Preamble: Diabetes mellitus (DM) is the most frequently encountered metabolic disorder by clinicians in their daily practice and thus deserves the utmost attention to reduce and/or avoid its mortality & morbidity.
Diabetes mellitus and coronavirus infection have all been in existence but with little focus on their pathologic relationships until the recent 2019 Covid-19 pandemic, unfolding new diabetes mellitus diagnoses and different responses to diabetic therapies in the already diabetic patients.
Diabetic Mellitus type-2 has taken a toll on the population worldwide, including children with almost all cases attributed to poor lifestyle and dietary practices. Diabetes mellitus results from the body’s inability to appropriately respond and process glucose from the food we eat and that generated by the body’s (liver) metabolic processes resulting in sustained high blood glucose levels. This is due to absolute insulin deficiency (type -1diabetes) or insulin resistance in type-2 DM.
According to Rothan HA & colleagues, coronavirus disease 2019(covid-19) is a viral infectious disease caused by the coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Diabetes mellitus can predispose our bodies to a wide range of chronic conditions including but not limited to diabetic foot infection, diabetic retinopathy (visual disturbance), cardiovascular disorders (silent myocardial ischemia & cerebrovascular disease), diabetic neuropathy(loss of sensation & altered pain perception), weight loss due to renal glucose loss to mention but a few.
According to the World Health Organization (WHO) covid-19 responses, its put that people with diabetes mellitus are more prone to serious complications & become seriously ill & more likely to die from Covid-19 compared to those without diabetes.
Our focus today, therefore, will be on the association between diabetes mellitus and covid-19 as diabetic and pre-diabetic patients have demonstrated a different trend of mortality (death) & morbidity compared to the general population when infected with covid-19.
It’s worth noting that both diabetes and Covid-19 are associated with acute and chronic inflammation & both disease conditions can impact each other in terms of clinical progression and outcome.
In a study about receptor recognition by coronavirus by Wan Y & colleagues, coronavirus depends on the host (human) cells to produce more copies in order to survive and cause infection. This is accomplished by binding the virus’s S-glycoprotein to the Angiotensin-converting enzyme-2(ACE-2) receptors in the host (patient), leading to fusion with the cell membrane initiating viral entry. Protease furin that enhances viral entry has been documented to be elevated in diabetic patients.
- Relationship between diabetes and Covid-19 infection at the Receptor level
- The incretin system and Presence of DPP4 enzyme in the bronchial tree
The incretin system which is composed of glucagon-like peptide-1, and gastric inhibitory peptide (GIP) works by enhancing insulin secretion but these are known to be defective in type-2 diabetic patients. Contrary to incretin action, dipeptidyl peptidase-4 enzyme (DPP4/CD26) works by degrading them hence reducing incretin activities
Dipeptidyl peptidase-4 enzyme is believed to be a component of an entry receptor for coronaviruses: human coronavirus-Erasmus Medical Centre and MERS-CoV, this is according to Raj VS and colleagues. Human coronavirus-Erasmus Medical Centre resembles other coronaviruses genetically. In an animal study conducted by Lwata Yoshikawa et al, transgenic mouse models become susceptible to MERS-CoV by expressing DPP4 after feeding them with high-fat diet which induced hyperglycemia and hyperinsulinemia, a typical characteristic of Type-2 diabetes. Infecting these mice with high DPP4 expression resulted in severe viral infection and delayed recovery. Since MERS-CoV and SARS-CoV-2 belong to the same subfamily, similar effects are were observed.
This means our patients with uncontrollably high blood glucose levels with hyperinsulinemia as evidenced in Type-2 diabetes mellitus coupled with high levels of DPP4 on a defective incretin system are susceptible to severe forms of Covid-19 once infected due to the enhanced viral entry.
- Angiotensin converting enzyme-2 (ACE2) receptor
Several studies have already postulated how vital ACE2 receptors are very vital in facilitating SARS-CoV-2 entry into human cells. Since the receptors are widely distributed in the kidneys, lungs and blood vessels, most covid-19 signs and symptoms are easily explained by this approach.
In one study conducted by Wan Yet al in march 2020, about receptor recognition by the novel coronavirus, it showed that people living with diabetes express a high concentration of ACE2 thus making them more susceptible to Covid-19 with rapid progression of symptoms. This was further supported when high levels of ACE2 receptors were found in the pancreatic beta cells causing increased beta-cell injury hence the impaired insulin secretion in diabetic patients.
- Direct effect of Covid-19 to the pancreas
According to Bornstein SR and colleagues, the worsening hyperglycemia in stable diabetic patients infected by Covid-19 requiring the use of high doses of insulin suggested the possibility of invasion of the pancreas by SARS-CoV-2.
The research conducted by Zhao Q and colleagues, studying the pancreatic injury patterns in patients with Covid-19 pneumonia concluded that systemic response to respiratory failure, direct cytopathic effect of SARS-CoV-2 replication, and harmful immune response induced by SARS-CoV-2 infection as the possible mechanisms of pancreatic injury.
Other existing links include;
- The “lazy” leukocyte syndrome. In this syndrome, there is impaired leukocyte function of phagocytosis predisposing the patient to both bacterial and viral infection. This condition is very common in diabetic patients.
- Gubbi S and colleague in their study about covid-19 and diabetes in 2020 suggested that diabetes mellitus increases the SARS-CoV-2 mortality and morbidity through; increased susceptibility to hyperinflamation & cytokine storm, increased cellular binding ability & efficient viral entry, reduced T-cell function and, decreased viral clearance in diabetic patients
Conclusion
- Everyone is susceptible to Covid-19 but diabetic patients are more likely to experience severe forms of the disease with higher chances of ICU admissions & high risk of death compared to the general population
- In one study conducted by Ferrario CM et al in 2005, about the effect of Angiotensin Converting Enzyme inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) on cardiac ACE2, ACEi & ARBs were found to increase ACE2. Well, according to the American Heart Association statement address concerning; using R.A.A.S antagonists in Covid-19, there use in patients living with diabetes & hypertension hasn’t been fully linked to worse covid-19 infection outcome and thus not fully refuted, as these interactions had left clinicians in doubt about their implications in Covid-19.
- Due to a higher degree of inflammation and coagulation in diabetic patients infected with Covid-19, these patients may require more integrated and intensive management than the non diabetic Covid-19 patients thus requiring High dependence units (HDUs) and intensive care units (ICUs) which comes with a higher cost of care and mortality.
- In one study titled “metformin in Covid-19” by Sharma S et al, the widely used drug in management of diabetes showed activity in retarding viral binding capacity to the ACE2 receptor thus decreasing rate of its entry into the human cells. This gives the drug beneficial effects in diabetic patients infected with Covid-19.
Diabetes is on the rise in low-income countries and WHO projects that diabetes will be the 7th leading cause of death by 2030. Therefore, it’s everyone’s responsibility to practice good dietary practices and lifestyle measures to chase diabetes and encourage people living with diabetes to observe clinicians’ & dietitians’ advice.
Observe Standard Operating Procedures to avoid the spread of Covid-19 and let’s get vaccinated
The author is; Kasadha Nasser, Chairperson; BCMCH graduate society of Uganda.
Tel- +256 703706927 (watsap & telegram)
Twitter -@Nasser99kasadha, [email protected]
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