Overview of Obesity PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Overview of Obesity Department of Medicine  LEARNING OUTCOMES 1. Define obesity 2. Recognise that obesity is a chronic disease 3. Explain the pathophysiology of obesity 4. List the complications of obesity...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Overview of Obesity Department of Medicine  LEARNING OUTCOMES 1. Define obesity 2. Recognise that obesity is a chronic disease 3. Explain the pathophysiology of obesity 4. List the complications of obesity 5. Outline the overarching principles of investigation and management of complications of obesity 6. Outline the different approaches to weight loss  LEARNING OUTCOME 1 Define Obesity  OBESITY Definition: Obesity is a complex chronic disease, characterised by dysfunctional or excess body fat (adiposity), that impairs health However, due to individual differences in body composition, body fat distribution and function, the threshold to which adiposity impairs health is highly variable among adults The causes of obesity are complex and result from interactions between genetic, biological, behavioural, psychosocial and environmental factors Bluher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab 2013; 27(2): 163-77.  BODY MASS INDEX (BMI) BMI = Weight in kilograms divided by the height in metres squared (kg/m 2) Historically, obesity has been defined based on the arbitrary cut-off off a BMI >30 kg/m² (overweight defined as BMI >25 kg/m2) At population level, health complications increase as BMI increases. Used in epidemiological studies to risk stratify and as indicator to screen for weight related health risks NOT an accurate standalone tool for identifying adiposity- related complications in individuals. Use in conjunction with other screening and assessment tools  EPIDEMIOLOGY Worldwide obesity has nearly tripled since 1975 In 2016, >1.9 billion adults were overweight (Of these >650 million had obesity) 39% of adults aged ≥18 were overweight in 2016, and 13% had obesity Prevalence Obesity Ireland– 21.0%, 35% overweight Prevalence Obesity Bahrain– 36.9%, 35.5% overweight Over 340 million children and adolescents aged 5-19 were overweight or had obesity https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight https://data.worldobesity.org  CAN YOU HAVE A HIGH BMI & BE HEALTHY? While there is a statistically significant relationship between increasing BMI and health risks, a given individual can present with virtually no relevant health issues over a wide range of BMI levels So how do you approach this?  AT WHAT POINT DOES ADIPOSITY IMPAIR HEALTH? At an individual level, health complications occur because of the mass, location & distribution of adiposity Plus genetics & health inequalities Threshold varies & there is no “one size fits all approach”  LEARNING OUTCOME 2 Recognize that obesity is a chronic disease  OBESITY IS A CHRONIC DISEASE The American Medical Association designated obesity as a disease in 2013 Obesity is associated with substantial burden of morbidity & premature death Obesity is a chronic disease & often progressive like diabetes or high blood pressure It is more than what you eat & how much you move. Even with the same diet or the same amount of exercise, people will vary widely in the amount or distribution of adiposity It is a chronic disease as it is a lifelong process. Our bodies defend against weight loss “starvation response” Move away from focusing solely on weight loss to overall health and wellbeing  OBESITY IS A CHRONIC DISEASE It is highly heritable neurobehavioral disorder that is strongly influenced by environmental factors Genetics Twin studies show a 50-80% degree of concordance of BMI & regional adiposity. I.E.