Obesity and Metabolic Syndrome

Key Terminology

• Patho (prefix): related to disease. Examples:

  • Pathology: study of disease.

  • Pathophysiology: disordered physiology underlying disease.

  • Pathogenesis: development of disease.

  • Pathogen: disease agent.

  • Etiology: the cause of disease.

Pathology and Obesity

• Pathology: The study of disease.

Body Mass Index (BMI)

• Benefits

  • Provides a risk indication for metabolic health.

  • Quick and easy to calculate.

• Limitations

  • Does not consider body composition or fat distribution.

  • Specific ethnic guidelines are not well established.

  • May not be accurate for individuals with kyphosis or high muscle mass.

  • A healthy BMI may not be the goal for everyone.

Diagnosing Clinical Obesity (New Approach)

• Focuses on measures of body fat and objective signs and symptoms of ill health.

• Introduces two new categories: preclinical and clinical obesity.

Preclinical Obesity

• Excess body fat with variable health risks but no ongoing illness.

  • No reduced organ/tissue function due to obesity.

  • Can complete day-to-day activities unhindered.

  • Higher risk of developing diseases (clinical obesity, CVD, type 2 diabetes, some cancers).

Clinical Obesity

• A chronic disease due to obesity alone.

• Characterized by signs and symptoms of ongoing organ dysfunction and/or reduced ability to conduct daily activities.

  • Reduced tissue or organ function due to obesity.

Diagnosing and Managing Obesity

• Diagnosis

  • Confirm excess body fat.

  • Assess for signs/symptoms of organ dysfunction and limitations of daily activities.

  • Determine if organ dysfunction is obesity-related.

  • Preclinical vs clinical obesity.

• Measurements of Body Size

  • Waist circumference:

  • ≥102 cm for men (Caucasian).

  • ≥88 cm for women (Caucasian).

  • Waist-to-hip ratio:

  • >0.90 for men (Caucasian).

  • >0.85 for women (Caucasian).

  • Waist-to-height ratio:

  • >0.50 for all.

  • Pragmatic assumption: BMI >40 kg/m^2.

Management of Preclinical and Clinical Obesity

• Preclinical Obesity Management

  • Focus on risk reduction and prevention.

  • Health counseling for weight loss or prevention of weight gain.

  • Monitoring over time.

• Clinical Obesity Management

  • Focus on improvement or reversal of organ dysfunction.

  • Evidence-based treatment and management.

  • Assess success by improvement of signs/symptoms rather than weight loss.

Healthy Body Composition (Adults)

• Healthy Body Fat Ranges for adults.

• Age

  • 20-39

  • 40-59

  • 60-79

• Muscle tissue

• Essential fat

• Non-essential fat (storage fat)

Global Prevalence of Overweight and Obesity

• In 2016, 39% of women and men worldwide were overweight.

• About 13% of the world’s adult population was obese in 2016 (650 million adults).

• Overweight/obesity trends have increased from 1975 to 2016.

Number of Deaths by Risk Factor (World, 2019)

• Top risk factors:

  • High blood pressure: 10.85 million.

  • Smoking: 7.69 million.

  • Air pollution: 6.67 million.

  • High blood sugar: 6.5 million.

  • Obesity: 5.02 million.

Incidence and Prevalence (Australia)

• In 2022, 65.8% of adults were overweight or obese.

  • 34.0% overweight.

  • 31.7% obese.

Higher Rates of Obesity (Australia)

• Males (71.2%) more likely than females (60.5%) to be overweight or obese (2022).

• ATSI people. The increase between 2012-13 and 2018-19 was driven by the proportion of people of ATSI descent who were overweight or obese.

Defining Obesity in Children and Adolescents

• Use CDC growth chart.

  • \geq 85th percentile = overweight.

  • \geq 95th percentile = obese.

Risk Factors

• Low socioeconomic status.

• ATSI.

• Men.

• Regional living.

• Inter-generational obesity.

Defining Obesity: Waist Circumference

• Increased risk of metabolic complications:

  • Men: \geq 94 cm.

  • Women: \geq 80 cm.

• Substantially increased risk:

  • Men: \geq 102 cm.

