brighton yr 2 lectures 2023 part two.pptx
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Health consequences of living with obesity Effects of obesity on the person Treatment options Lifestyle Drugs Surgery Obesity associated comorbidities Metabolic Depression Mechanical Anxiety CNS Asthma Fatty liver Sleep apnoea Cardiovascular diseases • Stroke • Dyslipidaemia • High blood press...
Health consequences of living with obesity Effects of obesity on the person Treatment options Lifestyle Drugs Surgery Obesity associated comorbidities Metabolic Depression Mechanical Anxiety CNS Asthma Fatty liver Sleep apnoea Cardiovascular diseases • Stroke • Dyslipidaemia • High blood pressure • Coronary artery disease Atrial fibrillation Heart failure Gallstones Cancers* Physical functioning Infertility Type 2 diabetes Prediabetes Gestational diabetes Incontinence Chronic back pain Joint disease CVD, cardiovascular disease; CNS, central nervous system *Including breast, colorectal, endometrial, oesophageal, kidney, ovarian, pancreatic and prostate Adapted from Sharma AM. Obes Rev. 2010;11:808-9; Guh et al. BMC Public Health 2009;9:88; Luppino et al. Arch Gen Psychiatry 2010;67:220–9; Simon et al. Arch Gen Psychiatry 2006;63:824–30; Church et al. Gastroenterology 2006;130:2023–30; Li et al. Prev Med 2010;51:18–23; Hosler. Prev Chronic Dis 2009;6:A48 Gout Comorbidities increase as obesity increases Comorbidities seen at ‘overweight’ BMI Relative risk of death, BMI, Waist circumference, Waist hip ratio Nadir for Men – 25.3, Women, 24.3 As BMI Increases, so life expectancy decreases 100 Normal BMI = almost 80% chance of reaching age 70 Proportion still alive (%) 80 60 BMI 35–40 = ~60% chance of reaching age 70 40 BMI range (kg/m2) 22.5–25 25–30 30–35 35–40 40–50 20 BMI 40–50 = ~50% chance of reaching age 70 0 35 40 50 60 70 Age (years) Data are based on male subjects; n=541,452 BMI, body mass index Prospective Studies Collaboration. Lancet 2009;373:1083–96 80 90 100 The Metabolic Syndrome ‘Constellation of closely associated CV risk factors’ ► Visceral ( central) obesity ► Dyslipidaemia ► Hyeprglycaemai ► blood volume and blood viscosity ► vascular resistance ► hypertension ► left ventricular hypertrophy ► coronary artery disease ► stroke ► INSULIN RESISTANCE is the underlying pathophysiological mechanism Fat distribution is as important as degree of adiposity. Pears are GOOD Apples are LESS GOOD, ( metabolically speaking ) Fat is not an inert substance ADIPOCYTOKINES Pathophysiology of insulin resistance and the Metabolic Syndrome ►? Pathophysiology ► free fatty acids (non-esterified fatty acids) ► Lipolysis of visceral fat ► Gluconeogenesis ► Dyslipidaemia ► Pro-inflammatory cytokines ► TNF- , IL-6 (from ‘overloaded’ white adipose tissue) ► insulin resistance ► expression GLUT-4 (insulin-sensitive glucose transporter) ► tyrosine kinase activity of insulin receptor TYPE 2 DM • ↑Prevalence Risk determined T2 DM by – – – – ↑Age population AGE OBESITY ↑Obesity • T2 DM younger FAMILY HISTORY ↑Detection ETHNICITY/ diagnosis • 50% cases T2 DM picked up on routine examination – ↑Survival with T2 DM • Targets – Rich in poor countries – Poor in rich countries • Source of socioeconomic inequality in health More than Metabolic syndrome – RESPIRATORY System ► Obstructive ► Hypoxia / hypercapnia ► Pulmonary ►Right sleep apnoea hypertension heart failure ► Accidents ►Daytime somnolence More than Metabolic syndrome – GI tract ► Non-alcoholic fatty liver disease (NAFLD) ► ‘Metabolic-associated ► 90% fatty liver disease’ of obese people have NAFLD ► 1:5 progress to non-alcoholic steatohepatitis (NASH) ► 1:5 progress to cirrhosis and chronic liver disease ► Gallstones ► Reflux More than Metabolic syndrome – CANCER ► Obesity has now overtaken smoking as the most important cancer risk factor ► Types of cancer include ► Breast, endometrial, oesophagus, colon, gall bladder, renal, thyroid ► Mechanisms include ► insulin, free IGF-I, oestrogen, adipo-cytokines, reflux More than Metabolic syndrome – Reproductive issues ► Polycystic ovarian syndrome ► Oligomenorrhoea, hirsutism, acne ► Subfertility ► Endometrial hyperplasia ► Insulin resistance ► Male hypogonadism ► Adverse pregnancy outcomes More than Metabolic