COVID-19 in Diabetics: Difference between revisions

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==Overview==
==Overview==
[[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]] in 2020. Numerous explanations have been developed for this [[Comorbidity]], such as [[immune system]] impairment due to abnormal production of [[Adipokine|adipokines]] and [[Cytokine|cytokines]] (eg, [[tumor necrosis factor-alpha]] and [[interferon|interferons]]),  as well as decreased [[Phagocytosis|phagocytic]] activity and [[chemotaxis]] among [[Diabetes mellitus|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 factor|risk factors]] and are also related to worse [[Clinical endpoint|outcome]]. There are some confirmed [[risk factor|risk factors]] for [[COVID-19]] in diabetics such as glycemic instability, [[Immunity (medical)|immune]] deficiency and related [[Comorbidity|comorbidities]], like [[obesity]] and [[Heart disease|cardiac]] and [[renal disease]]. There are also some hypothesized [[risk factor|risk factors]] such as reduced [[Angiotensin-converting enzyme|ACE]]2,  Increased [[furin]] and chronic [[inflammation]]. [[COVID-19]] among diabetic patients has been related to higher rate of [[Complication (medicine)|complications]]. [[Acute respiratory distress syndrome|Acute respiratory distress syndrome]] ([[Acute respiratory distress syndrome|ARDS]]), [[Septic shock|septic shock]], [[Acute kidney injury|acute kidney injury]], acute heart injury and [[diabetic ketoacidosis]] are some of the frequently reported [[Complication (medicine)|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 [[Lymphocyte|lymphocytes]], [[Red blood cell|red blood cells]] ([[RBC]]), [[albumin]] and [[hemoglobin]]. Conversely, higher levels of [[Neutrophil|neutrophils]], [[erythrocyte sedimentation rate]] ([[Erythrocyte sedimentation rate|ESR]]), [[D-dimer]], [[Interleukin 6|interleukin-6]] [[Interleukin 6|(IL-6]]) and [[Interleukin 10|interleukin-10]] [[Interleukin 10|(IL-10]]) have been reported in these patients. Bilateral [[Consolidation (medicine)|consolidation]] and [[Ground glass opacification on CT|ground‐glass opacification]] have been reported based on [[chest X-ray]] and [[Computed tomography|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 [[Anti-diabetic drug|antidiabetics]] and [[antihypertensive]] [[medication|medications]], their possible [[Adverse effect (medicine)|side effects]] and their effects on [[Angiotensin-converting enzyme|ACE2]] expression. [[Hyperglycemia]] has been reported with [[lopinavir]], [[ritonavir]] and [[glucocorticoids]] use. Furthermore, [[Antiviral drug (patient information)|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==
==Historical Perspective==


*On March 12, 2020, the [[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]].
*On March 12, 2020, the [[World Health Organization]] declared the [[COVID-19]] outbreak a [[pandemic]]
*[[Diabetes mellitus]], specifically [[Diabetes mellitus type 2|type 2 diabetes]] has been recognized as one of the most common [[Comorbidity|comorbidities]] of [[COVID-19]], caused by [[SARS-CoV-2|severe acute respiratory syndrome coronavirus-2]] ([[SARS-CoV-2]]). It has been estimated that 20-25% of patients with [[COVID-19]] had [[diabetes]].<ref name="pmid323346462">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>


==Classification==
==Classification==


* There is no classification for [[COVID-19]] in [[diabetes mellitus]].  
*There is no classification for [[COVID-19]] in [[diabetes mellitus]].


==Pathophysiology==
==Pathophysiology==
* [[COVID-19]] is caused by a [[virus]] named [[SARS-CoV-2|severe acute respiratory syndrome coronavirus-2]] ([[SARS-CoV-2]]) belong to the order [[Nidovirales|nidovirale]], family [[coronaviridae]][[COVID-19|.]]
 
*[[Diabetes mellitus]], specifically [[Diabetes mellitus type 2|type 2 diabetes]] has been recognized as one of the most common [[Comorbidity|comorbidities]] of [[COVID-19]].<ref name="pmid3233464622">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646 }}</ref>
*[[COVID-19]] is caused by a [[virus]] called [[SARS-CoV-2|severe acute respiratory syndrome coronavirus-2]] ([[SARS-CoV-2]]) that belongs to the order [[Nidovirales|nidovirale]], family [[coronaviridae]][[COVID-19|.]]<ref name="pmid32405783">{{cite journal| author=Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N | display-authors=etal| title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1440-1452 | pmid=32405783 | doi=10.1007/s00125-020-05164-x | pmc=7220850 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32405783 }} </ref>
*Abnormal production of [[Adipokine|adipokines]] and [[Cytokine|cytokines]] like [[Tumor necrosis factor-alpha]] and [[interferon]] in [[Diabetes mellitus|diabetic]] patients have been associated with impairment in [[immune system]] and increased susceptibility to [[Infection|infections]].
*Abnormal production of [[Adipokine|adipokines]] and [[Cytokine|cytokines]] such as [[tumor necrosis factor-alpha]] and [[interferon|interferons]] in [[Diabetes mellitus|diabetic]] [[patients]] have been associated with impairment in [[immune system]] and increased susceptibility to [[Infection|infections]].
*The following factors have been demonstrated as responsible mechanisms which increase the risk of infections in [[diabetes]]:<ref name="pmid22701840">{{cite journal| author=Casqueiro J, Casqueiro J, Alves C| title=Infections in patients with diabetes mellitus: A review of pathogenesis. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 Suppl 1 | issue=  | pages= S27-36 | pmid=22701840 | doi=10.4103/2230-8210.94253 | pmc=3354930 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22701840  }} </ref><ref name="pmid26198368">{{cite journal| author=Dryden M, Baguneid M, Eckmann C, Corman S, Stephens J, Solem C | display-authors=etal| title=Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections. | journal=Clin Microbiol Infect | year= 2015 | volume= 21 Suppl 2 | issue=  | pages= S27-32 | pmid=26198368 | doi=10.1016/j.cmi.2015.03.024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26198368  }} </ref>
*[[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:<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|volume=8|issue=9|year=2020|pages=782–792|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
**[[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 [[infection|infections]] in [[diabetes]]:<ref name="pmid22701840">{{cite journal| author=Casqueiro J, Casqueiro J, Alves C| title=Infections in patients with diabetes mellitus: A review of pathogenesis. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 Suppl 1 | issue=  | pages= S27-36 | pmid=22701840 | doi=10.4103/2230-8210.94253 | pmc=3354930 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22701840  }} </ref><ref name="pmid26198368">{{cite journal| author=Dryden M, Baguneid M, Eckmann C, Corman S, Stephens J, Solem C | display-authors=etal| title=Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections. | journal=Clin Microbiol Infect | year= 2015 | volume= 21 Suppl 2 | issue=  | pages= S27-32 | pmid=26198368 | doi=10.1016/j.cmi.2015.03.024 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26198368 }} </ref><ref name="pmid32405783">{{cite journal| author=Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N | display-authors=etal| title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1440-1452 | pmid=32405783 | doi=10.1007/s00125-020-05164-x | pmc=7220850 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32405783 }} </ref>
**Reduction of [[Interleukin]] production
**Reduction of [[Interleukin]] production
**[[Neutrophil]] dysfunction
**Decreased [[Phagocytosis|phagocytic]] activity and [[chemotaxis]]
**Decreased [[Phagocytosis|phagocytic]] activity and [[chemotaxis]]
**Decreased [[T cell]] activity
**Immobilized [[granulocyte|granulocytes]]
**Immobilized [[granulocyte|granulocytes]]
**Poor [[Circulatory system|circulation]], especially with concurrent [[Peripheral arterial disease|peripheral vascular disease]] ([[Peripheral arterial disease|PVD]])
**Poor [[Circulatory system|circulation]], especially with concurrent [[Peripheral arterial disease|peripheral vascular disease]] ([[Peripheral arterial disease|PVD]])


==Causes==
==Causes==
Disease name] may be caused by [cause1], [cause2], or [cause3].


==Differentiating [disease name] from other Diseases==
*[[COVID-19|Coronavrus Disease 2019]] ([[COVID-19]]) is caused by a [[virus]] named [[SARS-CoV-2|severe acute respiratory syndrome coronavirus-2]] ([[SARS-CoV-2]]).
*To browse the [[causes]] of [[diabetes]], [[Diabetes mellitus type 2 causes|click here]].
 
