Clinical considerations for patients with diabetes in times of COVID-19 epidemic
Identifieur interne : 000454 ( Pmc/Corpus ); précédent : 000453; suivant : 000455Clinical considerations for patients with diabetes in times of COVID-19 epidemic
Auteurs : Akhtar HussainSource :
- Diabetes & Metabolic Syndrome [ 1871-4021 ] ; 2020.
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DOI: 10.1016/j.dsx.2020.04.002
PubMed: 32344369
PubMed Central: 7146672
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Clinical considerations for patients with diabetes in times of COVID-19 epidemic</title><author><name sortKey="Hussain, Akhtar" sort="Hussain, Akhtar" uniqKey="Hussain A" first="Akhtar" last="Hussain">Akhtar Hussain</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32344369</idno><idno type="pmc">7146672</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146672</idno><idno type="RBID">PMC:7146672</idno><idno type="doi">10.1016/j.dsx.2020.04.002</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000454</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000454</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Clinical considerations for patients with diabetes in times of COVID-19 epidemic</title><author><name sortKey="Hussain, Akhtar" sort="Hussain, Akhtar" uniqKey="Hussain A" first="Akhtar" last="Hussain">Akhtar Hussain</name></author></analytic><series><title level="j">Diabetes & Metabolic Syndrome</title><idno type="ISSN">1871-4021</idno><idno type="eISSN">1878-0334</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wu, C" uniqKey="Wu C">C. Wu</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name></author><author><name sortKey="Cai, Y" uniqKey="Cai Y">Y. Cai</name></author><author><name sortKey="Xia, J" uniqKey="Xia J">J. Xia</name></author><author><name sortKey="Zhou, X" uniqKey="Zhou X">X. Zhou</name></author><author><name sortKey="Xu, S" uniqKey="Xu S">S. Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name></author><author><name sortKey="Zhao, F" uniqKey="Zhao F">F. Zhao</name></author><author><name sortKey="Zhi, L" uniqKey="Zhi L">L. Zhi</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Liu, L" uniqKey="Liu L">L. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gupta, R" uniqKey="Gupta R">R. Gupta</name></author><author><name sortKey="Ghosh, A" uniqKey="Ghosh A">A. Ghosh</name></author><author><name sortKey="Singh, A K" uniqKey="Singh A">A.K. Singh</name></author><author><name sortKey="Misra, A" uniqKey="Misra A">A. Misra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knapp, S" uniqKey="Knapp S">S. Knapp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abregu, A V" uniqKey="Abregu A">A.V. Abregú</name></author><author><name sortKey="Carrizo, T R" uniqKey="Carrizo T">T.R. Carrizo</name></author><author><name sortKey="Diaz, E I" uniqKey="Diaz E">E.I. Díaz</name></author><author><name sortKey="Velarde, M S" uniqKey="Velarde M">M.S. Velarde</name></author><author><name sortKey="Fonio, M C" uniqKey="Fonio M">M.C. Fonio</name></author><author><name sortKey="Bazan, M C" uniqKey="Bazan M">M.C. Bazán</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="letter"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Diabetes Metab Syndr</journal-id><journal-id journal-id-type="iso-abbrev">Diabetes Metab Syndr</journal-id><journal-title-group><journal-title>Diabetes & Metabolic Syndrome</journal-title></journal-title-group><issn pub-type="ppub">1871-4021</issn><issn pub-type="epub">1878-0334</issn><publisher><publisher-name>Published by Elsevier Ltd on behalf of Diabetes India.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32344369</article-id><article-id pub-id-type="pmc">7146672</article-id><article-id pub-id-type="publisher-id">S1871-4021(20)30061-8</article-id><article-id pub-id-type="doi">10.1016/j.dsx.2020.04.002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Clinical considerations for patients with diabetes in times of COVID-19 epidemic</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Hussain</surname><given-names>Akhtar</given-names></name><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1">NORD University, Norway</aff><aff id="aff2">Faculty of Medicine, Federal University of Ceará (FAMED-UFC), Brazil</aff><aff id="aff3">International Diabetes Federation (IDF)</aff><aff id="aff4">Diabetes Asian Study Group (DASG)</aff><contrib-group><contrib contrib-type="author" id="au2"><name><surname>Cristina do Vale Moreira</surname><given-names>Nayla</given-names></name></contrib></contrib-group><aff id="aff5">University of Oslo, Norway</aff><aff id="aff6">Faculty of Medicine, Federal University of Ceará (FAMED-UFC), Brazil</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author.