Type of diabetes and risk for COVID-19

ERN Webinar series: COVID-19: Endocrine conditions and increased risk

Eelco de Koning, M.D., Ph.D.Dept. of Internal Medicine, Section of EndocrinologyLeiden University Medical CenterMay 11, 2020

SARS-CoV-2 + COVID-19

COVID-19 outcome (severity pneumonia, complications,

mortality)

COVID-19 and the endocrine system

Target tissues/organs

Hormone production

Endocrine dysregulation

Endocrine dysregulation

Endocrine disorder

Associated features and

complications

Treatment

Treatment

COVID-19 in Italy

www.epicentro.iss.it Report May 7. Accessesd May 11, 2020

Median age of death: 80 yearsFemale: 39%

Death by age

In NL: > 75 years 17.5% of patients have diabetes

mellitus

Co-morbidities in subjects with COVID-19 - Italy

www.epicentro.iss.it Report May 7. AccessesdMay 11, 2020

n = 2,621

Co-morbidities in subjects with COVID-19 - Italy

www.epicentro.iss.it Report May 7. AccessesdMay 11, 2020

n = 2,621

Gender differenceType 2 diabetes: M 31.4% F 30.4%Ischemic Heart Disease: M 32.0%, F 21.1%Hypertension: M 67.3% F 70.1%COPD: M 18.4% F 12.8%

SARS epidemic in China (2003)

Yang JK et al, Diab Med 2005

Diabetes: OR 3.0 for death

Co-morbidity in COVID-19 – USA (New York)

Richardson et al, JAMA 202

• Hypertension 57%

• Obesity 42%

• Diabetes 34%

n = 5,700Admitted to hospitalAge: 63 yearsFemale 39.7%

www.stichting-nice.nl Accessed May 11, 2020

BMICOVID-19 (n=1,663) 28.6Severe Acute Respiratory Infection (SARI) 2017-2019 (n=19,470) 26.2

BMI in ICU patients (Netherlands)

Overweight/obesity (BMI >25):- COVID-19 78%- SARI 51%

• Hyperglycemia affects phagocytosis, neutrophil chemotaxis, cell-mediated immunity

• Many studies show relationship between diabetes and development of severe pneumonia and more severe outcome

• No data that risk of becoming infected is different from general population

Hyperglycemia

Role of glycemic control and risk of infections?

Hine JL et al, Diabetic Medicine 2016

Role of glycemic control and risk of infections?

Hine JL et al, Diabetic Medicine 2016

• Most data on type 2 diabetes (older age, obesity, hypertension, cardiovascular disease)

• Type 1 diabetes – in well controlled younger patients without complications no report of excess severe course or mortality of COVID-19

• Prevention of hyperglycemia important to reduce risk of super-infections

• Role for ENDO-ERN community

Type of diabetes: does it matter?

What is the effect of SARS-CoV-2 and COVID-19 on glucose control?

SARS-CoV-2 + COVID-19

Insulin effect in target organs

Insulin secretion

Glucose dysregulation

What is the effect of SARS-CoV-2 and COVID-19 on insulinsensitivity?

SARS-CoV-2 + COVID-19

Insulin effect in target organs

Glucose dysregulation

Hyperbolic relationship between insulin sensitivity and insulin secretion

Insulin

sensitivity

Beta-cell function

Diabetes

Normoglycemia

Adopted from Kahn et al., Diabetes 1993

ObesityLittle exercise

Pregnancy

(Extreme) insulin resistance in COVID-19

Insulin

sensitivity

Beta-cell function

Diabetes

Normoglycemia

Adopted from Kahn et al., Diabetes 1993

HyperinflammationSteroids

What is the effect of SARS-CoV-2 and COVID-19 on isletsecretion?

SARS-CoV-2 + COVID-19

Insulin secretion

Glucose dysregulation

SARS-CoV-2 binds to ACE2 with priming of serine protease TMPRSS2

• 4 proteins

• Spike (S)

• Membrane (M)

• Nucleocapside(N)

• Envelope (E)

ACE2 – friend or foe?

• More ACE2 – Acceleration of SARS-CoV-2 entry into cells?

• Less ACE2 – Detrimental effects during hyperinflammation/cytokine storm in the lung (clinical ARDS)?

• Increased ACE2 expression

• GLP1R-agonists

• Thiazolidinediones

• Statins

• ACEi

• ARBs

• Recommendations: Continue medication

Yang JK et al., Acta Diabetol 2010

Islet-HE Islet

Lung Kidney tubules

Liver

Heart

Does SARS-CoV-2 damage of insulin producing beta cells directly?

Gene expression of ACE2 and TMPRSS2 in single human islet cells

Groen N, Carlotti F, de Koning EJP et al., unpublished

SARS-CoV in different endocrine organs (autopsy)

Ding Y et al., J Pathol 2004

ControlSARS

Pancreas (acinar cells)

Parathyroid

Adrenal cortex

• Novel damage or unmasking of ongoing islet damage• Autoimmune (type 1A diabetes)

• Metabolic (type 2 diabetes)

• Case reports of diabetic ketoacidosis (Italy)• Chee JL, BioXRiV 2020

• Diabetic ketoacidosis precipitated by COVID-19 in a patient with newly diagnosed diabetes mellitus

• GlyHb 14.2 %

What is the clinical evidence of islet damage duringCOVID-19?

Are endocrine cells protected from SARS-CoV-2 infection and viral replication?

Lamers M, Science 2020

COVID-19 and diabetes: In need of answers – type of diabetes? Mechanisms? Metabolic interventions? - Endo-ERN!

SARS-CoV-2 + COVID-19

Insulin effect in target organs

Insulin secretion

Glucose dysregulation

COVID-19 outcome (severity pneumonia, complications,

mortality)

Glucose dysregulation

Diabetes mellitus

Higher age, obesity,

hypertension, coagulopathy, dyslipidemia,

CVD

Treatment

Treatment