Association of HDL subfraction profile with the progression of insulin resistance

Abstract

Abstract Background Type 2 diabetes mellitus (T2D) is a major global public health problem, as it is associated with increased morbidity, mortality, and healthcare costs. Insulin resistance (IR) is considered to be a condition characterized by disturbances in carbohydrate and lipid metabolisms that precede T2D. The correlation between IR and high-density lipoprotein cholesterol (HDL-C) levels is known, but the underlying mechanisms are not fully understood. The present study aimed to investigate the association between HDL subfraction profile and the development of IR. Methods The progression of IR was assessed using the Homeostatic Model Assessment for IR index (HOMA-IR), and IR was defined as those with a HOMA-IR greater than 3.63. The HDL-C was separated using the Lipoprint system, which identifies ten subfractions (HDL-1-10) and three classes: large- (HDL-L), intermediate- (HDL-I), and small-HDL (HDL-S). All analyses were performed on samples of 240 control subjects and 137 individuals with IR from the Hungarian general and Roma populations. Results The HDL-1 to -6 and the HDL-L and -I showed a significant negative association with elevated HOMA-IR and the presence of IR. Among them, HDL-2 (β = 42.2, p = 4.1 × 10-12) and HDL-L (β = 15.5, p = 2.2 × 10-10) showed the strongest correlation with the IR progression. The optimal cut-off value was found to be 0.264 mmol/L for HDL-L and 0.102 mmol/L and above for HDL-2. The risk of IR is 5.1 times higher for HDL-L levels below the cut-off (p = 2.2 × 10-7), and 4.2 times higher for HDL-2 (p = 3.0 × 10-6). Furthermore, the risk of early manifestation of IR are significantly higher in individuals with both HDL-L (HR = 3.5, p = 3.2 × 10-7) and HDL-2 (HR = 3.19, p = 2.0 × 10-6) levels below the cut-off. Key messages • HDL-2 and -L levels are strongly associated with the development of insulin resistance. • Elevated risk of early onset of insulin resistance is associated with HDL subfraction profile.