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