- identical twins raised apart found they had similar BMIs despite living in different environments. (link below) Environment Inexpensive highly processed foods and beverages Sugar sweetened beverages, Chronic sleep loss Rapid urbanisation in low- and middle-income countries (working/sleep pattern change) Health inequalities  LEARNING OUTCOME 3 Explain the pathophysiology of obesity  THE BRAIN & OBESITY The brain likely plays the most important role in obesity & energy balance A simple approach may be to divide the brain into three main areas that regulate weight 1. The hypothalamus (homeostatic area) 2. The mesolimbic system (hedonic area) 3. The frontal lobe (executive functioning) LET’S START WITH SOME PHYSIOLOGY Appetite Energy (Hunger, Expenditure Satiety) Peripheral Signals  PHYSIOLOGY Appetite Energy (Hunger, Expenditure Satiety) Ghrelin CCK GLP-1 PYY Amylin Leptin OXM Insulin Fat Cells Pancreas Small Intestine Stomach Large Intestine  GHRELIN The only circulating orexigenic (increases hunger) hormone Secreted by the gastric fundus & proximal small intestine ↑ gut motility, ↓ insulin secretion Stimulates increased food intake, increase energy balance, increases weight gain Peaks before meals to stimulate eating Levels drop after meal and nutrient ingestion Prader-Willi Syndrome: Increase in ghrelin causing hyperphagia and severe obesity  EFFECTS OF FOOD INTAKE- REGULATING GUT HORMONES Abbreviation Name Site of Synthesis Peripheral Effect on Food Intake Ghrelin Stomach Increase (orexigenic) CCK Cholecystokinin Intestinal L-cells in Decrease duodenum & (anorexigenic) jejunum GLP-1 Glucagon-like Intestinal L-cells in Decrease peptide-1 distal small bowel & (anorexigenic) colon OXM Oxytomodulin Intestinal L-cells in Decrease distal small bowel & (anorexigenic) colon PYY Peptide YY Intestinal L-cells in Decrease distal small bowel, (anorexigenic) colon, & rectum Perry and Wang. Appetite Regulation & Weight Control  ADIPOCYTE HORMONES Adipocyte tissue secretes hormones & cytokines Name Function Leptin Weight loss, fullness, satiety Adiponectin Insulin Sensitization Inflammatory Cytokines Inflammation (IL6, TNF, etc)  LEPTIN Secreted by white adipose tissue adipocytes Stimulates the anorexigenic neuron system in hypothalamus Inhibits the orexigenic neuron system in hypothalamus Net effect is to decrease appetite, increase thermogenesis, and reduce fat mass Circulating levels are directly proportional to body fat mass Levels decline with weight loss and thus increase in appetite Congenital Leptin Deficiency very rare  LEPTIN & GHRELIN HAVE COUNTERBALANCING EFFECTS ON ENERGY BALANCE Leptin Ghrelin Role Anorexigenic Orexigenic (Gain (Reduce Weight) Weight) Timing Long-term energy Acute appetite balance stimulatory hormone Outcome  energy balance  energy balance Released from Adipocytes Stomach  PHYSIOLOGY- SUMMARY Appetite Energy (Hunger, Expenditure Satiety) Ghrelin CCK GLP-1 PYY AmylinLeptin OXM Insulin Fat Cells Pancreas Small Intestine Stomach Large Intestine PHYSIOLOGY Ghrelin Leptin Insulin Nutrients Arcuate Nucleus part of the hypothalamus near the base and located near the blood brain barrier with a permeable barrier so it can take in peripheral circulating signals and relay them into the CNS takes in GI and Adipocyte hormones, glucose, fatty acids, amino acids  THE HYPOTHALAMUS (HOMEOSTATIC AREA) The Hypothalamus plays a central role in regulating energy intake & expenditure 1. Hunger sensation (Food seeking) Hormonal & neural signals from the gut, adipose tissue & peripheral hormones stimulate neurons co- expressing agouti-related protein (AgRP) & neuropeptide Y (NPY) in the arcuate nucleus & stimulate hunger. Work downstream on paraventricular neuron (PVC) via melanocortin 4 (MCR 4) Activity decreases rapidly after eating 2. Decreased food intake The AgRP/NPY neurons project directly to the second set of neurons co-expressing pro- opiomelanocortin (POMC) & cocaine and amphetamine-regulated transcript (CART), which suppress food intake Fire through the downstream inhibitory Y1 and gamma-aminobutyric acid (GABA) receptors These are normally in balance with each