Yr 1 Medicine 1H - Obesity B.Dalziel (1).pdf

obesity n i n o i t a ht regul g i e w l e 'the a n i m f r e o d n d b n a rlying esity a e b d o n h u t i s w m ociated e ch an is s s m a e s h e t g e d con e a b i t h r a c c i s c c i e o l s D o s 1. d its a metab n e a h t y t i e s b i e r b e' from o m 2. Desc g o n r i d s i n r y a s s...

obesity n i n o i t a ht regul g i e w l e 'the a n i m f r e o d n d b n a rlying esity a e b d o n h u t i s w m ociated e ch an is s s m a e s h e t g e d con e a b i t h r a c c i s c c i e o l s D o s 1. d its a metab n e a h t y t i e s b i e r b e' from o m 2. Desc g o n r i d s i n r y a s s c such as s metaboli mon complication m e l b o r with p s s com n s o u i c t s n i e D 3. interv h t l s a e e i t h i d c i i l morb of p u b e l o r e h t nise litus. 4. Recog and diabetes mel obesity What is overweight and obesity? Excess body weight BMI over 25 kg/m2 In Australia, an increasing number of people are obese. In 2017–18, 67% of adult Australians were overweight or obese (36% were overweight but not obese, and 31% were obese). 4/11/24 Obesity 2024 3 Based on the latest available data, 60% of men and 66% of women aged 18 and over have a waist circumference that indicated an increased or substantially increased risk of metabolic complications. Figure 10: Age-standardised proportion of overweight and obesity in persons aged 18 and over, by Primary Health Network (PHN) areas, 2017–18 Children and adolescents Overweight and obesity compared to other countries Obesity a risk factor contributing to disease burden: 4/11/24 8 Obesity – Risk Factors and Diseases The adipocyte is central to the regulation of systemic lipid metabolism. TAGs are stored during energy surplus and released as fatty acids to during fasting or times of high energy demand. 4/11/24 https://www.ncbi.nlm.nih.gov/books/NBK555602/ 10 APC – adipocyte precursor cell 4/11/24 https://www.mdpi.com/1422-0067/23/10/5511 11 Intra-Abdominal (Visceral) Adiposity Promotes Insulin Resistance and β-Cell Dysfunction é Hepatic insulin resistance Intra-abdominal adiposity é Small, é Hepatic dense LDL glucose output Lipolysis é TG-rich VLDL cholesterol é FFA CETP, Lipolysis Portal circulation Glucose utilization Long-term damage to b-cells by FFA éInsulin resistance é Splanchnic & systemic circulation é Systemic circulation Low HDL cholesterol Insulin secretion CETP: cholesteryl ester transfer protein FFA: free fatty acids TG: triglycerides Adapted from Lam TK et al. Am J Physiol Endocrinol Metab 2003;284:E281-90: Carr MC et al. J Clin Endocrinol Metab 2004;89:2601-7: Source: www.myhealthywaist.org Relative risk* of type 2 diabetes Nurses’ Health Study: Risk for Type 2 Diabetes Waist circumference (inches) * Controlled for age, family history of diabetes, exercise, smoking, saturated fat intake, calcium, potassium, magnesium and glycemic index. Adapted from Carey VJ et al. Am J Epidemiol 1997;145:614-9 Source: www.myhealthywaist.org Not all Fat Is the Same… Maria Age: 58 years Weight: 92 kg BMI: 35.4 kg/m2 Intra-abdominal (visceral) adiposity Subcutaneous fat Maria's metabolic cardiovascular profile: § Cholesterol 188 mg/dl (4.87 mmol/l) § LDL cholesterol 106 mg/dl (2.75 mmol/l) § HDL cholesterol 56 mg/dl (1.45 mmol/l) § Glucose 84 mg/dl (4.7 mmol/l) § Blood pressure 125/78 mm Hg Adapted from Van Gaal LF Eur Neuropsychopharmacol 2006;16:S142-8 Source: www.myhealthywaist.org Not all Fat Is the Same… Claudine Age: 58 years Weight: 92 kg BMI: 35.4 kg/m2 Intra-abdominal (visceral) adiposity Subcutaneous Maria's metabolic cardiovascular profile: fat § Cholesterol 4.87 mmol/l § LDL cholesterol 2.75 mmol/l § HDL cholesterol 1.45 mmol/l § Glucose 4.7 mmol/l § Blood pressure 125/78 mm Hg Claudine's metabolic cardiovascular profile: § Cholesterol 6.24 mmol/l § LDL cholesterol 4.79 mmol/l § HDL cholesterol (0.98 mmol/l § Glucose 7.3 mmol/l § Blood pressure 140/85 mm Hg Adapted from Van Gaal LF Eur Neuropsychopharmacol 2006;16:S142-8 Source: www.myhealthywaist.org Body shape matters: vs Central distribution of body fat: waist circumference Central fat accumulation tends to be intra-abdominal (visceral fat around the organs) Other types of obesity tend to be subcutaneous (fat under the skin) Intra-abdominal fat is more metabolically active (more lipids are released) and can interfere with hormone actions in the liver and pancreas Increased risk Substantially increased risk men > 94 cm > 102 cm women > 80 cm > 88 cm https://www.aihw.gov.au/reports/biomedical-risk-factors/risk-factors-to-health/contents/overweight-and-obesity Figure 3: Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome J Clin Invest DOI: 10.1172/JCI129187 Central obesity – link between inflammation and insulin resistance Subcutaneous fat cells appear to be able to store more fat without much change in their overall metabolism. In intra-abdominal fat cells, however, a “stress response” occurs when a certain degree of hypertrophy is reached. The stress response has two major outcomes: 1) insulin resistance first develops in the adipocyte, which reduces glucose uptake and lessens inhibition of lipolysis and 2) the stressed adipocyte secretes molecules that chemically attract cells of the immune system, TNF-α and IL-6 expression (both released by fat cells) may cause insulin resistance, they have both been shown to interfere with insulin signalling in adipose tissue and the liver. 