Translational Research on Overweight Children

1. Translational Research on Overweight Children Research Collaborative on Pediatric Overweight

2. Definition of overweight • CDC: term ‘obesity’ is not used for children • In children, body mass index (BMI) is charted by age and gender. • The normal range of weight for a given height varies with age. • In general, children younger than 3 years and older than 11 years have proportionately more weight for height than do school-aged children.

3. In children, body mass index (BMI) is charted by age and gender. • The normal range of weight for a given height varies with age. • Children younger than 4 and older than 9 years have proportionately more weight for height than do school-aged children.

4. Definition of overweight • BMI above 95th percentile = ~ corresponds to ‘obese’ label in adults • BMIs 85th to 95th percentile = ~ corresponds to ‘overweight’ label in adults overweight at risk for overweight

5. Definition of overweight In our research, the term, ‘overweight’ often is used to refer BMIs above the 85th percentile for age and gender. ~ highest 15% of weight for height among US children

6. Our Approach • Study childhood overweight with recognition of its complexity. • Compose teams of clinical researchers and basic scientists to study metabolic and physiologic bases of overweight in children. • A group of WCMC, HSS, and RU faculty have been working together for over two years to formulate a coordinated program of research on childhood overweight.

7. Clinical Pathway • CORE LAB SET LEVEL 1 (fasting) Fast of 8-12 hours for lipids; fast of 3-4 hours for insulin/glucose • Glucose (fluorinated [green] tube) • Fasting: if 100-125 mg/dL: Level 2 refer to Endo • Fasting: if > 126 mg/dL and confirmed fasting by history: page Endo STAT for possible diabetes • Non- Fasting: if > 140 mg/dL: Level 2 refer to Endo • Non- Fasting: if > 200 mg/dL: page Endo STAT for possible diabetes • HgbA1C if > 5.9% : Level 2 refer to Endo • Insulin Fasting: if > 14 uIU/: Level 2 refer to Endo • Lipid Profile • if LDL 130-199 or HDL 21-40 or TG 150-300:  repeat studies within 3 months • if values abnl at 3 mo  Level 2: refer to Dr. Hudgins • if LDL >200 or HDL <20 or TG >300:  Level 2: refer to Dr. Hudgins • Vitamin D, 25-Hydroxy • if < 30 ng/mL: prescribe 1,000 IU Vitamin D q day • if 10-20 ng/mL: prescribe 2,000 IU Vitamin D q day” • if <10 ng/mL: prescribe 2,000 IU Vitamin D q day” : Level 2 refer to Endo • LFT’s if ALT or AST >60:  Level 2 Liver US refer to Dr. Solomon (liver US) • LEVEL 1a: hypertension: • If BP > 95th% for age & height (per Harriet Lane)  repeat BP during visit. • If both values >95th% for age & height:  Level 2 serum electrolytes, plasma renin activity, urine microalbumin, urine Na, U/A • If results normal  F/U w/in 3 mo  if repeat BP >95th%: • If results abnormal  Level 2 refer to Renal, Peds Cardiology • LEVEL 1b: short stature (height < 5th% or decline in growth velocity): • TSH, free T4, IGF-1, IGFBP-3, cortisol • Refer to Endo (bone age will be done) • LEVEL 1c:joint malalignment/musculo-skeletal pain: • PE/screening for genu varum/genu valgum: if clinical concern  refer to Peds Ortho • PE/screening: if SCFE suspected  emergent X-ray of hip/thigh/knee/groin

8. Research Teams • Immunological Function in Nonalcoholic Fatty Liver Disease in Overweight Children • Vitamin D Deficiency and Atypical Glucose Metabolism in Overweight Children • Atypical Lipid Metabolism and Endothelial Dysfunction in Overweight Children • Angiogenic Markers in Overweight Children • Lower Extremity Alignment, Gait, and Joint Pathophysiology in Overweight Children • Health for Life Primary Care Intervention

9. Immunological Function in NAFLD • Susanna Cunningham-Rundles • Arzu Kovanlikaya • Ruben Cooper • Aliza Solomon

10. Immunological Function in NAFLD • NAFLD involves accumulation of fatty deposits on the liver. • Examine the associations among oxidative stress markers, anti oxidant reserve and inflammatory markers in children. • Introduce MRI to provide precise calculation of fat levels in the liver.

11. Vitamin D Deficiency and Atypical Glucose Metabolism • Maria Vogiatzi • Roja Motaghedi • Sunita Cheruvu

12. Vitamin D Deficiency and Atypical Glucose Metabolism • Vitamin D insufficiency is associated with insulin resistance, the metabolic syndrome and Types I and II diabetes. (1) prospective randomized trial of vitamin D supplementation in obese, insulin resistant, vitamin D deficient adolescents (2) basic science studies on insulin signaling and glucose transport as a function of varying levels of vitamin D concentrations in fat and muscle.

13. Angiogenic and Vasculogenic Markers in Overweight Children • David C. Lyden • Snezana M. Osorio • Rosandra Kaplan

14. Angiogenic and Vasculogenic Markers in Overweight Children • Sprouting of new blood vessels from pre-existing ones is termed angiogenesis. • Angiogenesis is tightly controlled by a balance between factors that stimulate endothelial cell growth and movement and anti-angiogenic factors, which inhibit these processes. • Angiogenic factors are elevated in overweight and obese adults. These factors have not yet been studied in children.

15. Atypical Lipid Metabolism and Endothelial Dysfunction • Ruben Cooper • Lisa Hudgins • Abraham Bornstein • Arzu Kovanlikaya • Maura Frank • Susanna Cunningham-Rundles • Mary J. Ward

16. Atypical Lipid Metabolism and Endothelial Dysfunction in Overweight Children • EndoPAT is a novel, non-invasive method for assessing endothelial function. • Endothelium is affected by overweight, as well as elevated lipids and dysregulated insulin.

17. Lower Extremity Alignment, Gait, and Joint Pathophysiology In Overweight Children • Howard Hillstrom • Peter Torzilli • Christopher Chen • Daniel Green • Siobhan Doyle • Mary J. Ward • Maria Vogiatzi

18. Lower Extremity Alignment, Gait, and Joint Pathophysiology In Overweight Children • Understand the role of joint malalignment and BMI in joint mechanics, joint physiology, and risk of osteoarthritis among overweight children. • Motion analysis methodology, assessment of Vitamin D metabolism, and laboratory assessment of joint physiology

19. Health for Life Primary Care Intervention • Maura Frank • Weill-Cornell Resident Group Practice staff

20. Health for Life Primary Care Intervention • Evidence-based program for 8-18 year-olds with BMI ≥ 85th %ile • Staff includes dietitians, physicians, physical therapists, social workers, nurses, and medical students • Individual sessions: medical, nutritional, psychosocial and physical fitness evaluations • 10 weekly group sessions on nutrition/behavior and physical activity

21. Wish List • What more should we know? • Researchers interested in collaboration?