adolescent obesity. objectives definition of overweight in youth prevalence and trends health...

Adolescent Obesity

Objectives

• Definition of overweight in youth

• Prevalence and trends

• Health implications

• Behavioral and pharmacological treatment

What Is BMI?

• Body mass index (BMI) = weight (kg)/height (m2)

• Or: BMI = [weight (pounds) X 703]/height (in2)

• BMI is an effective screening tool; it is not a diagnostic tool

• For children, BMI is age and gender specific, so BMI-for-age is the measure used for youth

BMI-for-Age Cutoffs for Children and Adolescents

≥ 95th percentile Overweight

85th to < 95th percentile Risk of overweight

< 5th percentile Underweight

Example: 95th Percentile Tracking

Age BMI

2 yrs 19.3 4 yrs 17.8 9 yrs 21.013 yrs 25.1

For Children, BMI Changes with Age

Boys: 2 to 20 years

BMI BMI

BMI BMI

Tracking BMI-for-Age from Birth to 18 Years with Percent of Overweight Children Who Are Obese at Age 25

16 15 12 11 10 917 19

55

7567

26

52

69

8377

36

0

20

40

60

80

100

Birth 1 to 3 3 to 6 6 to 10 10 to 15 15 to 18

Age of child (years)

% o

bese

as

adul

ts

BMI < 85th BMI ≥ 85th BMI ≥ 95th

Whitaker et al. NEJM. 1997;337:869-873.

Example: Adults overweight as teens had an increased relative risk of all-cause morbidity and of coronary heart disease

Childhood Obesity: Risk for Disease

Must A, et al. NEJM 1992;327:1350-1355.

• Cardiovascular disease

• Lipid disorders

• Hypertension

• Diabetes Mellitus type 2

• Gallbladder disease

• Obstructive sleep apnea

• Orthopedic problems

• Metabolic syndrome

• Cancer (breast, uterine, prostate, and colon)

• Sudden death

• Psychosocial distress/body image disparagement

• 439 obese children versus 51 overweight or non-obese (aged around 11-12 years)

• 3 of following− BMI > 97th • Systolic BP > 95th

− Triglyceride > 95th • HDL < 5th

− Impaired glucose tolerance

• Prevalence − 38.7% of moderately obese BMI SDS > +2 < +2.5

− 49.7% of severely obese BMI > +2.5

• Prevalence increases directly with degree of obesity

Weiss R et al. NEJM:2004;350,23.

Metabolic Syndrome in Childhood

Metabolic Syndrome Associated with Insulin Resistance

Weiss et al 2004.

Weiss R et al. NEJM 2004

BMI Is Associated with Metabolic Syndrome Risk Factors in Children

and Adolescents

VariableBMI z score

Log-Transformed Triglycerides

HDL Cholesterol

Log-Transformed

Insulin Resistance Glucose Blood Pressure

Baseline At 2 Hr Systolic DiastolicBMI z score Correlation coefficient 1.0 0.04 - 0.14 0.31 0.08 0.12 0.13 - 0.01 P value 0.33 0.001 < 0.001 0.08 0.007 0.003 0.82

Pearson Correlation Coefficients of Variables in the Analysis

Weiss et al. JAMA. 2004

Increasing Prevalence of Pediatric Type 2 Diabetes Mellitus in the US

• 15 years ago Type 2 diabetes mellitus accounted for less than 3% of all new cases of diabetes in children and adolescents in the USA

• The figure now stands at 45%

• Estimated that Type 2 diabetes will exceed Type 1 in childhood within 10 years*

* Report of American Academy of Pediatrics. 2003.112.

Etiology of Obesity

• Increased caloric consumption

• Sedentary lifestyle

• Genetic predisposition

• Medications: psychotropics, steroids

Long-Term Effects of Treating the Parent + Child (8 – 11 y/o)

Months

-12 0 12 24 36 48 60 72 84 96 108 120 132

Ch

an

ge

in %

ag

e o

verw

eig

ht

-25

-20

-15

-10

-5

0

5

10

15

20

25

Parent plus childChild aloneNon-specific control

Epstein, Valoski, Wing & McCurley. Health Psychology. 1994;13:373-383.

