Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes

JA Orozco Morales; AX Medina Urrutia; Tamayo MT; J Reyes Barrera; Galarza EJ; JG Juarez Rojas; P Dies Suarez; N Mendez Sanchez; LE Diaz Orozco; Velazquez-opez L; P Medina Bravo

doi:10.1530/ey.22.12.15

12.15

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 12.15 | DOI: 10.1530/ey.22.12.15

ESPEYB25 12. Type 2 Diabetes, Metabolic Syndrome and Lipid Metabolism Lipid Metabolism (6 abstracts)

12.15. Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes

Orozco Morales JA , Medina Urrutia AX , Tamayo MT , Reyes Barrera J , Galarza EJ , Juárez Rojas JG , Dies Suarez P , Méndez Sánchez N , Díaz Orozco LE , Velázquez-López L & Medina Bravo P

Front Pediatr. 2024 Dec 24;12:1462406. doi: 10.3389/fped.2024.1462406

Brief Summary: This cross-sectional study, in adolescents with T2D, found that metabolic-associated fatty liver disease (MAFLD) does not impair HDL’s cholesterol efflux capacity (CEC). However, MAFLD is associated with alterations in HDL structure and lipid content, which could affect HDL long-term protective role against cardiovascular disease.

Comment: High-density lipoproteins (HDLs) havea known protective role against cardiovascular disease (CVD). While low plasma HDL cholesterol (HDL-C) levels are an independent risk factor for CVD, recent evidence suggests that HDL functionality and physicochemical properties may provide a more accurate reflection of cardiovascular risk than HDL-C concentration alone.HDLs exert their protective effects through several mechanisms. One key process recognized is reverse cholesterol transport (RCT),in which HDL shuttles cholesterol from peripheral tissues back to the liver for biliary excretion. Another crucial process isthe cholesterol efflux capacity (CEC), referring to HDL’s ability to remove cholesterol from macrophages. Higher CEC is associated with a lower CVD. risk.

T2D is associated with metabolic-associated fatty liver disease (MAFLD). Previous studies have reported a reduced in CEC in adults with MAFLD. The aim of this study was to assess the impact of MAFLD on CEC in adolescents with T2D.

The study cohort comprised of three groups: adolescents with T2D without MAFLD group (n=16), T2D with MAFLD (n= 31) and health controls (n= 23). Surprisingly, no differences in HDL CEC were found between adolescents with T2D with and without MAFLD, nor between adolescents with T2D and healthy controls. However, in adolescents with T2D, higher liver fat content was associated with notable changes in HDL characteristics: lower levels of larger HDL2 particles, a shift towards smaller HDL3 particles, increased triglyceride content inside HDL, and reduced cholesterol esters and free cholesterol within HDL particles. These alterations suggest early

Key message: in adolescents with T2D, hepatic lipid accumulation drives changes in HDL function, increasing cardiovascular risk over time.