can we predict prediabetes and cardiac risk profile in overweight african american adolescents...

Can We Predict Can We Predict Prediabetes and Cardiac Prediabetes and Cardiac

Risk Profile in Risk Profile in Overweight African Overweight African

American AdolescentsAmerican Adolescents

Patricia A. Cowan, PhD, RNPatricia A. Cowan, PhD, RN

University of Tennessee Health Science CenterUniversity of Tennessee Health Science Center

Funded by NIH-NINR and GCRCFunded by NIH-NINR and GCRC

Childhood Obesity: Assessments, Cardiometabolic

Risk, and Interventions

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

Obesity Trends: U.S. Obesity Trends: U.S. AdultsAdults

BRFSS, 1990BRFSS, 1990

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends: U.S. Adults BRFSS, 2008

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

TN#2 –Adult

obesity

#6 –Childhood

obesity

Prevalence of Overweight & Obesity Among Youth in the United States (1999-2008)

YearOverweight

(BMI for age ≥85%)

Obese(BMI for age≥ 95%)

1999-2000 28.2 13.9

2001-2002 30.0 15.4

2003-2004 33.6 17.1

2007-2008 31.7 16.9

Ogden, C.L., et al. (2006). JAMA, 295 (13), 1549-1555 and Ogden et al (2010) JAMA, 303(3):242-249.

Disparities in Obesity and Overweight Among 6-19 Year Olds in 2007-2008

GroupsGroups BoysBoys GirlsGirls

Overweight%

Obese%

Overweight%

Obese%

Total 35.3 20.1 34.1 17.3

Caucasian

33.4 18.2 31.6 15.6

African American

34.4 18.9 43.3 25.9

Hispanic American

43.1 26.7 40.5 19.5

Ogden, C.L., et al. (2010). JAMA, 303(3):242-249

Why the Concern?Why the Concern? Childhood obesity persists into Childhood obesity persists into

adulthoodadulthood

Linked to subsequent morbidity & Linked to subsequent morbidity & mortality, including type 2 diabetes mortality, including type 2 diabetes and cardiovascular diseaseand cardiovascular disease

Costly--$129 billion directly Costly--$129 billion directly attributed to obesityattributed to obesity

Escalation in costs if development of Escalation in costs if development of diabetes and cardiovascular diseasesdiabetes and cardiovascular diseases

Evolution of Childhood Type 2 Diabetes in the Greater-Memphis Area

ADA estimates ADA estimates 2 million teens (or 1 in 6 2 million teens (or 1 in 6 overweight adolescents) aged 12-19 have pre-overweight adolescents) aged 12-19 have pre-diabetes.diabetes.

The NHANES 1999-2000 data revealed an 11% The NHANES 1999-2000 data revealed an 11% prevalence of prediabetes in children. prevalence of prediabetes in children.

Since 1990, in the Memphis area, 10-fold Since 1990, in the Memphis area, 10-fold increase in diagnosis of type 2 diabetes increase in diagnosis of type 2 diabetes mellitus in children.mellitus in children.

In children, shorter latency period from In children, shorter latency period from prediabetes to diabetes. prediabetes to diabetes.

Cardiovascular Risk Cardiovascular Risk (CVR) Factors in Obese (CVR) Factors in Obese YouthYouth

Current screening recommendations for Current screening recommendations for obese youth include fasting insulin and obese youth include fasting insulin and glucose, blood pressure, and lipid profile glucose, blood pressure, and lipid profile if family history of hyperlipidemia.if family history of hyperlipidemia.

Typically clinicians refer older, more Typically clinicians refer older, more severely obese youth with a family severely obese youth with a family history of diabetes for metabolic history of diabetes for metabolic evaluationevaluation

Perception that diabetes drove the Perception that diabetes drove the development of CVR factors in youth.development of CVR factors in youth.

Who Should be Who Should be Screened?Screened?

Inadequate resources to screen all Inadequate resources to screen all overweight youth for diabetes and overweight youth for diabetes and CVR factors.CVR factors.

