An Immediate and Long-Term Complication of COVID-19 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms

Abstract

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a pandemic by the WHO on 19 March 2020. This pandemic is associated with markedly elevated blood glucose levels and a remarkable degree of insulin resistance, which suggests pancreatic islet β-cell dysfunction or apoptosis and insulin’s inability to dispose of glucose into cellular tissues. Diabetes is known to be one of the top pre-existing co-morbidities associated with the severity of COVID-19 along with hypertension, cardiocerebrovascular disease, advanced age, male gender, and recently obesity. This review focuses on how COVID-19 may be responsible for the accelerated development of type 2 diabetes mellitus (T2DM) as one of its acute and suspected long-term complications. These observations implicate an active role of metabolic syndrome, systemic and tissue islet renin–angiotensin–aldosterone system, redox stress, inflammation, islet fibrosis, amyloid deposition along with β-cell dysfunction and apoptosis in those who develop T2DM. Utilizing light and electron microscopy in preclinical rodent models and human islets may help to better understand how COVID-19 accelerates islet and β-cell injury and remodeling to result in the long-term complications of T2DM.

Post-COVID Syndrome: An Insight on Its Pathogenesis

“…Post-viral infection destruction of β-pancreatic cells can occur and trigger the onset of diabetes mellitus. It has been shown that SARS-CoV-2 can infect and replicate in human pancreatic islets, in association with reduced insulin-secreting granules in pancreatic β-cells and impaired glucose-stimulated insulin secretion [ 65 ], which may explain the deterioration of glycemic control observed in diabetic patients with COVID-19 necessitating exceptionally high doses of insulin [ 66 ], but also increase the risk for onset of diabetes after COVID-19 [ 67 ]. Potential pathways of injury of pancreatic β-cells include a profound proinflammatory cytokine response, leading to a chronic low-grade inflammationactivation of the renin-angiotensin-aldosterone system, through the SARS-CoV-2 target ACE2 receptor, which is abundant in pancreatic β-cells, and enhances autoimmunity in genetically predisposed individuals [ 67 ].…”

Some Questions to Our Chinese Colleagues Pioneering Research Into Coronavirus Disease 2019 (COVID-19)

“…Furthermore, it is of high interest to know the long-term consequences of patients who have suffered from COVID-19. The Chinese collegues could be pioneers in assessing these questions by carrying out followup investigations regarding pulmonary, cardiac, endocrinologic, neurologic, psychiatric, and immunologic impairments of post-COVID-19 patients (27).…”

Viremia and Interaction of Endothelial Cells, Erythrocytes, Leukocytes and Platelets in Type 2 Diabetes Mellitus and COVID-19: A Closer Look at Proposed Mechanisms

“…The SARS-CoV-2 virus is known to preferentially infect the pulmonary tissues in the lower respiratory tracts via the naso-oropharynx route due to person-to-person aerosol inhalation where it is known to eventually result in symptomatic and severe cases as a bilateral pneumonia and acute respiratory distress syndrome (ARDS) with associated histopathologic findings including exudative and proliferative phases of diffuse alveolar disease (DAD) that have the complicated form of COVID-19 [1,2,6,8,15,16,17,18,19]. Additionally, there are numerous comorbidities that increase the risk of severe cases of COVID-19, which includes hypertension, obesity, metabolic syndrome, diabetes, cerebro-cardiovascular disease and older age [6,20].…”