Lipoprotein Subclasses and Cardiovascular Disease Risk in Insulin-Resistant Diabetes

Abstract

Insulin resistance, diabetes mellitus, and the metabolic syndrome are frequently associated with high plasma concentrations of triglyceride-rich lipoproteins (very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL)); an excess of small, dense low-density lipoprotein (LDL) particles; reductions in larger, more buoyant LDL subclasses; and lower levels of high-density lipoprotein (HDL) particles. This multifaceted pro-atherogenic dyslipidemia appears to be caused in part by the excess of triglyceride (TG)-rich lipoproteins in the plasma, and it predicts a higher risk of cardiovascular disease (CVD)-related events. The standard lipid panel (consisting of TG, total cholesterol, LDL-C, and HDL-C) is performed using automated chemistry analyzers, with LDL-C being calculated by the Friedewald equation. However, the standard lipid panel fails to identify many lipoprotein abnormalities that contribute to elevated CVD event risk. Advanced lipid profiles, employing gel electrophoresis (GGE), nuclear magnetic resonance (NMR), and density gradient ultracentrifugation (DGU), measure lipoprotein parameters beyond the standard lipid panel. These parameters, including lipoprotein subclass levels, provide more comprehensive assessment of dyslipidemias, which may help customize treatment strategies based on the patient’s particular dyslipidemic profile. Measurement of advanced lipid panels in many recent clinical trials and observational studies has explored the strengths and weaknesses of each methodology. These data provide evidence that more detailed lipoprotein information in general, and lipoprotein subclass profiles in particular, may help predict CVD risk. The so-called atherogenic dyslipidemia, often seen in patients with diabetes and prediabetes, is identified in the standard lipid panel by high levels of TG and non-high-density lipoprotein cholesterol (non-HDL-C) and low HDL-cholesterol (HDL-C). More comprehensive lipid testing helps further characterize atherogenic dyslipidemia. Specifically, identification of increased levels of small, dense LDL particles and of remnant lipoproteins may be helpful in characterizing this dyslipidemia since these particles appear to be especially atherogenic.