Need to identify which youth are at Need to identify which youth are at greater risk for developing metabolic greater risk for developing metabolic and cardiovascular abnormalities.and cardiovascular abnormalities.

Determine whether current screening Determine whether current screening recommendations relevant across recommendations relevant across ethnic groups.ethnic groups.

66% of youth who had IGT (pre-diabetes or diabetes based on OGTT) had normal fasting blood glucose

Diabetes Screening: 150 Diabetes Screening: 150 Overweight or Obese ChildrenOverweight or Obese Children

65

75

85

95

105

115

125

135

145

155G

LU

0

80 100 120 140 160 180 200 220

GLU120

OB_IGT

OB-NGT

Ctrl

Similar Cardiovascular Risk Factors in Obese AA Teens with T2DM and Obese AA Non-DM

Teens

0

20

40

60

FIB >400 CRP >0.5 BP>95th% Chol >170 LDL>110 TRI >150 HDL <35

Per

cen

t

T2DM Non-DM

*

*p<0.05 between groups

PurposePurpose

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

Design & SampleDesign & Sample

Descriptive, correlational Descriptive, correlational

122 overweight-obese 11-18 year 122 overweight-obese 11-18 year African-American (AA) adolescents African-American (AA) adolescents (age=14.8 (age=14.8 ± 2.1 yr), 57% female± 2.1 yr), 57% female

Non-diabetic, no medications that Non-diabetic, no medications that affect glucose tolerance, females-affect glucose tolerance, females-negative pregnancy test. 97% had negative pregnancy test. 97% had acanthosis nigricanacanthosis nigrican

Methods: Methods: Demographics and Demographics and Family HistoryFamily 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.

Methods: Obesity Methods: Obesity SeveritySeverity

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.

Methods: PrediabetesMethods: Prediabetes

Oral glucose tolerance test Oral glucose tolerance test (1mg/kg, 75 gm maximum)(1mg/kg, 75 gm maximum)

Prediabetes = Prediabetes = Fasting blood glucose Fasting blood glucose >> 100 mg/dl 100 mg/dl

oror 2-hr post load glucose 2-hr post load glucose >> 140 140

mg/dlmg/dl

Methods: Insulin Methods: Insulin ResistanceResistance

Fasting and Fasting and OGTT derived indices

QUICKI = 1/(log FIQUICKI = 1/(log FI μμU/mlU/ml+ log FBG)+ log FBG)

CISI= 10000 / [SQRT (FI x FBG) x CISI= 10000 / [SQRT (FI x FBG) x (mean insulin (0-120 min) x (mean insulin (0-120 min) x mean glucose (0-120 min)]mean glucose (0-120 min)]

Methods: CVR FactorsMethods: CVR FactorsFasting blood samples for Fasting blood samples for Homocysteine (>12 mcg/M)Homocysteine (>12 mcg/M) High-sensitivity C-reactive Protein (High-sensitivity C-reactive Protein (>>2 mg/L)2 mg/L) Fibrinogen (>350 mg/dl)Fibrinogen (>350 mg/dl) PAI-1 (>43 ng/ml)PAI-1 (>43 ng/ml) Standard lipid profile: triglycerides >150 mg/dl; Standard lipid profile: triglycerides >150 mg/dl;

cutpoints for total cholesterol, LDL-cholesterol, cutpoints for total cholesterol, LDL-cholesterol, HDL-cholesterol based on age and gender HDL-cholesterol based on age and gender normative data (Jolliffe 2006)normative data (Jolliffe 2006)

Lp(a) (Lp(a) (>>20 mg/dl)20 mg/dl) LDL particle size (<25.9=Pattern B)LDL particle size (<25.9=Pattern B)

Blood pressure (per NHLBI guidelines)Blood pressure (per NHLBI guidelines)

Self-report of tobacco use.Self-report of tobacco use.

Methods: Dietary IntakeMethods: Dietary Intake

3-day diet diary analyzed for 3-day diet diary analyzed for micro and macronutient micro and macronutient content using Nutribase Clinical content using Nutribase Clinical Nutritional dietary software Nutritional dietary software program.program.

