risk factors for atherosclerosis in obese children
DESCRIPTION
RISK FACTORS FOR ATHEROSCLEROSIS IN OBESE CHILDREN. Dyslipidemia High triglycerides, VLDL Low HDL High small, dense LDL Glucose intolerance, diabetes Hypertension. Pathobiological Determinants of Atherosclerosis in Youth Study (PDAY). - PowerPoint PPT PresentationTRANSCRIPT
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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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