HDL abnormalities in type 2 diabetes: Clinical implications.

Atherosclerotic cardiovascular disease (ASCVD) represents the primary cause of mortality among patients with Type 2 Diabetes Mellitus (T2DM). In this population, High-Density Lipoprotein (HDL) particles exhibit abnormalities in number, composition, and function, culminating in diminished anti-atherosclerotic capabilities despite normal HDL cholesterol (HDL-C) concentrations. Hyperglycemic conditions contribute to these alterations in HDL kinetics, composition, and function, causing T2DM patients' HDL particles to exhibit decreased concentrations of diverse lipid species and proteins. Treatment of hyperglycemia has the potential to correct abnormal HDL particle attributes in T2DM; however, pharmacological interventions, including metformin and thiazolidinediones, yield inconsistent outcomes with respect to HDL-C concentrations and functionality. Despite numerous attempts with diverse drugs, pharmacologically augmenting HDL-C levels has not resulted in clinical benefits in mitigating ASCVD risk. In contrast, reducing Low Density Lipoprotein cholesterol (LDL-C) via statins and ezetimibe has demonstrated significant efficacy in curtailing CVD risk among T2DM individuals. Promising results have been observed in animal models and early-phase trials utilizing recombinant HDL and Lecitin Cholesterol Acyl Transferase (LCAT) -enhancing agents, but the evaluation of their efficacy and safety in large-scale clinical trials is ongoing. While aberrant HDL metabolism constitutes a prevalent aspect of dyslipidemia in T2DM, HDL cholesterol concentrations and composition no longer offer valuable insights for informing therapeutic decisions. Nevertheless, HDL metabolism remains a critical research area in T2DM, necessitating further investigation to elucidate the role of HDL particles in the development of diabetes-associated complications.