Obesity treatment Flashcards
The impact of obesity: global prevalence obesity and T2DM, serious complications
- prevalence of overweight: 1.9 billion (39%)
- prevalence of obesity: 650 million (13%)
- 592 million with T2DM (accounts for 4.9 million deaths)
- complications: with every 5 kg/m2 increase in BMI, mortality from vascular complications (stroke) increases by 40%. Those with a BMI of 30-39 have a 3 year reduced life expectancy. Those with a BMI of 40-49 have a 8-10 year reduction in life expectancy
Benefits of 5-10% weight loss
- reduction in T2DM risk
- improvements in dyslipidemia and blood pressure
- reduction in severity of obstructive sleep apnoea
- better HR-QoL
- reduced CVD mortality
Homeostatic control of energy homeostasis
- in the arcuate nucleus of the hypothalamus, POMC neurons are activated by GLP1, PYY, oxyntomodulin, leptin and insulin. This activates the MC3/4R (melanocortin receptors) in the paraventricular nucleus which leads to increased satiety, decreases energy intake and increases energy expenditure
- Also in the arcuate nucleus, NPY/AgRP neurons are activated by ghrelin which leads to increased hunger, energy intake and reduced energy expenditure
- the brainstem also has the vagus nerve which increases gastric emptying, GLP1 can also act to decrease gastric emptying via the area posterma
Where peptides are secreted in the gut
- stomach: ghrelin
- pancreas: insulin, glucagon
- duodenum: cholecystekinin (slows gastric emptying), ghrelin
- ileum and colon: GLP1, PYY, oxyntomodulin
Key peptides and their actions: ghrelin, PYY, GLP1
- ghrelin: increases hunger, and is increased in obesity. Worsens blood glucose control
- PYY/GLP1: increases satiety and is reduced in obesity. Improves blood glucose control
3 core components of lifestyle modification: why doesnt this work?
1) caloric restriction (VLCD, regular restriction, limiting food groups)
2) 150 moderate activity every week
3) behavioural modification around food
- however, rarely sustained as ghrelin increases throughout diet and PYY/GLP1 reduces. Tend to increase ‘set-point’ each time go on a diet
Which medications should be minimised to mitigate weight gain?
- anti-diabetics: try to keep on 1L MTX
- anti-convulsants: gabapentin
- anti-depressants: mirtazapine (use citalopram instead)
- anti-hypertensives: beta-blockers (use ACEi, ARBs instead)
- anti-psychotics: olanzapine, clozapine (use aripiprazole instead)
- corticosteroids
Tier 3 pharmacotherapy management: Orlistat
- only drug approved in the UK
- gastric and pancreatic lipase inhibitor- interferes with 30% fat absorption in the diet
- leads to 3.4% weight loss in 1 year
- bad side effects: 80% have GI side effects such as oil spotting
- does seem to reduce incidence on T2DM though
Tier 3 pharmacotherapy management: Naltrexone/bupropion
- Used in the US only
- Naltrexone: opioid receptor antagonist
- Bupropion: dopamine and noradrenaline reuptake inhibitor
- together, active POMC
- leads to 4.8% weight loss at 1 year
Tier 3 pharmacotherapy management: Liraglutide
- GLP1 analog (usually produced by L cells in the colon and ileum) with 97% homology and half life of 13 hours
- once daily injection
- activates POMC and reduces gastric emptying
- increases satiety and fullness
- leads to 5.4% weight loss at 1 year (but can tell within 3 months if someone is a responder or not)
Tier 3 pharmacotherapy management: Semuglutide
- GLP1 analog with 93% homology, improved pharmacokinetics with 1 week half-life
- 12.4% weight loss at 1 year, increasing up to 16% at 68 weeks
NICE guidelines for bariatric surgery
- have to have a BMI of 35 + comorbidities or BMI of 40+
- need to show have tried all other approaches and unable to keep weight off for 6 months
- need to be fit for anesthesia
- need to also commit to long-term changes need to make
How metabolic bariatric procedures work
- only sleeve gastrectomy and roux-en-Y gastric bypass
- engenders the GI system to alter pattern of exposure to nutrients which changes hunger (reduced ghrelin) and increases satiety (increased PYY and GLP1), also changes hedonic rewards behaviours and alters taste perception
Levels of weight loss with different bariatric procedures
- at 15 years: 14% loss with banding, 16% with vertical banded gastroplasty and 25% gastric bypass
Benefits of bariatric surgery
- 80% of T2DM patients put into remission
- 80% reduction in MetS at 5 years
- 95% improvement in QoL at 5 years
- 89% reduction in relative mortality risk at 5 years due to improvements in hypercholesterolemia, hypertension and T2DM