==Differentiating 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:
*Two types of [[diabetes]] is better to be differentiated from each other for optimal approach.
*To browse the differential diagnosis of [[type 2 diabetes]], [[Differentiating Diabetes mellitus type 2 from other diseases|click here]].
*To browse the differential diagnosis of [[COVID-19]], [[COVID-19 differential diagnosis|click here]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
*It has been estimated that 20-25% of patients with [[COVID-19]] had [[Diabetes mellitus|diabetes]].<ref name="pmid3233464623">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
 
*It has been estimated that 20-25% of [[patients]] with [[COVID-19]] had [[Diabetes mellitus|diabetes]].<ref name="pmid3233464623">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
*Based on a [[Meta-analysis]], the [[prevalence]] of [[diabetes]] among Chinese population with [[COVID-19]] was 9·7%.<ref name="pmid32161990">{{cite journal| author=Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L | display-authors=etal| title=Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. | journal=Clin Res Cardiol | year= 2020 | volume= 109 | issue= 5 | pages= 531-538 | pmid=32161990 | doi=10.1007/s00392-020-01626-9 | pmc=7087935 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32161990  }} </ref>
*Based on a [[Meta-analysis]], the [[prevalence]] of [[diabetes]] among Chinese population with [[COVID-19]] was 9·7%.<ref name="pmid32161990">{{cite journal| author=Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L | display-authors=etal| title=Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. | journal=Clin Res Cardiol | year= 2020 | volume= 109 | issue= 5 | pages= 531-538 | pmid=32161990 | doi=10.1007/s00392-020-01626-9 | pmc=7087935 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32161990  }} </ref>
*A study done on 1317 participants reported that 88.5% of patients with [[COVID-19]] had concurrent [[diabetes mellitus type 2]].<ref name="pmid32472191">{{cite journal| author=Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I | display-authors=etal| title=Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1500-1515 | pmid=32472191 | doi=10.1007/s00125-020-05180-x | pmc=7256180 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32472191  }} </ref>  
*A study done on 1317 participants reported that 88.5% of [[patients]] with [[COVID-19]] had concurrent [[diabetes mellitus type 2]].<ref name="pmid32472191">{{cite journal| author=Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I | display-authors=etal| title=Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1500-1515 | pmid=32472191 | doi=10.1007/s00125-020-05180-x | pmc=7256180 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32472191  }} </ref>
*Based on a study done in Wuhan, 16.2% of [[patient|patients]] who experienced sever [[COVID-19]] were [[diabetes|diabetics]].<ref>{{cite journal|doi=10.3760/cma.j.cn112148-20200225-00123}}</ref> 


===Age===
*[[Diabetes mellitus|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.<ref name="ChenYang20202">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref><ref name="pmid32232322">{{cite journal| author=Dudley JP, Lee NT| title=Disparities in Age-specific Morbidity and Mortality From SARS-CoV-2 in China and the Republic of Korea. | journal=Clin Infect Dis | year= 2020 | volume= 71 | issue= 15 | pages= 863-865 | pmid=32232322 | doi=10.1093/cid/ciaa354 | pmc=7184419 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32232322  }} </ref>


===Age===
*[[Diabetes mellitus|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.<ref name="ChenYang20202">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref><ref name="pmid32232322">{{cite journal| author=Dudley JP, Lee NT| title=Disparities in Age-specific Morbidity and Mortality From SARS-CoV-2 in China and the Republic of Korea. | journal=Clin Infect Dis | year= 2020 | volume= 71 | issue= 15 | pages= 863-865 | pmid=32232322 | doi=10.1093/cid/ciaa354 | pmc=7184419 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32232322  }} </ref>
*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.<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|volume=8|issue=9|year=2020|pages=782–792|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*Individuals older than 80 years old have 12-times higher chance of worse outcome, compared to those aged 50-59 years old.<ref name="WilliamsonWalker2020">{{cite journal|last1=Williamson|first1=Elizabeth|last2=Walker|first2=Alex J|last3=Bhaskaran|first3=Krishnan J|last4=Bacon|first4=Seb|last5=Bates|first5=Chris|last6=Morton|first6=Caroline E|last7=Curtis|first7=Helen J|last8=Mehrkar|first8=Amir|last9=Evans|first9=David|last10=Inglesby|first10=Peter|last11=Cockburn|first11=Jonathan|last12=Mcdonald|first12=Helen I|last13=MacKenna|first13=Brian|last14=Tomlinson|first14=Laurie|last15=Douglas|first15=Ian J|last16=Rentsch|first16=Christopher T|last17=Mathur|first17=Rohini|last18=Wong|first18=Angel|last19=Grieve|first19=Richard|last20=Harrison|first20=David|last21=Forbes|first21=Harriet|last22=Schultze|first22=Anna|last23=Croker|first23=Richard T|last24=Parry|first24=John|last25=Hester|first25=Frank|last26=Harper|first26=Sam|last27=Perera|first27=Rafael|last28=Evans|first28=Stephen|last29=Smeeth|first29=Liam|last30=Goldacre|first30=Ben|year=2020|doi=10.1101/2020.05.06.20092999}}</ref>
===Gender===
*Male sex has been linked to higher [[prevalence]] of [[COVID-19]].<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|year=2020|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*Chance of worse [[Clinical endpoint|outcome]] has been estimated twice in male sex, compared to females.<ref name="WilliamsonWalker2020">{{cite journal|last1=Williamson|first1=Elizabeth|last2=Walker|first2=Alex J|last3=Bhaskaran|first3=Krishnan J|last4=Bacon|first4=Seb|last5=Bates|first5=Chris|last6=Morton|first6=Caroline E|last7=Curtis|first7=Helen J|last8=Mehrkar|first8=Amir|last9=Evans|first9=David|last10=Inglesby|first10=Peter|last11=Cockburn|first11=Jonathan|last12=Mcdonald|first12=Helen I|last13=MacKenna|first13=Brian|last14=Tomlinson|first14=Laurie|last15=Douglas|first15=Ian J|last16=Rentsch|first16=Christopher T|last17=Mathur|first17=Rohini|last18=Wong|first18=Angel|last19=Grieve|first19=Richard|last20=Harrison|first20=David|last21=Forbes|first21=Harriet|last22=Schultze|first22=Anna|last23=Croker|first23=Richard T|last24=Parry|first24=John|last25=Hester|first25=Frank|last26=Harper|first26=Sam|last27=Perera|first27=Rafael|last28=Evans|first28=Stephen|last29=Smeeth|first29=Liam|last30=Goldacre|first30=Ben|year=2020|doi=10.1101/2020.05.06.20092999}}</ref>
===Race===
*There are some data supporting that non-white ethnic groups have higher chance of developing [[COVID-19]].<ref name="WilliamsonWalker2020">{{cite journal|last1=Williamson|first1=Elizabeth|last2=Walker|first2=Alex J|last3=Bhaskaran|first3=Krishnan J|last4=Bacon|first4=Seb|last5=Bates|first5=Chris|last6=Morton|first6=Caroline E|last7=Curtis|first7=Helen J|last8=Mehrkar|first8=Amir|last9=Evans|first9=David|last10=Inglesby|first10=Peter|last11=Cockburn|first11=Jonathan|last12=Mcdonald|first12=Helen I|last13=MacKenna|first13=Brian|last14=Tomlinson|first14=Laurie|last15=Douglas|first15=Ian J|last16=Rentsch|first16=Christopher T|last17=Mathur|first17=Rohini|last18=Wong|first18=Angel|last19=Grieve|first19=Richard|last20=Harrison|first20=David|last21=Forbes|first21=Harriet|last22=Schultze|first22=Anna|last23=Croker|first23=Richard T|last24=Parry|first24=John|last25=Hester|first25=Frank|last26=Harper|first26=Sam|last27=Perera|first27=Rafael|last28=Evans|first28=Stephen|last29=Smeeth|first29=Liam|last30=Goldacre|first30=Ben|year=2020|doi=10.1101/2020.05.06.20092999}}</ref>
*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.<ref name="HaynesCooper2020">{{cite journal|last1=Haynes|first1=Norrisa|last2=Cooper|first2=Lisa A.|last3=Albert|first3=Michelle A.|title=At the Heart of the Matter|journal=Circulation|volume=142|issue=2|year=2020|pages=105–107|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.048126}}</ref>
*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.<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|volume=8|issue=9|year=2020|pages=782–792|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
 
==Risk Factors==
==Risk Factors==


*Some possible factors that lead to more severe [[COVID-19]] in diabetic patient have been summarized in the table below:<ref name="GuptaHussain20202">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
*Some possible factors that lead to more severe [[COVID-19]] in [[diabetic]] [[patient]] have been summarized in the table below:<ref name="GuptaHussain20202">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>


{| class="wikitable"
{| class="wikitable"
Line 60: Line 61:
|-
|-
|1- Glycemic instability
|1- Glycemic instability
2- Immune deficiency (specially [[T cell|T-cell]] response)
2- Immune deficiency (especially [[T cell|T-cell]] response)


3- Related [[Comorbidity|comorbidities]], like [[obesity]] and [[Heart disease|cardiac]] and [[renal disease]]
3- Related [[Comorbidity|comorbidities]], like [[obesity]] and [[Heart disease|cardiac]] and [[renal disease]]
Line 70: Line 71:
4- Increased [[furin]] (involved in [[virus]] entry into [[Cell (biology)|cell]])
4- Increased [[furin]] (involved in [[virus]] entry into [[Cell (biology)|cell]])
|}
|}
==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==


