COMORBIDITES OF PEDIATRIC OBESITY

1. COMORBIDITES OF PEDIATRIC OBESITY William J. Cochran, MD, FAAP Geisinger Clinic

3. WHY WORR ABOUT PEDIDATRIC OBESITY?

4. INTRODUCTION Pediatric obesity is of epidemic proportion Pediatric obesity is the most common chronic disease of childhood

5. Figure IV: Percent of obese children and adolescents

6. IS PEDIATRIC OBESITY A REAL HEALTH ISSUE OR JUST A COSMETIC PROBLEM?

7. ADULT OBESITY Type II Diabetes Coronary Heart Disease Hypertension Cancer Joint Disease Gallbladder Disease Pulmonary Disease

9. RISK OF CHILDHOOD OBESITY PERSISTING INTO ADULTHOOD Guo 1999 20% at 4 years of age 80% in adolescence

10. IMPACT OF CHILDHOOD OBESITY ON ADULT HEALTH Childhood obesity has significant impact on health in adulthood Hoffmans 1998 Dutch adolescent males followed for 32 years Increased mortality in obese vs. lean

11. IMPACT OF CHILDHOOD OBESITY ON ADULT HEALTH Mossberg 1989 Swedish adolescents studied after 40 years Increased mortality in obese vs. non-obese

12. IMPACT OF CHILDHOOD OBESITY ON ADULT HEALTH Must, 1992:Harvard growth study 13-18 year old adolescents 1922-1935, evaluated 1988 Obesity: BMI >75% on at least two occasions during adolescence

13. IMPACT OF CHILDHOOD OBESITY ON ADULT HEALTH Increased all cause mortality in males and females Increased mortality from CAD in males Increased morbidity from CAD in males and females Increased risk of colon cancer in males Increased risk of arthritis in females

14. IMPACT OF CHILDHOOD OBESITY ON ADULT HEALTH Obesity in childhood was a more powerful predictor of these risks than obesity in adulthood!

15. CHILDHOOD COMPLICATIONS OF PEDIATRIC OBESITY

16. PSYCHOSOCIAL Most common complication of childhood obesity Self Increased rates of depression Poor self esteem May carry over into adulthood Children are sensitized to obesity at young age

17. PSYCHOSOCIAL Self Mellbin, 1989 Increased rates of behavior and learning problems in those gaining weight rapidly Etiology uncertain, ? Sleep apnea

18. PEER RELATIONSHIPS Richardson, 1961 10-11 year old children prefer friends with various handicaps vs. obese Staffieri, 1967 Children 6-10 years of age associate obesity with laziness Obese children may choose younger friends, less judgmental

19. PSYCHOSOCIAL Adult Relationships May have false expectations of child based on their size

20. SOCIETAL DISCRIMINATION Canning, 1966 Acceptance rates at college lower for obese than non-obese females with the same credentials National Longitudinal Survey of Youth 1993 Obese adolescent females as young adults had less education, less income, higher poverty rate, and decreased rates of marriage

21. ENDOCRINE COMPLICATIONS Non-insulin-dependent diabetes mellitus Pinhas-Hamiel 1994 The incidence of NIDDM has increased 10 fold One third of new diabetic children 10-19 years of age had Type II DM 92% of these had a BMI >90% Geisinger weight management program 1-2% have type II DM

22. ENDOCRINE COMPLICATIONS Insulin resistance Elevated fasting insulin levels with normal Hgb A1C Ratio of fasting insulin to glucose Adult female: normal <1:4 Normal for children not established First step towards developing Type II DM

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24. ENDOCRINE COMPLICATIONS Geisinger weight management program 60% have insulin resistance 10% have fasting insulin level > 100 (Nl <17)

25. ENDOCRINE COMPLICATIONS Acanthosis nigricans Velvety, hyperpigmented, thickened skin Associated with obesity and insulin resistance Not sensitive for insulin resistance Resolves with weight loss

29. ENDOCRINE COMPLICATIONS Increased linear growth initially Growth plates may close earlier Advanced bone age Earlier onset of puberty