Multi-pass approach with the Multi-pass approach with the use of food models and queries.use of food models and queries.

Methods: Methods: Activity/FitnessActivity/Fitness

7-Day physical activity recall7-Day physical activity recall Days/week of Days/week of >> 30 minutes of 30 minutes of

moderate or more intense physical moderate or more intense physical activityactivity

Sit hours per daySit hours per day

Maximal cardiopulmonary Maximal cardiopulmonary exercise testing (VO2 peak)exercise testing (VO2 peak)

Statistical AnalysisStatistical Analysis

Data log-transformed if not normally Data log-transformed if not normally distributeddistributed

Logistic regression to predict pre-Logistic regression to predict pre-diabetesdiabetes

Multiple regression to predict cardiac Multiple regression to predict cardiac risk profilerisk profile

Substitution of DXA for BMI measures Substitution of DXA for BMI measures of obesity severity and fitness for of obesity severity and fitness for physical activity in models.

Results: Results: AnthropometricsAnthropometrics

BMI BMI 36.4 ± 7.936.4 ± 7.9

Relative BMI Relative BMI 185.1 185.1 ± 40.4± 40.4

Percent fat massPercent fat mass 42.4 42.4 ± 7.4± 7.4

Percent trunk massPercent trunk mass 42.2 42.2 ±± 8.3 8.3 activity activity (day/week)(day/week)

Physical Activity and Physical Activity and FitnessFitness

VO2peak VO2peak (mg/kg/min):(mg/kg/min): 21.5 21.5 ± 6.3± 6.3

>> 30 min moderate+ 30 min moderate+ 2.6 2.6 ±± 1.8 1.8 activity activity (day/week)(day/week)

Sit Sit (hours/day)(hours/day) 10.5 10.5 ± 2.7± 2.7

Walk Walk (min/day)(min/day) 81.9 81.9 ± 62.8 ± 62.8 Only 4 youth (3.3%) engaged in Only 4 youth (3.3%) engaged in

recommended amounts of physical recommended amounts of physical activity.activity.

97% had very poor or poor levels of 97% had very poor or poor levels of fitnessfitness

Results: MacronutrientsResults: Macronutrients

Kcal/dayKcal/day

(Mean (Mean ± SD)± SD)Percent of Percent of

Intake Intake

ProteinProtein 268 268 ± 99± 99 15.2 15.2 ± 3.1± 3.1

CarbohydratCarbohydrateses

865 ± 333865 ± 333 48.3 ± 6.248.3 ± 6.2

FatFat 657 ± 246657 ± 246 36.5 ± 5.536.5 ± 5.5

Energy intake 1791 ± 626 Energy intake 1791 ± 626 kcal/day; kcal/day; estimated underreporting of estimated underreporting of

940 kcal/day940 kcal/day

Physical Activity and Physical Activity and FitnessFitness

VO2peak VO2peak (mg/kg/min):(mg/kg/min): 21.5 21.5 ± 6.3± 6.3

>> 30 min moderate+ 30 min moderate+ 2.6 2.6 ±± 1.8 1.8 activity activity (day/week)(day/week)

Sit Sit (hours/day)(hours/day) 10.5 10.5 ± 2.7± 2.7

Walk Walk (min/day)(min/day) 81.9 81.9 ± 62.8 ± 62.8 Only 4 youth (3.3%) engaged in Only 4 youth (3.3%) engaged in

recommended amounts of physical recommended amounts of physical activity.activity.

97% had very poor or poor levels of 97% had very poor or poor levels of fitnessfitness

Results: Pre-diabetesResults: Pre-diabetes OGTT on 119OGTT on 119

28 (23.5%) had prediabetes 28 (23.5%) had prediabetes

8 of these youth had normal fasting, 8 of these youth had normal fasting, but but

abnormal 2 hr glucose abnormal 2 hr glucose

Thus, 29% of youth with prediabetes Thus, 29% of youth with prediabetes would have been missed if the OGTT would have been missed if the OGTT had not been performed.had not been performed.

