obesity Flashcards
obesity:
- Due to accumulation of body fat ( aka — )
-Fat is stored in special cells aka —
-Three types of adipocytes which are — , — , —
-Obesity is associated with — fat
- — fat is involved in heat production (aka — )
-Adipocytes are — active
-In obese patients adipocytes become —
adiposity
adipocyte
white brown beige
white
brown
hormonally
thermogenesis
pro inflammatory
obesity as a disease:
-Obesity accepted as a disease by American Medical Association in 2013
-Obesity is defined as “a chronic, relapsing, multifactorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”(Obesity Medicine Association)
Even when BMI returns to normal range, continued use of anti-obesity medications may be required to manage underlying —
metabolic dysfunction
1- percentage of – is the most important measure of obesity
-Multiple methods
-Skinfold measurements
-Electrical impedance measurements
-Calculated from average density
–>Requires a pool
-Dual energy X-Ray absorption
–>Most —
2- what is too fat:
-Depends!
-Cultural definition
-Scientific definition
-Depends on — , — , —
-Some cultures consider fat to be attractive
-Some consider slim to be attractive
-Changes with time
( palaoethic age believed in carved women )
body fat
accurate
sex age and lifestyle
1- obesity metrics include:
Body-mass index
Waist hip ratio
Waist-height ratio
Body Roundness Index
Weight-adjusted waist index
Tri-ponderal Mass Index
2- body mass index:
-Weight is not helpful as it does not take into consideration—
-% body fat — accurate but can be difficult to measure
- Body mass index (BMI)
–> Kg/m2
–>What about muscle?
- BMI is not ideal but if used should be tailored to — , – , –
height
most accurate
( info: MHO: Metabolically healthy obese
MUO: Metabolically unhealthy obese)
age sex and race
1-
- — more important than absolute weight reduction
- — changes in weight can produce significant health benefits
-Not necessary to achieve BMI 25
2- fat distribution:
-BMI relates to —
-Different body types
- – but not – adiposity is strongly associated with increased mortality
-Abdominal fat is associated with — fat ( — obesity)
-Visceral fat is — active
–>Adipokines
–> Associated with —
-Weight distribution is important
-Anthropometricmeasures of fat distribution
–> — circumference
–>— ratio
–> – circumference
-Typical cut-off is – cm men and — cm women
-All have been shown to be better predictors of outcome than BMI
% reduction
small
absolute weight
abdominal but not hip
visceral
central
hormonally
type ii diabetes
waist
waist hip
neck
38 cm
34 cm
Beyond BMI: Waist-height ratio (WHtR):
-Visceral fat is more harmful than —
-Increased visceral fat leads to increased — circumference
- – circumference needs to be included in any metric
- — ratio is a better predictor of mortality than —
-Increased mortality with accumulation of — but not lower limb fat (lipedemia).
subcutaneous
waist
waist
waist:height
BMI
visceral
- Beyond BMI: Body Roundness Index (BRI) :
-BRI uses — measurement and — to calculate — of the body
-Based on the concept of —
–> Deviation from circularity
–> Perfect circle = –
—> Straight line =–
-Value from 1 ( — ) to 20 (—)
check formula slide 32 - Beyond BMI: Weight-adjusted waist index (WWI):
-Weight-adjusted waist index (WWI) is a – marker of obesity that uses — and – measurements
WWI= waist circumference (cm)/√weight (kg)
-WWI has been shown to predict all cause
waist
height
shape
eccentricity
0
1
narrow
round
new
weight and waist
beyond BMI: TMI :
-BMI developed as a —-based tool not an — diagnostic
-Known to be inaccurate in—
–>Use Tri-ponderal Mass Index (TMI; kg/m3)
—>Overweight (Boy/Girl): 16.0 & 16.8 kg/m3
–>Obese (Boy/girl): 18.8 & 19.7 kg/m3
-Individuals with high — mass may be affected as well
population
indivuial
adolcencts
muscle mass
metabolic syndrom:
Three of the following:
-High —
- — levels of – cholesterol
- – levels of —
- Large – circumference
- – blood pressure
- A cluster of symptoms that are associated with the progression of atherosclerosis
-Adipocytes are not just fat storage cells, they are also — active and secrete multiple — including
–>Leptin
–>Adiponectin
–>Tumour necrosis factor a
–>Interleukin 6
-These cytokines are involved in – , — resistance and — and — syndrome
- info:
The relationship between increased visceral adipose tissue with an increased risk for endothelial dysfunction that manifests as hypertension, insulin resistance, and overt diabetes mellitus with left ventricular hypertrophy and long-term cardiovascular risk. RAAS indicates renin-angiotensin-aldosterone system; SNS, sympathetic nervous system; BP, blood pressure.