30. POLYCYSTIC OVARY SYNDROME Hyperandrogenism Ovarian dysfunction Oligomenorrhea Amenorrhea 55% of adolescent females have polycystic ovaries on US Cutaneous manifestations Hirsuitism Acne Acanthosis nigricans

31. POLYCYSTIC OVARY SYNDROME Insulin resistance Hyperlipidemia Infertility Premature adrenarche Bacha F, Arslanian S. Enod Trends 11(1)2004

32. HYPERTENSION Hypertension Primary hypertension uncommon in childhood 60% of children with persistently elevated blood pressure had weight >120% IBW Lauer J Pediatr 1975;86:697-706. Use pediatric standards Geisinger weight management program 45% have hypertension

33. HYPERTENSION Risk Overweight adolescents have 8.5 fold risk of hypertension as adults. Srinivasan Metab 1996;45:235-240. Cardiac hypertrophy/LVH on ultrasound. Long term risk of CVD and stroke

34. DYLIPIDEMIA The atherosclerotic process beings in childhood (Bogalusa Heart Study) Lipid levels tend to track with age

35. DYLIPIDEMIA Overweight during adolescence associated with 2.4 fold increase in prevalence of cholesterol >240mg/dl 3 fold increase in LDL values >160mg/dl 8 fold increase in HDL values<35 mg/dl in adults 27-31 years Srinivasan Metab 1996;45:235-240.

36. DYLIPIDEMIA Geisinger weight management program 45% have hypercholesterolemia Range of abnormal cholesterol: 175-338 Freeman 1999 65% of obese 5-10 year old children have at least one cardiovascular disease risk factor 25% of obese 5-10 year old children have 2 or more risk factors

37. NON-ALCOHOLIC FATTY LIVER DISEASE Hepatic steatosis Increased fat in the liver Steatohepatitis associated with liver inflammation and elevated liver enzymes 20%-25% obese children have evidence of steatohepatitis Tazawa Acta Paeditr 1997;86:238-241

38. INSULIN RESISTANCE AND FAT DEPOSITION Adipose tissue in obesity becomes refracdtory to insulins suppression of fat mobilization., Insulin resistance increases the release of FFA from the adipcyte. In the postprandial period there is an excess of FFA leading to fat deponsition in other tissues Hytperinsulinemiua stimulates fatty acid synthesi while inhibiting the oxidation of fatty acids.,sElevagted insulin may increase the degradation of apolipoprotein B100a component of VLDLcompromising triglyceride transport out of the liver causing anet accumulation of fat. ElevatedFFA and accumulagted triacylglycerol appear to inhibit insulin signalling leading to a reduction in insulin stimulated muscleglucose transporty,.The reduced muscle glucose transport leads to reduced glycogen syntethisisand glycolysisAdipose tissue in obesity becomes refracdtory to insulins suppression of fat mobilization., Insulin resistance increases the release of FFA from the adipcyte. In the postprandial period there is an excess of FFA leading to fat deponsition in other tissues Hytperinsulinemiua stimulates fatty acid synthesi while inhibiting the oxidation of fatty acids.,sElevagted insulin may increase the degradation of apolipoprotein B100a component of VLDLcompromising triglyceride transport out of the liver causing anet accumulation of fat. ElevatedFFA and accumulagted triacylglycerol appear to inhibit insulin signalling leading to a reduction in insulin stimulated muscleglucose transporty,.The reduced muscle glucose transport leads to reduced glycogen syntethisisand glycolysis

39. NON-ALCOHOLIC FATTY LIVER DISEASE Liver disease can progress to fibrosis or frank cirrhosis Obesity and type 2 diabetes are the strongest predictors of progression of fibrosis Age is also a risk factor for cirrhosis which may reflect increased duration of risk for the “second hit” thought to initiate fibrosis. Angulo P, Keach JC, Batts KP, Lindor KD. Hepatology 1999;30(6):1356-62

40. NON-ALCOHOLIC FATTY LIVER DISEASE Rashid 83% of children with steatohepatitis were obese 75% had fibrosis-cirrhosis Geisinger weight management program 50 % have hepatomegaly 15% have elevated liver enzymes

42. CHOLELITHIASIS Uncommon in children Increased risk in those with hemolytic disorders Obesity accounts for 8%-33% of gallstones in children Friesen Clin Pediatr 1989.7:294 May be associated with weight loss Crichlow Dig Dis. 1972;17:68-72

