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Year 2 Medicine > Physiology of Appetite and Weight > Flashcards

Physiology of Appetite and Weight Flashcards

1
Q

Obesity can be viewed in two ways:

  1. As a medical problem
    • aetiology - … and …
  2. As a personal failure
    • lack of …
A
  1. As a medical problem
    • aetiology - genetic and environmental
  2. As a problem failing
    • lack of self-discipline
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2
Q

Obesity definition - Prof Steve O’Rahilly:

  • ’ a … hereditary disorder heavily influenced by the … ‘
A
  • ’ a neurobehavioural hereditary disorder heavily influenced by the environment ‘
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3
Q

Homeostasis - precise matching of energy intake and energy expenditure:

  • average decade of adult life - we consume around how many calories?
  • tendency towards a slight average weight ….
A
  • average decade of adult life - we consume around how many calories? - 10 million
  • tendency towards a slight average weight gain
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4
Q

Measurements - weight

  • Body mass index (BMI) - measured in …
  • waist …
  • skin-… thickness
  • … impedance analysis
  • ethnicity specific …
A
  • Body mass index (BMI) - kg/m2
  • waist circumference
  • skin-fold thickness
  • bioelectrical impedance analysis
  • ethnicity specific cut-offs
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5
Q

Body mass index (BMI) ranges

  • Underweight = ?
  • Normal = ?
  • Overweight = ?
  • Obese = ?
  • Morbid Obesity = ?
A
  • Underweight = <18.5
  • Normal = 18.5-24.9
  • Overweight = 25-29.9
  • Obese = 30-39.9
  • Morbid Obesity = > (And including) 40
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6
Q

What trend is this showing? (prevalence increasing)

A

obesity trends among US adults

also in europe (shown below)

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7
Q

Medical Problems of Obesity:

  • … syndrome / type … diabetes
  • … disease
  • … disease
  • … disease
  • Cancer
  • Reproductive …
  • … problems
  • … health
A
  • Metabolic syndrome / type 2 diabetes
  • CVS disease
  • Respiratory disease
  • Liver disease
  • Cancer
  • Reproductive dysfunction
  • Joint problems
  • Mental health
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8
Q

Once you become significantly or morbidly obese, what happens to co-morbidities?

A

Will have more than 1 associated with your obesity

Some patients have 3 or more co-morbidities - this % rises as BMI rises

(>60 BMI = 90% have 3 or more co-morbidities)

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9
Q

Some of the health risks start to go up in the … category of BMI range

A

Some of the health risks start to go up in the overweight category of BMI range (25-30)

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10
Q

What is metabolic syndrome?

  • what are some examples of conditions involved?
  • what is the underlying pathophysiological mechanism?
A

A constellation of closely associated cardiovascular risk factors

  • e.g. visceral obesity, dsylipidaemia, hyperglycaemia, hypertension
  • underlying mechanism - insulin resistance
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11
Q

Obesity - Insulin resistance and the metabolic syndrome

  • BMI vs body fat distribution (central vs peripheral)
  • Metabolic syndrome is associated with 1) … fat distribution and 2) body mass index of over …
A
  • BMI vs body fat distribution (central vs peripheral)
  • Metabolic syndrome is associated with - central (visceral fat) and body mass index >30
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12
Q

Obesity - pathophysiology of insulin resistance

  • One idea - release of free … …
    • leading to … of visceral fat
    • -> gluconeogenesis
    • -> dyslipidaemia
  • other idea - release of pro-inflammatory …
    • TNF-a, IL-6 (from overload white adipose tissue)
    • causing insulin resistance
    • reduced expression of GLUT 4
    • decreased … kinase activity of insulin receptor
A
  • One idea - release of free fatty acids (non-esterified fatty acids)
    • lipolysis of visceral fat
    • gluconeogenesis
    • dyslipidaemia
  • other idea - release of pro-inflammatory cytokines
    • TNF-a, IL-6 (from overload white adipose tissue)
    • causing insulin resistance
    • reduced expression of GLUT 4
    • decreased tyrosine kinase activity of insulin receptor
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13
Q

fat is a very … tissue - it produces …

A

fat is a very active tissue and it produces adipocytokines

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14
Q

Type 2 diabetes

  • Risk is determined by 4 factors. What are they?
  • Targets: does it target rich or poor?
A
  • Age
  • Obesity
  • Family Hx
  • Ethnicity
  • Targets - rich in poor countries, poor in rich countries (source of socioeconomic inequality in health)
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15
Q

Why is the prevalence of Type 2 Diabetes rising?

