Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes

Murakami, Hiroshi; Tanabe, Jutaro; Tamasawa, Naoki; Matsumura, Kenta; Yamashita, Maki; Matsuki, Kota; Matsui, Jun; Suda, Toshio

doi:10.1016/j.diabres.2012.10.022

Cited by 27 publications

(25 citation statements)

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“…This was also demonstrated in a study by Khera and colleagues, where patients in secondary prevention (including 23% with T2D) had a reduced cholesterol efflux capacity independent of their HDL levels [36]. In agreement with this finding, recent data by another group showed that HDL particles obtained from T2D patients were characterized by a decreased paraxonase-1 activity, inversely correlated to HbA1c levels [37].…”

Section: Type 2 Diabetes and Dyslipidemiasupporting

confidence: 77%

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Rotella²,

2012

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■ AbstractPatients with diabetes frequently exhibit the combined occurrence of hyperglycemia and dyslipidemia. Published data on their coexistence are often controversial. Some studies provide evidence for suboptimal lifestyle and exogenous hyperinsulinism at "mild insulin resistance" in adult diabetic patients as main pathogenic factors. In contrast, other studies confirm that visceral adiposity and insulin resistance are the basic features of dyslipidemia in type 2 diabetes (T2D). The consequence is an excess of free fatty acids, which causes hepatic gluconeogenesis to increase, metabolism in muscles to shift from glucose to lipid, beta-cell lipotoxicity, and an appearance of the classical "lipid triad", without real hypercholesterolemia. Recently, it has been proposed that cholesterol homeostasis is important for an adequate insulin secretory performance of beta-cells. The accumulation of cholesterol in beta-cells, caused by defective high-density lipoprotein (HDL) cholesterol with reduced cholesterol efflux, induces hyperglycemia, impaired insulin secretion, and beta-cell apoptosis. Data from animal models and humans, including humans with Tangier disease, who are characterized by very low HDL cholesterol levels, are frequently associated with hyperglycemia and T2D. Thus, there is a reciprocal influence of dyslipidemia on beta-cell function and inversely of beta-cell dysfunction on lipid metabolism and micro-and macrovascular complications. It remains to be clarified how these different but mutually influencing adverse effects act in together to define measures for a more effective prevention and treatment of micro-and macrovascular complications in diabetes patients. While the control of circulating low-density lipoprotein (LDL) cholesterol and the level of HDL cholesterol are determinant targets for the reduction of cardiovascular risk, based on recent data, these targets should also be considered for the prevention of betacell dysfunction and the development of type 2 diabetes. In this review, we analyze consolidated data and recent advances on the relationship between lipid metabolism and diabetes mellitus, with particular attention to the reciprocal effects of the two features of the disease and the development of vascular complications.

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Section: Type 2 Diabetes and Dyslipidemiasupporting

confidence: 77%

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Rotella²,

2012

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“…Previously, it was shown that enrichment of HDL with SAA decreases its cholesterol efflux properties1840, which also translates into lower in vivo reverse cholesterol transport in a rodent model25. However, it should be noted that in a small-scale study in humans no impact of SAA on THP-1-mediated efflux towards HDL from T2DM patients has also been reported41. On the other hand, SAA has been linked to impairment of other key functions of HDL such as the protection against oxitative stress42 and inflammation43.…”

Section: Discussionmentioning

confidence: 98%

Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study

Annema

Dikkers

Boer

et al. 2016

Sci Rep

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Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross-sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I.

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“…PON-1 associates with HDL to prevent its oxidation by copper ions as well as reducing the peroxide and aldehyde content of HDL, this interaction also lessens LDL atherogenic potential, thus potentially reducing the risk of development of atherosclerosis [39]. Previous studies have found PON-1 activity to be lower in those with T2DM [40, 41] implicating the impairment of HDL antioxidant properties. However, when those taking insulin and GLP-1 analogues were excluded, serum-PON-1 activity was more comparable between groups, similar to that observed for PON-1 activity in HDL 2 and HDL 3 , which may result from a lack of change in apoAI concentration that is required for the stabilisation of PON-1 and its association with HDL.…”

Section: Discussionmentioning

confidence: 99%

Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL₂ and HDL₃

Griffiths

Pazderska

Ahmed

et al. 2017

Journal of Diabetes Research

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Persons with type 2 diabetes mellitus (T2DM) have an elevated risk of atherosclerosis. High-density lipoproteins (HDL) normally protect against cardiovascular disease (CVD), but this may be attenuated by serum amyloid A (SAA). In a case-control study of young females, blood samples were compared between subjects with T2DM (n = 42) and individuals without T2DM (n = 42). SAA and apolipoprotein AI (apoAI) concentrations, paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT) activities were measured in the serum and/or HDL2 and HDL3 subfractions. SAA concentrations were higher in T2DM compared to controls: serum (30 mg/L (17, 68) versus 15 mg/L (7, 36); p = 0.002), HDL2 (1.0 mg/L (0.6, 2.2) versus 0.4 mg/L (0.2, 0.7); p < 0.001), and HDL3, (13 mg/L (8, 29) versus 6 mg/L (3, 13); p < 0.001). Serum-PON-1 activity was lower in T2DM compared to that in controls (38,245 U/L (7025) versus 41,109 U/L (5690); p = 0.043). CETP activity was higher in T2DM versus controls in HDL2 (232.6 μmol/L (14.1) versus 217.1 μmol/L (25.1); p = 0.001) and HDL3 (279.5 μmol/L (17.7) versus 245.2 μmol/L (41.2); p < 0.001). These results suggest that individuals with T2DM have increased SAA-related inflammation and dysfunctional HDL features. SAA may prove to be a useful biomarker in T2DM given its association with elevated CVD risk.

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Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes

Abstract: We confirmed the functional changes in HDL particles in the patients. Efflux-hdl from macrophages was reduced depending upon the decrease in PON1 activity, which was inversely related to HbA1c levels.

Cited by 27 publications

References 50 publications

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study

Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL₂ and HDL₃

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Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes

Abstract: We confirmed the functional changes in HDL particles in the patients. Efflux-hdl from macrophages was reduced depending upon the decrease in PON1 activity, which was inversely related to HbA1c levels.

Cited by 27 publications

References 50 publications

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Dyslipidemia and Diabetes: Reciprocal Impact of Impaired Lipid Metabolism and Beta-Cell Dysfunction on Micro- and Macrovascular Complications

Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study

Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL2 and HDL3

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Type 2 Diabetes in Young Females Results in Increased Serum Amyloid A and Changes to Features of High Density Lipoproteins in Both HDL₂ and HDL₃