Results: Insulin Results: Insulin ResistanceResistance

CISI CISI << 2.0 2.0 77 (69.4%)77 (69.4%)

QUICKI QUICKI <<0.30.3 68 (57.1%)68 (57.1%)

Some degree of acanthosis nigricans Some degree of acanthosis nigricans in 97%.in 97%.

Results: CVR factorsResults: CVR factorsCVR Factor Abnormal

N (%)CVR Factor AbnormAbnorm

alal

N (%)N (%)

Lp(a)Lp(a) 94 (78.3)94 (78.3) Tobacco UseTobacco Use 9 (7.3)9 (7.3)

CRP-hsCRP-hs 71 (59.2)71 (59.2) HomocysteinHomocysteinee

7 (5.8)7 (5.8)

FibrinogenFibrinogen 71 (59.2)71 (59.2) LDL-LDL-cholesterolcholesterol

7 (5.8)7 (5.8)

PAI-1PAI-1 60 (50.4)60 (50.4) Total Total cholesterolcholesterol

4 (2.3)4 (2.3)

HDL-HDL-cholesterolcholesterol

58 (47.5)58 (47.5) Small LDL Small LDL particle sizeparticle size

1 (0.8)1 (0.8)

HypertensioHypertensionn

32 (29)32 (29) TriglyceridesTriglycerides 1 (0.8)1 (0.8)

Results: CVR FactorsResults: CVR Factors

# of CVR factors 3.9 ± 1.6# of CVR factors 3.9 ± 1.6

36% had five or more CVR 36% had five or more CVR factorsfactors

Model: Pre-diabetesModel: Pre-diabetes Logistic regression to predict Logistic regression to predict

prediabetesprediabetes

Variables entered: Obesity severity Variables entered: Obesity severity (BMI, RBMI or fat mass), physical (BMI, RBMI or fat mass), physical activity or fitness, family history, activity or fitness, family history, insulin indices, diet, adjusting for insulin indices, diet, adjusting for tanner stage, age, and gendertanner stage, age, and gender

Model did not predict prediabetesModel did not predict prediabetes

Model: Cardiac ProfileModel: Cardiac Profile Backwards multiple regression for Backwards multiple regression for

cardiac profile.cardiac profile.

Higher severity of obesity and Higher severity of obesity and positive family history of MI positive family history of MI predicted cardiac profile retained in predicted cardiac profile retained in all models.all models.

Age (younger), Tanner score (lower), Age (younger), Tanner score (lower), obesity severity, insulin resistance obesity severity, insulin resistance (greater), and positive family history (greater), and positive family history of MI predicted of MI predicted 33% 33% of the variance of the variance in the cardiac profile.in the cardiac profile.

DiscussionDiscussion

Compared to NHANES data:Compared to NHANES data:

prediabetes was more common in these prediabetes was more common in these predominantly sedentary, overweight predominantly sedentary, overweight AA adolescents. AA adolescents.

emerging cardiac risk factors were emerging cardiac risk factors were more prevalentmore prevalent

Contrary to the literature, fitness and Contrary to the literature, fitness and physical activity did not predict pre-physical activity did not predict pre-diabetes nor the cardiac profile. diabetes nor the cardiac profile.

Research ConclusionsResearch Conclusions Current screening recommendation Current screening recommendation

underestimate metabolic and cardiac underestimate metabolic and cardiac risk of obese AA adolescents.risk of obese AA adolescents.

Because neither age, severity of Because neither age, severity of obesity, or family history of T2DM obesity, or family history of T2DM predicted prediabetes in overweight predicted prediabetes in overweight AAA, these demographics should not AAA, these demographics should not be used to limit screening for be used to limit screening for prediabetes in this population.prediabetes in this population.

Research ConclusionsResearch Conclusions Future studies are needed to Future studies are needed to

determine the interactions between determine the interactions between biomarkers, behaviors, and obesity biomarkers, behaviors, and obesity severity to predict early CVD in severity to predict early CVD in obese AA adolescents.obese AA adolescents.

