L11 - Appetite and Weight

Question 1

Measurements that can be done

Answer 1

BMI (kg/m^2
Waist circumference 
Skinfold thickness 
Bioelectrical impedance analysis 
Ethnicity specific cut offs

Question 2

Epidemiology in UK

Answer 2

stabilised at 25% between 2010-13

Question 3

What are the associated health problems with obesity?

Answer 3

Metabolic syndrome, T2 diabetes, CVS disease, Resp disease, liver disease, cancer, reproductive dysfunction, joint problems, psychological morbidity

Question 4

Metabolic syndrome

what is it?

What is the underlying pathophysiological mechanism?

Answer 4

group of closely related CV risk factors:
Visceral obesity 
Dyslipidaemia 
Hyperglycaemia 
Hypertension

Insulin resistance

Question 5

Obesity

How can it be described / measured

Answer 5

BMI vs body fat distribution
—–Central vs peripheral

Metabolic syndrome associated with

• —Central (visceral) fat
• —BMI > 30

Question 6

T2 Diabetes Mellitus

risk is determined by what

why is the prevalence increasing

Answer 6

Age, obesity, family history, ethnicity

↑Age population, ↑ obesity (T2 younger), ↑ detection / diagnosis, ↑survival with T2 DM

Question 7

CV Disease

what happens with this

Answer 7

Metabolic syndrome AND 
↑blood volume and blood viscosity 
↑ vascular resistance 
↑ hypertension 
↑ left ventricular hypertrophy 
↑ coronary artery disease 
↑ stroke

Question 8

respiratory system - how can this be associated with obesity

Answer 8

Obstructive sleep apnoea
Hypoxia / hypercapnia
Pulmonary hypertension - right heart failure
Accidents - daytime somnolence

Question 9

Cancer

what types of cancer are associated with obesity

What is the mechanism of this

Answer 9

10% cancer deaths in non smokers attributable to obesity

Types: breast, endometrial, oesophagus, colon, gall bladder, renal, thyroid

Mechanisms: ↑ insulin, ↑ free IGF-I, ↑ oestrogen, apido-cytokines, reflux

Question 10

Reproductive system

how is this associated with obesity

Answer 10

Polycystic ovarian syndrome:

• —Oligomenorrhoea, hirsutism, acne
• —Subfertility
• —Endometrial hyperplasia
• —Insulin resistance

Male hypogonadism

Adverse pregnancy outcomes

Question 11

Joints

how are these associated with obesity

Answer 11

Osteoarthritis

Gout

Question 12

Psychological

how are these associated with obesity

Answer 12

Depression

Eating disorders

Question 13

Genetics of obesity

Answer 13

RARE:
Obesity associated syndromes
Prader-Willi
Bardet-Biedl

COMMON
Polygenic
Susceptibility genes
Heritability of weight ~ heritability of height

Question 14

Other causes of obesity

Answer 14

hypothyroidism

Cushing’s syndrome

Question 15

Environmental factors of obesity

Answer 15

Diet: high fat and sugar, ‘coca-colonisation’ of developing world, socio-economic factors

Physical activity: 20-50% total energy expenditure, obesity prevalence related to proxy measures of physical activity (car ownership, TV viewing), socioeconomic factors

Question 16

Fetal programming

what is it, how and why can this cause obesity

Answer 16

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 17

Life course model

what is it and why can this happen

Answer 17

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

Question 18

Gut microbiome

what can it be influenced by and what can it influence and alter and how

Answer 18

Influenced by diet
Influence disease risk: Obesity, T2 diabetes etc

Differences in gut bacteria can be induced by diet etc high fat diet
Faecal transplant alters insulin sensitivity

Question 19

What hormones regulate body weight and how

Answer 19

leptin , insulin

slow acting

signal % body fat to hypothalamus

decr food intake and ↑ energy expenditure

Question 20

What peptides regulate meal sizes

where are they released what do they act on

Answer 20

Released from GI tract

Cholecystokinin (CCK) - decr eating
Ghrenlin - ↑ eating
PYY – ¯ eating up to 12 hrs

