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 Table of Contents 
COMMENTARY
Year : 2020  |  Volume : 9  |  Issue : 9  |  Page : 4512-4515  

COVID 19 and diabetes: An endocrinologist's perspective


1 Department of Endocrinology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
3 Department of Microbiology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

Date of Submission27-Apr-2020
Date of Decision10-Jun-2020
Date of Acceptance24-Jun-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Dr. Kishore K Behera
Department of Endocrinology, All India Institute of Medical Sciences, Bhubaneswar - 751 019
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_710_20

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  Abstract 


The clinical manifestation of COVID-19 is diverse, oscillating from mild flu-like symptoms to more severe outcome, such as acute respiratory distress syndrome, multiple organ failure, and death. Advanced age and comorbidities, such as diabetes mellitus, high blood pressure, and history of cerebrovascular accidents are reported to have worse outcome. Chronic inflammation by cytokine storm and direct insult to pancreatic by COVID-19 might be postulated mechanisms of inducing or deteriorating diabetes. Individualized patient-centric treatment and optimal blood sugar control should be made based on disease severity, presence of comorbid condition, and complications related to diabetes, age, and other risk factors. Recent clinical trials have shown some hope to anti-interleukin antibody as a potential therapeutic option against COVID-19 especially in people with severe illness.

Keywords: Acute respiratory distress syndrome, angiotensin-converting enzyme 2, COVID-19, cytokine storm, diabetes


How to cite this article:
Behera KK, Hota D, Mahapatra A. COVID 19 and diabetes: An endocrinologist's perspective. J Family Med Prim Care 2020;9:4512-5

How to cite this URL:
Behera KK, Hota D, Mahapatra A. COVID 19 and diabetes: An endocrinologist's perspective. J Family Med Prim Care [serial online] 2020 [cited 2020 Oct 25];9:4512-5. Available from: https://www.jfmpc.com/text.asp?2020/9/9/4512/296323




  Introduction Top


Corona viruses are implicated for a number of communities acquired infection, such as Middle East Respiratory Syndrome (MERS), severe acute respiratory syndrome (SARS), and the novel corona virus now officially named SARS-CoV-2, is the causative agents corona virus disease (COVID-19) disease outbreaks.[1]

COVID-19 is a highly contagious disease with human to human transmission; has more mortality in compare to influenza (9 3.75 vs 1%), hence need prompt action to contain it.[2] The most common symptoms observed in COVID-19 illness are fever (99%), fatigue (70%), dry cough (60%), myalgia (44%), and dyspnea. Respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. Elderly patients with underlying co-morbidities including hypertension, diabetes is more likely to have adverse outcomes.[3]

Among the various non-communicable disease; type 2 diabetes mellitus (T2DM) looks to be a risk factor and poor prognosis for acquiring the COVID-19 infection.[1],[2] Although T2DM poses more risk of severe symptoms and mortality in many viral infections, there are some unique mechanism operate in COVID-19 infections that need a special discrete consideration, which will have clinical outcome for better management of badly affected patients.


  Immunity, Diabetes, and COVID-19 Top


Patients with diabetes have both compromised innate and acquired immunity.[4] Fasting hyperglycemia and diabetes are independent predictor of morbidity and mortality in SARS.[5] Elderly, metabolically compromised patients are risk for COVID-19 infections and more susceptible to high virus loads. They have a dysregulated cytokine/chemokine response and prone for cytokine storm. The characteristics of cytokine storm in severe COVID-19 are increased levels of chemokines (C-C motif chemokine ligand (CCL)-2, CCL-3, and CCL-5), tumor necrosis factor, and proinflammatory cytokines interleukin (IL)-1β, IL-6 along with low levels of the antiviral factors such as interferons.[6]

T2 DM with severe COVID-19 infection are more prone for a cytokine storm characterized by increased titer of inflammatory cytokines IL-2R and IL-6 and chemokines.[7] ARDS, an immunopathological changes in lungs and multi-organ failure leading to increased fatality, is due to the consequence of poorly regulated inflammatory cytokine storm.[7]


  Diabetes Increases Morbidity and Mortality in COVID-19 Corona Virus and ACE2 Top


From endocrine perspective, COVID-19 seems more severe in patients with diabetes.[1] COVID-19 virus enters human cells by attaching to the angiotensin-converting enzyme 2 (ACE2).[7],[8] In the lungs, COVID-19 after binding to its functional receptorACE2 enter primarily type II pneumocytes;[9] followed by downregulation of surface ACE2, resulting in unopposed angiotensin II accumulation. It is reported that the renin–angiotensin–aldosterone system gets activated locally, this may mediate lung injury responses to viral insults.[9]

The liver and in the pancreatic β- cells express ACE2.[8] The possible underlying mechanism that cause acute surge of hyperglycemia, and transient T2DM could be direct damage to the pancreatic β- cells by binding with ACE2 protein leading to decrease insulin secretion and development of insulin resistance by entry into the liver during the acute infection.[8]

