Aetiology and current evidence base for Weight Management

1. Aetiology and current evidence base for Weight Management Naveed Sattar Professor of Metabolic Medicine BHF GCRC, University of Glasgow & Hon Consultant Glasgow Royal Infirmary

2. Outline • How much obesity and where? • What are the medical consequences? • Mechanisms to metabolic disease – “ectopic fat” • Some hard truths about wt loss – • “why hard to lose…..” • What can be done about it

3. Rates • UK, social class variations • Worldwide • Children

4. UK rates since 1980 epidemic Lean, Gruer, Alberti, Sattar (2006) BMJ

6. FORESIGHT forecast • 2025 • 40% adults obese (2 in 5) • By 2050 – Britain a mainly obese society

8. Changing prevalence of obesity in the UK Prevalence of obesity (BMI > 30) in UK women 1994 - 2002

9. RISKS Which disease process is more closely linked to obesity?

10. 21% Retinopathy1 18% Nephropathy2 20% Erectile dysfunction1 12% Neuropathy1 Type 2 diabetes – the microvascular burden at diagnosis a decade or so ago 1. UKPDS Group. Diabetes Res 1990; 13: 1–11. 2. The Hypertension in Diabetes Study Group. J Hypertens 1993; 11: 309–317.

11. Yearly diabetes prevalence 1995-2005 Ontario Canada Lipscombe & Hux Lancet 2007

12. Summary on obesity rates • On rise globally • UK – ahead in Europe • 40% obesity in ~17 year time • Deprivation-linked • Diabetes most closely associated • T2DM in children Preventing Obesity is real target

13. Less well know risks of Obesity?

14. Medical Complications of Obesity Stroke Idiopathic intracranial hypertension Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Cataracts Coronary heart disease Pancreatitis Diabetes Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Dyslipidemia Hypertension Gynecologic abnormalities abnormal menses/ infertility polycystic ovarian syndrome Numerous pregnancy comps. Gall bladder disease Cancer breast, uterus, cervix, prostate, kidney colon, esophagus, pancreas, liver Osteoarthritis Phlebitis venous stasis Skin Gout

15. Populations more susceptible to adverse effects of weight gain?

16. Hot spots for type 2 diabetes 0 IDF Atlas 2003

17. The Middle-East – world diabetes hot-spot 18.7% 16.8% 15.4% 14.6% 13.4% DM prevalence for adults age 20-79

18. Diabetes Whites South Asians n=1557 n=2 1 0 Age at 57 46 diagnosis BMI 3 0 28. 7 Mukhopadhyay*, Forouhi*, Fisher, Kesson, Sattar. Diab Med 2005

19. Weight gain pulls trigger 60 OVERWEIGHT OBESE OVERWEIGHT OBESE 50 40 Risk of Type 2 diabetes 30 20 10 0 < 23 23– 23.9 24– 24.9 25– 26.9 27– 28.9 29– 30.9 31– 32.9 33– 34.9 > 35 BMI Chan JM et al. Diabetes Care 1994; 17: 961–969.

20. Research - ectopic fat Obesity to Diabetes – concept of ectopic fat….Or “fat in wrong places”

21. Most fat is healthy • Who has most fat? • Women • Less CHD? • Less diabetes? • Why? • More Subcutaneous fat

22. Men vs. Women – DM riskrisk? Logue et al (In press) Diabetologia 40 Average BMI (kg / m^2) 35 30 30 40 50 60 70 80 90 Age at diagnosis of diabetes (years) Men Women

23. ECTOPIC CONCEPT • Consider 100kg man • Total fat ~35kg • 70-75% will be Subcutaneous • 10-15% Visceral fat • 10-15% elsewhere (E)

24. Ethnicity Genes/ Programming Illness These sites empty quicker 5% weight loss (100kg man) ~ 30% VF loss Subcutaneous GOOD But if storage capacity exceeded Or diminished VF E Ectopic fat Muscle and Liver Elsewhere (0.5-6kg)

25. Excess calories (increased intake or reduced energy expenditure) Subcutaneous stores overwhelmed (genes, ethnicity, ageing) Hepatic lipid accumulation muscle FAT ‘Spill over’ Insulin resistance Hyperglycaemia pancreatic beta cell Perivascular fat  Endothelial dysfunction

