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Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance

56 Pages Posted: 30 Apr 2021 Publication Status: Published

See all articles by Moritz Reiterer

Moritz Reiterer

Weill Cornell Medicine - Weill Center for Metabolic Health

Mangala Rajan

Weill Cornell Medicine - Department of Medicine

Nicolás Gómez-Banoy

Weill Cornell Medicine - Weill Center for Metabolic Health

Jennifer D. Lau

Weill Cornell Medicine - Department of Medicine

Luis G. Gómez-Escobar

Weill Cornell Medicine - Division of Pulmonary and Critical Care Medicine

Ankit Gilani

Weill Cornell Medicine - Weill Center for Metabolic Health

Sergio Alvarez-Mulett

Weill Cornell Medicine- Division of Pulmonary and Critical Care Medicine

Evan T. Sholle

Weill Cornell Medicine - Information Technologies & Services Department

Vasuretha Chandar

Weill Cornell Medicine - Department of Physiology, Biophysics, and Systems Biology; Weill Cornell Medicine - Division of Gastroenterology and Hepatology

Yaron Bram

Weill Cornell Medicine - Division of Gastroenterology and Hepatology; Weill Cornell Medicine - Department of Physiology, Biophysics, and Systems Biology

Katherine L. Hoffman

Weill Cornell Medicine - Division of Pulmonary and Critical Care Medicine

Alfonso Rubio-Navarro

Weill Cornell Medicine - Weill Center for Metabolic Health

Skyler Uhl

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Alpana P. Shukla

Weill Cornell Medicine - Weill Center for Metabolic Health

Parag Goyal

Weill Cornell Medicine - Department of Medicine

Benjamin R. tenOever

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Laura C. Alonso

Weill Cornell Medicine - Weill Center for Metabolic Health

Robert E. Schwartz

Weill Cornell Medicine - Division of Gastroenterology and Hepatology

Edward James Schenck

Weill Cornell Medicine - Division of Pulmonary and Critical Care Medicine

Monika Safford

Weill Cornell Medicine - Department of Medicine

James C. Lo

Weill Cornell Medicine - Weill Center for Metabolic Health

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Abstract

COVID-19 has proven to be a metabolic disease resulting in adverse outcomes in individuals with diabetes or obesity. Patients infected with SARS-CoV-2 and hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality compared to those who do not develop hyperglycemia. We find the prevalence of hyperglycemia in patients with COVID-19 ARDS to be equal to those with non-COVID-19 ARDS. Nevertheless, the pathophysiological mechanism(s) of hyperglycemia in COVID-19 remains poorly characterized. Here we show that insulin resistance rather than pancreatic beta cell failure is the prevalent cause of hyperglycemia in COVID-19 patients with ARDS, independent of glucocorticoid treatment. A screen of protein hormones that regulate glucose homeostasis reveals that the insulin sensitizing adipokine adiponectin is reduced in hyperglycemic COVID-19 patients. Hamsters infected with SARS-CoV-2 also have diminished expression of adiponectin. Together these data suggest that adipose tissue dysfunction may be a driver of insulin resistance and adverse outcomes in acute COVID-19.

Funding Information: This work was supported by the following grants: NIH R01 DK121140 (J.C.L.) and R01 DK121844 (J.C.L.), NCI R01 CA234614 (R.E.S), NIAID 2R01 AI107301 (R.E.S), and NIDDK R01 DK121072 (R.E.S). R.E.S. and J.C.L are supported as Irma Hirschl Trust Research Award Scholars. In addition, this study received support from NewYork-Presbyterian Hospital (NYPH) and Weill Cornell Medical College (WCMC), including the Clinical and Translational Science Center (CTSC) (UL1 TR 0002384).

Declaration of Interests: R.E.S. is on the scientific advisory board of Miromatrix Inc. R.E.S. is a speaker and consultant for Alnylam Inc. The other authors have no conflict of interest.

Ethics Approval Statement: The registry was approved by the institutional review board of WCMC (1405015116, 20-05022072, 20-03021681).

All animal experiment procedures, breeding, and ethical use were performed in accordance with the guidelines set by the Institutional Animal Care and Use Committee at Mount Sinai School of Medicine.

Suggested Citation

Reiterer, Moritz and Rajan, Mangala and Gomez-Banoy, Nicolas and Lau, Jennifer D. and Gómez-Escobar, Luis G. and Gilani, Ankit and Alvarez-Mulett, Sergio and Sholle, Evan T. and Chandar, Vasuretha and Bram, Yaron and Hoffman, Katherine L. and Rubio-Navarro, Alfonso and Uhl, Skyler and Shukla, Alpana P. and Goyal, Parag and tenOever, Benjamin R. and Alonso, Laura C. and Schwartz, Robert E. and Schenck, Edward James and Safford, Monika and Lo, James C., Hyperglycemia in Acute COVID-19 is Characterized by Adipose Tissue Dysfunction and Insulin Resistance. Available at SSRN: https://ssrn.com/abstract=3837640 or http://dx.doi.org/10.2139/ssrn.3837640
This version of the paper has not been formally peer reviewed.

Moritz Reiterer

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

Mangala Rajan

Weill Cornell Medicine - Department of Medicine ( email )

1300 York Avenue
P.O. Box 24144
New York, NY 10065
United States

Nicolas Gomez-Banoy

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

Jennifer D. Lau

Weill Cornell Medicine - Department of Medicine ( email )

1300 York Avenue
P.O. Box 24144
New York, NY 10065
United States

Luis G. Gómez-Escobar

Weill Cornell Medicine - Division of Pulmonary and Critical Care Medicine ( email )

New York, NY
United States

Ankit Gilani

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

Sergio Alvarez-Mulett

Weill Cornell Medicine- Division of Pulmonary and Critical Care Medicine ( email )

New York, NY
United States

Evan T. Sholle

Weill Cornell Medicine - Information Technologies & Services Department ( email )

1300 York Avenue
New York, NY 10065
United States

Vasuretha Chandar

Weill Cornell Medicine - Department of Physiology, Biophysics, and Systems Biology

United States

Weill Cornell Medicine - Division of Gastroenterology and Hepatology ( email )

1300 York Avenue
P.O. Box 24144
New York, NY 10065
United States

Yaron Bram

Weill Cornell Medicine - Division of Gastroenterology and Hepatology ( email )

Weill Cornell Medicine - Department of Physiology, Biophysics, and Systems Biology

United States

Katherine L. Hoffman

Weill Cornell Medicine - Division of Pulmonary and Critical Care Medicine ( email )

New York, NY
United States

Alfonso Rubio-Navarro

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

Skyler Uhl

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Alpana P. Shukla

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

Parag Goyal

Weill Cornell Medicine - Department of Medicine ( email )

1300 York Avenue
P.O. Box 24144
New York, NY 10065
United States

Benjamin R. TenOever

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Laura C. Alonso

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

Robert E. Schwartz

Weill Cornell Medicine - Division of Gastroenterology and Hepatology ( email )

Edward James Schenck

Weill Cornell Medicine - Division of Pulmonary and Critical Care Medicine ( email )

New York, NY
United States

Monika Safford

Weill Cornell Medicine - Department of Medicine ( email )

1300 York Avenue
P.O. Box 24144
New York, NY 10065
United States

James C. Lo (Contact Author)

Weill Cornell Medicine - Weill Center for Metabolic Health ( email )

New York, NY
United States

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