Predictability of low-density lipoprotein levels during apheretic treatment of hypercholesterolemia

The efficiency and efficacy of low-density lipoprotein (LDL) apheresis performed with a dextran sulphate cellulose (DSC) regenerating unit were tested in five familial hypercholesterolaemic patients. LDL apheresis was repeated four times at both bi-weekly and weekly intervals, processing one plasma volume each time. The efficiency of the procedure (i.e., the extent of lipoprotein removal) was nearly identical with both schedules. Efficacy parameters, i.e., decreases of plasma total and LDL cholesterol (TC and LDL-C) and apo B, were highly correlated (r greater than 0.96) with preapheresis levels, allowing an accurate prediction of the absolute lipid removal in the single individual. Plasma triglycerides, high-density lipoprotein cholesterol, apo A-I and apo A-II recovered rather rapidly, reaching 91-96% of the pre-apheresis values in 48 hours; the recovery of TC, LDL-C and apo B was much slower, with a relatively rapid early phase (80% recovery after about 7 days) followed by a successive slower rise. This pattern was highly reproducible in the single patient, allowing the definition of a simple mathematical model for an accurate (error less than 20%) prediction of the individual process. Based on this model one can design the treatment schedule necessary to maintain lipid levels within the desired range in the single individual. The hypolipidaemic efficacy of DSC apheresis appears, otherwise, not to be dependent upon the procedure per se, but on other individual factors, e.g. the amount of removable lipoproteins and the rate of lipid recovery; both can be predicted with sufficient accuracy.     

Effects of Three Treatment Modes on Plasma Lipids and Lipoproteins in Uraemic Patients

Plasma lipids, chemical composition of various lipoprotein fractions, apolipoprotein B concentrations and apolipoprotein E phenotypes were studied in 12 uraemic patients on conservative treatment (CT), in 16 patients on haemodialysis (HD) and in 18 patients on continuous ambulatory peritoneal dialysis treatment (CAPD). Plasma total cholesterol and triglyceride concentrations were increased in the CAPD patients in comparison to the HD patients and the control subjects. Moreover, the CAPD patients had higher LDL cholesterol concentration than the CT and HD patients. The HDL cholesterol concentration was lower in the HD and CAPD patients than in the control subjects. The chemical composition of lipoproteins in all fractions of the CT and HD patients and in VLDL, IDL and LDL fractions of the CAPD patients differed from those of the control subjects. The main differences were the increased proportion of triglycerides in VLDL and LDL fractions of all the patient groups and in HDL fraction of the CT and HD patients in comparison to the control subjects. Moreover, the proportion of cholesterol was increased in VLDL and IDL fractions of the CT and the CAPD patients and decreased in HDL fraction of the CT and HD patients compared to the control subjects. In conclusion, in addition to the alterations in the lipoprotein concentrations in uraemic patients there are also marked changes in the chemical composition of the lipoprotein particles that may further contribute to the accelerated atherosclerosis among uraemic patients. The abnormalities are particularly prevalent in CAPD patients.     

Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus

Background: Patients with diabetes mellitus have been reported to show increased serum levels of modified low-density lipoprotein (LDL), including glycosylated, oxidized and small, dense LDL. This change has been suggested to represent an important risk factor for diabetic macroangiopathy. A common characteristic shared by these modified LDL species is the increase in electronegative charge on particle surfaces, which can be detected by agarose gel electrophoresis as “LDL charge modified frequency” (LDL-CMF) determined from the relative mobility of LDL fraction. Methods: LDL-CMF was measured in the sera from 129 outpatients with type 2 diabetes mellitus and compared with the data from 34 normal subjects. Results: The LDL fraction from diabetics migrates more closely to the anode side as compared with that from normal subjects. The LDL-CMF measured in diabetics, 5.5±8.1%, was significantly (p<0.0001) higher than 0.6±3.4% in normal subjects. Serum LDL-CMF showed significant positive correlations with triglyceride at r=0.552 (p<0.0001) and malondialdehyde modified LDL at r=0.390 (p<0.0001), as well as systolic blood pressure, body mass index, fasting plasma glucose, hemoglobin A_1c, total cholesterol, free fatty acid (FFA) and homeostasis model assessment ratio. It showed negative correlations with high-density lipoprotein and total superoxide dismutase activity. Conclusion: The results indicate that LDL-CMF reflects the degree of serum LDL modification in diabetics and can be regarded as an important risk factor for diabetic macroangiopathy.     

