brighton yr 2 lectures 2023 part one.pptx

People living with obesity, towards understanding and empathy rather than stigma and bias Sathish Babu Parthasarathy Consultant Endocrinologist/Bariatric Physician Princess Royal Hospital, Haywards Heath Dr Lorraine Albon Consultant Acute and Bariatric Physician. St Richards Hospital, Chichester P...

People living with obesity, towards understanding and empathy rather than stigma and bias Sathish Babu Parthasarathy Consultant Endocrinologist/Bariatric Physician Princess Royal Hospital, Haywards Heath Dr Lorraine Albon Consultant Acute and Bariatric Physician. St Richards Hospital, Chichester PART ONE ► To understand conscious/unconscious bias towards PLWO ► To understand the current understanding of aetiology of Obesity Genetics GI and Brain signalling PART TWO ► To Understand the effects of obesity on the body ► To understand the opportunities for treatment opportunities and barriers that exist to treatment ► A couple of cases to finish We all make assumptions. What jobs do they do? Where do they shop? Education level? Family Structure? Motivation for health behaviours? What its like to live in a larger body A thought experiment! Not Compulsory. Close your eyes……. Put your hand down if…. You have never disliked how you look in a photograph. Put your hand down if…. You have never disliked how you look in a photograph. You have never been concerned about your body shape/size Put your hand down if…. You have never disliked how you look in a photograph. You have never been concerned about your body shape/size You have never made changes to your food/activity levels to influence body shape Put your hand down if…. You have never disliked how you look in a photograph. You have never been concerned about your body shape/size You have never made changes to your food/activity levels to influence body shape You have never used alcohol, or food to manage stress or emotions Put your hand down if…. You have never disliked how you look in a photograph. You have never been concerned about your body shape/size You have never made changes to your food/activity levels to influence body shape You have never used alcohol, or food to manage stress or emotions There is not one thing about your body that you wouldn’t change Why is there such bias against people living in larger bodies? Is Obesity seen as: ► A personal failing ► lack of self-discipline Or ► A medical problem ► Aetiology ► genetic ► environmental Obesity Bias: Not so simple Explicit Bias Implicit Bias Conscious Automatic/Intrinsic Reflects own/family/societies opinions and beliefs Influences are outside our awareness Open to challenge, can shift over time. Difficult to challenge Some are trying to change this Obesity beliefs in UK society 53% felt ‘most overweight people could lose weight if they tried’ 75% felt that a person who is very overweight would be less likely to be offered a manager job About half identify when a woman is obese, <40% for a man Obesity bias – effect on care, and lifespan Spend less time Hebl MR, Xu J, Mason MF, Int J Obes Relat Metab Disord. 27(2):269-75. Build less emotional rapport Gudzune a, et al, Obesity v 21, 10, 2013 Provide less health education Bertakis KD, Azari R, Obes Res. 2005 Sep; 13(9):1615-23. Increased Mortality Sutin AR, Stephan Y, Terracciano A, Psychol Sci. 2015 Nov; 26(11):1803-11. 2003 Feb; Bias – Wider issues Public Policies ‘Moral undertone’ Focus on individual motivation Lack integration Dont address social inequality/stigma Research Less funding than HIV/digestive diseases in US ?Skewed allocation Commissioning/allocation of Health care resource Kidney transplant Joint replacement Pharmacotherapy/surgery for obesity Why is there such bias against people living in larger bodies? How to measure people? ► Waist circumference- can be ► ► hard to do ► kg / m2 ► Easy to do ► Accepted widely Skin-fold thicknesses – need training and special equipment ► Body mass index (BMI) Bioelectrical impedance analysis – not easily available < 18.5 underweight 18.5-24.9 normal 25-29.9 overweight 30-39.9 obese ► Ethnicity specific cut-offs ≥40 ‘morbid’ obesity Current Obesity Statistics. Obesity among adults Health Survey for England 2012 to 2014 (three-year average) One out of four men is obese (24.9%) One out of four women is obese (25.2%) Adult (aged 16+) obesity: BMI ≥ 30kg/m 2 Patterns and trends in adult obesity 21 Trend in severe obesity among adults 4.0% Health Survey for England 1993 to 2014 (three-year average) Women 3.5% Men Prevalence of severe obesity 3.0% 2.5% 2.0% 1.5% 1.0% 0.5% 0.0% Adult (aged 16+) severe obesity: BMI ≥ 40kg/m 2 Patterns and trends in adult obesity 22 More about this later An evolutionary perspective: ► Throughout evolution, eating, breeding and