Evaluation of a Homogeneous Direct LDL-Cholesterol Assay in Diabetic Patients: Effect of Glycemic Control

Abstract

Increased serum LDL-cholesterol (LDL-C) is associated with increased risk for ischemic heart disease, and lowering of LDL-C has been shown to decrease mortality in patients with known coronary heart disease (1)(2)(3). Persons with diabetes have a greatly increased risk for atherosclerosis and its complications. Many of these patients have increased plasma cholesterol (including LDL-C) and triglycerides (TGs). Additionally, glycation and oxidation of circulating LDL particles may further increase the risk for atherosclerotic disease in patients with diabetes (4)(5). Currently used methods for LDL-C include calculations [based on total cholesterol (TC), HDL-cholesterol (HDL-C), and TG concentrations], ultracentrifugation, and most recently, direct LDL-C assays. Calculation methods, such at the Friedewald formula (6), are well known to have a prominent negative bias in patients with TG concentrations >4.5 mmol/L (400 mg/dL) (6)(7). In addition, because TGs are measured, fasting blood samples are preferred. This can present a problem for certain patient populations, including many people with diabetes. Ultracentrifugation methods are time-consuming and expensive and generally are performed only in reference laboratories. Direct LDL-C assays have been developed recently and have been shown to provide accurate and precise measurements of LDL-C (8)(9)(10)(11)(12). They overcome the TG and fasting limitations of calculation methods, are readily adapted to clinical laboratories, are less expensive than ultracentrifugation methods, and provide greatly improved turnaround time. Direct LDL-C assays make use of either an immunoseparation step or specific detergents to separate LDL particles from other lipoproteins, followed by measurement of cholesterol by conventional enzymatic reactions. The N-geneousTM LDL-C assay is a solute-based homogeneous assay that agrees well with ultracentrifugation (11). The purpose of the present study was to evaluate the effect of glycemic control (as gauged by hemoglobin A1c) on the …