The Reciprocal Relationship between LDL Metabolism and Type 2 Diabetes Mellitus

Bonilha, Isabella; Hajduch, Éric; Luchiari, Beatriz; Nadruz, Wilson; Goff, Wilfried Le; Sposito, Andrei C.

doi:10.3390/metabo11120807

Cited by 20 publications

(13 citation statements)

References 179 publications

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“…For instance, the proportion of sdLDL can be used to predict the elevated intima-media thickness (IMT) as well as insulin resistance in patients with diabetes ( Gerber et al, 2013 ). The size of LDL-Ps decreases as insulin resistance becomes more severe ( Garvey et al, 2003 ; Bonilha et al, 2021 ). Of note, the elevated levels of carotid IMT and sdLDL are correlated with other well-known risk factors of CVD including sex, age, genetics, as well as unhealthy habits such as smoking.…”

Section: Atherogenic Mechanisms Of Ldlmentioning

confidence: 99%

Low-density lipoprotein particles in atherosclerosis

2022

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Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i.

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Section: Atherogenic Mechanisms Of Ldlmentioning

confidence: 99%

Low-density lipoprotein particles in atherosclerosis

2022

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“…In addition, we observed a possible positive relationship between cholesterol values (LDL and TC) and serum aspartate levels (Fig. 2 ), possibly due to the relationship of both to cardiovascular impairments 60 , 61 .…”

Section: Discussionmentioning

confidence: 73%

Integrative perspective of the healthy aging process considering the metabolome, cardiac autonomic modulation and cardiorespiratory fitness evaluated in age groups

Signini

Castro

Rehder-Santos

et al. 2022

Sci Rep

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The aging process causes changes at all organic levels. Although metabolism, cardiac autonomic modulation (CAM), and cardiorespiratory fitness (CRF) are widely studied as a function of age, they are mainly studied in isolation, thus making it difficult to perceive their concomitant variations. This study aimed to investigate the integrated changes that occur in the metabolome, CAM, and CRF throughout aging in apparently healthy individuals. The subjects (n = 118) were divided into five groups according to age (20–29, 30–39, 40–49, 50–59, and 60–70 years old) and underwent blood collection, autonomic assessment, and a cardiopulmonary exercise test for metabolomics analysis using mass spectrometry and nuclear magnetic resonance, cardiac autonomic modulation analysis, and CRF by peak oxygen consumption analysis, respectively. The Tukey’s post hoc and effect size with confidence interval were used for variables with a significant one-way ANOVA effect (P < 0.01). The main changes were in the oldest age group, where the CRF, valine, leucine, isoleucine, 3-hydroxyisobutyrate, and CAM reduced and hippuric acid increased. The results suggest significant changes in the metabolome, CAM, and CRF after the age of sixty as a consequence of aging impairments, but with some changes in the metabolic profile that may be favorable to mitigate the aging deleterious effects.

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“…HDL size of person with diabetes is altered, with loss of large and very large HDL2 and gain of small HDL3 (60). The same mechanism promotes the formation of small and dense LDL (61). In this group of individuals, sub analyses of studies with fibrates and studies with an eicosapentaenoic acid derivative, icosapent ethyl, were associated with a reduction in cardiovascular risk (62).…”

Section: Secondary Dyslipidemias With Low Hdl-cmentioning

confidence: 99%

Very low HDL levels: clinical assessment and management

Bonilha¹,

Luchiari²,

Nadruz³

et al. 2023

Archives of Endocrinology and Metabolism

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In individuals with very low high-density lipoprotein (HDL-C) cholesterol, such as Tangier disease, LCAT deficiency, and familial hypoalphalipoproteinemia, there is an increased risk of premature atherosclerosis. However, analyzes based on comparisons of populations with small variations in HDL-C mediated by polygenic alterations do not confirm these findings, suggesting that there is an indirect association or heterogeneity in the pathophysiological mechanisms related to the reduction of HDL-C. Trials that evaluated some of the HDL functions demonstrate a more robust degree of association between the HDL system and atherosclerotic risk, but as they were not designed to modify lipoprotein functionality, there is insufficient data to establish a causal relationship. We currently have randomized clinical trials of therapies that increase HDL-C concentration by various mechanisms, and this HDL-C elevation has not independently demonstrated a reduction in the risk of cardiovascular events. Therefore, this evidence shows that (a) measuring HDL-C as a way of estimating HDL-related atheroprotective system function is insufficient and (b) we still do not know how to increase cardiovascular protection with therapies aimed at modifying HDL metabolism. This leads us to a greater effort to understand the mechanisms of molecular action and cellular interaction of HDL, completely abandoning the traditional view focused on the plasma concentration of HDL-C. In this review, we will detail this new understanding and the new horizon for using the HDL system to mitigate residual atherosclerotic risk.

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The Reciprocal Relationship between LDL Metabolism and Type 2 Diabetes Mellitus

Cited by 20 publications

References 179 publications

Low-density lipoprotein particles in atherosclerosis

Low-density lipoprotein particles in atherosclerosis

Integrative perspective of the healthy aging process considering the metabolome, cardiac autonomic modulation and cardiorespiratory fitness evaluated in age groups

Very low HDL levels: clinical assessment and management

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