Almost 50 Percent Of COVID-19 Patients Will Develop Hyperglycemia

Researchers from Weill Cornell Medicine – New York City in a new study have found that the SARS-Cov-2 coronavirus is able to triggers adipose tissue dysfunction, driving insulin resistance and causing hyperglycemia in infected individuals.

In the study involving more than 3,800 COVID-19 patients, almost 50% developed high blood sugar levels.

The study findings were published in the peer reviewed journal: Cell Metabolism.
 https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00428-9

The deadly coronavirus disease 2019 (COVID-19) pandemic is underscored by high morbidity and mortality rates seen in certain vulnerable populations, including individuals with diabetes mellitus (DM), obesity, cardiovascular disease, and advanced age, with the latter associated with many chronic cardiometabolic diseases (Drucker, 2021; Holman et al., 2020; McGurnaghan et al., 2021; Yang et al., 2021; Zhou et al., 2020).

Hyperglycemia with or without a history of DM is a strong predictor of in-hospital adverse outcomes, portending a 7-fold higher mortality compared with patients with well-controlled blood glucose levels (Zhu et al., 2020). Thus, hyperglycemia may be seen as a biomarker that predicts poor prognosis.

A retrospective study that compared patients with hyperglycemia who were treated with insulin against those who were not showed increased mortality in those receiving insulin (Yu et al., 2021). However, it remains unclear whether insulin treatment is a surrogate for severity of hyperglycemia and overall morbidity or whether it is an actual causative factor for death.

There is, thus, uncertainty regarding specific treatments for hyperglycemia in acute COVID-19 (Lim et al., 2021).

Despite our early recognition of the association between hyperglycemia and perilous outcomes, the pathophysiological mechanisms that underlie hyperglycemia in COVID-19 remain undefined (Accili, 2021; Lockhart and O’Rahilly, 2020). Hypotheses have included a broad range of pathologies, such as direct infection of islets leading to beta cell failure (BCF) and systemic inflammation leading to insulin resistance (IR).

Dexamethasone substantially reduces mortality in patients with severe COVID-19 infection requiring oxygen or invasive mechanical ventilation (Horby et al., 2021). Glucocorticoids can also provoke hyperglycemia by inducing IR and beta cell dysfunction. The widespread usage of dexamethasone in severe SARS-CoV-2 infection is expected to exacerbate both the incidence and severity of hyperglycemia in COVID-19. However, the contribution of glucocorticoids to hyperglycemia in acute COVID-19 has not been defined.

Although COVID-19 is primarily marked by a respiratory tract infection, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to infect other cell types and often leads to extrapulmonary consequences (Gupta et al., 2020; Puelles et al., 2020).

For example, ACE2 and other entry receptors for SARS-CoV-2 can be expressed on pancreatic islet cells, and endocrine cells differentiated from human pluripotent stem cells are permissive to infection (Tang et al., 2021; Wu et al., 2021; Yang et al., 2020).

Early reports of unexpected diabetic ketoacidosis (DKA) in COVID-19 patients fueled concerns for a novel form of acute onset BCF. For example, one case described a patient with new-onset DKA who was found to be autoantibody negative for type 1 DM (T1DM) but showed evidence of prior SARS-CoV-2 infection based on serology results, suggesting the possibility of pancreatic beta cell dysfunction or destruction as a result of COVID-19 (Hollstein et al., 2020).

However, given the high rates of COVID-19 during this pandemic coupled with low background rates of new onset T1DM, the connection between these two events in this case could be “true, true, and unrelated.”

Recent studies disagree on whether ACE2 is expressed on pancreatic beta cells or whether the SARS-CoV-2 virus is found in pancreatic beta cells of deceased individuals with COVID-19 (Coate et al., 2020; Kusmartseva et al., 2020; Müller et al., 2021; Tang et al., 2021; Wu et al., 2021).

Conversely, the well-known connection between obesity and IR might lead to impaired immunity and more severe SARS-CoV-2 infection (Goyal et al., 2020a). In fact, population-level studies have reported a higher risk of complications in patients with obesity and COVID-19 (Barron et al., 2020; Docherty et al., 2020; Williamson et al., 2020). Viral infection may lead to systemic IR and worsened hyperglycemia. In sum, despite much attention, the pathophysiology of hyperglycemia observed in acute COVID-19 remains unknown.

In this study, we assessed the pathophysiological mechanism of hyperglycemia in acute and severe COVID-19 and analyzed protein hormones regulating glucose homeostasis. We compared patients with COVID-19 with critically ill control patient groups (those with acute respiratory distress syndrome [ARDS] and hyperglycemia but without COVID-19) and found striking differences in the characteristics associated with hyperglycemia, further highlighting the metabolic dysfunction seen in this disease.
Results