The Journal of Clinical Endocrinology and Metabolism, Dec 1, 2008
Context: Lecithin:cholesterol acyltransferase (LCAT), which esterifies free cholesterol to choles... more Context: Lecithin:cholesterol acyltransferase (LCAT), which esterifies free cholesterol to cholesteryl esters, is required for normal plasma lipoprotein structure and is instrumental in high density lipoprotein (HDL) remodeling, but the relationship of variation in plasma LCAT activity with subclinical atherosclerosis is unclear. Objectives: The aim of the study was to determine the effect of the metabolic syndrome (MetS) on plasma LCAT activity and its relationship with carotid artery intima media thickness (IMT). Setting: The study was conducted at the vascular laboratory of a university medical center. Methods: In 74 subjects with MetS and 90 subjects without MetS (National Cholesterol Education Program Adult Treatment Panel III criteria), mean carotid artery IMT, plasma lipids, LCAT activity (exogenous substrate method), high-sensitive C-reactive protein, and homeostasis model assessment insulin resistance (HOMA ir) were documented. Results: IMT was greater (P ϭ 0.01) and plasma LCAT activity was higher (P Ͻ 0.001) in subjects with MetS compared to subjects without MetS. Similar increases in IMT and LCAT were found in MetS subjects without type 2 diabetes mellitus. Multiple linear regression analysis demonstrated that plasma LCAT activity was independently and positively related to HOMA ir , plasma triglycerides, non-HDL cholesterol, and HDL cholesterol (all P Ͻ 0.001). After adjustment for age and sex, IMT was positively associated with LCAT activity (P Ͻ 0.01), independently of the presence of MetS (or alternatively of plasma lipids), HOMA ir , and high-sensitive C-reactive protein. Conclusions: Plasma LCAT activity is elevated in MetS and may be a marker of subclinical atherosclerosis. Our findings do not support the contention that strategies to elevate LCAT are necessarily beneficial for cardioprotection.
Since the primary and higher-order structures of hemocyanin from the crustacean arthropod Panulir... more Since the primary and higher-order structures of hemocyanin from the crustacean arthropod Panulirus interruptus have been elucidated completely, it should be possible to determine which regions of this immunogenic molecule are recognized most often by antibodies. Monoclonal antibodies were raised against subunits a and b of this hemocyanin, and fourteen of them were further characterized. The produced antibodies were of class IgG, subclasses 1 or 2a. Most of them had dissociation constants on the order of magnitude 10(-8)-10(-10), a few had lower affinities. Most clones showed no or negligible cross-reactivity with other crustacean hemocyanins. The reactivity of most other clones diminished with increasing sequence difference between the investigated hemocyanins. However, in a few instances a stronger reactivity with other hemocyanins was observed than with that from Panulirus interruptus. After complete denaturation of the hemocyanin there was no reaction with the monoclonal antibodies, indicating that the latter recognize conformational epitopes. Only one monoclonal antibody reacted with denatured hemocyanin. This antibody was also the only one which reacted with a CNBr digest, which means that it recognizes a sequential epitope. Several antibodies showed a faint reaction on Western blots, indicating the presence of some refolded native structure. Limited proteolysis of the hemocyanin molecule results in the formation of a 18 kDa fragment, representing domain 1, and a 55 kDa fragment representing domains 2 and 3. It was determined on Western blots of the digest on which fragment epitopes for eleven of the monoclonal antibodies were located.
Elevated plasma cholesteryl ester transfer but not cholesteryl ester transfer protein mass predicts incident cardiovascular disease independently of plasma lipids
Decreased circulating levels of free thiols (R-SH, sulfhydryl groups) reflect enhanced oxidative ... more Decreased circulating levels of free thiols (R-SH, sulfhydryl groups) reflect enhanced oxidative stress, which plays an important role in the pathogenesis of cardiometabolic diseases. Since hyperglycemia causes oxidative stress, we questioned whether plasma free thiols are altered in patients with type 2 diabetes mellitus (T2DM) without cardiovascular disease or renal function impairment. We also determined their relationship with elevated triglycerides and very low density lipoproteins (VLDL), a central feature of diabetic dyslipidemia. Fasting plasma free thiols (colorimetric method), lipoproteins, VLDL (nuclear magnetic resonance spectrometry), free fatty acids (FFA), phospholipid transfer protein (PLTP) activity and adiponectin were measured in 79 adult non-smoking T2DM subjects (HbA1c 51 ± 8 mmol/mol, no use of insulin or lipid lowering drugs), and in 89 non-smoking subjects without T2DM. Plasma free thiols were univariately correlated with glucose (r = 0.196, p < 0.05), but...
