COVID-19 in Diabetics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Anahita Deylamsalehi, M.D.[2]
Overview
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 [disease name] from other Diseases
- [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
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 these 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
- [Disease name] is usually asymptomatic.
- Symptoms of [disease name] may include the following:
Physical Examination
- Patients with [disease name] usually appear [general appearance].
- Physical examination may be remarkable for:
Laboratory Findings
- Diabetic patients with SARS-CoV-2 infection have lower levels of the following, compared to non-diabetics:[23][24]
- Diabetic patients with SARS-CoV-2 infection have higher levels of the following, compared to non-diabetics:[24][23][3][25][26]
- 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.[27] 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.[28]
- Sever COVID-19 in diabetic patients were related to higher levels of serum amyloid A (SAA) and low CD4+ T lymphocyte counts.[29]
- 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 [disease name].
X-ray
There are no x-ray findings associated with [disease name].
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
CT scan
There are no CT scan findings associated with [disease name].
MRI
There are no MRI findings associated with [disease name].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
Treatment
Medical Therapy
- Treatment with insulin was associated with poor prognosis in diabetic patients with COVID-19.[30] Although, Insulin is 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.[31]
- 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.[32] 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.[33][34]
- Due to increased risk of chronic kidney disease and acute kidney injury, renal function should be monitored in patients who take metformin.[35] There is also a recommendation to stop Metformin use in a patient with poor oral intake and vomiting.[36] 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.[37]
- 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.[38] 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.[39] Current database suggests benefit from discontinuation of Sodium glucose cotransporter 2 (SGLT-2) inhibitors in diabetic patient with COVID-19.[40]
- Initiation of Sodium-glucose-co-transporter 2 inhibitors should be avoided in respiratory illnesses.[41]
- 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.[42]
- Dipeptidyl peptidase-4 inhibitors has been well tolerated in some diabetic patients with concurrent SARS-CoV-2 infection.[43] It can be continue in mild to moderate COVID-19, nevertheless it is better to be discontinued in sever cases.[44]
- Use of thiazolidinediones has been linked with increased fluid retention and congestive heart failure in diabetic patients with SARS-CoV-2 infection.[45] Pioglitazone use can be continued in mild or moderate COVID-19.[46]
- 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.[47]
- A summary of anti-diabetic medications in diabetic patients with SARS-CoV-2 infection: [37][47][39]
Anti-diabetic medication |
Relation to ACE2 expression |
Advantage |
Disadvantage |
|---|---|---|---|
|
| ||
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
| |
|
|
|
- The following table is a summary of medications used for COVID-19 treatment in diabetic patients with this infection:[3][48]
| 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.[49]
- 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.[50][51]
- 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.[52]
- 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.[53]
Surgery
Prevention
- There are no primary preventive measures available for [disease name].
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.
- ↑ 23.0 23.1 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.
- ↑ 24.0 24.1 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.
- ↑ 37.0 37.1 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.
- ↑ 39.0 39.1 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.
- ↑ 47.0 47.1 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).