=== Complications ===
===Complications===


*Diabetic patients with [[SARS-CoV-2]] infection had higher rate of the following [[Complication (medicine)|complications]]: <ref name="pmid323346463">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref><ref name="SinghKhunti2020">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
*Diabetic patients with [[SARS-CoV-2]] infection had higher rate of the following [[Complication (medicine)|complications]]: <ref name="pmid323346463">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref><ref name="SinghKhunti2020">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref><ref name="pmid32421882">{{cite journal| author=Rayman G, Lumb A, Kennon B, Cottrell C, Nagi D, Page E | display-authors=etal| title=Guidance on the management of Diabetic Ketoacidosis in the exceptional circumstances of the COVID-19 pandemic. | journal=Diabet Med | year= 2020 | volume= 37 | issue= 7 | pages= 1214-1216 | pmid=32421882 | doi=10.1111/dme.14328 | pmc=7276743 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32421882  }} </ref>
**[[Acute respiratory distress syndrome|Acute Respiratory Distress Syndrome]] ([[Acute respiratory distress syndrome|ARDS]])  
**[[Acute respiratory distress syndrome|Acute Respiratory Distress Syndrome]] ([[Acute respiratory distress syndrome|ARDS]])
**[[Septic shock|Septic Shock]]
**[[Septic shock|Septic Shock]]
**A[[Acute kidney injury|cute kidney injury]]
**A[[Acute kidney injury|cute kidney injury]]
**Acute heart injury
**Acute heart injury
**Requirement of [[oxygen]] [[inhalation]]
**Requirement of [[oxygen]] [[inhalation]]
**M[[Multiple organ dysfunction syndrome|ulti-organ failure]]  
**M[[Multiple organ dysfunction syndrome|ulti-organ failure]]
**Both non-invasive and invasive ventilation (eg, [[extracorporeal membrane oxygenation]] ([[Extracorporeal membrane oxygenation|ECMO]])).
**Both non-invasive and invasive ventilation (eg, [[extracorporeal membrane oxygenation]] ([[Extracorporeal membrane oxygenation|ECMO]]))
**[[Diabetic ketoacidosis]]:
***Associate to higher [[mortality rate]]
**[[Hyperosmolar hyperglycemic state]]
*Optimal metabolic control reduces the chance of [[Complication (medicine)|complications]] in concurrent [[diabetes mellitus]] and [[COVID-19]] in outpatients.
*Optimal metabolic control reduces the chance of [[Complication (medicine)|complications]] in concurrent [[diabetes mellitus]] and [[COVID-19]] in outpatients.
 
*[[COVID-19]] has been related to high [[coagulation]] activity, probably due to [[endothelial dysfunction]] caused by [[Hypoxemia|hypoxia]]. The latter [[COVID-19]] consequence will be more augmented by the prothrombotic state in diabetic patients, which can lead to more [[thrombosis]] related [[complication (medicine)|complications]].<ref name="pmid15892651">{{cite journal| author=Dunn EJ, Grant PJ| title=Type 2 diabetes: an atherothrombotic syndrome. | journal=Curr Mol Med | year= 2005 | volume= 5 | issue= 3 | pages= 323-32 | pmid=15892651 | doi=10.2174/1566524053766059 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15892651  }} </ref>
=== Prognosis ===
 
===Prognosis===


*[[SARS-CoV-2]] infection has been linked with higher rate of [[hospitalization]] and [[mortality]] in diabetic patients compared to non-diabetics.
*[[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]] ([[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.<ref name="pmid32178769">{{cite journal| author=Remuzzi A, Remuzzi G| title=COVID-19 and Italy: what next? | journal=Lancet | year= 2020 | volume= 395 | issue= 10231 | pages= 1225-1228 | pmid=32178769 | doi=10.1016/S0140-6736(20)30627-9 | pmc=7102589 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32178769  }}</ref>]]
*Records from the [[Centers for Disease Control and Prevention]] ([[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.<ref name="pmid32178769">{{cite journal| author=Remuzzi A, Remuzzi G| title=COVID-19 and Italy: what next? | journal=Lancet | year= 2020 | volume= 395 | issue= 10231 | pages= 1225-1228 | pmid=32178769 | doi=10.1016/S0140-6736(20)30627-9 | pmc=7102589 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32178769  }}</ref>
*Based on a study done in Wuhan, 53.8% of [[patient|patients]] who died of [[COVID-19]] were [[diebetes|diabetics]].<ref name="pmid32405783">{{cite journal| author=Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N | display-authors=etal| title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1440-1452 | pmid=32405783 | doi=10.1007/s00125-020-05164-x | pmc=7220850 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32405783  }} </ref>
*Based on a study done in Italy, 35.5% of [[COVID-19]] death had concurrent [[diabetes]].<ref name="OnderRezza2020">{{cite journal|last1=Onder|first1=Graziano|last2=Rezza|first2=Giovanni|last3=Brusaferro|first3=Silvio|title=Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy|journal=JAMA|year=2020|issn=0098-7484|doi=10.1001/jama.2020.4683}}</ref>
*Another study done in the US reports more than fourfold [[mortality rate]] elevation in [[COVID-19]] in [[diabetic]] patients.<ref name="GuptaHussain2020">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
*Another study done in the US reports more than fourfold [[mortality rate]] elevation in [[COVID-19]] in [[diabetic]] patients.<ref name="GuptaHussain2020">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
*Study on [[COVID-19]] patients in [[intensive care unit]] showed a twofold increase in [[incidence]] of diabetes, compared to non-intensive care patients.
*Study on [[COVID-19]] [[patient|patients]] in [[intensive care unit]] demonstrated 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]] ([[intensive care unit|ICU]]) admission and death, compared to nondiabetics.<ref name="pmid32409504">{{cite journal| author=Shi Q, Zhang X, Jiang F, Zhang X, Hu N, Bimu C | display-authors=etal| title=Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. | journal=Diabetes Care | year= 2020 | volume= 43 | issue= 7 | pages= 1382-1391 | pmid=32409504 | doi=10.2337/dc20-0598 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32409504  }} </ref>
*Another study done among 1561 patients with [[COVID-19]] in Wuhan demonstrated that diabetic patients had higher rate of [[intensive care unit]] ([[intensive care unit|ICU]]) admission and death, compared to nondiabetics.<ref name="pmid32409504">{{cite journal| author=Shi Q, Zhang X, Jiang F, Zhang X, Hu N, Bimu C | display-authors=etal| title=Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study. | journal=Diabetes Care | year= 2020 | volume= 43 | issue= 7 | pages= 1382-1391 | pmid=32409504 | doi=10.2337/dc20-0598 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32409504  }} </ref>
*A [[cohort study]] done on 5693 patients in England demonstrated higher chance of death among patients with uncontrolled [[diabetes]].<ref name="WilliamsonWalker2020">{{cite journal|last1=Williamson|first1=Elizabeth|last2=Walker|first2=Alex J|last3=Bhaskaran|first3=Krishnan J|last4=Bacon|first4=Seb|last5=Bates|first5=Chris|last6=Morton|first6=Caroline E|last7=Curtis|first7=Helen J|last8=Mehrkar|first8=Amir|last9=Evans|first9=David|last10=Inglesby|first10=Peter|last11=Cockburn|first11=Jonathan|last12=Mcdonald|first12=Helen I|last13=MacKenna|first13=Brian|last14=Tomlinson|first14=Laurie|last15=Douglas|first15=Ian J|last16=Rentsch|first16=Christopher T|last17=Mathur|first17=Rohini|last18=Wong|first18=Angel|last19=Grieve|first19=Richard|last20=Harrison|first20=David|last21=Forbes|first21=Harriet|last22=Schultze|first22=Anna|last23=Croker|first23=Richard T|last24=Parry|first24=John|last25=Hester|first25=Frank|last26=Harper|first26=Sam|last27=Perera|first27=Rafael|last28=Evans|first28=Stephen|last29=Smeeth|first29=Liam|last30=Goldacre|first30=Ben|year=2020|doi=10.1101/2020.05.06.20092999}}</ref>
*A [[cohort study]] done on 5693 [[patient|patients]] in England demonstrated higher chance of [[death]] among [[patient|patients]] with uncontrolled [[diabetes]].<ref name="WilliamsonWalker2020">{{cite journal|last1=Williamson|first1=Elizabeth|last2=Walker|first2=Alex J|last3=Bhaskaran|first3=Krishnan J|last4=Bacon|first4=Seb|last5=Bates|first5=Chris|last6=Morton|first6=Caroline E|last7=Curtis|first7=Helen J|last8=Mehrkar|first8=Amir|last9=Evans|first9=David|last10=Inglesby|first10=Peter|last11=Cockburn|first11=Jonathan|last12=Mcdonald|first12=Helen I|last13=MacKenna|first13=Brian|last14=Tomlinson|first14=Laurie|last15=Douglas|first15=Ian J|last16=Rentsch|first16=Christopher T|last17=Mathur|first17=Rohini|last18=Wong|first18=Angel|last19=Grieve|first19=Richard|last20=Harrison|first20=David|last21=Forbes|first21=Harriet|last22=Schultze|first22=Anna|last23=Croker|first23=Richard T|last24=Parry|first24=John|last25=Hester|first25=Frank|last26=Harper|first26=Sam|last27=Perera|first27=Rafael|last28=Evans|first28=Stephen|last29=Smeeth|first29=Liam|last30=Goldacre|first30=Ben|year=2020|doi=10.1101/2020.05.06.20092999}}</ref>
*[[complication (medicine)|Complications]] of [[diabetes]] and higher [[prevalence]] of [[Comorbidity|comorbidities]] such as [[hypertension]], [[cardiovascular disease]], [[stroke|cerebrovascular disease]], [[chronic pulmonary disease|Pulmonology]] and [[Chronic renal failure|chronic kidney disease]].<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|volume=8|issue=9|year=2020|pages=782–792|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*[[complication (medicine)|Complications]] of [[diabetes]] and higher [[prevalence]] of [[Comorbidity|comorbidities]] such as [[hypertension]], [[cardiovascular disease]], [[stroke|cerebrovascular disease]], [[pulmonology|pulmonary disease]] and [[Chronic renal failure|chronic kidney disease]].<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|volume=8|issue=9|year=2020|pages=782–792|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*Estimated [[Glomerular filtration rate|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]].<ref name="ChengLuo2020">{{cite journal|last1=Cheng|first1=Yichun|last2=Luo|first2=Ran|last3=Wang|first3=Kun|last4=Zhang|first4=Meng|last5=Wang|first5=Zhixiang|last6=Dong|first6=Lei|last7=Li|first7=Junhua|last8=Yao|first8=Ying|last9=Ge|first9=Shuwang|last10=Xu|first10=Gang|title=Kidney disease is associated with in-hospital death of patients with COVID-19|journal=Kidney International|volume=97|issue=5|year=2020|pages=829–838|issn=00852538|doi=10.1016/j.kint.2020.03.005}}</ref>
*Estimated [[Glomerular filtration rate|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]].<ref name="ChengLuo2020">{{cite journal|last1=Cheng|first1=Yichun|last2=Luo|first2=Ran|last3=Wang|first3=Kun|last4=Zhang|first4=Meng|last5=Wang|first5=Zhixiang|last6=Dong|first6=Lei|last7=Li|first7=Junhua|last8=Yao|first8=Ying|last9=Ge|first9=Shuwang|last10=Xu|first10=Gang|title=Kidney disease is associated with in-hospital death of patients with COVID-19|journal=Kidney International|volume=97|issue=5|year=2020|pages=829–838|issn=00852538|doi=10.1016/j.kint.2020.03.005}}</ref>
*[[Glycosylated hemoglobin|HbA1C]] more than 86 mmol/mol (10%) has been related to worst outcome and higher chance of death, compared to [[Glycosylated hemoglobin|HbA1C]] less than 48 mmol/mol (6·5%), which further confirms the importance of desirable [[Diabetes management|glycemic control]].<ref name="HolmanKnighton2020">{{cite journal|last1=Holman|first1=Naomi|last2=Knighton|first2=Peter|last3=Kar|first3=Partha|last4=O’Keefe|first4=Jackie|last5=Curley|first5=Matt|last6=Weaver|first6=Andy|last7=Barron|first7=Emma|last8=Bakhai|first8=Chirag|last9=Khunti|first9=Kamlesh|last10=Wareham|first10=Nick J.|last11=Sattar|first11=Naveed|last12=Young|first12=Bob|last13=Valabhji|first13=Jonathan|title=Type 1 and Type 2 Diabetes and COVID-19 Related Mortality in England: A Cohort Study in People with Diabetes|journal=SSRN Electronic Journal |year=2020|issn=1556-5068|doi=10.2139/ssrn.3605226}}</ref>
*Elevation in the followings are related to poor [[prognosis]] among [[diabetes|diabetic]] [[patient|patients]] with [[COVID-19]]:<ref name="pmid32405783">{{cite journal| author=Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N | display-authors=etal| title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1440-1452 | pmid=32405783 | doi=10.1007/s00125-020-05164-x | pmc=7220850 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32405783  }} </ref>
**[[C-reactive protein]]
**[[Erythrocyte sedimentation rate]] ([[erythrocyte sedimentation rate|ESR]])
**[[Ferritin]]
**[[Procalcitonin]]
 
