Treating Obesity in Patients with Down Syndrome and other Developmental Delay Syndromes
Angela Fitch, MD, FACP, FOMA
Associate Director MGH Weight Center
Massachusetts General Hospital/Harvard Medical School
1 obesitymedicine.org
Disclosures
• Bariatrix/Set Point Health: Advisory Board • Phenomix Advisory Board • Gelesis Advisory Board • MsMedicine Advisory Board • FoundHealth Advisory Board
2 Objectives
• Recognize the special issues with obesity facing patients with Down Syndrome and other developmental delays • Review the outcomes of patients with Down Syndrome and other genetic disorders in our comprehensive center. • Understand that anti-obesity medications and surgery are options for patients with the developmental challenges and how to tailor them to their needs
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Syndromes and Obesity
Without Developmental Delay With Developmental Delay • POMC deficiency • Prader Willi • Leptin deficiency • Bardet-Biedl Syndrome • Alstrom Syndrome • MC4R deficiency • Cohen Syndrome • Carpenter Syndrome • Albright’s Hereditary Osteodystrophy • Rubinstein-Taybi Syndrome
4 Syndromes and Obesity
Genetic Syndromes Complicated by Obesity
• Turner Syndrome • Down Syndrome • Autism Spectrum Disorders
50% more likely to have obesity by age 5
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Obesity and Developmental Delay
• Children of mothers with obesity 70% more likely to fail fine motor test by age 3 • Children of fathers with obesity 75% more likely to fail the test’s personal-social domain — an indicator of how well they were able to relate to and interact with others by age 3 • Children with 2 parents with obesity 3 times more likely to fail problem solving test by age 3 6 Genetic Obesity Syndromes
• Typically associated with hyperphagia • Early onset obesity prior to age 6 • Many have a host of other identifiable characteristics • Most have fairly significant developmental delays
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What works for obesity treatment?
• Structure • Accountability • Metabolic advantage • Environmental/stimulus control
https://www.the-scientist.com/feature/the-enormity-of-obesity-50015 8 Obesity Treatment Pyramid Shared Decision Making
BMI > 40 Surgery 30-40% wt loss BMI > 35 w/comorbidity (60-80% EWL)
Endoscopic therapy 10-20% wt loss BMI > 30 10% wt loss BMI > 27 with Pharmacotherapy Some get 20% comorbidity Treatment Intensity Prescriptive Nutritional Interventions 5-10% wt loss
Lifestyle Modification 2-5% wt loss Health Risks BMI 9
10 https://www.mc4r.org.uk/ POMC Deficiency – Early onset obesity without developmental delay • Normal development • Early onset obesity and hyperphagia • Red hair and pale skin • Adrenal insufficiency • Prevalence: < 50 cases reported • Targeted treatment with setmelanotide
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MC4R Deficiency
• Heterozygote MC4R mutations most common form of monogenetic obesity (5-6% of people with obesity) • No specific targeted treatment • Increased lean mass, increased linear growth • Hyperphagia, early onset obesity • ? Benefit of setmelanotide (MC4R agonist)
12 Prader Willi
• Loss of function on chromosome 15 (paternal) • 1 in 10,000-30,000 worldwide • Hyperphagia, behavior issues, developmental delay, poor feeding and hypotonia early in life, delayed linear growth • Studies looking at specific medication options • Treat with intensive behavior and medications/surgery if able.
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Syndromes and Obesity
Genetic Syndromes Complicated by Obesity
• Turner Syndrome • Down Syndrome • Autism Spectrum Disorders
50% more likely to have obesity by age 5
14 Turner Syndrome and Obesity
• 1 in 2,500 live born females • 10% of all first trimester miscarriage • One functioning X Chromosome (XO) • Females only • Associated with short stature, delayed puberty, learning disabilities (ADHD) • Impaired glucose metabolism noted
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Autism and Obesity
• 10-17 yo with autism and intellectual disability 20% have obesity while 15% have obesity in general population. (CDC) • Overlap with ADHD • Treatment can be difficult due to medication side effects • Medications can lead to weight gain • Metformin, GLP-1 can be useful, surgery when indicated • Motivational behavioral interventions
16 Down Syndrome Overview
• Most common chromosomal disorder – 1:700 live births in US • Trisomy 21 • Life expectancy – 60 years today – 25 yo in 1983
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Brian Skotko, M.D.
