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BSMS203 endocrinology (Theme 1) > 11. Physiology of appetite and weight > Flashcards

11. Physiology of appetite and weight Flashcards

1
Q

Obesity

A

A medical problem

Aetiology: genetic & environmental

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2
Q

Homeostasis

A

Precise matching of energy intake and energy expenditure

  • average decade of adult life
  • ~10 million kcal consumed
  • tendency towards slight average weight gain
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3
Q

Measurements

A 
BMI - kgm^2
Waist circumference
Skin-fold thicknesses
Bioelectrical impedance analysis
Ethnicity specific cut-offs
BMI:
<18.5 underweight
18.5 - 24.9 normal
25 - 29.9 overweight
30 - 39.9 obesity
>40 morbid obesity
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4
Q

Medical problems

A 
6% UK deaths attributable to obesity
Metabolic syndrome/type 2 diabetes
Cardiovascular disease
Respiratory disease
Liver
Cancer
Reproductive dysfunction
Joint problems
Psychological morbidity
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5
Q

Metabolic syndrome

A

constellation of closely associated cardiovascular risk factors:

  • visceral obesity
  • dyslipidaemia
  • hyperglycaemia
  • hypertension

Insulin resistance is the underlying pathophysiological mechanism

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6
Q

Obesity in relation to insulin resistance and metabolic syndrome

A

BMI vs body fat distribution: central vs peripheral fat distribution
Metabolic syndrome associated with central (visceral) fat, and BMI >30

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7
Q

Pathophysiology

A

Increase in free fatty acids (non-esterified):
- lipolysis of visceral fat -> gluconeogenesis, dyslipidaemia

Pro-inflammatory cytokines:

  • TNF-a, IL-6 (from overladed with white adipose tissue) -> insulin resistance.
  • Decrease in expression of GLUT-4 (insulin-sensitive glucose transporter)
  • Decrease in tyrosine kinase activity of insulin receptor
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8
Q

Role of adipocytokines

A

Regulator of food intake
vasoconstriction, endothelial dysfunction, thrombosis
Anti-atherogenic effects

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9
Q

Type 2 diabetes mellitus risk factors and targets

A

Age, obesity, family history, ethnicity

Rich people in poor countries
Poor people in rich countries - source of socioeconomic inequality in health

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10
Q

What factors contribute to increased prevalence of T2DM?

A

Increased age population
increased obesity - getting more younger obesity
Increased detection/diagnosis - 50% of cases T2DM picked up on routine examination
Increased survival with T2 DM

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11
Q

Cardiovascular disease

A

Metabolic syndrome plus:

  • increased blood volume and blood viscosity
  • increased vascular resistance
  • increased hypertension
  • increased left ventricular hypertrophy
  • increased coronary artery disease
  • increased stroke
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12
Q

Respiratory system effects of obesity

A

Obstructive sleep apnoea
Hypoxia/hypercapnia
pulmonary hypertension - due to right heart failure
Accidents - daytime somnolence

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13
Q

GI/liver effects of obesity

A 
Non-alcoholic fatty liver
Non-alcoholic steatohepatitis
May progress to cirrhosis, portal hypertension, hepatocellular cancer
Gallstones
Reflux
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14
Q

Cancer effects of obesity

A

~10% cancer deaths in non-smokers attributed to obesity
Types:
breast, endometrial, oesophagus, colon, gall bladder, renal, thyroid
Mechanisms: increased insulin, increased free IGF-I, increased oestrogen, adipo-cytokines, reflux

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15
Q

Reproductive system effects of obesity

A

Polycystic ovarian syndrome: oligomenorrhea, hirsutism, acne, subfertility, endometrial hyperplasia, insulin resistance
Male hypogonadism
Adverse pregnancy outcomes

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16
Q

Obesity effects on joints

A

osteoarthritis

gout

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17
Q

Psychological effects of obesity

A

Depression

eating disorders

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18
Q

Aetiology of obesity

A

Genetic factors
Environmental factors
Programming
Gut microbiome

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19
Q

Obesity associated syndromes

A

Rare:
Prader-Willi
Bardet-Biedi

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20
Q

Genetics in obesity

A

Commonly:
polygenic
susceptibility genes
heritability of weight is similar to the heritability of height

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21
Q

Other medical causes of obesity

A

Hypothyroidism

Cushing’s syndrome

22
Q

Environmental factors on obesity

A 
Diet:
high fat
high sufar
Coca-colanisation of developing world
Socioeconomic factors

Physical activity:
20-50% total energy expenditure
Obesity prevalence related to proxy measures of physical activity: car ownership, TV viewing
Socioeconomic factors
Social - more likely to be obese if friends are obese

23
Q

Foetal programming

A

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

E.g. programmed adrenal axis overactivity in adulthood, causal factor for metabolic syndrome, increased vulnerability to coronary heart disease

