Obesity Study Guide Typed Notes PDF

OBESITY Introduc)on: Obesity occurs when there is an imbalance between energy intake and energy expenditure over 9me. This results in increased energy storage. E)ology: Obesity’s e9ology is unknown, it is likely due to a variety of factors including: • Gene9cs • Environmental • Physiologic Factors...

OBESITY Introduc)on: Obesity occurs when there is an imbalance between energy intake and energy expenditure over 9me. This results in increased energy storage. E)ology: Obesity’s e9ology is unknown, it is likely due to a variety of factors including: • Gene9cs • Environmental • Physiologic Factors Gene9cs appears to be the primary determinate. Environmental factors include lack of physical ac9vity and abundant food supply. Medical condi9ons associated with obesity • • • • • Cushing syndrome – Makes too much cor9sol Growth hormone deficiency Insulinoma Lep9n deficiency Psychiatric disorders (depression, binge ea9ng disorders, schizophrenia, gene9c syndromes) Pathophysiology: Many neurotransmiMers and neuropep9des s9mulate or depress the brain’s appe9te network, impac9ng total calorie intake. Appe9te is a neural network involving the • Hypothalamus • Limbic system • Brain stem • Hippocampus • Elements of the cortex • Pituitary Gland The degree of obesity is determined by the net balance of energy ingested rela9ve to energy expended over 9me. The lateral hypothalamus has been referred to as the hunger center within the brain. S9mulators of the hypothalamus include: • 1 pep9de Orexin – s9mulates food intake • Melanocyte concentra9ng hormone – communicates with other neurons affec9ng a number of func9ons beyond appe9te Other major hormones playing a factor in obesity: Ghrelin and Lep9n • Ghrelin is a hormone that increases appe9te • Lep9n is a hormone that decreases appe9te • Lep9n is higher in obese pa9ents due to lep9n resistance Exogenous lep9n produces considerable weight loss in lep9n deficient pa9ents, but it is not proven in pa9ents with sufficient lep9n. Some gut hormones are also important to the brain’s processing of appe9te: • GLP-1 • Oxyntomodulin • Pep9de YY Although hunger/sa9ety are primarily regulated by the hypothalamus humans eat to a broad set of s9muli such as: • Reward • Pleasure • Learning and memory An individual’s metabolic rate is the largest determinate of energy expenditure. The metabolic rate increases aZer ea9ng based on the size and composi9on of the meal. Max metabolic rate = 1 hour aZer a meal and basal metabolic rate occurs 4 hours aZer a meal. Res9ng Energy Expenditure (REE) is defined as the energy expended by a person at rest. Basal metabolic rate (BMR) is REE measured soon aZer awakening in the morning at least 12 hours aZer last meal. Adipose cellularity increases when obese but shrinks smaller when reduced further than a pa9ent who was never obese. An issue that can occur in obese pa9ents is Non-Alcoholic FaMy Liver Disease (NAFLD) • Can become cirrho9c NASH (non-alcohol steatohepa99s) • Prevalence of NAFLD is 80-90% in obese pa9ents Several risk factors are involved for NAFLD/NASH • Step 1 NAFLD/NASH 1. Obesity 2. Arterial hypertension 3. Diabetes 4. Dyslipidemia • Step 2 Cirrho9c NASH 1. Obesity 2. Diabetes 3. Advanced Factors Stages of NAFLD Insulin Resistance Dyslipidemia Obesity Fa5y Liver Visceral Adipose Tissue Insulin Resistance Obesity is associated with insulin resistance in skeletal muscle, liver, etc… This prevents glucose uptake by the liver and skeletal muscle. Increases liver kidney mediated gluconeogenesis. Increases inflammatory markers in circula9on. Cardiovascular/HTN During obesity and diabetes, the heart progresses from compensated to decompensated cardiac hypertrophy or diabe9c cardiomyopathy. Early indica9ons are myocardial remodeling and contrac9le dysfunc9on associated with energy dysregula9on and lipid accumula9on. Clinical Presenta)ons: Central obesity is high levels of intrabdominal or visceral fat. BMI = weight (kg)/square of the height (M2) WC = waist circumference – narrowest circumference between the last rib and the top of the iliac crest. Category BMI Class Comorbidity Underweight Normal Weight Overweight