Insulin resistance in COVID-19 and diabetes

Abstract

Background: The epidemiology of COVID-19 and its association with cardiometabolic disorders is poorly understood. This is a narrative review that investigates the effects of COVID-19 infection on insulin resistance in patients with diabetes.

Methods: An online search of all published literature was done via PubMed and Google Scholar using the MeSH terms "COVID-19," "SARS-CoV-2," "coronavirus," "insulin resistance," and "diabetes." Only articles that were directly applicable to insulin resistance in COVID-19 and diabetes was reviewed.

Results: Current data shows an increased risk of mortality in patients with diabetes and COVID-19 compared to those without diabetes. COVID-19 triggers insulin resistance in patients, causing chronic metabolic disorders that were non-existent prior to infection.

Conclusion: Patients with diabetes are more susceptible to COVID-19 infection than those without diabetes. ACE2 expression decreases with infection, exaggerating Ang II activity with subsequent insulin resistance development, an exaggerated immune response and severe SARS-COV-2 infection.

Keywords: Angiotensin 2 converting enzyme; Cardiometabolic disorders; Diabetes mellitus; Insulin resistance; SARS-COV-2.

Fig. 1

The role of the Renin Angiotensin Aldosterone System (RAAS) pathway in COVID-19, Insulin resistance and diabetes infection. Adapted from Huang et al., 2020. This diagram illustrates the RAAS pathway, highlighting the cleavage of angiotensinogen by renin to produce angiotensin I (AngI) and Ang II via angiotensin-converting enzyme (ACE). AngII receptors type 1 (AT1R) and type 2 (AT2R), initiates the biological functions of AngII. ACE2 (homologue of ACE) cleaves Ang II and generates Ang (1–7) which exerts its function via the Mas receptor. The SARS CoV-2 binds to ACE2 receptor and decreases its expression and subsequently increases AngII resulting in multi-systemic inflammatory responses

Fig. 2

The Insulin signalling pathway and Insulin resistance in COVID-19 and Diabetes infection. Adapted from Jung & Choi (2014), Finucane and Davenport (2020), Rajpal et al. (2020) and Santos et al. (2021). Insulin binds to the insulin receptor (IR) to produce the activated insulin receptor substrate (IRS1). This leads activates phosphatidylinositol-3 kinase (PI3K), which binds to its receptor phosphatidylinositol-4,5-biphosphate (PIP₂) to form a second messenger, phosphatidylinositol-3, 4, 5-triphosphate (PIP₃). This activates Protein kinase B (AKT/PBK) which binds to the membrane, and is phosporylated by protein kinase-1(PDK1). Protein kinase B is essential for glucose transport activation, glycogenesis and lipogenesis. A dysregulation of the insulin signalling pathway due to viral infection disrupts the function of AKT/PKB and may lead to commodities such as hyperglycemia, dyslipidemia, Type 2 diabetes, obesity, chronic cardiovascular disease, and hypertension. The binding of the spike protein of SARS-CoV-2 in patients with commobidities and advanced age results in a hyperactive immune response and increases the severity of the virus after infection. Insulin resistance together with the hyperinflammation exacerbates the onset of all commodities and increase the pancreatic ACE2 expression. Increased pancreatic ACE2 expression creates a higher binding affinity for SARS-CoV-2. This predisposes patients with diabetes mellitus to suffer from a more aggressive pathology of COVID-19 infection.