26. Fat accumulation in liver – when and what signs? oxidation  glucose Production (FBG) Fat Fatty acids Glucose (protein)  trigs DNL Liver Enzymes ALT GGT fat cells larger Sattar et al (2007) Diabetes Less insulin 

27. ALT > AST GGT high Overweight Glucose high normal HDL-C often low AST>ALT MCV high HDL-C higher than expected! Not necessarily overweight or high glucose Liver fat vs. alcohol

28. Case MR RCN • BMI 34 • FBG 6.2 mmol/l • ALT 67 (<50) AST 34 (<50) • Trig 3.9 (<2.3mmol/l) HDL-c 0.9 (>1.0 mmol/l) • IF AST starts to rise >0.8 of ALT (e.g. AST 80 vs ALT 85) – then think of NASH

29. Keeping liver fat down? N=8 subjects with diabetes - Hypocaloric low fat diet (3%) Wt 86 to 78 kg Glucose 8.8 to 6.6 mmol/l Insulin 174 to 66 pmol/l Percent fat 12% to ~2% Petersen et al Diabetes. 2005

30. Research summary • Diabetes unmasked by excess weight gain • if family Hx DM, South Asian, at lower BMI • weight leads toectopic fat • Ectopic fat makes organs insulin resistant • Signs of excess ‘ectopic’ liver fat common • Expanding visceral fat – i.e. waist line – a marker of ‘saturated’ subcutaneous fat store

31. Reality PART 2 – treatment of obesitythoughts on prevention

32. Why are we in this mess?Foresight

33. Simple surely “Too much in, not enough out”

34. Moving on from Foresight Understanding obesity hampered by inaccurate data on energy intake and expenditure Heavier people have higher energy expenditure and intake Almost all the increase in weight in US can be attributed to Total Energy Intake (rather than PA) (500kcal adults, 300kcal children)

35. Data from Swinburn et al 2009Heavier people have higher energy expenditure, and thus intake Children x Adults

36. Implications People with lower BMIs need substantially less food energy to maintain weight To achieve and maintain “healthy” weight, obese individuals need big sustained reduction in energy intake or huge increases in PA

37. Are we lazier and greedier than prior generations? • What did foresight conclude? • People in the UK are not more glutinous that previous generations, and their biology is not different • But major changes in society, work patterns, transport, food production and sales • Pace of technology exceeding human evolution

39. “What is provided is what is eaten So what is provided has to change” Lean, Gruer, Alberti, Sattar (2006) BMJ

40. Recommended for 5-10yr olds. Contains 40g of sugar per 100g 174 calories per bowl Salt also is its third biggest ingredient The label boasts virtually fat free • Contains Artificial sweeteners 108 calories and 9.6g of sugar per 100g

42. Other facts about food changes • Cost of fruit & veg:  • Sugar and fat cost:  • Overproducing food • 80% of daily salt intake via processed foods – cereals etc • Products designed to be tastier •  Sugar, fat, salt

43. 1978 • Crisp packet once per week, if lucky • Perhaps one biscuit per day, if lucky • No coke, yogurts, fast foods except chip shops • All meals at home cooked by mum • Walked everywhere, played outside all time • No computer, etc

44. Much more complex

45. FORESIGHT The full obesity system map with thematic clusters

46. Environment  obesogenic

47. Primary driver for epidemicOvereating or under activity? Jeffery RW, Harnack LJ. Evidence Implicating Eating as a Primary Driver for the Obesity Epidemic. Diabetes 2007;56:2673-6

48. Simple considerations • We all love food – even…. • Food more plentiful • Increasing density, less time, consume fast • Sugary drinks abound • How fast can you eat 200 calories? • How fast can you burn 200 calories? • A moment on the lips….

49. 1949 “…an epidemic; under the right economic & social circumstances, obesity from overeating will be a dominant nutritional problem.” Ancel Keys

50. Government Leadership People and the public (you and me) Public education little effect on behaviour sets the scene, increase awareness, helps support for action recognise inequalities Public sector work (Schools, prisons, hospital ) Food industry (the Five Ps product, promotion, portion size, packaging, pricing) Re-formulations and labelling; Portions and promotions Advertising and marketing Huge Tin of Roses £4