CC BY-NC-ND 4.0 · Horm Metab Res 2022; 54(08): 503-509
DOI: 10.1055/a-1878-9566
Review

Diabetes and COVID-19: Short- and Long-Term Consequences

1   Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Mohamed Hassanein
2   Department of Diabetes and Endocrinology, Dubai Hospital, Dubai, United Arab Emirates
,
Emran G. Khan
3   Endocrinology and Diabetology, King’s College Hospital London, Dubai, United Arab Emirates
,
Mohamad Yaman
4   Building 6, Nesmah Technology, Dubai, United Arab Emirates
,
Margrit Kamel
1   Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Mahmoud Barbir
5   Department of Cardiology, Harefield Hospital, Harefield, United Kingdom of Great Britain and Northern Ireland
,
Dietrich E. Lorke
6   Department of Anatomy and Cellular Biology, Khalifa University, Abu Dhabi, United Arab Emirates
,
John A. Rock
7   College of Medicine & Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
,
Dean Everett
8   Department of Pathology and Infectious Diseases, Khalifa University, Abu Dhabi, United Arab Emirates
,
Saqipi Bejtullah
9   Research Unit, College Heimerer, Prishtina, Republic of Kosovo
,
Adrian Heimerer
9   Research Unit, College Heimerer, Prishtina, Republic of Kosovo
,
Ermal Tahirukaj
1   Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Petrit Beqiri
9   Research Unit, College Heimerer, Prishtina, Republic of Kosovo
,
Stefan R. Bornstein
1   Department of Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
10   School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK
› Author Affiliations

Abstract

When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in single cases to new-onset metabolic disorders. In addition to the increased risk for people with diabetes in the acute phase of COVID-19, this patient group also seems to be more often affected by long-COVID and to experience more long-term consequences than people without diabetes. The mechanisms behind these discrepancies between people with and without diabetes in relation to COVID-19 are not completely understood yet and will require further research and follow-up studies during the following years. In the current review, we discuss why patients with diabetes have this higher risk of developing severe COVID-19 symptoms not only in the acute phase of the disease but also in relation to long-COVID, vaccine breakthrough infections and re-infections. Furthermore, we discuss the effects of lockdown on glycemic control.



