Aetiology and current evidence Aetiology and current evidence base for Weight Managementbase for Weight Management

Naveed SattarNaveed SattarProfessor of Metabolic MedicineProfessor of Metabolic Medicine

BHF GCRC, University of GlasgowBHF GCRC, University of Glasgow& Hon Consultant& Hon Consultant

Glasgow Royal InfirmaryGlasgow Royal Infirmary

Outline Outline

How much obesity and whereHow much obesity and where??What are the medical consequences?What are the medical consequences?Mechanisms to metabolic disease – Mechanisms to metabolic disease –

“ectopic fat”“ectopic fat”Some hard truths about wt loss – Some hard truths about wt loss –

““why hard to lose…..” why hard to lose…..” What can be done about itWhat can be done about it

RatesRates

UK, social class variationsUK, social class variationsWorldwideWorldwideChildrenChildren

UK rates since 1980UK rates since 1980

Lean, Gruer, Alberti, Sattar (2006) BMJ

epidemicepidemic

FORESIGHT forecastFORESIGHT forecast

2025202540% adults obese (2 in 5)40% adults obese (2 in 5)

By 2050 – Britain a mainly obese societyBy 2050 – Britain a mainly obese society

Changing prevalence of obesity in the UKChanging prevalence of obesity in the UK

Prevalence of obesity (BMI > 30) in UK women 1994 - 2002

Which disease process is more Which disease process is more closely linked to obesity?closely linked to obesity?

1. UKPDS Group. Diabetes Res 1990; 13: 1–11.2. The Hypertension in Diabetes Study Group. J Hypertens 1993; 11: 309–317.

Type 2 diabetes – the microvascular burden Type 2 diabetes – the microvascular burden at diagnosis a decade or so agoat diagnosis a decade or so ago

Erectile

dysfunction1

20%20%

Retinopathy1 21%21%

Neuropathy1 12%12%

Nephropathy2 18%18%

Yearly diabetes prevalence 1995-2005 Ontario Canada

Lipscombe & Hux Lancet 2007

Summary on obesity ratesSummary on obesity rates

On rise globallyOn rise globallyUK – ahead in EuropeUK – ahead in Europe40% obesity in ~17 year time40% obesity in ~17 year timeDeprivation-linked Deprivation-linked Diabetes most closely associatedDiabetes most closely associatedT2DM in childrenT2DM in children

Preventing Obesity is real targetPreventing Obesity is real target

Less well know risks of Obesity?Less well know risks of Obesity?

Medical Complications of ObesityMedical Complications of Obesity

Phlebitisvenous stasis

Coronary heart disease

Pulmonary diseaseabnormal functionobstructive sleep apneahypoventilation syndrome

Gall bladder disease

Gout

Diabetes

Osteoarthritis

Nonalcoholic fatty liver diseasesteatosissteatohepatitiscirrhosis

HypertensionDyslipidemia

Cataracts

Skin

Pancreatitis

Idiopathic intracranial hypertension

Cancerbreast, uterus, cervix, prostate, kidneycolon, esophagus, pancreas, liver

Gynecologic abnormalitiesabnormal menses/ infertilitypolycystic ovarian syndromeNumerous pregnancy comps.

Stroke

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

Hot spots for type 2 diabetes

IDF Atlas 2003

The Middle-East – world diabetes The Middle-East – world diabetes hot-spothot-spot

18.7%18.7%

16.8%16.8%

15.4%15.4%

14.6%14.6%

13.4%13.4%

DM prevalence for adults age 20-79

Mukhopadhyay*, Forouhi*, Fisher, Kesson, Sattar. Diab Med 2005 Mukhopadhyay*, Forouhi*, Fisher, Kesson, Sattar. Diab Med 2005

Whites n=1557

South Asians n=210

Age at diagnosis

57 46

BMI 30 28.7

Chan JM Chan JM et alet al. . Diabetes Care Diabetes Care 1994; 1994; 1717: 961–969.: 961–969.

BMIBMI

Ris

k of

Typ

e 2

diab

etes

Ris

k of

Typ

e 2

diab

etes

6060

23–23–23.923.9

< 23< 23 24–24–24.924.9

25–25–26.926.9

27–27–28.928.9

29–29–30.930.9

31–31–32.932.9

33–33–34.934.9

> 35> 35

00

5050

4040

3030

2020

1010

OVERWEIGHTOVERWEIGHT OBESEOBESEOVERWEIGHTOVERWEIGHT OBESEOBESE

Weight gain pulls trigger

Obesity to Diabetes – concept of Obesity to Diabetes – concept of ectopic fat….ectopic fat….

