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Oxysterol as a Marker of Atherogenic Dyslipidemia in Adolescence

School of Dietetics and Human Nutrition (D.A., G.E., S.K.), McGill University, Québec, Canada H9X 3V9; Laboratory of Natural Medicinal Compounds (J.V.), Migal-Galilee Technology Center, Kiryat Shmona 11016, Israel; and Department of Medicine (S.M.), Division of Endocrinology and Metabolism, McGill University Health Center, Royal Victoria Hospital, Montréal, Québec, Canada H3H 2R9

Address all correspondence and requests for reprints to: Dr. Stan Kubow, School of Dietetics and Human Nutrition, McGill University, 21,111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec H9X 3V9, Canada. E-mail: stan.kubow{at}mcgill.ca.

Context: Oxysterols represent potentially important oxidative stress biomarkers in adolescence.

Objective: The objective of the study was to examine the relationship between the concentrations of serum enzymatically and nonenzymatically generated oxysterols, measures of obesity, and metabolic components including insulin resistance and levels of blood pressure and serum lipids.

Design: This was a cross-sectional study.

Setting: All subjects were examined between 2003 and 2005 at a hospital, a part of a follow-up evaluation mother-daughter pairs representing pregnancies affected or unaffected by gestational diabetes that resulted in the deliveries in 1989–1991.

Subjects: Subjects included a subset (n = 89) of the total study population of 189 adolescent girls with a mean age of 15.32 ± 0.65 yr and body mass index of 22.54 ± 3.98 kg/m².

Main Outcome Measures: Measures included serum levels of the oxysterols 7-hydroxy-cholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol; and body mass index, homeostasis model assessment insulin resistance index, fasting insulin, fasting glucose, blood pressure, total cholesterol, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B (ApoB).

Results: Serum oxysterol concentrations in the adolescent cohort correlated positively with insulin (P < 0.05), total cholesterol (P < 0.05), non-high-density lipoprotein cholesterol (P < 0.05), low-density lipoprotein cholesterol (P < 0.05), and ApoB (P < 0.01). ApoB and fasting insulin were found to be the major determinants of serum oxysterols after adjustment for body mass index. Being a daughter of gestational diabetes pregnancy alone did not seem to be a predisposing factor to increased oxidative stress in our cohort.

Conclusion: Serum oxysterol concentrations increase with obesity, insulin, and ApoB, which are established derangements associated with the metabolic syndrome.

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