Obesity Flashcards
What units are BMI measured in?
Kg/m2
What issues are found with BMI?
Inability to differentiate muscle from fat and further to this, the distribution of body fat (high waist circumference indicates higher risk – ‘android’ obesity vs gynoid obesity). Ethnicity may increase risk of comorbidities – hence a different BMI index for those of Asian background
Why is obesity classified as a disease?
It is associated with increased risk of morbidity and mortality. for each increment of 1 in BMI, there is an increase heart failure risk of 5% in men, 7% in women
How are classes 1,2 and 3 of obesity classified? How are Asians classified?
Class 1 Obesity = 30-34.9, Class 2 Obesity= 35-39.9 and Class 3=40-50, morbid obesity.
Above 25 is considered obese and above 30 is severe obesity.
How is waist circumference measured, how effective is it as a measurement?
Mid-point between lowest
rib & iliac crest - ~1cm above naval, better than BMI. Indicates a potential impact on liver, glucose and lipid metabolism and
& insulin release.
Why does abdominal obesity lead to increased CHD?
• Abdominal obesity is associated with greater:
o Insulin insensitivity: insulinaemia and glycaemia
o Abnormal lipid profile
o Susceptibility to thrombosis
o Inflammation markers
o Endothelial function
What should be done at waist circumference action level 1 and 2?
What should be done at waist circumference action level 1 and 2?
If waist circumference is at action level 1 (W=>80cm, M=>94cm) the health risk is increasing and personal action should be taken to avoid weight gain. Action level 2 (W>88cm, M>102cm) has multiple health problems and need professional help.
•
Why is being overweight and obese so common?
- Food is cheaper, so there’s increased snacking
- Increase in proportion of foods derived from fat and increased energy density
- Energy intake is greater than expenditure
- Increasing inactivity amongst people and a mismatch between greatly decreased energy requirements and inability of physiological mechanisms to down regulate energy intake to a similar extent
- Thrifty gene hypothesis to select those wth the ability to survive famines, ie obese; very few systems say stop eating
What’s the main cause of premature death in obese people?
Ischaemic heart disease; hypertension, coronary thrombosis and congestive heart failure are more likely. CHD is the biggest killer.
Obese women are 3x as likely to have MI and men & women are 2x as likely to experience angina than non-obese
What other conditions has obesity been linked to?
1. Cancer, through effects on hormones • Breast, endometrial, stomach, colon 2. Type 2 Diabetes (80x more likely to develop) • 80x more likely • 3. Osteoarthritis • Hips, knees • >2x more likely 4. Mental health • Obese women less likely to be hired or promoted or receive positive performance reviews and have a higher incidence of depression 5. Infertility/PCOS 6. Gallstones due to improper gall bladder emptying and/or excess cholesterol and/or bilirubin and/or a lack of bile salts, in bile 7. sleep apnoea 8. gout
How is obesity related to energy expenditure?
energy intake > energy expenditure for extended period of time
What are the 3 components of energy expenditure?
1. Resting metabolic rate/obligatory expenditure – 50-70% Correlated to body weight 2. Thermogenesis – 5-15% Linked to temperature and diet 3. Physical activity – 20-40%
Why does BMR increase with body weight
This is because increase in weight is not just fat, usually about 25% is lean tissue, comprising heart, skeletal muscle, and enlargement of GIt and liver.
What are the molecules in the CNS that tightly regulate body weight?
It’s likely we have a hypothalamic set weight. The hypothalamus integrates metabolism and receives neural and hormonal inputs.
Lateral Hypothalamus feeding centre
Orexigenic/anabolic:
Neuropeptide Y (NPY)
Agouti-gene related Peptide (AGRP)
Melanin-concentrating hormone (MCH)
VMH satiety centre
Anorexigenic/catabolic molecules
Leptin receptor (LEPR); leptin is synthesized in fat and results in less cortisol, insulin and food intake and increased energy expenditure.
Pro-opiomelanocortin (POMC)
Melanocortin receptor 4 (MCR4)
Glucagon-like peptide 1 receptor (GLP-1R)
¥ CASE STUDY: Framingham study revealed that average body weight increases by less that 1 lb per year from age 25-55
What are the molecules in the peripheral tissues that tightly regulate body weight?
Skeletal muscle o Myostatin, myogenin Brown adipose tissue o Uncoupling protein 1 (UCP-1) White adipose tissue o Leptin, lipoprotein lipase Gut o Glucagon-like peptide 1 (GLP-1) ¥ CASE STUDY: Framingham study revealed that average body weight increases by less that 1 lb per year from age 25-55
What are the benefits of a 10% weight loss?
