Can We Predict Prediabetes and Cardiac Risk Profile in Overweight African American Adolescents

1. Childhood Obesity: Assessments, Cardiometabolic Risk, and Interventions Can We Predict Prediabetes and Cardiac Risk Profile in Overweight African American Adolescents Patricia A. Cowan, PhD, RN University of Tennessee Health Science Center Funded by NIH-NINR and GCRC

2. Obesity: A Worldwide Concern Worldwide there are 1 billion overweight or obese adults. In the United States, 65% of adults are overweight or obese---The prevalence has doubled since 1980. Parental obesity associated with childhood obesity. (2004). Obesity—Big is beautiful? The Globalist: retrieved March 1, 2003 from www.theglobalist.com/DBWeb/printStoryId.aspx?StoryId=3326

3. Obesity Trends: U.S. AdultsBRFSS, 1990 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14%

4. Obesity Trends: U.S. Adults BRFSS, 2008 TN #2 –Adult obesity #6 –Childhood obesity (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

5. Prevalence of Overweight & Obesity Among Youth in the United States (1999-2008) Ogden, C.L., et al. (2006). JAMA, 295 (13), 1549-1555 and Ogden et al (2010) JAMA, 303(3):242-249.

6. Disparities in Obesity and Overweight Among 6-19 Year Olds in 2007-2008 Ogden, C.L., et al. (2010). JAMA, 303(3):242-249

7. Why the Concern? • Childhood obesity persists into adulthood • Linked to subsequent morbidity & mortality, including type 2 diabetes and cardiovascular disease • Costly--$129 billion directly attributed to obesity • Escalation in costs if development of diabetes and cardiovascular diseases

8. Evolution of Childhood Type 2 Diabetes in the Greater-Memphis Area Since 1990, in the Memphis area, 10-fold increase in diagnosis of type 2 diabetes mellitus in children. In children, shorter latency period from prediabetes to diabetes. The NHANES 1999-2000 data revealed an 11% prevalence of prediabetes in children. ADA estimates 2 million teens (or 1 in 6 overweight adolescents) aged 12-19 have pre-diabetes.

9. Cardiovascular Risk (CVR) Factors in Obese Youth • Current screening recommendations for obese youth include fasting insulin and glucose, blood pressure, and lipid profile if family history of hyperlipidemia. • Typically clinicians refer older, more severely obese youth with a family history of diabetes for metabolic evaluation • Perception that diabetes drove the development of CVR factors in youth.

10. Who Should be Screened? • Inadequate resources to screen all overweight youth for diabetes and CVR factors. • Need to identify which youth are at greater risk for developing metabolic and cardiovascular abnormalities. • Determine whether current screening recommendations relevant across ethnic groups.

11. 155 145 135 125 115 GLU0 105 95 85 75 65 80 100 120 140 160 180 200 220 GLU120 66% of youth who had IGT (pre-diabetes or diabetes based on OGTT) had normal fasting blood glucose Diabetes Screening: 150 Overweight or Obese Children

12. Similar Cardiovascular Risk Factors in Obese AA Teens with T2DM and Obese AA Non-DM Teens * *p<0.05 between groups

13. Purpose • Examine the interaction of severity of obesity, physical activity (fitness), diet, insulin resistance and family history in predicting pre-diabetes and a cardiac risk profile in overweight-obese AA adolescents.

14. Design & Sample • Descriptive, correlational • 122 overweight-obese 11-18 year African-American (AA) adolescents (age=14.8 ± 2.1 yr), 57% female • Non-diabetic, no medications that affect glucose tolerance, females-negative pregnancy test. 97% had acanthosisnigrican

15. Methods: Demographics and Family History • Age • Gender • Tanner Stage • Parental report of family history of type 2 diabetes or early myocardial infarction in child’s parents or blood relatives.

16. Methods: Obesity Severity • Body Mass Index (BMI) BMI= Weight in kg Height in m² Relative BMI= BMI x 100 50th% BMI • Whole body DXA scan (Hologics) with segment measures of fat, bone, and lean mass.