Or “fat in wrong places”Or “fat in wrong places”

Most fat is healthyMost fat is healthy

Who has most fat?Who has most fat?Women Women Less CHD?Less CHD?Less diabetes?Less diabetes?Why? Why?

More Subcutaneous fatMore Subcutaneous fat

Men vs. Women – DM riskrisk?

Logue et al (In press) Diabetologia

Age at diagnosis of diabetes (years)

Ave

rage

BM

I (k

g /

m^2

)

30

35

40

30 40 50 60 70 80 90

Men Women

ECTOPIC CONCEPTECTOPIC CONCEPT

Consider 100kg manConsider 100kg manTotal fat ~35kgTotal fat ~35kg70-75% will be Subcutaneous 70-75% will be Subcutaneous 10-15% Visceral fat 10-15% Visceral fat 10-15% elsewhere (E)10-15% elsewhere (E)

SubcutaneousGOOD

But if storage capacity exceeded

Or diminished VF E

(0.5-6kg)

Ethnicity Ethnicity

Genes/ Programming Genes/ Programming

IllnessIllness

These sites emptyThese sites empty

quicker quicker

5% weight loss 5% weight loss

(100kg man)(100kg man)

~ 30% VF loss~ 30% VF loss

Ectopic fatEctopic fat

Muscle and LiverMuscle and Liver

ElsewhereElsewhere

Excess calories(increased intake or reduced energy expenditure)

FAT ‘Spill over’

pancreatic beta cell

muscle

Subcutaneous stores overwhelmed

(genes, ethnicity, ageing)Hepatic lipid accumulation

Perivascular fat Endothelial dysfunction

Insulin resistance

Hyperglycaemia

glucoseglucoseProduction (FBG)Production (FBG)

fat cells larger

Fat accumulation in liver – when and what signs?Fat accumulation in liver – when and what signs?

Liver Liver EnzymesEnzymesALTALTGGTGGT

trigstrigs

Sattar et al (2007)

Diabetes

FatFat

GlucoseGlucose

(protein)(protein)

Fatty Fatty

acidsacids

DNLDNL

oxidationoxidation

Less insulin Less insulin

Liver fat vs. alcoholLiver fat vs. alcohol

ALT > ASTALT > AST GGT highGGT high OverweightOverweight Glucose high normalGlucose high normal HDL-C often lowHDL-C often low

AST>ALTAST>ALT MCV highMCV high HDL-C HDL-C higherhigher than than

expected!expected! Not necessarily Not necessarily

overweight or high overweight or high glucoseglucose

Case MR RCNCase MR RCN

BMI 34BMI 34FBG 6.2 mmol/lFBG 6.2 mmol/lALT 67 (<50) AST 34 (<50)ALT 67 (<50) AST 34 (<50)Trig 3.9 (<2.3mmol/l) HDL-c 0.9 (>1.0 Trig 3.9 (<2.3mmol/l) HDL-c 0.9 (>1.0

mmol/l)mmol/l)

IF AST starts to rise >0.8 of ALT (e.g. AST IF AST starts to rise >0.8 of ALT (e.g. AST 80 vs ALT 85) – then think of NASH80 vs ALT 85) – then think of NASH

Keeping liver fat down?Keeping liver fat down?

Petersen et al Diabetes. 2005

N=8 subjects with diabetes - Hypocaloric low fat diet (3%)

Wt 86 to 78 kgGlucose 8.8 to 6.6 mmol/lInsulin 174 to 66 pmol/l

Percent fat 12% to ~2%Percent fat 12% to ~2%

Research summaryResearch summary

Diabetes unmasked by excess weight gainDiabetes unmasked by excess weight gain if family Hx DM, South Asian, at lower BMIif family Hx DM, South Asian, at lower BMIweight leads toweight leads to ectopic fatectopic fatEctopic fat makes organs insulin resistantEctopic fat makes organs insulin resistantSigns of excess ‘ectopic’ liver fat commonSigns of excess ‘ectopic’ liver fat commonExpanding visceral fat – i.e. waist line – a Expanding visceral fat – i.e. waist line – a

marker of ‘saturated’ subcutaneous fat storemarker of ‘saturated’ subcutaneous fat store

PART 2 – PART 2 – treatment of obesitytreatment of obesity

thoughts on preventionthoughts on prevention

Why are we in this mess?Why are we in this mess?

