Diabetes Metab J.  2020 Jun;44(3):372-381. 10.4093/dmj.2020.0138.

Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective

• Noh J
• Chang HH
• Jeong IK
• Yoon KH

• KMID: 2512995
• DOI: http://doi.org/10.4093/dmj.2020.0138

Abstract

Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.

Keyword

COVID-19; Diabetes mellitus; Severe acute respiratory syndrome coronavirus 2

Figure

• 

  Fig. 1 Outcomes of coronavirus disease 2019 (COVID-19) in patients with diabetes. Diabetes prevalence among (A) all COVID-19 patients, (B) non-severe cases and severe cases, and (C) survivors and non-survivors. (D) Mortality in patients with and without diabetes. DM, diabetes mellitus.

• 

  Fig. 2 The potential mechanisms linking diabetes and coronavirus disease 2019 (COVID-19). There are several suggested mechanisms that might play a role in an association between diabetes and COVID-19. Uncontrolled hyperglycemia, impaired immune system, pre-existing proinflammatory state, diabetic complications, multiple comorbidities, dysregulated state of angiotensin-converting enzyme 2 (ACE2) signaling. SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.

Reference

1. World Health Organization. Coronavirus disease 2019 (COVID-19) situation report 109. cited 2020 Jun 22. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

2. Korean Ministry of Health and Welfare. Cases in Korea. cited 2020 Jun 22. Available from: http://ncov.mohw.go.kr/en/bdBoardList.do?brdId=16&brdGubun=161&dataGubun=&ncvContSeq=&contSeq=&board_id=.

3. Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, Baghbanzadeh M, Aghamohammadi N, Zhang W, Haque U. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned. Int J Epidemio. 2020; 2. 22. DOI: 10.1093/ije/dyaa033.[Epub].

4. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, Yu T, Wang Y, Pan S, Zou X, Yuan S, Shang Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020; 8:475–481. PMID: 32105632.

5. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS. China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020; 382:1708–1720. PMID: 32109013.

6. COVID-19 National Emergency Response Center. Epidemiology and Case Management Team. Korea Centers for Disease Control and Prevention. Coronavirus disease-19: the first 7,755 cases in the Republic of Korea. Osong Public Health Res Perspect. 2020; 11:85–90. PMID: 32257774.

7. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia: a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2020; 14:395–403. PMID: 32334395.

8. Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of infection in type 1 and type 2 diabetes compared with the general population: a matched cohort study. Diabetes Care. 2018; 41:513–521. PMID: 29330152.

9. Schoen K, Horvat N, Guerreiro NFC, de Castro I, de Giassi KS. Spectrum of clinical and radiographic findings in patients with diagnosis of H1N1 and correlation with clinical severity. BMC Infect Dis. 2019; 19:964. PMID: 31718571.

10. Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, Zhu H, Zhao W, Han Y, Qin C. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019; 11:59.

11. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020; 3. 13. DOI: 10.1001/jamainternmed.2020.0994. [Epub].

12. Deng Y, Liu W, Liu K, Fang YY, Shang J, Zhou L, Wang K, Leng F, Wei S, Chen L, Liu HG. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020; 133:1261–1267. PMID: 32209890.

13. Chen Q, Zheng Z, Zhang C, Zhang X, Wu H, Wang J, Wang S, Zheng C. Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19) in Taizhou, Zhejiang, China. Infection. 2020; 4. 28. DOI: 10.1007/s15010-020-01432-5. [Epub].

14. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020; 323:1061–1069.

15. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020; 2. 19. DOI: 10.1111/all.14238. [Epub].

16. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395:1054–1062. PMID: 32171076.

17. Guo W, Li M, Dong Y, Zhou H, Zhang Z, Tian C, Qin R, Wang H, Shen Y, Du K, Zhao L, Fan H, Luo S, Hu D. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev. 2020; 3. 31. DOI: 10.1002/dmrr.3319. [Epub].

18. Yan Y, Yang Y, Wang F, Ren H, Zhang S, Shi X, Yu X, Dong K. Clinical characteristics and outcomes of patients with severe COVID-19 with diabetes. BMJ Open Diabetes Res Care. 2020; 8:e001343.

19. Chung SM, Lee YY, Ha E, Yoon JS, Won KC, Lee HW, Hur J, Hong KS, Jang JG, Jin HJ, Choi EY, Shin KC, Chung JH, Lee KH, Ahn JH, Moon JS. The risk of diabetes on clinical outcomes in patients with coronavirus disease 2019: a retrospective cohort study. Diabetes Metab J. 2020; 44:405–413.

20. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Vital surveillances: the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19): China, 2020. China CDC Wkly. 2020; 2:113–122.

21. CDC COVID-19 Response Team. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019: United States, February 12-March 28, 2020. MMWR Morb Mortal Wkly Rep. 2020; 69:382–386. PMID: 32240123.

22. Shi Q, Zhang X, Jiang F, Zhang X, Hu N, Bimu C, Feng J, Yan S, Guan Y, Xu D, He G, Chen C, Xiong X, Liu L, Li H, Tao J, Peng Z, Wang W. Clinical characteristics and risk factors for mortality of COVID-19 patients with diabetes in Wuhan, China: a two-center, retrospective study. Diabetes Care. 2020; 5. 14. DOI: 10.2337/dc20-0598. [Epub].

23. Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, Cai J, Lei F, Wang H, Xie J, Wang W, Li H, Zhang P, Song X, Chen X, Xiang M, Zhang C, Bai L, Xiang D, Chen MM, Liu Y, Yan Y, Liu M, Mao W, Zou J, Liu L, Chen G, Luo P, Xiao B, Zhang C, Zhang Z, Lu Z, Wang J, Lu H, Xia X, Wang D, Liao X, Peng G, Ye P, Yang J, Yuan Y, Huang X, Guo J, Zhang BH, Li H. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metab. 2020; 31:1068–1077. PMID: 32369736.

24. Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I, Amadou C, Arnault G, Baudoux F, Bauduceau B, Borot S, Bourgeon-Ghittori M, Bourron O, Boutoille D, Cazenave-Roblot F, Chaumeil C, Cosson E, Coudol S, Darmon P, Disse E, Ducet-Boiffard A, Gaborit B, Joubert M, Kerlan V, Laviolle B, Marchand L, Meyer L, Potier L, Prevost G, Riveline JP, Robert R, Saulnier PJ, Sultan A, Thebaut JF, Thivolet C, Tramunt B, Vatier C, Roussel R, Gautier JF, Gourdy P. CORONADO investigators. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020; 5. 29. DOI: 10.1007/s00125-020-05180-x. [Epub].

25. Sardu C, D'Onofrio N, Balestrieri ML, Barbieri M, Rizzo MR, Messina V, Maggi P, Coppola N, Paolisso G, Marfella R. Outcomes in patients with hyperglycemia affected by COVID-19: can we do more on glycemic control. Diabetes Care. 2020; 5. 19. DOI: 10.2337/dc20-0723. [Epub].

26. Moutschen MP, Scheen AJ, Lefebvre PJ. Impaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections. Diabete Metab. 1992; 18:187–201. PMID: 1397473.

27. Knapp S. Diabetes and infection: is there a link? A mini-review. Gerontology. 2013; 59:99–104. PMID: 23182884.

28. Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients. Diabet Med. 1997; 14:29–34. PMID: 9017350.

29. Chang FY, Shaio MF. Respiratory burst activity of monocytes from patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1995; 29:121–127. PMID: 8591699.

30. Kohio HP, Adamson AL. Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate influenza viral infection. Virology. 2013; 444:301–309. PMID: 23876457.

31. Bastard JP, Jardel C, Bruckert E, Vidal H, Hainque B. Variations in plasma soluble tumour necrosis factor receptors after diet-induced weight loss in obesity. Diabetes Obes Metab. 2000; 2:323–325. PMID: 11225749.

32. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340:115–126. PMID: 9887164.

33. Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020; 201:1299–1300. PMID: 32228035.

34. Maddaloni E, Buzzetti R. Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics. Diabetes Metab Res Rev. 2020; 3. 31. DOI: 10.1002/dmrr.3321. [Epub].

35. Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, Li Q, Jiang C, Zhou Y, Liu S, Ye C, Zhang P, Xing Y, Guo H, Tang W. Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis. J Infect. 2020; 4. 23. DOI: 10.1016/j.jinf.2020.04.021. [Epub].

36. Cai Q, Chen F, Wang T, Luo F, Liu X, Wu Q, He Q, Wang Z, Liu Y, Liu L, Chen J, Xu L. Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. Diabetes Care. 2020; 5. 14. DOI: 10.2337/dc20-0576. [Epub].

37. Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; 181:271–280. PMID: 32142651.

38. Li XC, Zhang J, Zhuo JL. The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res. 2017; 125(Pt A):21–38. PMID: 28619367.

39. Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010; 47:193–199. PMID: 19333547.

40. Rodrigues Prestes TR, Rocha NP, Miranda AS, Teixeira AL, Simoes-E-Silva AC. The anti-inflammatory potential of ACE2/angiotensin-(1–7)/mas receptor axis: evidence from basic and clinical research. Curr Drug Targets. 2017; 18:1301–1313. PMID: 27469342.

41. Arabi YM, Balkhy HH, Hayden FG, Bouchama A, Luke T, Baillie JK, Al-Omari A, Hajeer AH, Senga M, Denison MR, Nguyen-Van-Tam JS, Shindo N, Bermingham A, Chappell JD, Van Kerkhove MD, Fowler RA. Middle East respiratory syndrome. N Engl J Med. 2017; 376:584–594. PMID: 28177862.

42. Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013; 495:251–254. PMID: 23486063.

43. Drucker DJ. Coronavirus infections and type 2 diabetes-shared pathways with therapeutic implications. Endocr Rev. 2020; 41:bnaa011. PMID: 32294179.

44. Kim NY, Ha E, Moon JS, Lee YH, Choi EY. Acute hyperglycemic crises with coronavirus disease-19: case reports. Diabetes Metab J. 2020; 44:349–353. PMID: 32347027.

45. Li J, Wang X, Chen J, Zuo X, Zhang H, Deng A. COVID-19 infection may cause ketosis and ketoacidosis. Diabetes Obes Metab. 2020; 4. 20. DOI: 10.1111/dom.14057. [Epub].

46. Garg SK, Rodbard D, Hirsch IB, Forlenza GP. Managing new-onset type 1 diabetes during the COVID-19 pandemic: challenges and opportunities. Diabetes Technol Ther. 2020; 22:431–439. PMID: 32302499.

47. Rhee SY, Lee J, Nam H, Kyoung DS, Kim DJ. Effects of a DPP-4 inhibitor and RAS blockade on clinical outcomes of patients with diabetes and COVID-19. Medrxivpreprint. DOI: 10.1101/2020.05.20.20108555.

48. Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, Hausvater A, Newman JD, Berger JS, Bangalore S, Katz SD, Fishman GI, Kunichoff D, Chen Y, Ogedegbe G, Hochman JS. Renin-angiotensin-aldosterone system inhibitors and risk of COVID-19. N Engl J Med. 2020; 382:2441–2448. PMID: 32356628.

49. Zhang X, Yu J, Pan LY, Jiang HY. ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis. Pharmacol Res. 2020; 158:104927. PMID: 32422341.