24
Q

Barker’s group evidence

A

Babies with lowest birth weight ended up with highest morning cortisol as adults

25
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 outcome associated with: - Low birth weight - Excessive weight gain in infancy/childhood - Adult obesity
26
Gut microbiome
10^4 - 10^14 cells/g in colon, 10-100 times as many genes as human genome Integral to host homeostasis (physiology): absorption of nutrients in duodenum and jejunum Reabsorption of bile acids in ileum Fermentation of fibre & bile acid metabolism in colon Influenced by diet: high fat, high fibre etc, chronic & acute (meal by meal) Influence disease risk: obesity, T2DM etc
27
Gut microbiome in obesity and T2DM vs normal
Differences in gut bacteria can be induced by diet e.g. high fat diet Transplantation of faecal material alters insulin sensitivity in mice and humans
28
Regulation of appetite and weight - slow acting
Leptin Insulin Signal % body fat to hypothalamus -> decrease food intake, increase energy expenditure
29
Regulation of appetite and weight - fast acting
Rapid-acting peptides regulate meal sizes ``` released from GI tract cholecystokinin (CCK) inhibits eating ghrelin increases eating PYY inhibits eating up to 12 hours Act via hypothalamus ```
30
Hypothalamus
Accelerator neurons: NPY/AgRP neurons Neuropeptide Y (NPY) encourages eating Agouti-related peptide (AgrP) blocks melanocortin receptor Brake neurons: POMC neurons Melanocortin peptides (alpha-MSH, CART) discourage eating
31
Leptin mice
Ob/ob mouse - leptin deficient Db/db mouse - mutation of leptin receptor Ob gene product = leptin Mouse models of obesity Leptin treatment reduces obesity in ob/ob mouse
32
Leptin in humans
Starvation signal Permissive effect on puberty/reproduction ``` Obese humans: - very rare leptin deficiency or mutation of leptin receptor - increased [leptin] with increased fat ? leptin resistant ? decreased CNS leptin transport ```
33
Treatment for obesity
lifestyle modification pharmacological surgical public health/social
34
Diet modifications to treat obesity
500-1000kcal energy deficiency Low energy density: decreased saturated fat, decreased sugar increased fruit and veg (sub for other foods) Decrease portion sizes, decrease snacking Structured meals/meal replacements may help promote greater weight loss
35
Physical activity to treat obesity
Exercise 7 days a week 30 mins moderate-high intensity or 60 mins low intensity Target 10,000 steps/day, increase 500 step increments Regardless of weight/weight loss, exercise increases health
36
Very low calorie diets (VLCD) and T2DM
Principle: Primary care programme with T2DM patients diagnosed less than 6 years ago, put on a VLCD (830kcal/day) for 3-5 month Initially, total diet replacement with formulae, then stopped food reintroduction (2-8 weeks), long-term maintenance with structured support Outcomes: 12 month outcomes reported 24% of participants lost 15kg or more 46% induced remission of T2DM: normal HbA1c off all medication for 2 months, >10kg weight loss: 73% remission
37
Lifestyle modifications
USUAL TARGETS • 10% weight loss (doesn't equal 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, decreased satiety, decreased metabolic rate BEST HOPE • Sustainable lifestyle changes • Diet combined with exercise / physical activity • Ongoing management is required to maintain weight loss
38
Pharmacological therapy for obesity
25 years research many products, only orlistat
39
Orlistat mechanism
Binds & inhibits lipases in lumen of gut, stops fat absorption Prevents the hydrolysis of dietary fat into absorbable free fatty acids/glycerol Excrete 1/3rd dietary fat
40
Orlistat adverse effects
Flatulence, oily faecal leakage, diarrhoea | stops absorption of fat soluble vitamins (ADEK), but can take supplement
41
Metformin
best 1st line agent for overweight/obese patients with type 2 diabetes All other oral hypoglycaemic agents and insulin cause weight gain used to prevent diabetes but not licensed for this use NICE recommended in preventing type 2 DM in adults at high risk
42
Pharmacological therapy problems
Can only increase by 3-4 fold the proportion who achieve a 5% weight loss in a year Weight re-gained after treatment stopped
43
Pharmacological therapy future
All identified gut peptides/neuropeptides/their receptors are potential therapeutic targets/options Gut hormones in combination most likely way forwards
44
Surgical treatment for obesity
Laparoscopic adjustable banding | Roux-en-Y gastric bypass
45
Laparoscopic adjustable banding
restrictive only | Inject/withdraw saline to adjust the diameter of the band
46
Roux-en-Y gastric bypass
Restrictive, malabsorptive, alterations in gut hormones and bile acid flow contribute to weight loss Endocrine factors important in effects: plasma from operated rats to sham-operated rates - ate 1/3rd less Increased satiety seems to be key, shown by F-MRI studies
47
Roux-en-Y bypass complications
Micronutrient deficiencies - supplement with iron, B12, folate, calcium vitamin D Dumping syndrome - GI & vasomotor symptoms
48
Advantages of surgical treatment
Weight loss 25-30% Resolve or improve co-morbidities Brings cost savings
49
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
50
Swedish obesity subjects (SOS) study
Ongoing, non-randomised, prospective, controlled study 2010 obese subjects who had bariatric surgery vs 2037 matched obesity controls Banding & bypass operations Outcomes were improved through bariatric surgery
51
UK position on bariatric surgery
``` 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 ``` UK position bariatric surgery: NHS guidelines 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
52
Public health/societal approaches to overcoming obesity
``` • Schools ○ PE, lunches, vending machines • Urban design • Marketing/media/social media ○ Food labelling, food advertisements ```

BSMS203 endocrinology (Theme 1) (26 decks)

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