Physiology of appetite and weight Flashcards
Obesity measurements
BMI
Waist circumference
Skin fold thickness
Bioelectrical impedance analysis
Ethnicity specific cut offs
Medical problems associated with obesity
Metabolic syndrome/ type 2 diabetes
Cardiovascular disease
Respiratory disease
Liver disease
Cancer
Reproductive dysfunction
Joint problems
Psychological morbidity
Metabolic syndrome
Constellation of closely associated CV risk factors
- visceral obesity
- dyslipidaemia
- hyperglycaemia
- hypertension
Insulin resistance is the underlying pathophysiological mechanism
Pathophysiology of insulin resistance and the metabolic syndrome
Increased free fatty acids
Lipolysis of visceral fat
Glucoenoegenesis
Dyslipidaemia
Pro-inflammatory cytokines and insulin resistance resistance and the metabaolic syndrome
TNF-a, IL 6
Leads to increased insulin resistance
Decreased expression of GLUT-4 (insulin sensitive glucose transporter)
Decreased tyrosine kinase activity of insulin receptor
CV disease
Metabolic syndrome and
- increased blood volume and blood viscosity
- increased vascular resistance
- increased hypertension
- increased left ventricular hypertrophy
- increased coronary artery disease
- increased stroke
Respiratory disease
Obstructive sleep apnoea
Hypoxia/ hypercapnia
Pulmonary hypertension
- right heart failure
Accidents
- daytime somnolence
GI/ liver
Non-alcoholic fatty liver
Non-alcoholic steatohepatitis
May progress to cirrhosis, portal hypertension, hepatocellular cancer
Gallstones
Reflux
Cancer
10% cancer deaths in non-smokers attributable to obesity
Types of cancer include: breast, endometrial, oesophagus, colon, gall bladder, renal, thyroid
Mechanisms include: increased insulin, increased free IGF-I, increased oestrogen, adipo-cytokines, reflux
Reproductive system
Polycystic ovarian syndrome
- oligomenorrhoea, hirsutism, acne
- subfertility
- endometrial hyperplasia
- insulin resistance
Male hypogonadism
Adverse pregnancy outcomes
Joints
Osteoporosis
Gout
Psychological
Depression
Eating disorders
Genetics of obesity
Rare
- obesity associated syndromes
- Prader-Willi
- Bardet- Biedl
Common
- polygenic
- susceptibility genes
- heritability of weight/ height
Other causes of obesity
Hypothyroidism
Cushing’s syndrome
Environmental causes: diet
High fat
High sugar
Socio-economic factors
Environmental causes: physical activity
20-50% total energy expenditure
Obesity prevalence related to proxy measures of physical activity
Socio-economic factors
Fetal programming
Stimuli/ insults at critical periods have persistent biological effects
Stressors in utero
- undernutrition, trace elements
- crudely represented by birth weight
Mechanism: epigenetic modification of gene expression
Life course model
Factors operating at every stage of life affect health outcomes later in life
Pathway of risk between events and health outcomes
Worst outcomes associated with:
- low birth weight
- excessive weight gain in infancy
- adult obesity
Gut microbiome
10^4 cells/g in jejunum to 10^14 cells in colon
Integral to host homeostasis
- absorption of nutrients
- reabsorption of bile acids
- fermentation of fibre and bile acid metabolism
Influenced by diet
- high fat, high fibre
Influence disease risk
- obesity, T2 diabetes
Slow acting hormones that regulate body weight
Leptin
Insulin
Signal % body fat to hypothalamus
- decrease food intake
- increase energy expenditure
Rapid acting peptides that regulate meal sizes
Released from GI tract
- cholecystokinin: decreases eating
- ghrelin: increased eating
- PYY: decreases eating (up to 12 hours)
Act via hypothalamus
Accelerator neurones
NPY/ AgRP neurones
Neuropepetide Y: increases eating
AgRP: blocks melanocortin receptor
Brake neurones
POMC neurones
Melanocortin peptides
- a-MSH, CART: decrease eating
Leptin
Starvation signal
Permissive effect on puberty/ reproduction
Obese humans
- very rare: leptin deficiency, mutation of leptin receptor
- usually: increased leptin with increased fat, decreased CNS leptin transport
Lifestyle modification: diet
500-1000 kcal energy deficiency
Low energy density
- decreased sat fat, decreased sugar
- increased fruit and veg
Decreased portion sizes and snacking
Structured meals/ meal replacements may help promote greater weight loss
Lifestyle modification: physical activity
Exercise 7 days/ week
Target 10000 steps/ day
Regardless of weight/ weight loss, exercise increases health
Orlistat mechanism
Binds and inhibits lipase in the lumen of the gut
Prevents the hydrolysis of dietary fat into absorbable free fatty acids/ glycerol
Excrete 1/3rd dietary fat
Adverse effects of orlistat
Flatulence, oily faecal leakage, diarrhoea
Decreased absorption fat soluble vitamins (ADEK)
Metformin
Best 1st line agent for over weight/ obese patients with T2 diabetes
All other oral hypoglycaemic agents and insulin cause weight gain
Used in diabetes prevention trials but not licensed for this use
Laparoscopic adjustable banding
Restrictive only
Inject/ withdraw saline to adjust the diameter of the band
Roux en- Y gastric bypass
Restrictive
Malabsorptive
Alterations in gut hormones and bile acid flow contribute to weight loss
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
- brings cost savings
Disadvantages of surgical treatment
Perioperative mortality/ morbidity
Long term follow up
Some weight re-gain
Expense
NICE guidelines for bariatric surgery 2014
Recent onset T2DM
Expedite bariatric surgery if BMI>35
Consider surgery if BMI > 30
NHS England 2013 bariatric guidelines
As per NICE but
- must have been obese for at least 5 years
- must engage with non-surgical weight loss programme for 12-24 months first
