1. Dr Michal Ajzensztejn The Evelina London Children’s Hospital July 2014
Childhood obesity
Dr Michal Ajzensztejn
The Evelina London Children’s Hospital July 2014

2. Overview Definition Size of the problem? Aetiology
What is the cause for concern?
Management
prevention
Investigation
Treatment

3. Definition of obesity Gold standard is body composition
MRI / Dexa / bioimpedence (proxy)
Waist circumference
BMI = Kg/M²
A child's weight status is determined using an age- and sex-specific percentile for BMI rather than the BMI categories used for adults because children's body composition varies as they age and varies between boys and girls.

4. Definition
Obesity expert committee- pediatrics 1998 Overweight: 85-95th Centile Obese: >95th Centile International Obesity Task Force Overweight>91st centile Obese>99th centile

5. International obesity task force definition (IOTF) Cole et al BMJ 2000;320:1
Centiles for body mass index for British males and females. Centile curves are spaced two thirds of z score apart. Also shown are body mass index values of 25 and 30 kg/m2 at age 18, with extra centile curves drawn through them

6. Types of obesity in childhood

7. The scale of the problem
WHO- childhood obesity one of the most serious global public health challenges of 21st century.
The National Child Measurement Program (CCMP) measures the height and weight of ~1M school children in England/yr. Latest figures show:
14.4% of children aged 10-11yrs – obese
18.9% of children aged 10-11yrs- overweight
9.3% of children aged 4-5yrs – obese
13% of children aged 4-5yrs - overweight.
1/3rd of 10-11yrs old + >1/5th of 4-5 yr olds were overweight or obese.
According to the National Audit Office- weight problems costs the Health Service £500million in consultations, drugs and other therapies.
Obesity causes 30,000 deaths a year.
Research from British Heart Foundation suggests children and young people could die from complications of obesity before their parents
By 2030 up to 48% of men and 43% of women in the UK could be obese if current trends in rise of obesity continue

8. Trends in adult prevalence of obesity (BMI > 30kg/m2)

9. Trend in childhood obesity US children 1971-2006

10. Causes of primary obesity
Interaction between genetic predisposition (50- 90%)& environment affecting food intake and energy expenditure
Twin studies offer some insight into the genetics of common obesity
Data from > 25,000 twin pairs and 50,000 biological and adoptive family members
Estimates for mean correlations for BMI are:
0.74 for monozygotic twins,
0.32 for dizygotic twins
0.25 for siblings
0.19 for parent–offspring pairs,
0.06 for adoptive relatives
0.12 for spouses

11. Environmental factors
Increase risk
History of SGA- increased rates of obesity and metabolic syndrome
Poor infant feeding
Reduced energy expenditure
Social concerns- fear to let children play outside
Parental obesity/ eating disorders
Increased high fat / carb food intake
Increased sedentary lifestyle
Screen time (TV, computers, phones, ipad)
Protective factors
Family meals
Self esteem
Breastfeeding

12. Foetal origin hypothesis “Barker Hypothesis”
‘Foetal undernutrition in middle to late gestation leads to disproportionate foetal growth’ programmes later coronary heart disease’
‘The most unfavourable outcome is thinness at birth followed by a rapid increase in body weight’

13. Foetal programming
The way the mother prepares the foetus for the world in which it will be born
A communication through placental nutrition
Nutrition may alter the expression of maternal genes involved in foetal growth – ‘imprinting’ – gene methylation
The ‘Thrifty Phenotype’ - a mismatch between fetal programming and the environment

14. Genetics
Polygenic inheritance pattern with 2 subtypes (generalised and abdominal)
multiple polymorphic single genes likely involved
no genes for common obesity identified
very rare monogenic forms of obesity
Gene defects
ob/ob mouse – genes mutant – leptin deficient
db/db mouse- mutation in leptin receptor
POMC/ MC4R / neuronal insulin receptor mutations
Polygenic inheritance is when a single trait is controlled by 2 or more sets of alleles. A polygenic variant by itself has a small effect on the phenotype; only in combination with other predisposing variants does a sizeable phenotypic effect arise.
As a phenotype obesity is also heterogeneous, and there are at least two distinct but frequently overlapping subtypes: general obesity, which results in increased body fat mass, and abdominal obesity. These subtypes have different physiological, clinical, and prognostic implications. The phenotypes seem to have some of the same genetic and environmental influences in common
The strong environmental effects that have been observed lead to the belief that obesity is the result of an interaction between a genetic predisposition and environmental influences, although the specific evidence for these interactions is weak.

