COMORBIDITES OF PEDIATRIC OBESITY William J Cochran MD

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

WHY WORR ABOUT PEDIDATRIC OBESITY?

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

Figure IV: Percent of obese children and adolescents

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

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

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

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

IMPACT OF CHILDHOOD OBESITY ON ADULT HEALTH n Mossberg 1989 – Swedish adolescents studied after 40 years – Increased mortality in obese vs. nonobese

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

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

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

CHILDHOOD COMPLICATIONS OF PEDIATRIC OBESITY

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

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

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

PSYCHOSOCIAL n Adult Relationships – May have false expectations of child based on their size

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

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

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

Obesity Insulin Resistance Metabolic Syndrome Type 2 DM NASH PCOS Hypertension Dyslipidemia

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

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

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

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

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

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

HYPERTENSION n Risk – Overweight adolescents have 8. 5 fold risk of hypertension as adults. n Srinivasan Metab 1996; 45: 235 -240. – Cardiac hypertrophy/LVH on ultrasound. – Long term risk of CVD and stroke

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

DYLIPIDEMIA n Overweight during adolescence associated with – 2. 4 fold increase in prevalence of cholesterol >240 mg/dl – 3 fold increase in LDL values >160 mg/dl – 8 fold increase in HDL values<35 mg/dl in adults 27 -31 years – Srinivasan Metab 1996; 45: 235 -240.

DYLIPIDEMIA n Geisinger weight management program – 45% have hypercholesterolemia – Range of abnormal cholesterol: 175 -338 n 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

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

INSULIN RESISTANCE AND FAT DEPOSITION Muscle Insulin resistance insulin Insulin resistance Liver Free Fatty Acids Insulin resistance

NON-ALCOHOLIC FATTY LIVER DISEASE n n n 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. n Angulo P, Keach JC, Batts KP, Lindor KD. Hepatology 1999; 30(6): 1356 -62

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

CHOLELITHIASIS n Uncommon in children – Increased risk in those with hemolytic disorders n Obesity accounts for 8%-33% of gallstones in children – Friesen Clin Pediatr 1989. 7: 294 n May be associated with weight loss – Crichlow Dig Dis. 1972; 17: 68 -72

CHOLELITHIASIS n Relative risk of gallstones in adolescent girls with obesity is 4. 2 – Honore Arch Surg 1980; 115: 62 -64 n 50% of cholecystitis in adolescents associated with obesity – Crichlow Dig Dis. 1972; 17: 68 -72

SLIPPED CAPITAL FEMORAL EPIPHYSIS n 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. n Can also present with complaints of groin, thigh, or knee pain n

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

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

OBSTRUCTIVE SLEEP APNEA n 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 n Schechter MS. Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 2002; 109(4): e 69 -79.

OBSTRUCTIVE SLEEP APNEA n 40% of severely obese children demonstrated central hypoventilation – Silvesti Pediatr Pulmonol 1993; 16: 124139 n 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.

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

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

OSAS-DIAGNOSIS n n 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 n Severity of obstruction may not correlate with either degree of obesity or severity of sleep symptoms

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.

OBSTRUCTIVE SLEEP APNEA n 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

OSAS - TREATMENT n 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) n Tonsilladenoidectomy n

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

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

John A Moran Eye Center, Salt Lake City UT

PSUEDOTUMOR CEREBRI n 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. n Increased intracranial pressure may lead to visual impairment or blindness.

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

CONCLUSIONS REGARDING PEDIATRIC OBESITY

PEDIATRIC OBESITY IS NOT JUST A COSMETIC PROBLEM!

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

COMPLICATIONS ARE COMMON IN PEDITRIC OBESITY n Laboratory evaluation – Fasting lipid profile – Liver panel – Fasting insulin and glucose – Hgb A 1 C n To be considered – Polysomnogram – Abdominal US

THANK YOU!

SCFE: ASSOCIATED CAUSES n n n 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

Pseudotumor Cerebri - Associated Conditions Mastoiditis. n Lateral sinus thrombosis. n Hypoparathyroidism, n Steroid treatment and withdrawal. n Thyroid replacement, n SLE. n n n n 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. Del. Giudice GC, Scher CA, Athreya BH, Diamond GR. . J Rheumatol 1986; 13(4): 748 -52.

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