Previous Behavioral/Diet/Exercise Approaches to Weight Management in Adolescents

• Few controlled studies on the treatment of adolescent obesity

• Comprehensive family-based behavioral programs are the most studied interventions

• Behavior therapy: self-monitoring, goal setting, positive reinforcement, stimulus control, contingency management focused upon changing eating and physical activity habits

• The inclusion of parents in treatment is less clear than for the treatment of children; parents are usually included.

• Most studies report weight losses of only 1 to 4 kg

• Participants typically remain obese at the end of studies

• New approaches are needed

Berkowitz et al. JAMA 2003; 289: 1805-1812.

-5

-4

-3

-2

-1

0

0 1 2 3 4

Months

Wei

gh

t L

oss

(kg

) Child Alone

Mother-Child Alone

Mother-Child Together

Wadden TA, Stunkard AJ, Rich L, Rubin CJ, Sweidel G, McKinney S. Pediatrics. 1990; 85(3):345-52.

Obesity Pharmacotherapy: NHLBI Adult Recommendations

• “Appropriate weight-loss drugs can augment diet, physical activity, and behavior therapy in weight loss”

• BMI 30 or 27 with co-morbidities

• Pharmacotherapy should only be given in conjunction with lifestyle modification

National Institutes of Health. Obes Res. 1998;6(suppl 2):51S–209S.

Behavioral and Pharmacological Treatment Combined

• Behavioral treatment helps the overweight person to develop skills to cope with an environment which promotes overeating and inactivity

• Pharmacological treatment may minimize the effects of biological factors relating to weight gain

• Behavioral and pharmacological treatments appear to be additive in adult studies

Wadden TA. Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg C. Arch Gen Internal Med 2001;161:218-227.

Obesity Pharmacotherapy

There have been no comparative safety and efficacy trials between orlistat and sibutramine or phentermine.Refer to Physicians’ Desk Reference for other products.

Systemically ActingSystem Mechanism Examples

CNS Noradrenergic

Stimulates norepinephrine and dopamine release

Phentermine

CNS Noradrenergic & serotonergic

Blocks norepinephrine, serotonin and dopamine reuptake

Sibutramine

Nonsystemically ActingSystem Mechanism Examples

Digestive Inhibition of lipase Orlistat

Ryan DH et al. Obes Res. 1995;3(suppl 4):553S.

S = sibutramine = norepinephrine = serotonin

Norepinephrine

Serotonin SSSS

SSSS

SSSS

SSSS

Reuptake

Reuptake

Mechanisms of ActionSibutramine’s Active Metabolites Block Serotonin and Norepinephrine Reuptake

Behavior Therapy and Sibutramine for the Treatment of Adolescent Obesity:

A Randomized Controlled TrialRobert I Berkowitz, MD, Thomas A Wadden, PhD,

Andrew M Tershakovec, MD, Joanna L Cronquist, BA

JAMA 2003; 289:1805-1812Support: NIH, Abbott Laboratories

• 6 month randomized, double-blind, placebo-controlled evaluation of efficacy and safety of sibutramine (final dose 15 mg) when added to a comprehensive family-based behavioral program

• Open label sibutramine months 7 – 12

• Objectives: Percent change in BMI, hunger and disinhibition of eating (Stunkard Messick Eating Inventory), adherence to self-monitoring, lipids, insulin, HOMA, BP, pulse, adverse events

Berkowitz et al, JAMA 2003; 289: 1805-1812.

Behavior Therapy and Sibutramine for the Treatment of Adolescent Obesity:

A Randomized Controlled Trial

• Week 1: placebo

• Week 2: sibutramine 5 mg or placebo



• If systolic or diastolic BP increased from baseline by ≥ 10 mm Hg or pulse increased by 15%, dose decreased by 5 mg decrements

Sibutramine Dosage Titration


• Phase 1− 13 weekly group sessions followed by

− 6 biweekly group sessions

• Phase 2− Biweekly group sessions months 7 – 9

− Monthly group sessions months 10 – 12

• Behavior therapy: self-monitoring, goal setting, positive reinforcement, stimulus control, slowing eating rate, parents involved

