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Poor glycemic control in type 2 diabetes enhances functional and compositional alterations of small, dense HDL3c
Leonardo Gomez Rosso1, Marie Lhomme2, Tomas Meroño3
1INSERM UMR_S 1166, Faculte de Medecine Pitie-Salpetriere, 91 Bld de l'Hopital, 75013 Paris, France; University of Pierre and Marie Curie - Paris 6, Paris, France; Laboratory of Lipids and Atherosclerosis, Department of Clinical Biochemistry, INFIBIOC, University of Buenos Aires, CONICET, Buenos Aires, Argentina.
Insights
High-density lipoprotein (HDL) functionality is impaired in type 2 diabetes (T2D). Poor glycemic control and dyslipidemia significantly alter HDL composition and reduce its antiatherogenic properties.
Area of Science:
- Cardiovascular Research
- Metabolic Syndrome
- Lipidomics
Background:
- High-density lipoprotein (HDL) has crucial antiatherogenic properties, particularly small, dense HDL3c particles.
- These functions can be compromised in insulin resistance, dyslipidemia, and hyperglycemia associated with type 2 diabetes (T2D).
- The specific impact of glycemic control and dyslipidemia on HDL composition and function in T2D remains unclear.
Purpose of the Study:
- To investigate the relationship between HDL composition, glycemic control, and HDL functionality in T2D patients.
- To determine if altered HDL function originates from dyslipidemia, dysglycemia, or both.
- To analyze HDL subpopulations and HDL3c particle activity in relation to diabetes control.
Main Methods:
- Analysis of HDL subpopulations and small, dense HDL3c particle function in treatment-naïve T2D patients (well-controlled and poorly-controlled) and normolipidemic controls.
- Assessment of lipidomic composition and functional activities, including antioxidative capacity.
- Correlation analysis with clinical parameters like HbA1c and markers of dyslipidemia and inflammation.
Main Results:
- Patients with both well- and poorly-controlled T2D exhibited dyslipidemia and low-grade inflammation with altered HDL composition.
- HDL compositional changes in small, dense HDL subfractions correlated significantly with plasma HbA1c levels.
- Poor glycemic control in T2D was associated with further chemical modifications in HDL3c particles, diminishing their antioxidative activity against LDL oxidation.
Conclusions:
- Defective functionality of small, dense HDL particles in T2D is influenced by both atherogenic dyslipidemia and the level of glycemic control.
- Compositional alterations in HDL are directly linked to glycemic control (HbA1c levels).
- These findings highlight the complex interplay between diabetes metabolic status and HDL's protective cardiovascular functions.
Abstract:
High-density lipoprotein (HDL) possesses multiple biological activities; small, dense HDL3c particles displaying distinct lipidomic composition exert potent antiatherogenic activities which can be compromised in dyslipidemic, hyperglycemic insulin-resistant states. However, it remains indeterminate (i) whether such functional HDL deficiency is related to altered HDL composition, and (ii) whether it originates from atherogenic dyslipidemia, dysglycemia, or both. In the present work we analyzed compositional characteristics of HDL subpopulations and functional activity of small, dense HDL3c particles in treatment-naïve patients with well-controlled (n=10) and poorly-controlled (n=8) type 2 diabetes (T2D) and in normolipidemic age- and sex-matched controls (n=11). Our data reveal that patients with both well- and poorly-controlled T2D displayed dyslipidemia and low-grade inflammation associated with altered HDL composition. Such compositional alterations in small, dense HDL subfractions were specifically correlated with plasma HbA1c levels. Further analysis using a lipidomic approach revealed that small, dense HDL3c particles from T2D patients with poor glycemic control displayed additional modifications of their chemical composition. In parallel, antioxidative activity of HDL3c towards oxidation of low-density lipoprotein was diminished. These findings indicate that defective functionality of small, dense HDL particles in patients with T2D is not only affected by the presence of atherogenic dyslipidemia, but also by the level of glycemic control, reflecting compositional alterations of HDL.
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