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RISK FACTORS FOR ATHEROSCLEROSIS IN OBESE CHILDREN
DyslipidemiaHigh triglycerides, VLDLLow HDLHigh small, dense LDL
Glucose intolerance, diabetes
Hypertension
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Pathobiological Determinants of Atherosclerosis in Youth Study (PDAY)
Strong, et al. JAMA 281:727-735, 1999
• 3000 autopsies after trauma, age 15-34y, 9 centers• 15-19y: fatty streaks in all aortas, half of coronaries • More fatty streaks and advanced plaque with
» high LDL, VLDL» low HDL» high blood pressure» smoking» obesity» glucose intolerance
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McGill et al Am J Clin Nutr 72:1307S-15S, 2000
PDAY: Low Risk vs. High Risk Lipid Profiles
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Title: Differences in Vascular Compliance in Pediatric Patients at Risk for Cardiovascular Disease as Measured by Endo-PAT Technology
PI: Rubin Cooper, M.D., Dept. of Cardiology
Subjects: age 8-18, 20 per group:1) healthy controls2) overweight (BMI>95%)3) high cholesterol and/or triglycerides4) fatty liver
Study Design: at baseline, 6 and 12 months:1) endo-PAT test2) carotid artery wall thickness by ultrasound3) fasting blood sample
Pediatric Obesity Council Protocol
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Does sugar make us Does sugar make us fatfat, , dyslipidemicdyslipidemic and and diabeticdiabetic??
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Duffey, K. J et al. Am J Clin Nutr 2008;88:1722S-1732S
Major Sources of Calories as High-fructose Corn syrup (HFCS) and Sucrose
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Nutritional Studies of:
1) Chronic effects of the equicaloric substitution of carbohydrate for fat
1) Acute effects of oral challenges with fructose
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Dietary Fructose:- Does not acutely raise glucose or insulin- Raises plasma triglycerides more than glucose- Rapidly increases palmitate synthesis?
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AU
C T
G %
16:0
AU
C T
G %
16:0
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Hypothesis: In overweight subjects, the synthesis of palmitate from dietary fructose will be
1) greater when consumed with glucose2) show a dose-response.
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Study Design:Outpatient, random order, cross-over, single blinded study in 15 overweight subjects
1)Screening visit with 3h OGTT (75 g glucose, mean 0.9g/kg)
2)Sugar in 12 oz water, 15 min:• Fructose, 0.5g/kg• Fructose:Glucose 1g/kg• Fructose:Glucose 2g/kg
3)Blood sampling at 0, 1, 2, 3, 4h
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Lessons Learned:
• The equicaloric substitution of fat with sugar does not increase body fat.
• The equicaloric substitution of fat with sugar, fructose more than glucose, causes dyslipidemia by increasing the production of fat from sugar in the liver.
• The large within-subject variability in response may be partially explained by differences in insulin sensitivity.
• Dyslipidemia associated with obesity is readily corrected by modifications in diet and physical activity.
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Some unanswered questions:
1)Does the lipogenic response to sugar predict susceptibility to diabetes, fatty liver and atherosclerosis?
2)Are there age- and family-specific differences in sugar-induced lipogenesis?
3)What are optimal levels of HFCS/sucrose in the diet?
4)What are the best ways to evaluate extent and progression of insulin resistance and atherosclerosis?
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% De Novo Lipogenesis Pre- and Post-FructoseControls (n=15)
Hours Post-Fructose
-5 0 5 10 15 20 25 30
% D
NL
0
10
20
30
40
50
%%
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