Act via hypothalamus

Question 21

Leptin

what happens with it in mice and humans

Answer 21

deficiency in mice causes obesity

In humans has permissive effect on puberty

very rare for humans to have leptin deficiency / receptor mutation

usually incr in leptin with incr in fat

Question 22

Lifestyle modification for obese patients: DIET

Answer 22

200-1000 kcal energy deficiency

low energy density

decr sat fat an d sugar
incr fruit and veg
decr portion sizes and snacking

structured meals / meal replacements may help promote weight loss

Question 23

Lifestyle modification for obese patients: PHYSICAL ACTIVITY

Answer 23

7 days a week
30 min moderate-high intensity
60 low intensity
target 10,000 steps
in increasing 500 step increments

Question 24

VLCD and T2 DM

what are usual targets

what are the problems for obese people to loose weight

Answer 24

10% weight loss
0.5-1kg per week

evidence that more ambitous goals promote weight loss

PROBLEMS:
most can achieve 5-10% weight loss but yo yo dieting / regaining weight lost

also obesogenic environment

weight loss results in hunger and decr in satiety and metabolic rate

BEST HOPE
-Sustainable lifestyle changes
–Diet combined with exercise / physical activity
–Ongoing management is required to maintain weight loss

Question 25

Pharacological Therapy:

what is available. what do they do and what are the adverse effects

Answer 25

ORLISTAT
binds to an inhibits lipases in gut lumen
prevents hydrolysis of dietary fat into absorbably FA+glycerol.
ADVERSE EFFECTS: flatulence, oily faecal leakage diarrhoea
—-decr in absorption in fat sol vitamins

METFORMIN
best 1st line agent for obese and T2 DM patients
all other hypoglycaemic and insulin cause weight gain
Used unlicensed in dM prevention trials

Question 26

Pharmacological Therapy: general terms what are the problems and what is the future

Answer 26

prob - weight gain after treatment stopped

future: All identified gut peptides / neuropeptides / their receptors are potential therapeutic targets / options

Question 27

Surgical Treatment

what is available and what do they do

Answer 27

Laparoscpoic adjustable banding
Restrictive only
Inject / withdraw saline to adjust the diameter of the band

Roux-en-Y gastric bypass
Restrictive
Mal-absorptive
Alterations in gut hormones and bile acid flow contribute to weight loss

Question 28

What happens with Rout-en-Y gastric bypass

effects and adverse effects

Answer 28

Micronutrient deficiencies
—Supplement with iron, B12, folate, calcium, Vit D
Dumping Syndrome
—-GI and vasomotor symptoms

Endocrine factors important in effects
—-Plasma from operated rats to sham-operated rats ate 1/3 less
Increased satiety seems to be the key
—Don’t enjoy the same junk foods anymore
—-F-MRI studies

Question 29

Surgical Treatment

general terms advantages and disadvantages

Answer 29

ADVANTAGES OF SURGICAL
Weight loss 25-30%. Resolve or improve comorbidities, brings cost savings

DISADVANTAGES
Perioperative mortality / morbidity
—Depends on procedure and surgeon experience
Long term follow up
—Micronutrient deficiencies
Some weight re-gain
Expense: though cost effective by 2-5 years

Question 30

NICE guidelines and NHS England on bariatric surgery

Answer 30

NICE 2006
After failure of other options if BMI > 40kg/m2 or >35 with comorbid conditions

Or first line if BMI >50

Nice 2014
Recent onset T2DM:
Expedite bariatric surgery if BMI > 35
Consider surgery if BMI > 30

NHS England 2013
As per nice but
Mist have been obese for at least 5 years
Must engage with no surgical weight loss programme for 12-24 months first

Question 31

Public health and societal factors in obesity and weight loss

Answer 31

School: PE, lunches vending machines
Urban design
Marketing / media / social media
Food labelling, flood advertisements