17. Methods: Prediabetes • Oral glucose tolerance test (1mg/kg, 75 gm maximum) • Prediabetes = • Fasting blood glucose > 100 mg/dl or • 2-hr post load glucose > 140 mg/dl

18. Methods: Insulin Resistance • Fasting and OGTT derived indices • QUICKI = 1/(log FIμU/ml+ log FBG) • CISI= 10000 / [SQRT (FI x FBG) x (mean insulin (0-120 min) x mean glucose (0-120 min)]

19. Methods: CVR Factors Fasting blood samples for • Homocysteine (>12 mcg/M) • High-sensitivity C-reactive Protein (>2 mg/L) • Fibrinogen (>350 mg/dl) • PAI-1 (>43 ng/ml) • Standard lipid profile: triglycerides >150 mg/dl; cutpoints for total cholesterol, LDL-cholesterol, HDL-cholesterol based on age and gender normative data (Jolliffe 2006) • Lp(a) (>20 mg/dl) • LDL particle size (<25.9=Pattern B) Blood pressure (per NHLBI guidelines) Self-report of tobacco use.

20. Methods: Dietary Intake • 3-day diet diary analyzed for micro and macronutient content using Nutribase Clinical Nutritional dietary software program. • Multi-pass approach with the use of food models and queries.

21. Methods: Activity/Fitness • 7-Day physical activity recall • Days/week of > 30 minutes of moderate or more intense physical activity • Sit hours per day • Maximal cardiopulmonary exercise testing (VO2 peak)

22. Statistical Analysis • Data log-transformed if not normally distributed • Logistic regression to predict pre-diabetes • Multiple regression to predict cardiac risk profile • Substitution of DXA for BMI measures of obesity severity and fitness for physical activity in models.

23. Results: Anthropometrics • BMI 36.4 ± 7.9 • Relative BMI 185.1 ± 40.4 • Percent fat mass 42.4 ± 7.4 • Percent trunk mass 42.2 ± 8.3 activity (day/week)

24. Physical Activity and Fitness • VO2peak (mg/kg/min): 21.5 ± 6.3 • > 30 min moderate+ 2.6 ± 1.8 activity (day/week) • Sit (hours/day) 10.5 ± 2.7 • Walk (min/day) 81.9 ± 62.8 • Only 4 youth (3.3%) engaged in recommended amounts of physical activity. • 97% had very poor or poor levels of fitness

25. Results: Macronutrients Energy intake 1791 ± 626 kcal/day; estimated underreporting of 940 kcal/day

26. Physical Activity and Fitness • VO2peak (mg/kg/min): 21.5 ± 6.3 • > 30 min moderate+ 2.6 ± 1.8 activity (day/week) • Sit (hours/day) 10.5 ± 2.7 • Walk (min/day) 81.9 ± 62.8 • Only 4 youth (3.3%) engaged in recommended amounts of physical activity. • 97% had very poor or poor levels of fitness

27. Results: Pre-diabetes • OGTT on 119 • 28 (23.5%) had prediabetes • 8 of these youth had normal fasting, but abnormal 2 hr glucose • Thus, 29% of youth with prediabetes would have been missed if the OGTT had not been performed.

28. Results: Insulin Resistance • CISI < 2.0 77 (69.4%) • QUICKI <0.3 68 (57.1%) • Some degree of acanthosisnigricans in 97%.

29. Results: CVR factors

30. Results: CVR Factors • # of CVR factors 3.9 ± 1.6 • 36% had five or more CVR factors

31. Model: Pre-diabetes • Logistic regression to predict prediabetes • Variables entered: Obesity severity (BMI, RBMI or fat mass), physical activity or fitness, family history, insulin indices, diet, adjusting for tanner stage, age, and gender • Model did not predict prediabetes

32. Model: Cardiac Profile • Backwards multiple regression for cardiac profile. • Higher severity of obesity and positive family history of MI predicted cardiac profile retained in all models. • Age (younger), Tanner score (lower), obesity severity, insulin resistance (greater), and positive family history of MI predicted 33% of the variance in the cardiac profile.

33. Discussion Compared to NHANES data: • prediabetes was more common in these predominantly sedentary, overweight AA adolescents. • emerging cardiac risk factors were more prevalent Contrary to the literature, fitness and physical activity did not predict pre-diabetes nor the cardiac profile.

34. Research Conclusions • Current screening recommendation underestimate metabolic and cardiac risk of obese AA adolescents. • Because neither age, severity of obesity, or family history of T2DM predicted prediabetes in overweight AAA, these demographics should not be used to limit screening for prediabetes in this population.

35. Research Conclusions • Future studies are needed to determine the interactions between biomarkers, behaviors, and obesity severity to predict early CVD in obese AA adolescents.