  • Women: \geq 88 cm.

• Different cut-offs for certain populations.

Measurements of Regional Fat Distribution

• Waist Circumference (IDF method).

  • Midway between last costal rib & iliac spine.

  • Better predictor of visceral adipose tissue area.

BMI vs Waist Circumference

• Waist circumference is a better predictor of vascular mortality and major coronary events than BMI.

Why Care? Obesity Costs

• Obesity has cost Australia billions of dollars.

• Costs are estimated

Etiology of Obesity

• Weight homeostasis, involves balancing energy intake (EI), energy expenditure (EE), and energy storage (ES).

• Macronutrients: Carbohydrates, Fats, Protein, Alcohol.

• Micronutrients: Vitamin C, Magnesium, Calcium, Zinc.

Weight Homeostasis - Energy Expenditure and Appetite Hormones

• Energy expenditure (EE):

  • Basal Metabolic Rate (BMR) & Lean mass.

  • Physical activity - Energy used for movement.

  • Thermogenesis: Energy used for digestion

• Appetite hormones:

  • Orexigenic (promotes hunger): ghrelin.

  • Anorexigenic (promotes fullness): leptin, cholecystokinin, PYY, GLP1, insulin.

• Gut microbiota.

Psychological, Genetics & Environmental Weight factors

• Complex interaction of psychological factors, genetics, and environmental factors including policy and access to food all affect weight.

Factors Affecting Weight Regulation

• Dietary: Portion size, hedonistic factors.

• Sleep: Deprivation, circadian misalignment.

• Genetics: FTO gene.

• Psychosocial: Emotional eating, disinhibition.

• Environmental: Food availability, active transport.

• Political: Food taxation, advertising.

Pathophysiology of Clinical Obesity

• Causes of adipose tissue expansion: mechanical, environmental, psychological, unknown.

• Mechanisms: alterations of homeostatic regulation, appetite/satiety.

• Systemic pathophysiology: low-grade inflammation, lipotoxicity, increased activity of renin-angiotensin system and sympathetic nervous system.

• Adipose tissue pathophysiology: increased turnover and release of free fatty acids, mitochondrial damage.

Genetic Disorder: Prader Willi Syndrome (PWS)

• Rare genetic disorder - causes disruption to hypothalamus.

• Constant appetite resulting in obesity.

• Developmental and reproductive delay.

• Often growth hormone deficient.

Why is Obesity Unhealthy?

• Hypertrophy of fat cells induces pro-inflammatory cytokines, chemokines which recruit pro-inflammatory M1 Macrophages and T-Cells which are also responsible for local Hypoxia.

• Chronic, low grade state of inflammation -> insulin resistance.

• Visceral Fat has more macrophages, T cells and inflammatory markers than subcutaneous fat.

Moderate Weight Loss (5-10%)

• Can result in metabolic improvements.

Comorbidities associated with Obesity

• Hyper-tension

• Hyper-lipidemia

• Type 2 Diabetes

• Cardio- vascular disease

• Peripheral Vascular Disease

• Stroke

• Back Pain

• Osteo-arthritis

• Functional Impairment

• Sleep Apnea

• Depression

Normal Adiposity

• Dysfunctional adipose tissue -> Metabolic Syndrome -> Altered metabolic Profile.

Effect of Weight Loss and Obesity

• Weight loss required for improvement in obesity complications.

Treatment - Pharmacological

• Five TGA-approved anti-obesity drugs:

  • Phentermine: inhibits hunger; stimulating neural release of noradrenaline, serotonin and dopamine.

  • Orlistat: reduces fat absorption.

  • Liraglutide 3mg: reduces appetite; stimulating GLP‐1 receptors in several brain areas.

  • Naltrexone-bupropion: reduces appetite; stimulating activity of POMC neurons in the hypothalamus.

  • Semaglutide 2.4mg (2022): reduces appetite; stimulating GLP‐1 receptors in several brain areas.

Semaglutide GLP-1 Medications

• GLP-1 medications work by mimicking naturally produced hormones: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP)

• GLP-1

  • Brain: Appetite+, Satiety+.

  • Hear: Risk of heart attack-, risk of cardiovascular death-.

