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Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome

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ByCrossFitOctober 7, 2019

In this highly cited 1998 review, Dr. Scott Grundy reviews the association of hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome with heart disease risk.

High triglyceride levels contribute to higher numbers of LDL particles. These high triglyceride levels are packaged into VLDL, which transforms into LDL over time as these triglycerides are passed on to other tissues. High triglyceride levels also lead to smaller LDL particles. When triglyceride levels are high, VLDL particles transfer some of their triglycerides to LDL particles; as these triglycerides are taken up by other tissues, the LDL particles shrink. The small LDL particles are hypothesized to be more atherogenic than larger particles.

The “lipid triad” of high triglycerides, small LDL particles, and low HDL is common among those with metabolic syndrome and insulin resistance. These conditions may also be mechanistically linked. Insulin resistance leads to increased liver fat, which increases fat VLDL production — in other words, insulin resistance may directly cause the lipid triad. Simultaneously, this condition persists alongside muscular insulin resistance, hyperglycemia and/or hyperinsulinemia, all of which would maintain elevated triglyceride levels.

At the time this paper was written, many of these mechanisms were preliminary, but the paper nonetheless established the pathways by which metabolic dysregulation — i.e., insulin resistance and the metabolic syndrome — could directly lead to a more atherogenic lipoprotein profile.

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