Association of HDL subfraction profile with the progression of insulin resistance

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.