2型糖尿病患者血清小而密低密度脂蛋白胆固醇水平与脂类代谢异常及胰岛素抵抗的关系

目的探讨2型糖尿病患者血清小而密低密度脂蛋白胆固醇（sdLDL-C）水平与脂类代谢异常及胰岛素抵抗的关系。方法 193例2型糖尿病患者按胰岛素抵抗情况分为胰岛素抵抗组144例与非胰岛素抵抗组49例。采用奥林巴斯AU2700全自动生化仪检测血清小而密低密度脂蛋白（sdLDL-C）、三酰甘油（TG）、总胆固醇（TC）、空腹血糖（FBG）等,采用化学发光法检测空腹胰岛素（FIN）、C肽,并计算胰岛素抵抗指数（HOMA-IR）等。结果 2型糖尿病患者中,与非胰岛素抵抗组相比,胰岛素抵抗组TG、TG/高密度脂蛋白（HDL）、TC/HDL、sdLDL-C水平显著升高（P〈0.05）,而HDL、载脂蛋白A（apo AⅠ）、脂蛋白（Lpa）水平显著降低（P〈0.05）;对2型糖尿病患者sdLDL-C、胰岛素抵抗指数进行多元逐步回归分析,sdLDL-C与TG（Log）、LDL-C/HDLC及TG/HDL-C（Log）呈正相比关性（r=0.638、0.601、0.290,P〈0.01）,与TG/HDL（Log）和LDL-C/apoB呈负相关关系（r=-0.589、-0.342,P〈0.01）;HOMA-IR与TG/HDL和sdLDL-C呈正相关关系（r=0.281、0.250,P〈0.01）,而与TC呈负相关（r=-0.233,P〈0.01）。结论 SdLDL-C能较好地反映2型糖尿病患者胰岛素抵抗对脂类代谢的影响,TG/HDL-C、LDL-C/HDL-C等提供的重要临床信息应在以后的临床应用中得到进一步认识和重视。     

Hepatic and extrahepatic triglyceride lipase activity in uraemic patients on chronic haemodialysis

Abstract. In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group.
The uraemic subjects showed a moderate hypertri-glyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019g/ml (LDL₁) The concentration of low density lipoproteins of the density between 1.019 and 1.063g/ml (LDL₂) was decreased. LDL₂ were relatively rich in triglycerides when compared with LDL₂ from the control group.     

Hepatic and extrahepatic triglyceride lipase activity in uraemic patients on chronic haemodialysis.

In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group. The uraemic subjects showed a moderate hypetriglyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019 g/ml (LDL1). The concentration of low density lipoproteins of the density between 1.019 and 1.063 g/ml (LDL2) was decreased. LDL2 were relatively rich in triglycerides when compared with LDL2 from the control group.     

Oxidized low-density lipoprotein and atherosclerosis

Atherosclerosis is the leading cause of morbidity and mortality in western society. The most important risk factors for atherosclerosis include smoking, hypertension, dyslipidemia, diabetes and a family history of premature atherosclerosis. Several studies indicate that an increased plasma low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerosis. Many data support a proatherogenic role for oxidized LDL and its in vivo existence. The oxidative susceptibility of LDL is increased with established cardiovascular risk factors, such as diabetes, smoking and dyslipidemia. Supplementation with antioxidants such as ascorbate and alpha-tocopherol can decrease LDL oxidation as well as cardiovascular mortality and thus shows promise in the prevention of atherosclerosis.     

不同血液净化方法对Leptin的清除比较

目的 :探讨不同血液净化方法对血 L eptin的清除效果。方法 :选 31例因慢性肾衰竭而进行维持性血液透析的患者进行研究。于 31例患者单次普通血液透析前后 ,其中 1 2例于单次血液透析滤过前后、8例于单次血液吸附治疗前后分别采静脉血 ,采用放射免疫分析法测定血清 L eptin水平。结果 :慢性肾衰竭血液透析患者常规透析前后血 L eptin水平无显著差异〔(1 1 .82 0± 5 .5 0 7) μg/ L 比 (1 2 .2 5 5± 5 .1 72 ) μg/ L,P>0 .0 5〕。单次血液透析滤过和血液吸附治疗可分别降低血 L eptin(2 9.0 7± 8.5 6 ) %和 (4 0 .2 9± 8.33) % ,两种治疗方法清除效果比较有显著性差异 (P=0 .0 0 1 )。结论 :常规血液透析对慢性肾衰竭血液透析患者体内高 L eptin血症无影响 ;单次血液透析滤过和血液吸附治疗均可降低血 L eptin水平 ;血液吸附治疗对血 L eptin的清除效果优于血液透析滤过治疗。     