blood glucose
low
hdl
high
tricgylcrides
waist
high
hormonally active
cytokines
obesity , insulin , inflammation , metabolic syndrome
- true or false being metabolically healthy is more important than weight for risk in heart failure
- weight loss in elderly:
Hazzard rate (HR) for all cause mortality in adults > 70 years of age - stable ( <5% weight change ) f:m 1:1
- 5-10% weight loos female 1.33 and male is 1.26
->10% females 3.89 and makes 2.14
true
-BMI v’s fitness:
- — fitness reduced all-cause and CVD mortality (HR: 0.7/0.73)
- – fitness reduced all-cause and CVD mortality (HR: 0.61/0.58)
-1 metabolic equivalent (MET) gain in fitness associated with — reduction in all-cause mortality
- — change had no effect on mortality when controlled for –
- MET stands for —
-1 MET is an approximate measure of— metabolic rate 3.5 mL O2/kg/min
-Measured in kcal.kg-1.hr-1
-A 2 METs task is — the energy use of—
stable
increased
15%
BMI
fitness
metabolic equivalent of task
basal
double
resting
exercise:
1- type:
-A combination of – and — produced the best cardiometabolic health-related outcomes.
-Next best was — exercise
- – training (at least once per week) added additional benefit on top of aerobic exercise
2- duration;
-Maximum benefit with
- — min/week vigorous physical activity
- — min/week moderate physical activity
-Moderate activity — METs,
walking, weightlifting, calisthenics.
-Vigorous activity — METs, including jogging/running, swimming, cycling, playing squash/racquetball or tennis, climbing stairs.
info:
Strength training (at least once per week) added additional benefit on top of aerobic exercise
RR total mortality 0.89
aerobic and resistance
hybrid
strength
15-300
600
less than 6
more than 6
- — is not very effective at losing weight , Very difficult to burn off excess calories
-However, people often do not feel hungry after a work out
-In mice exercise – production of N-lactoyl-phenylalanine (Lac-Phe)
-Administration of Lac-Phe to obese mice – calorie intake
-Humans also produce Lac-Phe
-May have potential in treating – - — and – to exercise in mice is impacted by gut microbiome and not –
- — therapy reduced exercise levels , — level of gut microbiome
-Microbiome produces — that activate the endocannabinoid system
excercise
increases
reduces
obesity
motivation and capacity
not genetics
antibiotic
reduced
fatty acids amides
low risk factors:
Exercise
Healthy diet
Non-smoker
Moderate alcohol intake
Risk factors more important than BMI
Comparison of sedentary Western people with African hunter-gather tribe (Hadza) and humans with great apes
Despite much higher activity levels in Hadza, their daily energy expenditure is similar to sedentary individuals
Humans have higher energy expenditure than apes
Humans have fixed energy expenditure - increased activity does not lead to reduced obesity
- EXCERSISE PARADOXES:
-Increased physical activity does not lead to increased —
-Occupational physical activity is related to increased — impairment and — disease which is greater with jobs involving — and —
-Likely due to many factors including:
Lack of — , — , low — stimuli, — factors
increased weight loss
cognitive and cardiovascular
lifting and carrying
autonomy , stress , cognitive , socioeconomics
-causes of obesity:
-Primarily due to — imbalance aka energy — exceeds energy —
-Energy expenditure depends on – and level of —
-Obesity is a disease of — not —
- set point theory:
-Body has a– weight (set point) determined by environment, genetics etc
