My NMD

• The 4 measurements of obesity

  BMI , WHR , skinfold thickness, bioimoedence
• more expensive measurement of obesity

  DXA, MRI, CT
• Obesity co morbidities

  Diabetes

  hypertension

  coronary heart disease

  stroke

  obstructive sleep apnoea

  dyslipidaemia

  gout

  gall stones

  osteoarthritis

  infertility

  cancer
• Fat distribution

  • Not all fat is equal!
  • Central obesity (apple-shaped) - Abdominal and visceral fat - Particularly associated with increased risk of disease
  • Peripheral obesity (pear shaped) - Gluteal, femoral fat - Lower associated risk - Feminine pattern of fat deposition
• The medical risks from obesity are higher when

  • The fat is concentrated around the middle (abdominal or visceral) of the body than the hips and femoral parts (gluteal or subcutaneous) of the body
• Waist-to-hip ratio

  Used clinically to assess whether weight is collected primarily in the abdomen (apple shape, common in males; 'Android') or in the hips and buttocks (pear shape, common in females; 'Gynoid')
• Waist circumference

  Used as a measure of visceral fat
• depot specific risks

  Generalised obesity; alterations in total blood volume resulting in impaired cardiac function Deposition around the thoracic cage and abdomen;  restriction of respiratory function.Intra-abdominal visceral deposition; major contributor to NIDDM, dyslipidaemia and hypertension
• benefits of weight loss

  sustained moderate weight loss has genuine health benefits in reducing illness and death from a number of obesity related diseases
• benefits of weight loss

  There is significant evidence that sustained moderate weight loss (5 -10% decrease from initial body weight) has genuine health benefits in reducing illness and death from a number of obesity related diseases, such as,

  Type II diabetes.Dyslipidaemia.Cardiovascular disease.Obesity-related cancers
• causes of obesity

  Obesity is a heterogenous group of conditions with multiple causes. BMI is determined by an interaction between genetic, environmental and psychosocial factors acting through the physiological mediators of energy intake and expenditure
• ob/ ob mice

  leptin deficiency so no leptin to decrease food intake
• obesity and genetics

  §Homologous human traits are observed, but are very rare (eg. leptin deficiency, Agrp/melanocortin signalling disruption)§§Majority of human obesity maps to different loci (multiple genes involved)–Heritability of 50-90%–Numerous susceptibility genes; environment determines phenotypic expression–The genes involved may indicate targets for drugs to treat obesity
• 3 ways to achieve weight loss

  –Lifestyle changes•Dietary management and physical activity»–Bariatric surgery––Pharmacotherapy
• dietary management

  §Most successful if–Realistic goals are set–A balanced diet is stressed–A support network is in place–A safe rate of weight loss is achieved through a combination of moderate calorie restriction and increased physical activity»§Fad diets should be avoided–Often lead to an imbalance in macronutrients–May lead to restricted intake of healthful foods
• bbc diet trials

  §Four commercially available strategies–Equally effective after 6 months–Clinically beneficial weight loss–Reduced blood pressure and waist circumference––Follow up at 12 months indicated that programmesbased on group support were more effective–Those who adhered lost ~10% of starting weight––‘Best effect’ that motivated individuals can expect to achieve within 1 year
• Management of Obesity

  §The focus of obesity treatment is dietary restriction, especially caloric restriction (low fat, low carbohydrate diets), together with physical activity and behavioural modification.§The overall goal is to obtain a negative energy balance by reducing energy intake (i.e. eating less) and increasing energy expenditure (i.e. performing more physical activity).
• 2 types of obesity surgery

  restrictive: induces early satiety and limits the rate of food intake . e.g laparoscopic gastric banding. malabsorptive: shorten gut to reduce food absorbed, e.g biliopancreatic jejunoileal or roux en y gastric bypass
• bariatric surgery complications

  Any complication:

  • Laparoscopic gastric band:   9%•• Roux-en-Y gastric bypass:   23%•• Biliopancreatic diversion:   25%•

  Serious complications:

  • Laparoscopic gastric band:   0.2%•• Roux-en-Y gastric bypass:   2%•• Biliopancreatic diversion:   5%
• surgery in obesity

  Gastric surgery is used for the treatment of severe and very severe obesity.

  There is compelling evidence that co-morbidities are reduced or delayed in severely obese patients who have lost weight as a result of gastric surgery.
• what causes met syn?

  excess adipose tissue and insulin resistance
• raised ldl cholesterol is not one of the symptoms of met son but

  they frequently occur together up to 33% of people with raised ldl also have met syn
• prevalence of met syn

  20-30% of adult population of most countries
• role of insulin in adipose tissue

  stimulates fatty acid and glucose uptake, inhibits fatty acid release
• role of insulin in muscle tissue

  stimulates glucose uptake
• role of insulin in the liver

  stimulates glycogen synthesis, inhibits gluconeogenesis and glycogenolysis
• gluconeogenesis 


  the generation of glucose from non carb sources
• gluconeogenesis


  make glucose from non carb substrates
• lipogenesis

  can convert carb to lipid
• lipolysis

  TAG breakdown into fatty acids
• insulin resistance changes in adipose tissue

  as adipocytes become bigger they are thought to become less responsive to insulin. the type of macrophage also changes
• hormone sensitive lipase is inhibited by insulin. lipoprotein lipase is stimulated by insulin
• fatty acid theory 


  used to be thought that the cause was high levels of nefarious released from adipose tissue, this lead to the uptake if fatty acids by muscle and liver which were then incorperated into TAG and stored inside the cells, accumulation of ectopic fat is known to reduce insulin sensitivity of cells
• reduced uptake of TAG by adipose tissue may be responsible for insulin resistance
• alternative suggestion as to how obesity causes insulin resistance

  expanded amount of adipose tissue reduces the amount of NEFA released to protect the body, to compensate for this they reduce the amount of TAG removed from circulation meaning the amount of plasma TAG increases this is then taken up by muscle and liver, it accumulates inside cells making them insulin resistant
• obesity also induces a pro inflammatory state 


  macrophages normally associated with adipose tissue, obesity induces a phenotypic switch in adipose tissue from anti inflammatory M2 to pro inflammatory M1 macrophages, in obesity adipose production of insulin sensitising adipokines with anti inflammatory properties is decreased and pro inflammatory is increased
• adipokines with pro and anti inflammatory

  pro = TNF- alpha anti = adiponectin
• possible aetiology of metabolic disease

  obesity leads to expansion of visceral adipose tissue mass which becomes resitant to action of insulin and reduces uptake of TAG from blood stream. there's an increase in inflammatory adipokines. muscle becomes insulin resistant and reduced glucose uptake leads to hyperglycaemia. may be further impacted by resistance in the liver meaning gluconeogenesis is always on.excessive TAG accumulation may lead to increased vldl secretion
• why is hypertension associated with met syn?

  stimulation of renin angiotensin aldosterone systems, abnormal renal sodium handling and endothelial dysfunction
• why is hdl cholesterol reduced

  inverse relationship with VLDL triglyceride and HDL cholesterol, may be associated with reduced cholesterol ester transfer activity, may also be responsible for production of small dense LDL