</corresp></author-notes><pub-date pub-type="pmc-release"><day>10</day><month>4</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>10</day><month>4</month><year>2020</year></pub-date><permissions><copyright-statement>© 2020 Published by Elsevier Ltd on behalf of Diabetes India.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder></copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></article-meta></front><body><p content-type="salutation">Dear Sir,</p><p id="p0010">As of today’s reports, the global number of confirmed cases of COVID-19 has surpassed 150,000. The number of known cases is increasing by several thousand every day. On March 11, 2020, WHO publicly characterized COVID-19 as a pandemic. The issue is of serious concern and deserves momentous attention.</p><p id="p0015">Coronaviruses are a family of viruses that cause respiratory illnesses. Most of them cause illness in animals, but seven known types of coronaviruses cause illness in humans. The coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is one of those viruses – it causes the illness currently known as Coronavirus Disease-2019 (COVID-19).</p><p id="p0020">Though we are still learning what exactly puts someone at greater risk of developing a severe illness with COVID-19, early information indicates older patients and those with chronic medical conditions such as hypertension, diabetes and cardio-cerebrovascular diseases may be at higher risk (<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>). Infection caused by COVID-19 is likely to disturb metabolic regulation. Diabetic patients with COVID-19 may face an altered immune response on the background of an already compromised health status owing to the diabetes-related complications and/or aging.</p><p id="p0025">The most important findings in patients with hyperglycemia and a viral infection were significant worsening of symptoms, which implies greater morbidity in these patients when compared to those without diabetes (<xref rid="bib3" ref-type="bibr">3</xref>). However, the pathophysiology of this association remains uncertain. It is not known whether hyperglycemia changes the virulence of the infection, or if the virus modifies the glycemic metabolism. What we know is that diabetic patients are more susceptible to infection, and this can impact on glucose metabolism (<xref rid="bib4" ref-type="bibr">4</xref>). DM is not just a disorder of glucose metabolism, but a chronic inflammatory condition characterized by multiple changes in lipid, carbohydrate and protein profiles (<xref rid="bib5" ref-type="bibr">5</xref>). Such inflammatory processes are due to hyperglycemia which leads to increased synthesis of glycosylation end products (AGEs), activates macrophages and other cells of the immune system, increase oxidative stress and promote the synthesis of pro-inflammatory cytokines, besides stimulating the synthesis of adhesion molecules that facilitate inflammation in the tissues (<xref rid="bib5" ref-type="bibr">5</xref>). The inflammatory process and its complications might provide a higher propensity to infections or a greater severity of these conditions. Another important issue is how this inflammatory and immune response occur in diabetic patients who acquire a viral infection, as well as whether the virus itself interferes with insulin secretion or the glycemic control.</p><p id="p0030">At this stage, the biological mechanism of the relationship between COVID-19 and diabetes is not known, but the association for the severity of cases and death is pronounced. We need to develop a hypothesis to explain the causal path underlying the more severe clinical presentation of COVID-19 infection and subsequent death in diabetic patients. Biochemical tests are also essential to clarify the molecular pathophysiology involved.</p><p id="p0035">The association of COVID-19 and DM is of substantial public health importance and deserves proper attention, since a large and diverse population is being affected globally. Nowadays this comorbidity poses a relevant threat to human health, and prospective well-designed studies to elucidate the biological mechanism and the best clinical management of this association are urgently needed.<boxed-text id="dtbox1"><sec-meta><contrib-group><contrib contrib-type="author" id="au3"><name><surname>Home</surname><given-names>Philip</given-names></name><email>philip.home@newcastle.ac.uk</email></contrib><aff id="aff7">Translational and Clinical Research Institute, The Medical School, Framlington Place, Newcastle Upon Tyne, NE20 9HU, UK</aff></contrib-group></sec-meta><p id="p0040">Dear Sir</p><p id="p0045">It was very useful to see the review published in the journal on diabetes and COVID 19 infection [<xref rid="bib6" ref-type="bibr">6</xref>]. In it you highlight that people with diabetes have a death rate perhaps around four times that of the background population, and I note that it has been suggested over 20-40 % of deaths in China/Wuhan were in people with diabetes [<xref rid="bib7" ref-type="bibr">7</xref>,<xref rid="bib8" ref-type="bibr">8</xref>], Clearly it is important to understand why.