Obese <18.5 18.5-24.9 25.0-29.9 30.0-34.9 35.0-39.9 ³40 N/A N/A N/A I II III Low Average Increase Moderate Severe Very Severe Severe Obesity For each standard devia9on of a higher BMI. The risk of Type 2 diabetes increases by 67% and coronary artery disease by 20% Comorbidi9es associated with obesity can affect virtually all organ systems. Treatment Reduced calorie intake Comprehensive lifestyle interven9on Pharmacotherapy Medical Devices Bariatric Surgery Weight management is commonly considered successful when a predefined amount of weight has been lost so that a final goal is achieved. Primary goal is to improve weight related complica9ons and ul9mately improve pa9ents health. AACE and ACE outlined interven9on from at least 5% to 40% based on severity 3 phases were set for treatment and preven9on of obesity • Primary phase – prevent overweight and obesity • Secondary phase – prevent progressive weight gain or achieve weight loss to prevent complica9ons • Third Phase – achieve sufficient weight loss to improve obesity-related complica9ons and prevent further deteriora9on. Cornerstone of weight management Incorpora9on of healthy lifestyles such as healthy diet, adequate physical ac9vity or behavioral modifica9ons Bariatric surgery Most powerful and effec9ve interven9on for treatment of obesity recommended ³40 or 35 BMI with one major comorbidity (HTN, Type 2 DM, Obstruc9ve sleep apnea) Specific weight loss goals should be established. Reduced Caloric Intake Lower calorie diet (LCD) provides a daily energy deficit of 500-750 kcal 1200-1500 kcal/day women 1500-1800 kcal/day men This is also variable based on lifestyle. Implantable medical devices are an op9on for individuals who do not qualify for surgery. Pharmacologic Therapy: Have failed to lose weight or sustain weight loss, and have a BMI greater than or equal to 30 kg/M2 or BMI greater than or equal to 27 kg/M2 with a least one weight related comorbidity. Long term pharmacotherapy may have a role for pa9ents with no contraindica9ons but guidelines recommend discon9nua9on aZer 3 months Drugs Orlistat – (180 or 360 mg) lipase inhibitor that induces weight loss by lowering dietary fat absorp9ons, improves lipid profiles, glucose control, and other metabolic markers Side effects - soZ stools, abdominal pain or colic, flatulence, fecal urgency and/or incon9nence It interferes with absorp9on of fat-soluble vitamins, cyclosporine, levothyroxine and an9retrovirals. Phentermine in combina@on with Topiramate – sympathomime9c amine with pharmacologic proper9es similar to the amphetamines with the MOA of reducing appe9te secondary to CNS effects including s9mula9on of the hypothalamus to release norepinephrine. Its acts as an appe9te suppressant and increases energy expenditure. Topiramate blocks sodium channels enhances GABA ac9vity, antagonizes glutamate receptors, weakly inhibits carbonic anhydrase; suppresses appe9te. Makes you feel full. Contraindica9ons MAO inhibitor use with 14 days, pregnancy, breaspeeding, hypothyroidism, glaucoma Cau9on ca increase heart rate, cogni9ve dysfunc9on/psychiatric disturbances can occur; associated with acute myopia and secondary angle closure glaucoma Naltrexone/Bupropion – Opioid antagonist/Dopamine and norepinephrine reuptake inhibitor – reduces cravings. Bupropion enhances POMC cell produc9on and release of alpha MSH and Beta endorphin and suppresses appe9te. Together they work on the hypothalamus and mesolimbic dopamine circuit. ADRS include headache, sleep disorder, nausea, vomi9ng, cons9pa9on, diarrhea, dry mouth, insomnia, dizziness Contraindica9ons MAO inhibitor use with 14 days, ESRD, Uncontrolled HTN, Seizure disorder/history, bulimia, anorexia Cau9on suicidality, psychiatric disorder, bipolar disorder, acute opioid withdrawal Liraglu@de (SAXENDA) GLP -1 Agonist – ac9vates GLP-1 receptor in the brain, regula9ng appe9te and caloric intake. Increases sa9ety, slows gastric emptying. ADRS- nausea, diarrhea, cons9pa9on vomi9ng, abdominal pain dyspepsia, hypoglycemia, headache, tachycardia Contraindica9ons Pregnancy, Personal/Family history of medullary thyroid carcinoma, mul9ple endocrine neoplasia syndrome type 2