==Diagnosis==


==Diagnosis==
===History and Symptoms===
===History and Symptoms===


*[Disease name] is usually asymptomatic.
*Symptoms of [[COVID-19]] may include the following:<ref name="LiWang2020">{{cite journal|last1=Li|first1=Juyi|last2=Wang|first2=Xiufang|last3=Chen|first3=Jian|last4=Zuo|first4=Xiuran|last5=Zhang|first5=Hongmei|last6=Deng|first6=Aiping|title=
*Symptoms of [disease name] may include the following:
            COVID
            ‐19 infection may cause ketosis and ketoacidosis
          |journal=Diabetes, Obesity and Metabolism|year=2020|issn=1462-8902|doi=10.1111/dom.14057}}</ref>
**[[fever]]
**[[Cough]]
**[[Dyspnea|Shortness of breath]]
**[[Fatigue]]
**[[Chest pain]]
**Chest tightness
**[[Headache]]
**Mild gastrointestinal disease ([[diarrhea]], [[nausea and vomiting]])
*For explore further about symptoms of [[COVID-19]], [[COVID-19 history and symptoms|click here]]
*To browse the [[Symptom|Symptoms]] of [[type 2 diabetes]], [[Differentiating Diabetes mellitus type 2 from other diseases|click here]].


===Physical Examination===
===Physical Examination===


*Patients with [disease name] usually appear [general appearance].
*To browse the [[Physical examination|physical examination]] of [[COVID-19]], [[COVID-19 physical examination|click here]].
*Physical examination may be remarkable for:
*To browse the [[Physical examination|physical examination]] of [[type 2 diabetes]], [[Diabetes mellitus type 2 physical examination|click here]].


===Laboratory Findings===
===Laboratory Findings===


*Diabetic patients with [[SARS-CoV-2]] infection have lower levels of the following, compared to non-diabetics:<ref name="GuoLi2020">{{cite journal|last1=Guo|first1=Weina|last2=Li|first2=Mingyue|last3=Dong|first3=Yalan|last4=Zhou|first4=Haifeng|last5=Zhang|first5=Zili|last6=Tian|first6=Chunxia|last7=Qin|first7=Renjie|last8=Wang|first8=Haijun|last9=Shen|first9=Yin|last10=Du|first10=Keye|last11=Zhao|first11=Lei|last12=Fan|first12=Heng|last13=Luo|first13=Shanshan|last14=Hu|first14=Desheng|title=Diabetes is a risk factor for the progression and prognosis of COVID-19|journal=Diabetes/Metabolism Research and Reviews|year=2020|pages=e3319|issn=15207552|doi=10.1002/dmrr.3319}}</ref><ref name="GuptaHussain20203">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
*Diabetic patients with [[SARS-CoV-2]] [[infection]] have lower levels of the following, compared to non-diabetics:<ref name="GuoLi2020">{{cite journal|last1=Guo|first1=Weina|last2=Li|first2=Mingyue|last3=Dong|first3=Yalan|last4=Zhou|first4=Haifeng|last5=Zhang|first5=Zili|last6=Tian|first6=Chunxia|last7=Qin|first7=Renjie|last8=Wang|first8=Haijun|last9=Shen|first9=Yin|last10=Du|first10=Keye|last11=Zhao|first11=Lei|last12=Fan|first12=Heng|last13=Luo|first13=Shanshan|last14=Hu|first14=Desheng|title=Diabetes is a risk factor for the progression and prognosis of COVID-19|journal=Diabetes/Metabolism Research and Reviews|year=2020|pages=e3319|issn=15207552|doi=10.1002/dmrr.3319}}</ref><ref name="GuptaHussain20203">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
**[[Lymphocyte|Lymphocytes]]
**[[Lymphocyte|Lymphocytes]]
**[[Red blood cell|Red blood cells]] ([[RBC]])
**[[Red blood cell|Red blood cells]] ([[RBC]])
**[[Albumin]]
**[[Albumin]]
**[[Hemoglobin]]
**[[Hemoglobin]]
*Diabetic patients with [[SARS-CoV-2]] infection have higher levels of the following, compared to non-diabetics:<ref name="GuptaHussain20203" /><ref name="GuoLi2020" /><ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|year=2020|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*Diabetic patients with [[SARS-CoV-2]] [[infection]] have higher levels of the following, compared to non-diabetics:<ref name="GuptaHussain20203" /><ref name="GuoLi2020" /><ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|year=2020|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref><ref name="ZhangDong2020">{{cite journal|last1=Zhang|first1=Jin-jin|last2=Dong|first2=Xiang|last3=Cao|first3=Yi-yuan|last4=Yuan|first4=Ya-dong|last5=Yang|first5=Yi-bin|last6=Yan|first6=You-qin|last7=Akdis|first7=Cezmi A.|last8=Gao|first8=Ya-dong|title=Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China|journal=Allergy|volume=75|issue=7|year=2020|pages=1730–1741|issn=0105-4538|doi=10.1111/all.14238}}</ref><ref name="pmid32286245">{{cite journal| author=Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G| title=Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. | journal=Clin Chem Lab Med | year= 2020 | volume= 58 | issue= 7 | pages= 1021-1028 | pmid=32286245 | doi=10.1515/cclm-2020-0369 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32286245  }} </ref>
**[[Neutrophils]]
**[[Neutrophils]]
**[[Erythrocyte sedimentation rate]] ([[Erythrocyte sedimentation rate|ESR]])
**[[Erythrocyte sedimentation rate]] ([[Erythrocyte sedimentation rate|ESR]])
Line 124: Line 152:
**[[Ferritin]]
**[[Ferritin]]
**[[Interleukin 6|Interleukin-6]] [[Interleukin 6|(IL-6]])
**[[Interleukin 6|Interleukin-6]] [[Interleukin 6|(IL-6]])
**[[Interleukin 10|Interleukin-10]] [[Interleukin 10|(IL-10]])
**[[Gamma-glutamyltransferase|γ-glutamyl transferase]]
**[[Gamma-glutamyltransferase|γ-glutamyl transferase]]
*High [[C-reactive protein]] ([[Cardiopulmonary resuscitation|CPR]]) level is one of the [[Risk factor|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]] ([[C-reactive protein|CRP]]) as a tool to identify patients with higher chance of dying during hospitalization.<ref name="ChenYang2020">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref>
**[[Procalcitonin]]
*High [[C-reactive protein]] ([[Cardiopulmonary resuscitation|CPR]]) level is one of the [[Risk factor|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]] ([[C-reactive protein|CRP]]) as a tool to identify patients with higher chance of dying during hospitalization.<ref name="ChenYang2020">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref> 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]].<ref name="pmid32444366">{{cite journal| author=Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell L, Chernyak Y | display-authors=etal| title=Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. | journal=BMJ | year= 2020 | volume= 369 | issue=  | pages= m1966 | pmid=32444366 | doi=10.1136/bmj.m1966 | pmc=7243801 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32444366  }} </ref [[Ferritin]] elevation could be related to secondary bacterial [[infection]] in [[COVID-19]] [[patient|patients]].<ref name="pmid32405783">{{cite journal| author=Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N | display-authors=etal| title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1440-1452 | pmid=32405783 | doi=10.1007/s00125-020-05164-x | pmc=7220850 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32405783  }} </ref>
*Sever [[COVID-19]] in diabetic patients were related to higher levels of [[serum amyloid A]] ([[SAA1|SAA]]) and low [[CD4]]+ [[T cell|T lymphocyte]] counts.<ref name="pmid32636061">{{cite journal| author=Zhang Q, Wei Y, Chen M, Wan Q, Chen X| title=Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes. | journal=J Diabetes Complications | year= 2020 | volume=  | issue=  | pages= 107666 | pmid=32636061 | doi=10.1016/j.jdiacomp.2020.107666 | pmc=7323648 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32636061  }}</ref>
*Sever [[COVID-19]] in diabetic patients were related to higher levels of [[serum amyloid A]] ([[SAA1|SAA]]) and low [[CD4]]+ [[T cell|T lymphocyte]] counts.<ref name="pmid32636061">{{cite journal| author=Zhang Q, Wei Y, Chen M, Wan Q, Chen X| title=Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes. | journal=J Diabetes Complications | year= 2020 | volume=  | issue=  | pages= 107666 | pmid=32636061 | doi=10.1016/j.jdiacomp.2020.107666 | pmc=7323648 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32636061  }}</ref>
*There is a J-curve association between [[Glycosylated hemoglobin|HbA1c]] and risk of [[infection|infections]] in general, particularly [[Respiratory tract infection|respiratory tract infections]].<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|year=2020|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*There is a J-curve association between [[Glycosylated hemoglobin|HbA1c]] and risk of [[infection|infections]] in general, particularly [[Respiratory tract infection|respiratory tract infections]].<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|year=2020|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref>
*Increased concentrations of [[N-terminal prohormone of brain natriuretic peptide]] ([[N-terminal prohormone of brain natriuretic peptide]]) and cardiac [[troponin]] I have been related to [[myocardial infarction]].<ref name="pmid32405783">{{cite journal| author=Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N | display-authors=etal| title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. | journal=Diabetologia | year= 2020 | volume= 63 | issue= 8 | pages= 1440-1452 | pmid=32405783 | doi=10.1007/s00125-020-05164-x | pmc=7220850 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32405783  }} </ref> Since [[diabetes|diabetic]] [[patient|patients]] may already suffer from cardiac [[complication (medicine)|complications]], checking these lab values could be helpful.


