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.
Causes
Disease name] may be caused by [cause1], [cause2], or [cause3].
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
Age
- Diabetic patients of all age groups may develop COVID-19, although older age has been related to higher mortality rate.[4]
Gender
- [Disease name] affects men and women equally.
Race
- There is no racial predilection for [disease name].
Risk Factors
| 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 |
Natural History, Complications and Prognosis
Complications
- Diabetic patients with SARS-CoV-2 infection had higher rate of the following complications: [6][7]
- 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)).
- Optimal metabolic control reduces the chance of complications in concurrent diabetes mellitus and COVID-19 in outpatients.
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.[8]
- Another study done in the US reports more than fourfold mortality rate elevation in COVID-19 in diabetic patients.[9]
- Study on COVID-19 patients in intensive care unit showed a twofold increase in incidence of diabetes, compared to non-intensive care patients.
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:[10][11]
- Diabetic patients with SARS-CoV-2 infection have higher levels of the following, compared to non-diabetics:[11][10]
- Neutrophils
- Erythrocyte sedimentation rate (ESR)
- D-dimer
- A-hydroxybutyrate dehydrogenase
- Lactic dehydrogenase
- Alanine aminotransferase (ALT)
- Fibrinogen
- C reactive protein
- Ferritin
- Interleukin-6 (IL-6)
- 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.[12]
- Sever COVID-19 in diabetic patients were related to higher levels of serum amyloid A (SAA) and low CD4+ T lymphocyte counts.[13]
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.[14] 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.[15]
- 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.[16] 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.[17]
- Due to increased risk of chronic kidney disease and acute kidney injury, renal function should be monitored in patients who take metformin.[18] There is also a recommendation to stop Metformin use in a patient with poor oral intake and vomiting.[19] 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.[20]
- 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.[21] 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.[22] Current database suggests benefit from discontinuation of Sodium glucose cotransporter 2 (SGLT-2) inhibitors in diabetic patient with COVID-19.[23]
- Initiation of Sodium-glucose-co-transporter 2 inhibitors should be avoided in respiratory illnesses.[24]
- 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.[25]
- Dipeptidyl peptidase-4 inhibitors has been well tolerated in some diabetic patients with concurrent SARS-CoV-2 infection.[26] It can be continue in mild to moderate COVID-19, nevertheless it is better to be discontinued in sever cases.[27]
- Use of thiazolidinediones has been linked with increased fluid retention and congestive heart failure in diabetic patients with SARS-CoV-2 infection.[28] Pioglitazone use can be continued in mild or moderate COVID-19.[29]
- 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.[30]
- A summary of anti-diabetic medications in diabetic patients with SARS-CoV-2 infection: [20][30][22]
Anti-diabetic medication |
Relation to ACE2 expression |
Advantage |
Disadvantage |
|---|---|---|---|
|
|
| |
|
|
| |
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| |
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| |
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| |
|
|
|
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.[31]
- 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.[32][33]
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). - ↑ 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.
- ↑ 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). - ↑ 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.
- ↑ 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.
- ↑ 10.0 10.1 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.
- ↑ 11.0 11.1 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.
- ↑ 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.
- ↑ 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). - ↑ 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.
- ↑ 20.0 20.1 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.
- ↑ 22.0 22.1 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.
- ↑ 30.0 30.1 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). - ↑ 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.