</p><p id="p0050">There will be some confounders here in the form of associations with other risk factors for dying with a Covid-19 infection, notably age and cardiovascular disease, but these cannot explain all the excess. We need to understand this better to mitigate the risk.</p><p id="p0055">It is reported that most of the deaths are occurring in the context of pneumonitis [<xref rid="bib7" ref-type="bibr">7</xref>,<xref rid="bib8" ref-type="bibr">8</xref>], and in particularly onset of adult respiratory distress syndrome (ARDS), a condition in which excess fluid in the alveoli blocks gas exchange between air and blood.</p><p id="p0060">People with diabetes, and many with cardiovascular disease (CVD) without diabetes, have a very permeable vasculature, identified since the 1980s as albumin lead through the kidneys (micro- and macro-albuminuria), but even prior to that as a late blush over the retina with intravenous fluorescence marker injection [<xref rid="bib9" ref-type="bibr">9</xref>]. This leaky vasculature is associated with vascular inflammation, metabolic syndrome, and steatohepatitis, as well as CVD per se.</p><p id="p0065">It would seem not too far a stretch, in the absence of further research as yet, to assume that prior enhancement of vascular permeability could account for the increased rate of ARDS and death in people with diabetes, particularly type 2 diabetes, and also some with CVD.</p><p id="p0070">Aside from further research I would suggest that those already with albuminuria (a routine yearly test for people with diabetes), those with higher liver enzyme markers (ALT), and perhaps those with diabetes associated dyslipidaemia (low HDL cholesterol) should take particular steps to self-isolate.</p><p id="p0075">It is unclear to me how fast vascular inflammation can be ameliorated by improved blood glucose control (nearly all glucose-lowering medications reduce microalbuminuria in time), but tight glucose control in infected persons with insulin would meanwhile seem sensible. Very poor glucose control is further known to interfere with leukocyte/lymphocyte function [<xref rid="bib10" ref-type="bibr">10</xref>].</p><p id="p0080">Yours sincerely.</p><p id="p0085">Philip Home.</p><p id="p0090">Translational and Clinical Research Institute, Newcastle University, UK.</p><ref-list id="fread0010"><title>References</title><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Gupta</surname><given-names>R.</given-names></name><name><surname>Ghosh</surname><given-names>A.</given-names></name><name><surname>Singh</surname><given-names>A.K.</given-names></name><name><surname>Misra</surname><given-names>A.</given-names></name></person-group><article-title>Clinical considerations for patients with diabetes in times of COVID-19</article-title><source>Diabetes Metabolic Syndr Clin Res Rev</source><volume>14</volume><year>2020</year><fpage>211e212</fpage></element-citation></ref><ref id="bib7"><label>7</label><mixed-citation publication-type="other" id="sref2">Joint Commission. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 16-24 February 2020. Available at <ext-link ext-link-type="uri" xlink:href="https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf" id="intref0010">https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf</ext-link> (accessed 13 March 2020)</mixed-citation></ref><ref id="bib8"><label>8</label><mixed-citation publication-type="other" id="sref3">The novel coronavirus pneumonia emergency response epidemiology team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) — China 2020. China CDC Weekly 2020; 2(x): 1-10. Available from <ext-link ext-link-type="uri" xlink:href="https://github.com/cmrivers/ncov/blob/master/COVID-19.pdf%20for%20china%20CVD%20weekly" id="intref0015">https://github.com/cmrivers/ncov/blob/master/COVID-19.pdf for china CVD weekly</ext-link> (accessed 13 March 2020)</mixed-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sref4"><person-group person-group-type="author"><name><surname>Rask-Madsen</surname><given-names>C.</given-names></name><name><surname>King</surname><given-names>G.L.</given-names></name></person-group><article-title>Vascular complications of diabetes: mechanisms of injury and protective factors</article-title><source>Cell Metab</source><volume>17</volume><year>2013</year><fpage>20</fpage><lpage>33</lpage><pub-id pub-id-type="pmid">23312281</pub-id></element-citation></ref><ref id="bib10"><label>10</label><mixed-citation publication-type="other" id="sref5">Pozzilli P, Signore E, Leslie RDG. Infections, immunity and diabetes. In, Alberti KGMM, Zimmet P, DeFronzo RA (ed) International Textbook of Diabetes, Second Edition. Chichester: John Wiley, 1997, 1231-1241.