiazolidinediones and ibuprofen augment the risk of a severe and lethal SARS-CoV-2 infection.[34][35]
- Due to increased risk of chronic kidney disease and acute kidney injury, renal function should be monitored in patients who take metformin.[36] There is also a recommendation to stop Metformin use in a patient with poor oral intake and vomiting.[37] There are other data that suggest metformin as a possibly helpful anti-diabetic agent in concurrent SARS-CoV-2 infection. Since metformin leads to less elevation in interleukin-6 level, compared to other anti-diabetic agents. These data also assert an association between metformin use and albumin level elevation and a lower COVID-19 related death in patients who took metformin.[38]
- A hypothesis state that since Sodium glucose cotransporter 2 (SGLT-2) inhibitors decrease lactate production and subsequently increase the cytosolic pH, they interfere with virus entry into the cells.[39] Conversely, based on another study Sodium glucose cotransporter 2 (SGLT-2) inhibitors are also indirectly responsible for high ACE2 level, which is attributed as a risk factor for SARS-CoV-2 infection. High ACE2 level can be further elevated by concurrent Angiotensin-converting-enzyme inhibitors (ACEI) use.[40] Current database suggests benefit from discontinuation of Sodium glucose cotransporter 2 (SGLT-2) inhibitors in diabetic patient with COVID-19.[41]
- Initiation of Sodium-glucose-co-transporter 2 inhibitors should be avoided in respiratory illnesses.[42]
- Although lactic acidosis due to metformin use and euglycaemic or moderate hyperglycaemic diabetic ketoacidosis associated with Sodium-glucose-co-transporter 2 inhibitors are rare, their usage has not been recommended. Nevertheless, there is no need to stop these medications prophylactically in diabetic patients with no sign of COVID-19.[43]
- Dipeptidyl peptidase-4 inhibitors has been well tolerated in some diabetic patients with concurrent SARS-CoV-2 infection.[44] It can be continue in mild to moderate COVID-19, nevertheless it is better to be discontinued in sever cases.[45]
- Use of thiazolidinediones has been linked with increased fluid retention and congestive heart failure in diabetic patients with SARS-CoV-2 infection.[46] Pioglitazone use can be continued in mild or moderate COVID-19.[47]
- Dehydration in diabetic patients with COVID-19 should be avoided. Based on a practical recommendation, medications with possible dehydration side effect like Metformin, Sodium-glucose-co-transporter 2 inhibitors and Glucagon-like peptide-1 receptor agonists should be avoided to prevent further complications.[48]
- A summary of anti-diabetic medications in diabetic patients with SARS-CoV-2 infection: [38][48][40]
Anti-diabetic medication |
Relation to ACE2 expression |
Advantage |
Disadvantage |
|---|---|---|---|
|
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- The following table is a summary of medications used for COVID-19 treatment in diabetic patients with this infection:[3][49]
| COVID-19 treatment | Advantages in diabetics | disadvantages in diabetics | Explanation |
|---|---|---|---|
| Chloroquine/Hydroxychloroquine | None |
|
|
| Lopinavir/Ritonavir | None |
|
|
| Glucocorticoids | None |
|
|
Management Considerations:
- Evaluation of electrolytes, blood glucose, blood PH, blood ketones or beta-hydroxybutyrate should be considered in patients in intensive care unit (ICU). Since hypokalemia is a feature of COVID-19 (possibly as a result of high angiotensin 2 concentration and consequent hyperaldosteronism), potassium level should be checked. Specially in concurrent insulin treatment.[50]
- Plasma glucose concentration goal for diabetic outpatients infected with SARS-CoV-2 is 72-144 mg/dl, while plasma glucose concentration of patients in intensive care unit is recommended to be maintained between 72 and 180 mg/dl.[51][52]
- The glycemic control during hospital stay plays an important role in the overall outcome of diabetic patients with COVID-19. Based on a study done on 1122 patients with COVID-19 in the US, hyperglycaemia during the hospitalization has been associated with four time increase in mortality rate, compared to normoglycemia.[53]
- The importance of a careful glycemic control is further supported by a study done in china, which demonstrated that patients with blood glucose concentration median less than 6·4 mmol/L during their hospital stay had higher rate of lymphopenia. These patients also had lower chance of neutrophilia, high C-reactive protein and procalcitonin levels.[54]
Surgery
- Surgical intervention is not recommended for management of COVID-19 in diabetic patients.