15. Genetics Of Obesity Study (GOOS) Cambridge
Sadaf Farooqi and Stephen O’Rahilly
BMI >4SDs for age /sex
Consanguineous or
FH of early onset < 10 yrs
Over 3000 samples analysed

16. Monogenic causes of obesity
Leptin deficiency
Leptin receptor deficiency
Hypogonadotrophin hypogonadism and other pituitary hormone abnormalities
Prohormone convertase1 (PC1) defect
Abnormal glucose tolerance
Hypocortisolism, hypog/hypog.
Melanocortin – 4-receptor defect
POMC deficiency
Red hair, adrenal insufficiency
PPARγ defect
Normally, a gene known as PPAR controls the amount of fat cells that are made and the size of those cells. "With this mutation, the gene gets stuck in the 'on' position causing more fat cells to form,"
The protein produced by the PPAR gene appears to regulate insulin resistance in diabetics. People with the mutation seem to use insulin more effectively to control their blood sugar, although some of them do develpe diabetes

17. Ghrelin Hunger-stimulating peptide
produced by P/D1 cells in lining of the fundus of stomach
Ghrelin receptors are expressed in the pituitary, stomach, intestine + pancreas.
Gherlin levels increase before meals and decrease post meals
When a person loses weight-  ghrelin levels , which causes food consumption and weight gain
When a person gains weight  ghrelin levels, causing a  in food consumption and weight loss

18. Leptin "satiety hormone"
Leptin is made by adipose tissue, it acts via receptors in the brain (LRb) to regulate energy balance and satiety.
Leptin stimulates the hypothalamus to give us the sensation of satiety resulting in decreased appetite and increases metabolism to aid wt loss.
The less fat you have, the less leptin you produce, resulting in increased appetite and decreased metabolism to enables wt gain.
However if you have increased fat stores there is increased leptin, which can lead to leptin resistance. So despite lots of leptin, appetite is not suppressed, metabolism is slowed down resulting in increased appetite and wt gain.

19. Ghrelin-hunger-stimulating peptide produced by P/D1 cells in lining of the fundus of stomach.
Ghrelin receptors are expressed in the pituitary, stomach, intestine, pancreas.
Gherlin levels increase before meals and decrease post meals and is the counterpart of the hormone leptin (produced by adipose tissue), which induces satiation.
Ghrelin is a potent stimulator of GH secretion.
Body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. Studies have shown that ghrelin levels are negatively correlated with weight. This data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain.[33] When a person loses weight their ghrelin levels increase, which causes increased food consumption and weight gain. On the other hand, when a person gains weight, ghrelin levels drop, leading to a decrease in food consumption and weight loss (Tung, 2005). This suggests that ghrelin acts as a body weight regulator, continuously keeping one's body weight and energy stores in check
Leptin is a hormone made by fat tissue that acts on the brain to regulate food intake and body weight

20. Medical causes of obesity
Endocrine
Hypothyroid
Cushing syndrome
Pseudohypoparathyroidism
PCOS
Monogenic
Leptin deficiency
POMC deficiency
MC4R mutation 5% BMI>3 or 4SD
Hypothalamic
Eg tumours/craniopharyngioma
Syndromes
Prader-Willi
Bardel-Biedl
Cohen
Carpenter

21. Why is childhood obesity getting so much attention!
Tracking into adult life( 60%)
Metabolic syndrome (IRS)
Secondary effects

22. Implications of childhood obesity
Obese children become obese adults
Comorbidities:
Hypertension
Metabolic syndrome: hyperlipidaemia
PCOS
Non-alcoholic fatty liver
Insulin resistance/ impaired fasting and glucose tolerance Type 2 DM
Slipped femoral capital epiphysis/ joint pain
Sleep apnea
Asthma
Benign raised intracranial pressure
Emotional + psychological effects of being overweight
Teasing/ bullying
Low self esteem
Anxiety
Depression

23. Insulin resistance Syndrome
Metabolic syndrome (syndrome X)
Central obesity (apple shape)
Hypertension
Raised triglycerides
Low HDL
Insulin resistance PCOS
Steatohepatitis
Glomerulonephritis
Atherosclerosis
Impaired glucose tolerance

25. Insulin resistance syndrome
A velvety brown change to the skin
Mostly in neck, axilla, groin
Looks like dirt but doesn’t wash off!
Usually obese
Almost always have insulin resistance
Leads to Type 2 diabetes

26. Local problem
In 2000, the first cases of Type 2 diabetes in children were diagnosed in overweight girls aged 9 to 16 of Pakistani, Indian or Arabic origin in the UK.
Nationally incidence of type 2 diabetes amongst children is 1.5%
In Lambeth and Southwark the incidence of type 2 is closer to 5%.