50% ↓ in FBS
10% ↓ total cholesterol, 15% ↓ in LDL, 30% ↓ total triglycerides, 8% ↑ HDL
Average improvements of BP by 10/20mmHg
o 20-25% reduction in all mortality
o 30-40% in diabetes related mortality
o 40-50% reduction in certain cancers
What are NICE recommendations for weight loss?
Diet Exercise Behavioural Therapy Drug therapy e.g. Orlistat Surgery (if BMI>40)
What are the components involved in regulating appetite?
Sensory systems, anterior cingulate cortex, orbital and prefrontal cortex, amygdala, nucleus accumbens, insula cortex, hormones, ANS visceral motor and visceral sensory nerves.
In a malnourished patients, and following
sepsis, which marker falls?
Albumin – the liver slows down its synthesis and makes CRP instead; levels are therefore inversely correlated. Sepsis ACCUTELY affects albumin levels
What should be recorded whenever seeing a patient? How does fluid overload, malnourishment and renal failure affect this?
Body weight should be recorded. Fluid overload causes a rapid increase in weight. Malnourishment causes a chronic reduction in weight. Dry weight is useful in renal failure patients.
(The weight you put on during the day is usually lost overnight, but renal patients cant do this. Dry weight is when you clear any excess water. Thus renal patients require dialysis to get rid of extra weight)
Name 4 mechanisms for unintentional weight loss
- Low grade infection eg sepsis
- Undiagnosed malignancy
- Loss of appetite
Paraneoplastic syndrome
What happens to insulin and fats during starvation?
Insulin levels fall since it signals postprandially energy release is therefore triggered through glycogenolysis(NOT glycolysis). Liver glycogen lasts <24hr. Fats are converted to ketones by the liver. Other substrates include glucose, glycogen and proteins.
Describe bicarbonate, ketone (and thus pH) and BXS levels in a very obese patient on water only. What will be seen in the urine dipstick?
¥ mild ketoacidosis (6mM) suggesting a pH 7.3
¥ bicarbonate falling from 24 to 18
BXS -6
¥ Urine dipstick +ve for ketones
Why isn’t true acidosis seen during starvation?
Respiratory compensation; impaired in co-existant disease.
What are the other effects of insulin?
- Glycolysis in liver and muscle and glycogen synthase is switched on. Gluconeogenesis is switched off.
- Fat generation is stimulated
Ketone (acid) production is suppressed
How does the deficiency of insulin differ between type 1 and type 2 diabetics?
Deficiency is absolute in type 1 and relative in type 2
Describe pathophysiology in T1 diabetes
The islets of lagerhans in the pancrease are destroyed by the immune system, resulting in a total insulin deficiency. Since insulin signals post-prandially, effectively patients are forced to respond as if they were starving; cells of the body are unable to uptake glucose. Rising plasma glucose means glucose leaks into the urine, and its osmotic effect
Wha happens when insulin levels are 0?
the liver behaves (wrongly) as if there is absolutely no fuel for the brain to keep working and makes huge amounts of ketones (acids)
The blood turns acidic with ketones in the urine
The brain cannot function in an acid pH
What happens in diabetic ketoacidosis
Blood full of ketone (acids)
Severe dehydration
Air hunger
If there is insulin resistance only some glucose enters cells. This leads to more insulin release. What eventually happens and what is this condition called?
¥ after several years the pancreas becomes exhausted and type 2 diabetes ensues
How does the prevalence of ketoacidosis differ between diabetics?
In T2DM, There is sufficient insulin here to suppress ketogenesis.
If this patient is also starving (eg found on the floor) then like anyone else, there will be minimal but sufficient ketone generation to supply fuel, but NOT to generate ketoacidosis.
Only COMPLETE insulin deficiency causes true ketoacidosis
Describe differences between T1 and T2 diabetics
Acute vs insidious onset Non obese vs overweight Young vs old HLA DR3 and DR4 vs no HLA assoiations Islet cells abs vs none 30_50% concordance vs 100% always need insulin vs diet control/oral hypoglycaemic agents and insulin if needed
What does the 100% concordance in T2DM suggest?
Obesity is strongly heritable, may be due to the hypothalamic set point in body weight. This may be polygenetic
Describe a case study which investigated the effect of lifestyle modification in overweight people
¥ NEJM – 3234 ps randomized to metformin, placebo, lifestyle modification which consisted of 16 1:1 sessions and moderate physical activity for 150 mins per week and subsequent monthly group sessions. Lifestyle highest loss in weight and most effective at reducing plasma glucose and T2DM incidence. 7 persons would have to participate in lifestyle modification to prevent one case of diabetes
¥ 14 would have to receive metformin to prevent 1 case
