Physiology of Appetite and Weight

Question 1

What are the various measurements of obesity?

Answer 1

• Body mass index (BMI) kg / m2
  
  • < 18.5 underweight
  • 18.5-24.9 normal
  • 25-29.9 overweight
  • 30-39.9 obese
  • ≥40 morbid obesity
• Waist circumference
• Skin-fold thicknesses
• Bioelectrical impedance analysis
• Ethnicity specific cut-offs

Question 2

What are the medical problems associated with Obesity?

Answer 2

• Metabolic syndrome / type 2 diabetes
• Cardiovascular disease
• Respiratory disease
• Liver disease
• Cancer
• Reproductive dysfunction
• Joint problems
• Psychological morbidity
• the higher the BMI the greater the percentage of patients with co-morbidities

Question 3

What is metabolic syndrome?

Answer 3

• a constellation of closely associated CV risk factors
  
  • Visceral obesity
  • Dyslipidaemia
  • Hyperglycaemia
  • Hypertension
• Insulin Resistance is the underlying pathophysiological mechanism

Question 4

What is the epidemiology of Type 2 DM?

Answer 4

• Risk is determined by
  
  • Age, Obesity, Family History, Ethnicity
• Prevalent in
  
  • the rich in poor countries
  • in the poor in rich countries

Question 5

What does CV disease cause

Answer 5

All the following are increased

• ­ blood volume and blood viscosity
• ­ vascular resistance
• ­ hypertension
• ­ left ventricular hypertrophy
• ­ coronary artery disease
• ­ stroke

Question 6

How is the respiratory system effected in obesity?

Answer 6

• Obstructive sleep apnoea
• Hypoxia / hypercapnia
• Pulmonary hypertension
  
  • Right heart failure
• Accidents
  
  • Daytime somnolence

Question 7

how does obesity effect the GI/ Liver

Answer 7

• Non-alcoholic fatty liver
• Non-alcoholic steatohepatitis
• May progress to cirrhosis, portal hypertension, hepatocellular cancer
• Gallstones
• Reflux

Question 8

Wha is the prevalence of cancer in obesity?

Answer 8

• ~ 10% cancer deaths in non-smokers attributable to obesity
• Types of cancer include
  
  • Breast, endometrial, oesophagus, colon, gall bladder, renal, thyroid
• Mechanisms include
  
  • ­increase insulin, ­increase free IGF-I, ­increase oestrogen,
  • adipocytokines, reflux

Question 9

How does obesity effect the reproductive system?

Answer 9

• Polycystic ovarian syndrome
  
  • Oligomenorrhoea, hirsutism, acne
  • Subfertility
  • Endometrial hyperplasia
  • Insulin resistance
• Male hypogonadism
• Adverse pregnancy outcomes

Question 10

How are joints affected by obesity?

Answer 10

• Osteoarthritis
• Gout

Question 11

What psychological effects of obesity?

Answer 11

• Depression
• Eating disorders

Question 12

What are the genetic components of obesity?

Answer 12

• Rare
  
  • obesity-associated syndromes
    
    • Prader-Willi
    • Bardet-Biedl
• Common
  
  • Polygenic
  • Susceptibility genes
  • Heritability of weight ~ heritability of height

Question 13

What are other causes of obesity?

Answer 13

• Hypothyroidism
• Cushing’s syndrome

Question 14

How does the environment contribute to obesity?

Answer 14

• High fat
• High sugar
• ‘Coca-colonization’ of developing world
• Socio-economic factors
• 20-50% total energy expenditure
• Obesity prevalence related to proxy measures of physical activity
  
  • Car ownership
  • TV viewing
• Socio-economic factors
• Social Networking

Question 15

Explain Fetal programming and it’s relation to obesity

Answer 15

• ‘Programming’: stimuli /insults at critical periods have persistent biological effects
• ‘Stressors’ in utero
  
  • ?undernutrition, ?trace elements, ?other
  • crudely represented by birth weight
• Mechanism: epigenetic modification of gene expression
• Example:
  
  • ‘Programmed’ adrenal axis overactivity in adulthood
  • Causal factor for metabolic syndrome
  • Increased vulnerability to coronary heart disease

Question 16

How does the ‘Life Course Model’ explain obesity?

Answer 16

• factors operating at every stage of life affect health outcomes later in life
  
  • there is a ‘pathway of risk’ between events and health outcomes
• the ‘worst outcomes’ are associated with:
  
  • low birth weight
  • excessive weight gain in infancy/childhood
  • adult obesity

Question 17

What role does the Gut Microbiome play in Obesity and T2 Diabetes

Answer 17

• Differences in gut bacteria
  
  • can be induced by diet e.g high-fat diet
• Transplantation of faecal material alters insulin sensitivity
  
  • mice and humans

Question 18

How are weight and appetite regulated?

