HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease

Abstract

Background and Aims We have previously shown that the anti-inflammatory and anti-oxidant functions of HDL are impaired in T2D patients. In this study, we examined whether HDL from T2D patients contains elevated levels of oxidized fatty acids and whether those levels correlate with cardiovascular disease (CVD). Methods and Results HETEs and HODEs on HDL were determined by LC-MS/MS in 40 non-diabetic controls (ND), 40 T2D without CVD (D+CVD−) and 38 T2D with known history of CVD (D+CVD+). HDL oxidant index was evaluated by a cell-free assay using dichlorofluorescein. Twenty-six randomly selected subjects from the three groups underwent coronary calcium score evaluation (CAC). Major cardiovascular risk factors were similar among the groups. HETEs and HODEs content were significantly increased in HDL from D+CVD+ when compared to D+CVD− and ND patients. HDL oxidant index was not different among the three groups; however, it was significantly higher in patients with CAC score >100 when compared to patients with CAC score <100. Conclusion Patients with D+CVD− and D+CVD+ are characterized by a severe, graded enrichment of oxidized fatty acids on HDL. In the present study, a loss of HDL function (as estimated by the HDL oxidant index) is observed only in patients with more advanced atherosclerosis.

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

“…42 There are also data indicating that the concentration of lipid peroxidation products is higher in HDL from type 2 diabetic patients with cardiovascular disease than in patients with type 2 diabetes but no known cardiovascular disease. 147 …”

High levels of oxidized fatty acids in HDL are associated with impaired HDL function in patients with active rheumatoid arthritis

“…Oxidation products of arachidonic acid and linoleic acid including hydroxyeicosatetraenoic acids (HETES) and hydroxyoctadecadienoic acids (HODES) contribute to the oxidation of LDL, and their accumulation in high-density lipoprotein (HDL) has been proposed to inhibit HDL function, increasing atherosclerotic risk [8–10]. Previous work has shown increased HETES and HODES in HDL of patients with diabetes and atherosclerotic vascular disease [11] as well as in plasma of humans and rodents with pulmonary hypertension [12, 13]. …”

The Therapeutic Potential of Resistant Starch in Modulation of Insulin Resistance, Endotoxemia, Oxidative Stress and Antioxidant Biomarkers in Women with Type 2 Diabetes: A Randomized Controlled Clinical Trial

“…However, other studies have informed researchers about the mechanisms underlying the effects of RS on oxidative stress. Some proposed mechanisms for prebiotics antioxidant effects include the scavenging ability of reactive oxygen species (ROS) [32] , SCFAs [33] , reduction of inflammation and endotoxin [34] , a change in microflora toward Lactobacilli which contain antioxidants [35] , suppression of CD11c expression in adipose tissue [36] and reduction of the levels of FFAs [37] .…”