Prevention
- To browse the prevention of COVID-19, click here.
- To browse the prevention of type 2 diabetes, click here.
References
- ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Apicella, Matteo; Campopiano, Maria Cristina; Mantuano, Michele; Mazoni, Laura; Coppelli, Alberto; Del Prato, Stefano (2020). "COVID-19 in people with diabetes: understanding the reasons for worse outcomes". The Lancet Diabetes & Endocrinology. 8 (9): 782–792. doi:10.1016/S2213-8587(20)30238-2. ISSN 2213-8587.
- ↑ Casqueiro J, Casqueiro J, Alves C (2012). "Infections in patients with diabetes mellitus: A review of pathogenesis". Indian J Endocrinol Metab. 16 Suppl 1: S27–36. doi:10.4103/2230-8210.94253. PMC 3354930. PMID 22701840.
- ↑ Dryden M, Baguneid M, Eckmann C, Corman S, Stephens J, Solem C; et al. (2015). "Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections". Clin Microbiol Infect. 21 Suppl 2: S27–32. doi:10.1016/j.cmi.2015.03.024. PMID 26198368.
- ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L; et al. (2020). "Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China". Clin Res Cardiol. 109 (5): 531–538. doi:10.1007/s00392-020-01626-9. PMC 7087935 Check
|pmc=value (help). PMID 32161990 Check|pmid=value (help). - ↑ Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I; et al. (2020). "Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study". Diabetologia. 63 (8): 1500–1515. doi:10.1007/s00125-020-05180-x. PMC 7256180 Check
|pmc=value (help). PMID 32472191 Check|pmid=value (help). - ↑ Chen, Yuchen; Yang, Dong; Cheng, Biao; Chen, Jian; Peng, Anlin; Yang, Chen; Liu, Chong; Xiong, Mingrui; Deng, Aiping; Zhang, Yu; Zheng, Ling; Huang, Kun (2020). "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication". Diabetes Care. 43 (7): 1399–1407. doi:10.2337/dc20-0660. ISSN 0149-5992.
- ↑ Dudley JP, Lee NT (2020). "Disparities in Age-specific Morbidity and Mortality From SARS-CoV-2 in China and the Republic of Korea". Clin Infect Dis. 71 (15): 863–865. doi:10.1093/cid/ciaa354. PMC 7184419 Check
|pmc=value (help). PMID 32232322 Check|pmid=value (help). - ↑ 11.0 11.1 11.2 11.3 Williamson, Elizabeth; Walker, Alex J; Bhaskaran, Krishnan J; Bacon, Seb; Bates, Chris; Morton, Caroline E; Curtis, Helen J; Mehrkar, Amir; Evans, David; Inglesby, Peter; Cockburn, Jonathan; Mcdonald, Helen I; MacKenna, Brian; Tomlinson, Laurie; Douglas, Ian J; Rentsch, Christopher T; Mathur, Rohini; Wong, Angel; Grieve, Richard; Harrison, David; Forbes, Harriet; Schultze, Anna; Croker, Richard T; Parry, John; Hester, Frank; Harper, Sam; Perera, Rafael; Evans, Stephen; Smeeth, Liam; Goldacre, Ben (2020). doi:10.1101/2020.05.06.20092999. Missing or empty
|title=(help) - ↑ Haynes, Norrisa; Cooper, Lisa A.; Albert, Michelle A. (2020). "At the Heart of the Matter". Circulation. 142 (2): 105–107. doi:10.1161/CIRCULATIONAHA.120.048126. ISSN 0009-7322.