A
  • Increasing age of population
  • Increasing obesity levels
    • T2 DM younger
  • Increased detection/diagnosis - 50% cases picked up on routine examination
  • Increased survival with T2 DM
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16
Q

Cardiovascular disease - associated with obesity

  • ‘… syndrome’ PLUS
    • increased blood … and blood …
    • increased vascular …
    • increased …tension
    • increased left ventricular …
    • increased … artery disease
    • increased risk of …
A
  • ‘Metabolic syndrome’ PLUS
    • increased blood volume and blood viscosity
    • increased vascular resistance
    • increased hypertension
    • increased left ventricular hypertrophy
    • increased coronary artery disease
    • increased risk of stroke
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17
Q

Respiratory System - associated with obesity

  • Obstructive … …
  • Hyp../hyper…
  • Pulmonary … - cause of … heart failure
  • Accidents - daytime …
A
  • Obstructive sleep apnoea
  • Hypoxia/hypercapnia
  • Pulmonary hypertension - right heart failure
  • Accidents - daytime somnolence
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18
Q

GI/liver - associated with obesity

  • NAFLD - what does this stand for?
    • may be called MAFLD
    • …% of obese people have NAFLD
  • 1:5 progress to NASH - what does this stand for?
  • 1:5 progress to … and chronic liver disease
  • Can also have …stones
  • Reflux
A
  • _​_Non-alcoholic fatty liver disease (NAFLD)
    • ‘Metabolic-associated fatty liver disease’
    • 90% of obese people have NAFLD
  • 1:5 progress to non-alcoholic steatohepatitis (NASH)
  • 1:5 progress to cirrhosis and chronic liver disease
  • Gallstones
  • Reflux
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19
Q

Obesity and cancer

  • Is obesity or smoking the most important cancer risk factor?
  • What types of cancer are linked to obesity? (7)
  • Mechanisms include … (5)
A
  • Is obesity or smoking the most important cancer risk factor? - obesity has overtaken smoking
    • What types of cancer are linked to obesity? (7)
      • breast
      • endometrial
      • oesophagus
      • colon
      • gall bladder
      • renal
      • thyroid
  • Mechanisms include … (5)
    • increased insulin
    • increased free IGF-1
    • Increased oestrogen
    • adipo-cytokines
    • reflux
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20
Q

Reproductive system and Obesity

  • In women - PCOS is strongly associated with obesity - what does this stand for? what does it cause? (6 things)
  • In men - male hypo..
  • adverse … outcomes
A
  • In women - PCOS is strongly associated with obesity - what does this stand for? Polycystic ovarian syndrome what does it cause? (6 things)
    • oligomenorrhoea, hirsutism, acne, subfertility, endometrial hyperplasia, insulin resistance
  • male hypogonadism
  • adverse pregnancy outcomes
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21
Q

Effect of weight loss on testosterone

The bigger weight loss, the … the testerone

A

higher testosterone - levels increase

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22
Q

Joints and obesity

  • osteo…
  • also g…
A
  • osteoarthritis
  • gout
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23
Q

Mental Health and Obesity

  • obesity is associated with:
    • …
    • … disorders
    • …
A
  • depression
  • eating disorders
  • dementia
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24
Q

Covid 19 and Obesity

  • impact of obesity on C19
    • increased prevalence
    • increase risk of …
    • increased risk of … admission
    • increased …
    • ‘…-response’ with BMI
      • independent of…
      • related to increased … fat
A
  • impact of obesity on C19
    • increased prevalence
    • increase risk of hospitalisation
    • increased risk of ICU admission
    • increased mortality
    • ‘dose-response’ with BMI
      • independent of co-morbities
      • related to increased visceral fat
25
Q

Covid 19 and Impact of lockdown on Obesity

  • increased … of food
  • increased …-induced eating
  • decreased … health
  • reduced …
  • less access to …-management services
A
  • increased stockpiling of food
  • increased stress-induced eating
  • decreased mental health
  • reduced exercise
  • less access to weight-management services
26
Q
A
27
Q

Aetiology of obesity

  • … factors
  • … factors
  • programming
  • gut …
A
  • genetic factors
  • environmental factors
  • programming
  • gut microbiome
28
Q

Genetics - obesity

  • Rare - Obesity-associated syndromes
    • …-willi
    • …-biedl
  • Common - polygenic
    • … genes
    • heritability of weight - similar to heritability of …
A
  • Rare - Obesity-associated syndromes
    • prader-willi
    • bardet-biedl
  • Common - polygenic
    • susceptibility genes
    • heritability of weight - similar to heritability of height
29
Q