</mixed-citation></ref></ref-list></boxed-text><boxed-text id="dtbox2"><sec-meta><contrib-group><contrib contrib-type="author" id="au4"><name><surname>Gupta</surname><given-names>Ritesh</given-names></name></contrib><aff id="aff8">Fortis CDOC Hospital, Chirag Enclave</aff></contrib-group></sec-meta><p id="p0095">Renin Angiotensin System Blockade and COVID-19 Disease</p><p id="p0100">Dear editor,</p><p id="p0105">We recently published an article highlighting the special concerns while managing patients with diabetes in the times of COVID-19 pandemic<xref rid="bib11" ref-type="bibr"><sup>11</sup></xref>. There have been some concerns about the use of Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), which were not clarified in our publication<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref>. We are summarising the current evidence in this regard and will try to arrive at a reasonable conclusion.</p><p id="p0110">In the absence of a vaccine and an antiviral drug for the COVID-19 infection, several therapeutic approaches are being studied. One such approach is the use of inhibitors of the renin angiotensin system, namely ACE inhibitors and ARBs. On the other hand, some concern has been raised about the fact that patients on these agents might be at an increased risk of infection by Severe Acute Respiratory Syndrome coronavirus-2 (SARS CoV-2).</p><p id="p0115">Angiotensin converting enzyme-2 (ACE-2) is the receptor for SARS CoV-2 as well as other coronaviruses and is expressed in type 2 alveolar epithelial cells and endothelium. The S-glycoprotein on the surface of coronavirus binds to ACE2. This leads to a conformational change in the S-glycoprotein and allows proteolytic digestion by host cell proteases (TMPRSS2) ultimately leading to internalization of the virion<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref>. Viral S-glycoprotein, TMPRSS2 and ACE-2 inhibition are potential targets of therapy and possibly vaccine development.</p><p id="p0120">As ACE-2 is essential to coronavirus infection, its blockade is thought to be beneficial in preventing/treating this infection. A retrospective analysis found reduced rates of death and endotracheal intubation in patients with viral pneumonia who were continued on ACE inhibitors<xref rid="bib14" ref-type="bibr"><sup>14</sup></xref>. Mice with coronavirus induced lung injury showed improvement when treated with losartan<xref rid="bib15" ref-type="bibr"><sup>15</sup></xref>. As far as CVID-19 infection is concerned, the data on RAS activation or the effect of its blockade is limited at present. Hypokalaemia could be a marker of RAS activation and high incidence of hypokalaemia has been reported in patients with COVID-19 infection<xref rid="bib16" ref-type="bibr"><sup>16</sup></xref>.</p><p id="p0125">Despite these small studies suggesting the benefit of drugs acting on RAS, there is some data, albeit scarce, from animal models and human studies that treatment with ACE inhibitors and ARB could cause up regulation of ACE2<xref rid="bib17" ref-type="bibr"><sup>17</sup></xref>. Ibuprofen and thiazolidinediones have also been shown to do the same<xref rid="bib18" ref-type="bibr"><sup>18</sup></xref><sup>,</sup><xref rid="bib19" ref-type="bibr"><sup>19</sup></xref>. Increased expression of ACE2 could theoretically increase the risk of infection with SARS CoV-2. This could be a concern in people with diabetes who are at already elevated risk of infections because of many other factors. However, currently, there is no evidence to support this hypothesis. In view of lack of robust evidence for either benefit or harm, it is reasonable for patients to continue using ACE inhibitors and ARB, as recommended by European Society of Cardiology Council on Hypertension and European Society of Hypertension.<xref rid="bib20" ref-type="bibr"><sup>20</sup></xref><sup>,</sup><xref rid="bib21" ref-type="bibr"><sup>21</sup></xref>.</p><ref-list id="fread0015"><title>References</title><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sref6"><person-group person-group-type="author"><name><surname>Gupta</surname><given-names>R.</given-names></name><name><surname>Ghosh</surname><given-names>A.</given-names></name><name><surname>Singh</surname><given-names>A.K.</given-names></name><name><surname>Misra</surname><given-names>A.</given-names></name></person-group><article-title>Clinical considerations for patients with diabetes in times of COVID-19 epidemic</article-title><source>Diabetes Metab 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