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Fasting Remnant Lipoprotein Cholesterol and Triglyceride Concentrations Are Elevated in Nondiabetic, Insulin-Resistant, Female Volunteers¹

Stanford University School of Medicine, Stanford, California 94305; Tokyo Medical Dental University, Tokyo 113-8519, Japan; and Otsuka America Pharmaceutical, Inc., Rockville, Maryland 20850

Address all correspondence and requests for reprints to: G. M. Reaven, M.D., 213 East Grand Avenue, South San Francisco, California 94080. E-mail: greaven{at}shaman.com

This study was initiated to test the hypothesis that plasma concentrations of remnant lipoproteins would be higher after an overnight fast in insulin-resistant compared to insulin-sensitive volunteers. Forty-three healthy nonobese women were studied, divided into insulin-resistant (n = 21) and insulin-sensitive (n = 22) groups on the basis of their steady state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide acetate, insulin, and glucose. Under these conditions, steady state plasma insulin concentrations are similar in all subjects (60 µU/mL), and the higher the SSPG concentrations, the more insulin resistant the individual. By selection, mean (±SEM) SSPG concentrations were significantly higher (P < 0.001) in the insulin-resistant group (210 ± 7 vs. 78 ± 3 mg/dL). In addition, the insulin-resistant group had higher triglycerides (198 ± 27 vs. 101 ± 12 mg/dL; P < 0.005) and lower high density lipoprotein cholesterol (48 ± 4 vs. 60 ± 4 mg/dL; P < 0.05) concentrations. Finally, insulin resistance was associated with higher remnant lipoprotein particle concentrations of cholesterol (7.2 ± 0.8 vs. 4.4 ± 0.3; P < 0.005) and triglycerides (22.2 ± 3.4 vs. 8.5 ± 1.0; P < 0.001). All of these differences were seen despite the fact that the two groups were similar in terms of age and body mass index. These results identify additional abnormalities in lipoprotein metabolism that may contribute to the increased risk of coronary heart disease seen in insulin-resistant, nondiabetic subjects (syndrome X).

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