L14 - Appetite and Weight COPY

Question 1

OBESITY - MEASUREMENTS

i) what is principally used to measure obesity?
ii) name three other methods of measuring
iii) what is a BMI of an individual who is overweight?
iv) what is an obese BMI?
v) what is a morbidly obese BMI?

Answer 1

i) BMI = kg/m2
ii) waist circumference, skin fold thickness, bioelectric impedance analysis
iii) overweight = 25-29.9
iv) obese = 30-39.9
v) morbidly obese >40

Question 2

METABOLIC SYNDROME

i) what can it be defined as?
ii) name four characteristics associated with metabolic syndrome
iii) what is the underlying pathological mechanism?
iv) name two principal things the syndrome is associated with

Answer 2

i) constellation of closely associated CV risk factors
ii) visceral obesity (fat around organs), dyslipidaemia (high choles), hyperglycaemia, hypertension
iii) insulin resistance
iv) central/visceral fat and BMI >30

Question 3

INSULIN RESISTANCE AND METABOLIC SYNDROME

i) how are fatty acid levels affected? name three things that mediate this
ii) what molecules are released from tissues? name two
iii) how is expression of the GLUT4 receptor affected?
iv) how is tyrosine kinase activity of the insulin receptor affected?
v) what is an adipocytokine?

Answer 3

i) increase in free fatty acids
- lipolysis of visceral fat, gluconeogenesis and dyslipidaemia

ii) release of pro-inflam cytokines eg TNFa and IL-6
iii) decreased expression of GLUT4
iv) decreased tyrosine kinase activity of insulin R
v) cytokines produced by fat that have diffuse effects

Question 4

OBESITY AND T2DM

i) name four things risk is determined by
ii) what two main groups of people does it affect?
iii) what % of T2DM cases are picked up on routine examination?

Answer 4

i) age, obesity, family history and ethnicity determine risk
ii) rich in poor countries and poor in rich countries
iii) 50% cases picked up on routine exam

Question 5

CV DISEASE & OBESITY

associated with metabolic disease plus:

i) how is blood volume/viscosity affected
ii) how is vascular resistance affected
iii) what does strain on the heart cause?

Answer 5

i) increase in blood volume and viscosity
ii) increased vascular resistance
iii) strain on the heart causes left ventricular hypertrophy

Question 6

OBESITY & RESPIRATORY SYSTEM

i) how can sleep be affected? what can this lead to?
ii) what condition can develop and cause right heart failure

Answer 6

i) can cause obstructive sleep apnoea which can lead to hypoxia and hypercapnia
ii) pulmonary hypertension can cause right heart failure

Question 7

OBESITY & GI/LIVER

i) what type of liver disease do 90% of obese people have?
ii) what do 1 in 5 of these people progress to?
iii) what do 1 in 5 of these patients progress to?
iv) name two other things obesity can be associated with?

Answer 7

i) non alcoholic fatty liver disease (NAFLD)
ii) 20% of NAFLD progress to non alcoholic steatohepatitis (NASH)
iii) 20% of NASH progress to cirrhosis and chronic liver disease
iv) obesity can also be associated with gallstones and reflux

Question 8

OBESITY AND CANCER

i) what has obesity recently overtaken as the most important cancer risk factor
ii) name three mechanisms cancer can be mediated by?
iii) what may be associated with oesophageal cancer?

Answer 8

i) obesity has recently overtaken smoking
ii) increased insulin, increased free IGF1 and increased oestrogen
iii) reflux can be associated with oesophageal cancer

Question 9

OBESITY AND THE REPRODUCTIVE SYSTEM

i) what syndrome can obesity cause? give four associated symptoms
ii) how can male sex hormones be affected? why?
iii) how does weight loss affect testosterone levels?

Answer 9

i) PCOS
- oligomenorrhoea, hair growth, acne, subfertility, endometrial hyperplasma and insulin resistance

ii) can cause male hypogonadism due to conversion of testosterone to oestrogen in adipose tissue
iii) weight loss can increase total testosterone

Question 10

OBESITY GENETICS

i) name two rare obesity associated syndromes
ii) what type of genetic profile is more commonly seen?
iii) name two other causes of obesity (not genetic)

Answer 10

i) prader willi and bardet biedl
ii) polygenic
iii) cushings and hypothyroidism

Question 11

FOETAL PROGRAMMING

i) what is ‘programming’
ii) name two stressors in utero
iii) what is the mechanism of FP? give three examples of this
iv) what can be associated with high cortisol in later life?