4/11/24 Key: TNF-α – Tumor necrosis factor alpha IL-6 – Interleukin 6 18 Body shape matters: vs Key concepts about central obesity: 1. Intra-abdominal adipocytes (fat cells) are more metabolically active. They release and absorb more free fatty acids than subcutaneous fat. 2. Adipocytes doesn’t just store fat, they also secretes hormones that can increase atherogenic or diabetogenic risk 3. Obesity, especially intra-abdominal (visceral) obesity, is associated with chronic low-grade inflammation. 4. This inflammation may lead to insulin resistance and dyslipidemia The metabolic syndrome The metabolic syndrome is characterized by a group of metabolic risk factors in one person. They include: }Abdominal obesity }Atherogenic dyslipidemia }Elevated blood pressure }Insulin resistance or glucose intolerance }Prothrombotic state }Proinflammatory state Increased risks of coronary heart disease (including stroke & peripheral vascular disease) as well as type 2 diabetes http://www.blueprintsolution.com/store/fitcommerce/abdominal_obesity_2.jpg High body weight is also associated with: Psychological distress – Obesity is frequently accompanied by depression and the two can trigger and influence each other Osteoarthritis - Obesity is associated with the incidence and progression of OA in both weight-bearing and non weight-bearing joints. Evidence points to weight bearing, hormonal and cytokine dysregulation (inflammation) causes. Hernias - Obesity increases risk of hernia (particularly in areas of abdominal surgery) and decreases success of hernia repair. Gallstones - Obesity increases gallstone incidence. Losing weight very quickly can also raise chances of forming gallstones Back strain - Obesity associated with increased risk of back strain After the repair of an umbilical hernia, the patient formed a large incisional hernia High body weight is also associated with: Sleep apnoea – Around 58% or moderate-to-severe obstructive sleep apneoa (OSA) is due to obesity. The subsequent sleep fragmentation can in turn accelerate weight gain. Some studies report sleep deprivation associations with increased appetite hormones and subsequent altered eating patterns, including a preference for calorie dense foods. High body weight is also associated with: Menstrual abnormalities – Obesity (particularly central) increases risk of irregular and/or heavy menstruation. This might be a symptom of PCOS (Polycystic ovary syndrome) linked to insulin resistance and hormonal imbalance Increased cancer risk – Obesity is associated with increased risk of many cancers. Need to determine if it is lifestyle or the increased adiposity that is causing the link. e.g.: Endometrial – 2-4 times risk in women Liver – 2 times the risk Kidney – 2 times the risk Pancreatic – 1.5 times the risk Obesity – Genetic and Environmental Causes Genetic risk factors - why are some overweight and others thin? Generally obesity is a complicated mix of genetic predisposition and lifestyle factors Evidence for a genetic link: 1. Overweight tends to cluster in families (including in twins raised apart) 2. There is evidence of monogenic obesity (only 78 cases from 7 genes worldwide) 3. Sequence variations in genes have been associated with obesity phenotypes (and accumulative variations increase your risk of obesity) 4/11/24 PAGE 25 SECTION TITLE GOTHAM NARROW BOLD 7PT Obesity – single nucleotide polymorphisms (SNPs) SNPs are identified when scientists sequence the DNA from several different people’s genes. The genes involved are probably genes that interact with environment factors related to energy intake and expenditure to increase risk of obesity Images - http://learn.genetics.utah.edu/content/precision/snips/ 4/11/24 PAGE 26 Obesity: Bronwen Dalziel 2018 Where might the genetic disorders occur? — Peripheral signals —Appetite stimulating: ghrelin (stomach) —Appetite suppressing: e.g. leptin (adipose), insulin (pancreas), CCK, GLP1, stretch receptors, PYY — Hypothalamic centres that receive and integrate the signals —Appetite stimulating: