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(Circulation. 2005;111:3465-3472.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Nuclear Magnetic Resonance Lipoprotein Abnormalities in Prediabetic Subjects in the Insulin Resistance Atherosclerosis Study

Andreas Festa, MD; Ken Williams, MS; Anthony J.G. Hanley, PhD; James D. Otvos, PhD; David C. Goff, MD, PhD; Lynne E. Wagenknecht, DrPH; Steven M. Haffner, MD

From the Department of Medicine, University of Texas Health Science Center, San Antonio (A.F., K.W., S.M.H.); Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (A.J.G.H.); LipoScience, Inc, Raleigh, NC (J.D.O.); Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (D.C.G., L.E.W.); and Eli Lilly & Company, Area Medical Center, Vienna, Austria (A.F.).

Correspondence to Steven M. Haffner, MD, Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Dr, MC 7873, San Antonio, TX 78229-3900. E-mail haffner{at}uthscsa.edu

Received October 5, 2004; revision received February 22, 2005; accepted March 16, 2005.

Background— Subjects with type 2 diabetes have smaller LDL and HDL particles in addition to higher levels of triglycerides and lower HDL cholesterol. Elevated insulin resistance, blood pressure, and dyslipidemia (including small dense LDL) predicted incident diabetes. In the Insulin Resistance Atherosclerosis Study (IRAS) we studied nuclear magnetic resonance (NMR) lipoprotein particle measures in prediabetic individuals, considering potentially modifying covariates, including insulin resistance, as directly measured using a frequently sampled intravenous glucose tolerance test.

Methods and Results— Of 830 subjects who were nondiabetic at baseline, 130 (15.7%) developed diabetes after a mean follow-up of 5.2 years. Various lipoprotein abnormalities were found in prediabetic subjects compared with subjects who stayed nondiabetic at follow-up. In logistic regression analyses (demographically adjusted), VLDL particles, large VLDL, LDL particles, small LDL, large HDL, small HDL, VLDL size, LDL size, and HDL size were related to incident diabetes. The relation of VLDL size and small HDL to incident diabetes was independent of waist (odds ratio [OR] [95% CI], 1.43 [1.18 to 1.73] and 1.23 [1.01 to 1.51] for VLDL size and small HDL, respectively) and independent of conventionally (chemically) measured triglycerides and HDL cholesterol (OR [95% CI], 1.45 [1.18 to 1.78] and 1.30 [1.06 to 1.60], respectively). Insulin sensitivity attenuated the relation to incident diabetes of VLDL size (OR [95% CI], 1.25 [1.01 to 1.53]) but not of small HDL particles (OR [95% CI], 1.25 [1.02 to 1.54]).

Conclusions— We have shown a range of lipoprotein abnormalities in prediabetic individuals, including compositional changes in HDL and VLDL. These findings extend previous work indicating a proatherogenic state in healthy, nondiabetic subjects who subsequently develop diabetes.

Key Words: diabetes mellitus • epidemiology • lipids • lipoproteins

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