Foresight Foresight

Simple surelySimple surely

““Too much in, Too much in, not enough not enough

out”out”

Moving on from ForesightMoving on from Foresight

Understanding obesity hampered by Understanding obesity hampered by inaccurate data on energy intake and inaccurate data on energy intake and expenditureexpenditure

– Heavier people have higher energy Heavier people have higher energy expenditure and intakeexpenditure and intake

– Almost all the increase in weight in US can Almost all the increase in weight in US can be attributed to be attributed to Total Energy Intake (rather Total Energy Intake (rather than than PA) (500kcal adults, 300kcal children)PA) (500kcal adults, 300kcal children)

Children

Adultsx

Data from Swinburn et al 2009Data from Swinburn et al 2009

Heavier people have higher Heavier people have higher energy expenditure, and energy expenditure, and

thus intakethus intake

ImplicationsImplications

People with lower BMIs need People with lower BMIs need substantially less food energy to maintain substantially less food energy to maintain weightweight

To achieve and maintain “healthy” weight, To achieve and maintain “healthy” weight, obese individuals need big obese individuals need big sustainedsustained reduction in energy intake or huge reduction in energy intake or huge increases in PAincreases in PA

Are we lazier and greedier than Are we lazier and greedier than prior generations?prior generations?

What did foresight conclude?What did foresight conclude?People in the UK are People in the UK are notnot more glutinous more glutinous

that previous generations, and their that previous generations, and their biology is biology is notnot different different

But major changes in society, work But major changes in society, work patterns, transport, food production and patterns, transport, food production and salessales

Pace of technology exceeding human Pace of technology exceeding human evolution evolution

“What is provided is what is eatenSo what is provided has to change”

Lean, Gruer, Alberti, Sattar (2006) BMJ

Recommended for 5-10yr olds.

The label boasts virtually fat free•Contains Artificial sweeteners108 calories and 9.6g of sugar per 100g

Contains40g of sugar per 100g174 calories per bowlSalt also is its third biggest ingredient

Other facts about food changesOther facts about food changes

Cost of fruit & veg: Cost of fruit & veg: Sugar and fat cost: Sugar and fat cost: Overproducing foodOverproducing food80% of daily salt intake via processed 80% of daily salt intake via processed

foods – cereals etcfoods – cereals etcProducts designed to be tastierProducts designed to be tastier

Sugar, fat, saltSugar, fat, salt

1978 1978

Crisp packet once per week, Crisp packet once per week, if luckyif luckyPerhaps one biscuit per day, Perhaps one biscuit per day, if luckyif luckyNo coke, yogurts, fast foods except chip No coke, yogurts, fast foods except chip

shopsshopsAll meals at home cooked by mumAll meals at home cooked by mumWalked everywhere, played outside all Walked everywhere, played outside all

timetimeNo computer, etc No computer, etc

Much more complexMuch more complex

FORESIGHT The full obesity

system map with thematic clusters

Environment

Environment obesogenic

obesogenic

Primary driver for epidemicPrimary driver for epidemicOvereating or under activity?Overeating or under activity?

Jeffery RW, Harnack LJ. Jeffery RW, Harnack LJ.

Evidence Implicating Eating as a Primary Driver Evidence Implicating Eating as a Primary Driver

for the Obesity Epidemic. Diabetes 2007;56:2673-6for the Obesity Epidemic. Diabetes 2007;56:2673-6

Simple considerationsSimple considerationsWe all love food – even…. We all love food – even…. Food more plentifulFood more plentiful

Increasing density, less time, consume fastIncreasing density, less time, consume fastSugary drinks abound Sugary drinks abound

How fast can you eat 200 calories?How fast can you eat 200 calories?How fast can you burn 200 calories?How fast can you burn 200 calories? A moment on the lips…. A moment on the lips….

19491949“…“…an epidemic; under the right economic an epidemic; under the right economic

& social circumstances, obesity from & social circumstances, obesity from overeating will be a dominant nutritional overeating will be a dominant nutritional problem.”problem.”

Ancel Keys

Government LeadershipGovernment Leadership People and the public (you and me)People and the public (you and me)

Public educationPublic education

little effect on behaviourlittle effect on behaviour

sets the scene, increase awareness, helps support for actionsets the scene, increase awareness, helps support for action

recognise inequalitiesrecognise inequalities

Public sector work (Schools, prisons, hospital )Public sector work (Schools, prisons, hospital )

Food industry (the Five Ps product, promotion, portion Food industry (the Five Ps product, promotion, portion size, packaging, pricing)size, packaging, pricing)

Re-formulations and labelling; Portions and promotionsRe-formulations and labelling; Portions and promotions

Advertising and marketingAdvertising and marketing

Huge Tin of Roses £4 Huge Tin of Roses £4

Food, retail and catering Industry

“Increase healthy options”

“increase range of portion sizes”

“promoting fruits and vegetables”

Food, retail and catering Industry- HALF A STORY! “Increase healthy options” “increase range of portion sizes” “promoting fruits and vegetables

DECREASE LESS HEALTHY OPTIONS DECREASE LARGE PORTION SIZES DECREASE CONFECTIONERY OPTIONS

At very least …?Level playing field…….