conserving energy is the prime “motto” of human race for survival achieved by adaptive neuro-gut hormonal regulation ► This has led to a bigger brain volume which consumes more resting energy (20%) than the apes (8%) An evolutionary perspective: change in food sources ► Most of the world get more calories from wheat, rice, corn, sugar, oil crops, and animal products. ► Meanwhile, consumption of grains, eg sorghum, millet, and rye and root crops such as cassava and yams has fallen ( 36% Change on average) ► Sugar consumption in Congo Increased by 858% since 1961. policy_brief_global_diets.pdf (publishing.service.gov.uk) Obesity is genetically mediated (in part) Obesity is genetically mediated (in part) Heritability of obesity – 140 loci related to obesity found so far related to obesity found so far Those with obesity have higher numbers of these variants Normal weight or ‘skinny’ people less. Riveros-McKay F, et al. PLoS Genet 2019;15:E1007603 Polygenic ‘Simple’ Obesity Gene Wide Association Scores Identifies SNP’s Obesity Risk score uses 97 of these FTO Gene Fat Mass and Obesity alpha-ketoglutarate-dependent dioxygenase Upregulated in food deprivation First SNP identified to be associated with fat mass - 2007 Effect modest – homozygous for risk allele? 3kg more than homozygous for protective allele Obesity is genetically mediated (in part) Overfeeding studies Obesity is genetically mediated (in part) Effect of calorie restriction The body will defend against calorie deficit ► Your body doesn’t know the difference between a ‘diet’ and a famine ► Multiple SUBCONCIOUS pathways exist to restore you to your set weight ► Usually a bit higher – ‘for the next famine) Minnesota Starvation Experiment 1945 ► Lost about 25% , Very variable ► Lethargic ► Obsessed about food ► Social isolation ► Reduced comprehension, Judgement ► Reduced temp and BMR ► Lost interest in sex! ‘Dieting’ activates powerful countermeasures in metabolism Diet = famine  Hunger  Energy expenditure  Interest in food Evolution has favoured genes that reduce energy expenditure, and increase energy storage Sumithran P, Proietto J. Clin Sci (Lond) 2013;124:231–41 The body will defend against calorie deficit The Biggest Loser – Gains most back 14 Participants, 30 week competition Average calories burned at rest: Start of competition: 2,607 Kcal/day at rest End of competition: 2,000 Kcal/day. 6 years later : 1900KCal/day Weight Start---Average weight of 328 pounds (about 149 kg) End- Average weight of 200 pounds (about 91 kg). Body fat Start- Average of 49 % Dipped to 28 % End- 45 % Individual changes in body composition – This Biggest Loser. The Biggest Loser – Gains most back 14 Participants, 30 week competition Baseline End of competition at 30 weeks Follow-up p-value p-value at 6 years Baseline vs. 30 weeks Baseline vs. 6 years p-value 30 weeks vs. 6 years Age (y) 34.9±10.3 35.4±10.3 41.3±10.3 <.0001 <.0001 <.0001 Weight (kg) 148.9±40.5 90.6±24.5 131.6±45.3 <.0001 0.0294 0.0002 BMI (kg/m2) 49.5±10.1 30.2±6.7 43.8±13.4 <.0001 0.0243 0.0002 % Body fat 49.3±5.2 28.1±8.9 44.7±10 <.0001 0.0894 0.0003 RQ 0.77±0.05 0.75±0.03 0.81±0.02 0.272 0.0312 <.0001 Imagine the feeling of FAILURE – when its ‘just’ evolutionary adaptation to famine Baseline End of competition at 30 weeks Follow-up p-value p-value at 6 years Baseline vs. 30 weeks Baseline vs. 6 years p-value 30 weeks vs. 6 years Age (y) 34.9±10.3 35.4±10.3 41.3±10.3 <.0001 <.0001 <.0001 Weight (kg) 148.9±40.5 90.6±24.5 131.6±45.3 <.0001 0.0294 0.0002 BMI (kg/m2) 49.5±10.1 30.2±6.7 43.8±13.4 <.0001 0.0243 0.0002 % Body fat 49.3±5.2 28.1±8.9 44.7±10 <.0001 0.0894 0.0003 RQ 0.77±0.05 0.75±0.03 0.81±0.02 0.272 0.0312 <.0001 The Biggest Loser – Gains most back 14 Participants, 30 week competition RMR measured (kcal/d) RMR predicted (kcal/d) Metabolic adaptation (kcal/d) TEE (kcal/d) Physical Activity (kcal/kg/d) 2607±649 1996±358 1903±466 0.0004 <.0001 0.3481 2577±574 2272±435 2403±507 <.0001 0.0058 0.0168 29±206 −275±207 −499±207 0.0061 <.0001 0.0075 3804±926 3002±573 3429±581 0.0014 0.0189 0.0034 5.6±1.8 10.0±4.6 10.1±4.0 0.0027 0.001 0.8219 Metabolic adaptation to calorie restriction ► Decreased energy expenditure ► Improving metabolic efficiency ► Increased cues for energy intake, ► Decreased satiety ► Hormones play their part: ► Thyroid ► Gut hormone, Testosterone and Cortisol hormones ► Leptin How the body controls food intake Peripheral signals – Gut Hormones Central Signals – Neural Pathways Gut Hormones ►Key regulators of bodyweight ►Act on homeostatic and hedonic brain circuits to modify eating behaviour. ►Excellent review… Gut Hormones ► EEC (Enteroendocrine cells) sense nutrients ► Present throughout GI tract ► Releases host of Gut hormones as autocrine, paracrine, and endocrine