Excess Triglycerides in Very Low-Density Lipoprotein (VLDL) Estimated from VLDL-Cholesterol could be a Useful Biomarker of Metabolic Dysfunction Associated Steatotic Liver Disease in Patients with Type 2 Diabetes

Abstract

Aims: We report that small dense low-density lipoprotein cholesterol (sdLDL-C) levels are sensitive biomarkers of metabolic dysfunction-associated steatotic liver disease (MASLD). Since triglyceride (TG)-rich very low-density lipoprotein (VLDL) is a precursor of sdLDL and is overproduced by MASLD, the composition of VLDL may be more directly associated with MAFLD than sdLDL-C or plasma TG. To identify TG-rich VLDL, this author proposed "Excess TG" and examined its association with MASLD.

Methods: Patients with type 2 diabetes (n=1295), excluding fasting hypertriglyceridemia (TG ≥ 400 mg/dL) and heavy drinkers were examined. Liver steatosis and visceral fat area (VFA) were evaluated using CT. VLDL-C was calculated as the total C minus direct LDL-C minus HDL-C. The average VLDL-TG level can be estimated using VLDL-C×5, according to the principle of the Friedewald equation for LDL-C. Thus, VLDL-TG was estimated as VLDL-C×5, and Excess TG was calculated as plasma TG minus VLDL-C×5.

Results: Patients with MASLD were younger, more likely to be men and drinkers, and had higher VFA, TG, sdLDL-C, and excess TG, while VLDL-C was comparable. Excess TG was found to be the most sensitive lipid parameter for identifying MASLD, independent of sdLDL-C, TG, TG/VLDL-C, and VFA. The odds ratios for MASLD were 2.4-, 3.7-, and 3.9-fold higher for Excess TG ranges of 0-24, 25-49, and ≥ 50 mg/dL, respectively, relative to ＜0 mg, and a close relationship remained significant after adjustment for lipid- and adiposity-related parameters.

Conclusions: Excess TG in VLDL was strongly associated with MASLD beyond TG and sdLDL-C levels, which may reflect the presence of TG-rich VLDL.

Keywords: Excess triglycerides; MASLD; Small dense LDL; VLDL.

Fig.1. Distribution of excess TG values in 1295 patients with type 2 diabetes and receiver operator characteristic (ROC) curves for the determination of Excess TG cutoff values for prevalence of MASLD

MASLD=metabolic dysfunction associated steatotic liver disease; TG=triglycerides; Excess TG=TG minus 5 x VLDL-C (Total-C minus LDL-C minus HDL-C) AUC=area under the curve

Supplemental Fig.1.

The effect of excess TG on MASLD for non-drinkers and current drinkers, respectively

Fig.2. A conceptual diagram of Excess TG

In the case of hypertriglyceridemia, VLDL-TG level (150 mg/dL) was 50 mg/dL higher than the estimated average VLDL-TG level (100 mg/dL) based on VLDL-C (T-C minus LDL-C minus HDL-C)(20 mg/dL). Thus, the Excess TG would be 50 mg/dL.