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Comorbidities of Childhood Obesity

Sandra G. Hassink, MD, FAAP
Director of the Weight Management Clinic A.I. Dupont Hospital for Children Wilmington, DE

Insights Into Obesity

Complex

Gene-Environment Interaction Metabolically active organ system Structural, Functional and Metabolic effects

Dynamic

Multisystem

Pathologic

Complex Gene Environment Interaction

Genetic Predisposition
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Parental obesity Risk for co morbidity Intrauterine environment Periods of critical growth Nutritional Genomics

Environmental interaction

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.Dynamic Metabolically Active Organ System.  Adipocytes      Storage Cytokine production Hormonal regulation Energy regulation at the level of the CNS and periphery.

Multisystem  Effects on all major organ systems        Skeletal Muscular Endocrine Gastrointestinal Reproductive Cardiovascular Pulmonary .

Pathologic  Results in earlier onset of adult disease  Type II diabetes NASH  Results in end stage disease   Provides new explanations for ―old‖ disease  Sleep apnea syndrome .

Severe Obesity Related Emergencies     Hyperglycemic Hyperosmolar state DKA Pulmonary emboli Cardiomyopathy of obesity .

" Morales AE.J Pediatric 2004 Feb 144 (2) 270-3.‖ .  ―Seven obese African American youth were considered to have died from diabetic ketoacidosis. Rosenbloom AL.Hyperglycemic Hyperosmolar State “Death caused by hyperglycemic Hyperosmolar state at the onset of type 2 diabetes.

‖ ―All had previously unrecognized type 2 diabetes.‖ .Hyperglycemic Hyperosmolar State   ―Despite meeting the criteria for Hyperglycemic Hyperosmolar state and not for DKA. and death may have been prevented with earlier diagnosis or treatment.

 Diarrhea. .  Dizziness.  Weight loss.  Vomiting.Hyperglycemic Hyperosmolar State  Patients presented to medical care with symptoms which were not linked to presentation of type 2 diabetes.  Weakness.  Abdominal Pain.  Polyuria/Polydipsia.

diagnostic criteria       plasma glucose > 600mg/dl serum CO2 > 15 mmol/l small ketonuria absent to low ketonemia effective serum osmolality >320 mOsm/kg stupor or coma   Rubin HM J Pediatr 1969:74:`77-86 Morales A J Pediatr 2004 Feb.Hyperglycemic Hyperosmolar State  HHS. 270-273 .

.  In some studies up to 25%.Diabetic Ketoacidosis   Type 2 DM may present with diabetic ketoacidosis. If basal insulin sensitivity is low there is increasing susceptibility to relative insulin deficiency.  May be more common in African American and Hispanic patients with Type 2 Diabetes.

Diabetic Ketoacidosis Hyperglycemia Insulin secretion Beta Cell Toxicity + Insulin resistance Relative Insulin Deficiency Lipolysis Free Fatty Acids Ketonemia Ketonuria .

Pulmonary Embolism  Symptoms     Dyspnea Chest pain Decreased O2 Hemoptysis  Most common complication of gastric bypass/banding in adults .

2003 Jan: 7(1):102-07  Risk factors    Obesity Obesity hypoventilation syndrome/OSAS Coagulation disorder (i. DeMaria EJ. Leiden V) . Sugerman EL. Mowery Y. Wolfe LG.Pulmonary Embolism  Has been reported in adolescence  Sugerman HJ.e. Kellum JM. J Gastrointest Surg. Kennedy C.

    dilation increased left ventricular wall stress compensatory (eccentric) left ventricular hypertrophy left ventricular diastolic dysfunction Exacerbated by pulmonary hypertension due to UAO   Right Ventricular dysfunction  Alpert. . MA Am J Med Sci 2001 Apr. 321(4).225-36. Left ventricular dysfunction.Cardiomyopathy of Obesity   High metabolic activity of excessive fat increases total blood volume and cardiac output.

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Co-morbidity's Requiring Immediate Attention       Pseudotumor Cerebri Slipped Capital Femoral Epiphysis Blount’s Disease Sleep Apnea Non alcoholic hepatosteatosis Cholelithiasis .

.Obesity Related Central Nervous System Morbidity  Definition.  Raised intracranial pressure with papilledema and a normal cerebrospinal fluid in the absence of ventricular enlargement.Pseudotumor Cerebri .

John A Moran Eye Center. Salt Lake City UT .

  May present with headaches. Surv Ophthalmol 1992. and back pain have also been reported.  Lessell S. shoulder. . Neck.  Papilledema is part of pathology but may not occur on presentation.Pseudotumor Cerebri  Diagnosis.37(3):155-66. vomiting. blurred vision or diplopia.