Answer 18

• slow-acting hormones that regulate body weight
  
  • Leptin
  • Insulin
• Signal % body fat to the hypothalamus
  
  • decrease food intake
  • increase energy expenditure
• Rapid-acting peptides that regulate meal sizes are released from GI tract
  
  • CCK: decreases eating
  • Ghrelin: increases eating
  • Peptide YY (PYY): decreases eating (up to 12 hours)
  • they act via the hypothalamus

Question 19

How does the Hypothalamus control appetite?

Answer 19

Via the Arcuate nucleus

Increases eating

• NPY (Neuropeptide Y)
  
  • increases eating
• AgRP neurons
  
  • Blocks melanocortin receptor

Decreases eating

• POMC neurons
• Melanocortin peptides
  
  • alpha-MSH, CART

Question 20

What is Leptins role in Obese humans?

Answer 20

• usually acts as a starvation signal
• Obesity rarely caused by
  
  • leptin deficiency
  • mutation of leptin receptor
• Obesity usually caused by
  
  • increased leptin with increased fat
  • potentially leptin resistant
  • potentially decreased CNS leptin transport

Question 21

Review this overview of how appetite is controlled

Answer 21

Question 22

What pathways could be taken to control/ treat obesity?

Answer 22

• Lifestyle modification
• Pharmacological
• Surgical
• Public health/ Societal

Question 23

What Lifestyle modifications need to be made?

Answer 23

• Diet
  
  • 500-1000 kcal energy deficiency
  • low energy density: decrease sat fat & sugar, increase fruit and veg
  • decreased portion sizes, decreased snacking
  • Structured meals/ meal replacements
• Physical activity
  
  • exercise 7 days/wk
    
    • 30 mins moderate-high intensity or 60 mins low intensity
  • target 10,000 steps/day

Question 24

What is a VLCD and what are it’s outcomes in T2 DM patients?

Answer 24

• a very low-calorie diet used in patients diagnosed with T2DM <6 yrs prior
• VLCD (830kcal/day) for 3-5 months
  
  • initially, total diet replacement with formulae
  • stepped food introduction
  • long term maintenance with structured support

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
• >10 kg weight loss: 73% remission

Question 25

What are the usual targets and problems with Lifestyle Modification?

Answer 25

• USUAL TARGETS
  
  • 10% weight loss (¹ ideal weight)
  • 1-2 lb (0.5 – 1 kg) per week
  • Some evidence that ‘ambitious’ goals promote more weight loss
• PROBLEMS
  
  • Most patients can achieve ~ 5-10 % weight loss / 1 year
  • ‘Yo-yo’ dieting / regaining weight lost
  • ‘Obesogenic environment’
  • Weight loss results in increased ­hunger, increased satiety, increased metabolic rate
• BEST HOPE
  
  • Sustainable lifestyle changes
  • Diet combined with exercise / physical activity
  • Ongoing management is required to maintain weight loss

Question 26

What is the Mechanism of Orlistat?

Answer 26

• BInds & inhibits lipases in the lumen of the gut
• prevents the hydrolysis of dietary fat into absorbable free fatty acids/ glycerol
• Excrete ~1/3 of dietary fat

Question 27

What are the adverse effects of Orlistat?

Answer 27

• Flatulence, oily faecal leakage
• Diarrhoea
• decreased absorption of fat soluble vitamins
  
  • vit. ADEK
  • take supplements

Question 28

What is the indication of Metformin?

Answer 28

• 1st line agent for over-weight/ obese patients with Type 2 diabetes
  
  • all other oral hypoglycaemic agents and insulin causes weight gain
• used in diabetes prevention trials
• recommended by NICE for prevention of T2DM in adults at high risk

Question 29

What surgical treatment can be done to treat obesity?

Answer 29

• Laparoscopic adjustable banding
  
  • restrictive only- inject/withdraw saline to adjust the diameter of the band
• Roux-en-Y gastric bypass
  
  • Restrictive
    
    • increased satiety
  • malabsorptive
    
    • micronutrient deficiencies: iron, B12, folate, Ca++, Vit D
  • alteration in gut hormones and bile acid flow contribute to weight loss
  • causes dumping syndrome

Question 30

What are the pros and cons of surgical treatment?

Answer 30

Advantages

• weight loss 25-30%
• resolves or improve co-morbidities

Disadvantages

• Perioperative mortality/morbidity
  
  • depends on the procedure and experience of the surgeon
• Long-term follow-up
  
  • micronutrient deficiencies
• Some weight re-gain
  
  • patients will still be obese
• Expense
  
  • cost-effective after some time depending on co-morbidities

Question 31

What are the NICE guidelines for bariatric surgery?

Answer 31

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

Question 32

What are the NHS guidelines on bariatric surgery

Answer 32

NHS England 2013

• 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

Question 33

What are Public Health/ Societal approaches to tackling obesity?

Answer 33

• Schools
  
  • PE, lunches, vending machines
• Urban design
• Marketing/ media/ social media
  
  • food labelling, food advertisements