Angiotensin-II (AngII) is produced from Angiotensin-I by angiotensin converting enzyme (ACE) in the lungs. AngII cause vasoconstriction of vessels, pro-oxidative, and pro-inflammatory effects through acting at AngII receptor type 1 (AT1). Angiotensin 1-7 (Ang1-7) is produced when ACE2 act upon AngII, which binds Mas receptor (MasR) mediates anti-oxidative and vasodilatory anti-inflammatory affects.[10] It is assumed that binding to ACE2 by COVID-19 may attenuate activity of remaining ACE2, further awry the ACE/ACE2 balance to a state of predominant ACE/AngII/AT1 axis signaling, in which AngII causes inflammatory pulmonary vasoconstriction and oxidative organ damage.[11] This assumption can be extrapolated as Liu et al., demonstrated that COVID-19 infected patients have higher serum AngII levels, viral load, and lung injury than in non-infected.[11],[12] It is hypothesized that patients with fatal COVID-19 infection may cause an increase in the activation of predominant ACE/AngII/AT1 axis signaling, particularly in T2DM, insulin-resistant states, and hypertension.[7] Poorly controlled diabetes leads to more glycation of ACE2 with reduced ACE2; this could explain the increased susceptibility to severe lung damage and ARDS with COVID-19.[13]

There is paucity of evidence in patients with diabetes with COVID-19. Fang et al. has recently documented 15-20% increase in severity and morbidity of COVID-19 infected diabetes patents in three different study from China.[14] Analysis of data from 11 studies regarding laboratory abnormalities in patients with COVID-19 did not describe elevated blood glucose or diabetes as predictor of severe disease.[15]

Reported data from an epidemiological study by Chinese Centre for Disease Control and Prevention consisting of 72,314 COVID patients described increased mortality in people with diabetes (7.3%, patients with diabetes 2.3%, overall).[16] Study by Wang et al. showed that patients admitted in intensive care unit (ICU) with corona virus infection were more than 3 times likely to have underlying diabetes than non-ICU patients.[17]

Responsibility of primary care physician to prevent COVID-19 infection in the diabetics

The primary care physicians have paramount responsibility as they are the initial contacts of their patients in the prevention of COVID-19 infection because of their close long-term association and patient trust they enjoy. Some basic general preventive measures to be followed are depicted below.[18]

  1. Simple measures should be taken to avoid infection from the virus
  2. Frequent hand rubbing with alcohol-based sanitizer or readily available soap and before eating and after being in public place
  3. Sharing of foods, glasses, and towels among ourselves should be avoided
  4. Utmost care should be taken not to have contact with someone is febrile or having flu like illness
  5. Health-care personals to be informed promptly if someone ill with respiratory symptoms
  6. Mouth and nosed to be covered with tissue or crook of the elbow. Tissue should be discarded properly
  7. Avoid contact with wildlife and farm animal
  8. Unnecessary travel to the major hot spot should be avoided
  9. It is advisable to diabetic patients to keep good amount of insulin vials and refills and oral diabetic drugs with them.


What primary care physicians can do if they suspect COVID-19 in the diabetic patient?

Based upon the initial symptomatology of COVID infection, the primary care physician must take immediate and appropriate steps to prevent patient from worsening. As such diabetic population is at higher risk of rapid downhill course once COVID infection sets in. Patients with diabetes and COVID-19 infection should follow several protective measurements.[18]

  1. To notify the appropriate health-care authority with clinical suspicion for COVID-19, as screening of covid-19 is available at specific designated center
  2. Quarantine the suspected case for 14 days or until symptoms resolve
  3. Adequate hydration to be maintained and treatment for fever and cough to be treated appropriately
  4. ”Sick day rules” should be followed as for any emergency or stressful situation to improve their diabetes control and related complication. If someone is on insulin regular checking ketone bodies, blood glucose level to maintain euglycemic state, and adjust insulin dose accordingly
  5. When patents get admitted to hospital due to uncontrolled blood sugar. Monitoring blood glucose and to stop the use of oral diabetic agents, especially metformin and sodium-glucose cotransporter-2 inhibitors (i.e. empagliflozin), as in this situation is insulin is recommended
  6. If the patient develops any life-threatening complication, such as ketoacidosis (DKA) or any systemic infection, must be hospitalized for prompt treatment as an emergency.



  Recent Drug Development Targeting Inflammation Could Help Treat COVID-19 in Diabetes Top


Guo and colleagues[1] have reported that patients with diabetes has more elevated levels of cardiac, renal and liver enzymes than the patients without diabetes, indicating injury to these vital organs, some of them are predisposed to multiple organ failure.