Other causes of obesity (endocrine) include… (2)

A
  • hypothyroidism
  • Cushing’s syndrome
30
Q

Environment and Obesity

  • Diet
    • which is high in … and …
    • ‘Coca-colanisation’ of developing world
    • …-… factors
  • Physical activity
    • …-…% of total energy expenditure
    • obesity prevalence related to proxy measures of physical activity - … ownership, … viewing
    • …-… factors
A
  • Diet
    • high fat and sugar
    • ‘Coca-colanisation’ of developing world
    • socio-economic factors
  • Physical activity
    • 20-50% of total energy expenditure
    • obesity prevalence related to proxy measures of physical activity - car ownership, TV viewing
    • Socio-economic factors
31
Q

Fetal Programming - Obesity

  • ‘programming’: stimuli/insults at critical periods have persistant biological effects
  • ‘…’ in utero
    • undernutrition? trace elements? other?
    • crudely represented by birth …
  • mechanism - epigenetic modification of gene expression
    • example?
A
  • ‘programming’: stimuli/insults at critical periods have persistant biological effects
  • ‘stressors’ in utero
    • undernutrition? trace elements? other?
    • crudely represented by birth weight
  • mechanism - epigenetic modification of gene expression
    • example - low birth weight - programmed adrenal axis overactivity in adulthood
    • causal factor for metabolic syndrome
    • increased vulnerability to coronary heart disease
32
Q

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 … ..
    • excessive … gain in infancy/childhood
    • adult …
A
  • 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
33
Q

Gut Microbiome

  • Gut microbiome - lots of cells in colon
  • More genes than in human genome
  • Integral to host …
  • Influenced by diet
    • high in .., high … etc
  • Influences disease risk
    • such as … and … diabetes
A
  • Gut microbiome - lots of cells in colon
  • More genes than in human genome
  • Integral to host homeostasis
  • Influenced by diet
    • high in fat, high fibre etc
  • Influences disease risk
    • obesity, T2 DM
34
Q

Gut Microbiome - Obesity and T2 Diabetes vs Normal

  • There are differences in gut …
    • can be induced by diet e.g. high fat diet
  • transplantation of faecal material alters … sensitivity
A
  • There are differences in gut bacteria
    • can be induced by diet e.g. high fat diet
  • transplantation of faecal material alters insulin sensitivity
35
Q

Regulation of Appetite & Weight

  • Slow-acting hormones that regulate body weight - what are 2 examples?
  • these signal % of … to hypothalamus
    • decreased …
    • increased … expenditure
  • rapid-acting peptides that regulate meal sizes - released from GI tract
    • PYY - does it inhibit eating?
    • Ghrelin - does it inhibit eating?
    • CCK - does it inhibit eating?
      • (act via …)
A
  • Slow-acting hormones that regulate body weight
    • leptin
    • insulin
  • signal %body fat to hypothalamus
    • leading to decreased food intake
    • increased energy expenditure
  • rapid-acting peptides that regulate meal sizes - released from GI tract
    • PYY - does it inhibit eating? - yes (up to 12 hours)
    • Ghrelin - does it inhibit eating? - no - stimulates it
    • CCK - does it inhibit eating? - yes
      • (act via hypothalamus)
36
Q

Hypothalamus - Arcuate nucleus

  • 2 groups of neurons - ‘… neurons’ and ‘… neurons’
  • Different peptides affect … behaviour and expenditure
A
  • ‘Acceletor neurons’ and ‘brake neurons’
  • Different peptides affect eating behaviour and expenditure
37
Q

Leptin and appetite/weight

  • ob/ob mouse on left - did it have leptin?
  • db/db mouse - plenty of leptin but …
  • ob gene product =
A
  • No - leptin deficient
  • db/db mouse - plenty of leptin but mutation of leptin receptor
  • ob gene product = lectin
38
Q

Leptin treatment … obesity in ob/ob mouse

A

Leptin treatment reduces obesity in ob/ob mouse

39
Q

Leptin (Humans)

