JC35 (Medicine) - Obesity Flashcards
Clinical methods to quantify obesity
Weight
BMI
Waist to hip ratio
Skin fold thickness
Waist circumference
Total body fat estimate
Cut-off points of BMI
Underweight: <18.5
Acceptable risk: 18.5-23
Increased risk: 23-27.5
High risk: >27.5
Or
Underweight: <18.5
Normal: 18.5-23
Overweight: 23-25
Obese: >25
Obese Class I: 25-30
Obese Class II: >30
Measures of fat distribution
Function
Assessed clinically by:
Waist:hip ratio (WHR): defined as ≥0.95 (M) or ≥0.80 (F)
Waist circumference: Chinese: ≥90cm (M), ≥80cm (F)
Function: Measure Central (abdominal) obesity: intra-abdominal fat accumulation
→ Stronger relationship with metabolic syndrome, T2DM, cardiovascular diseases
Definition of metabolic syndrome (NCEP ATP)
NCEP ATP III (2005) definition of
metabolic syndrome (syndrome X):
≥3 out of 5 of
(1) Central obesity: waist circumference >40 inches (M), >35 inches (F)
(2) Insulin resistance or diabetes: fasting glucose ≥5.5mmol/L or on treatment
(3) Hypertriglyceridaemia: >1.7mmol/L
(4) Low HDL-C: <1.034mmol/L (M), <1.293mmol/L (F) or on treatment
(5) Hypertension: >130 SBP or >85 DBP or on treatment
Cardiovascular and Metabolic diseases linked to obesity
□ CVS: HTN, CAD, stroke
□ Metabolic: T2DM, dyslipidemia, insulin resistance, polycystic ovary disease
GI and Resp. and Neurological diseases linked to obesity
□ GI: hiatus hernia, gallstones, colorectal cancer, non-alcoholic fatty liver disease
□ Respiratory: obesity-hypoventilation syndrome, dyspnoea, OSA
□ Neurological: nerve entrapment, sciatica
Breast, Genitourinary, Orthopaedic and Psychological diseases linked to Obesity
□ Breast: breast cancer, gynaecomastia
□ Genitourinary: stress incontinence, ↓fertility (due to PCOS), pregnancy complications
□ Orthopaedics: OA of weight-bearing joints
□ Psychological: poor self-esteem, depression
Causes of primary obesity
- Mismatch between energy intake and energy expenditure
- Multiple influences including genetic, environmental and behavioural factors
Genetic influences:
- Generally polygenic
- ~33% hereditability
Environmental factors:
- Food intake and dietary fat content
- Sedentary lifestyle
- Socio-economic status (inverse relationship)
Causes of secondary obesity (medical causes)
Medical conditions:
□ Hypothyroidism (commonest)
□ Cushing’s syndrome
□ Hypogonadism in male
□ Polycystic ovary syndrome in female
□ GH deficiency
□ Hypothalamic tumours
Causes of secondary obesity (drug causes)
Antidepressants
Antipsychotics
Diabetic medication
Glucocorticoids
Anticonvulsants
Physiological control of energy balance and adiposity
Peripheral signals:
Long-term signals of energy stores + short-term fluctuations in food intake released from adipose tissues and gut endocrine system > Release mixture of Insulin, CCK, GLP-1, Leptin, Ghrelin…etc
Integrated in hypothalamus and brainstem
→ modulate neuropeptide release, autonomic nervous system
→ changes in appetite, behaviour, energy expenditure
→ stable weight maintained
Function of hypothalamus in weight control
Mechanism
Hypothalamus
- Function: integrates neural, hormonal and nutrient messages from body
send signals to higher centres - Mediate feeling of hunger or satiety
- Cause changes in appetite, behaviour, energy expenditure
Mechanisms:
- Variety of hypothalamic neurotransmitters controls food intake and thermogenesis
- ↑intake: opioid, GHRH, neuropeptide Y
- ↓intake: 5HT, GLP-1, DA, cholecystokinin - Acts via ANS and pituitary hormones to control energy expenditure
Neurotransmitters released by hypothalamus that affect food intake
Increase food intake:
\Opioids. Growth-hormone releasing hormone, Neuropeptide Y
Inhibit food intake:
Serotonin, Glucagon-like peptide 1, CCK, Dopamine, Corticotrophin-releasing factor
Function of adipose tissue in weight control
Mechanism
Adipose tissue - active endocrine and secretory organ
- Adipokines:
Examples: adiponectin, TNF-α, IL-1β, IL-6, IL-8, IL-1
Variety of effect on body functions and energy balance
- Leptin: peptide hormone made by adipocytes
Normal: acts on hypothalamus to lower food intake + increase energy expenditure
High fat: Increase leptin level and concentration with increase fat mass >> hypothalamus gain partial resistance to leptin
- Release fatty acid and other lipid moieties
Pathophysiology of weight retention
Gut endocrine and adipose tissue >> hormonal and autonomic signal to hypothalamus
Sustained release of stimulating hormones and decrease in appetite-suppression hormones >> hypothalamic resistance/ partial resistance
>> adaptation to defend against weight loss
Aims of obesity management
- Weight reduction with maintenance of weight loss
- Modify concurrent risk factors for mortality and morbidity (smoking, DM, HTN, HL…etc)
5-10% weight loss required for therapeutic benefits
Strategies for weight reduction
Lifestyle modification - diet therapy + exercise
Drug therapy
Surgery
Outline lifestyle modifications for weight reduction
Dietary therapy:
Low-calorie diet (LCD): ≥800kcal/d (typically 800-1500)
Very low-calorie diet (VLCD): <800kcal/d
Optimal weight loss = ~0.5kg/week (600kcal/day deficit)
Physical activity:
