Lipoprotein insulin resistance index: a lipoprotein particle-derived measure of insulin resistance.

Abstract

Abstract Background: Lipoprotein particle sizes and concentrations are characteristically altered in patients with insulin resistance (IR) or type 2 diabetes mellitus (T2DM). This study assessed the ability of an IR score, based on nuclear magnetic resonance (NMR)-derived lipoprotein information, to detect IR in otherwise healthy individuals. Lipoprotein subclass and size information were evaluated for strength of association with IR, as measured by homeostasis model assessment of insulin resistance (HOMA-IR) in the Multi-Ethnic Study of Atherosclerosis (MESA). To increase the likelihood of identifying subjects with IR, six lipoprotein measures were combined into a single algorithm. The resulting assay [Lipoprotein Insulin Resistance Index (LP-IR)] was developed using HOMA-IR in 4972 nondiabetic subjects from MESA and verified independently using glucose disposal rates (GDRs) measured during hyperinsulinemic-euglycemic clamps in 56 insulin-sensitive, 46 insulin-resistant, and 46 untreated subjects with T2DM. LP-IR exhibited stronger associations with HOMA-IR (r=0.51) and GDR (r=-0.53) than each of the individual lipoprotein parameters as well as the triglycerides/high-density lipoprotein cholesterol (TGs/HDL-C) ratio (r=0.41 and -0.44, respectively). In MESA, associations between the LP-IR score and HOMA-IR were strong in men (r=0.51), women (r=0.52), European Americans (r=0.58), African Americans (r=0.48), Chinese Americans (r=0.49), and Hispanic Americans (r=0.45). When LP-IR was categorized by HOMA-IR and either body mass index (BMI) or fasting plasma glucose (FPG), subgroups were revealed whose LP-IR scores were high (≥ 50), despite having normal BMIs (<24 kg/m(2)) or FPG (<100 mg/dL). LP-IR scores had strong associations with multiple measures, HOMA-IR, and GDR, the former being more reflective of hepatic and the latter of peripheral insulin sensitivity, and may represent a simple means to identify individuals with IR.