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
 
*There are no [[The electrocardiogram|ECG]] findings associated with [[COVID-19]] in diabetics.
 
===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
 
*[[Chest X-ray]] could be normal in early stages of [[COVID-19]] or in mild disease.
*Bilateral [[Consolidation (medicine)|consolidation]] or airspace opacities is one the findings of [[Chest X-ray]].
 
===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound findings associated with [disease name].
 
*There are no [[echocardiography]]/[[ultrasound]] findings associated with [[COVID-19]] in diabetics.
 
===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
 
*[[Ground glass opacification on CT|Ground‐glass opacification]]
 
===MRI===
===MRI===
There are no MRI findings associated with [disease name].
 
*There are no [[Magnetic resonance imaging|MRI]] findings associated with [[COVID-19]] in diabetics.
 
===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
 
*There are no other imaging findings associated with [[COVID-19]] in diabetics.
 
===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
 
*There are no other diagnostic studies associated with [[COVID-19]] in diabetics.
 
==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===


**[[Treatment]] with [[insulin]] was associated with poor [[prognosis]] in diabetic patients with [[COVID-19]].<ref name="ChenYang202022">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref> Although, [[Insulin]] is the choice agent to control [[Blood sugar|blood glucose]] in hospitalized diabetic patients with [[COVID-19]].
*Even though some studies reported that [[insulin]] was associated with poor [[prognosis]] in diabetic patients with [[COVID-19]]<ref name="ChenYang202022">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref>, [[Insulin]] is still the choice agent to control [[Blood sugar|blood glucose]] in hospitalized diabetic patients with [[COVID-19]].
**Possible [[Beta cell|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 therapy|intravenous]] infusion must be considered.<ref name="pmid32334646">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
**Possible [[Beta cell|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 therapy|intravenous]] infusion must be considered.<ref name="pmid32334646">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
**Although [[Angiotensin-converting enzyme|angiotensin-converting enzyme II]] ([[Angiotensin-converting enzyme|ACE]]) expression has been reduced in [[COVID-19]], treatment with [[ACE inhibitor|ACE inhibitors]] ([[ACE inhibitor|ACEI]]) or [[Angiotensin II receptor antagonist|angiotensin II type-I receptor blockers]] ([[Angiotensin II receptor antagonist|ARB]]) in diabetic patient with [[hypertension]] had no significant difference compared to other [[Antihypertensive|anti-hypertensive]] treatments based on one study.<ref name="ChenYang20203">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref> On the other hand, another study done on diabetic patients showed higher risk of [[SARS-CoV-2]] infection with [[Angiotensin-converting enzyme 2|ACE2]]-increasing drugs. Elevated [[Angiotensin-converting enzyme|ACE2]] level can ease the entry of [[virus]]. Therefore It is hypothesized that medications like, [[ACE inhibitor|Angiotensin-converting-enzyme inhibitors]] ([[ACE inhibitor|ACEI]]), [[Angiotensin II receptor antagonist|angiotensin II type-I receptor blockers]] ([[Angiotensin II receptor antagonist|ARB]]), [[Thiazolidinedione|thiazolidinediones]] and [[ibuprofen]] augment the risk of a severe and lethal [[SARS-CoV-2]] infection.<ref name="pmid32171062">{{cite journal| author=Fang L, Karakiulakis G, Roth M| title=Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= e21 | pmid=32171062 | doi=10.1016/S2213-2600(20)30116-8 | pmc=7118626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171062  }}</ref><ref name="pmid31537750">{{cite journal| author=Arendse LB, Danser AHJ, Poglitsch M, Touyz RM, Burnett JC, Llorens-Cortes C | display-authors=etal| title=Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure. | journal=Pharmacol Rev | year= 2019 | volume= 71 | issue= 4 | pages= 539-570 | pmid=31537750 | doi=10.1124/pr.118.017129 | pmc=6782023 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31537750  }} </ref>
**The following table is a summary of some [[insulin]] regimens and their effects in management of [[diabetes|diabetic]] [[patients]] infected with [[COVID-19]], who are receiving nutritional [[therapy]]:<ref name="pmid32444458">{{cite journal| author=Hamdy O, Gabbay RA| title=Early Observation and Mitigation of Challenges in Diabetes Management of COVID-19 Patients in Critical Care Units. | journal=Diabetes Care | year= 2020 | volume= 43 | issue= 8 | pages= e81-e82 | pmid=32444458 | doi=10.2337/dc20-0944 | pmc=7372048 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32444458  }} </ref>
**Due to increased risk of [[Chronic renal failure|chronic kidney disease]] and [[acute kidney injury]], [[renal function]] should be monitored in patients who take [[metformin]].<ref name="pmid323346466">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646 }}</ref> There is also a recommendation to stop [[Metformin]] use in a patient with poor oral intake and [[Nausea and vomiting|vomiting]].<ref name="GuptaHussain20207">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref> 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|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]].<ref name="SinghSingh2020">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Singh|first2=Ritu|title=Is metformin ahead in the race as a repurposed host-directed therapy for patients with diabetes and COVID-19?|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108268|issn=01688227|doi=10.1016/j.diabres.2020.108268}}</ref>
<br>
**A hypothesis state that since [[SGLT2|Sodium glucose cotransporter 2]] ([[Sodium-glucose transport proteins|SGLT-2]]) inhibitors decrease [[Lactic acid|lactate]] production and subsequently increase the [[Cytosol|cytosolic]] [[pH]], they interfere with [[virus]] entry into the cells.<ref name="pmid31783199">{{cite journal| author=Couselo-Seijas M, Agra-Bermejo RM, Fernández AL, Martínez-Cereijo JM, Sierra J, Soto-Pérez M | display-authors=etal| title=High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment. | journal=Atherosclerosis | year= 2020 | volume= 292 | issue= | pages= 60-69 | pmid=31783199 | doi=10.1016/j.atherosclerosis.2019.11.016 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31783199  }}</ref> Conversely, based on another study [[SGLT2|Sodium glucose cotransporter 2]] ([[SGLT2|SGLT-2]]) inhibitors are also indirectly responsible for high [[Angiotensin-converting enzyme|ACE2]] level, which is attributed as a [[risk factor]] for [[SARS-CoV-2]] infection. High [[Angiotensin-converting enzyme|ACE2]] level can be further elevated by concurrent [[ACE inhibitor|Angiotensin-converting-enzyme inhibitors]] ([[ACE inhibitor|ACEI]]) use.<ref name="GuptaHussain20205">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref> Current database suggests benefit from discontinuation of [[SGLT2|Sodium glucose cotransporter 2]] ([[SGLT2|SGLT-2]]) inhibitors in diabetic patient with [[COVID-19]].<ref name="GuptaHussain20206">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
{| border="1"
**Initiation of [[SGLT2|Sodium-glucose-co-transporter 2 inhibitors]] should be avoided in respiratory illnesses.<ref name="pmid323346465">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
! [[Insulin]] Regimen !! [[Diabetes management|Glycemic Control]] !! Glycemic Variability !! [[Hypoglycemia]] Rate ¶
**Although [[lactic acidosis]] due to [[metformin]] use and euglycaemic or moderate hyperglycaemic [[diabetic ketoacidosis]] associated with [[SGLT2|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]].<ref name="pmid321710622">{{cite journal| author=Fang L, Karakiulakis G, Roth M| title=Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= e21 | pmid=32171062 | doi=10.1016/S2213-2600(20)30116-8 | pmc=7118626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171062 }}</ref>
|-
**[[Dipeptidyl peptidase-4 inhibitor|Dipeptidyl peptidase-4 inhibitors]] has been well tolerated in some diabetic patients with concurrent [[SARS-CoV-2]] infection.<ref name="pmid323346467">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref> It can be continue in mild to moderate [[COVID-19]], nevertheless it is better to be discontinued in sever cases.<ref name="SinghKhunti20203">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
! [[Insulin]] [[Intravenous therapy|Infusion]]
**Use of [[Thiazolidinedione|thiazolidinediones]] has been linked with increased [[Water retention|fluid retention]] and [[congestive heart failure]] in diabetic patients with [[SARS-CoV-2]] infection.<ref name="GuptaHussain20204">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref> [[Pioglitazone]] use can be continued in mild or moderate [[COVID-19]].<ref name="SinghKhunti20202">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
| ++++ || + || -
