type of diabetes and risk for covid-192020/05/12 · • case reports of diabetic ketoacidosis...

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

• 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?


Insulin effect in target organs

Insulin secretion

Glucose dysregulation

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




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?


Insulin secretion


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!



Insulin secretion


COVID-19 outcome (severity pneumonia, complications,

mortality)


Diabetes mellitus

Higher age, obesity,

hypertension, coagulopathy, dyslipidemia,

CVD

Treatment

Treatment

type of diabetes and risk for covid-192020/05/12 · • case reports of diabetic ketoacidosis...

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