**4.3 Diabetes mellitus**

Insulin resistance and type 2 diabetes mellitus are associated with increased production of TRLs, such as VLDL-C and chylomicrons, as well as smaller and denser LDL-C particles (sdLDL-C), which makes LDL-C particles more compressed and therefore more prone to induce atherosclerosis. ApoB-100, the primary lipoproteins in VLDL-C, IDL-C, and sdLDL-C, as well as ApoB-48, the major lipoproteins in chylomicrons, have a significant risk of causing atherosclerosis. Despite effective LDL-C control with statin treatment, severe vascular events such as myocardial infarction, stroke, stable angina, and other vascular events, along with mortality from CV causes, occur substantially more frequently in diabetic patients. This has been shown to be related to TG [88, 104] because hyperglycemia is prevalent in those with type 2 diabetes mellitus [106]. Therefore, elevated TG is an important residual CV risk factor that should be considered in the treatment of diabetes.

In recent years, LDL-C-lowering treatments and other risk factor control strategies have significantly reduced the incidence of CVD, but in patients with type 2 diabetes there is still continue to increase the risk of ASCVD. Based on the evidence to date, it is suggested that non-LDL-C is a necessary therapeutic target in the prevention of CV events, especially in the TRLs group, in the setting of type 2 diabetes [107]. Furthermore, numerous studies suggest that low HDL-C levels and high TG, particularly TRLs, predict the risk of ASCVD in diabetes 2 which explains how low HDL-C levels impact cholesterol conversion from intravascular atherosclerotic plaque via CETP in TG metabolism. The consequence of all lipid abnormalities in type 2 diabetes is an increased risk of ASCVD. There is strong evidence, both genetic and clinical, that reducing residual TRLs and TG is likely to reduce the risk of CVD in CKD. diabetic patients with 2-insulin resistance [88, 104, 107]. Interventions on ApoC3, ANGPTL3, and ANGTL4 factors are being examined as potential TG- and TRL-lowering treatments and risk reductions in CVD, according to preclinical and human genetic research.
