Obesitas

• Overweight and obesity


  Abnormal or excessive fat accumulation (>20% of body weight) that may impair health
• Obesity is a chronic medical condition responsible for serious co-morbidity and mortality: medical, psychological, social, physical, and economic
• Body Mass Index (BMI)


  Weight/height squared (kg/m²)
• BMI categories


  • <18 kg/m² = underweight
  • 18-25 kg/m² = normal body weight
  • > 25 kg/m² : overweight
  • > 30 kg/m² = obesity class 1
  • > 35 kg/m² = obesity class 2
  • > 40 kg/m² = obesity class 3
• Limitations of BMI


  • It does not distinguish between muscle and fat
  • It does not account for body fat distribution
• Techniques to measure body fatness


  • Skinfold thickness measurements
  • Bioelectrical impedance
  • Underwater weighing
  • Magnetic resonance imaging (MRI)
  • CAT scans
  • Ultrasound
  • Total body electrical conductivity
  • Magnetic resonance spectroscopy
• Waist to hip ratio


  Indicator of central body fat distribution. More than 0.80 in women and 0.95 in men indicate central obesity
• Waist circumference


  Over 40" (102 cm) in men and over 35" (88 cm) in women indicate increased risk for health problems
• Physiologic functions of body fat

  • Subcutaneous and visceral fat depots serve mainly as fuel storage capacity
  • We need 3-5% body fat for men and 10-12% for women (essential fat)
  • Too low body fat is associated with delayed physical maturation, infertility, and accelerated bone loss
• WHO reported in 2008 that 1.4 billion adults were overweight, of which 500 million were obese (more women than men)
• WHO reported in 2011 that more than 40 million children under 5 years old were overweight, 30 million of them in developing countries
• Obesity is caused by an energy imbalance between calories consumed and calories expended
• Major factors contributing to obesity

  • Dietary intake
  • Physical activity
  • Environmental and social factors
  • Genetic background
• Basic Metabolic Rate (BMR)

  The energy needed for basal metabolic processes (70%) and thermogenesis (10%), highly conserved
• Physical activity


  Accounts for 10% of total energy expenditure, with large intra- and inter-individual variation
• Dietary thermogenesis (NEAT) accounts for 10% of total energy expenditure
• Importance of energy balance: energy input from diet and stored energy versus energy output from basal metabolism, physical activity, and dietary thermogenesis
• Recommended daily energy intake ranges from 1600-2400 kcal for young adult women and 2400-3100 kcal for young adult men
• In Western societies, there is permanent availability of food with high caloric density
• Macronutrient energy content and properties

  • Proteins: 4 kcal/g, high ability to suppress hunger, low storage capacity, excellent ability to stimulate own oxidation
  • Carbohydrates: 4 kcal/g, moderate ability to suppress hunger, low storage capacity, excellent ability to stimulate own oxidation
  • Fats: 9 kcal/g, low ability to suppress hunger, high storage capacity, poor ability to stimulate own oxidation
• Observational studies show an inverse relation between body weight and fat intake, but low-fat diets do not outperform low-carbohydrate or low-protein diets
• Technological advances have reduced physical activity in our lives, leading to a prevalence of physical activity levels below 1.75 (needed to prevent unhealthy weight gain)
• Medical conditions causing obesity

  • Endocrine diseases (hypothyroidism, hypogonadism, growth hormone deficiency, hypercortisolism, acromegaly, polycystic ovarian syndrome)
  • Movement disorders (arthrosis, paralysis)
  • Affective disorders (depression, binge-eating disorders)
  • Hypothalamic disease
  • Genetic and congenital disorders
• Drugs that can cause obesity

  • Corticosteroids
  • Anti-hormonal treatment (aromatase-inhibitors, anti-androgen)
  • Antidepressants and antipsychotics
  • Anti-epileptic drugs
  • Diabetes drugs (sulfonylurea, insulin)
  • Beta blockers
• Genes contribute 25-40% to the obese phenotype
• Medical conditions causing obesity

  • Endocrine diseases:
  • Hypothyroïdism, (male) hypogonadism, growth hormone deficiency
  • Hypercortisolism, acromegaly
  • Polycystic ovarian syndrome (cause/consequence?)
  • Movement disorders
  • Arthrosis
  • Paralysis
  • Affective disorders
  • Depression
  • Binge-eating disorders
  • Hypothalamic disease
  • Genetic and congenital disorders
• Drug therapy causing obesity

  • Corticosteroids
  • E.g. methylprednisolone for rheumatoid arthritis
  • Anti-hormonal treatment
  • Aromatase-inhibitors for breast cancer
  • Anti-androgen treatment for metastasized prostate cancer
  • Antidepressants and antipsychotics
  • Anti-epileptic drugs
  • Diabetes drugs
  • Sulfonylurea, insulin
  • Beta blockers
  • 5-10 jaar dient men dit te nemen => zorgt vaak tot gewichtstoename
• Obesity – Genetic background
• Genetic background


  • Genes contribute 25-40% to the obese phenotype
  • Rare cases of childhood obesity: monogenic
  • General population: polygenic inheritance
  • Important familial risk!
  • Discordance in monogenic twins for BMI = 3-4%
  • ∆BMI 4 kg/m² between twins
• Mutations


  Uncommon (<1%), high penetrance, high individual risk, high attributable risk
• Polymorphisms


  Common (10-20%), low penetrance, low individual risk, low attributable risk
• Monogenic obesity is only a minor % of obese, extreme obesity, early (childhood) onset, due to genetic mutations in MC4R (18q), leptin (7q), LEPR (1p), POMC (2p); involved in appetite regulation
• At population level: obesity is a polygenic trait, >360 genes have been associated with an obesity phenotype in at least one study, several genes are supported by at least 5 studies
• Obesity Predisposition


  • Resistant
  • Prone
• BMI


  • Obesogenic environment
  • Restrictive environment
• FTO Gene Linked To Obesity In People Born After 1942, no link between the FTO gene and obesity for people born prior to 1942; but a very strong link between the gene and obesity in those born after 1942
• Thrifty genotype - feast & famine theory


  Those who are most efficient in storing energy as fat during time of feast are the survivors during famine, therefore that genetic predisposition is favoured in a population, when that population experiences times of constant 'feast' i.e. a western diet, they become obese and develop diabetes
• Aboriginal Australians exposed to Western diet/lifestyle develop type 2 diabetes and obesity in alarming proportions, similar to native Americans (e.g. Pima indians), lean individuals: average BMI 16 kg/m2, they are relatively hypoglycemic (68 mg/dl) while having relative hyperinsulinemia (13 mU/L)
• Thrifty phenotype


  Higher prevalence of obesity, T2DM and atherosclerotic disease in generation born during famine, development of insulin resistance as a preparation for a life of starvation, importance of adequate fetal and infant growth; avoidance of nutritional stresses in early life
• Hunger & satiety – an integrated network, it is possible to be satiated, but also still have a feeling of hunger