  • Liver: Insulin sensitivity+.

  • GI tract: Stomach emptying-, GI Motility-.

  • Pancreas: Glucagon secretion-, Insulin secretion+.

• GIP

  • Brain: Appetite-.

  • Adipose tissue:

  • Insulin sensitivity+.

  • Fat metabolism and storage+.

  • GI Tract,

  • Stomach acid secretion-.

  • Pancreas:

  • Glucagon Secretion+.

  • Insulin Secretion+.

Treatment-Other

• Supervised Lifestyle Interventions

• VLED + Pharmacotherapy

Current Treatment Paradigm = Caloric Deficit

• Hypocaloric Diet, Exercise/Physical activity & Bariatric surgery.

Key Facts Regarding Obesity Treatment

01: Pharmacotherapy is recommended
02: TGA - Fivemedications approved
03: Gastrointestinal devices
04: Bariatric surgery

Treatment - Lifestyle

• Reduce current intake by

  • Reduce energy diet reduce 2000- 4000 kJ/day

  • Low energy diet eat 1000-1200 kcal/day

  • formulated meal replacements e.g. OptiFast.

• Psychological therapy

  • Promotion of mindful eating behaviours

  • Manage reaction to external cues

  • Manage catastrophising and sabotaging thoughts

Treatment - Surgery

• Gastric bypass, gastric sleeve, lap band surgery.

• Bariatric surgery is associated with significant short-term improvements.

Exercise Considerations post-surgery

• Physical activity = integral part of pre-surgical and aftercare management.

• Patients may be prone to nutritional deficiencies and hypoglycaemia.

• Resistance exercise = lessens loss of Fat-free mass.

Complications/Follow Up post-surgery

• Acute post surgery complications are often related to eating, that may cause abdominal pain to the back or chest due slipping.

Summary of Weight Loss Interventions (NHMRC table 6.4)

• Lifestyle change.

• Combined lifestyle change and pharmacotherapy.

• Bariatric surgery with maintained lifestyle changes.

Tailored Intensive Interventions

• The choice of intervention is individualised.

• Rapid results promote long-term maintenance - reduce obesity-related comorbidities..,

The Effect of Exercise on Obesity

• Guidelines for meaningful weight and total adiposity loss are a minimum of 300 – 420 min per week.

ACSM and CDC Recommendations

• 150 minutes of moderate- intensity aerobic activity every week.

• 2X per week of Muscle-strengthening activities.

ACSM – Exercise and Resistance Training

• On the basis of the available scientific literature, the ACSM recommends 150 min*wk.

• Resistance training does not enhance weight loss but may increase fat- free mass.

Summary: Exercise Programming in Obesity

• Program for achieving calories goal and for the management of Lower intensity volume, Resistance Training, Fat volume control.

Exercise in Children and Adolescents

• Exercise can have a small but significant effect on body weight and body fat.

• Greater volumes (frequency and duration) associated with greater benefit

Weight loss with Exercise Interventions

• Greater volumes equal a greater benefit.

The Effect of Exercise vs Diet on Weight

• Combined diet and exercise vs diet = Weight Loss.

• Diet and Exercise VS Exercise - significant benefit ( BW, FM) with diet and exercise.

• A combination of both ( 500 KCAL DEFICIT ) and also resistance training can improve body composition profile.

Summary of Prescription

F: Most days.
I: Moderate (55–69% of maximal heart rate)
T: 150 minutes / week .
T: Cardiorespiratory favoured, role of PRT in sustaining lean muscle mass during weight loss.

Summary of exercise for the management of obesity

ACSM recommends * minutes/week can maintain the weight or prevent.
ACSM recommends 250-300 minutes/week* to illicit meaningful weight loss.
There can be weight decrease if the person can promote the right exercise and also preserve lean tissues, even though there is absence in weight loss!

Exercise Programming For Individual Consideration

• Osteoarthritis of lower extremities and back.

• Any co-morbidity if it is to be considered on exercise testing. prescription and objectives.

Key items to monitor

• Pain, walking, progression/Adherence to program and Self Esteem.

• 20–30% of weight loss is from lean tissue.