• Dietary recommendation: 1200 – 1500 kcal/day, 30% fat, 15% protein

• Physical activity target of 120 minutes per week (e.g. walking)

Family-Based Bbehavioral Therapy Program


Placebo + BT (n = 39)

Sibutramine + BT (n = 43)

Sex, No. (%) Female 24 (61.5) 31 (72.1)

Male 15 (38.5) 12 (27.9)

Race, No. (%) White 24 (61.5) 21 (48.8)

Black 13 (33.3) 21 (48.8)

Other 2 (5.2) 1 (2.3)

Age, mean (SD), yrs 14.1 (1.2) 14.1 (1.3)

Weight, mean (SD), kg 105.3 (16.2) 102.0 (14.7)

Height, mean (SD), cm 166.2 (8.4) 164.6 (7.7)

BMI, mean (SD) 38.0 (3.6) 37.5 (4.0)

Characteristics of Aadolescents at Baseline


*** P = 0 .001

-10

-9

-8

-7

-6

-5

-4

-3

-2

-1

0

0 3 6

Month of Treatment

% c

han

ge

in B

MI

***

***

Placebo + BT(n = 39)

Sibutramine + BT(n = 43)

Mean Percentage Change in Initial BMI (Intention-to-Treat Analysis)


Percentage of Adolescents Achieving 5%, 10%, and 15% Rreductions in BMI

at Mmonth 6

0

10

20

30

40

50

60

70

> 5% > 10% > 15%

63*

40*

19*

36

15

3

* P = 0.02

Placebo + BT, months 1-6

Sibutramine + BT, months 1-6

% c

han

ge

in B

MI


Self-Monitoring and Percentage Change in BMI at Month 6

-16

-14

-12

-10

-8

-6

-4

-2

0High self-monitoring Low self-monitoring

(n = 25)

(n = 18)

(n = 23)

(n = 16)

Placebo + BT Sibutramine + BT

% c

han

ge

in B

MI


-10

-9

-8-7

-6

-5

-4

-3-2

-1

0

0 3 6 9 12

Month of Treatment

% c

han

ge in

BM

I

Placebo + BT group received sibutramine during months 7 –

12

***

***

*** P = 0 .001

Placebo + BT(n = 39)

Sibutramine + BT(n = 43)

Placebo controlled All subjects received sibutramine

Mean Percentage Change in Initial BMI (Intention-to-Treat Analysis)


Change (%) in Lipids at Month 6 (n = 74) and Month 12 (n = 62)†

-12

-10

-8

-6

-4

-2

0

2

4

6

8

10

6 months

12 months

-9.0-9.3

Triglyceride

Total cholesterol

HDL cholesterol

LDL cholesterol

-2.3-3.2

7.6

2.3

-4.6

-2.5

(101.7)

(165.5) (45.4)

(99.8)

* P = 0.02 **P = 0.05***P = 0.01

****P = 0.001*

***

**

****

**

Baseline values

(mg/dL)

† Pooled data (no significant difference between placebo + BT and sibutramine + BT groups)

% c

han

ge


Change (%) in Insulin, Glucose and HOMA at Months 6 (n = 74) & 12 (n = 62)†

(Baseline values)Insulin

(27 U/mL)

% c

han

ge

-20.2

-12.8

-2.6-1.9

Serum glucose(90.3 mg/dL)

-14.8

-22.8

HOMA(6.1)

0

-5

-10

-15

-20

-25

***

*** **

*† Pooled data (no significant difference between placebo + BT and sibutramine + BT groups)

6 months

12 months

* P = 0.02** P = 0.01

***P < 0.001


Blood Pressure (Mean mm Hg)

Mean

BP (

mm

Hg

)

P = 0.02

Systolic

Diastolic

P = 0.06

0

20

40

60

80

100

120

140

Baseline Month 3 Month 6 Month 12

BT + placebo BT + sibutramine

Sibutramine added to placebo group


Pulse Rate (mean beats/min)Pu

lse r

ate

(b

eats

/min

)

P < 0.001

P < 0.001P =

0.007

50

55

60

65

70

75

80

85

90

Baseline Month 3 Month 6 Month 12


BT + placebo BT + sibutramine

Sibutramine added to placebo group

Reason #

Increases in blood pressure and/or pulse( BP alone = 1; BP & pulse = 4; Pulse alone = 1)