**[[Dehydration]] in diabetic patients with [[COVID-19]] should be avoided. Based on a practical recommendation, medications with possible [[dehydration]] [[Adverse effect (medicine)|side effect]] like [[Metformin]], [[SGLT2|Sodium-glucose-co-transporter 2 inhibitors]] and [[Glucagon-like peptide-1|Glucagon-like peptide-1 receptor agonists]] should be avoided to prevent further [[Complication (medicine)|complications]].<ref name="pmid323346468">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
|-
**A summary of anti-diabetic medications in diabetic patients with [[SARS-CoV-2]] infection: <ref name="SinghSingh2020" /><ref name="pmid323346468" /><ref name="GuptaHussain20205" />
! [[Basal (medicine)|Basal]] [[Insulin]] (Every 12 Hours) + [[insulin|Regular Insulin]] (Every 6 Hours)
| +++ || ++ || ++++
|-
! [[NPH Insulin]] (Every 8 hours) + [[insulin|Regular Insulin]] (Every 8 Hours)
| ++ || +++ || +++
|-
! [[insulin|Regular Insulin]] (Every 6 Hours)
| + || ++++ || ++
|}
<sub>¶ Upon discontinuation of medical nutritional [[therapy]].</sub>
<br>
*Although [[Angiotensin-converting enzyme|angiotensin-converting enzyme II]] ([[Angiotensin-converting enzyme|ACE]]) expression has been reduced in [[COVID-19]], [[treatment]] with [[ACE inhibitor|ACE inhibitors]] ([[ACE inhibitor|ACEI]]) or [[Angiotensin II receptor antagonist|angiotensin II type-I receptor blockers]] ([[Angiotensin II receptor antagonist|ARB]]) in diabetic patient with [[hypertension]] had no significant difference compared to other [[Antihypertensive|anti-hypertensive]] treatments based on one study.<ref name="ChenYang20203">{{cite journal|last1=Chen|first1=Yuchen|last2=Yang|first2=Dong|last3=Cheng|first3=Biao|last4=Chen|first4=Jian|last5=Peng|first5=Anlin|last6=Yang|first6=Chen|last7=Liu|first7=Chong|last8=Xiong|first8=Mingrui|last9=Deng|first9=Aiping|last10=Zhang|first10=Yu|last11=Zheng|first11=Ling|last12=Huang|first12=Kun|title=Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication|journal=Diabetes Care|volume=43|issue=7|year=2020|pages=1399–1407|issn=0149-5992|doi=10.2337/dc20-0660}}</ref> On the other hand, another study done on diabetic patients showed higher risk of [[SARS-CoV-2]] [[infection]] with [[Angiotensin-converting enzyme 2|ACE2]]-increasing drugs. Elevated [[Angiotensin-converting enzyme|ACE2]] level can ease the entry of [[virus]]. Therefore It is hypothesized that medications such as [[ACE inhibitor|Angiotensin-converting-enzyme inhibitors]] ([[ACE inhibitor|ACEI]]), [[Angiotensin II receptor antagonist|angiotensin II type-I receptor blockers]] ([[Angiotensin II receptor antagonist|ARB]]), [[Thiazolidinedione|thiazolidinediones]] and [[ibuprofen]] augment the risk of a severe and lethal [[SARS-CoV-2]] infection.<ref name="pmid32171062">{{cite journal| author=Fang L, Karakiulakis G, Roth M| title=Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= e21 | pmid=32171062 | doi=10.1016/S2213-2600(20)30116-8 | pmc=7118626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171062 }}</ref><ref name="pmid31537750">{{cite journal| author=Arendse LB, Danser AHJ, Poglitsch M, Touyz RM, Burnett JC, Llorens-Cortes C | display-authors=etal| title=Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure. | journal=Pharmacol Rev | year= 2019 | volume= 71 | issue= 4 | pages= 539-570 | pmid=31537750 | doi=10.1124/pr.118.017129 | pmc=6782023 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31537750  }} </ref>
*Due to increased risk of [[Chronic renal failure|chronic kidney disease]] and [[acute kidney injury]], [[renal function]] should be monitored in patients who take [[metformin]].<ref name="pmid323346466">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref> There is also a recommendation to stop [[Metformin]] use in a patient with poor oral intake and [[Nausea and vomiting|vomiting]].<ref name="GuptaHussain20207">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref> There are other data that suggest [[metformin]] as a possibly helpful anti-diabetic agent in concurrent [[SARS-CoV-2]] [[infection]]. [[Metformin]] leads to less elevation in [[Interleukin 6|interleukin-6]] level, compared to other [[Anti-diabetic drug|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]].<ref name="SinghSingh2020">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Singh|first2=Ritu|title=Is metformin ahead in the race as a repurposed host-directed therapy for patients with diabetes and COVID-19?|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108268|issn=01688227|doi=10.1016/j.diabres.2020.108268}}</ref>
*Based on a study done in china on 1200 hospitalized [[diabetes|diabetic]] [[patients]] with [[COVID-19]] [[infection]] [[metformin]] use has been related to significantly high [[acidosis|lactic acidosis]] incidence. <ref name="pmid33515493">{{cite journal| author=Pasquel FJ, Lansang MC, Dhatariya K, Umpierrez GE| title=Management of diabetes and hyperglycaemia in the hospital. | journal=Lancet Diabetes Endocrinol | year= 2021 | volume= 9 | issue= 3 | pages= 174-188 | pmid=33515493 | doi=10.1016/S2213-8587(20)30381-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33515493  }} </ref>
*A hypothesis state that since [[SGLT2|Sodium glucose cotransporter 2]] ([[Sodium-glucose transport proteins|SGLT-2]]) inhibitors decrease [[Lactic acid|lactate]] production and subsequently increase the [[Cytosol|cytosolic]] [[pH]], they interfere with [[virus]] entry into the cells.<ref name="pmid31783199">{{cite journal| author=Couselo-Seijas M, Agra-Bermejo RM, Fernández AL, Martínez-Cereijo JM, Sierra J, Soto-Pérez M | display-authors=etal| title=High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment. | journal=Atherosclerosis | year= 2020 | volume= 292 | issue= | pages= 60-69 | pmid=31783199 | doi=10.1016/j.atherosclerosis.2019.11.016 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31783199 }}</ref> Conversely, based on another study [[SGLT2|Sodium glucose cotransporter 2]] ([[SGLT2|SGLT-2]]) inhibitors are also indirectly responsible for high [[Angiotensin-converting enzyme|ACE2]] level, which is attributed as a [[risk factor]] for [[SARS-CoV-2]] [[infection]]. High [[Angiotensin-converting enzyme|ACE2]] level can be further elevated by concurrent [[ACE inhibitor|Angiotensin-converting-enzyme inhibitors]] ([[ACE inhibitor|ACEI]]) use.<ref name="GuptaHussain20205">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref> Current database suggests benefit from discontinuation of [[SGLT2|Sodium glucose cotransporter 2]] ([[SGLT2|SGLT-2]]) inhibitors in diabetic patient with [[COVID-19]].<ref name="GuptaHussain20206">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref>
*Initiation of [[SGLT2|Sodium-glucose-co-transporter 2 inhibitors]] should be avoided in respiratory illnesses.<ref name="pmid323346465">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
*Although [[lactic acidosis]] due to [[metformin]] use and euglycaemic or moderate hyperglycaemic [[diabetic ketoacidosis]] associated with [[SGLT2|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]].<ref name="pmid321710622">{{cite journal| author=Fang L, Karakiulakis G, Roth M| title=Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? | journal=Lancet Respir Med | year= 2020 | volume= 8 | issue= 4 | pages= e21 | pmid=32171062 | doi=10.1016/S2213-2600(20)30116-8 | pmc=7118626 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32171062  }}</ref>
*[[Dipeptidyl peptidase-4 inhibitor|Dipeptidyl peptidase-4 inhibitors]] has been well tolerated in some diabetic patients with concurrent [[SARS-CoV-2]] [[infection]].<ref name="pmid323346467">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref> It can be continue in mild to moderate [[COVID-19]], nevertheless it is better to be discontinued in sever cases.<ref name="SinghKhunti20203">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
*Use of [[Thiazolidinedione|thiazolidinediones]] has been linked with increased [[Water retention|fluid retention]] and [[congestive heart failure]] in diabetic patients with [[SARS-CoV-2]] [[infection]].<ref name="GuptaHussain20204">{{cite journal|last1=Gupta|first1=Ritesh|last2=Hussain|first2=Akhtar|last3=Misra|first3=Anoop|title=Diabetes and COVID-19: evidence, current status and unanswered research questions|journal=European Journal of Clinical Nutrition|volume=74|issue=6|year=2020|pages=864–870|issn=0954-3007|doi=10.1038/s41430-020-0652-1}}</ref> [[Pioglitazone]] use can be continued in mild or moderate [[COVID-19]].<ref name="SinghKhunti20202">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
*[[Dehydration]] in diabetic patients with [[COVID-19]] should be avoided. Based on a practical recommendation, medications with possible [[dehydration]] [[Adverse effect (medicine)|side effect]] like [[Metformin]], [[SGLT2|Sodium-glucose-co-transporter 2 inhibitors]] and [[Glucagon-like peptide-1|Glucagon-like peptide-1 receptor agonists]] should be avoided to prevent further [[Complication (medicine)|complications]].<ref name="pmid323346468">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
*A summary of anti-diabetic medications in diabetic patients with [[SARS-CoV-2]] infection: <ref name="SinghSingh2020" /><ref name="pmid323346468" /><ref name="GuptaHussain20205" />


