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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 . Trend in Overweight Prevalence for Youths 6-17 yrs. Troiano et. al (Pediatrics 1998).

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case 1
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
case 110
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%
case 112

62 yo hypertension stroke

53 yo

diabetes

MI

72 yo

hypertension

69 yo healthy

38 yo

obese

CH 204

TG 204

HDL 42

48 yo

stroke

39 yo

obese

hypertension

CH 236

TG 499

HDL 28

9 yo

healthy

CH ?

12 yo

obese

CH 210

TG 201

HDL 38

15 yo

obese

Hypertension

Type II

diabetes

CH 226

TG 320

HDL 30

Case #1
case 113
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 114
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
Acanthosis Nigricans
  • Occurs in skin fold areas, especially neck and arm pits
  • Associated with hyperinsulinemia
case 116
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 117
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
Risk Factors for Premature Atherosclerotic Heart Disease
  • Dyslipidemia (high LDL, low HDL)
  • Diabetes
  • Hypertension
  • Obesity
  • Sedentary lifestyle
  • Smoking
  • Male sex
coronary heart disease

BP Systolic

Cholesterol

HDL-C

Diabetes

Cigarettes

LHV by ECG

120

220

50

-

-

-

160

220

50

-

-

-

160

260

50

-

-

-

160

260

35

-

-

-

160

260

35

+

-

-

160

260

35

+

+

-

160

260

35

+

+

+

Coronary Heart Disease

Wilson, AmJHypertens, 1994)

slide20
Effect of Multiple Risk Factors on Atherosclerosis in the Aorta and Coronary Arteries in Children and Young Adults

3

2

3

2

1

1

0

0

Aorta

Coronary Arteries

Number of Risk Factors

Berenson et. al (NEJM 1998)

obesity and inflammation
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

slide22

% of High School Students Not Enrolled in Physical Education Class, 1997

Data

missing

8

From 1997 Youth Risk Behavior Survey

syndrome x
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
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
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
Obesity and Diabetes Risk

Knowler WC, et al. Am J Epidemiol. 1981;113:144-156.

complications of diabetes
Complications of Diabetes
  • Retinopathy
  • Nephropathy
  • Neuropathy
  • Atherosclerosis
non alcoholic steatohepatitis nash
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
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
Beneficial Effects of Exercise in Type II Diabetes

exercise

increased insulin

sensitivity

decreased counter-

regulatory hormones

increased glucose

utilization

decreased hepatic

gluconeogenesis

improved blood

glucose control

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