□ Combination with dietary modification important for initial weight loss and long-term weight
maintenance
□ Target: Increase until energy expenditure of 1000-1500kcal/w
Behavioral treatment: Increase compliance:
Relapse prevention therapy, Problem-solving therapy, Social support, Telephone contact, Structured meal plans…etc
Compare Low-calorie diet and Very low calorie diet
- Calories limit
- Effectiveness
Low-calorie diet (LCD): ≥800kcal/d (typically 800-1500)
Very low-calorie diet (VLCD): <800kcal/d
VLCD:
- Faster rate of weight reduction in first 2-3mo but not superior in maintenance of weight loss after 1y
- Should only be used under medical supervision
- Faster rate of weight loss asso. with concurrent fat and lean muscle loss
Treatment effects:
Effective in promoting significant weight loss (max 4-7%)
Long-term weight loss in most trials ~2-6kg
Drug therapy for weight loss
- All options
- Banned options
- Indications
Indication:
- Obesity pose medical risk: BMI >30 or BMI = 27-29 + comorbidities
- NOT responded to traditional conservative management
Options:
- Orlistat (Xenical) - GI lipase inhibitor
- Phentermine/ Topiramate (Qsymia) - noradrenaline + anti-epileptic
- Bupoprion/ Naltrexone (Contrave) - dopamine reuptake inhibitor + opioid agonist
- Liraglutide - GLP-1 receptor agonist
Withdrawn options:
Serotonergic agents (Sibutramine, Lorcaserin), Endocannabinoid receptor antagonists (Rimonabant)
Orlistat
- MoA
- Effect
- S/E
MoA: GI lipase inhibitor → ↓absorption of dietary fat
Effect: can ↓dietary fat by 30% with dose of 12mg TDS
S/E:
→ GI: GI upset, steatorrhoea, ↓fat soluble vitamin absorption, fecal urgency, oily spotting
→ Systemic: minimal (minimal systemic absorption)
Phentermine/topiramate (Qsymia)
- MoA
- S/E
MoA:
Phentermine: ↑noradrenaline release + possibly blockade of NA reuptake → anorexia
Topiramate: anti-epileptic, migraine prophylaxis (mechanism unknown)
S/E:
teratogenicity, slight ↑HR, psychiatric/cognitive S/E, metabolic acidosis
Bupoprion/Naltrexone (Contrave)
- MoA
- S/E
*
MoA: ↓appetite and cravings for food
Bupoprion: dopamine/noradrenaline reuptake inhibitor, usually as antidepressant and aid
smoking cessation
Naltrexone: opioid antagonist, usually for treating alcohol and opioid dependence
S/E: nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhoea
→ Also monitor for mood changes, suicidal thoughts and actions
Liraglutide (Saxenda)
- MoA
- Administration
- S/E
Liraglutide (Saxenda):
MoA: GLP-1 receptor agonist
- ↑glucose-stimulated insulin secretion,
- ↓glucagon secretion,
- delayed gastric emptying,
- ↑satiety by direct central effect on hypothalamus
RoA: subcutaneous injections
S/E: mainly GI upset
Surgery for obesity
- Indications
- Types
- All options
Indications:
- BMI ≥40 kg/m2 without comorbidity
- BMI ≥35 kg/m2 with comorbidity, eg. DM, respiratory insufficiency
- Refractory to medical treatments
Types:
□ Restrictive: ↓size of reservoir for intake
□ Malabsorptive: ↓efficacy of absorption
Restrictive bariatric surgery:
- Vertical sleeve gastrectomy (VSG)
- Adjustable gastric banding (AGB)
- Roux-en-Y gastric bypass (RYGB)
- Biliopancreatic Diversion with duodenal switch (BPD-DS)
Malabsorptive options:
- Small bowel bypass surgery
- Bioenterics intragastric balloon
Describe Roux-en-Y gastric bypass
Stomach stapled → formation of small gastric pouch
Roux-en-Y anastomosis to allow gastric, pancreatic, biliary and duodenal secretions to enter distal intestine
Describe Vertical sleeve gastrectomy (VSG)
Laparoscopic excision of greater curvature by staples
creation of a new 150mL banana-shaped gastric pouch
Allow restriction of amount of food intake without any small bowel bypass and
malabsorption
More effective than AGB and comparable to RYGB
Describe Adjustable gastric banding
Pros and Cons
Small inflatable belt placed around upper portion of stomach
induce early satiety → restrict amount of food consumed
Tightness of banding can be adjusted by saline infusion
allow gradual deflation after weight loss
Pros: least invasive form → ↓mortality, ↓complications
Cons: ↑relapse rate and ↓weight loss
Describe Bioenterics intragastric ballon
□ Non-surgical procedure: balloon placed inside stomach by endoscope → acts as bezoar
to partially fill stomach → induce early satiety
□ Reversible, usually removed after 6-9mo
□ Considered a type of behavioural therapy to induce changes in eating habit
Complications of ABG surgery
Band slippage
Leakage
Erosion
Complications of bypass surgery
Anastomotic strictures
Marginal ulcers
Bowel obstruction
Complications of Roux-en-Y surgery
Micronutrient and Macronutrient deficiency
- Iron deficiency**
- Calcium
- Vitamin B12
- Vitamin D
- Fat-soluble vitamin (A,D,E,K)
- Protein
Compare efficacy of bariatric surgeries: Gastric bypass, Adjustable gastric banding, Sleeve gastrectomy
Gastric bypass: Most effective in weight loss, more complications
Adjustable gastric banding: Reoperation rate higher, Least weight loss, Lower mortality and overall complication rate
Sleeve gastrectomy: Similar effectiveness as gastric bypass
Effects of bariatric surgery
- Long-term weight loss, superior to medical Tx
- Improve metabolic diseases
- Reduce CVD risks
- Improve morbidity and mortality
