COVID-19 induced Diabetes: A novel presentation

Abstract

Introduction: The COVID-19 pandemic disproportionately affected patients who had comorbid diabetes mellitus. COVID-19 patients with diabetes experience significantly higher rates of complications and mortality. COVID-induced diabetes is a novel phenomenon observed in critically ill patients. The aims of this review were to explore the literature about COVID-induced diabetes and the pathophysiological mechanisms that could lead to this novel presentation.

Methods: A literature search was performed using PUBMED, Google Scholar, MEDLINE and Embase for original studies (meta-analyses, cross-sectional studies, case series, case reports) about new-onset diabetes following COVID infection, and the proposed biochemical pathways behind this presentation. It was assumed that the authors of the studies used the current diagnostic criteria for diagnosis of type 1 and type 2 diabetes.

Results: COVID-19 causes dysregulation of glucose homeostasis leading to new-onset diabetes and hyperglycaemia. This is also seen in patients with no previous risk factors for diabetes mellitus. The atypical glycaemic parameters and increased rates of DKA suggest that COVID-induced diabetes is a novel form of diabetes. A spectrum of COVID-induced diabetes has also been noted. COVID-induced diabetes is associated with remarkably higher mortality rates and worse outcomes compared to COVID-19 patients with pre-existing diabetes. The novel presentation of COVID-induced diabetes could be due to beta cell damage and insulin resistance caused by SARS-CoV-2.

Conclusion: COVID-induced diabetes is essential to detect early, owing to its implications on prognosis. Further studies must include follow-up of these patients to better understand the trajectory of COVID-induced diabetes and the best management plan. It is also important to assess the beta cell function and insulin resistance of COVID-induced diabetes patients over time to better understand the underlying biochemical mechanisms.

Keywords: Beta cells; COVID-19; Diabetes mellitus; Insulin resistance; Pathogenesis; SARS-CoV-2.

Fig. 1

Mechanisms of COVID-19 induced diabetes. The mechanisms behind new-onset diabetes following COVID-19 infection are likely multifaceted. Insulin resistance and beta cell damage are the two crucial mechanisms that have been proposed by several studies. A multitude of signalling pathways have been postulated to be responsible for the presentation of COVID-induced diabetes. Other considerations not explored in this paper include stress-induced hyperglycaemia, steroid-induced hyperglycaemia, and the unmasking of pre-existing diabetes , , , , , , , , , , , , , .

Fig. 2

SARS-COV-2 causes direct beta cell damage. Multiple receptors have been identified with affinity to SARS-CoV-2 in pancreatic beta cells. It has been shown that SARS-CoV-2 can replicate in beta cells and cause them to transdifferentiate , , , , , , .

Fig. 3

SARS-COV-2 causes indirect beta cell damage through autoimmunity and inflammation. Several mechanisms have been postulated behind the apparent rise in autoimmune diabetes following COVID-19 infection. These include molecular mimicry, neoisotope formation and NETosis. SARS-CoV-2 also downregulates ACE2, an important enzyme which degrades angiotensin II. Unopposed actions of angiotensin II lead to deleterious effects , , , , , , .

Fig. 4

SARS-COV-2 causes insulin resistance through multiple mechanisms. 1. COVID-19 patients have been shown to have a downregulated REST transcription factor, which has been linked to altered expression of proteins important for the insulin signalling pathway. 2. SARS-COV-2 may cause downregulation of insulin signalling pathway through activation of serine/threonine kinases via RNA fragments and cytokine storm. 3. Viral activation of immune cells causes release of IFN-gamma, which has been shown to downregulate insulin receptors on skeletal muscle cells, exacerbating insulin resistance , , , , , .