Altered small dense LDL profiles in long-standing controlled Type 1 Diabetes
Sardà, Helena (Universitat Autònoma de Barcelona)
Solé, Arnau (Institut de Recerca Sant Pau)
Colom, Cristina (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Borràs, Carla (Institut de Recerca Sant Pau)
Carreras, Gemma (Universitat Autònoma de Barcelona. Departament de Pediatria, Obstetrícia i Ginecologia i de Medicina Preventiva i Salut Pública)
Benitez, Sonia (Institut de Recerca Sant Pau)
Miñambres, Inka (Universitat Autònoma de Barcelona. Departament de medicina)
Escolà-Gil, Joan Carles (Institut de Recerca Sant Pau)
Sánchez Quesada, José Luis
Pérez, Antonio (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))

Data:	2026
Resum:	Introduction: Small dense low-density lipoprotein (sdLDL) is a highly atherogenic LDL subclass associated with cardiovascular disease (CVD). While type 1 diabetes confers increased cardiovascular risk despite adequate glycemic control, the role of sdLDL and its regulators remains unclear. Methods: In this cross-sectional observational study, plasma from individuals with long-standing type 1 diabetes and 24 healthy controls was analyzed. sdLDL-cholesterol (sdLDL-C) concentration, sdLDL-C/LDL-cholesterol ratio, LDL size and subclasses were assessed using homogeneous assays, NMR spectroscopy, and gradient gel electrophoresis. Apolipoprotein C3 (ApoC3), hepatic lipase (HL), endothelial lipase (EL), and cholesteryl ester transfer protein (CETP) activity were measured by immunoturbidimetric, ELISA and functional assays. Results: Despite adequate glycemic control (mean HbA1c 7. 6% [60 mmol/mol]) and near-normal lipid levels, individuals with type 1 diabetes had significantly higher sdLDL-C (0. 56 ± 0. 28 mmol/L vs 0. 43 ± 0. 26 mmol/L), increased sdLDL-C/LDL-cholesterol ratio (0. 20 ± 0. 08 vs 0. 12 ± 0. 06) and smaller LDL particle size (26. 32 ± 1. 08 nm vs 26. 81 ± 0. 68 nm) compared with controls. ApoC3 and HL mass/activity were significantly increased (8. 67 ± 3. 22 mg/dL vs 6. 53 ± 2. 42; 46. 60 ± 16. 12 ng/mL vs 15. 45 ± 7. 40 ng/mL and 1. 03 ± 0. 24 U/mL vs 0. 89 ± 0. 23 U/mL; respectively), CETP activity significantly reduced (808. 8 ± 197. 0 pmol/mL/h vs 929. 7 ± 149. 6 pmol/mL/h), and endothelial lipase levels unchanged. sdLDL-C positively correlated with ApoC3 (r = 0. 7517) and inversely with CETP activity (r = -0. 2682). Conclusion: Long-standing type 1 diabetes with adequate glycemic control is associated with an atherogenic sdLDL profile despite near-normal conventional lipid levels. This first multi-method characterization study of sdLDL in type 1 diabetes highlights the contribution of ApoC3, CETP and HL to sdLDL-C enrichment and suggests that direct assessment of sdLDL may improve cardiovascular risk stratification.
Ajuts:	Ministerio de Economía y Competitividad PI16/00471 Instituto de Salud Carlos III PI20/00334 Instituto de Salud Carlos III PI2300232 Generalitat de Catalunya 2017/SGR-01149
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Llengua:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Matèria:	Small dense LDL cholesterol ; Type 1 diabetes ; Cardiovascular disease risk ; Direct assay ; Apolipoprotein C3 ; Hepatic lipase ; Cholesteryl ester transfer protein
Publicat a:	Frontiers in endocrinology, 2026 , ISSN 1664-2392

Disponible a partir de: 2099-01-01 Postprint 16 p, 223.8 KB

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