Publication History

Received: 16 March 2022

Accepted after revision: 04 April 2022

Accepted Manuscript online:
20 June 2022

Article published online:
09 August 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Steenblock C, Schwarz PEH, Ludwig B. et al. COVID-19 and metabolic disease: mechanisms and clinical management. Lancet Diabetes Endocrinol 2021; 9: 786-798
  • 2 Bechmann N, Barthel A, Schedl A. et al. Sexual dimorphism in COVID-19: potential clinical and public health implications. Lancet Diabetes Endocrinol 2022; 10: 221-230
  • 3 Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and Insulin-resistant states. Cold Spring Harb Perspect Biol 2014; 6: a009191
  • 4 Esser N, Legrand-Poels S, Piette J. et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 2014; 105: 141-150
  • 5 Bornstein SR, Rubino F, Ludwig B. et al. Consequences of the COVID-19 pandemic for patients with metabolic diseases. Nat Metab 2021; 3: 289-292
  • 6 Santos A, Magro DO, Evangelista-Poderoso R. et al. Diabetes, obesity, and insulin resistance in COVID-19: molecular interrelationship and therapeutic implications. Diabetol Metab Syndr 2021; 13: 23
  • 7 Montefusco L, Ben Nasr M, D’Addio F. et al. Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection. Nat Metab 2021; 3: 774-785
  • 8 Langouche L, Van den Berghe G, Gunst J. Hyperglycemia and insulin resistance in COVID-19 versus non-COVID critical illness: are they really different?. Crit Care 2021; 25: 437
  • 9 Laurenzi A, Caretto A, Molinari C. et al. No evidence of long-term disruption of glycometabolic control after SARS-CoV-2 infection. J Clin Endocrinol Metab 2021; 107: e1009-e1019
  • 10 Muller JA, Gross R, Conzelmann C. et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab 2021; 3: 149-165
  • 11 Qadir MMF, Bhondeley M, Beatty W. et al. SARS-CoV-2 infection of the pancreas promotes thrombofibrosis and is associated with new-onset diabetes. JCI Insight 2021; 6: e151551
  • 12 Steenblock C, Richter S, Berger I. et al. Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun 2021; 12: 3534
  • 13 Zinserling VA, Bornstein SR, Narkevich TA. et al. Stillborn child with diffuse SARS-CoV-2 viral infection of multiple organs. IDCases 2021; 26: e01328
  • 14 Barrett CE, Koyama AK, Alvarez P. et al. Risk for newly diagnosed diabetes>30 days after SARS-CoV-2 infection among persons aged<18 years - United States, March 1, 2020-June 28, 2021. MMWR Morb Mortal Wkly Rep 2022; 71: 59-65
  • 15 Birabaharan M, Kaelber DC, Pettus JH. et al. Risk of new-onset type 2 diabetes in 600 055 people after COVID-19: a cohort study. Diabetes Obes Metabol 2022; 24: 1176-1179
  • 16 Perez A, Jansen-Chaparro S, Saigi I. et al. Glucocorticoid-induced hyperglycemia. J Diabetes 2014; 6: 9-20
  • 17 Catriona C, Paolo P. SARS-CoV-2 induced post-translational protein modifications: a trigger for developing autoimmune diabetes?. Diabetes Metab Res Rev 2022; 38: e3508
  • 18 Darrah E, Andrade F. Rheumatoid arthritis and citrullination. Curr Opin Rheumatol 2018; 30: 72-78
  • 19 Sollid LM, Jabri B. Celiac disease and transglutaminase 2: a model for posttranslational modification of antigens and HLA association in the pathogenesis of autoimmune disorders. Curr Opin Immunol 2011; 23: 732-738
  • 20 James EA, Pietropaolo M, Mamula MJ. Immune recognition of beta-cells: neoepitopes as key players in the loss of tolerance. Diabetes 2018; 67: 1035-1042
  • 21 Strollo R, Vinci C, Arshad MH. et al. Antibodies to post-translationally modified insulin in type 1 diabetes. Diabetologia 2015; 58: 2851-2860
  • 22 Strollo R, Vinci C, Napoli N. et al. Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies. Diabetes Metab Res Rev 2019; 35: e3132
  • 23 Raveendran AV, Jayadevan R, Sashidharan S. Long COVID: an overview. Diabetes Metab Syndr 2021; 15: 869-875