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

.Pseudotumor Cerebri  Risk.37(3):155-66. obesity and recent weight gain were the only factors found significantly more often in pseudotumor cerebri patients than control patients. 124:253-255  In a series of case-controlled studies in adolescents and adults. Surg Ophthalmol 1992.  Obesity occurs in 30%-80% of affected children.  Scott Am J Opth 1997.  Lessell S.

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

Weight loss.  Newborg B.133(5):802-7. Arch Intern Med 1974. Lumboperitoneal shunt (in severe cases). .Treatment    Acetazolamide.

When suspicious – test Pseudotumor cerebri is essentially a diagnosis of exclusion after other causes of increased intracranial pressure are eliminated.Points to Remember    A fundiscopic examination should be a routine part of the examination of the obese child Children may not complain of visual field disturbances. .

.Slipped Capital Femoral Epiphysis  Diagnosis  Suspect and immediately evaluate in an obese patient who presents with limp.  50%-70% patients with SCFE are obese.  Wilcox J Pediatr Orthop 1988:8:196-200. thigh.  Can also present with complaints of groin. or knee pain referred by sensory cutaneous nerves passing close to the hip capsule.

 Comparison of the hips  Bilateral disease occurs in up to 20% of patients.Slipped Capital Femoral Epiphysis Diagnosis Motion of the hip in abduction and internal rotation is limited on examination.ray  Anteroposterior view of the pelvis that includes both hips.    . X.

18(4):637-47. a slipped epiphysis when one is suspected clinically. Morrissy RT.Diagnosis  Medial and posterior displacement of the femoral epiphysis through the growth plate relative to the femoral neck  Busch MT. but not completely rule out. Orthop Clin North Am 1987. and so they can confirm.  All studies have a small rate of false negative results. .SCFE .

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SCFE. .14(6):729-34. CanJ Pediatr Endocrinol Metab 2001.Pathology  The preferential site of slipping within the epiphysis is a zone of hypertrophic cartilage cells under the influence of both gonadal hormones and growth hormone  Kempers MJ. Noordam C. Rouwe CW. Otten BJ.

Growth hormone therapy.41-57. Noordam C. Grumbach MM. Greenfield ML. Bin-Abbas BS.14(6):729-34. 2001.49(Suppl 2).   Kempers MJ. Horm Res 1998..SCFE . J Pediatr Orthop .  Loder RT. Rouwe CW. Otten BJ. J Pediatr Endocrinol Metab 2001. . Kaplan SL. Primary hypothyroidism.Associated Causes     Continued weight gain. Renal failure. History of radiation therapy.   Gonadotropin-releasing hormone agonists.21(4):481-7.

. In an obese child. groin. an unusual or abnormal gait should not be attributed to ―excess weight‖ but should be thoroughly investigated with a careful hip and knee examination. including radiological studies. knee. or thigh pain should have a complete and thorough examination of his/her hips. An obese child complaining of or presenting with hip.Points to Remember    A careful hip and knee examination should be a routine part of the evaluation and follow-up of every obese child.

 Treatment   Requires evaluation and correction by orthopedic surgeon. Weight loss .   Etiology   Dietz J Pediatr 1982:101:735-737. 2/3 of patients with Blount’s disease may be obese. Results from overgrowth of the medial aspect of the proximal tibial metaphysis.Obesity Related Orthopedic Morbidity  Diagnosis  Bowing of tibia and femur either unilateral or bilateral.Blount’s Disease .

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

.         Nighttime awakening. Pediatrics 1998.102(3 Pt 1):61620. Restless sleep. Sleep-disordered breathing and school performance in children. Napping. Daytime somnolence. Poor school performance. Enuresis.  Gozal D. Decreased concentration. Difficulty awaking in the morning.OSAS -Symptoms  Symptoms of sleep apnea can include.

Pearsall SM. Donaghue KC. . J Pediatr 2002.16(2):124-9. Pediatr Pulmonol 1993.140(6):654-9.OSAS .  Increased muscle relaxation during sleep.Etiology Increased fat mass.  Enlarged tonsils and adenoids.  Elevated insulin  de la Eva RC. Baur LA.. Bass MT. Weese-Mayer DE. Hauptman SA. Waters KA.   Silvestri JM. Kenny AS.