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Conditions associated with Down Syndrome
• Hearing loss (up to 75% may be affected) • Obstructive sleep apnea (between 50 -75%) • Eye diseases, like cataracts (up to 60%) • Heart defects present at birth (50%) • Intestinal blockage at birth requiring surgery (12%) • Hip dislocation (when the thigh bone slips out of the hip socket) (6%) • Thyroid disease (4-18%) • Iron deficiency anemia (10%) • Leukemia (1%) in infancy or early childhood • Hirschsprung disease (<1%) • Alzheimer’s Disease with age • Obsessive Compulsive disorder/anxiety • Cervical spine instability
20 • Gait disorders Down Syndrome and Obesity
• 25-75% of people with Down Syndrome in various publications with overweight or obesity • OR 2.17 for women and 0.85 for men for obesity
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Factors predisposing to obesity
• Short stature • Low resting metabolic rate • Sleep apnea • Gait/orthopedic abnormalities • Metabolic syndrome • Eating behaviors/OCD • Low testosterone levels
22 Considerations in treatment
• Living situation (home vs group home) • Working situation • Cardiac history • Osteoporosis • Behavior and mood disorders • Other medications • Increase celiac disease
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Anti-obesity Medications
Adjunct to nutritional, physical activity, and behavioral therapies for patients with BMI ≥ 30 or BMI ≥ 27 with co-morbidities
Objectives: • Treat disease ‒ Adiposopathy or sick fat disease (SFD) ‒ Fat mass disease (FMD) • Facilitate management of eating behavior • Slow progression of weight gain/regain • Improve the health, quality of life, and body weight of the patient with overweight or obesity
5-10 percent weight loss may improve both metabolic and fat mass disease
24 Obesity Algorithm®. ©2017-2018 Obesity Medicine Association. Reference/s: [239] Central Mechanisms of Action of Anti-obesity Meds
GLP-1 Food Intake 5HT Lorcaserin* Dexfenfluramine* GLP-1 NPY Topiramate POMC NE CART Phentermine Dopamine Bupropion/ Naltrexone POMC = ProOpioMelanoCortin neuron lisdexamphetamine NPY = NeuroPeptide Y AgRP = Agouti-Related Peptide
25 * Off market
Current Anti-Obesity Medications
FDA Approved Off label Use FDA approved for BED Phentermine Metformin lisdexamphetamine Schedule IV Diethylpropion Semaglutide/Exenatide Phendimetrazine Canagliflozin for diabetes Schedule III Benzphetamine (Dapa-,Empa-) Orlistat Pramlintide
Phentermine/Topiramate Schedule IV Topiramate for seizures, Zonisamide migraines Naltrexone/Bupropion Bupropion for depression Liraglutide
Naltrexone for addiction 26 Case 1 - AT
• 34yo female lives with a caregiver/roommate • Champion Special Olympic weight lifter
27 https://www.guelphmercury.com/community-story/8296492-hefty-competition-in-guelph-for-special-olympics-athletes/
Case 1-AT
• Phentermine 18.75mg • Topiramate 100mg BID • 203lbs to 167lbs • 20% weight loss • BMI 40 to 33
28 Case 2- MG
• 35yo living with parents • Phentermine, semaglutide, topiramate
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• Initial weight 341lbs to 308lbs, up to 318lbs with COVID • BMI 64 to 56 • > 10% weight loss
30 Case 3-TW
• 19yo lives with parents • Fasting insulin 61 • A1c normal
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• Metformin 2000mg – (wt 250lbs to 231lb 10% weight loss) • Phentermine 18.75mg – (wt 231lb to 221lb 5% wt loss) • Dance video 60 min daily
32 Case 3 - CO
• 40 yo male • Fasting insulin 31 • Lived in a group home • Nephrectomy for until COVID hydronephrosis • BMI 39 • Dementia
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Case 3 - CO
34 • Therapeutic carbohydrate reduction • Initial wt 208lbs to 201lbs came to live with mom 35
Case 4 - NB
• 26yo male • Lives with mom and dad who are divorced • Loves to work out • Father with obesity, mom very lean • Father enables • BMI 34, wt 206 lbs
36 169lbs 20% weight loss Metformin alone
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Case 5 - AW
• 27yo female • Lives with mom and dad • Goes to gym every day • Dad tends to enable • On sertraline, Vyvanse at baseline
38 • Liraglutide 3mg • 147lbs to 135lbs almost 10% • Trial of Gelesis 100 next
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Gelesis100 for obesity treatment
40 Gelesis100 Use
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Gelesis100 outcomes
42 In Summary
• Medications likely work for obesity in patients with developmental delay and other syndromes associated with obesity! Treat obesity in this population! • Use medications that fit the patient best in their treatment goals and side effect profile • Consider medication cost and coverage • Discuss long term use • Work on behavior charts, motivation and physical activity • Identify secondary issues and treat (hypothyroid, insulin resistance, sleep apnea) • Environmental issues can be challenging
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Questions?
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