  • Leptin is more of a ‘… signal’
  • Has a permissive effect on …/…
  • In obese humans - very rare examples of people who are …
    • leptin …
    • … of leptin receptor
  • Usually
    • increased leptin with … fat
    • in obesity - develop some form of leptin …
    • Also decreased … leptin transport with … fat
A
  • Leptin is more of a ‘Starvation signal’
  • Has a permissive effect on puberty/reproduction
  • In obese humans - very rare examples of people who are …
    • leptin deficient
    • mutation of leptin receptor
  • Usually:
    • increased leptin with increased fat
    • in obesity - develop some form of leptin resistance
    • Also decreased CNS leptin transport with increased fat
40
Q

Talking with patients - Obesity

  • Language matters
    • obesity is a medical definition but can be a problematic term for patients - why?
  • seek … to discuss weight
  • preferred terms to consider - what are these?
A
  • Language matters
    • obesity is a medical definition but can be a problematic term for patients - negative connotations and stigmatising
  • seek permission to discuss weight
  • preferred terms to consider - what are these?
    • Overweight
    • Carrying too much weight
41
Q

Lifestyle modifications - Obesity: Diet

  • Deficiency of … - … kcal energy deficiency
  • Low energy density
    • decrease … fats and …
    • increase … and …
  • decreased … sizes and snacking
  • structured meals / meal … may help promote greater weight loss
A
  • Diet
    • Deficiency of 500-1000 kcal energy deficiency
  • Low energy density
    • decrease saturated fats and sugar
    • increase fruit and beg
  • decreased portion sizes and snacking
  • structured meals / meal replacements may help promote greater weight loss
42
Q

Lifestyle modifications - Obesity: Physical Activity

  • Exercise … days a week
    • … mins moderate-high intensity OR
    • … mins low intensity
  • taking … steps / day
    • increase in … step increments
  • regardless of weight / weight loss, exercise increases health
A
  • Exercise 7 days a week
    • 30 mins moderate-high intensity OR
    • 60 mins low intensity
  • taking 10,000 steps / day
    • increase in 500 step increments
  • regardless of weight / weight loss, exercise increases health
43
Q

Very Low Calorie Diet and T2 Diabetes

  • Principle:
    • Primary care programme
    • Patients with T2 DM diagnosis <6 years prior
    • VLDC (830 kcal/day) for how long?
      • initially, total diet replacement with formulae
      • then stopped food reintroduction … - … weeks
      • long-term maintenance with structured support
  • Outcomes:
    • 12 month outcomes
    • …% of participants achieved 15kg loss or more
    • …% induced remission of T2DM
      • Normal HbA1c off all medication for 2 months
    • >10kg weight loss -…% remission
A
  • Principle:
    • Primary care programme
    • Patients with T2 DM diagnosis <6 years prior
    • VLDC (830 kcal/day) for 3-5 months
      • initially, total diet replacement with formulae
      • then stopped food reintroduction 2-8 weeks
      • long-term maintenance with structured support
  • Outcomes:
    • 12 month outcomes
    • 24% of participants achieved 15kg loss or more
    • 46% induced remission of T2DM
      • Normal HbA1c off all medication for 2 months
    • >10kg weight loss - 73% remission
44
Q

Lifestyle modification - Obesity and weight loss

  • Usual targets
    • …% weight loss
    • …-… lb per week
    • some evidence that ambitious goals promote … weight loss
  • problems
    • most patients can achieve 5-10% weight loss in a year
    • ‘yo-yo’ dieting / regaining weight lost
    • obesogenic environment
    • weight loss results in increased …, decreased …, decreased … rate
  • best hope :
    • sustainable lifestyle changes
    • diet combined with exercise / physical activity
    • ongoing management is required to maintain weight loss
A
  • Usual targets
    • 10% weight loss
    • 1-2 lb (0.5-1kg) per week
    • some evidence that ambitious goals promote more weight loss
  • problems
    • most patients can achieve 5-10% weight loss in a 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
45
Q

Pharmacological Therapy for Obesity

  • only 1 currently licensed drug - what is this?
A
  • orlistat
46
Q

Orlistat

  • Mechanism
    • Binds and inhibits … in the lumen of the gut
    • prevents the … of dietary fat into absorbable free fatty acids/ glycerol
    • excrete - …rd dietary fat
  • Adverse effects include:
    • flatulence, oily … leakage, diarrhoea
    • decreased absorption of … soluble vitamins
      • ADEK
        • Supplement
A
  • 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
  • Adverse effects include:
    • flatulence, oily faecal leakage, diarrhoea
    • decreased absorption of fat soluble vitamins
      • ADEK
      • Supplement
47
Q