28. Obesogenic Environement
Family
Excess weight in parents
Breast feeding practices
Parent’s health
Much Sedentary activity e.g
TV, computers etc.
Knowledge
Budgeting, shopping and cooking skills
Genetic predisposition
Education & information
School lessons
Lifestyles
Nutrition
Cooking
Media messages
Fashions
Body image
Cultural beliefs
Conflicting information
Sports & Leisure
Lack of school facilities
Few local playing areas
Widely available indoor-
passive entertainment
Unsafe streets
Few cycle routes
Obesogenic Environement

29. Social + economic inequalities in diet and physical activity

30. Management Primary Prevention
Community based weight management service
Tertiary obesity service
Severe obesity
Obesity with co-morbidities

31. Primary Prevention Ante-natal care of the obese mother
Use of appropriate standards
WHO-UK Growth charts
Focus on early intervention (under 5s)
Education of midwives and HVs
Better infant feeding advice
Promotion of breast feeding
Better management of SGA/IUGR infants

32. Community based services
Not just an issue for health workers-
community-wide approach
Input from education, LAs, sports bodies and voluntary groups
Specialised school nurse
An Information Resource
Educators
Give basic dietary advice
Risk assessment for referral
MEND- Mind, Exercise, Nutrition, Do it / Ready Steady Go
Planning permission- locality of sweet shops / fast food shops to schools
Media + Advertising companies- also have a duty

33. Tertiary level Severe ‘morbid’ obesity
Pre-diabetic, insulin resistance, Type 2 diabetes
Adverse FH diabetes, ↑BP, ↑cholesterol, Ischaemic heart disease
Health co-morbidities
Cardiac
Renal
Neurological/muscular disorders
Steroids induced
Monogenic / syndrome

34. Tertiary service Multi-disciplinary team Psychologist / Family therapy
Dietician
Sports trainer
Paediatrician
?Social worker
An initial team assessment
Motivational Interviewing skills
Understanding eating behaviours
Fuller family analysis

35. Classification for Investigation
Primary obesity with no family risk
Primary obesity with adverse family risk or signs/ suspicion of hyperinsulinism/ type II diabetes
Suspicion of secondary obesity/ genetic cause

36. Investigations Simple obesity with no adverse family risk
If well grown in height and normal on examination:
liver & renal function +/- liver USS
TFT
Fasting lipids
Fasting glucose/insulin
blood pressure (ambulatory if possible)
Simple obesity with family risk history or clinical suspicion of hyperinsulinism
As above plus
OGTT with insulins
Secondary / genetic cause
Investigate cause Eg UFC for cushings. Overnight Dex suppression test
Genetics for GOOS study

37. Who to treat? Those with BMI > IOTF 30
Those with BMI >IOTF 25 with
strong family history diabetes/early CVD
impaired glucose tolerance
Age:
Rx should focus on >8 yrs
Those obese < 8yrs with obese parents
IOTF- international obesity task force

38. Treatment Treatment of obesity Diet Drugs Exercise programs
Psychological approaches
Multi-disciplinary approaches
Surgery- Bariatric surgery / intragastric balloon
Treatment of obesity complications

39. Treatment targets 5% loss is standard adult weight loss target
10% is doing very well!
but losses are maintained better in children than adults
Weight maintenance in growing children
Imperative to start Rx before growth ceases

40. Treatment of Choice comprehensive treatments including:
behavioral modification procedures
dietary intervention
an exercise program
reduction of sedentary behaviours
family centred
motivational enhancement

41. Drugs Drug trials for obesity in children & adolescents
Extremely few published
Drugs not licensed
We cannot assume risks and benefits same as in adult

42. What’s available 2.5 kg to 3.0 kg over 3-4 yrs. Compared with placebo
Orlistat – binds intestinal and pancreatic lipase and reduces dietary fat absorption by 30%
2.5 kg to 3.0 kg over 3-4 yrs. Compared with placebo
Reduces absorption of fat soluble vitamins
Metformin – useful in diabetes, impaired glucose intolerance and possibly insulin resistance
May improve cardiovascular outcome and reduce risk of PCOS/ metabolic syndrome

43. Surgery
UK: NICE guidelines recommend consideration of surgery for young people in exceptional circumstances
“Surgery...has the best chance of significant weight loss, reversal or improvement of current co-morbidities, and reduction of risk for future co-morbidities” Brown &Inge 2009

44. Criteria for Bariatric Surgery in children
BMI of 40 (kg/m2) or more - OR
BMI > other significant disease
All non-surgical measures have failed for at least 6 months
Receiving intensive management in a specialist service
Generally fit for anaesthesia and surgery
Commitment to long-term follow-up
Physiological and psychological maturity

45. Bariatric Surgery Types No surgery without risk- High risk group
Gastric banding
Gastric bypass
Gastric sleeve surgery
No surgery without risk- High risk group
Post surgical complications
Long term follow up
Long term supplement therapy

46. Intragastric balloon Rx?
Less invasive
No long term complications
However are the results as sustainable?

47. The Evelina London Children’s Hospital obesity service
Still in the job planning phase
Will integrate community to tertiary level care
Bridge between medical and surgical intervention
Provide intragastric balloons
Multidisciplinary team:
Psychological/ family approach
Dietician
Sport/ activity
Nurse
Doctor
Speciality care: sleep study, orthopaedic, referral to King’s for liver and bariatric surgery

48. Thank you
QUESTIONS?