Figure 1.

Potential combination of the physiopathological mechanisms of diabetes and familial hypercholesterolemia in the same individual. Diabetic dyslipidemia. Insulin resistance reduces lipoprotein lipase activity (LPL) ①, decreasing plasma triglyceride clearance, and promotes the release of free fatty acids ②, which are taken up by the liver and used for the synthesis and release of VLDL ③. VLDL exchange triglycerides and cholesterol esters with LDL ④ and HDL ⑤ through the action of cholesteryl ester transfer protein (CETP). Triglyceride-rich HDL particles, through the action of hepatic lipase (HL), are converted into smaller particles, with less anti-atherogenic properties, which are cleared more rapidly in the kidney ⑥. LDL particles also become smaller and denser (LDL phenotype B), more pro-atherogenic ⑦. Familial hypercholesterolemia. The genetic defect in LDL receptor prevents its uptake and metabolism in the liver, favoring the accumulation of LDL particles ⑧. This generates an increase in the uptake of chylomicrons and remnants in the liver ⑨, in turn boosting the synthesis of VLDL.