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

Reichelderfer Dis Chest 1969. Pooya M. et al. .OSAS  Abnormal sleep patterns reported in 94% of obese children studied. Sarin RK.12(5):430-8. Sottiaux M. Rebuffat E. Burniat W. Sottiaux M. Sleep 1989. Kahn A. Burniat W. Shepherd S. Shepherd S.  Kahn A.55(2):110-4. Mozin MJ. Mozin MJ.12(5):430-8. et al.   Massumi RA. Obstructive sleep apnea has been noted in obese infants as young as five months of age. Sleep 1989.  Obstructive sleep apnea has been noted in obese infants as young as five months of age. Rebuffat E.

Leiberman A.Risk  Children with sleep apnea demonstrate significant decreases in learning and memory.Tal A.55(2):110-4.4(3):13943.127:741-744.systemic hypertension. Deptula D. Marcus CL. motor efficiency and graphomotor ability.10(3):254-62.  Greenberg GD.    .  Pulmonary hypertension. Sleep 1987. Sofer S. Pediatr Pulmonol 1988. Sarin RK.Obstructive Sleep Apnea. Carroll JL. Greene MG. Margulis G. Watson RK. Massumi RA.  Deficits in attention. Am J Respir Crit Care Med 1998. .157(4 Pt 1):1098-103..  Rhodes J Pediatr 1995. right heart failure. Pooya M. Reichelderfer Dis Chest 1969.

hypoxemia. if indicated Continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP).Treatment  Weight loss reduced apneic episodes. Key LL Jr. Wright NM.OSAS .  Willi SM. and daytime sleepiness in a group of obese children. Pediatrics 1998.101(1 Pt 1):61-7. Collop NA. Oexmann MJ.   Tonsilladenoidectomy. .

intercurrent upper respiratory infections. and Tonsillar enlargement can provoke symptoms.Points to Remember    Ask specifically about sleep disturbances. snoring. . Sleep symptoms can evolve over time. Weight gain. and sleep position. Keep asking about sleep disturbance as you follow these children. Obstructive sleep apnea syndrome should be especially considered in obese children with poor school performance and concentration difficulties. Families will often disregard these symptoms.

through nonalcoholic steatohepatitis (NASH).NAFLD and NASH  Nonalcoholic fatty liver disease (NAFLD) describes a continuum of conditions that range from simple steatosis at the most clinically benign end of the spectrum. Diehl AM. to cirrhosis and end-stage liver disease  Harrison SA. Semin Gastrointest Dis 2002. . Fat and the liver—a molecular overview.13(1): 3-16.

86:238-241.Non Alcoholic Steatohepatitis .  Diagnosis   Increased liver enzymes and fatty liver on ultrasound in the absence of other causes of liver disease. .   Etiology  Tazawa Acta Paeditr 1997. Liver Biopsy 20%-25% obese children have evidence of steatohepatitis.Obesity Related Gastrointestinal Morbidity.

NAFLD to NASH Obesity Genetic Predisposition Fatty Liver 2nd “Hit” Inflammation Fibrosis Day Cirrhosis CP. James OF.114(4):842-5. Gastroenterology 1998. .

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30(6):1356-62.NASH . Keach JC. Lindor KD. Hepatology 1999. Batts KP. .  Angulo P.Risk   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.

125(2):239-41. Perna C. Tedesco M. those who lost at least 10% of their excess weight normalized ALT and AST values and decreased ultrasound evidence of fatty infiltration  Vajro P. J Pediatr 1994. De Vincenzo A. Fontanella A. Orso G. .NASH .Treatment  In a small series of pediatric patients with elevated aminotransferases and fatty liver on ultrasound.

13(1):17-30. Rapid weight loss may actually increase fibrosis due to an increase of free fatty acids to the liver and increased lipid peroxidation with resultant increased oxidative stress. all had reduced steatosis.  . but only 50% had a reduction in fibrosis. McCullough AJ. Semin Gastrointest Dis 2002. leading to the conclusion that rapid weight loss should be avoided in these patients  Youssef W.NASH .Cautions   When liver biopsies were performed in adults after weight loss.

other causes of liver disease should be ruled out before a diagnosis is made.Points to Remember    Obesity is a risk factor for NAFLD. Metabolic evaluation of the obese child should include evaluation of liver function. . Nonalcoholic fatty liver disease is a diagnosis of exclusion. and even mild obesity may be associated with elevation of liver enzymes and hepatic steatosis.

  Etiology  Friesen Clin Pediatr 1989. tenderness .Obesity Related Gastrointestinal Morbidity  Diagnosis   Abdominal pain.7:294. . Obesity accounts for 8%-33% of gallstones in children. 1972.Cholelithiasis.17:68-72. laboratory studies.  Crichlow Dig Dis. Ultrasound.  May be associated with weight loss.