Impact of postprandial lipaemia on low-density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease

BACKGROUND: Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD). MATERIALS AND METHODS: Eighty men and 27 women with clinically suspected CAD underwent quantitative coronary angiography (QCA). TRLs were isolated by density gradient ultracentrifugation before and 6 h after an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by ELISA, and LDL size by gradient gel electrophoresis. RESULTS: Triglycerides, apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units (Sf) > 400 and in Sf 12-400 fractions were markedly increased at 6 h. Postprandial cholesterol content of RLPs (RLP-C) correlated with respective triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf > 400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r = -0.459 and r = -0.442, respectively). (P < 0.001 for all). OxLDL was elevated postprandially (P < 0.001). In multivariate analysis, oxLDL was a determinant of severity and extent of CAD. CONCLUSION: Postprandial state is associated with oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and is associated with coronary atherosclerosis.     

Anti-oxidized low-density lipoprotein antibody levels are associated with the development of type 2 diabetes mellitus

Background  Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM).
Materials and methods  We selected 391 non-diabetic women aged 18–65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile.
Results  Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65·1% were still OGTT-N after 6 years versus 79·5% of those who had anti-oxidized LDL antibody levels above the 50th percentile ( P  = 0·015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9·79 (95% confidence interval, 1·40–68·45) of developing diabetes ( P  < 0·001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index ( P  < 0·001) and the levels of anti-oxidized LDL antibodies ( P  = 0·042).
Conclusions  Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women.     

Decreased in vitro oxidizability of low-density lipoprotein in hypercholesterolaemic patients treated with 3-hydroxy-3-methyIgIutaryl-CoA reductase inhibitors

Abstract. We studied the effects of the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors simvastatin and pravastatin on the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation. Twenty-three hypercholesterolaemic patients (mean serum cholesterol 9.7 mmol 1^-1) were treated with increasing doses of either simvastatin or pravastatin for 18 weeks. No significant differences in effect on lipid levels between the two drugs were found. Treatment resulted in lowering of total cholesterol and LDL-cholesterol by maximally 30% and 34%, respectively. Chemical composition analysis showed that LDL particles contained relatively more protein and less free cholesterol and cholesteryl-ester after treatment. The LDL cholesterol/protein ratio decreased from 1.24 ± 0.21 to 0.97 ± 0.23 ( n = 20). By continuous monitoring of in vitro oxidation it appeared that LDL was less susceptible to oxidation after drug treatment. Maximal rate of diene production was significantly decreased from 19.7 ± 3.1 to 18.5 ± 3.3 nmol min^-1 mg^-1 LDL; total diene production decreased significantly from 420.3 ± 67.6 to 380.5 ± 49.1 nmol mg-¹ LDL; the lag time was unchanged throughout the study. These studies show that HMG-CoA reductase inhibitors reduce the oxidizability of LDL by altering its composition.     

Direct adsorption of low-density lipoprotein and lipoprotein(a) from whole blood: results of the first clinical long-term multicenter study using DALI apheresis

Direct adsorption of lipoproteins (DALI) is the first low-density lipoprotein (LDL)-apheresis technique by which atherogenic LDL and lipoprotein(a) (Lp(a)) can be selectively removed from whole blood without plasma separation. The present study was performed to evaluate the efficacy, selectivity and safety of long-term DALI apheresis. Sixty-three hypercholesterolemic coronary patients were treated by weekly DALI sessions. Initial LDL-cholesterol (C) plasma levels averaged 238 +/- 87 mg/dl (range 130-681 mg/dl). On average, 34 sessions (1-45) were performed processing 1.5 patient blood volumes. The primary aim was to acutely reduce LDL-C by >or=60% per session. To this end, three different adsorber sizes could be employed, i.e., DALI 500, 750, and 1000, which were used in 4, 73, and 23% of the 2156 sessions, respectively. On average, 7387 ml of blood were processed in 116 min per session. This resulted in the following mean acute changes: LDL-C 198 --> 63 mg/dl (-69%), Lp(a) 86 --> 32 mg/dl (-64%), triglycerides 185 --> 136 mg/dl (-27%). HDL-C (-11%) and fibrinogen (-15%) were not significantly influenced. The mean long-term reduction of LDL-C was 42% compared to baseline while HDL-C slightly increased in the long run (+4%). The selectivity of LDL removal was good as recoveries of albumin, immunoglobulins, and other proteins exceeded 85%. Ninety-five percent of 2156 sessions were completely uneventful. The most frequent adverse effects were hypotension (1.2% of sessions) and paresthesia (1.1%), which were probably due to citrate anticoagulation. Access problems had to be overcome in 1.5%, adsorber and hardware problems in 0.5% of the sessions. In this multicenter long-term study, DALI apheresis proved to be an efficient, safe, and easy procedure for extracorporeal LDL and Lp(a) elimination.     