  • 24 Blomberg B, Mohn KG, Brokstad KA. et al. Long COVID in a prospective cohort of home-isolated patients. Nat Med 2021; 27: 1607-1613
  • 25 Pavli A, Theodoridou M, Maltezou HC. Post-COVID syndrome: incidence, clinical spectrum, and challenges for primary healthcare professionals. Arch Med Res 2021; 52: 575-581
  • 26 Tabacof L, Tosto-Mancuso J, Wood J. et al. Post-acute COVID-19 syndrome negatively impacts physical function, cognitive function, health-related quality of life, and participation. Am J Phys Med Rehabil 2022; 101: 48-52
  • 27 Alkodaymi MS, Omrani OA, Fawzy NA. et al. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis. Clin Microbiol Infect 2022; 28: 657-666
  • 28 Bansal R, Gubbi S, Koch CA. COVID-19 and chronic fatigue syndrome: An endocrine perspective. J Clin Transl Endocrinol 2022; 27: 100284
  • 29 Kim Y, Bitna H, Kim SW. et al. Post-acute COVID-19 syndrome in patients after 12 months from COVID-19 infection in Korea. BMC Infect Dis 2022; 22: 93
  • 30 Nasserie T, Hittle M, Goodman SN. Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA Netw Open 2021; 4: e2111417
  • 31 Rogers JP, Chesney E, Oliver D. et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry 2020; 7: 611-627
  • 32 Sudre CH, Murray B, Varsavsky T. et al. Attributes and predictors of long COVID. Nat Med 2021; 27: 626-631
  • 33 Korompoki E, Gavriatopoulou M, Hicklen RS. et al. Epidemiology and organ specific sequelae of post-acute COVID19: a narrative review. J Infect 2021; 83: 1-16
  • 34 Gavriatopoulou M, Korompoki E, Fotiou D. et al. Organ-specific manifestations of COVID-19 infection. Clin Exp Med 2020; 20: 493-506
  • 35 Ramakrishnan RK, Kashour T, Hamid Q. et al. Unraveling the mystery surrounding post-acute sequelae of COVID-19. Front Immunol 2021; 12: 686029
  • 36 Wang T, Du Z, Zhu F. et al. Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet 2020; 395: e52
  • 37 Mittal J, Ghosh A, Bhatt SP. et al. High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: a case-control study. Diabetes Metab Syndr 2021; 15: 102302
  • 38 Raveendran AV, Misra A. Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management. Diabetes Metab Syndr 2021; 15: 102235
  • 39 Oz M, Lorke DE. Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury. Biomed Pharmacother 2021; 136: 111193
  • 40 Swamy S, Koch CA, Hannah-Shmouni F. et al. Hypertension and COVID-19: updates from the era of vaccines and variants. J Clin Transl Endocrinol 2022; 27: 100285
  • 41 Oz M, Lorke DE, Kabbani N. A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor. Pharmacol Ther 2021; 221: 107750
  • 42 Carboni E, Carta AR, Carboni E. Can pioglitazone be potentially useful therapeutically in treating patients with COVID-19?. Med Hypotheses 2020; 140: 109776
  • 43 Rangarajan S, Bone NB, Zmijewska AA. et al. Metformin reverses established lung fibrosis in a bleomycin model. Nat Med 2018; 24: 1121-1127
  • 44 Tsaknis G, Siempos II, Kopterides P. et al. Metformin attenuates ventilator-induced lung injury. Crit Care 2012; 16: R134
  • 45 Chen X, Walther FJ, Sengers RM. et al. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response. Am J Physiol Lung Cell Mol Physiol 2015; 309: L262-L270
  • 46 Oh TK, Song IA. Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study. Acta Diabetol 2021; 58: 771-778
  • 47 Crouse AB, Grimes T, Li P. et al. Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes. Front Endocrinol (Lausanne) 2020; 11: 600439
  • 48 Ganesh A, Randall MD. Does metformin affect outcomes in COVID-19 patients with new or pre-existing diabetes mellitus? A systematic review and meta-analysis. Br J Clin Pharmacol 2022; 88: 2642-2656
  • 49 Hariyanto TI, Kurniawan A. Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection. Obes Med 2020; 19: 100290
