Why is diabetes a risk factor for coronavirus disease 2019 (COVID-19)?

Updated: Aug 03, 2020
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Michael Stuart Bronze, MD  more...
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Answer

High plasma glucose levels and diabetes mellitus (DM) are known risk factors for pneumonia. [385, 386] Potential mechanisms that may increase the susceptibility for COVID-19 in patients with DM include the following: [387]

  • Higher-affinity cellular binding and efficient virus entry
  • Decreased viral clearance
  • Diminished T-cell function
  • Increased susceptibility to hyperinflammation and cytokine storm syndrome
  • Presence of cardiovascular disease

SARS-CoV-2 is known to utilize angiotensin-converting enzyme 2 (ACE2) receptors for entry into target cells. Insulin administration attenuates ACE2 expression, while hypoglycemic agents (eg, glucagonlike peptide 1 [GLP-1] agonists, thiazolidinediones) up-regulate ACE2. [387] Dipeptidyl peptidase 4 (DPP-4) is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19. [388]

The relationship between diabetes, coronavirus infections, ACE2, and DPP-4 has been reviewed by Drucker. Important clinical conclusions of the review include the following: [386]

  • Hospitalization is more common for acute COVID-19 among patients with diabetes and obesity.
  • Diabetic medications need to be reevaluated upon admission.
  • Insulin is the glucose-lowering therapy of choice, not DPP-4 inhibitors or GLP-1 receptor agonists, in patients with diabetes who are hospitalized with acute COVID-19.

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