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Case #1
• 15 yo white male• Referred for evaluation and treatment of obesity
and hyperlipidemia detected on routine screening• Otherwise healthy• Past medical history is unremarkable• No current medications
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1991Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1991BRFSS, 1991
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1992Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1992BRFSS, 1992
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1993Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1993BRFSS, 1993
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1994Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1994BRFSS, 1994
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1995Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1995BRFSS, 1995
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1996Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1996BRFSS, 1996
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Prevalence of Obesity* Among U.S. AdultsBRFSS, 1997Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1997BRFSS, 1997
(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)
<10% 10% to 15% >15% N/A
Trend in Overweight Prevalence for Youths 6-17 yrs
0
5
10
15
NHES II/III, 1963-70
NHANES I,1971-74
NHANES II,1976-1980
NHANES III,1988-94
Troiano et. al (Pediatrics 1998)
Case #1• Activity
– Watching TV, playing video games
• Diet– Frequent high-fat fast foods, high-sugar snacks
– Skips breakfast
• Analysis of 3-day food diary
– Average 3360 kcal/day
– Diet composition (% of total calories)• Protein 18%
• Fat 36%
• Carbohydrate 46%
Effect of Television Watching on US Children: 8-16 years old
20
25
30
< 2 2 to 3 4 and up
Hours of TV per Day
Su
m o
f T
run
k S
kin
fold
s, m
m
boys girls
Andersen et. al. (JAMA 1998)
Case #153 yo
diabetesMI
62 yo hypertension
stroke
72 yohypertension
69 yo healthy
39 yoobese
hypertensionCH 236TG 499HDL 28
38 yoobese
CH 204TG 204HDL 42
48 yostroke
9 yohealthyCH ?
12 yoobese
CH 210TG 201HDL 38
15 yoobese
HypertensionType IIdiabetesCH 226TG 320HDL 30
Case #1
• Social– Freshman in high school. Described as “average”
student.– Smokes 2-3 cigarettes/day– Denies alcohol/substance abuse– Mother accompanies patient to clinic. Parents are
separated. Lives with mother, who works two jobs.– Has few friends
Case #1
• Physical exam– BP 142/90 right arm sitting (normal 135/85)– Ht 178 cm (90th percentile)– Wt 96 kg (> 95th percentile)– BMI (wt/ht2) 30.3 (> 95th percentile)– Hyperpigmented, rough plaques on neck, groin, inner
thigh (acanthosis nigricans)– Mild hepatomegaly
Acanthosis Nigricans
• Occurs in skin fold areas, especially neck and arm pits
• Associated with hyperinsulinemia
Case #1
• Fasting serum lipid profile– Total cholesterol 220 mg/dl, repeat 226 mg/dl (normal
< 200 mg/dL)– Triglycerides 320 mg/dL (normal < 200 mg/dL)– HDL cholesterol 30 mg/dL (normal > 35 mg/dL)– LDL cholesterol 131 mg/dl (normal < 130 mg/dL)
Case #1• Other lab
– Normal thyroid profile– 8 AM serum cortisol 19 µg/dL (normal 5-23 µg/dL) – Fasting glucose 190 mg/dL (diabetic >115 mg/dL)– Glucose tolerance test
• 60 min 223 mg/dL (diabetic > 200 mg/dL)• 90 min 233 mg/dL (diabetic > 200 mg/dL)• 120 min 188 mg/dL (diabetic > 140 mg/dL)
– Fasting insulin 48 mU/L (normal 7-24 mU/L)– Serum/urine ketones negative– Serum transaminases
• ALT 119 U/L (normal 5-45 U/L)• AST 98 U/L (normal 5-45 U/L)
Risk Factors for Premature Atherosclerotic Heart Disease
• Dyslipidemia (high LDL, low HDL)
• Diabetes
• Hypertension
• Obesity
• Sedentary lifestyle
• Smoking
• Male sex
Coronary Heart Disease
010
2030
4050
60E
sti
ma
ted
10
Ye
ar
Ra
te (
%)
men
women
BP SystolicCholesterolHDL-CDiabetesCigarettesLHV by ECG
12022050---
16022050---
16026050---
16026035---
16026035+--
16026035++-
16026035+++
Wilson, AmJHypertens, 1994)
Effect of Multiple Risk Factors on Atherosclerosis in the Aorta and Coronary Arteries in Children and
Young Adults
0
2
4
6
8In
tim
al-
Su
rfa
ce
In
vo
lve
me
nt
(%)
Aorta Coronary Arteries
Number of Risk Factors
0 01 12
23
3
Berenson et. al (NEJM 1998)
Obesity and Inflammation
• N-HANES III• 3512 kids (age 8-16)• Kids with elevated CRP (>.22mg/dL) or WBC > 10,000• Overweight (>85%) vs < 85%• Odds Ratio (OR) of 3.7 (M) and 3.1 for correlation of
CRP with overweight• Also elevated risk for WBC
M Visser et al Pediatrics e13, January 2001
68.7 - 62.5 % (8)62.3 - 52.7 % (8)51.2 - 41.9 % (8)38.9 - 0.8 % (8)
% of High School Students Not Enrolled in Physical Education Class, 1997
8Data missing
From 1997 Youth Risk Behavior Survey
Syndrome X
• Metabolic syndrome associated with greatly increased risk for premature cardiovascular disease
• Syndrome– Obesity– Hypertension– Insulin resistance– Dyslipidemia
• Increased triglycerides• Low HDL cholesterol
Insulin Resistance• Associated with Type II diabetes
• Closely linked with obesity (direction?)
• Decreased insulin-stimulated glucose transport and metabolism in adipocytes and skeletal muscle
• Impaired suppression of hepatic glucose output
• Tissue specific signaling abnormalities
• “Dose” of body fat affects resistance, especially central fat
Complications of Obesity• Cardiovascular-hypertension, heart disease• Insulin resistance/Type II diabetes mellitus• Hyperlipidemia• Growth-advanced bone age, increased height, early menarche • Psychosocial• Hepatobiliary-non-alcoholic steatohepatitis, cholelithiasis• Pulmonary-sleep apnea, Pickwickian syndrome• Orthopedic-slipped capital femoral epiphysis, Blount disease• Cancer-endometrial, breast, prostate, colon• CNS-pseudotumor cerebri
Obesity and Diabetes Risk
0
20
40
60
80
100
<20 20-25 25-30 30-35 35-40 >40
Body Mass Index
Knowler WC, et al. Am J Epidemiol. 1981;113:144-156.
Complications of Diabetes
• Retinopathy
• Nephropathy
• Neuropathy
• Atherosclerosis
Non-Alcoholic Steatohepatitis(NASH)
• Associated with obesity and insulin resistance• Presents with hepatomegaly and mild serum
transaminase elevation• Lipid accumulation within hepatocytes with
inflammation and fibrosis/cirrhosis• Pathogenesis: “two hit” hypothesis
– 1st hit: triglyceride accumulation– 2nd hit: generation of reactive oxygen species and
lipid peroxidation
Goals for Therapy for Type II Diabetes
• Focus on glucose and lipid goals– Modify fat intake
– Improve food choices
– Space meals throughout the day
• If obese, reduce calories for moderate weight loss• Increase physical activity• Monitor blood glucose, glycohemoglobin, lipids, blood
pressure• Add diabetes medication, if needed
American Diabetes Assoc.
Beneficial Effects of Exercise in Type II Diabetes
exercise
increased glucoseutilization
increased insulinsensitivity
decreased counter-regulatory hormones
decreased hepaticgluconeogenesis
improved bloodglucose control