type of diabetes and risk for covid-192020/05/12 · • case reports of diabetic ketoacidosis...
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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
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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
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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
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Co-morbidities in subjects with COVID-19 - Italy
www.epicentro.iss.it Report May 7. AccessesdMay 11, 2020
n = 2,621
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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%
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SARS epidemic in China (2003)
Yang JK et al, Diab Med 2005
Diabetes: OR 3.0 for death
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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%
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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%
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• 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
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Role of glycemic control and risk of infections?
Hine JL et al, Diabetic Medicine 2016
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Role of glycemic control and risk of infections?
Hine JL et al, Diabetic Medicine 2016
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• 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?
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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
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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
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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
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(Extreme) insulin resistance in COVID-19
Insulin
sensitivity
Beta-cell function
Diabetes
Normoglycemia
Adopted from Kahn et al., Diabetes 1993
HyperinflammationSteroids
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What is the effect of SARS-CoV-2 and COVID-19 on isletsecretion?
SARS-CoV-2 + COVID-19
Insulin secretion
Glucose dysregulation
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SARS-CoV-2 binds to ACE2 with priming of serine protease TMPRSS2
• 4 proteins
• Spike (S)
• Membrane (M)
• Nucleocapside(N)
• Envelope (E)
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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
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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?
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Gene expression of ACE2 and TMPRSS2 in single human islet cells
Groen N, Carlotti F, de Koning EJP et al., unpublished
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SARS-CoV in different endocrine organs (autopsy)
Ding Y et al., J Pathol 2004
ControlSARS
Pancreas (acinar cells)
Parathyroid
Adrenal cortex
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• 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?
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Are endocrine cells protected from SARS-CoV-2 infection and viral replication?
Lamers M, Science 2020
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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