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Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols^1,2,3

¹ From the Department of Medicine, Division of Nephrology, San Francisco General Hospital; the University of California San Francisco; and the Department of Medicine, Division of Endocrinology and Metabolism, Stanford University School of Medicine, Stanford, CA.

Background: It is not known whether total circulating lipid hydroperoxides are increased in insulin-resistant individuals and whether this correlates with depletion of liposoluble antioxidant vitamins that are consumed during lipid peroxidation.

Objective: The goal of this study was to define the relation between resistance to insulin-mediated glucose disposal and plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins in healthy volunteers.

Design: Insulin-mediated glucose disposal was determined in 36 healthy, nondiabetic volunteers by measuring their steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min constant infusion of octreotide, insulin, and glucose. In addition, fasting plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins were determined by using the FOX 2 assay and liquid chromatography.

Results: Statistically significant direct relations were observed between SSPG and mean arterial blood pressure (r = 0.44, P = 0.008) and plasma lipid hydroperoxide concentrations (r = 0.42, P = 0.01), whereas significant inverse correlations were found between SSPG and -carotene (r = -0.58, P = 0.0002), ß-carotene (r = -0.49, P = 0.004), lutein (r = -0.35, P = 0.04), -tocopherol (r = -0.36, P = 0.04), and -tocopherol (r = -0.45, P = 0.007).

Conclusions: Variations in insulin-mediated glucose disposal in healthy individuals are significantly related to plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins. These findings suggest that total plasma lipid peroxidation is increased in insulin-resistant individuals at an early, preclinical stage, ie, well before the development of glucose intolerance and type 2 diabetes.

Key Words: Insulin resistance • carotenoids • tocopherols • lipid hydroperoxides • oxidative stress • lipid peroxidation • glucose disposal

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