L11 - Physiology of appetite and weight Flashcards
Measurements - obesity
- BMI kg/m^2
- Waist circumference
- Skin-fold thickness
- Bioelectrical impedance analysis
- Ethnicity specific cut-offs
Co-morbidities associated with obesity
- Metabolic syndrome/type 2 diabetes
- Cardiovascular disease
- Respiratory disease
- Liver disease
- Cancer
- Reproductive dysfunction
- Joint problems
- Psychological morbidity
In which BMI range do health risks start to increase
- Overweight
What is metabolic syndrome
Metabolic syndrome is a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes
Closely associated CV risk factors - Metabolic syndrome
○ Visceral obesity
○ Dyslipidaemia
○ Hyperglycaemia
○ Hypertension
Insulin resistance is the underlying pathophysiological mechanism
Factors associated with metabolic syndrome
- Central (visceral) fat
- Body mass index > 30
Obesity - pathophysiology
- Increase in free fatty acids (non-esterified fatty acids)
- Lipolysis of visceral fat leading to gluconeogenesis and dyslipidaemia
- Pro-inflammatory cytokines
- TNF-alpha, IL-6 (from ‘overloaded’ white adipose tissue) leads to insulin resistance
- Decrease in expression of GLUT-4 (insulin-sensitive glucose transporter)
- Decrease in tyrosine kinase activity of insulin receptor
What is the risk of type 2 diabetes determined by
- Age
- Obesity
- Family history
- Ethnicity
Factors that increase the risk of CV disease
- Metabolic syndrome PLUS
- Increase in blood volume and blood viscosity
- Increase in vascular resistance
- Increase in hypertension
- Increase in left ventricular hypertrophy
- Increase in coronary artery disease
- Increase in risk of stroke
How does obesity affect the respiratory system
- Obstructive sleep apnoea
- Hypoxia / hypercapnia
- Pulmonary hypertension
- Right heart failure
- Accidents - daytime somnolence
How does obesity affect the GI/liver
- Non-alcoholic fatty liver
- Non-alcoholic steatohepatitis
- May progress to cirrhosis, portal hypertension, hepatocellular cancer
- Gallstones
- Reflux
What percentage of cancer deaths in non-smokers are attributable to obesity
- 10% cancer deaths
Examples of types of cancers linked to obesity
- breast, endometrial, oesophagus, colon, gall bladder, renal, thyroid
Examples of mechanisms that contribute to cancer in obesity
- Increase in insulin levels
- Increase in free IGF-I
- Increase in oestrogen levels
- Adipo-cytokines
What is polycystic ovarian syndrome
a set of symptoms due to elevated androgens (male hormones) in females
How does obesity affect the reproductive system
- Polycystic ovarian syndrome
- Oligomenorrhoea, hirsutism, acne
- Subfertility
- Endometrial hyperplasia
- Insulin resistance
- Male hypogonadism
- Adverse pregnancy outcomes
How does obesity affect joints
- Osteoarthritis
- Gout
Psychological effects of obesity
- Depression
- Eating disorders
Genetic syndromes associated with obesity
- Prader-willi
- Bardet-biedl
What is prader-willi syndrome
Is a genetic disorder due to loss of function of specific genes. In newborns, symptoms include weak muscles, poor feeding, and slow development.
Beginning in childhood, the person becomes constantly hungry, which often leads to obesity and type 2 diabetes
What is bardet-biedl syndrome
is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, hypogonadism, and kidney failure in some cases
Link between diet and obesity
- High fat
- High sugar
What is fetal programming
Fetal programming, also known as prenatal programming, is a theory which suggests that the environment surrounding the fetus during its developmental phase, plays a seminal role in determining its disease risk during the later stages.