  • 50 Smati S, Tramunt B, Wargny M. et al. COVID-19 and diabetes outcomes: rationale for and updates from the CORONADO study. Curr Diab Rep 2022; 22: 53-63
  • 51 Solerte SB, Di Sabatino A, Galli M. et al. Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19. Acta Diabetol 2020; 57: 779-783
  • 52 Oktay AA, Akturk HK, Paul TK. et al. Diabetes, cardiomyopathy, and heart failure. In: Feingold KR, Anawalt B, Boyce A et al. (eds). Endotext. South Dartmouth (MA): 2000. https://www.ncbi.nlm.nih.gov/books/NBK560257/
  • 53 Alshnbari A, Idris I. Can sodium-glucose co-transporter-2 (SGLT-2) inhibitor reduce the risk of adverse complications due to COVID-19? - targeting hyperinflammation. Curr Med Res Opin 2022; 38: 357-364
  • 54 Pasrija R, Naime M. Resolving the equation between mucormycosis and COVID-19 disease. Mol Biol Rep 2022; 49: 3349-3356
  • 55 Chander J, Kaur M, Singla N. et al. Mucormycosis: battle with the deadly enemy over a five-year period in India. J Fungi (Basel) 2018; 4: 46
  • 56 Garg D, Muthu V, Sehgal IS. et al. Coronavirus disease (Covid-19) associated mucormycosis (CAM): case report and systematic review of literature. Mycopathologia 2021; 186: 289-298
  • 57 Pal R, Singh B, Bhadada SK. et al. COVID-19-associated mucormycosis: an updated systematic review of literature. Mycoses 2021; 64: 1452-1459
  • 58 Sen M, Lahane S, Lahane TP. et al. Mucor in a viral land: a tale of two pathogens. Indian J Ophthalmol 2021; 69: 244-252
  • 59 Divakar PK. Fungal taxa responsible for mucormycosis/”black fungus” among COVID-19 patients in India. J Fungi (Basel) 2021; 7: 641
  • 60 Ravani SA, Agrawal GA, Leuva PA. et al. Rise of the phoenix: mucormycosis in COVID-19 times. Indian J Ophthalmol 2021; 69: 1563-1568
  • 61 Kumar M, Sarma DK, Shubham S. et al. Mucormycosis in COVID-19 pandemic: risk factors and linkages. Curr Res Microb Sci 2021; 2: 100057
  • 62 Gupta A, Sharma A, Chakrabarti A. The emergence of post-COVID-19 mucormycosis in India: can we prevent it?. Indian J Ophthalmol 2021; 69: 1645-1647
  • 63 John TM, Jacob CN, Kontoyiannis DP. When uncontrolled diabetes mellitus and severe COVID-19 converge: the perfect storm for mucormycosis. J Fungi (Basel) 2021; 7: 298
  • 64 Gianchandani R, Esfandiari NH, Ang L. et al. Managing hyperglycemia in the COVID-19 inflammatory storm. Diabetes 2020; 69: 2048-2053
  • 65 Tamez-Perez HE, Quintanilla-Flores DL, Rodriguez-Gutierrez R. et al. Steroid hyperglycemia: prevalence, early detection and therapeutic recommendations: a narrative review. World J Diabetes 2015; 6: 1073-1081
  • 66 Shakir M, Maan MHA, Waheed S. Mucormycosis in a patient with COVID-19 with uncontrolled diabetes. BMJ Case Rep 2021; 14: e245343
  • 67 Vellingiri B, Jayaramayya K, Iyer M. et al. COVID-19: A promising cure for the global panic. Sci Total Environ 2020; 725: 138277
  • 68 Baldin C, Ibrahim AS. Molecular mechanisms of mucormycosis - the bitter and the sweet. PLoS Pathog 2017; 13: e1006408
  • 69 Ibrahim AS, Spellberg B, Walsh TJ. et al. Pathogenesis of mucormycosis. Clin Infect Dis 2012; 54: S16-S22
  • 70 Dagan N, Barda N, Kepten E. et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Eng. J Med 2021; 384: 1412-1423
  • 71 Stefan N. Metabolic disorders, COVID-19 and vaccine-breakthrough infections. Nat Rev Endocrinol 2022; 18: 75-76
  • 72 Juthani PV, Gupta A, Borges KA. et al. Hospitalisation among vaccine breakthrough COVID-19 infections. Lancet Infect Dis 2021; 21: 1485-1486
  • 73 Agrawal U, Katikireddi SV, McCowan C. et al. COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2.57 million people in Scotland (EAVE II): a prospective cohort study. Lancet Respir Med 2021; 9: 1439-1449
  • 74 Stefan N, Birkenfeld AL, Schulze MB. Global pandemics interconnected — obesity, impaired metabolic health and COVID-19. Nat Rev Endocrinol 2021; 17: 135-149