17:68-72.2.Cholelithiasis.  Honore Arch Surg 1980. 1972.Obesity Related Gastrointestinal Morbidity  Risk  50% of cholecystitis in adolescents associated with obesity.  Crichlow Dig Dis.115:62-64.  Relative risk of gallstones in adolescent girls with obesity is 4.  Surgical Intervention .

Chronic .Obesity Related Co Morbid Conditions       Metabolic Syndrome Type II Diabetes Polycystic Ovary Syndrome Hypertension Hyperlipidemia Psychological .

Obesity

Insulin Resistance Metabolic Syndrome Syndrome Type 2DM
NASH PCOS Dyslipidemia

Hypertension

Components of the Metabolic Syndrome in Childhood

Obesity (BMI >95% for age and sex) Elevated blood pressure (SBP or DBP > 90% for age).

Components of the Metabolic Syndrome in Childhood

Abnormal blood lipids (HDL cholesterol <40mg/dl or triglycerides >150mg/dl LDL>130mg/dl).

Impaired glucose tolerance (fasting glucose > 100 (110) mg/dl, random glucose >200mg/dl).

Sinaiko AR, Donahue RP, Jacobs DR, et al. The Minneapolis Children’s Blood Pressure Study. Circulation 1999;99(11)1471-6.

axillae. Journal of Peds 2001 . Also seen in malignancies and other insulin resistant syndromes. and other skin folds In pediatrics. Obese pediatric pts with acanthosis have higher fasting insulin and lower insulin sensitivity than acanthosis negative obese patients Insulin resistant pts were more likely to be obese (88%) than have acanthosis (65%)  Yanovski et al. seen most commonly in obese children.Acanthosis Nigricans     Skin lesion characterized by hyperpigmentation and velvety thickening that occurs in neck.

Insulin Resistance and Fat Deposition Muscle Insulin resistance insulin Insulin resistance Liver Free Fatty Acids Insulin resistance .

Polycystic Ovarian Syndrome  Polycystic Ovary Syndrome. Enod Trends 11(1)2004 . Arslanian S. Girls with premature adrenarche   Increased risk  Bacha F. Hirsuitism Acne Polycystic ovaries and eventual infertility.      Hyperandrogenism Oligomenorrhea/amenorrhea.

and weight loss.128:608-615.  Pinhas-Hamiel J Pediatr 1996. .  Only 20% present with polyuria. polydipsia. Etiology  One third of new diabetics presenting between 10-19 years had NIDDM.Type 2 Diabetes   Diagnosis  Elevated fasting insulin and hyperglycemia.

One End of the Continuum Genetic Predisposition Environmental Trigger Beta Cell Obesity Hyperglycemia Dysfunction Type 2 Diabetes Insulin Resistance .Type 2 Diabetes .

Pathologic Defect in Type 2 DM  Excessive hepatic glucose production Defective beta-cell secretion and function (loss of first-phase response and erratic response to oscillations in glucose levels) Peripheral insulin resistance Duration and severity of hyperglycemia dictate the micro vascular complications     NEDI Publications Practical Diabetology Haffner. S .

. Etiology  60% of children with persistently elevated blood pressure had weight >120%.86:697-706.  20%-30% of obese children have elevated blood pressure.  Lauer J Pediatr 1975.Hypertension   Diagnosis  Screen all obese children with correct cuff.

 Long term risk of CVD and stroke.pharmacotherapy.45:235-240.   Intervention  Weight loss.Hypertension  Risk  Overweight adolescents have 8. low salt diet.5 fold risk of hypertension as adults.  Srinivasan Metab 1996. Cardiac hypertrophy/LVH on ultrasound. .

 Elevated LDL cholesterol.  Component of the metabolic syndrome   Etiology Increased central fat distribution  Hyperinsulinemia  .Hyperlipidemia  Diagnosis Screen all obese adolescents. triglycerides and lowered HDL cholesterol .

 Srinivasan Metab 1996.  Intervention  Weight loss .4 fold increase in prevalence of cholesterol >240mg/dl.Hyperlipidemia  Risk  Overweight during adolescence associated with 2. 3 fold increase in LDL values >160mg/dl and 8 fold increase in HDL values<35 mg/dl in adults 27-31 years.45:235-240.

Psychological Morbidity  Obesity Associated Psychological Conditions     Depression Anxiety Low self esteem Teasing/Bullying  Associated conditions impacting treatment    ADHD Bipolar Illness Adjustment Disorder .

 . Reducing morbidity should be a primary goal of obesity therapy.  Obesity related comorbidities can be improved with weight loss.Conclusion  Every obese child should be evaluated for the co morbid conditions of obesity.