- ↑ Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ Holman, Naomi; Knighton, Peter; Kar, Partha; O’Keefe, Jackie; Curley, Matt; Weaver, Andy; Barron, Emma; Bakhai, Chirag; Khunti, Kamlesh; Wareham, Nick J.; Sattar, Naveed; Young, Bob; Valabhji, Jonathan (2020). "Type 1 and Type 2 Diabetes and COVID-19 Related Mortality in England: A Cohort Study in People with Diabetes". SSRN Electronic Journal. doi:10.2139/ssrn.3605226. ISSN 1556-5068.
- ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.
- ↑ Rayman G, Lumb A, Kennon B, Cottrell C, Nagi D, Page E; et al. (2020). "Guidance on the management of Diabetic Ketoacidosis in the exceptional circumstances of the COVID-19 pandemic". Diabet Med. 37 (7): 1214–1216. doi:10.1111/dme.14328. PMC 7276743 Check
|pmc=value (help). PMID 32421882 Check|pmid=value (help). - ↑ Dunn EJ, Grant PJ (2005). "Type 2 diabetes: an atherothrombotic syndrome". Curr Mol Med. 5 (3): 323–32. doi:10.2174/1566524053766059. PMID 15892651.
- ↑ Remuzzi A, Remuzzi G (2020). "COVID-19 and Italy: what next?". Lancet. 395 (10231): 1225–1228. doi:10.1016/S0140-6736(20)30627-9. PMC 7102589 Check
|pmc=value (help). PMID 32178769 Check|pmid=value (help). - ↑ Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ Shi Q, Zhang X, Jiang F, Zhang X, Hu N, Bimu C; et al. (2020). "Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study". Diabetes Care. 43 (7): 1382–1391. doi:10.2337/dc20-0598. PMID 32409504 Check
|pmid=value (help). - ↑ Cheng, Yichun; Luo, Ran; Wang, Kun; Zhang, Meng; Wang, Zhixiang; Dong, Lei; Li, Junhua; Yao, Ying; Ge, Shuwang; Xu, Gang (2020). "Kidney disease is associated with in-hospital death of patients with COVID-19". Kidney International. 97 (5): 829–838. doi:10.1016/j.kint.2020.03.005. ISSN 0085-2538.
- ↑ Li, Juyi; Wang, Xiufang; Chen, Jian; Zuo, Xiuran; Zhang, Hongmei; Deng, Aiping (2020). "COVID
‐19 infection may cause ketosis and ketoacidosis". Diabetes, Obesity and Metabolism. doi:10.1111/dom.14057. ISSN 1462-8902. line feed character in
|title=at position 6 (help) - ↑ 24.0 24.1 Guo, Weina; Li, Mingyue; Dong, Yalan; Zhou, Haifeng; Zhang, Zili; Tian, Chunxia; Qin, Renjie; Wang, Haijun; Shen, Yin; Du, Keye; Zhao, Lei; Fan, Heng; Luo, Shanshan; Hu, Desheng (2020). "Diabetes is a risk factor for the progression and prognosis of COVID-19". Diabetes/Metabolism Research and Reviews: e3319. doi:10.1002/dmrr.3319. ISSN 1520-7552.
- ↑ 25.0 25.1 Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ Zhang, Jin-jin; Dong, Xiang; Cao, Yi-yuan; Yuan, Ya-dong; Yang, Yi-bin; Yan, You-qin; Akdis, Cezmi A.; Gao, Ya-dong (2020). "Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China". Allergy. 75 (7): 1730–1741. doi:10.1111/all.14238. ISSN 0105-4538.
- ↑ Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G (2020). "Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis". Clin Chem Lab Med. 58 (7): 1021–1028. doi:10.1515/cclm-2020-0369. PMID 32286245 Check
|pmid=value (help). - ↑ Chen, Yuchen; Yang, Dong; Cheng, Biao; Chen, Jian; Peng, Anlin; Yang, Chen; Liu, Chong; Xiong, Mingrui; Deng, Aiping; Zhang, Yu; Zheng, Ling; Huang, Kun (2020). "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication". Diabetes Care. 43 (7): 1399–1407. doi:10.2337/dc20-0660. ISSN 0149-5992.