syndrome – OTHER ISSUES ► JOINTS ► Osteoarthritis ► Gout ► MENTAL HEALTH ISSUES ► Disordered eating, Binge eating, anorexia ► OCD, ADHD, ASD ► Depression ► Anxiety ► Agoraphobia ASSESSING A PATIENT LIVING WITH OBESITY. Assessing the patient living with Obesity History • • • • • • • • • Family History Age of onset, Hyperphagia, Endocrine or other issues Drug History Reproductive/menstrual history Mental health – OCD, Depression, Disorders of eating Sleep patterns ?OSA Smoking/alcohol/drug history Restrictions to ADL’s – Gait issues, continence/self care Readiness to change • Motivation – why now? What does healthy look like? Drug Treatment associated with weight gain Antipsychotics Risperidone Lithium Quetiapine Aripiprazole Olanzapine Valproic acid Antidepressants Citalopram Duloxetine Venlafaxine Sleep inducing agents Zopiclone Trazadone Zolpidem Neuropathic agents Pregabalin Gabapentin Others Steroids Insulin Assessing the patient living with Obesity Examination Accurate weight and height •O2 Saturations •BP ( large cuff) •CV and respiratory exam. •Skin ( Intertrigo, Hydradenitis) •Signs of insulin resistance – Acanthosis Assessing the patient living with Obesity Blood Tests • HbA1C • 41-47 – prediabetes • >48 Type 2 diabetes • Lipid profile • Liver function tests ( NAFLD/NASH) • FBC • Renal function • Iron studies, B12, Folate • Reproductive hormones if indicated Other tests • Sleep studies • ECG/Echocardiogram The treatment of obesity. Lifestyle change Pharmacology Surgery What are aims of treatment To improve health ► Improvement or resolution of obesity associated complications ► Reduce adipose tissue but protecting lean muscle mass ► Improve quality of life ► Increased life expectancy Even modest weight loss can improve health Greater weight loss leads to more health improvement1–5 Urinary stress incontinence1 Cardiovascular1 disease Prevention of T2D1 PCOS1 NASH1 NASH1 Dyslipidaemia1 OSA1 T2D remission1,3,5 Hypertension1 Asthma/Airway disease1 GERD1 CV mortality1,4 Hyperglycaemia1 NAFLD1 Knee OA1 HFpEF1,4,5 0–5% DIET Lifestyle 5–10% 10–15% ≥15% Pharmacotherapy CV, cardiovascular; GERD, gastroesophageal reflux disease; HFpEF, heart failure with preserved ejection fraction; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; OA, osteoarthritis; OSAS, obstructive sleep apnoea syndrome; PCOS, polycystic ovary syndrome 1. Garvey WT et al. Endocr Pract 2016;22(Suppl. 3):1–203; 2. Look AHEAD Research Group. Lancet Diabetes Endocrinol 2016;4:913–21; 3. Lean ME et al. Lancet 2018;391:541–51; 4. Benraoune F and Litwin SE. Curr Opin Cardiol 2011;26:555–61; 5. Sundström J et al. Circulation 2017;135:1577–85 Surgery LIFESTYLE CHANGE Diet 500-1000 kcal energy deficiency -500Kcal/day 0.5kg loss a week Low energy density Decrease saturated fats and sugar Increased physical activity Exercise 7 days / wk ► 30 mins moderate-high intensity OR ► 60 mins low intensity Decrease portion sizes. Decrease snack Increase protein Target 10,000 steps / day ► 500 step increments Increase fruit & veg Structured meals Very low Calorie Diets ? greater weight loss Regardless of weight / weight loss, exercise increases health Very Low Calorie Diets and T2DM PRINCIPLE OUTCOME ► Primary care programme ► 12 month outcomes ► Patients with T2DM diagnosis < 6 years prior ► 24% of participants achieved 15 kg weight loss or more ► 46% induced remission of T2DM ► VLCD (830 kcal/day) for 3-5 months ► Initially, total diet replacement with formulae ► Then stepped food reintroduction (2-8 weeks) ► Long-term maintenance with structured support ► ► Normal HbA1c off all medication for 2 months >10 kg weight loss: 73% remission Long Term adherence to lifestyle change Majority achieve 1 – 2 lb per week with 500 – 1000Kcal/day 5% loss achievable in 12 weeks 102kg =16stones 5%= 5kg BUT: The larger the weight loss, the harder it is to maintain The message is ‘boring’. The metabolic adaptation to reduced calorie intake slows progress Weight is lost but co-morbidity is still present Losing weight is ‘easy’, Maintaining that loss is hard. 5 Anderson et al. Foster et al. Graham et al. Hensrud et al. Jordan et al. Kramer et al. Lantz et al. Murphy Pekkarinen Stalonas et al. & Mustajoki et al. Weight change (kg) 0 -5 -10 -15 -20 -25 -30 Mean change from baseline to end of diet (kg) Mean change from baseline to follow-up (kg) Follow up range from 4 to 7 years Mann et al. Am Psychol 2007;62:220–33 Stunkard & Penik Wadden & Frey Wadden et al. Walsh & Flynn PHARMACOTHERAPY Pharmacotherapy - Drugs acting on the gut Orlistat Positive effects on weight and diabetes prevention XENDOS: 1 and 4 year data Orlistat Baseline Weight: 110.5 kg BMI: 37 kg/m2 Placebo Cumulative incidence of T2D IGT patients only Change in weight -3 −3.0 kg -6 −6.2 kg −5.8 kg -9 −10.6 kg -12 Cumulative incidence of T2D (%) 30 Change in weight (kg) 0 *P=0.0024 25 -45%* 20 15 10 5 0 0 52 104 Weeks Torgerson et al. Diabetes Care 2004;27:155–61 156 208 0 52 104 Weeks 156 208 Orlistat - ► Flatulence and more ► Oily stools ► Decreased fat sol vitamins - ADEK Drugs that mimic GI hormones – GLP1 Agonists Extensive experience in T2DM and now in the arena of weight management The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; CV: cardiovascular; HR: hazard ratio. Marso SP et al. N Engl J Med 2016; 375:311-322. GLP1 and the Incretin System >15 years experience treating T2DM GLP-1R are expressed in Brain Nucleus tractus solitarius GLP-1 is secreted by Endothelium Myocardium Pancreas L-cells of the gut Kidney Gastrointestinal tract Merchenthaler et al. J Comp Neurol. 1999;403:261–80; Baggio & Drucker. Gastroenterology 2007;132:2131–57; Ban et al. Circulation 2008;117:2340–50; Vrang et al. Prog Neurobiol 2010;92:442–62; Pyke et al. Endocrinology 2014;155:1280–90 Liraglutide ► GLP-1 receptor agonist ► At low dose: Used to treat Type 2 DM and called VICTOZA (daily sc injection) ► At higher dose used to treat obesity and called SAXENDA ‘Saxenda’ 3mg max dose Licenced for BMI>30 or >27 in presence of one co morbidity Approved for BMI >35, HbA1C 42-47 AND high risk CV disease Must be within an integrated ‘Tier 3 Weight management programme https://www.nice.org.uk/guidance/TA664/chapter/1-Recommendations Dec 2020 Semaglutide ► For diabetes = OZEMPIC – dose 1mg ► For Obesity= Wegovy – dose 2.4mg ► NICE FAD ( Final appraisal document) published June 2022 Pharmacotherapy - Drugs on the horizon - Twincretins Drugs – the issues ► COST ► INFRASTRUCTURE ► WEIGHT REGAIN ► ?DELAY to other effective treatment? METABOLIC SURGERY Formerly known as Bariatric or Weight loss surgery Patients live longer, (and cheaper) 2500 surgical patients, 7400 matched controls JAMA. 2015;313(1):62-70. doi:10.1001/jama.2014.16968 For BMI ≥40, incremental cost effectiveness ratios : £2000 - £4000 per QALY over 20 years Weight is ( mostly) kept off L.Sjostrom. Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery (Review). J Intern Med 2013; 273: 219–234. Surgery can treat T2DM BMI HbA1C Diabetes medications Stampede – RCT – 3yr Outcomes Adapted from Schauer P NEJM 2014;370:20022013 Roux en y gastric bypass Mean = 31% weight loss Best for: ► The larger person (?) ► Sweet eaters ► People with diabetes Mortality risk 1:1000 Morbidity risk 1:75 The problem?The body's defence against calorie restriction Mean = 25% weight loss Best for ► All BMI – ‘somewhere to go’ ► Those ► Less who may not adhere aggressive Mortality risk 1:1000 Morbidity risk 1:75 Why does it work when diets don’t? The other side of Metabolic Surgery All procedures ► Food restriction ► Cant eat /drink together ► Vitamin mineral deficiencies ► Loose skin ► Pregnancy ► Psychological dysfunction ► Operative complications ► Risk of transfer addiction – Alcohol ► Bypass specific ► Dumping syndrome ► Hypoglycaemia ► Hyperoxalouria and renal stones ► Significant nutritional disturbance LOOSE SKIN ► ► Protein energy malnutrition ► Wernickes encelpahlopathy Unexplained pain NICE position on Metabolic Surgery NICE 2006 NICE 2014 ► For those with recent onset T2DM: ► Expedite bariatric surgery if BMI > 35 ► Consider surgery if BMI > 30 ► Lower BMI by 2.5 points if from high risk population After failure of other options if ► ► BMI > 40 kg/m-2 ► BMI > 35 with co-morbid conditions Or first line ► BMI > 50 kg/m-2 NHS England position statement on Bariatric/metabolic surgery. ► NHS England 2013 ► As per NICE but….. ► Must have been obese for at least 5 years ► Must engage with non-surgical weight-loss