- — factors regulate energy expenditure and hunger to maintain set point
-Obesity arises when — principles fail
-New set point is established
-Makes body – actions of dieting
energy
consumption
expenditure
basal metabolic rate and level of activity
over eating
metabolism
fixed
homeostatic
homeostatic
resist
Obesogens are – disrupting — (EDC) that trigger —
-Many are found in our environment
-Approximately 1,000 chemicals have been identified as EDCs
-Components of – :
–>Bisphenol A (BPA)
–> Phthalates
-Polycyclic aromatic hydrocarbons (PAHs)
-Polychlorinated biphenyls (PCB)
endocrine
chemicals
obesity
plastic
eating and hormones:
1- Ghrelin
- – hormone triggers the desire to—
- Produced in —
-Ghrelin/growth hormone secretagogue receptor (GHS-R )
-Arcuate–
-Activates — pathways triggering – signal
2- Leptin
-Satiety hormone – further eating
-Produced by — tissue
- – secretion pro-opiomelanocortin (POMC)
- precursor for —- stimulating hormone
-Arcuate –
3- treatment of obesity:
Behavioural therapy
Dietary therapy
Pharmacological therapy
Surgery
hunger
eat
stomach
nucleas
dopamine
reward
stops
adipose tissue
increases
alpha and beta melanocyte
nucleas
weight loss:
1- decrease —
Diet
22 kcal required to maintain – kg
100 kg woman requires 1860-2620 kcal per day
Reduction in intake of — kcal/day below maintenance level results in 0.5 kg loss/week
2- increase —-
For average adult
Staying in bed 1150 kcal/day
For a distance of 1,600 m (1 mile)
Running (M/F) 124/105 calories
Walking (M/F) 88/74 calories
- sumo diet :
is a very — calorie intake (6,000-20,000 kcal/day)
No breakfast
Large lunch followed by sleep
Late dinner with lots of beer
- other diet types:
Balanced low calorie
Low-fat
Low-carbohydrate
High-protein
Mediterranean
Very low-calorie diet
Fasting
Fad
energy consumption
1 kg
500
energy ependiture
high
1- Network meta-analysis of moderate macronutrient (MM) diet, high fat low carbohydrate (HFLC) and low fat high carbohydrate (LFHC) diet for minimum of 12 months.
All diets worked
— diet tended to be better than others
Depends of adherence!
2- fasting:
Animal data: fasting prolongs life
Fasting
3.5 days no food
Alternative day fasting (ADF)
Day 1: 0% (ADF) or 20% of calories (400-500 kcal) (modified ADF)
Day 2 no restrictions
5:2 diet
5-days normal diet
2 non-consecutive fasting days (20%)
Time-restricted eating
>12 hrs fasting per day
MADF and 5:2 were associated with significant —
Weight-loss plateaued at 6 months
Reduction in multiple— markers
3- sleep and obesity:
-Sleep plays a role in obesity
-Extending sleep from by average 1.2 hrs per day in volunteers sleeping less than 6.5 hrs per day reduced energy intake by 270 kcal per day
-Reduced sleep is associated with increased— levels
HFLC
weight loss
metabolic
gherlin
weight cycling:
-Patients often lose and regain weight (weight cycling)
-This variability in weight is an — risk factor for all-cause and—- mortality
-Quartile — with the highest variability in BMI had a hazard ratio of – for all-cause mortality and — for CV mortality
-Possibly due to increased formation of metabolically active— tissue and increased—
- best diet:
-Acute v’s chronic weight loss
-Adherence is critical
-All of the diets seem to work
if you stick to them
- >800 kcal/day should be used
-Loss of fat v’s muscle/water
-Fasting diets may prolong life
-Maintaining weight loss
Exercise beneficial here
-Health risk of diets
-Atkins diet associated with increase — mortality
Due to increased —