other however in obesity there is a dysregulation. THE MESOLIMBIC SYSTEM (HEDONIC AREA) Hedonic area = the emotional, pleasurable & rewarding aspects of eating Hedonic eating is based on the feelings of reward & pleasure that are associated with anticipating, seeing, smelling or eating food Hedonic eating: Involves food enjoyment and craving driven by reward and pleasure. Signals via dopamine, opioid, and endocannabinoid pathways Through this pathway, food can be craved or enjoyed, even after complete satiation Obesity may result in heightened food anticipation (wanting) due to dopamine issues, leading to overeating. THE FRONTAL LOBE (EXECUTIVE FUNCTION) The frontal lobe is responsible for executive functioning & overriding primal behaviours driven by the mesolimbic system Cognitive functioning works best under optimal conditions of rest, adequate oxygenation, decreased stress & can be adversely affected by medications, such as steroids or by the use of alcohol or illicit drugs. People living with obesity may have disruption of the connection between the frontal lobe and the rest of the brain, which leads to diminished control of eating behaviors.  SET POINT In states of decreasing fat stores, circulating leptin and insulin (hormones) levels fall and signal the hypothalamus to inactivate the POMC/CART-expressing neurons to promote feeding It simultaneously lowers the inhibitory effect on the AgRP/Neuropeptide Y (NPY)- expressing neurons to increase appetite and decrease energy expenditure. As adiposity increases, leptin levels increase in the circulation and exert negative feedback to Summary: Body is fighting to regain the suppress appetite to prevent weight back to a certain set point further weight gain.  HORMONAL ADAPTATION TO WEIGHT LOSS Weight regain is common due to hormonal counter regulatory adaptations Sumithran P et al. N Engl J Med 2011; 1597-604  HORMONAL ADAPTATION TO WEIGHT LOSS Weight loss produced changes in hormones that encourage weight regain; i.e.- sustained elevations in appetite-stimulating hormone and decreases in appetite- suppressing hormones Sumithran P et al. N Engl J Med 2011; 1597-604 GENETICS & OBESITY Obesity is highly heritable (For further reading see notes) Single gene mutation (monogenic) = rare Most are polygenic (smaller variations in a large amount of genes). Only some have been described to date This explains populations influences dietary behaviours and explains why not all people exposed to a “health disrupting environment” will develop obesity.  FURTHER READING Association for the Study of Obesity on the Island of Ireland (ASOI) – The science of obesity. https://asoi.info/guidelines/science/  LEARNING OUTCOME 4 List the complications of obesity  MEDICAL COMPLICATIONS OF OBESITY Stroke Idiopathic Pulmonary disease intracranial hypertension obstructive sleep apnea hypoventilation syndrome Coronary heart disease Pancreatitis Diabetes Nonalcoholic fatty liver Dyslipidemia disease (steatosis, Hypertension steatohepatitis, cirrhosis) Gynecologic abnormalities abnormal menses Gall bladder disease infertility polycystic ovarian syndrome Cancer (breast, uterus, cervix, prostate, kidney, colon, Osteoarthritis esophagus, pancreas, liver) Phlebitis Skin venous stasis Gout National Geographic; Aug 2004, Vol. 206, Issue 2, p54  LEARNING OUTCOME 5 Outline the overarching principles of investigation and management of complications of obesity  PRINCIPLES OF INVESTIGATIONS & MANAGEMENT OF COMPLICATIONS 1. Obesity-centred history 2. Obesity-centred Physical Exam 3. Metabolic Investigations to assess obesity  HISTORY Should include all elements of routine history i.e past medical, surgical history, meds allergies, social and family history. However, emphasis on the underlying cause and complications of obesity Key elements – screen for causes include hypothyroidism & Cushing's. Screen for sleep disorders; physical, sexual & psychological abuse; description of eating patterns; previous attempts to lose weight; physical activity; screen time; mood; anxiety; internalized weight bias; substance abuse & addiction EXAM Baseline anthropometric measurements and look for complications Ensure BP measure with appropriate cuff size OSA high prevalence Cardio, GI and Resp exam MSK – Assess barriers to mobility, look for complications. Skin – common findings in obesity Endocrine – rule out alternative cause of weight gain (e.g.