programme for 12-24 months first How are weight management services provided in the community? So to get to surgery, you need to go through a tier 3 service first… How are weight management services provided in the community? The ‘Tiered’ approach to weight management The Tiered approach to weight management services Semaglutide/wegovy NHS COMMISSIONING Liraglutide/saxenda Orlistat LOCAL AUTHORITY COMMISSIONED Problem with Tier 3? ► Variable provision ► Variable outcomes ► Variable structure ► Variable length needed to be ‘engaged’ ► Decision to refer for surgery may sit with the Tier 3 provider – limited medical input Problem with Tier 3? ► Variable provision ► Variable outcomes ► Variable structure ► Variable length needed to be ‘engaged’ ► Decision to refer for surgery may sit with the Tier 3 provider – limited medical input COULD THEY BE A BARRIER TO EARLY EFFECTIVE CARE? West Sussex and South Coast Tier 3 services ► Feeling Good 6-12 months diet/activity, psychology No face to face medical assessments ► Why Weight 12-18 months, heavily psychology based No medical assessments ► St Richards Integrated Bariatric Service. (Non commissioned) ► (Brighton/Eastbourne) 6 months ► full medical assessment, ► concentrates on optimisation and education for surgery s TALKING TO PATIENTS ABOUT WEIGHT Language has power Education Obesity medicine as part of Seek permission Don’t judge or blame Empathetic, Respectful Collaborative, Empowering ‘Would you mind if we talked about your weight, where do you think you're at?’ ‘Some people with your symptoms find losing some weight helps them, I could recommend some services if you would like?’ ‘You may not have thought of it before, but you could potentially qualify for medical or surgical help with your weight Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2-3 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPASP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started Cambridge Diet Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2-3 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPASP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started Cambridge Diet Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPASP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started Cambridge Diet Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2-3 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPASP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started Cambridge Diet Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2-3 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPAP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started Cambridge Diet Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2-3 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPASP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started Cambridge Diet Emily ► Born at term, ‘normal weight family’ ► Normal developmental milestones ► Weight gain from age of 2-3 – out of keeping with siblings – s/b Paeds – Nil to find ► Genetics of Obesity bloods sent aged 11 – nil mutations found ► Age 11 – OSA diagnosed – started CPAP then had tonsillectomy ► Age 11 –started Orlistat ► Age 12 – wt 100kg >99.6th Centile Started very low calorie (Cambridge) Diet Emily ► Age 21 – Privately fitted laparoscopic gastric band – lost 2 stones ► Age 22 – Referred to Tier 3 weight management Service ► Age 22 – GOOS contacted her ► ► GPR10 mutation, loss of function ► Cambridge suggest Pharmacotherapy +/- revision ► Referred to Tier 3 service 1year 3kg gain Age 24 St Richards ? Revision surgery – Bypass ► Started on Liraglutide ( via individual funding request) • Oct 2020 114kg , BMI 39 • November 2021 95kg, lost 17% Emily ► I’m still big, but I'm finally ok with it Age 21 – Privately fitted laparoscopic gastric band – lost 2 stones ► Age 22 – Referred to Tier 3 weight management Service ► Age 22 – GOOS contacted her ► ► GPR10 mutation, loss of function ► Cambridge suggest Pharmacotherapy +/- revision ► Referred to Tier 3 service 1year 3kg gain People see ME Age 24 St Richards ? Revision surgery – Bypass ► Started on Liraglutide ( via individual funding request) • Oct 2020 114kg , BMI 39 • November 2021 95kg, lost 17% My life has totally changed Thank you