NPY, AgRP and LepR (when leptin low) —Appetite suppressing: POMC/CART, Mc4R —Mood and reward: psychological reasons for eating or not eating — Effector systems that influence energy intake and energy expenditure —Autonomic nervous system e.g. thermogenesis —Ingestive behaviour 4/11/24 PAGE 27 Genetic syndromes https://www.youtube.com/watch?v=03DFb72zZ8w https://www.youtube.com/watch?v=qF3xl6OBIwU Monogenic disorders - Prader Willi — Dysfunction of the hypothalamic-pituitary axis — Obesity — Muscular hypotonia — Mental retardation — Short stature (low GH) — Small hands and feet — Hypogonadotropic hypogonadism Why are PWS obese? The proposed mechanisms include: disruption in pathways of satiety control resulting in hyperphagia reduced energy expenditure. Persistent increase in ghrelin (hunger hormone) results in increased appetite Decreased plasma pancreatic polypeptide (PP) and peptide YY (PYY) contribute to failure to satiety control Deficiency of growth hormone and hypogonadism result in reduced muscle mass and increased body fat. Note: Prof Hardikar’s lecture on Metabolic and regulatory response to food intake will give more details on these hormones Mutations in Leptin/Leptin Receptor Leptin increases with increasing fat Leptin is appetite suppressing and acts on the CNS Obese individuals can have high leptin levels but can be leptin resistant – (low leptin receptor activity so the message to stop eating is not passed on) Broberger (2005) Brain regulation of food intake and appetite: molecules and networks J Intern Med 258: 301-327 Genetics and obesity conclusion In the general population, it is likely that small sequence variations in genes (SNPs) could account for genetic predisposition to weight gain A higher number of “obesity genes” causes a lower response to feeling full and a larger BMI and waist Satiety/appetite plays a large role in ability to self regulate food intake Healthy lifestyle can largely counteract these genetic effects van Jaarsveld CHM, Boniface D, Llewellyn CH, Wardle J. Appetite and GrowthA Longitudinal Sibling Analysis. JAMA Pediatr. 2014;168(4):345–350. doi:10.1001/jamapediatrics.2013.4951 4/11/24 32 Lifestyle influences on obesity Energy intake Increased energy intake and low quality nutrition Refined grains, red meat, unhealthy fat, sugar Lack of whole grains, veg and fruit and nuts Obesity linked to lower socioeconomic status Too much screen, lack of activity and lack of sleep 4/11/24 33 Obesity – Treatment recommendations and research Obesity interventions A handful of key behaviours should be targeted: 1. Limiting unhealthy foods (refined grains and sweets, potatoes, red meat, processed meat) and beverages (sugary drinks) 2. Increasing physical activity 3. Limiting television time, screen time, and other “sit time” 4. Improving sleep 5. Reducing stress 4/11/24 35 Obesity interventions Families Healthy lifestyle begins at home Parents can role-model healthy choices to their children and ensure the fridge and pantry has no junk food options (softdrink, sweets, chips) 4/11/24 Eat together Take interest in food and cooking, even gardening 36 Obesity interventions Health care Help patients navigate the overwhelming amount of bad information. Have clear, evidence-based messages Understand the diet trends so that you can help patients understand the pros and cons of what they are trying to achieve Hospitals should make it easy for staff and patients to make health food choices 4/11/24 37 Obesity interventions Healthy food environments Improved food marketing and labeling Don’t target children Restaurant nutrition labeling, limit toys 4/11/24 38 Obesity interventions Healthy lifestyle check list Make your calories count: Minimally processed Vegetables and fruit (whole) Nuts, seeds, beans and healthy protein Healthy fat Limit sugar Eat breakfast Small portions and eat slowly Eat at home Eat mindfully (are you really hungry)? Stay active (walk, ride, housework, resistance training, stretching) Sleep: Adults 7-8 hours a night / Adolescents 8.5 – 9.25 hours a night 4/11/24 39 Obesity interventions A quick comment on ‘popular’ nutrition Nutrition is a rapidly changing field Not all published papers are good quality Some research is sensationalised too early in the research process Understanding research helps navigate good from bad Some fad diets will actually help your patients (but might not be sustainable) We are changing the way we think about fat and carbohydrate Government guidelines will always be slower than current diet trends 4/11/24 40 SECTION TITLE GOTHAM NARROW BOLD 7PT Dr Bronwen Dalziel Senior Lecturer in Medical Education (level 2 office) Questions: Energy balance Prac 1 or 2 or [email protected] 4/11/24 PAGE 41