COVID-19 in Diabetics

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Anahita Deylamsalehi, M.D.[2]"

Overview

World Health Organization declared the COVID-19 outbreak a pandemic in 2020. Numerous explanations have been developed for this Comorbidity, such as immune system impairment due to abnormal production of adipokines and cytokines (eg, tumor necrosis factor-alpha and interferons), as well as decreased phagocytic activity and chemotaxis among diabetics. These explanations justify the higher prevalence of COVID-19 among diabetic patients. Old age, male sex and some ethnic minority groups, such as Hispanic, Latino and African American, are considered as risk factors and are also related to worse outcome. There are some confirmed risk factors for COVID-19 in diabetics such as glycemic instability, immune deficiency and related comorbidities, like obesity and cardiac and renal disease. There are also some hypothesized risk factors such as reduced ACE2, Increased furin and chronic inflammation. COVID-19 among diabetic patients has been related to higher rate of complications. Acute respiratory distress syndrome (ARDS), septic shock, acute kidney injury, acute heart injury and diabetic ketoacidosis are some of the frequently reported complications. Diabetic patients with COVID-19 have higher rate of hospitalization, intensive care unit admission and death, compared to non-diabetics. These patients are presented with fever, cough, dyspnea, fatigue, chest pain, headache and some gastrointestinal complains. Concurrent COVID-19 and diabetes have been related to lower levels of lymphocytes, red blood cells (RBC), albumin and hemoglobin. Conversely, higher levels of neutrophils, erythrocyte sedimentation rate (ESR), D-dimer, interleukin-6 (IL-6) and interleukin-10 (IL-10) have been reported in these patients. Bilateral consolidation and ground‐glass opacification have been reported based on chest X-ray and CT scan, respectively. Insulin is used for hospitalized patients in order to maintain a desirable glycemic control and higher insulin requirements have been reported among diabetic patients. There are numerous considerations regarding antidiabetics and antihypertensive medications, their possible side effects and their effects on ACE2 expression. Hyperglycemia has been reported with lopinavir, ritonavir and glucocorticoids use. Furthermore, antivirals such as lopinavir and ritonavir should be used with caution with statin therapy due to augmented risk of hepatic and muscle toxicity.

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating from other Diseases

Epidemiology and Demographics

Age

Risk Factors

Confirmed factors hypothesized factors
1- Glycemic instability

2- Immune deficiency (especially T-cell response)

3- Related comorbidities, like obesity and cardiac and renal disease

1- Chronic inflammation (elevated interleukin-6)

2- Elevated plasmin

3- Reduced ACE2

4- Increased furin (involved in virus entry into cell)

Natural History, Complications and Prognosis

Complications

Prognosis


Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

  • There are no ECG findings associated with COVID-19 in diabetics.

X-ray

Echocardiography or Ultrasound

CT scan

MRI

  • There are no MRI findings associated with COVID-19 in diabetics.

Other Imaging Findings

  • There are no other imaging findings associated with COVID-19 in diabetics.

Other Diagnostic Studies

  • There are no other diagnostic studies associated with COVID-19 in diabetics.

Treatment

Medical Therapy

Anti-diabetic medication

Relation to ACE2 expression

Advantage

Disadvantage

Metformin

None
  • Lower level of IL-6
  • Higher albumin level
  • Lower COVID-19 related death
  • Potential cardiovascular benefits

Pioglitazone

Increased ACE2 production in animal models
  • Reduction in proinflammatory cytokines
  • Lower chance of lung injury

Sulfonylurea

None
  • No specific advantage has been found in patients with COVID-19

Dipeptidyl peptidase-4 inhibitors

None
  • No specific disadvantage has been found in patients with COVID-19

Sodium-glucose-co-transporter 2 inhibitors

Increased ACE2 production by kidney in human studies

Glucagon-like peptide-1 receptor agonists

Liraglutide has been linked with elevated ACE2 production in lung and heart in animal models
  • Potential cardiovascular benefits

Insulin

Increased Renal ACE2 production in animal models
  • No specific disadvantage has been found in patients with COVID-19
COVID-19 treatment Advantages in diabetics disadvantages in diabetics Explanation
Chloroquine/Hydroxychloroquine None
Lopinavir/Ritonavir None
Glucocorticoids None

Management Considerations:

Surgery

  • Surgical intervention is not recommended for the management of COVID-19 in diabetic patients.

Prevention

References

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