3.18 - Obesity Flashcards
What is obesity?
A condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health is impaired
What BMI range is classed as underweight?
<18.5 kg/m2
What BMI range is classed as healthy weight?
18.5-24.9 kg/m2
What BMI range is classed as overweight?
25-29.9 kg/m2
What BMI range is classed as obesity I?
30-34.9 kg/m2
What BMI range is classed as obesity II (extremely obese)?
35-39.9 kg/m2
What BMI range is classed as obesity III (extremely obese)?
40+ kg/m2
What are some issues with using BMI to measure obesity?
- poor for those with high muscle mass
- set up for white Europeans (healthy BMI may vary between populations)
How much of our chance of being obese is dictated by genes?
And what is an example of a mutation seen?
70-80% (obesity can be inherited) e.g. mutation in MC4R gene
Where are the genes that dictate BMI and what do they respond to?
e.g. MC4R mutation
- many genes in hypothalamus
- regulate food intake
- respond to signals from periphery (GI hormones)
- longer term signals from adipose tissue
How has the incidence of obesity changed overall?
Obesity has increased rapidly
What drives obesity? (8)
- diet and food industry
- not living near parks/playgrounds
- using cars instead of walking
- increased screen time
- lower education level and educational achievement
- poverty
- social deprivation
- sedentary lifestyle
What are some obesity and overweight stats (2016)?
- > 1.9 billion adults were overweight
- of these, >650 million obese
How do genetics and the environment come together in obesity?
- tendency to become obese is heritable but dependent on environment you are in
- obesogenic environment - people with genetic predisposition are at increased risk of obesity
- over years, genetic tendency has not changed but the environment has
What comorbidities are associated with obesity? (11)
- depression
- sleep apnoea
- stroke
- MI
- hypertension
- diabetes
- bowel cancer
- osteoarthritis
- peripheral vascular disease
- gout
- infertility
What do we do if someone comes into the GP with obesity?
- determine degree of overweight/obesity
- assess lifestyle, comorbidities and willingness to change
- management - lifestyle changes; drug treatment
- consider referral to specialist care
- specialist assessment and management - surgery and follow up
What is leptin?
- necessary for normal physiological function
- acts in feedback loop to brain from adipose tissue
- signals to brain that we are not starving
What does leptin do? (8)
- regulate appetite, control of metabolism and energy homeostasis
- helps regulate thyroid hormone synthesis
- decreases glucose-stimulated insulin secretion
- increased heart rate
- regulate bone mass
- regulate menstrual cycle
- activation of immune cells
- high BP
What happens in leptin deficiency? (5)
- infertility
- stunted linear growth
- decreased body temperature
- decreased energy expenditure
- decreased immune function
- (hyperphagia: increased appetite)
How do you treat leptin deficiency in children?
- leptin administration
- reduces appetite and body weight in leptin deficient children
- restores LH pulsatility - puberty and fertility
How can leptin be used in women with amenorrhoea?
Restores LH pulsatility in women with amenorrhoea - tells brain that there is increased fat to restore menstruation
What is leptin resistance?
And what kind of hormone is leptin?
- absence of leptin –> hyperphagia, lowered energy expenditure, sterility etc
- leptin is an anti-starvation hormone rather than an anti-obesity hormone
- presence of leptin is signal to CNS that system has sufficient fat reserves for normal functioning but high leptin has little effect
What is the main drug we give to obesity patients?
- Orlistat - derivative of endogenous lipstatin produced by Streptomyces toxytricini
- gastric and pancreatic lipase inhibitor
- reduces dietary fat absorption by 30%
What is the efficacy, side effects and attrition level of Orlistat?
- reduces weight by 3%
- side effects - fatty and oily stool, faecal urgency, oily spotting, faecal incontinence in 7%
- possible deficiencies of fat-soluble vitamins
- no long-term data on Orlistat on obesity-related morbidity and mortality
- attrition rates (no. who stop) high - 33%
What are the effects of GLP-1?
- reduced appetite, increased satiety
- increased insulin, decreased glucagon
- reduced liver fat, inflammation, insulin resistance
- increased sodium excretion and diuresis
- increased endothelial function, decreased arterial stiffness and inflammation
- increased myocardial contractility and ischaemic preconditioning, decreased glucose uptake
Body weight, BP, plasma glucose and plasma lipids decreased
What is Liraglutide/Saxenda?
- long-acting glucagon-like peptide-1 receptor agonist
- daily injection
- double the dose used for T2DM
- 4-5% weight loss
What levels of BMI do we consider bariatric surgery? (4)
- first line for BMI >50 kg/m2
- BMI 40 kg/m2 or more
- BMI 35-40 kg/m2 and other comorbidities
- BMI 30-35 kg/m2 for newly diagnosed T2DM
What are other requirements for bariatric surgery? (4)
- non-surgical measures have failed to achieve/maintain adequate clinically beneficial weight loss for at least 6 months
- receiving/will receive intense specialist management
- generally fit for anaesthesia and surgery
- commit to the need for long-term follow-up
What are the three types of bariatric surgery?
- gastric bypass
- gastric band
- sleeve gastrectomy
What is gastric bypass surgery?
Top part of stomach is joined to small intestine, so you feel fuller and do not absorb as many calories from food
What is a gastric band?
A band is placed around your stomach so you do not need to eat as much to feel full (less effective)
What is a sleeve gastrectomy?
Some of your stomach is removed, so you cannot eat as much as you could before and you feel full sooner
How effective is bariatric surgery?
Very effective - you can lose up to 1/4 of body weight through it
What is Semaglutide?
Long-acting GLP-1 receptor agonist
What is Tirzepatide?
Long-acting GLP-1 receptor and GIP (glucose-dependent insulinotropic polypeptide) receptor co-agonist
What is Cagrilintide?
Long-acting amylin analogue given in combination with semaglutide
Semaglutide = long acting GLP-1 agonist
What is Retatrutide?
Triple agonist of GIP, GLP-1 and glucagon receptors
Summary of drugs given for obesity. (4)
- semaglutide (and liraglutide) - long acting GLP-1 receptor agonist
- tirzepatide - long-acting GLP-1 receptor and GIP agonist
- cagrilintide - long-acting amylin analogue given in combination with semaglutide
- retatrutide - triple agonist of GLP-1, GIP and glucagon receptors
