Dysfunctional High-Density Lipoproteins in Type 2 Diabetes Mellitus: Molecular Mechanisms and Therapeutic Implications

Bonilha, Isabella; Zimetti, Francesca; Zanotti, Ilaria; Papotti, Bianca; Sposito, Andrei C.

doi:10.3390/jcm10112233

Cited by 20 publications

(29 citation statements)

References 182 publications

(210 reference statements)

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“…The presence of dysfunctional and compositionally altered HDL particles has been described in T2D [ 14 , 15 , 16 ]; however, to the best of our knowledge, alterations in HDL lipidome in individuals with prediabetes have not yet been investigated. In the present study, we investigated the HDL lipidome in patients with prediabetes and compared it to that of normoglycemic individuals and patients with established T2D.…”

Section: Introductionmentioning

confidence: 99%

Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes

et al. 2022

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Prediabetes is a clinically silent, insulin-resistant state with increased risk for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD). Since glucose homeostasis and lipid metabolism are highly intersected and interrelated, an in-depth characterization of qualitative and quantitative abnormalities in lipoproteins could unravel the metabolic pathways underlying the progression of prediabetes to T2D and also the proneness of these patients to developing premature atherosclerosis. We investigated the HDL lipidome in 40 patients with prediabetes and compared it to that of 40 normoglycemic individuals and 40 patients with established T2D using Nuclear Magnetic Resonance (NMR) spectroscopy. Patients with prediabetes presented significant qualitative and quantitative alterations, potentially atherogenic, in HDL lipidome compared to normoglycemic characterized by higher percentages of free cholesterol and triglycerides, whereas phospholipids were lower. Glycerophospholipids and ether glycerolipids were significantly lower in prediabetic compared to normoglycemic individuals, whereas sphingolipids were significantly higher. In prediabetes, lipids were esterified with saturated rather than unsaturated fatty acids. These changes are qualitatively similar, but quantitatively milder, than those found in patients with T2D. We conclude that the detailed characterization of the HDL lipid profile bears a potential to identify patients with subtle (but still proatherogenic) abnormalities who are at high risk for development of T2D and CVD.

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Section: Introductionmentioning

confidence: 99%

Progressive, Qualitative, and Quantitative Alterations in HDL Lipidome from Healthy Subjects to Patients with Prediabetes and Type 2 Diabetes

et al. 2022

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“…Крупные эпидемиологические исследования продемонстрировали обратную связь между концентра-цией сывороточного холестерина (ХС) ЛПВП (ХС-ЛПВП) и риском развития ишемической болезни сердца (ИБС). Каждое увеличение ХС-ЛПВП на 0,026 ммоль/л снижает риск развития ИБС на 2-3% [5,6]. Пациенты с низким уровнем ЛПВП в 2 раза чаще страдают СД и имеют более высокий риск развития связанных с ним сердечно-сосудистых осложнений, периферической невропатии и диабетической нефропатии [7,8].…”

Section: Introductionunclassified

“…Помимо прямого воздействия на метаболизм глюкозы, ЛПВП влияют на обратный транспорт ХС из артериальной стенки и периферических тканей в печень; предохраняют липопротеины низкой плотности (ЛПНП) от окисления; оказывают противовоспалительное и сосудорасширяющее действия на клетки сосудистой стенки [6,8].…”

Section: Introductionunclassified

“…Более того, при плохо контролируемом СД2 ЛПВП могут терять свои полезные функции и приобретать проатерогенные, провоспалительные свойства. Такие ЛПВП принято называть дисфункциональными, а в случае СДдиабетическиеми ЛПВП [6,8,15,16].…”

Section: Introductionunclassified

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Dysfunctional high-density lipoproteins in diabetes mellitus

Poteryaeva

Usynin

2022

Probl Endokrinol (Mosk)

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The risk of cardiovascular disease (CVD) in persons with type 2 diabetes mellitus (DM2) increases two to four times. One of the main factors increasing cardiovascular risk is dyslipidemia, which includes abnormalities in all lipoproteins, including high-density lipoproteins (HDL). The development of DM2 is accompanied not only by a decrease in the level of HDL, but also by significant changes in their structure. This leads to the transformation of native HDL into so-called dysfunctional or diabetic HDL, which loses their antiatherogenic, cardioprotective, anti-inflammatory and anti-diabetic properties. In poorly controlled diabetes mellitus HDL can not only lose its beneficial functions, but also acquire proatherogenic, proinflammatory ones. Diabetic HDL can contribute to the accumulation of such unfavorable qualities as increased proliferation, migration, and invasion of cancer cells. Given that HDL, in addition to participation in cholesterol transport, performs important regulatory functions in the body, there is reason to assume that structural modifications of HDL (oxidation, glycation, triglyceride enrichment, loss of HDL-associated enzymes, etc.) are one of the causes of vascular complications of diabetes.

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“…The correlation between HDLs and the onset of diabetes has been the subject of several studies, clearly demonstrating an inverse association between low levels of these lipoproteins and high risk of the disease [ 61 ]. Modifications of HDL structure and function in the setting of altered glucose metabolism play pivotal roles in the onset and progression of diabetes [ 62 ], but Mendelian randomization studies do not provide evidence supporting a causal association between genetically low levels of HDL and an increased risk to develop this disease [ 63 , 64 ].…”

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confidence: 99%