3yr old WCC w/ pt Not Mykid Obesity Webcast Department of Pediatrics, GCH@URMC New York State, Department of Health 2 16 yr old WCC, Last Yr Obesity w/ BMI Pt WLF 16 yr old w/ Cough. 3 4 Stigma of Child Obesity Pseudotumor Cerebri Hypothalamic Inflammation The lot of fat children is a sad one. They are bashful and ashamed of their shapeless figures, yet unable to conceal them. Wherever they go they attract attention..obesity is a serious handicap in the social life of a child, even more so of a teenager. Obesity does not have the dignity of other diseases 5 http://mytrainerchris.wordpress.com/2013/12/07/childhood-obesity/ Bruch H. Pediatric Annals: 1975 1
Percentage of teen girls who report frequent weight teasing Consider Waist Circumference Measure at the superior iliac crest with tape parallel to floor Adults Woman 35 inches Men 40 inches Waist to Height ratio >0.5 Neumark-Sztainer. J Adolesc Health. 2009;44:206-213. 7 Instructional Video from CDC http://www.cdc.gov/nchs/video/nhanes3_anthropometry/ circumference/circumference.htm Consider Waist Circumference Age (yr) Boys / 90 th & 95 th (cm) Girls / 90 th & 95 th (cm) 3 54.7 56.5 55.3 57.4 4 57.4 59.9 58.1 60.8 5 60.1 63.4 60.6 64.1 6 63.2 67.2 63.4 67.7 7 66.7 71.7 66.8 71.9 8 70.4 76.3 70.3 76.1 9 74 80.8 73.8 80 10 77.5 84.8 77.2 83.5 11 80.8 88.5 80.4 86.8 12 83.8 92 83.3 89.9 13 86.7 95.1 85.9 92.7 14 89.2 97.8 87.9 95 15 91.5 100.2 89.4 96.6 16 93.5 102.2 90.4 97.8 Cook S, Auinger P, Huang TT. "Growth curves for cardio-metabolic risk factors in children and adolescents." The Journal of pediatrics. 2009 Sep; 155(3):S6.e15-26. NOW Laboratory Testing BMI 85-94%ile Without Risk Factors Non-Fasting Lipid Profile Once 9-11yr and then 17-18yr BMI 85-94%ile Age 10 Years & Older With Risk Factors Non-Fasting Lipid Profile ALT and AST Blood Glucose/HgbA1C 10 NOW Laboratory Testing BMI 95%ile Age 10 Years & Older Non-Fasting Lipid Profile ALT and AST Every 2 Glucose/HgbA1C Years Other Tests as Indicated by Health Risks Yogi on life in an obese teen s arteries - It gets late early out there ABNORMAL BLOOD GLUCOSE IN GENERAL PEDIATRICS 11 12 2
Summary of Issues in Pediatric Practice 1. Definitions Polling Question I am confident that I can identify the obese children who are at the highest risk of developing diabetes before they age out of my practice. Yes No 2. Predicting Type 2 Diabetes Risk Factors in the History Risk Factors on Physical Examination Screening Tests Who to test When to test 3. What type of diabetes is it? Type 1 can t wait 13 14 Type 2 Diabetes Diagnostic Criteria 2010 Fasting Blood Glucose 126 mg/dl OR Casual Blood Glucose 200 mg/dl OR 2 hour OGTT sample 200 mg/dl OR HbA1c 6.5% If symptoms not present, need to have 2 abnormal samples Increased Risk for Diabetes Impaired Fasting Glucose 100 125 mg/dl Abnormal Glucose Tolerance 2 hour glucose 140-199 mg/dl on OGTT Borderline HbA1c HbA1c 5.7 6.4% Diabetes Care January 2010 vol. 33 no. Supplement 1 S11-S61 & S62-69 Diabetes Care January 2010 vol. 33 no. Supplement 1 S11-S61 & S62-69 Type 2 Diabetes A Two-Hit Disease Predicting Type 2 Diabetes High Insulin Production Low Type 2 Diabetes It s tough to make predictions; especially about the future. Low High Insulin Sensitivity 3
Identifying Those At Risk of T2DM Prenatal Environment Prenatal Exposure PAF* Maternal Diabetes 4.7% Maternal Obesity 19.7% Diabetes + Obesity 22.8% Total all Categories 47.2% Putative Predictors of T2DM in Children Odds Ratio IFG 8.2 HOMA-IR / Insulin 1.6 Insulin Calorie Intake 1.02 Metabolic Syndrome 11.5 Race 2.2 Parental History 5.0 Age at Follow-Up 1.1 *PAF Population Attributable Fraction Dabelea et al. Diab Care (2008) 31:1422. Morrison et al. Am J Clin Nut 2008. 88:778 Morrison et al. J Pediatr 2008. 