Type 2 diabetes mellitus and insulin resistance feature substantial modifications of the lipoprotein profile, including a higher proportion of smaller and denser low-density lipoprotein (LDL) particles. In addition, qualitative changes occur in the composition and structure of LDL, including changes in electrophoretic mobility, enrichment of LDL with triglycerides and ceramides, prolonged retention of modified LDL in plasma, increased uptake by macrophages, and the formation of foam cells. These modifications affect LDL functions and favor an increased risk of cardiovascular disease in diabetic individuals. In this review, we discuss the main findings regarding the structural and functional changes in LDL particles in diabetes pathophysiology and therapeutic strategies targeting LDL in patients with diabetes.

In individuals with very low high-density lipoprotein (HDL-C) cholesterol, such as Tangier disease, LCAT deficiency, and familial hypoalphalipoproteinemia, there is an increased risk of premature atherosclerosis. However, analyzes based on comparisons of populations with small variations in HDL-C mediated by polygenic alterations do not confirm these findings, suggesting that there is an indirect association or heterogeneity in the pathophysiological mechanisms related to the reduction of HDL-C. Trials that evaluated some of the HDL functions demonstrate a more robust degree [...] ABSTRACT In individuals with very low high-density lipoprotein (HDL-C) cholesterol, such as Tangier disease, LCAT deficiency, and familial hypoalphalipoproteinemia, there is an increased risk of premature atherosclerosis. However, analyzes based on comparisons of populations with small variations in HDL-C mediated by polygenic alterations do not confirm these findings, suggesting that there is an indirect association or heterogeneity in the pathophysiological mechanisms related to the reduction of HDL-C. Trials that evaluated some of the HDL functions demonstrate a more robust degree

Stricter control of risk factors has been pursued as a compelling strategy to mitigate cardiovascular events (CVE) in type 2 diabetes (T2D) individuals. However, the achievement rate of the recommended goals has remained low in clinical practice. This study investigated the 2019 ESC guideline recommendation attainment among T2D individuals enrolled in a national cohort held in Brazil. Data from 1030 individuals (mean age: 58 years old; 54% male; mean T2D duration: 9.7 years) were analyzed. The control rates were 30.6% for SBP, 18.8% for LDL-C, and 41% for A1c, and only 3.2% of the study participants met all three targets. Statins and high-intensity lipid-lowering therapy prescription rates were 45% and 8.2%, respectively. Longer T2D duration and those at higher CV risk were less likely to be controlled. Longer diabetes duration and higher CV risk were inversely related to the chance of achieving the recommended targets. Treatment escalation using conventional therapies would be sufficient to gain optimal control in most of the study sample. In conclusion, a minimal proportion of T2D individuals comply with guidelines-oriented CV prevention targets. Given the significant burden of the disease, and the substantial effect size predicted for these therapies, bridging this gap between guidelines and clinical practice should be considered an urgent call to public health managers.