What is the life course model
- Factors operating at every stage of life affect health outcomes later in life
What is the worst outcome in the life course model associated with
- Low birth weight
- Excessive weight gain in infancy/childhood
- Adult obesity
Link between gut microbiome and diet
- High fat, high fibre etc; chronic and acute (meal by meal)
- Influence disease risk - obesity, T2 diabetes etc
- Differences in gut bacteria can be induced by diet
- Transplantation of faecal material alters insulin sensitivity(mice and humans)
What are slow-acting hormones that regulate body weight
- Leptin
- Insulin
What are rapid-acting peptides that regulate meal sizes
Released from GI tract:
- Cholecystokinin (CCK)
- eating
- Ghrelin
+ eating - PYY
eating (up to 12 hrs)
Act via hypothalamus
What are accelerator neurons
- NPY/AgRP neurons
- Neuropeptide Y (NPY)
+ eating
Agouti-related peptide (AgRP)
blocks melanocortin receptor
What are brake neurons
- POMC neurons
- Melanocortin peptides
- alpha-MSH, CART
- eating
What is leptin predominantly made by
- Adipose cells
Function of leptin
- Helps to regulate energy balance by inhibiting hunger. Leptin is opposed by the actions of the hormone ghrelin, the “hunger hormone”
Link between fat and leptin levels
Usually:
- Increase in leptin levels with increase in fat
- ‘Leptin resistant’
- Decrease in leptin transport
Effect of leptin on puberty/reproduction
- Leptin controls the onset of puberty
- High levels of leptin, as usually observed in obese females, can trigger neuroendocrine cascade resulting in early menarche
VLCD - principles
- Primary care programme
- Patients with T2DM diagnosis < 6 years prior
- VLCD (830 kcal/day) for 3-5 months
- Initially, total diet replacement with formulae
- Then stepped food reintroduction (2-8 weeks)
- Long-term maintenance with structured support
VLCD - outcomes
- 12 month outcomes reported
- 24% of participants achieved 15 kg weight loss or more
- 46% induced remission of T2DM
- Normal HbA1c off all medication for 2 months
- > 10kg weight loss: 73% remission
Orlistat - Mechanism
- Binds and inhibits lipases in the lumen of the gut
- Prevents the hydrolysis of dietary fat into absorbable free fatty acids/ glycerol
- Excrete - 1/3rd dietary fat
Orlistat - adverse effects
- flatulence, oily faecal leakage, diarrhoea
- Decrease in absorption of fat soluble vitamins - ADEK, supplement
What is metformin
- Best 1st line agent for over-weight/obese patients with type 2 diabetes
- All other oral hypoglycaemic agents and insulin cause weight gain
- Used in ‘diabetes prevention’ trials but not licensed for this use
- Recommended by NICE for prevention of type 2 DM in adults at high risk
Problems with pharmacological therapy
- Can only increase by 3-4 fold the proportion of patients who achieve 5% weight loss in a year
- Weight re-gain after treatment stopped
Surgical treatment for obesity
- Laparoscopic adjustable banding
- Roux-en-Y gastric bypass
Features of laparoscopic adjustable banding
- Restrictive only
- Inject/withdraw saline to adjust the diameter of the band
Features of roux-en-Y gastric bypass
- Restrictive
- Malabsorptive
- Alterations in gut hormones and bile acid flow contribute to weight loss
Risk factors of gastric bypass surgery
- Micronutrient deficiencies (Supplement with iron, B12, folate, calcium, vitamin D)
- Dumping syndrome (GI and vasomotor symptoms)
Advantages of surgical treatment
- Weight loss 25-30%
- Resolve or improve co-morbidities
Disadvantages of surgical treatment
- Perioperative mortality/morbidity (depends on procedure and experience of surgeon)
- Long-term follow-up (micronutrient deficiencies)
- Some weight re-gain (patients will still be obese)
- Expense (though cost effective by 2-5 years, depending on co-morbidities and weight)
UK position - bariatric surgery NICE guidelines
- NICE 2006
- After failure of other options if
- BMI > 40 kg/m-2
- BMI > 35 with co-morbid conditions
- Or first line
- BMI > 50 kg/m-2
- NICE 2014
- Recent onset T2DM:
- Expedite bariatric surgery if BMI > 35
- Consider surgery if BMI > 30