152:201 Screening for Diabetes ADA Recommendations 2010 Screen Child for T2DM if 10 yrs old or at puberty BMI >85 th percentile PLUS Any 2 of Family History High Risk Race Insulin resistance* Maternal Diabetes or Gestational DM Re-check negatives every 3 years Associations With Insulin Resistance Acanthosis Nigricans Hypertension Dyslipidemia PCOS IUGR * Defined in next slide Diabetes Care January 2010 vol. 33 no. Supplement 1 S11-S61 & S62-69 http://care.diabetesjournals.org/content/37/supplement_1/s14.full.pdf+html (pg S17-S18) Diabetes Care January 2010 vol. 33 no. Supplement 1 S11-S61 & S62-69 http://care.diabetesjournals.org/content/37/supplement_1/s14.full.pdf+html (pg S17-S18) Incidence of Childhood Diabetes 2002-2003 Type 1 vs Type 2 TODAY Study 1,206 children 10-17 yo with type 2 diagnosis 118 (9.8%) autoantibody positive (GAD & IA-2) 71 single autoab 47 double autoab AutoAb-pos behaved like Type 1 over time The Writing Group for the SEARCH for Diabetes in Youth Study Group, JAMA 2007;297:2716-2724. If you come to a fork in the road, take it Klingensmith et al Diabetes Care Sept 2010. 33:1970-75 4
Steatosis (NAFL) 30% of adults 9% of children NAFLD: Quick Review Steatohepatitis (NASH) 3-5% of adults and children Why are we worried about NASH? NASH-related cirrhosis in the United States alone has increased 6 fold over the last decade. Now 3 rd leading cause for liver transplantation 2-12% of adults with NASH cirrhosis Cirrhosis Predicted to outpace all other etiologies for liver transplant in adults by 2030. Hepatocellular carcinoma 10-29% of adults with NASH within 10 years Afzali, A. Liver Transpl 2012;18(1):29-37 Fibrotic NASH can worsen significantly during adolescence Progression of fibrosis over 5 years Patient Initial Visit Follow Up Age (years) BMI 28 (97%ile) 11 16 38 (99%ile) AST 59 114 ALT 134 172 GGT 73 105 Patient lost to follow-up x 5 years BMI up 10 units RUQ tenderness Multiple abdominal striae Hepatomegaly 3cm below right costal margin Age 11 Age 16 Stage 1c fibrosis Stage 3 fibrosis Kohli R, anthakos SA et al. JPGN 2009 Kohli, anthakos et al. JPGN 2010 Kohli R, anthakos SA et al. JPGN 2009 Available Society Guidelines re: Screening overweight/obese children for NAFLD SOCIETY YES NO UNCERTAIN NOT STATED American Academy of Family Physicians American Academy of Pediatrics Does NAFLD fit criteria of screenable disease? Common? American Association for the Study of Liver Diseases High morbidity and mortality? American College of Gastroenterology American Gastroenterological Society Endocrine Society European Society for Pediatric GI, Hepatology and Nutrition National Association of Nurse Practitioners North American Society for Pediatric GI, Hepatology and Nutrition Accurate screening tool? Widely available therapy? +/- Schwimmer JB. Aliment Pharmacology & Therapeutics 2013;38:1267 5
Treatment Goals - Weight Loss Targets Age 2-5 Years BMI 85-94%ile BMI 85-94%ile BMI 95-98%ile No Risks With Risks Maintain weight Decrease weight Weight velocity velocity or maintenance weight maintenance Age 6-11 Years Maintain weight velocity Age 12-18 Years Maintain weight velocity. After linear growth is complete, maintain weight 3yr old WCC w/ pt Not Mykid BMI >= 99%ile Gradual weight loss of up to 1 pound a month if BMI is very high (>21 or 22 kg/m2) Decrease weight velocity or weight maintenance Decrease weight velocity or weight maintenance Weight maintenance or gradual loss (1 lb per month) Weight loss (average is 2 pounds per week)* Weight loss (average is 2 pounds per week)* Weight loss (average is 2 pounds per week)* * Excessive weight loss should be evaluated for high risk behaviors 32 Pt MN Pt NW, first seen at 3yrs and noted to be obese PNP informed pt in Red zone as unhealthy. Can we discuss? 33 Pt WLF 16 yr old w/ Cough. 34 Pt WLF 16 yr old w/ Cough. 35 36 6
16 yr old WCC, Last Yr Obesity w/ BMI 16 yr old WCC, Last Yr Obesity w/ BMI 37 38 SUPPLEMENTAL SLIDES Diagnosis of NASH 39 40 What is an abnormal ALT value? ALT Abnormal Values VARY WIDELY at children s hospitals (range >30-90 U/L) do not exclude overweight/obese or other causes of liver disease 95% percentile ALT for healthy weight, metabolically normal, teens in NHANES is: ALT 25.8 U/L for MALES ALT 22.1 U/L for FEMALES If ALT persistently > 2 x ULN (>50 U/L), more likely to have liver disease Limitations of ALT Cannot reliably differentiate NAFL from NASH Broad differential diagnosis if abnormal: need exclusionary testing ($$$) e.g. viral hepatitis, autoimmune, alpha 1 antitrypsin, hemochromatosis, Wilson disease Schwimmer JB. Gastroenterology 2010;138:1357 Schwimmer JB. Gastroenterology 2010;138:1357 Loomba R, Clin Gastro Hep 2008; 6(11):1243-8. 7