血清脂蛋白（a）水平及其对低密度脂蛋白测定值的影响

为了解国人血清脂蛋白（ａ）分布情况，调查了１０３２名５０岁以上干部的血清脂蛋白（ａ）［Ｌｐ（ａ）］水平，着重观察Ｌｐ（ａ）对低密度脂蛋白胆固醇（ＬＤＬ－Ｃ）测定值的影响。由于目前所用ＬＤＬ－Ｃ测定法的结果都包含Ｌｐ（ａ）胆固醇［Ｌｐ（ａ）－Ｃ］在内，故以测定值减去０．３Ｌｐ（ａ）作为ＬＤＬ－Ｃ校正值。本组Ｌｐ（ａ）的平均值为１７４ｍｇ／Ｌ，中位数１０５ｍｇ／Ｌ，，实测范围１０～１２００ｍｇ／Ｌ，呈明显正偏态分布。Ｌｐ（ａ）－Ｃ平均占ＬＤＬ－Ｃ实测值的４．３３％，校正后ＬＤＬ－Ｃ平均下降０．１３ｍｍｏｌ／Ｌ，Ｌｐ（ａ）＞３００ｍｇ／Ｌ时半数标本Ｌｐ（ａ）－Ｃ占ＬＤＬ－Ｃ的１０％以上，在ＬＤＬ－Ｃ较低而Ｌｐ（ａ）较高时对ＬＤＬ－Ｃ的影响更大，此时Ｌｐ（ａ）－Ｃ可占ＬＤＬ－Ｃ的２０％～３０％。单因素相关分析示Ｌｐ（ａ）与校正后ＬＤＬ－Ｃ之间无明显相关，因为两者都是冠心病的重要危险因素，比较这两项指标对评价冠心病危险的贡献大小时，最好对ＬＤＬ－Ｃ值进行校正。     

Concentrations of apolipoproteins B, C-I, C-II, C-III and E in sera from normal men and their relation to serum lipoprotein levels

The concentrations of apolipoproteins B, C-I, C-II, C-III and E (by enzyme immunoassay), and cholesterol, triglycerides and phospholipids both in while serum and in serum very low (VLDL), low (LDL) and high (HDL) density lipoproteins, HDL2 and HDL3, were determined in sera from 29 randomly selected normolipidemic men, age 40-60 years, in Stockholm, Mean values, +/- SD, were for, apolipoprotein B, 720 +/- 162; C-I, 63 +/- 14; C-II, 27 +/- 11; C-III, 125 +/- 57; and for E, 25 +/- 6 mg/l. A skewness to the right of the distributions was found for apolipoproteins B and C-II and for serum triglycerides and VLDL lipids. The relations between the different variables were studied by linear correlation analysis. Several significant correlations existed between the lipoprotein levels. Apolipoprotein C-I, C-II and C-III were significantly correlated with each other, whereas neither apolipoprotein B nor apolipoprotein E was correlated with any other apolipoprotein. The following significant, positive correlations existed between the apolipoproteins and total serum lipids and/or lipids of lipoprotein density classes: apolipoprotein B with serum cholesterol and LDL lipids, apolipoprotein C-I with HDL3 cholesterol, apolipoprotein C-II with serum triglycerides and VLDL lipids, apolipoprotein C-III with serum cholesterol and phospholipids. Apolipoprotein E showed no correlation with either serum lipids or lipoproteins.     

Detection of electronegative low density lipoprotein (LDL-) in plasma and atherosclerotic lesions by monoclonal antibody-based immunoassays

OBJECTIVES: To produce a monoclonal antibody (MAb) against electronegative LDL (LDL-) for detecting this modified lipoprotein in blood plasma and tissues. DESIGN AND METHODS: LDL- was isolated from human blood plasma and used as an antigen for immunization of Balb/c mice. Lymphocytes of immunized mice were fused with myeloma cells (SP2/0) to obtain the hybridomas. LDL- was detected in blood plasma and atherosclerotic lesions of humans and rabbits by MAb-based ELISA and immunohistochemistry, respectively. RESULTS: LDL- concentrations were higher (P < 0.05) in the blood plasma of hypercholesterolemic subjects (HC, 248 +/- 77 mg/dL of total cholesterol) than in normolipidemic subjects (NL, 173 +/- 82 mg/dL of total cholesterol) and rabbits (HC, 250 +/- 15 mg/dL of cholesterol versus NL, 81 +/- 12 mg/dL of cholesterol). Moreover, LDL- was detected in the atherosclerotic lesions of humans and rabbits. CONCLUSION: These MAb-based immunoassays are adequate to detect LDL- in biological samples and represent an important tool for investigating the role of LDL- in atherosclerosis.     