{| class="wikitable"
{| class="wikitable"
Line 178: Line 245:
*Potential cardiovascular benefits
*Potential cardiovascular benefits


<br />
|
|
*Higher chance of [[lactic acidosis]] and [[Renal insufficiency|renal dysfunction]]
*Higher chance of [[lactic acidosis]] and [[Renal insufficiency|renal dysfunction]]
Line 205: Line 271:
|<center>None</center>
|<center>None</center>
|
|
*Some [[Anti-inflammatory (patient information)|anti-inflammatory]] properties are reported
*Some [[Anti-inflammatory (patient information)|anti-inflammatory]] properties are reported <br> *There are some evidences about possible effectiveness of [[sitagliptin]] in survival of [[diabetes|diabetic]] [[patients]] who are [[infection|infected]] with [[COVID-19]]. <ref name="pmid33515493">{{cite journal| author=Pasquel FJ, Lansang MC, Dhatariya K, Umpierrez GE| title=Management of diabetes and hyperglycaemia in the hospital. | journal=Lancet Diabetes Endocrinol | year= 2021 | volume= 9 | issue= 3 | pages= 174-188 | pmid=33515493 | doi=10.1016/S2213-8587(20)30381-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33515493  }} </ref><ref name="pmid33033068">{{cite journal| author=Nauck MA, Meier JJ| title=Reduced COVID-19 Mortality With Sitagliptin Treatment? Weighing the Dissemination of Potentially Lifesaving Findings Against the Assurance of High Scientific Standards. | journal=Diabetes Care | year= 2020 | volume= 43 | issue= 12 | pages= 2906-2909 | pmid=33033068 | doi=10.2337/dci20-0062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33033068  }} </ref>
|
|
*No specific disadvantage has been found in patients with [[COVID-19]]
*No specific disadvantage has been found in patients with [[COVID-19]]
* Due to limitted data more study is required.
|-
|-
|
|
Line 235: Line 302:
*No specific disadvantage has been found in patients with [[COVID-19]]
*No specific disadvantage has been found in patients with [[COVID-19]]
|}
|}
*The following table is a summary of [[COVID-19]] [[treatment]] and possible effects on [[diabetes]]:<ref name="ApicellaCampopiano2020">{{cite journal|last1=Apicella|first1=Matteo|last2=Campopiano|first2=Maria Cristina|last3=Mantuano|first3=Michele|last4=Mazoni|first4=Laura|last5=Coppelli|first5=Alberto|last6=Del Prato|first6=Stefano|title=COVID-19 in people with diabetes: understanding the reasons for worse outcomes|journal=The Lancet Diabetes & Endocrinology|volume=8|issue=9|year=2020|pages=782–792|issn=22138587|doi=10.1016/S2213-8587(20)30238-2}}</ref><ref name="BrunoSacchi2006">{{cite journal|last1=Bruno|first1=R.|last2=Sacchi|first2=P.|last3=Maiocchi|first3=L.|last4=Patruno|first4=S.|last5=Filice|first5=G.|title=Hepatotoxicity and antiretroviral therapy with protease inhibitors: A review|journal=Digestive and Liver Disease|volume=38|issue=6|year=2006|pages=363–373|issn=15908658|doi=10.1016/j.dld.2006.01.020}}</ref>
{| class="wikitable"
|+
!COVID-19 treatment
!Advantages in diabetics
!disadvantages in diabetics
!Explanation
|-
|'''[[Chloroquine]]/[[Hydroxychloroquine]]'''
|None
|
*[[Hypoglycemia]] (specially in patients on [[insulin]] or [[Sulfonylurea|sulfonylureas]])
|
*These [[Medication|medications]] interfere with [[insulin]] metabolism and action
|-
|'''[[Lopinavir]]/[[Ritonavir]]'''
|None
|
*[[Hyperglycemia|hyperglycaemia]]
*Hepatic toxicity
*Muscle toxicity
*Possible [[drug interaction]] with anti-diabetic [[Treatment|treatments]]
|
*Due to the hepatic and muscle toxicity, should be used under caution in patients with [[statin]] [[therapy]] or history of  [[Alcoholic liver disease|fatty liver disease]]
|-
|'''[[Glucocorticoids]]'''
|None
|
*Resistance to [[Insulin]]
*[[Hyperglycemia]]
|
*[[Glucocorticoids]] interfere with [[insulin]] metabolism and action
*[[Glucocorticoids]] can worsen [[Diabetes management|glycaemic control]] by enhancing production of [[glucagon]] due to interfering with [[Glucagon-like peptide-1|GLP-1]] effects.
|}
====Management Considerations:====
====Management Considerations:====


*Evaluation of [[Electrolyte disturbance|electrolytes]], [[Blood sugar|blood glucose]], [[PH|blood PH]], blood [[Ketone|ketones]] or [[Beta-Hydroxybutyric acid|beta-hydroxybutyrate]] should be considered in patients in [[intensive care unit]] ([[Intensive care unit|ICU]]). Since [[hypokalemia]] is a feature of [[COVID-19]] (possibly as a result of high [[Angiotensin|angiotensin 2]] concentration and consequent [[hyperaldosteronism]]), [[potassium]] level should be checked. Specially in concurrent [[insulin]] treatment.<ref name="pmid323346464">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
*Evaluation of [[Electrolyte disturbance|electrolytes]], [[Blood sugar|blood glucose]], [[PH|blood PH]], blood [[Ketone|ketones]] or [[Beta-Hydroxybutyric acid|beta-hydroxybutyrate]] should be considered in patients in [[intensive care unit]] ([[Intensive care unit|ICU]]). Since [[hypokalemia]] is a feature of [[COVID-19]] (possibly as a result of high [[Angiotensin|angiotensin 2]] concentration and consequent [[hyperaldosteronism]]), [[potassium]] level should be checked. Specially in concurrent [[insulin]] [[treatment]].<ref name="pmid323346464">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
*[[Blood sugar|Plasma glucose concentration]] goal for diabetic outpatients infected with [[SARS-CoV-2]]  is 72-144 mg/dl, while [[Blood sugar|plasma glucose]] concentration of patients in [[intensive care unit]] is recommended to be maintained between 72 and 180 mg/dl.<ref name="pmid323346469">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref><ref name="SinghKhunti20204">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
*[[Blood sugar|Plasma glucose concentration]] goal for diabetic outpatients infected with [[SARS-CoV-2]]  is 72-144 mg/dl, while [[Blood sugar|plasma glucose]] concentration of patients in [[intensive care unit]] is recommended to be maintained between 72 and 180 mg/dl.<ref name="pmid323346469">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref><ref name="SinghKhunti20204">{{cite journal|last1=Singh|first1=Awadhesh Kumar|last2=Khunti|first2=Kamlesh|title=Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review|journal=Diabetes Research and Clinical Practice|volume=165|year=2020|pages=108266|issn=01688227|doi=10.1016/j.diabres.2020.108266}}</ref>
*The [[Diabetes management|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, [[Hyperglycemia|hyperglycaemia]] during the hospitalization has been associated with four time increase in [[mortality rate]], compared to normoglycemia.<ref name="pmid32389027">{{cite journal| author=Bode B, Garrett V, Messler J, McFarland R, Crowe J, Booth R | display-authors=etal| title=Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States. | journal=J Diabetes Sci Technol | year= 2020 | volume= 14 | issue= 4 | pages= 813-821 | pmid=32389027 | doi=10.1177/1932296820924469 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32389027  }} </ref>
*The importance of a careful [[Diabetes management|glycemic control]] is further supported by a study done in china, which demonstrated that patients with [[Blood sugar|blood glucose]] concentration [[median]] less than 6·4 mmol/L during their hospital stay had lower rate of [[Lymphocytopenia|lymphopenia]]. These patients also had lower chance of [[neutrophilia]], high [[C-reactive protein]] and [[procalcitonin]] levels.<ref name="pmid32369736">{{cite journal| author=Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J | display-authors=etal| title=Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. | journal=Cell Metab | year= 2020 | volume= 31 | issue= 6 | pages= 1068-1077.e3 | pmid=32369736 | doi=10.1016/j.cmet.2020.04.021 | pmc=7252168 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32369736  }} </ref>


===Surgery===
===Surgery===


*Surgical intervention is not recommended for the management of [[COVID-19]] in diabetic patients.


