Multiple lipoprotein abnormalities associated with insulin resistance in healthy volunteers are identified by the vertical auto profile-II methodology.

Abstract

The lipoprotein abnormalities first associated with insulin resistance (IR) and compensatory hyperinsulinemia were high plasma triglyceride (TG) and low HDL-cholesterol (HDL-C) concentrations (1)(2). It is now known that the characteristic IR-associated dyslipidemia also includes a shift to smaller, denser LDL particles (pattern B), enhanced postprandial lipemia, and decreased concentration of the more buoyant HDL particle, HDL2 (3)(4)(5). Recently, the IR-associated lipoprotein abnormalities that increase risk of coronary heart disease (CHD) have continued to expand. In addition to high plasma TG and low HDL-C concentrations (6)(7), at least three classes of TG-rich lipoproteins are both atherogenic and associated with increased CHD risk, including intermediate density lipoprotein (IDL; a TG-rich remnant product derived from VLDL metabolism) (8)(9), VLDL3 (the dense VLDL subclass) (10)(11), and TG-rich chylomicron remnants (8)(12)(13). Despite awareness of the myriad IR-associated proatherogenic lipoprotein abnormalities (1)(2)(3)(4)(5)(14)(15)(16)(17), we are unaware of previous publications in which both IR and all relevant lipoproteins were quantified in the same cohort of individuals. This is likely partly attributable to the unavailability of analytical methods to measure multiple lipoprotein CHD risk factors in a clinically useful manner. However, the validated vertical auto profile-II (VAP-II) methodology (18) provides a means to comprehensively identify the IR-associated dyslipidemic profile, and we have used VAP-II to compare lipoprotein characteristics of nondiabetic individuals stratified into IR and insulin-sensitive (IS) groups. The Stanford University Human Subjects Committee approved this study, and healthy volunteers from the San Francisco Bay Area gave informed consent. Participants underwent medical interview, anthropometric measurements, and a physical examination. Exclusion criteria included fasting plasma glucose >7.0 mmol/L (126 mg/dL), total bilirubin >34 μmol/L (2.0 …