Background: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol ... more Background: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). Methods: In 75 T2D subjects and 75 nondiabetic subjects, Ac-terAA1 and AAA1 plasma levels were measured by enzyme-linked immunosorbent assay. CEC was measured as [3H]-cholesterol efflux from human cultured fibroblasts to diluted individual subject plasma. Plasma EST and CET were assayed by isotope methods. Results: Ac-terAA1 and AAA1 levels and were similar between T2D and control subjects. Univariate regression analysis (n = 150) demonstrated that Ac-terAA1 levels were inversely correlated with CEC, EST, CET, total cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B, (p < 0.05 to p < 0.01), but not with glucose and HbA1c. In separate multivariable linear ...
Background High density lipoprotein (HDL) cholesterol is not decreased in hypercortisolism despit... more Background High density lipoprotein (HDL) cholesterol is not decreased in hypercortisolism despite high triglycerides, which may be ascribed to effects on the cholesteryl ester transfer protein (CETP) pathway. We explored if CETP mRNA expression is modulated by glucocorticoid treatment in vitro. Effects of doubling the hydrocortisone (HCT) replacement dose on plasma CETP activity, and HDL characteristics were tested in patients with secondary adrenal insufficiency. Materials and methods Human THP-1 macrophages were incubated with corticosterone in vitro in the presence or absence of a liver X receptor (LXR) agonist, followed by determination of CETP mRNA levels by quantitative real-time PCR. In addition, a randomised double-blind cross-over study was performed in 47 patients with secondary adrenal insufficiency (university medical setting; 10 weeks exposure to a higher HCT dose (0Á4-0Á6 mg/kg body weight) vs. 10 weeks of a lower HCT dose (0Á2-0Á3 mg/kg body weight). Results Corticosterone dose dependently decreased CETP mRNA in THP-1 macrophages. Corticosterone also decreased CETP mRNA expression after LXR pretreatment. In patients, CETP activity decreased with doubling of the HCT dose (P = 0Á049), coinciding with an increase in HDL cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio (reflecting HDL size; P < 0Á01 for each). The increase in the HDL cholesterol/ apolipoprotein A-I ratio was correlated with the decrease in plasma CETP activity (r = À0Á442, P = 0Á002). Conclusion Glucocorticoids downregulate CETP gene expression in a human macrophage cell system. In line, a higher glucocorticoid replacement dose decreases plasma CETP activity in patients, thereby contributing to higher HDL cholesterol and an increase in estimated HDL size.
Aim: We assessed the proportion of individuals with T2DM and CVD who attain a LDL-C goal of <2.5 ... more Aim: We assessed the proportion of individuals with T2DM and CVD who attain a LDL-C goal of <2.5 or <1.8 mmol/l and/or a non-HDL-C goal of <3.3 or <2.6 mmol/l, the extent to which triglycerides influence this goal attainment, and their relationship with remnant cholesterol (R-C). Methods: In Hungarian MULTI GAP (Goal Attainment Problem) study data of 5040 statin treated patients following cardio-and cerebrovascular events were analysed. We compared the lipid results and the proportion of the patients reaching target levels of LDL-C, A-C (atherogenic cholesterol ¼ non-HDL-C) depending on fasting triglyceride (TG) levels. Results: In 2674 T2DM patients comparing the groups with TG<1.0 vs. >2.3 mmol/l the mean A-C: 2.77±1.19 vs. 4.37±1.16 mmol/l, HDL-C: 1.44±0.45 vs. 1.23±0.44 mmol/l (p<0.001) and R-C: 0.43±0.09 vs. 1.27±0.13 mmol/l (p<0.001). The success rate of goal achievement for LDL-C was 41.7 % (<2.5 mmol/l) and 26.1 % (<1.8 mmol/l). The achievement rate for 2.5 mmol/l LDL-C target was 99.1 % and that for 1.8 mmol/l 55.1 % in group of patients with A-C <2.6 mmol/l and TG<1.0 mmol/l. In group of patients with LDL-C<1.8 mmol/l and TG<1.0 mmol/l 100 % did attain their A-C targets (<2.6 mmol/l). Among patients attaining the 1.8 mmol/l LDL-C target and TG levels >2.3 mmol/l, we found significantly higher R-C levels (1.61±0.09 vs. 0.38±0.08 mmol/l (TG<1.0)(p<0.001)). Conclusions: Fasting triglyceride <1.0 mmol/l (or non-fasting triglyceride >2.0 mmol/l) levels are very important additional factors in residual risk estimation of high and very high risk patients, particularly in T2DM.
