Hypertriglyceridemia contributes significantly to high prevalence of small dense LDL-cholesterol in patients with type 2 diabetes, even when LDL-C targets are achieved.

Background: Small-dense (sd)LDL-cholesterol (C) is a potent risk factor for atherosclerotic cardiovascular disease (ASCVD) beyond LDL-C, and 35 mg/dL has been proposed as a cut-off value for high-sdLDL-C. sdLDL-C levels are strongly regulated by triglycerides (TG) and LDL-C levels. LDL-C has detailed targets for the prevention of ASCVD, while TG is only defined as abnormal at  ≥ 150 mg/dL. We investigated the effect of hypertriglyceridemia on the prevalence of high-sdLDL-C in patients with type 2 diabetes and explored the optimal TG levels that would suppress high-sdLDL-C.

Methods: Fasting plasma was obtained from 1569 patients with type 2 diabetes who were enrolled in the regional cohort study. sdLDL-C concentrations were measured by the homogeneous assay established by us. High-sdLDL-C was defined as ≤ 35 mg/dL according to the Hisayama Study. Hypertriglyceridemia was defined as ≥ 150 mg/dL.

Results: All lipid parameters except HDL-C were higher in the high-sdLDL-C group than in the normal-sdLDL-C group. The receiver operating characteristic (ROC) curves revealed that high sdLDL-C was identified sensitively by TG and LDL-C, with cut-off values of 115 mg/dL for TG and 110 mg/dL for LDL-C. The presence of hypertriglyceridemia increased the prevalence of high-sdLDL-C sixfold more than the normotriglyceridemic counterpart, regardless of statin use. This substantial influence of hypertriglyceridemia was found even within the control target of LDL-C levels (70-120 mg/dL) for diabetic subjects.

Conclusions: The TG cut-off for high-sdLDL-C was well below 150 mg/dL in a diabetic population. Amelioration of hypertriglyceridemia is needed even when LDL-C targets for diabetes are achieved.