Metformin

  • The best 1st line agent for … patients with … diabetes
    • ​used in diabetes prevention trials but not licensed for this use
  • recommended by NICE for prevention of … in adults at … risk
A
  • The best 1st line agent for over-weight/obese patients with Type 2 diabetes
    • ​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
48
Q

Pharmacological therapy for obesity

  • Problems
    • can only increase by …-… fold the proportion of patients who achieve 5% weight loss in a year
    • weight … after treatment stopped
  • The Future:
    • all identified … are potential therapeutic targets / options
      • … in combination most likely way forwards
A
  • Problems
    • 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
  • the future:
    • all identified gut peptides / neuropeptides / their receptors are potential therapeutic targets / options
      • gut hormones in combination most likely way forwards
49
Q

Surgical Treatment - Obesity

  • 2 options - what are they?
A
  • 2 options:
  1. Laparoscopic adjustable banding
  2. Roux-en Y gastric bypass
50
Q

Laparoscopic adjustable banding

  • Restrictive or not?
  • Inject/withdraw … to adjust … of the band
A
  • Restrictive or not - yes
  • Inject/withdraw saline to adjust diameter of the band
51
Q

Roux-en Y gastric bypass

  • It is both … and ….
  • Alterations in gut … and … acid flow contribute to weight loss
  • Complications include:
    • … deficiencies such as …
    • … syndrome
      • GI and vasomotor symptoms
    • Post-prandial …
A
  • Restrictive and malabsorptive
  • Alterations in gut hormones and bile acid flow contribute to weight loss
  • Complications include:
    • Micronutrient deficiencies such as iron, B12, folate, calcium, vitamin D - important to supplement
    • Dumping syndrome
      • GI and vasomotor symptoms
    • Post-prandial hypoglycaemia
52
Q

Roux-en Y gastric bypass - rat experiment

  • Plasma from operated rats to sham-operated rats - what was the effect?
A
  • ate 1/3rd less
53
Q

People who have had Roux-en Y gastric bypass surgery claim to feel …

A

more full - increased satiety

54
Q

Surgical treatment for Obesity

  • Advantages include:
    • weight loss of …%
    • resolve or improve …
      • brings …-savings
  • Disadvantages
    • Perioperative mortality/morbidity
      • depends on procedure and experience of surgeon
    • complications
      • requires … term follow up
    • some weight …
      • patients will still be obese
    • expense
      • though cost effective by … - … years, depending on co-morbidities and weight
A
  • Advantages include:
    • weight loss of 25-30%
    • resolve or improve co-morbitities
      • brings cost-savings
  • Disadvantages
    • Perioperative mortality/morbidity
      • depends on procedure and experience of surgeon
    • complications
      • requires long term follow up
    • some weight re-gain
      • patients will still be obese
    • expense
      • though cost effective by 2-5 years, depending on co-morbidities and weight
55
Q

UK position bariatric surgery - NICE guidelines

  • NICE 2005
    • referal only when?
    • BMI must be > … or > … with co-morbid conditions
    • First line treatment if BMI is > …
  • NICE 2014
    • Recent onset of … means you can:
      • Expedite surgery if BMI is > ….
      • Consider surgery if BMI > …
A
  • NICE 2005
    • referal only if failure of other options
    • BMI must be > 40 or > 35 with co-morbid conditions
    • First line treatment if BMI is > 50
  • NICE 2014
    • Recent onset of T2DM
      • Expedite surgery if BMI is > 35
      • Consider surgery if BMI > 30
56
Q

UK position bariatric surgery - NHS guidelines

  • NHS England 2013:
    • As per NICE but…
      • must have been obese for how long?
      • must engage with what?
A
  • must have been obese for at least 5 years
  • must engage with non-surgical weight-loss programme for 12-24 months first
57
Q

Public Health/Societal - Obesity

  • Schools - whats important?
  • Urban design to encourage …
  • Marketing/Media/Social media
    • food …, food …
A
  • Schools - PE, lunches, vending machines
  • Urban design - encouraging walking and cycling
  • Marketing/Media/Social media
    • food labelling, food adverts
58
Q
  • The combination of hypertension, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance, and obesity, particularly central obesity, has been termed the “…. syndrome.”
  • It has been proposed that this syndrome is a powerful determinant of … and … disease.
A
  • The combination of hypertension, dyslipidemia, insulin resistance, hyperinsulinemia, glucose intolerance, and obesity, particularly central obesity, has been termed the “metabolic syndrome.”
  • It has been proposed that this syndrome is a powerful determinant of diabetes and cardiovascular disease.

Year 2 Medicine (162 decks)

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