Objectives: Low-normal thyroid function within the euthyroid range may influence plasma lipoprote... more Objectives: Low-normal thyroid function within the euthyroid range may influence plasma lipoprotein levels. Associations between variation in thyroid function and pre-β-high density lipoproteins (pre-β-HDL), i.e. lipid-poor or lipid free HDL particles that act as initial acceptor of cell-derived cholesterol, are unknown. We determined relationships of plasma pre-β-HDL with thyroid function in euthyroid subjects with and without type 2 diabetes mellitus (T2DM). Design and Subjects: TSH, free T4, plasma (apo)lipoproteins, pre-β-HDL, pre-β-HDL formation (pre-β-HDL generation during incubation with lecithin:cholesterol acyltransferase being inhibited) and phospholipid transfer protein (PLTP) activity were measured in fasting plasma from 72 T2DM and 82 non-diabetic subjects. Results: TSH was similar and free T4 was slightly higher (P b 0.05) in T2DM vs. non-diabetic subjects. HDL cholesterol and apoA-I were lower, whereas pre-β-HDL (expressed as % of apoA-I), triglycerides and PLTP activity were higher in T2DM (P b 0.05 to P b 0.001). In T2DM, pre-β-HDL formation (in apoA-I concentration and in % of apoA-I) was positively related to free T4, PLTP activity, total cholesterol and triglycerides (P b 0.05 for each). Multivariable linear regression analyses, adjusted for age, sex, PLTP activity, total cholesterol and triglycerides, demonstrated that pre-β-HDL formation was positively related to free T4 (in apoA-I concentration: β = 0.278, P = 0.014; in % of apoA-I: β = 0.343, P = 0.003) in T2DM, but not in non-diabetic subjects (both P N 0.30; interaction terms: both P b 0.05). Conclusions: Variations in thyroid function within the euthyroid range may influence the metabolism of preβ-HDL in T2DM.
Background Plasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters fro... more Background Plasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters from high density lipoproteins (HDL) towards apolipoprotein B-containing lipoproteins, may promote atherosclerosis development, and is elevated in Type 2 diabetes mellitus (T2DM). We determined the extent to which the relationship of plasma CET with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) subfractions is modified in T2DM. Materials and methods Plasma CET, cholesteryl ester transfer protein (CETP) mass, as well as VLDL and LDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 62 patients with T2DM and 53 nondiabetic subjects. Results Plasma CET and CETP mass were increased in T2DM, coinciding higher triglycerides and large VLDL particles (all P < 0Á02). Plasma CET was positively related to the VLDL and the LDL particle concentration in age-, sex-and diabetes status-adjusted analysis (both P < 0Á001). Multivariable linear regression analysis demonstrated an independent positive interaction between the presence of T2DM and the VLDL concentration on plasma CET (b = 0Á238, P = 0Á033). The relationship of plasma CET with the VLDL concentration was also positively modified by plasma glucose (b = 0Á211, P = 0Á004) and glycated haemoglobin (b = 0Á190, P = 0Á012). Of the individual VLDL subfractions, a positive interaction of diabetes status with large VLDL on plasma CET was observed (b = 0Á280, P = 0Á003). Neither the relationship of the LDL particle concentration nor of CETP mass with plasma CET was modified by the presence of T2DM (P > 0Á15). Conclusion Abnormalities in the concentration and composition of large VLDL particles are likely to contribute to elevated plasma CET in T2DM.
Negatively stained complexes of Panulirus interruptus (spiny lobster) hemocyanin with two differe... more Negatively stained complexes of Panulirus interruptus (spiny lobster) hemocyanin with two different monoclonal antibodies, named E and J, were studied by electron microscopy and image processing. The attachment site of the antibodies to the hexameric hemocyanin molecule was deduced from two perpendicular views of hernocyanidantibody complexes, in which either the threefold axis or one of the twofold axes was oriented perpendicular to the supporting film. Images of complexes in these orientations were searched with reference images simulated from the known X-ray structure of P. interruptus hemocyanin. The two sites were further characterized by combining our results from electron microscopy with structural data obtained by X-ray diffraction and other methods. These two antibodies recognize different non-overlapping epitopes. The epitope for clone E is located on domain 3 at the surface of the p barrel and consists of certain loops, which form connections between /3-strand structures. The epitope for clone J is situated on domain 1 at the surface of an a-helical region and consists mainly of certain a-helices connecting loops. The orientation of the hemocyanin hexamers in the two complexes is very different, as is demonstrated most clearly when they form chains. Clone E forms complexes with the threefold axes perpendicular to the chain direction, while for clone J the threefold axes seem to be parallel to the main direction. The angle between the Fab part of an IgG molecule and the threefold axis of the hexamer is 60 5 5" for clone E and 35 5 7" for clone J. This observation is clearly related to the difference in orientation of the hexamers for the two complexes.