36. Childhood Obesity Treatments

37. Energy In > Energy Out Target Factors Contributing to Obesity in Youth • Nutritional Factors • Physical Inactivity

38. Consider Other Factors Contributing to Childhood Obesity • Medical Conditions • Pharmacological Treatments • Genetic Conditions • Other (Abuse, etc)

39. Lifestyle and Behavioral Interventions • Family-based behavioral weight-management interventions have generally yielded positive results in children (McLean, 2003; Epstein, 1994; Reinehr, Brylak, Alexy, Kersting, and Andler, 2003). • Parents strongly influence their children’s dietary intake and level of activity through modeling and reinforcement of eating and lifestyle habits. • Additionally parents determine food options and opportunities for physical activity (Morgan, 2002 ).

40. Dietary-Behavioral-Physical Activity Interventions • Three month duration effectively decreased BMI • Exercise minimally 3 x week 45 minutes • Balanced hypocaloric diet • Counseling • Modest BMI reductions -1.7 vs. a gain of 0.6 for the control group

41. Inpatient (Immersion) Programs? • 2006 study • Diet-based on RDA for age and low fitness level • Physical activity-90 minutes 3x week or more • Cognitive behavioral therapy: modification-individual and group sessions • Impressive BMI decline!! -Girls-38.4 ± 4.1 down to 28.4 ± 4.1 -Boys-34.5 ± 3.2 down to 25.5 ± 2.3 • 2011 review: 191% greater reductions in % overweight at post-treatment and 130% greater reduction at 12month follow-up Kelly, K. P., & Dirschenbaum, D. S. (2011). Obesity Reviews, 12(1):37-49.

42. Challenges with Home Lifestyle Behavioral Treatments

43. Portion Sizes

44. How Much Exercise Is Needed? • Physical activity 60 minutes everyday • Limit physical inactivity • Issues with length of school day, homework, technology (computer, gaming, TV), safety concerns

45. Anti-Obesity Medications • Anti-obesity medications are usually reserved for those patients who have failed diet, exercise, and behavioral interventions (Kaplan, 2005). • Approved by the Federal Drug Administration for weight loss in adults: appetite depressant (phentermine, sibutramine), and inhibitors of fat absorption (orlistat). • (Ionnides-Demos, Proietto, & McNeil, 2005)

46. In Overweight Youth with Impaired Glucose Tolerance Impaired glucose tolerance is characterized by insulin resistance with high levels of insulin production (beta-cell function is preserved) Treatment should be geared toward improving insulin sensitivity (decreasing insulin resistance) while preserving beta-cell function. Treatment focus is on diet, weight loss, increase physical activity, medications to improve insulin sensitivity…also look at other risk factors that may need intervention

47. Additional Treatments if Associated Co-Morbidities • Metformin and other insulin-lowering drugs • Lipid-lowering drugs • High blood pressure medicines Ornstein, R.M. & Jacobson, M.S. (2006). Adolescent Medicine Clinics, 17 (3), 565-587.

48. Bariatric Surgery for Obese Youth • Medically supervised weight loss management Failed at ≥6 months • BMI ≥40 with serious obesity-related co-morbidities • or BMI ≥ 50 with less severe co- morbidities • Physiologic maturity Attained or nearly attained • Medical and Psychological evaluations Demonstrated commitment before and after surgery • Agreement to avoiding Pregnancy At 1 year postoperatively • Informed consent Must provide • Decisional Capacity Must provide • Family environment Supportive • _____________________________________________________________________________ • Inge et al., 2004. Serious obesity-related co-morbities (Diabetes type 2, obstructive sleep apnea, and pseudotumor cerebri);  less severe co-morbidities (hypertension, dyslipidemia, nonalcoholic steatohepatitis, venous stasis disease, significant impairment in activities of daily living, interiginous soft-tissue infections, stress urinary incontinence, gastroesophageal reflux disease, weight-related arthropaties that impair physical activity, and obesity related psychosocial distress

49. Evidence for Management • Multidisciplinary approach • Family involvement • Behavioral/Lifestyle remains key component • Medication MAY be used as adjunct • Bariatric surgery—last resort

50. COFFEE 20 Years Ago Coffee(with whole milk and sugar) Today Mocha Coffee(with steamed whole milk and mocha syrup) 45 calories 8 ounces How many calories are in today's coffee?