Abstract
Individuals with diabetes face increased risk of atherosclerotic cardiovascular disease (ASCVD), in part due to hyperlipidemia. Even after LDL cholesterol-lowering, residual ASCVD risk persists, part of which may be attributed to elevated remnant cholesterol. We describe the impact of elevated remnant cholesterol on ASCVD risk in diabetes. Preclinical, observational, and Mendelian randomization studies robustly suggest that elevated remnant cholesterol causally increases risk of ASCVD, suggesting remnant cholesterol could be a treatment target. However, the results of recent clinical trials of omega-3 fatty acids and fibrates, which lower levels of remnant cholesterol in individuals with diabetes, are conflicting in terms of ASCVD prevention. This is likely partly due to neutral effects of these drugs on the total level of apolipoprotein B(apoB)-containing lipoproteins. Elevated remnant cholesterol remains a likely cause of ASCVD in diabetes. Remnant cholesterol-lowering therapies should also lower apoB levels to reduce risk of ASCVD.
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