The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in... more The impact of apolipoprotein C-I (apoC-I) deficiency on hepatic lipid metabolism was addressed in mice in the presence or the absence of cholesteryl ester transfer protein (CETP). In addition to the expected moderate reduction in plasma cholesterol levels, apoCIKO mice showed significant increases in the hepatic content of cholesteryl esters (158%) and triglycerides (1118%) and in biliary cholesterol concentration (135%) as compared with wild-type mice. In the presence of CETP, hepatic alterations resulting from apoC-I deficiency were enforced, with up to 58% and 302% increases in hepatic levels of cholesteryl esters and triglycerides in CETPTg/apoCIKO mice versus CETPTg mice, respectively. Biliary levels of cholesterol, phospholipids, and bile acids were increased by 88, 77, and 20%, respectively, whereas total cholesterol, HDL cholesterol, and triglyceride concentrations in plasma were further reduced in CETPTg/apoCIKO mice versus CETPTg mice. Finally, apoC-I deficiency was not associated with altered VLDL production rate. In line with the previously recognized inhibition of lipoprotein clearance by apoC-I, apoC-I deficiency led to decreased plasma lipid concentration, hepatic lipid accumulation, and increased biliary excretion of cholesterol. The effect was even greater when the alternate reverse cholesterol transport pathway via VLDL/LDL was boosted in the presence of CETP.-Gautier, T., U.
The competitive binding of a panel of monoclonal antibodies against hemocyanin of Panulirus inter... more The competitive binding of a panel of monoclonal antibodies against hemocyanin of Panulirus interruptus hemocyanin was investigated with three different methods. A competitive-binding immunoassay method was more successful in the determination of ternary complexes than gel electrophoresis and gel filtration. The latter two methods could only be applied with antibodies possessing a higher affinity. Eleven monoclonal antibodies were assigned to groups on the basis of their interactions with five antigenic regions.
The Journal of Clinical Endocrinology & Metabolism, 2011
Context:Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts incident cardiovascular... more Context:Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density lipoprotein cholesterol and small, dense low-density lipoproteins, is affected by the composition and concentration of apolipoprotein B-containing cholesteryl ester acceptor lipoproteins.Objective:We tested relationships of CET with Lp-PLA2 in subjects with and without metabolic syndrome (MetS).Design and Setting:In 68 subjects with MetS and 74 subjects without MetS, plasma Lp-PLA2 mass, cholesterol esterification (EST), lecithin:cholesterol acyltransferase (LCAT) activity level, CET, CET protein (CETP) mass, and lipoproteins were measured.Results:EST, LCAT activity, CET (P < 0.001 for all), and CETP (P = 0.030) were increased, and Lp-PLA2 was decreased (P = 0.043) in MetS. CET was correla...
Oxygen binding behavior of monomeric subunit a and the hexameric form of this subunit of hemocyan... more Oxygen binding behavior of monomeric subunit a and the hexameric form of this subunit of hemocyanin of Panulirus interruptus is influenced by the binding of various monoclonal antibodies. These antibodies react with other surface parts of the subunit than its second domain in which the oxygen binding site is located. The influence of three monoclonal antibodies and their antigen binding fragments (F a b) has been investigated. Two antibodies increase the oxygen affinity of monomeric hemocyanin from that observed in its low affinity T-state, while the third has little influence on this property. F a i, fragments abolish almost completely the cooperativity of oxygen binding by the hexameric hemocyanin molecule. The two antibodies which increase the oxygen affinity of the monomeric molecule stabilize high-affinity states of the hexameric molecule, while the third stabilizes the low-affinity state.
Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL
European Journal of Clinical Investigation, 2011
Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidat... more Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes mellitus and aimed to identify potential determinants of this parameter. In a cross-sectional study, we investigated 74 patients with type 2 diabetes and 75 control subjects. Antioxidative properties of HDL were measured and expressed as either (i) HDL antioxidative capacity or (ii) HDL antioxidation index after multiplying HDL antioxidative capacity results with individual plasma HDL cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) and paraoxonase-1 (PON-1) activities were determined. HDL antioxidative capacity was similar in patients with diabetes and controls, while the HDL antioxidation index was decreased in patients with diabetes (P = 0.005) owing to lower plasma HDL cholesterol (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). LCAT activity was higher and PON-1 activity lower in type 2 diabetes mellitus (each P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In the combined subjects, HDL antioxidative capacity was inversely related to LCAT activity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The HDL antioxidation index correlated negatively with blood glucose (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), HbA1c and LCAT activity (each P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), and positively with PON-1 activity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Multiple linear regression analysis demonstrated that high LCAT activity was associated with both decreased HDL antioxidation capacity (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and index (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) independent of diabetes status, glycaemic control and PON-1. Overall, the antioxidative functionality of HDL is impaired in type 2 diabetes mellitus mostly because of lower HDL cholesterol. Hyperglycaemia, increased LCAT activity and lower PON-1 activity likely contribute to impaired antioxidative functionality of HDL.
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