Answer 11

i) stimuli or insults at critical periods in utero that have persistent biological effects
ii) undernutrition and lack of availability of trace elements

iii) FP mechanism is epigenetic modification of gene expression
- eg programmed adrenal axis overactivity in adulthood, causal factors for metabolic syndrome and increased vuln to CVD

iv) low birth weight

Question 12

LIFE COURSE MODEL

i) what is the basis of it?
ii) name three things worst outcomes are associated with?

Answer 12

i) factors operating at every stage of life affect health outcomes later in life

ii) worse outcomes associated with
- low birth weight
- excess weight gain in childhood/infancy
- adult obesity

Question 13

GUT MICROBIOME

i) what influences the microbiome?
ii) what does the microbiome influence?
iii) what has been observed in patients with T2DM? what can this be induced by?
iv) what has transplantation of faecal matter been shown to alter in mice and humans?

Answer 13

i) diet
ii) disease risk
iii) differences in gut bacteria have been shown in T2DM which can be induced by diet (high fat)
iv) transplantation of faecal matter has been shown to alter insulin sensitivity

Question 14

REGULATION OF APPETITE AND WEIGHT

i) name two slow acting hormones that regulate body weight
ii) which brain area recieves signals from body fat? what two things does it adjust accordingly?
iii) name three rapid acting peptides released from the GI tract that regulate meal size and the effects of each?

Answer 14

i) leptin and insulin
ii) hypothalamus recieves signals from body fat and this adjusts food intake and energy expenditure

iii) CCK - inhibits eating
Ghrelin - stimulates eating
PYY - inhibits eating by acting on the hypothalamus

Question 15

HYPOTHALAMUS

i) what two classes of neurons are found that are associated with eating heaviour and energy expenditure
ii) what effect does neuropeptide Y have on eating?
iii) where does the HT receive lots of info from in order to regulate eating and energy expenditure?

Answer 15

i) accelerator neurons eg NPY and brake neurons eg POMC
ii) neuropeptide Y promotes eating
iii) HT receives input from the gut and adipose tissue

Question 16

LEPTIN MICE

i) what is the ob/ob mouse?
ii) what is the db/db mouse?
iii) what is the ob gene product?
iv) what happens if you treat an ob/ob mouse with leptin?

Answer 16

i) leptin deficient mouse = obese
ii) mutation in the leptin receptor = obese
iii) ob gene product is leptin
iv) the ob mouse will lose weight

Question 17

LEPTIN IN HUMANS

i) what can it be used to signal?
ii) what effect does it have on puberty/reproduction?
iii) what two things are very rarely seen in obese humans (think mice)
iv) what usually happens in humans with increased fat
v) what happens to CNS leptin transport as body fat increases?

Answer 17

i) satiety

ii) permissive effects on puberty/reproduction
- signalling sufficient body fat stores

iii) leptin deficiency or mutation in the leptin receptor
iv) increased leptin production with increased fat
v) as body fat increases CNS leptin transport decreases

Question 18

LIFESTYLE MODIFICATION

i) what Kcal deficiency should patients be aiming for?
ii) which two things may help promote greater weight loss when used initially?
iii) how much high and low intensity exercise should be aimed for per week?

Answer 18

i) 500-1000 per day
ii) structured meals or meal replacements
iii) 30 mins moderate/high intensity or 60 mins low intensity

Question 19

V LOW CALORIE DIET (VLCD) AND T2DM

i) name two conditions that should be met for patients to enrol on this diet
ii) how many kcal per day are advised and for how long?
iii) what does the diet start with? what happens at 2-8 weeks?
iv) over 12 months - what % of participants achieved 15kg weight loss or more?
v) what % had induced remission of T2DM
vi) what % had normal HbA1c off all meds for 1 month and >10kg weight loss?
vii) what is the name of the study that investigated this

Answer 19

i) T2DM and < 6 years since dx
ii) 830kcal per day for 3-5 months
iii) start with total diet replacement with formulae then at 2-8 weeks start food reintroduction
iv) 24% had >15kg of weight loss
v) 46% had remission of T2DM
vi) 73% had normal HbA1c/off meds>10kg weight loss
vii) DIRECT trial

Question 20

LIFESTYLE MODIFICATION TARGETS AND CHALLENGES

i) what is the usual target % weight loss? what does this equate to per week?
ii) what can weight loss result in due to homeostatic mechanisms trying to match energy expend and food intake?