Metabolic clearance rate of immunoreactive vasopressin in man

Abstract. Metabolic clearance of synthetic arginine vasopressin (AVP) has been measured in sixteen healthy subjects and ten uraemic patients on maintenance haemodialysis. Plasma AVP was measured using a specific radioimmunoassay at different intervals after a single injection of 2 μg AVP. The theoretical curve which fitted best with the disappearance curve was the sum of two exponentials in twenty-two subjects and of three exponentials in the other four. Metabolic clearance rate and the volume of fast initial distribution were 287·1 ml min^-1 (m²)^-1 and 219·3 ml/kg b.w., respectively, in normal subjects. Metabolic clearance rate was considerably lower in the uraemic group. This emphasizes the role of kidneys in the degradation of AVP and may account, at least in part, for the higher basal plasma value of this hormone observed in uraemic patients.     

Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency

Abstract. We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinae-mic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the poly-disperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)-like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 gmL^-1) from the CETP-deficient patients contained HDLc-like particles, these particles were removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with ¹²⁵I-labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of ¹²⁵I-labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE. This modulation of LDL by CETP may enhance the affinity of LDL for LDL receptors to deliver cholesterol to peripheral tissues.     

Effect of insulin treatment on serum lipoprotein(a) in non-insulin-dependent diabetes

Abstract. In order to evaluate whether Lp(a), a lipoprotein that is potentially thrombogenic and atherogenic, is a potential risk factor for CAD in non-insulin-dependent diabetes (NIDDM), we compared the Lp(a) and its distribution in 145 NIDDM patients with that in 94 healthy control subjects. Furthermore, we studied the effect of insulin treatment on serum Lp(a) in 108 patients with NIDDM. Male and female NIDDM patients had similar Lp(a) concentrations to healthy controls (median value 167 mg L^-1, range 15–1550 mg L^-1 vs. 157 mg L^-1, range 15–919 mg L^-1, NS and 92, range 15–1190 mg L^-1 vs. 103 mg L^-1, range 15–842 mg L^-1, NS). Also, the cumulative distribution of Lp(a) did not differ between the NIDDM patients and healthy subjects. Insulin treatment increased Lp(a) in diabetics with a Lp(a) concentration of less than 300 mg ^-1L, but this effect was not related to the concomitant improvement in metabolic control (mean change (±SEM) of HbA_1c from 9.80±0.15 to 8.00±0.12; P < 0.001). In subjects with elevated Lp(a) concentrations (>300 mg L^-1) the Lp(a) concentration was unaffected by insulin, despite a similar improvement in glycaemic control. These results suggest that insulin may modulate the concentration of Lp(a).     

Lipid peroxidation and susceptibility of low-density lipoprotein to in vitro oxidation in hyperhomocysteinaemia

Abstract. The pathobiochemical mechanism of arteriosclerosis in hyperhomocysteinaemia has not yet been elucidated. In vitro studies have shown that the cytotoxic properties of homocysteine can be ascribed to its generation of reactive oxygen species. We studied lipid peroxidation, both in vivo and in vitro , in 10 homozygous cystathionine synthase-deficient (CSD) patients and in a control group of 10 healthy subjects of comparable age and sex. The susceptibility of low-density lipoprotein (LDL) from hyperhomo-cysteinaemic patients to oxidation was determined in vitro by continuously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed as total diene production) of LDL from CSD patients were not significantly different from those of LDL from controls. Furthermore, the time needed to reach maximal diene production, i.e. t(max), was similar for LDL from patients and controls. In addition, the vitamin E concentrations in LDL of CSD patients and controls were similar. The mean concentration (± SD) of plasma thiobarbituric acid reactive substances (TBARS), an indicator of in vivo lipid peroxidation, was 2.2 ± 0.7 μmol L^-1 in CSD patients, a lower value than that measured in the matched controls (50± 2.0 μmol L^-1). Investigation of in vivo and in vitro parameters of lipid peroxidation shows that the increased risk of arteriosclerosis in hyperhomocysteinaemia is unlikely to be due to increased lipid peroxidation.