6

Ecchymoses 2

Ventricular premature beats 1

Rash of unclear etiology 1

Total number of subjects 10

Reasons for Discontinuation (Entire Study)


Mechanism of Action: Orlistat1,2

1. Zhi et al. J Clin Pharmacol. 1995;35:1103-1108. 2. Zhi et al. Clin Pharmacol Ther. 1994;56:82-85.

• Inhibition of lipases by orlistat blocks systemic absorption of dietary fat2

• Unabsorbed fat is excreted into feces (up to one-third of ingested fat)2

Three-Month Tolerability of Orlistat in Adolescents with Obesity-Related

Comorbid ConditionsMcDuffie JR, Calis KA, Uwaifo GI, Sebring NG,

Fallon EM, Hubbard, Yanovski JA.

Obesity Research. 2002;10:642-650

Objective

• Study safety, tolerability, and potential efficacy of orlistat in adolescents with obesity and its comorbid conditions

Mc Duffie JR, et al. Obesity Research. 2002;10:642-650.

Research Methods and Procedures

• 20 adolescents

– Age: 14.6 ± 2.0 yrs

– BMI: 44.1 ± 12.6 kg/m2

• Subjects took orlistat (120 mg 3 times daily) and a multivitamin for 3 months

• Subjects were simultaneously enrolled in a 12-week lifestyle modification program, with emphasis on:

– Diet

– Exercise

– Behavior modification


Results

• 85% completed treatment

– Took 80% of prescribed medication

• Adverse effects generally mild

– Limited to GI effects observed in adults


Results (cont.)

Variable Baseline 3 months Net change Significance

Weight 123.4 ± 43.0 119.0 ± 43.1 -4.4 ± 4.6 kg p < 0.001

Body Mass Index (BMI) kg/m2 44.1 ± 12.4 42.2 ± 13.0 -1.9 ± 2.5 kg/m2 p < 0.0002

Total Cholesterol (mg/dL)

177.8 ± 41.2 156.6 ± 34.2 -21.3 ± 24.7 mg/dL p < 0.001

LDL cholesterol (mg/dL)

120.2 ± 30.1 102.9 ± 29.5 -17.3 ± 15.8 mg/dL p < 0.0001


Results (cont.)

Variable Baseline 3 months

Net Change SignificanceFasting 2 hours Fasting 2 hours

Glucose (mg/dL)

101.7±38.3 123.1±64.2 86.3±6.4 106.4±21.5 -15.4±7.4 p < 0.003

Insulin (µU/ml)

34.0±16.3 117.0±71.7 20.3±10.6 94.3±85.4 13.7±19.0 p < 0.02


Summary• Comorbid conditions associated with obesity in this patient sample

included: – Hyperinsulinemia: 100%

– Hyperlipidemia: 20%

– Hypertension: 10%

– Type 2 diabetes: 5%

– Impaired glucose tolerance: 5%

• In adolescents, short-term treatment with orlistat in the context of a behavioral program is well-tolerated and has a side effect profile similar to that observed in adults

• True benefit versus conventional therapy remains to be determined in placebo-controlled trials


Conclusions

• Overweight is defined by BMI ≥ 95th percentile for age and gender

• Increased co-morbidities, including metabolic syndrome and type 2 diabetes mellitus with increasing BMI

• Increasing prevalence of overweight among youth

• Overweight tracks from childhood to adulthood

• Additive effects of behavior + sibutramine in adolescents for weight loss by month 6 in teens

• Continuation of sibutramine resulted in maintenance of weight loss by month 12

• Blood pressure and pulse effects (n = 19), similar to those in adults, resolved through dose reduction (n = 15) in BT + sibutramine group

• Significant improvements in lipids, insulin and HOMA

• Orlistat: Promising initial uncontrolled study of weight loss with orlistat

• Orlistat: improvements in lipids, insulin

Conclusions

adolescent obesity. objectives definition of overweight in youth prevalence and trends health...

Documents

years bmi slide

tracking bmi

bmi changes

following bmi

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youth slide

th percentileunderweight

obese bmi sds