  • 75 Rahman S, Rahman MM, Miah M. et al. COVID-19 reinfections among naturally infected and vaccinated individuals. Sci Rep 2022; 12: 1438
  • 76 Cena H, Fiechtner L, Vincenti A. et al. COVID-19 pandemic as risk factors for excessive weight gain in pediatrics: the role of changes in nutrition behavior. a narrative review. Nutrients 2021; 13: 4255
  • 77 Dun Y, Ripley-Gonzalez JW, Zhou N. et al. Weight gain in Chinese youth during a 4-month COVID-19 lockdown: a retrospective observational study. BMJ Open 2021; 11: e052451
  • 78 Kang HM, Jeong DC, Suh BK. et al. The impact of the Coronavirus disease-2019 pandemic on childhood obesity and vitamin D status. J Korean Med Sci 2021; 36: e21
  • 79 Silverii GA, Delli Poggi C, Dicembrini I. et al. Glucose control in diabetes during home confinement for the first pandemic wave of COVID-19: a meta-analysis of observational studies. Acta Diabetol 2021; 58: 1603-1611
  • 80 Garofolo M, Aragona M, Rodia C. et al. Glycaemic control during the lockdown for COVID-19 in adults with type 1 diabetes: a meta-analysis of observational studies. Diabetes Res Clin Pract 2021; 180: 109066
  • 81 Prabhu Navis J, Leelarathna L, Mubita W. et al. Impact of COVID-19 lockdown on flash and real-time glucose sensor users with type 1 diabetes in England. Acta Diabetol 2021; 58: 231-237
  • 82 Hakonen E, Varimo T, Tuomaala AK. et al. The effect of COVID-19 lockdown on the glycemic control of children with type 1 diabetes. BMC Pediatr 2022; 22: 48
  • 83 Wu X, Luo S, Zheng X. et al. Glycemic control in children and teenagers with type 1 diabetes around lockdown for COVID-19: a continuous glucose monitoring-based observational study. J Diabetes Investig 2021; 12: 1708-1717
  • 84 Predieri B, Leo F, Candia F. et al. Glycemic control improvement in Italian children and adolescents with type 1 diabetes followed through telemedicine during lockdown due to the COVID-19 pandemic. Front Endocrinol (Lausanne) 2020; 11: 595735
  • 85 Cheng HP, Wong JSL, Selveindran NM. et al. Impact of COVID-19 lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 and type 2 diabetes mellitus. Endocrine 2021; 73: 499-506
  • 86 Steenblock C, Schwarz PEH, Perakakis N. et al. The interface of COVID-19, diabetes, and depression. Discover Mental Health 2022; 2: 5
  • 87 Steenblock C, Todorov V, Kanczkowski W. et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the neuroendocrine stress axis. Mol Psychiatry 2020; 25: 1611-1617
  • 88 Khaledi M, Haghighatdoost F, Feizi A. et al. The prevalence of comorbid depression in patients with type 2 diabetes: an updated systematic review and meta-analysis on huge number of observational studies. Acta Diabetol 2019; 56: 631-650
  • 89 Messina R, Iommi M, Rucci P. et al. Is it time to consider depression as a major complication of type 2 diabetes? Evidence from a large population-based cohort study. Acta Diabetol 2021; 59: 95-104
  • 90 Roy T, Lloyd CE. Epidemiology of depression and diabetes: a systematic review. J Affect Disord 2012; 142: S8-S21
  • 91 Wang F, Wang S, Zong QQ. et al. Prevalence of comorbid major depressive disorder in Type 2 diabetes: a meta-analysis of comparative and epidemiological studies. Diabet Med 2019; 36: 961-969
  • 92 Knol MJ, Twisk JW, Beekman AT. et al. Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia 2006; 49: 837-845
  • 93 Rotella F, Mannucci E. Depression as a risk factor for diabetes: a meta-analysis of longitudinal studies. J Clin Psychiatry 2013; 74: 31-37
  • 94 Holt RI, de Groot M, Golden SH. Diabetes and depression. Curr Diab Rep 2014; 14: 491
  • 95 Bellass S, Lister J, Kitchen CEW. et al. Living with diabetes alongside a severe mental illness: a qualitative exploration with people with severe mental illness, family members and healthcare staff. Diabet Med 2021; 38: e14562