===Prevention===
===Prevention===
*There are no primary preventive measures available for [disease name].
 
*Here is a list of precautions that can prevent [[COVID-19]] [[infection]] in [[diabetic]] [[patients]]:<ref name="KatulandaDissanayake2020">{{cite journal|last1=Katulanda|first1=Prasad|last2=Dissanayake|first2=Harsha A.|last3=Ranathunga|first3=Ishara|last4=Ratnasamy|first4=Vithiya|last5=Wijewickrama|first5=Piyumi S. A.|last6=Yogendranathan|first6=Nilukshana|last7=Gamage|first7=Kavinga K. K.|last8=de Silva|first8=Nipun L.|last9=Sumanatilleke|first9=Manilka|last10=Somasundaram|first10=Noel P.|last11=Matthews|first11=David R.|title=Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature|journal=Diabetologia|volume=63|issue=8|year=2020|pages=1440–1452|issn=0012-186X|doi=10.1007/s00125-020-05164-x}}</ref>
**Continue to take [[medications]] regularly.
**Check the [[blood sugar]] regularly and adjust the dose of [[medications]] based on activity level and [[Diet (nutrition)|diet]].
**Consider checking the [[ketone]] level in [[patients]] with [[insulin]]-dependent [[diabetes]] ([[type 1 diabetes mellitus|type 1]] or [[type 2 diabetes mellitus|2]]) who are persistently [[hyperglycemic]].
**Follow a healthy [[Diet (nutrition)|diet]] composed of green vegetables, fruits, nuts, and green leaves.
**Follow routine [[vaccination]] plan.
**Stay physically active and consider indoor [[Physical exercise|exercise]] and walking.
**Manage the [[Stress (medicine)|stress]].
**Avoid [[smoking]] and drinking [[alcohol]].
*To browse the [[prevention medical|prevention]] of [[COVID-19]], [[COVID-19 primary prevention|click here]].
*To browse the [[prevention medical|prevention]] of [[type 2 diabetes]], [[Diabetes mellitus type 2 primary prevention|click here]].


==References==
==References==
{{Reflist|2}}{{WS}}{{WH}}
{{Reflist|2}}
[[Category:COVID-19]]
[[Category:Endocrinology]]

Latest revision as of 16:23, 7 May 2021

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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. 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

Classification

Pathophysiology

Causes

Differentiating from other Diseases

Epidemiology and Demographics

Age

Risk Factors

Confirmed factors hypothesized factors
1- Glycemic instability

2- Immune deficiency (especially 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

4- Increased furin (involved in virus entry into cell)

Natural History, Complications and Prognosis

Complications

Prognosis


Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with COVID-19 in diabetics.

X-ray

Echocardiography or Ultrasound

CT scan

MRI

  • There are no MRI findings associated with COVID-19 in diabetics.

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


Insulin Regimen Glycemic Control Glycemic Variability Hypoglycemia Rate ¶
Insulin Infusion ++++ + -
Basal Insulin (Every 12 Hours) + Regular Insulin (Every 6 Hours) +++ ++ ++++
NPH Insulin (Every 8 hours) + Regular Insulin (Every 8 Hours) ++ +++ +++
Regular Insulin (Every 6 Hours) + ++++ ++

¶ Upon discontinuation of medical nutritional therapy.

Anti-diabetic medication

Relation to ACE2 expression

Advantage

Disadvantage

Metformin
None
  • Lower level of IL-6
  • Higher albumin level
  • Lower COVID-19 related death
  • Potential cardiovascular benefits

Pioglitazone
Increased ACE2 production in animal models
  • Reduction in proinflammatory cytokines
  • Lower chance of lung injury

Sulfonylurea
None
  • No specific advantage has been found in patients with COVID-19

Dipeptidyl peptidase-4 inhibitors
None
  • No specific disadvantage has been found in patients with COVID-19
  • Due to limitted data more study is required.

Sodium-glucose-co-transporter 2 inhibitors
Increased ACE2 production by kidney in human studies

Glucagon-like peptide-1 receptor agonists
Liraglutide has been linked with elevated ACE2 production in lung and heart in animal models
  • Potential cardiovascular benefits

Insulin
Increased Renal ACE2 production in animal models
  • No specific disadvantage has been found in patients with COVID-19
COVID-19 treatment Advantages in diabetics disadvantages in diabetics Explanation
Chloroquine/Hydroxychloroquine None
Lopinavir/Ritonavir None
Glucocorticoids None

Management Considerations:

Surgery

  • Surgical intervention is not recommended for the management of COVID-19 in diabetic patients.

Prevention

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N; et al. (2020). "Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature". Diabetologia. 63 (8): 1440–1452. doi:10.1007/s00125-020-05164-x. PMC 7220850 Check |pmc= value (help). PMID 32405783 Check |pmid= value (help).
  2. ↑ 2.0 2.1 2.2 2.3 2.4 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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).
  6. ↑ 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).
  7. ↑ 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).
  8. ↑ . doi:10.3760/cma.j.cn112148-20200225-00123. Missing or empty |title= (help)
  9. ↑ 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.
  10. ↑ 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. ↑ 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.
  12. ↑ 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).
  13. ↑ 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.
  14. ↑ 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).
  15. ↑ Dunn EJ, Grant PJ (2005). "Type 2 diabetes: an atherothrombotic syndrome". Curr Mol Med. 5 (3): 323–32. doi:10.2174/1566524053766059. PMID 15892651.
  16. ↑ 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).
  17. ↑ Onder, Graziano; Rezza, Giovanni; Brusaferro, Silvio (2020). "Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy". JAMA. doi:10.1001/jama.2020.4683. ISSN 0098-7484.
  18. ↑ 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.
  19. ↑ 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).
  20. ↑ 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)
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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. ↑ 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. ↑ 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.
  26. ↑ 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.
  27. ↑ 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).
  28. ↑ 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.
  29. ↑ 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).
  30. ↑ 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.
  31. ↑ 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).
  32. ↑ Hamdy O, Gabbay RA (2020). "Early Observation and Mitigation of Challenges in Diabetes Management of COVID-19 Patients in Critical Care Units". Diabetes Care. 43 (8): e81–e82. doi:10.2337/dc20-0944. PMC 7372048 Check |pmc= value (help). PMID 32444458 Check |pmid= value (help).
  33. ↑ 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.
  34. ↑ 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).
  35. ↑ 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.
  36. ↑ 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).
  37. ↑ 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. ↑ 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.
  39. ↑ 39.0 39.1 Pasquel FJ, Lansang MC, Dhatariya K, Umpierrez GE (2021). "Management of diabetes and hyperglycaemia in the hospital". Lancet Diabetes Endocrinol. 9 (3): 174–188. doi:10.1016/S2213-8587(20)30381-8. PMID 33515493 Check |pmid= value (help).
  40. ↑ 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.
  41. ↑ 41.0 41.1 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.
  42. ↑ 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.
  43. ↑ 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).
  44. ↑ 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).
  45. ↑ 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).
  46. ↑ 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. ↑ 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.
  48. ↑ 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.
  49. ↑ 49.0 49.1 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).
  50. ↑ Nauck MA, Meier JJ (2020). "Reduced COVID-19 Mortality With Sitagliptin Treatment? Weighing the Dissemination of Potentially Lifesaving Findings Against the Assurance of High Scientific Standards". Diabetes Care. 43 (12): 2906–2909. doi:10.2337/dci20-0062. PMID 33033068 Check |pmid= value (help).
  51. ↑ 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.
  52. ↑ 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).
  53. ↑ 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).
  54. ↑ 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.
  55. ↑ 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).
  56. ↑ 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).
  57. ↑ Katulanda, Prasad; Dissanayake, Harsha A.; Ranathunga, Ishara; Ratnasamy, Vithiya; Wijewickrama, Piyumi S. A.; Yogendranathan, Nilukshana; Gamage, Kavinga K. K.; de Silva, Nipun L.; Sumanatilleke, Manilka; Somasundaram, Noel P.; Matthews, David R. (2020). "Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature". Diabetologia. 63 (8): 1440–1452. doi:10.1007/s00125-020-05164-x. ISSN 0012-186X.
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