- ↑ Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell L, Chernyak Y; et al. (2020). "Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study". BMJ. 369: m1966. doi:10.1136/bmj.m1966. PMC 7243801 Check
|pmc=value (help). PMID 32444366 Check|pmid=value (help). - ↑ Zhang Q, Wei Y, Chen M, Wan Q, Chen X (2020). "Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes". J Diabetes Complications: 107666. doi:10.1016/j.jdiacomp.2020.107666. PMC 7323648 Check
|pmc=value (help). PMID 32636061 Check|pmid=value (help). - ↑ Chen, Yuchen; Yang, Dong; Cheng, Biao; Chen, Jian; Peng, Anlin; Yang, Chen; Liu, Chong; Xiong, Mingrui; Deng, Aiping; Zhang, Yu; Zheng, Ling; Huang, Kun (2020). "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication". Diabetes Care. 43 (7): 1399–1407. doi:10.2337/dc20-0660. ISSN 0149-5992.
- ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Chen, Yuchen; Yang, Dong; Cheng, Biao; Chen, Jian; Peng, Anlin; Yang, Chen; Liu, Chong; Xiong, Mingrui; Deng, Aiping; Zhang, Yu; Zheng, Ling; Huang, Kun (2020). "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication". Diabetes Care. 43 (7): 1399–1407. doi:10.2337/dc20-0660. ISSN 0149-5992.
- ↑ Fang L, Karakiulakis G, Roth M (2020). "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?". Lancet Respir Med. 8 (4): e21. doi:10.1016/S2213-2600(20)30116-8. PMC 7118626 Check
|pmc=value (help). PMID 32171062 Check|pmid=value (help). - ↑ Arendse LB, Danser AHJ, Poglitsch M, Touyz RM, Burnett JC, Llorens-Cortes C; et al. (2019). "Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure". Pharmacol Rev. 71 (4): 539–570. doi:10.1124/pr.118.017129. PMC 6782023 Check
|pmc=value (help). PMID 31537750. - ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ 38.0 38.1 Singh, Awadhesh Kumar; Singh, Ritu (2020). "Is metformin ahead in the race as a repurposed host-directed therapy for patients with diabetes and COVID-19?". Diabetes Research and Clinical Practice. 165: 108268. doi:10.1016/j.diabres.2020.108268. ISSN 0168-8227.
- ↑ Couselo-Seijas M, Agra-Bermejo RM, Fernández AL, Martínez-Cereijo JM, Sierra J, Soto-Pérez M; et al. (2020). "High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment". Atherosclerosis. 292: 60–69. doi:10.1016/j.atherosclerosis.2019.11.016. PMID 31783199.
- ↑ 40.0 40.1 Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Fang L, Karakiulakis G, Roth M (2020). "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?". Lancet Respir Med. 8 (4): e21. doi:10.1016/S2213-2600(20)30116-8. PMC 7118626 Check
|pmc=value (help). PMID 32171062 Check|pmid=value (help). - ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.
- ↑ Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
- ↑ Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.
- ↑ 48.0 48.1 Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Bruno, R.; Sacchi, P.; Maiocchi, L.; Patruno, S.; Filice, G. (2006). "Hepatotoxicity and antiretroviral therapy with protease inhibitors: A review". Digestive and Liver Disease. 38 (6): 363–373. doi:10.1016/j.dld.2006.01.020. ISSN 1590-8658.
- ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check
|pmc=value (help). PMID 32334646 Check|pmid=value (help). - ↑ Singh, Awadhesh Kumar; Khunti, Kamlesh (2020). "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review". Diabetes Research and Clinical Practice. 165: 108266. doi:10.1016/j.diabres.2020.108266. ISSN 0168-8227.
- ↑ Bode B, Garrett V, Messler J, McFarland R, Crowe J, Booth R; et al. (2020). "Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States". J Diabetes Sci Technol. 14 (4): 813–821. doi:10.1177/1932296820924469. PMID 32389027 Check
|pmid=value (help). - ↑ Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J; et al. (2020). "Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes". Cell Metab. 31 (6): 1068–1077.e3. doi:10.1016/j.cmet.2020.04.021. PMC 7252168 Check
|pmc=value (help). PMID 32369736 Check|pmid=value (help).