- Cushing’s disease, hypothyroidism) INVESTIGATIONS FOR COMPLICATIONS No single blood test or diagnostic evaluation Investigations based on presenting symptoms, risk factors & clinical suspicion Metabolic syndrome – HbA1C, Lipid Profile for most High risk of non-alcoholic fatty liver – LFT & US (consider Fibroscan) TSH - Underlying cause Uric acid - ?gout If suspicion for Cushing’s -> screen for it  LEARNING OUTCOME 6 Outline the different approaches to weight loss.  OF NOTE Treatment of obesity should NOT focus just on weight loss alone Should consider the individual and outcomes such as adequate nutrition, increase in cardiorespiratory reserve, mobility, self-esteem and quality of life. “Best Weight” - Whatever weight can be achieved while living the healthiest lifestyle you can enjoy  MEDICAL NUTRITION (INVOLVE DIETICIAN EARLY) Flexible, individualized and Best Weight. There is no one-size-fits-all eating pattern for obesity management! Nutrition interventions for obesity management should emphasise individualised eating patterns, food quality and a healthy relationship with food. Caloric restriction can achieve short-term reductions in weight (i.e., < 12 months) but has not shown to be sustainable long term (i.e., > 12 months). People living with obesity are at increased risk for micronutrient deficiencies including but not limited to vitamin D, vitamin B12 and iron deficiencies. MEDICAL NUTRITION THERAPY – IRISH CLINICAL PRACTICE GUIDELINES 2022 PHYSICAL ACTIVITY- IRISH CLINICAL PRACTICE GUIDELINES 2022 Regular physical activity - wide range of health benefits across all body weight categories, even in the absence of weight loss. Aerobic and resistance exercise - maintenance or improvements in cardiorespiratory fitness, mobility, strength and muscle mass during obesity-management interventions. (This can be important, as sometimes negatively affected by other therapies, such as caloric restriction, medications and bariatric surgery.) Weight stigma is linked to reduced engagement in physical activity. In Ireland body weight tends to increase with age. Physical activity important for preserving lean tissue and reducing metabolic effects of higher levels of fat mass in older adults due to the changes in body composition associated with ageing (higher levels of fat tissue and lower levels of lean tissue).  PSYCHOLOGY AND BEHAVIOURAL INTERVENTIONS - IRISH CLINICAL PRACTICE GUIDELINES 2022 Realistic and achievable goals Behaviour-change strategies underlying dietary, medical and activity programmes should be identified. Psychological interventions, such as cognitive behavioural therapy, acceptance and commitment therapies and compassion-focused therapies.  INDICATIONS FOR FOR THE USE OF ANTI- OBESITY MEDICATIONS BMI ≥ 30 or BMI ≥ 27 and co-morbidities Pharmacotherapy is approved by the FDA for chronic weight management Recommended as an adjunct to diet and exercise BENEFITS OF COMBINED TREATMENT Pharmacotherapy Lifestyle Modification Modifies Modifies Internal External Environment Environment Hunger Exposure to foods Food preoccupation Cues to eat Satiation Dietary restraint Nutrient Physical absorption activity Additive Effect Wadden et al. Arch Int Med 2001;161:218-227.  