Advanced Imaging: Transient Elastography Ultrasound limitations Transient Elastography- Fibroscan AUROC 0.99 for prediction of significant ( 2 fibrosis in Can evaluate liver structure/gall bladder Italian children with NAFLD, mean BMI 26, mean age 14) NO ROLE IN CONFIRMING OR DIAGNOSING NASH! Not reliable in identifying and measuring steatosis Cannot differentiate NAFL from NASH Marginean C. European Journal of Radiology 2012 (81): e870 Liver MRE Case Advanced Imaging: MRI Elastography (MRE) 4 yo with progressive intrahepatic cholestasis type 2 Mean liver stiffness 3.3 kpa = stage 2 fibrosis GE healthcare Images courtesy of Drs. Daniel Podberesky and Suraj Serai, Dept of Radiology, CCHMC Liver biopsy remains gold standard 35 children (majority NAFLD) with liver biopsy and MREL P=0.03 AUROC 0.92 (0.79,1.00) 88% sens, 85% specific at 2.71 kpa to detect fibrosis 2 PROS Can distinguish between NAFLD and NASH Clinical prognosis depends on histology NASH 25-30% risk of progression Early onset pediatric fibrosis more aggressive? Rule out other liver diseases (AIH, Wilson) Initiate more aggressive Rx and assess response CONS Fib 1 versus Fib 2 Risk 1:10,000 risk of death (in adults) Sampling error Expense anthakos et al; J Pediatr, 2014 Jan;164(1):186-8. 8
Pediatric NASH Treatment Recommendations 2012 ACG, AGA, AASLD Guidelines: Treatment of NASH Lifestyle modification always first step No medications recommended Metformin not recommended. Do not start Vitamin E More confirmatory studies needed 49 Severe NASH has been recommended as an indication for adolescent bariatric surgery, but supportive data still weak SELECTION CRITERIA FOR ADOLESCENT BARIATIC SURGERY BMI Comorbidities > 35 Type 2 DM moderate-severe OSA (AHI 15 events/hr) pseudotumor cerebri severe NASH > 40 Mild OSA (AHI>5 events/hr) HTN Insulin resistance/igt Dyslipidemia impaired QOL or ADL SUPPLEMENTAL SLIDES - DIABETES 52 Pratt, JSA et al. Obesity 2009; 17:901 Insulin Resistance (IR) & Acanthosis Nigricans Acanthosis Nigricans Sensitivity 0.48 (0.35-0.61) Specificity 0.94 (0.90-0.99) BMI 85 th percentile 0.74 (0.63-0.85) 0.58 (0.48-0.67) IR (by HOMA-IR>4) in 161 Native American Indians (aged 5-18 years) Acanthosis Nigricans in 15.1% of 5-11 yo and 30.9% of 12-18 yo % overweight 25.8% (5-11) vs 19.1 (12-18) % obese 32.3 (5-11) vs 29.4 (12-18) BMI 95 th percentile About 80% of subjects with glucose intolerance had acanthosis Nigricans 0.57 (0.44-0.70) 0.84 (0.77-0.91) Nsiah-Kumi et al. J Natl Med Assoc. Oct 2010. 102:944 Clinical Screening for IGT 1004 overweight/obese German children 113 found to have pre-diabetes Correlation with pre-diabetes found with Parental diabetes history Pubertal Stage Extreme obesity (>99.5 % ile) 90% sensitivity if positive screen defined as: parental history OR Extreme obesity AND entered puberty No association with acanthosis Nigricans, waist circumference, hypertension, lipids, birth weight Reinehr et al. Pediatr Diabetes Sept 2009. 10:395. 9
What Does Fasting Insulin Tell Us? High insulin level (resistance) Does not predict diabetes in subjects without Fam Hx of T2DM High insulin is predictive when both of subject s parents have T2DM What Happens to Children with IGT? 128 German children with IGT 13.5 ± 2.1 years 53% female BMI = 31.7 ± 6.1 6 FH- and 25FH+ developed T2DM during follow-up Goldfine et al: PNAS, 2003. 100 : 2724-2729 Kleber et al: Exp Clin Endocrinol Diabetes 2011; 119(3): 172-176 Natural History of IGT in Children 3.9 yr F/U Normal Imp Gluc Toler Type 2 Diabet Lost to F/U N 96 20 3 9 Higher 2-hour blood glucose, but not fasting blood glucose correlated with progression to T2DM and persistent IGT More subjects and longer follow-up is needed Kleber et al: Exp Clin Endocrinol Diabetes 2011; 119(3): 172-176 10