Answer 20

i) 10% weight loss - equals 1-2lb per week
ii) increased hunger, decrease satiety and decreased metabolic rate

Question 21

PHARMACOLOGICAL THERAPY FOR OBESITY

i) what is the only current licensed treatment?
ii) what mechanism does it work via in relation to the gut and dietary fat?
iii) what does this result in?
iv) name four adverse effects
v) what may be needed to be given along side it to prevent some of the SEs?

Answer 21

i) orlistat

ii) binds and inhibits lipases in the lumen of the gut
- prevents hydrol of dietary fat into absorbable FFAs and glycerol

iii) this results in excretion of 1/3 of dietary fats
iv) adverse effects = flatulence, oily faecal leakage, diarrhoea and decreased abs of fat soluble vitamins
v) vitamins ADEK

Question 22

METFORMIN

i) which group of patients does this aid weight loss in?
ii) is it licenced for use in weight loss?
iii) what do the NICE guidelines reccomend it should be used for?

Answer 22

i) patients with T2DM
ii) no
iii) NICE say it should be used for the prevention of T2DM in adults at high risk (not weight loss)

Question 23

PROBLEMS/FUTURE OF PHARMA THERAPY FOR OBESITY

i) name two main problems of this treatment in relation to amount of weight loss and relapse
ii) give three things that are potential therapeutic targets for weight loss

Answer 23

i) pharma therapy helps patients achieve around 5% weight loss in a year and many will therefore still be obese
- weight re gain can occur after treatment is stopped

ii) gut peptides, neuropeptides and their receptors in the hypothalamus may all be targets

Question 24

SURGERY - LAPROSCOPIC ADJUSTABLE BANDING

i) what does it do?
ii) how do you adjust the diameter of the band?

Answer 24

i) makes stomach smaller = restrictive
ii) injecting or withdrawing saline

Question 25

ROUX EN Y GASTRIC BYPASS

i) which two ways does it work? how does it do this?
ii) alterations in which two things contribute to weight loss?
iii) name three complications and four things patients may need to be supplemented with
iv) how long do patients need to be followed up for?
v) what endocrine effects were seen in rats that had the surgery compared to those that didnt?
vi) what effect may it have on satiety?

Answer 25

i) both restrictive and malabsorptive
- allows bypass of early duodenum where lots of abs happens

ii) alterations in bile acid flow and gut hormones help weight loss

iii) micronutrient deficiencies, dumping syndrome and post prandial hypoglycaemia
- supplement with B12, folate, calcium and vitamin D

iv) patients need life long follow up
v) rats that had the surgery ate 1/3 less than those who didnt
vi) can increase satiety - patients eat less and feel fuller earlier

Question 26

ADV/DISADV OF SURGICAL TREATMENT

i) what % of weight loss does it often give?
ii) what effect may it have on other co-morbidities?
iii) name four disadvantages

Answer 26

i) 25-30%
ii) may resolve or improve other comorbidities
iii) perioperative mort or morbid, complications, some weight regain and expense

Question 27

SWEDISH OBESITY SUBJECTS STUDY

i) what does it do?
ii) which two operations are involved?
iii) what did it show?
iv) what effect did surgery have on fatal CV events?
v) name three things changes were also seen in

Answer 27

i) ongoing non randomised trial that compares patients receiving surgery to obese controls
ii) look at banding and bypass operations
iii) showed that those having surgery are more likely to have more weight loss (espec bypass sx)
iv) decreased fatal CV events
v) changes in BP, cholesterol and HbA1c

Question 28

NICE GUIDELINES ON BARIATRIC SURGERY

i) at what BMI does NICE 2006 advise patients should have surgery after failure of other options - with and without comorbid conditions?
ii) at what BMI should surgery be given first line?
iii) at what BMI does NICE 2014 advise that bariatric surgery should be expedited if the patient has T2DM? at what BMI should sx at least be considered?
iv) according to NHS england - what two conditions must a patient meet to get bariatric sx?

Answer 28

i) no co morbid = BMI > 40
co morbid = BMI >35

ii) BMI > 50 = give sx first line

iii) if patient has T2DM sx should be expedited if BMI >35
- consider if BMI is >30

iv) obese for last 5 years and must have engaged with non surgical weight loss for 12-24 mnths prior