Introduction:
Since the onset of the COVID-19 pandemic, the relationship between type 2 diabetes and COVID-19 has a great deal with emerging evidence. Pre-existing diabetes is reported to be the high-risk factor for developing COVID-19 and its associated complications. The COVID-19-induced severe metabolic decompensation of pre-existing or new-onset diabetes, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state, has been reported. Moreover, SARS-CoV-2 has been characterized as a potential inducer of new-onset type 1 diabetes mellitus.
How Does COVID-19 Induce Diabetes?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, binds to angiotensin-converting enzyme 2 (ACE2) receptors that act in vital metabolic pathways, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys. Thus, states that SARS-CoV-2 cause pleiotropic alterations of glucose metabolism that complicate the pathophysiology of pre-existing diabetes or the new onset of the disease mechanism.
Other variants, such as the viral cause of ketosis-prone diabetes, including coronaviruses binding to ACE2 receptors, incidences of fasting glycemia, and acute-onset diabetes also been reported among COVID-19 patients.
How does Coronavirus cause Diabetes?
The relationship between viral infections and type 1 diabetes mellitus is challenging as it is an autoimmune condition in which the auto-reactive CD4+ and CD8+ T cells destroy beta-cells.
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Virus-Induced Beta-cell Damage:
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A virus induces beta-cell damage by the direct lytic effect of viral replication or by host inflammatory response mediated by autoreactive CD+ T cell damage, leading to autoimmunity. However, the destruction of more than 90 % of beta-cells by direct viral mediates damage leads to non-autoimmune diabetes, limited by lysis, releases islet cells antigens, which in association with enhanced immune response enables autoimmunity.
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It is limited to beta-cell destruction with the release of sequestered islet cell antigens and activation of autoreactive T-cells, resulting in prolonged damage of auto-immunity and type 1 diabetes.
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In children diagnosed with diabetes, a major histocompatibility complex is expressed, and interferon-alpha is observed within the islets devoid of these markers. They characteristically increase antigen-mediated activation of CD8+T cells, and it is most likely that their enhanced production is viral-mediated.
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Mediators Of Chronic Beta-cell Destruction:
The pathological processes mediating chronic beta-cell damage are varied. In susceptible individuals, the molecular mimic and resemblance of viral epitope with host islet protein cause cross-reactivity and autoimmune T cell response against host tissue. This mimicking effect of molecules accelerates the autoimmune process rather than initiating it. Other possible mechanisms are bystander T-cell activation, the activation of T cell-independent of an antigen-specific T-cell receptor stimulation, and damage where destruction of beta-cells is accelerated by proinflammatory cytokines released by infection of pancreatic cells like alpha, exocrine, endothelial, and neuronal cells.
The reduced insulin production due to beta cell damage and proinflammatory mediators results in functional defects such as defective glucose-mediated insulin release and delay in converting proinsulin to insulin. Another vital element is the inability of beta cells to clear viral infections compared with alpha cells. Chronic disease of beta cells results in persistent overexpression of MHC-1, leading to a continuous presentation of beta cell epitopes to the immune system, leading to autoimmunity.
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Possible Viruses Causing Beta Cell Damage:
Many viruses are known to be associated with type 1 diabetes mellitus (T1DM), namely enterovirus, mumps, rubella, and CMV (cytomegalovirus), whereas there is evidence to prove viral infections associated with diabetes. There is also data showing the viral origins of beta cell autoimmunity. Early exposure to conditions was also deemed to educate the immune system leading to reduced incidence of autoimmune diseases like T1DM.
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Sars-CoV-2 And Diabetes:
Angiotensin-converting enzyme (ACE) is essential in mediating the renin-angiotensin-aldosterone system by converting angiotensin I to II. The functional receptor of SARS-CoV- 1 and 2 are recently identified as an ACE2 novel homolog of ACE that degrades angiotensin-II to angiotensin-I-VII. Studies have reported that during the SARSCoV-1 epidemic, an individual who did not receive glucocorticoid medications had higher fasting blood glucose, and hyperglycemia was the possible predictor of increased mortality and morbidity.
What Is The Connection Between COVID19 And Type 1 Diabetes Mellitus?
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Diabetes is associated with increased susceptibility to and severity of infections. Hyperglycemia alters immune response and causes cytokine dysregulation,, which is an inherently proinflammatory and procoagulant state. Therefore, type 1 and 2 diabetes mellitus with poor glycemic control is a high-risk-pre-existing condition for bacterial and viral infections, including SARS-CoV-2. Various centers reported that COVID-19 induces diabetic ketoacidosis, prolongs hospitalization for diabetes patients, and increases the risk of co-morbidities like hypertension, obesity, cardiovascular disease, etc. COVID-19 increases mortality in T1DM, older age groups with renal or cardiac disease.
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The prolonged hospital stay, risk of complications, and overall mortality from COVID-19 are higher with poor glycemic control, and the adverse effects of coronavirus infection are under study to treat them. Hydroxychloroquine was used during the initial stages of a pandemic that reduces insulin degradation at the cellular level and stimulates insulin-mediated glucose transport, resulting in potential hypoglycemia. In addition, the , antiviral drugs such as lopinavir and ritonavir lead to hyperglycemia and worsen glycemic control.
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The effect of lockdown also impacted people with type 1 diabetes due to a lack of physical interaction, reduced physical activity, increased screen time, intake of less healthy food, stress, and irregular sleeping pattern.
Can COVID-19 Trigger Diabetes?
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New Onset Diabetes And COVID-19:
New onset diabetes is increasingly reported in COVID-19 individuals with no history of diabetes. Infection-induced inflammation and cytokine activation and resultant insulin resistance could lead to stress hyperglycemia which is uncertain to determine the extent of direct viral destruction of islet cells with decreased insulin production and release. COVID-19 also acts as an infectious trigger that decompensates and precipitates diabetes ketoacidosis in patients with new-onset type 1 and 2 DM. A recent study from the UK reported an increase in new-onset of T1DM in children with SARSCoV-2 infection.
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COVID-19 And Pancreatitis:
SARs-CoV-2 infection patients showed more acute pancreatitis than SARs-CoV-1 epidemic patients due to infection of islet cells, new-onset diabetes, and hyperglycemia. Distinctive moderate pancreatitis with a benign course was reported by researchers in the United Kingdom Liverpool. The patients showed pancreatic injury from an abnormal elevation of lipase or amylase. Still, the cytopathic effect of the virus and the result of systemic inflammatory response and multiorgan dysfunction is yet to establish.
Conclusion:
COVID-19 is an infectious disease and can affect people of any age. Hyperglycemia seems to increase morbidity and mortality concerning COVID-19; the virus can induce or worsen hyperglycemia developing a highly vicious cycle. Yet the association between diabetes and COVID-19 is still not established. Some challenges need to be addressed such as beta cell damage, hyperglycemia, effects of lockdown, and destruction of islet cells. Cases with new onset of diabetes were reported post COVID-19 infection among children and adults.
