aetiology and current evidence base for weight management naveed sattar professor of metabolic...
TRANSCRIPT
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.