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

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

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.

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

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

Types of obesity in childhood

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

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

Trend in childhood obesity US children 1971-2006

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

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

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’

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

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.

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

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

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

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.

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

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

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

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

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

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

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%.

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

Social + economic inequalities in diet and physical activity

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Criteria for Bariatric Surgery in children BMI of 40 (kg/m2) or more - OR BMI >30 + 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

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

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

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

Thank you QUESTIONS?