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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
_Covid 19 and Impact of lockdown on Obesity_ * increased ... of food * increased ...-induced eating * decreased ... health * reduced ... * less access to ...-management services
* increased **stockpiling** of food * increased **stress**-induced eating * decreased **mental** health * reduced **exercise** * less access to **weight**-management services
26
27
_Aetiology of obesity_ * ... factors * ... factors * programming * gut ...
* genetic factors * environmental factors * programming * gut microbiome
28
_Genetics - obesity_ * Rare - Obesity-associated syndromes * ...-willi * ...-biedl * Common - polygenic * ... genes * heritability of weight - similar to heritability of ...
* Rare - Obesity-associated syndromes * prader-willi * bardet-biedl * Common - polygenic * susceptibility genes * heritability of weight - similar to heritability of height
29
Other causes of obesity (endocrine) include... (2)
* hypothyroidism * Cushing's syndrome
30
_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
* 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
_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?
* '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
_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 ...
* 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
_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
* 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
_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
* There are differences in gut **bacteria** * can be induced by diet e.g. high fat diet * transplantation of faecal material alters **insulin** sensitivity
35
_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 ...)
* 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
_Hypothalamus - Arcuate nucleus_ * 2 groups of neurons - '... neurons' and '... neurons' * Different peptides affect ... behaviour and expenditure
* '**Acceletor** neurons' and '**brake** neurons' * Different peptides affect **eating** behaviour and expenditure
37
_Leptin and appetite/weight_ * ob/ob mouse on left - did it have leptin? * db/db mouse - plenty of leptin but ... * ob gene product =
* **No - leptin deficient** * db/db mouse - plenty of leptin but **mutation of leptin receptor** * ob gene product = **lectin**
38
Leptin treatment ... obesity in ob/ob mouse
Leptin treatment **reduces** obesity in ob/ob mouse
39
_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
* 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
_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?
* 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
_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
* 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
_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**
* 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
_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
* 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
_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
* 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
_Pharmacological Therapy for Obesity_ * only 1 currently licensed drug - what is this?
* orlistat
46
_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
* 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
_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
* 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
_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
* 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
_Surgical Treatment - Obesity_ * 2 options - what are they?
* 2 options: 1. **Laparoscopic adjustable banding** 2. **Roux-en Y gastric bypass**
50
_Laparoscopic adjustable banding_ * Restrictive or not? * Inject/withdraw ... to adjust ... of the band
* **Restrictive or not - yes** * Inject/withdraw **saline** to adjust **diameter** of the band
51
_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 ...
* **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
_Roux-en Y gastric bypass - rat experiment_ * Plasma from operated rats to sham-operated rats - what was the effect?
* ate 1/3rd less
53
People who have had Roux-en Y gastric bypass surgery claim to feel ...
more full - increased satiety
54
_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
* 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
_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 \> ...
* 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
_UK position bariatric surgery - NHS guidelines_ * NHS England 2013: * As per NICE but... * must have been obese for how long? * must engage with what?
* must have been obese for **at least 5 years** * must engage with **non-surgical weight-loss programme for 12-24 months first**
57
_Public Health/Societal - Obesity_ * Schools - whats important? * Urban design to encourage ... * Marketing/Media/Social media * food ..., food ...
* Schools - **PE, lunches, vending machines** * Urban design - **encouraging walking and cycling** * Marketing/Media/Social media * **food labelling, food adverts**
58
* 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.
* 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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