PHARMACOTHERAPY Agent Action Approval Phentermine (short Sympathomimetic 1959 term weight loss only) Orlistat (Xenical) Lipase inhibitor 1999 Phentermine/Topiramat Sympathomimetic 2012 e ER (Qsymia) GABA receptor modulation Carbonic Anhydrase inhibition Naltrexone/Bupropion Dopamine/Noradrenaline 2014 SR (Contrave) reuptake inhibitor Opioid receptor antagonist Liraglutide (Saxenda) GLP-1 receptor agonist 2014 Semaglutide (Wegovy) GLP-1 receptor agonist 2021 Tirzepatide (Mounjaro) GIP/GLP-1 receptor co-agonist 2023 PHARMACOTHERAPY- AVERAGE WEIGHT LOSS WEIGHT REGAIN OCCURS WHEN ANTI-OBESITY MEDICATIONS ARE STOPPED Smith SR et al. N Engl J Med 2010; 363:245-56  BARIATRIC SURGERY Bariatric surgery is indicated in patients greater than 18 y/o with – Body mass index (BMI) greater than or equal to 35 kg/m², who have at least one major adiposity-related complication. – BMI greater than or equal to 40 kg/m², independent of the presence of obesity-related complications. – BMI between 30 and 34.9 kg/m² who have been refractory to non-surgical weight loss with obesity-related complications, especially T2DM.  BARIATRIC SURGERY Pories W: Weight-information network. Bariatric surgery for severe obesity. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). http://win.niddk.nih.gov/publications/gastric.htm  MOST COMMON SURGERIES Sleeve gastrectomy (SG) relative technical simplicity and outcomes comparable to gastric bypass led to a worldwide surge in popularity as a standalone procedure. Excision of approximately 70% of the patient’s stomach, leaving a narrow gastric tube that remains in continuity with the gastrointestinal tract and without disruption of the pylorus. Roux-en-Y gastric bypass (RYGB) involves the creation of a small lesser curve-based gastric pouch. The first 75 cm – 150 cm of small bowel from the duodenojejunal flexure is measured and then transected (the biliopancreatic limb). The distal small bowel is brought up to the pouch and anastomosed, then approximately 100 cm of the alimentary limb is measured, and the biliopancreatic limb is anastomosed. Adjustable gastric banding (AGB) has evolved over the last 20 years from an open technique with a non-adjustable gastric band to laparoscopic adjustable gastric banding. OUTCOMES FROM BARIATRIC SURGERY  BENEFITS OF WEIGHT LOSS Progression from prediabetes to diabetes1 -3.0% Triglycerides and HDL cholesterol 1 Systolic and diastolic blood pressure1 -5.0% Lifestyle Hepatic Steatosis2 Measures of feeling and function Modification -10.0% Symptoms of urinary stress incontinence1 Measures of sexual function 3 QOL measures4 NASH Activity Score1 -15.0% Apnea Hypopnea Index1 Reduction in CV events, mortality, remission of T2DM5,6 1. Cefalu WT et al. Diabetes Care 2015;38:1567-1582 4. Kolotkin RL et al. Obes Res 2001;33:2156-2163 2. Lazo M et al. Diabetes Care 2010;33:2156-2163 5. Sjostrom L et al. JAMA 2012;307:56-65 3. Wing R et al. Diabetes Care 2013;36:2937-2944 6. Sjostrom L et al. JAMA 2014;311:2297-2304  KEY POINTS Obesity is a complex chronic disease that is characterised by adiposity that impairs health. BMI is not an accurate standalone tool for individuals. It is a lifelong disease that requires a long-term approach. Do not focus on numbers on the scale alone but on the individual and their best weight. People living with obesity face bias and stigma – it is not as simple as eat less and move more! We need to change this narrative as HCP.  KEY POINTS The brain and hormonal signals plays a key role in energy homeostasis, appetite regulation and executive control. Genetic predisposition is very important. Environment plays a key role and explains the rise in levels of obesity. Prevention is still important, but the treatment of a disease is not the same as prevention. Holisitic approach including dietetics, physical activity, behaviour change strategies, psychology, pharmacotherapy and bariatric surgery are needed. RESOURCES Clinical Practice Guidelines for the Management of Obesity in Adults in Ireland. Association for the Study of Obesity on the Island of Ireland. (ASOI) Obesity Canada Resources World Health Organization – Framework for prevention and management of obesity 2023