COVID-19 infected diabetes patients have increased markers of inflammation, especially IL6 is responsible for inducing the cytokine storm. The anti-IL-6 chimeric monoclonal antibody siltuximab; (Siltuximab In Serious COVID-19) SISCO study, in COVID-19 patients who have developed serious respiratory complications has shown efficacy of IL-6 inhibition.[19] In some Italian centers off-label the use of monoclonal antibody against the IL-6 receptor, tocilizimab has been shown positive results in patients with COVID-19; it is also recently being tested as an ad hoc randomized controlled trial.[8] Additionally, the new Janus Kinase inhibitors drugs, like upadacitinib, baricitinib, tofacitinib, could novel approaches to deal against COVID-19 subjects, mostly with diabetes subjects that might inhibit both inflammation and cellular viral entry in COVID-19.[2],[8]


  Conclusion Top


It is now clear that COVID-19 infection is confined to respiratory system and complications are associated in all vital organs. People with comorbidities are especially vulnerable to the complications of COVID-19. There is recent surge of publications on COVID infection mostly from one region of China and hence generalization of the finding may not be possible because of paucity of data from other parts of the world. The present commentary focusses primarily on how to clinically examine and manage diabetes in the current COVID pandemic. It is expected that with availability of more credible data, the guidelines will be further refined and the management will become simpler.

Learning points

  1. Diabetes patients with COVID-19 infection are more prone for increased mortality, ICU admission, and prolonged hospital stay compared to their non-diabetic counterparts
  2. COVID-19 with diabetes need strict glycemic control with insulin, and oral diabetic agents should be avoided when admitted to ICU
  3. Diabetic patients should keep their blood sugar under control by doing frequent monitoring using digital appliance and to contact with their physician to remain in good glycemic control.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest by the authors to declare.



 
  References Top

1.
Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020;31:e3319.  Back to cited text no. 1
    
2.
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4.  Back to cited text no. 2
    
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Chatterjee P, Nagi N, Agarwal A, Das B, Banerjee S, Sarkar S, et al. The 2019 novel coronavirus disease (COVID-19) pandemic: A review of the current evidence. Indian J Med Res 2020;151:147-59.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Zhou T, Hu Z, Yang S, Sun L, Yu Z, Wang G. Role of adaptive and innate immunity in type 2 diabetes mellitus. J Diabetes Res 2018;8;2018:7457269. doi: 10.1155/2018/7457269.  Back to cited text no. 4
    
5.
Yang JK, Feng Y, Yuan MY, Yuan SY, Fu HJ, Wu BY, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med 2006;23:623-8.  Back to cited text no. 5
    
6.
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the 'Cytokine Storm' in COVID-19. J Infect 2020;80:607-13.  Back to cited text no. 6
    
7.
Bornstein SR, Dalan R, Hopkins D, Mingrone G, Boehm BO. Endocrine and metabolic link to coronavirus infection. Nat Rev Endocrinol 2020;16:297-8.  Back to cited text no. 7
    
8.
Maddaloni E, Buzzetti R. Covid-19 and diabetes mellitus: Unveiling the interaction of two pandemics. Diabetes Metab Res Rev 2020:e33213321. doi: 10.1002/dmrr. 3321.  Back to cited text no. 8
    
9.
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med 2020;382:1653-9.  Back to cited text no. 9
    
10.
Tikellis C, Thomas MC. Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. Int J Pept 2012;2012:25694. doi: 10.1155/2012/256294.  Back to cited text no. 10
    
11.
BMJ 2020;368:m406. Available from: https://www.bmj.com/content/368/bmj.m406/rr-19. [Last accessed on 2020 Apr 20].  Back to cited text no. 11
    
12.
Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020;63:364-74.  Back to cited text no. 12
    
13.
Pal R, Bhansali A. COVID-19, diabetes mellitus and ACE2: The conundrum. Diabetes Res Clin Pract 2020;162:108-32.  Back to cited text no. 13
    
14.
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020;8:e21.  Back to cited text no. 14
    
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Gupta R, Ghosh A, Singh AK, Mishra A. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr 2020;14:211-2.  Back to cited text no. 15
    
16.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72,314 cases from the Chinese Centre for Disease Control and Prevention. JAMA 2020. doi: 10.1001/jama. 2020.2648.  Back to cited text no. 16
    
17.
Wang A, Zhao W, Xu Z, Gu J. Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID-19) is urgently needed. Diabetes Res Clin Pract 2020;162:108118.  Back to cited text no. 17
    
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COVID-19 and diabetes-International Diabetes Federation. Available from: https://www.idf.org/aboutdiabetes/what-is-diabetes/covid-19-and-diabetes.html. [Last acessed on 2020 Apr 20].  Back to cited text no. 18
    
19.
EUSA Pharma and Papa Giovanni XXIII Hospital, Italy, Provide Interim Analysis Data for Siltuximab-Treated COVID-19 Patients from the SISCO Study. Available from: https://clinicaltrials.gov/ct2/show/NCT04322188.  Back to cited text no. 19
    




 

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