Aetiology and current evidence
base for Weight Management
Naveed Sattar
Professor of Metabolic Medicine
BHF GCRC, University of Glasgow
& Hon Consultant
Glasgow Royal Infirmary
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
Rates
UK, social class variations
 Worldwide
 Children

UK rates since 1980
epidemic
Lean, Gruer, Alberti, Sattar (2006) BMJ
FORESIGHT forecast

2025


40% adults obese (2 in 5)
By 2050 – Britain a mainly obese society
Changing prevalence of obesity in the UK
Prevalence of obesity (BMI > 30) in UK women 1994 - 2002
Which disease process is more
closely linked to obesity?
Type 2 diabetes – the microvascular burden
at diagnosis a decade or so ago
Retinopathy1
21%
Nephropathy2
18%
20%
Neuropathy1
Erectile
dysfunction1
12%
1. UKPDS Group. Diabetes Res 1990; 13: 1–11.
2. The Hypertension in Diabetes Study Group. J Hypertens 1993; 11: 309–317.
Yearly diabetes prevalence
1995-2005 Ontario Canada
Lipscombe & Hux Lancet 2007
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
Less well know risks of Obesity?
Medical Complications of Obesity
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Stroke
Idiopathic intracranial hypertension
Cataracts
Coronary heart disease
Pancreatitis
Nonalcoholic fatty liver
disease
steatosis
steatohepatitis
cirrhosis
Gall bladder disease
Cancer
breast, uterus, cervix, prostate, kidney
colon, esophagus, pancreas, liver
Skin
Gout
Diabetes
Dyslipidemia
Hypertension
Gynecologic abnormalities
abnormal menses/ infertility
polycystic ovarian syndrome
Numerous pregnancy comps.
Osteoarthritis
Phlebitis
venous stasis
Populations more susceptible to
adverse effects of weight gain?
Hot spots for type 2 diabetes
IDF Atlas 2003
The Middle-East – world diabetes
hot-spot
18.7%
15.4%
16.8%
14.6%
13.4%
DM prevalence for
adults age 20-79
Age at
diagnosis
BMI
Whites
n=1557
57
30
South Asians
n=210
46
28.7
Mukhopadhyay*, Forouhi*, Fisher, Kesson, Sattar. Diab Med 2005
Weight gain pulls trigger
Risk of Type 2 diabetes
60
OVERWEIGHT
OVERWEIGHT
OBESE
OBESE
50
40
30
20
10
0
< 23
23–
23.9
24–
24.9
25–
26.9
27–
28.9
BMI
Chan JM et al. Diabetes Care 1994; 17: 961–969.
29–
30.9
31–
32.9
33–
34.9
> 35
Obesity to Diabetes – concept of
ectopic fat….
Or “fat in wrong places”
Most fat is healthy
 Who
has most fat?
 Women
 Less CHD?
 Less diabetes?
 Why?
 More
Subcutaneous fat
Average BMI (kg / m^2)
Men vs. Women – DM riskrisk?
Men
Women
40
35
30
30
40
50
60
70
80
Age at diagnosis of diabetes (years)
Logue et al (In press) Diabetologia
90
ECTOPIC CONCEPT
Consider 100kg man
 Total fat ~35kg
 70-75% will be Subcutaneous
 10-15% Visceral fat
 10-15% elsewhere (E)

Ethnicity
Genes/ Programming
Illness
Subcutaneous
GOOD
But if storage
capacity exceeded
Or diminished
These sites empty
quicker
5% weight loss
(100kg man)
~ 30% VF loss
VF
(0.5-6kg)
E
Ectopic fat
Muscle and Liver
Elsewhere
Excess calories
(increased intake or
reduced energy expenditure)
Subcutaneous stores
overwhelmed
(genes, ethnicity, ageing)
Hepatic lipid
accumulation
muscle
FAT
‘Spill over’
Insulin resistance
pancreatic
beta cell
Perivascular fat 
Endothelial dysfunction
Hyperglycaemia
Fat accumulation in liver – when and what signs?
oxidation
Fat
Glucose
(protein)
 glucose
Production (FBG)
Fatty
acids
 trigs
DNL
fat cells
larger
Liver
Enzymes
ALT
GGT
Sattar et al
(2007)
Diabetes
Less insulin 
Liver fat





ALT > AST
GGT high
Overweight
Glucose high normal
HDL-C often low
vs.




alcohol
AST>ALT
MCV high
HDL-C higher than
expected!
Not necessarily
overweight or high
glucose
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
Keeping liver fat down?
N=8 subjects with diabetes - Hypocaloric low fat diet (3%)
Wt
Glucose
Insulin
86 to 78 kg
8.8 to 6.6 mmol/l
174 to 66 pmol/l
Percent fat 12% to ~2%
Petersen et al
Diabetes. 2005
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
PART 2 –
treatment of obesity
thoughts on prevention
Why are we in this mess?
Foresight
Simple surely
“Too much in,
not enough
out”
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)
Children
x
Adults
Data from Swinburn et al 2009
Heavier people have higher
energy expenditure, and
thus intake
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
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

“What is provided is what is eaten
So what is provided has to change”
Lean, Gruer, Alberti, Sattar
(2006) BMJ
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
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
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

Much more complex
FORESIGHT The full obesity
system map with thematic clusters
Primary driver for epidemic
Overeating or under activity?
Jeffery RW, Harnack LJ.
Evidence Implicating Eating as a Primary Driver
for the Obesity Epidemic. Diabetes 2007;56:2673-6
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….

1949
“…an epidemic; under the right economic
& social circumstances, obesity from
overeating will be a dominant nutritional
problem.”

Ancel Keys
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
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 AND
sustain weight loss
Very hard to lose weight by
physical 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
Appetite/satiety signals impaired
when obese
Stanley S et al. Physiol Rev 2005; 85: 1131
Obesity – public health issue –
prevention must be priority
Limit “energy dense”
foods
 sat fat,
 refined sugar
Fruit & Veg.
fibre….
Snacking – eat more
fruit…. Chew etc
Less smoothies /
fruit juices
Treating obesity?
Systematic reviews - SIGN
Dietary and lifestyle up to 5kg (2-4 yrs)
 Drugs 5-10kg (1-2 yrs)
 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 spoons of sugar
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
Ask – not all patients ready to discuss
weight
 Assess – BMI still best (accuracy – more
data on longer associations)
 Advice – health service may not be best
place to improve weight


Susan Jebb (Foresight report)
Weight watchers beats GP practice (Jebb et al
Lancet 2011 RCT, 722 patients)
WW - good for wider use
Referral to WW with regular weighing, advice
about diet and activity, motivational sessions
and group support
can offer early intervention for weigh
management in overweight and obese that can
be delivered at large scale

What do we tell our patients
Body weight
50-100kcal per day for weight maintenance
Successes
1. Sustained weight, no increase.
Obese
2. Minor weight loss with dietary change
to reduce risk of complications.
Overweight
Normal
3. Weight normalisation: rare
Treatment strategies
Years of management or intermittent monitoring
Adapted from Rössner, 1992 by U.S. Institute of Medicine, 1995.
Graded reductions in energy intake & effect over time
Retrain your taste buds
gradually – goal setting
1st
change
2nd
change
3rd
change
Final summary
Rates – epidemic – 40% by 2025
 Risks – plentiful – all body systems, QOL
 Research – ectopic fat  many effects
 Reality – prevention must be key as once
obese, reversal v. hard by any medical
method
 Patients – emphasise small and
sustainable changes…intake and
activity…achieve and extend if needed.
