Metabolic Disease, Obesity and COVID-19 Flashcards
What is obesity?
Abnormal or excessive fat accumulation that may impair health
What waist circumferences for men and women show an increased rate of obesity related morbidity?
Men ≥202cm
Women ≥88cm
Name some factors influencing obesity
Genetics
Environment
Energy balance
Fetal nutrition
How does fetal nutrition affect obesity?
Under-nutrition of the fetus during intrauterine development may lead to later onset of metabolic disease, and an adverse nutritional environment in utero can lead to programmed susceptibility to disease
Why in the UK do we live in an obesogenic environment?
Availability of energy dense foods
Large portion sizes
Cheap food outside of home
Altered eating patterns (snacks instead of meals)
More sedentary lifestyles
Car travel
Name some chronic illnesses that can arise from obesity
T2DM
Heart disease
Obstructive sleep apnoea
Cancer
Osteoarthritis
Hypertension
How does obesity cause T2DM?
Higher plasma FFA causes increased glucose production with reduced hepatic glucose utilisation, leading to hyperinsulinaemia and hyperglycaemia
How does obesity cause heart disease?
Larger body mass causes higher oxygen consumption and cardiac output, leading to myocardial hypertrophy, congestive heart failure or coronary heart disease and sudden death
How does obesity cause obstructive sleep apnoea?
Increased chest and abdominal fat causes alterations in breathing which is exaggerated when lying flat
What types of cancer does a BMI ≥30 increase your risk of?
Prostate
Breast
Endometrial
Cervical
Colorectal
Gallbladder
How does obesity cause osteoarthritis?
Increased weight puts increased pressure on the joints and wears away cartilage
What joints are mostly affected by arthritis in obese individuals?
Lower back, knees, hips
What metabolic diseases can increased fructose intake cause?
Dyslipidaemia - NASH
Hypertension via increased uric acid
Obesity and insulin resistance
Accelerated ageing process
What is metabolic syndrome?
At least 1 of:
- T2DM
- Insulin resistance
- Impaired glucose tolerance
Plus at least 2 of:
- Hypertension
- Obesity
- Hypertriglyceridaemia
- Microalbuminuria
What is the link between T2DM and Alzheimer’s disease?
T2DM patients are at a 1.5-2.5% increased risk of dementia
AD patients are more prone to T2DM
Apart from T2DM, what metabolic features increase the risk of Alzheimer’s disease?
Body weight extremes and hypercholesterolaemia
AD is associated with increased/reduced glucose metabolism and insulin signalling in the brain
Reduced
How can we fix the problem of obesity?
Societal engagement
Inform
Motivate - individual sets personal goals
Incentive
Influence - changes in advertising and pricing to alter societal attitudes
Describe the structure of SARS-CoV-2
Contains glycoprotein spikes
Has a membrane layer which is alcohol/detergent sensitive
Inside is the virus genome which is RNA and encodes ~27 proteins
How does SARS-CoV-2 enter cells?
The spike proteins allow it to bind and enter healthy cells
How is SARS-CoV-2 detected by the immune system?
By the spike proteins
What are the functions of S1 and S2 of the spike protein of SARS-CoV-2?
S1 - recognition site. Allows the recognition and binding to the cell receptor
S2 - facilitates fusion of viral membrane with the cell
What cleaves the viral S glycoprotein in SARS-CoV-2?
Transmembrane serine protease 2 (TMPRSS2)
ACE2:
What is it?
What is its function?
Zinc metalloprotease involved in BP control
Catalyses the hydrolysis of angiotensin II to angiotensin 1-7
What is the primary receptor for SARS-CoV-2?
ACE2 receptor
How many cleavage sites are on SARS-CoV-2?
3, cleavage occurs after binding to ACE2
Symptoms of mild-moderate SARS-CoV-2 infection
Headache
Loss of smell
Cough
Nasal obstruction
Lack of energy
Myalgia
Runny nose
Sore throat
Fever
Symptoms of severe SARS-CoV-2 infection
Fever
Joint pain
Abdominal pain
SOB
Pneumonia
Cough
Vomiting
Fatigue/malaise
Confusion
Symptoms that patients in ICU with SARS-CoV-2 had
ARDS
Acute respiratory failure
Dyspnoea
Myocardial injury
Arrhythmias
Heart failure
Kidney failure
Encephalopathy
Co-morbidities for SARS-CoV-2
Hypertension
CKD
Liver disease
Immunocompromised
COPD
CVD
Cancer
True or false:
Diabetes is a risk factor for SARS-CoV-2 infection
False
Not a risk factor for infection but major risk factors for progression to critical illness
Increased risk of hospitalisation, intensive care, ARDS, mechanical ventilation and death
In what groups is obesity associated with increased mortality from COVID-19?
Younger (18-59) rather than older
Males
Non-white ethnicity
What is long COVID?
When symptoms remain after clearance of acute infection (~4 weeks) and cannot otherwise be explained
Symptoms of long COVID
Fatigue
Dyspnoea
Cardiac abnormalities
Cognitive impairment
Sleep disturbances
PTSD-like symptoms
Muscular pain
Headache
Who are the people most at risk after vaccination?
Less healthy lifestyles
Older frail people
Higher BMI
Living in areas of high deprivation
Three stages of the overactive inflammatory response in SARS-CoV-19
Early infections stage
Pulmonary phase
Hyper-inflammatory stage
What is involved in the early infections stage?
Fever, dry cough etc.
What is involved in pulmonary phase?
Shortage of breath, chest abnormalities on imaging
What is involved in the hyper-inflammatory stage?
Cytokine storm leading to ARDS, multiple organ failure and death
Elevated IL-6, TNF-alpha, IL-1b, CRP
A Western diet leads to activation/inhibition of the innate immune system and activation/inhibition of the adaptive immune response
Leads to activation of innate immune system and inhibition of the adaptive immune system
What happens when there is overnutrition of adipose tissue?
Overnutrition driver hyperplasia and hypertrophy and causes adipose tissue expansion with vascularisation, leads to hypoxia and cell death and increased numbers of immune cells
How is insulin resistance fuelled in obese adipose tissue?
Via inflammation and increased lipolysis
How do fat cells effect the immune response in SARS-CoV-2?
Increased inflammation and there is death through virally driven hyperinflammation
Suppressed immune responses
More pro-inflammatory mediators
Reduced antiviral and anti-inflammatory responses
How does adipose tissue act as a virus reservoir?
Higher viral load for longer
Poor recovery from disease
Prolonged viral shed from obese individuals
Reduced efficacy of vaccines and antivirals
True or false:
Obesity exacerbates the ageing of the immune system
True - mirrors immune deficit in elderly individuals
What do interferons do?
Lead to RNA and viral protein destruction
What are the three main classes of interferons?
Type I - IFN alpha, IFN beta
Type II - IFN gamma
Type III - IFNI
What do type I interferons do?
Stimulate resistance to viral replication in all cells
Leads to viral RNA destruction
Promotes NK cell activation
What do type II interferons do?
Immune-induced responses
Coordinates response from innate to adaptive immunity (T-cells)
What do type III interferons do?
Present the antiviral activity
First line of defence against viral infections
Regulates innate and adaptive immune responses
How does obesity cause impaired virus clearance and high viral load?
By regulating ACE2 and raising ER stress