Reality: incredibly hard to lose Reality: incredibly hard to lose ANDAND sustain weight losssustain weight loss

Very hard to lose weight by Very hard to lose weight by physical activity alonephysical activity alone

“Most do not wish to be overweight”

Up to half who are obese will not

lose weight by any medical method

Lean, Gruer, Alberti, Sattar (2006) BMJ

Stanley S et al. Physiol Rev 2005; 85: 1131

Appetite/satiety signals impaired when obese

Obesity – public health issue – prevention must be priority

Limit “energy dense” foods

sat fat, refined sugarFruit & Veg.

fibre….

Snacking – eat more fruit…. Chew etc

Less smoothies / fruit juices

Treating obesity?Treating obesity?

Systematic reviews - SIGNSystematic reviews - SIGN

Dietary and lifestyle up to 5kg (2-4 yrs)Dietary and lifestyle up to 5kg (2-4 yrs)Drugs 5-10kg (1-2 yrs)Drugs 5-10kg (1-2 yrs)Surgery ~25-75kg (2-4 years)Surgery ~25-75kg (2-4 years)

1. Cut sugary drinks – Asked how many spoonfuls of sugar in x,y,

z etc • Coca-Cola • Red Bull• Irn Bru

“Healthy drinks?” • Copella Apple Juice• Frijj Chocolate Milk Shake• Lucozade Orange• Pom Wonderful• Ribena• Innocent Smoothie• Tropicana Orange

Tea

spoo

ns o

f sug

ar

Drinks sugar content not understood

• People slightly overestimated the amount of sugar in carbonated drinks,

• BUT significantly underestimated sugar levels in– milkshake, – a smoothie, – a leading sports drink and – a variety of fruit juices – – by as much as 17 tea spoons for one fruit juice drink

• An example of lack of clarity / miss-selling? • Paper being written up……..

In clinical practice? Refer to where? NHS not alone

AskAsk – not all patients ready to discuss – not all patients ready to discuss weightweight

AssessAssess – BMI still best (accuracy – more – BMI still best (accuracy – more data on longer associations)data on longer associations)

AdviceAdvice – health service may not be best – health service may not be best place to improve weight place to improve weight Susan Jebb (Foresight report)Susan Jebb (Foresight report)

Weight watchers beats GP practice (Jebb et al Weight watchers beats GP practice (Jebb et al Lancet 2011 RCT, 722 patients)Lancet 2011 RCT, 722 patients)

WW - good for wider use WW - good for wider use

Referral to WW with Referral to WW with regular weighingregular weighing, , adviceadvice about diet and activity, motivational sessions about diet and activity, motivational sessions and group supportand group support

can offer early intervention for weigh can offer early intervention for weigh management in overweight and obese that can management in overweight and obese that can be be delivered at large scaledelivered at large scale

Adapted from Rössner, 1992 by U.S. Institute of Medicine, 1995.

1. Sustained weight, no increase.

2. Minor weight loss with dietary change to reduce risk of complications.

3. Weight normalisation: rare

Body weight

Obese

Normal

Years of management or intermittent monitoring

Overweight

Treatment strategies

Successes

Natural course of furth

er

weight gain.

What do we tell our patientsWhat do we tell our patients

50-100kcal per day for weight maintenance50-100kcal per day for weight maintenance

Graded reductions in energy intake & effect over timeGraded reductions in energy intake & effect over time

Retrain your taste budsRetrain your taste budsgradually – goal settinggradually – goal setting

1st1st

changechange22ndnd

changechange 3rd 3rd

changechange

Final summaryFinal summary

RatesRates – epidemic – 40% by 2025 – epidemic – 40% by 2025RisksRisks – plentiful – all body systems, – plentiful – all body systems, QOLQOLResearchResearch – ectopic fat – ectopic fat many effects many effectsReality Reality – prevention must be key as once – prevention must be key as once

obese, reversal v. hard by any medical obese, reversal v. hard by any medical methodmethod

PatientsPatients – emphasise small and – emphasise small and sustainablesustainable changes…intake and changes…intake and activity…achieve and extend if needed. activity…achieve and extend if needed.