Childhood Obesity Childhood Obesity TreatmentsTreatments

Target Factors Contributing to Obesity in Youth

Nutritional Factors Physical Inactivity

Consider Other Factors Contributing to Childhood Obesity

Medical Conditions

Pharmacological Treatments

Genetic Conditions

Other (Abuse, etc)

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 ).

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

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.

Challenges with Home Challenges with Home Lifestyle Behavioral Lifestyle Behavioral TreatmentsTreatments

Portion Sizes

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

Anti-Obesity Medications

• Anti-obesity medications are usually Anti-obesity medications are usually reserved for those patients who have reserved for those patients who have failed diet, exercise, and behavioral failed diet, exercise, and behavioral interventions (Kaplan, 2005). interventions (Kaplan, 2005).

• Approved by the Federal Drug Approved by the Federal Drug Administration for weight loss in adults: Administration for weight loss in adults: appetite depressant (phentermine, appetite depressant (phentermine, sibutramine), and inhibitors of fat sibutramine), and inhibitors of fat absorption (orlistat). absorption (orlistat).

(Ionnides-Demos, Proietto, & McNeil, 2005)

In Overweight Youth with Impaired Glucose Tolerance

Impaired glucose tolerance is characterized by insulin Impaired glucose tolerance is characterized by insulin resistance with high levels of insulin productionresistance with high levels of insulin production (beta- (beta-cell function is preserved) cell function is preserved)

Treatment should be geared toward improving insulin Treatment should be geared toward improving insulin sensitivity sensitivity (decreasing insulin resistance) (decreasing insulin resistance) while while preserving beta-cell function.preserving beta-cell function.

Treatment focus is on diet, weight loss, increase physical Treatment focus is on diet, weight loss, increase physical activity, medications to improve insulin sensitivity…also activity, medications to improve insulin sensitivity…also look at other risk factors that may need interventionlook at other risk factors that may need intervention

Additional Treatments if Associated Co-Morbidities

Metformin and other insulin-Metformin and other insulin-lowering drugslowering drugs

Lipid-lowering drugsLipid-lowering drugs High blood pressure medicinesHigh blood pressure medicines

Ornstein, R.M. & Jacobson, M.S. (2006). Adolescent Medicine Clinics, 17 (3), 565-587.

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

Evidence for Management

Multidisciplinary approach Family involvement Behavioral/Lifestyle remains

key component Medication MAY be used as

adjunct Bariatric surgery—last resort

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?

COFFEE 20 Years Ago

Coffee(with whole milk and sugar)

Today

Mocha Coffee(with steamed whole milk and mocha syrup)


350 calories16 ounces

Calorie Difference: 305 calories

How long will you have to walk in order to burn those extra 305 calories?*

*Based on 130-pound person

Maintaining a Healthy Weight is a Balancing Act: Calories In = Calories Out

If you walk 1 hour and 20 minutes, you will burn approximately 305 calories.*


Calories In = Calories Out

MUFFIN

20 Years Ago Today

210 calories 1.5 ounces

How many calories are in today’s muffin?

20 Years Ago Today



MUFFIN

210 calories 1.5 ounces

How long will you have to vacuum in order to burn those extra 290 calories?*


Maintaining a Healthy Weight is a Balancing Act: Calories In = Calories Out

If you vacuum for 1 hour and 30 minutes you will burn approximately 290 calories.*



CHICKEN CAESAR SALAD

20 Years Ago Today

390 calories 1 ½ cups

How many calories are in today’s chicken Caesar salad?

CHICKEN CAESAR SALAD

20 Years Ago Today

390 calories 1 ½ cups

790 calories3 ½ cups


How long will you have to walk the dog in order to burn those extra 400 calories?*


Maintaining a Healthy Weight is a Balancing ActCalories In = Calories Out

If you walk the dog for 1 hour and 20 minutes, you will burn approximately 400 calories.*


can we predict prediabetes and cardiac risk profile in overweight african american adolescents...

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