Modification of lipoprotein metabolism and function driving atherogenesis in diabetes
Open accessAbstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, characterized by raised blood glucose levels and impaired lipid metabolism resulting from insulin resistance and relative insulin deficiency. In diabetes, the peculiar plasma lipoprotein phenotype, consisting in higher levels of apolipoprotein B-containing lipoproteins, hypertriglyceridemia, low levels of HDL cholesterol, elevated number of small, dense LDL, and increased non-HDL cholesterol, results from an increased synthesis and impaired clearance of triglyceride rich lipoproteins. This condition accelerates the development of the atherosclerotic cardiovascular disease (ASCVD), the most common cause of death in T2DM patients. Here, we review the alteration of structure, functions, and distribution of circulating lipoproteins and the pathophysiological mechanisms that induce these modifications in T2DM. The review analyzes the influence of diabetes-associated metabolic imbalances throughout the entire process of the atherosclerotic plaque formation, from lipoprotein synthesis to potential plaque destabilization. Addressing the different pathophysiological mechanisms, we suggest improved approaches for assessing the risk of adverse cardiovascular events and clinical strategies to reduce cardiovascular risk in T2DM and cardiometabolic diseases.
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In metabolic disorders such as insulin resistance, type 2 diabetes, chronic kidney disease, and nephrotic syndrome, an imbalance between production and clearance of TRLs favors their accumulation, promoting a lipid profile characterized by elevated TG, increased remnant particles, and changes in lipoprotein composition associated with atherogenic risk.
“However, in metabolic disorders such as insulin resistance, type 2 diabetes, chronic kidney disease, and nephrotic syndrome, an imbalance between production and clearance of TRLs favors their accumulation, promoting a lipid profile characterized by elevated TG, increased remnant particles, and changes in lipoprotein composition often associated with atherogenic risk [12, 13].”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [13]
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- Authors
- Luciani, L., Pedrelli, M., & Parini, P.
- Affiliations
- Scuola Superiore Sant'Anna (IT)
- Karolinska University Hospital (SE)
- Corresponding author
- Parini, Paolo
- Venue
- Atherosclerosis
- Publisher
- Elsevier BV
- Published
- 2024-07
- Volume
- 394
- Pages
- 117545
- ISSN
- 0021-9150 (ISSN-L)
- OpenAlex
- W4394875384
- Cited by
- 72
- References
- 268
- Citations by year
- 2026: 30 · 2025: 32 · 2024: 9
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Atherosclerosis (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Commission
- Karolinska Institutet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- type 2 diabetes, atherogenesis, lipoprotein metabolism, atherosclerotic cardiovascular disease, apolipoprotein B, small dense LDL, hypertriglyceridemia, HDL cholesterol, triglyceride-rich lipoproteins, insulin resistance, atherosclerotic plaque formation, plaque destabilization, cardiovascular risk assessment, cardiometabolic disease
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Lipoproteins, Biomarkers, Dyslipidemias, Atherosclerosis, Plaque, Atherosclerotic
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