regulators Gut Hormones Appetite Suppressing (Anorexigenic) Appetite Inducing ►Peptide ► Ghrelin ► BUT – powerful CENTRAL signals in the brain drive eating behaviour YY 36 (PYY) ►Glucagon-like peptide 1 (GLP-1) ►Oxyntomodulin (OXM) ►Cholecystokinin (CCK) ►Glucose-dependent ►insulinotropic ►polypeptide (GIP) ►Bile Acids ►Neurotensin (NT) ►Uroguanylin ►Gastric leptin ►Amylin ►FGF19 ( Orexigenic) Gut Hormones ► Act synergistically ► Interact with GUT Microbiome ► Interract with Bile acids ► Vagal signals PYY Belongs to NPY family The release of PYY begins before nutrients arrive in the lower small intestine and the colon. Further release of PYY is stimulated by nutrients within the lower small intestine and the colon. PYY decreases food intake by inhibiting gut motility. Blood remain high between meals PYY (3-36) has more central effects How exercise affects gut hormones Increase in circulating PYY levels Leads to Suppression in appetite and ghrelin levels following exercise eg low volume sprint and endurance exercises Glucagon Like Peptide 1 GLP1 ► Produced and secreted by intestinal EEC- L cells and certain neurons within the nucleus of the solitary tract in the brainstem ► Secreted in response to food consumption ► Glucose-dependent insulinotropic peptide(GIP) is co secreted. ► Enhances Insulin secretion in a glucose-dependent manner. ► Numerous regulatory and protective effects Glucagon Like Peptide 1 GLP1 Pancreas Brain ê Body weight5* ê Food intake6  Satiety7,8  Beta-cell function1*  Insulin biosynthesis1*  Glucose-dependent insulin secretion1  Glucose-dependent glucagon secretion1 Stomach ê Gastric emptying9  Cardiovascular risk2  Fatty acid metabolism3  Cardiac function3  Systolic blood pressure3  Inflammation4 Liver ê Endogenous glucose production10  Hepatic insulin sensitivity10 ê De novo lipogenesis10 ê Lipotoxicity10  Steatosis11 GLP1 and DPP4 – effects on blood glucose Its not all about the gut Central pathways The brains role in appetite, reward and satiety Signals from fat cells Leptin , adipose secreted cytokine/procytokine Secreted mainly by white adipose tissue. Levels are positively correlated with the amount of body fat Leptin has Central hypothalamic and peripheral tissues effects Has permissive effects on reproduction Leptin interacts with both: the mesolimbic dopamine system, involved in motivation for and reward of feeding, and the nucleus of the solitary tract of the brainstem to contribute to satiety Leptin - The ob ob mouse! ‘ob/ob mouse Leptin Deficient ‘db/db mouse’ Mutation of leptin receptor ‘ob’ gene product = leptin Mouse models of obesity Regulation of appetite: Slow acting and fast acting peripheral signals fron GIT tract and fat cells Slow acting signals ► Slow-acting hormones that regulate body weight LEPTINperipheral INSULIN peripheral Rapid acting signals ► Rapid-acting peptides that regulate meal sizes Cholecystokinin (CCK) PYY DECREASE eating ► Signal % body fat to hypothalamus food intake energy expenditure Ghrelin INCREASE eating - Act via hypothalamus It’s a complex system with multiple inputs Gastric leptin Uroguanylin FGF 19 NT Bile acids from Liver http://sigmanutrition.com/wp-content/uploads/2015/02/Food-Related-Hormones.jpg Its not all about the gut Central pathways The brains role in appetite, reward and satiety CNS role in appetite, reward and satiety The Arcuate nucleus – The accelerator and brake on appetite ACCELERATOR NEURONS BRAKE NEURONS NPY / AgRP neurons POMC neurons Neuropeptide Y (NPY) Melanocortin peptides  -MSH, CART Agouti-related peptide (AgRP) Blocks melanocortin receptor ► All INCREASE eating behaviours ► All DECREASE eating behaviour- What happens when it goes wrong? Multiple pathways Multiple hormones/cytokines Each can be perturbed leading to obesity More on genetics… Rare Genetic causes for obesity. Syndromic Single gene issue Leptin deficiency Prader Wili Syndrome Alstrom syndrome Bardet biedel syndrome Usually associated with other anomalies Leptin receptor deficiency POMC MC4R PSK1 SEVERE Hyperphagia Starts EARLY Extreme obesity at an early age Target for therapy Monogenic – Non syndromic Obesity Leptin Melanocortin pathway Gene Reported frequency childhood Reported frequency MC4R 5% POMC 0.9% 1% Obese Adults 0.2% Normal wt PSK1 0.83% 0.19% >BMI35 AgRP <1/1000 LEP RARE LEPR RARE SIM1 1.2% Adult cohort Genetic obesity PWS Bardet Biedel Congenital leptin deficiency So now you know ► How society is biased against those living with obesity ► How Its not just eat less and move more ► How there are signals from the gut, fat stores and the brain that regulate appetite and satiety ► That the body defends against calorie restriction ► That there is huge amount of genetics involved both polygenic ( ‘simple obesity’) and monogenic issues