43. CHOLELITHIASIS Relative risk of gallstones in adolescent girls with obesity is 4.2 Honore Arch Surg 1980;115:62-64 50% of cholecystitis in adolescents associated with obesity Crichlow Dig Dis. 1972;17:68-72

44. SLIPPED CAPITAL FEMORAL EPIPHYSIS 50%-70% patients with SCFE are obese. Wilcox J Pediatr Orthop 1988:8:196-200 Suspect and immediately evaluate in an obese patient who presents with limp. Can also present with complaints of groin, thigh, or knee pain

45. SLIPPED CAPITAL FEMORAL EPIPHYSIS Diagnosis Physical examination Motion of the hip in abduction and internal rotation is limited on examination. Xray AP view of pelvis to include both hips Bilateral disease occurs in up to 20% of patients Medial and posterior displacement of the femoral epiphysis through the growth plate relative to the femoral neck Busch MT. Orthop Clin North Am 1987;18(4):637-47

46. BLOUNT’S DISEASE Diagnosis Bowing of tibia and femur either unilateral or bilateral. Etiology Results from overgrowth of the medial aspect of the proximal tibial metaphysis 2/3 of patients with Blount’s disease are obese Dietz J Pediatr 1982:101:735-737 Treatment Surgery associated with weight loss

47. OBSTRUCTIVE SLEEP APNEA OSAS in children is defined as a disorder of breathing during sleep characterized by: prolonged partial upper airway obstruction and/or intermittent complete obstruction (obstructive apnea) that disrupts normal ventilation during sleep and normal sleep patterns Schechter MS. Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2002;109(4):e69-79.

48. OBSTRUCTIVE SLEEP APNEA 40% of severely obese children demonstrated central hypoventilation Silvesti Pediatr Pulmonol 1993;16:124-139 Abnormal sleep patterns reported in 94% of obese children studied Kahn A, Mozin MJ, Rebuffat E, Sottiaux M, Burniat W, Shepherd S, et al. Sleep 1989;12(5):430-8.

49. OBSTRUCTIVE SLEEP APNEA Symptoms of sleep apnea Nighttime awakening / restless sleep Excessive snoring / apnea Difficulty awaking in the morning Daytime somnolence Nocturnal enuresis Decreased ability to concentrate Poor school performance. Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics 1998;102(3 Pt 1):616-20.

50. OSAS - ETIOLOGY Increased fat mass in pharynx, neck, chest and diaphragm Increased muscle relaxation during sleep Enlarged tonsils and adenoids Silvestri JM, Weese-Mayer DE, Bass MT, Kenny AS, Hauptman SA, Pearsall SM. Pediatr Pulmonol 1993;16(2):124-9

51. OSAS-DIAGNOSIS History, audio and video taping, and overnight oximetry are poor predictors The definitive diagnosis of OSAS is made by nighttime polysomnography Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. [No authors listed.] Pediatrics 2002;109(4):704-12 Severity of obstruction may not correlate with either degree of obesity or severity of sleep symptoms

52. OBSTRUCTIVE SLEEP APNEA Children with sleep apnea demonstrate significant decreases in learning, attention span and memory Rhodes J Pediatr 1995;127:741-744. Greenberg GD, Watson RK, Deptula D.. Sleep 1987;10(3):254-62.

53. OBSTRUCTIVE SLEEP APNEA Pulmonary hypertension,systemic hypertension, right heart failure .Tal A, Leiberman A, Margulis G, Sofer S. Pediatr Pulmonol 1988;4(3):139-43 Marcus CL, Greene MG, Carroll JL. Am J Respir Crit Care Med 1998;157(4 Pt 1):1098-103 Massumi RA, Sarin RK, Pooya M, Reichelderfer Dis Chest 1969;55(2):110-4

54. OSAS - TREATMENT Weight loss Willi SM, Oexmann MJ, Wright NM, Collop NA, Key LL Jr. Pediatrics 1998;101(1 Pt 1):61-7 Continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) Tonsilladenoidectomy

