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Treating Obesity in Patients with Down Syndrome and Other Developmental Delay Syndromes Disclosures

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Treating Obesity in Patients with Down Syndrome and Other Developmental Delay Syndromes Disclosures 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 3 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 5 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 7 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 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 11 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. 13 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 15 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 17 Brian Skotko, M.D. 18 19 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 21 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 23 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 29 • 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 31 • 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 33 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 37 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 39 Gelesis100 for obesity treatment 40 Gelesis100 Use 41 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 43 Questions? [email protected] 44.
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