-Erythritol (artificial sweetener) associated with increased —
Due to increased – activation
independent
cardiovascular
4
4
15
adipose tissue
inflammation
CVD
cholesterol
MI
platelt
-Weight loss in people with obesity causes changes in — hormones that increase hunger and the desire to eat for at least 1 year
-Multiple hormones, such as ghrelin, glucagon-like peptide-1 (GLP-1) and leptin, play an important role in regulating –
pharmacotherapy:
1- Semaglutideproduced – reduction in weight compared with placebo over 104 weeks (Step 5 Trial)
-Semaglutide – than liraglutide
-Tirzepatideproduced 15% reduction in weight compared with placebo over 72 weeks (SURMOUNT-1 trial)
-Use in obesity has lead to shortage of drugs for —
There is significant increase in GI adverse effects:
— , — obstruction , —
2-Ozempic face:
Semaglutide ( — ) causes significant weight loss
Leads to — of the face making them appear older
Patients often seek plastic surgery
appetite
appetite
15%
better
diabetics
pancreatitis , bowel , gastroparesis
ozempic
wrinkling
1- benefit of surgery:
-Recommended for patients with BMI > —
-Average 60% weight in excess of BMI of 25 lost
-Hyperlipidemia, hypertension and diabetes resolved (70% cases)
-Increased risk of – and —
No evidence of benefit for –
- — is better than GLP-1 agonists for weight loss
- Equipotent for – control
2- non surgical approach:
Gelesis100(Plenity®)
- – that absorbs water, expands and shrinks the –
-Made from plant/fruit fibres
-Weight loss with Gelesis100(24-week study)
5%: 59% vs 27%
10%: 42% vs 15%
-Approved by FDA in 2019
No —
40
suicide and self harm
liposuction
Bariatric surgery
glycemic
hydrogel
stomach
adverse effects
- determine the risk m BMI is a start but we need to consider:
Muscle mass
Patient profile
Age
Race
Sex
Metabolic health
Blood pressure
Blood sugar
Cholesterol
Life style
Diet
Exercise
Smoking habit
Alcohol intake - treating obesity:
- Focus on — changes
-Exercise
-Weight-loss diet
-Any diet that works for the patient
-Reduced calorie intake and adherence are most important
-Maintenance diet
->Needs to be healthy
->Low salt and sugar
->High fibre - — if life style therapy does not work
- — an option if pharmacotherapy is not effective or not desirable
- — changes essential to maintain weight-loss and to achieve health benefits
-Weight loss
–> — changes <10%
–> — <21%
–>– <30%
lifetsyle changes
pharmacotherapy
surgery
lifestyle chnmages
behavioural changes
pharmotheroay
bariatric surgery
Strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index >30 kg/m2, or >27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions.
Semaglutide 2.4 mg
Liraglutide 3.0 mg
Phentermine-topiramate ER
Naltrexone-bupropion ER (moderate certainty evidence)
Phentermine and diethylpropion (low certainty evidence)
Recommend not using orlistat.
Gelesis100 oral superabsorbent hydrogel lack of evidence
- GLP1 agonist - paradigm shift in obesity:
In US GLP-1 agonists cost $12 000 pa with discounts as low as $6 500
If all eligible US patient receive GLP-1 agonists $600 billion pa
Treatment must be maintained for life as weight gain occurs on stopping
As a result $237 000 to $483 000 per quality-adjusted life-year
QALY during the rapid weight-loss phase is – but much – during maintenance
Not possible to sustain this
Potential for a combined system
Initial GLP-1 agonist for weight-loss
Lifestyle changes for maintenance
Top up with GLP-1 agonist or cheaper pharmacotherapy when needed
low
higher