55. PSUEDOTUMOR CEREBRI Definition Raised intracranial pressure with papilledema and a normal cerebrospinal fluid in the absence of ventricular enlargement Obesity occurs in 30%-80% of children with psuedotumor cerebri Scott Am J Opth 1997; 124:253-255

56. PSUEDOTUMOR CEREBRI May present with headaches, vomiting, blurred vision or diplopia Neck, shoulder, and back pain have also been reported Lessell S. Surv Ophthalmol 1992;37(3):155-66 Papilledema is part of pathology but may not occur at presentation

57. Papilledema is a bilateral swelling or edema of the optic disc secondary to any factor which may increase cerebral spinal fluid pressure. Fundus examination reveals a swollen optic nerve head with elevation, edema and narrowing of the physiological cup, vascular congestion with small areas of flame-shaped hemorrhage and exudates, and possible surrounding retinal edema (#22092). Papilledema is a bilateral swelling or edema of the optic disc secondary to any factor which may increase cerebral spinal fluid pressure. Fundus examination reveals a swollen optic nerve head with elevation, edema and narrowing of the physiological cup, vascular congestion with small areas of flame-shaped hemorrhage and exudates, and possible surrounding retinal edema (#22092).

58. PSUEDOTUMOR CEREBRI Loss of peripheral visual fields and reduction in visual acuity may be present at diagnosis Baker RS, Carter D, Hendrick EB, Buncic JR. Arch Ophthalmol 1985;103(11):1681-6. Increased intracranial pressure may lead to visual impairment or blindness.

59. PSUEDOTUMOR CEREBRI Weight loss Newborg B. Arch Intern Med 1974;133(5):802-7 Acetazolamide Lumboperitoneal shunt in severe cases

60. CONCLUSIONS REGARDING PEDIATRIC OBESITY

61.  PEDIATRIC OBESITY IS NOT JUST A COSMETIC PROBLEM!

62. COMPLICATIONS ARE COMMON IN PEDITRIC OBESITY All children with BMI> 95% should be evaluated for associated co-morbidities Physical examination BP Fundiscopic exam Hip and knee examination Acanthosis nigricans Hirsutism / acne Hepatomegaly

63. COMPLICATIONS ARE COMMON IN PEDITRIC OBESITY Laboratory evaluation Fasting lipid profile Liver panel Fasting insulin and glucose Hgb A1C To be considered Polysomnogram Abdominal US

64. THANK YOU!

65. SCFE: ASSOCIATED CAUSES Continued weight gain Renal failure History of radiation therapy Primary hypothyroidism Loder RT, Greenfield ML.. J Pediatr Orthop . 2001;21(4):481-7 Gonadotropin-releasing hormone agonists Growth hormone therapy Kempers MJ, Noordam C, Rouwe CW, Otten BJ. J Pediatr Endocrinol Metab 2001;14(6):729-34

66. Pseudotumor Cerebri - Associated Conditions Mastoiditis. Lateral sinus thrombosis. Hypoparathyroidism, Steroid treatment and withdrawal. Thyroid replacement, SLE. Green M. Pediatr Clin North Am 1967;14(4):819-30. Palmer RF, Searles HH, Boldrey EB.. J Neurosurg 1959;16(4):378-84. Baker RS, Baumann RJ, Buncic JR. Pediatr Neurol 1989;5(1):5-11. Walker AE, Adamkiewicz JJ. JAMA 1964;188:779-84. Neville BG, Wilson J.. Br Med J 1970;3(722):554-6. Huseman CA, Torkelson RD.. Am J Dis Child 1984;138(10):927-31. DelGiudice GC, Scher CA, Athreya BH, Diamond GR.. J Rheumatol 1986;13(4):748-52.

67. Drugs Associated With Pseudotumor Cerebri Growth hormone therapy Nalidixic acid,Ciprofloxacin,Tetracycline therapy No clear dose-response relationship Lessell S. Surv Ophthalmol 1992;37(3):155-66. Vitamin A and isoretinoin therapy are established causes of pseudotumor cerebri. Morrice G Jr, Havener WH, Kapetansky F. JAMA 1960;173:1802-5. Roytman M, Frumkin A, Bohn TG. Cutis 1988;42(5):399-400.