COVID-19 Triggers Hyperglycemia And Also Disrupts Fat Cells And Causes Decreased Production Of The Hormone Adiponectin Especially In Severe Stages
Hyperglycemia and COVID-19
: A new study by researchers from Weill Cornell Medicine-New York, USA has shown that COVID-19 not only is able to trigger hyperglycemia but it also disrupts fat cells and causes decreased production of the hormone Adiponectin especially in stages of disease severity.
Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ADIPOQ gene and it is produced in primarily in adipose tissue, but also in muscle, and even in the brain.
To date it has been observed that individuals infected with SARS-CoV-2 coronavirus who also display hyperglycemia, suffer from longer hospital stays, have a higher risk of developing acute respiratory distress syndrome (ARDS) and have and increased mortality.
However the pathophysiological mechanism of hyperglycemia in COVID-19 has so far remained poorly characterized.
The study team showed that hyperglycemia is similarly prevalent among patients with ARDS independent of COVID-19 status. Yet, among patients with ARDS and COVID-19, insulin resistance is the prevalent cause of hyperglycemia, independent of glucocorticoid treatment, which is unlike patients with ARDS but without COVID-19, where pancreatic beta cell failure predominates.
Furthermore a screen of glucoregulatory hormones revealed lower levels of adiponectin in patients with COVID-19. Hamsters infected with SARS-CoV-2 demonstrated a strong antiviral gene expression program in the adipose tissue and diminished expression of adiponectin.
Shockingly the study team also demonstrated that SARS-CoV-2 can infect adipocytes.
The study findings in summary suggest that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.
The study findings were published in the peer reviewed journal: Cell Metabolism. https://www.sciencedirect.com/science/article/pii/S1550413121004289
The study by researchers from Weill Cornell Medicine and NewYork-Presbyterian hence shows that COVID-19 may bring high risks of severe disease and death in many patients by disrupting key metabolic signals and thereby triggering hyperglycemia.
study team found that hyperglycemia ie having high blood sugar levels is common in hospitalized COVID-19 patients and is strongly associated with worse outcomes.
The study team also found evidence suggesting that SARS-CoV-2, the coronavirus that causes COVID-19, can induce hyperglycemia by disrupting fat cells' production of adiponectin, a hormone that helps regulate blood sugar levels.
Corresponding author, Dr James Lo, an associate professor of medicine in the Weill Center for Metabolic Health and the Cardiovascular Research Institute at Weill Cornell Medicine and a cardiologist at NewYork-Presbyterian/Weill Cornell Medical Center told Thailand Medical News, "We normally don't think that fat cells are very active, but in fact they synthesize many protective proteins for your body and it appears that SARS-CoV-2 may disable that protection in many patients."
The medical condition of hyperglycemia, the core feature of diabetes, is associated with inflammation and weakened immunity against infections, and was recognized as a significant risk factor for severe COVID-19 early in the pandemic.
Physicians however later began finding evidence that COVID-19 is associated with hyperglycemia in patients who have no history of diabetes.
In order to better understand this important but mysterious aspect of COVID-19, Dr Lo and colleagues analyzed the records of 3,854 patients who were hospitalized with COVID-19 at NewYork-Presbyterian /Weill Cornell Medical Center, NewYork-Presbyterian Queens and NewYork-Presbyterian Lower Manhattan Hospital, in the first few months of the pandemic in the United States.
The study team found that a remarkably high proportion (49.7 percent) of these patients presented with hyperglycemia or developed it during their hospital stays.
Significantly hyperglycemia in these COVID-19 patients was also strikingly associated with worse outcomes. Compared to patients with normal blood sugar levels, the patients with hyperglycemia were 9 times more likely to develop severe lung dysfunction (acute respiratory distress syndrome, or ARDS), 15 times more likely to be given mechanical ventilation, and 3 times more likely to die.
The study team surprisingly found that hyperglycemia and the dire risks it brings also occur in other, non-COVID-19 forms of severe lung dysfunction.
The team found it in the same proportion in ARDS cases associated with COVID-19 and in ARDS cases from non-COVID-19 causes such as severe influenza or bacterial pneumonia. However, hyperglycemia in the latter cases appeared to be caused mostly by the death or dysfunction of beta cells that produce insulin, the principal hormone that regulates blood sugar levels.
First author Dr Moritz Reiterer, a postdoctoral fellow in Dr Lo's laboratory added, "In contrast, hyperglycemia in COVID-19 patients is mainly caused by insulin resistance, in which insulin is present but the tissues it normally acts upon are no longer sensitive to it."
Importantly further tests revealed that the COVID-19 ARDS patients had severe declines in blood levels of adiponectin, a hormone produced by fat cells which normally has a protective effect against diabetes by enhancing insulin sensitivity.
To date, how exactly SARS-CoV-2 disrupts fat cells' production of adiponectin isn't yet clear. It may do so indirectly, by raising the general level of inflammation, which in turn disrupts fat cells.
However the study team demonstrated that SARS-CoV-2 can infect human and mouse fat cells, hinting at the possibility that the virus disrupts adiponectin production in this direct way in COVID-19 patients.
The study findings open up a novel perspective on COVID-19, offering, among other things, a new explanation for why some people have worse COVID-19 outcomes.
Dr Lo commented, "Patients with obesity, for example, may be more vulnerable to COVID-19 because they may already have some degree of insulin resistance and fat cell dysfunction, and possibly their fat cells are more susceptible to infection."
The study findings also suggest that a class of diabetes drugs called thiazolidinediones, which boost adiponectin production, may be useful in treating COVID-19 when it includes hyperglycemia. Further research is needed before this becomes clinically actionable.
The study team is now investigating whether COVID-19 induced hyperglycemia persists and develops into diabetes even after the recovery from COVID-19.
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