Glycosylation of low density lipoprotein in patients with Type I (insulin-dependent) diabetes: Correlations with other parameters of glycaemic control

Summary Glycosylation of low density lipoproteins obtained from 16 patients with Type 1 (insulin-dependent) diabetes and from 16 age-, sex-, and race-matched controls, was determined. The diabetic patients were normolipaemic and were in good or fair glycaemic control. Eleven patients performed home blood glucose monitoring. Glycosylation of low density lipoproteins in the diabetic patients was significantly higher (p < 0.001) than in the control subjects, and was significantly correlated with haemoglobin A_1c, (p < 0.01), glycosylation of plasma proteins, (p < 0.001), and mean home blood glucose, (p < 0.01). This study confirms that, in diabetic patients, increased glycosylation of low density lipoprotein occurs to an extent which correlates closely with other commonly used indices of glycaemic control.     

The distribution profiles of very low density and low density lipoproteins in poorly-controlled male,Type 2 (non-insulin-dependent) diabetic patients

Summary The distribution and composition of lipoproteins spanning the very low density and low density lipoprotein spectra have been analysed in ten poorly-controlled, male, Type 2 (non-insulin-dependent), diabetic patients pre-disposed to mild, secondary hypertriglyceridaemia. As compared to age-matched control subjects, the diabetic patients displayed grossly modified, distinctly atherogenic lipoprotein profiles. Modifications were not limited to the very low density lipoprotein profile, as would be expected from the pre-treatment hypertriglyceridaemia. There was also an aberrant low density lipoprotein profile, which was not evident from plasma cholesterol measurements, especially as the diabetic patients at entry were well matched to control subjects with respect to plasma levels of this lipid. Compositional abnormalities were also observed in the poorly-controlled diabetic group, although these were less marked than the distributional changes. There were substantial improvements of the abnormalities detailed above, even over a short treatment period (two weeks), with therapy designed primarily to ameliorate metabolic control. The data suggest that, in the presence of poor metabolic control and hypertriglyceridaemia, occult, atherogenic modifications of low density lipoproteins can occur. The results argue in favour of strict control of triglyceride levels even in diabetic patients with apparently acceptable cholesterol levels.     

糖化和糖氧化低密度脂蛋白与糖尿病合并颈动脉粥样硬化的关系

目的　观察糖化低密度脂蛋白 (Gly LDL)和糖氧化低密度脂蛋白 (Gly ox LDL)与非胰岛素依赖型糖尿病(NIDDM)合并颈动脉粥样硬化 (AS)的关系。方法　Gly LDL采用微柱亲和层析法。Gly ox LDL采用微柱亲和层析加荧光分光光度法观察。NIDDM合并颈AS者 (病例 1组 ) 30例 ,无糖尿病的颈AS者 (病例 2组 ) 4 8例。对照组 32例。结果　两病例亚组Gly LDL和Gly ox LDL含量显著高于对照组 (P均 <0 .0 5 )。病例 1组Gly LDL和Gly ox LDL含量显著高于病例 2组 (P <0 .0 5 )。结论　Gly LDL和Gly ox LDL在颈AS中起重要作用 ,尤其在糖尿病病人颈AS形成中起重要作用。     

Serum lipids and apoprotein composition (%) of the very low density lipoprotein (VLDL) fraction in two groups of diabetic patients: Effects of oral as compared to insulin therapy

Summary Forty-one diabetic patients (21 males and 20 females) were divided into two groups according to treatment. One group (n=22) was treated with insulin and the other with oral therapy (tolbutamide) (n=19). The two groups of patients were in a good metabolic control in that the glucose loss in the urine was less than 10 g/24 h. In these two groups we have evaluated total serum cholesterol (TC), triglycerides (TG), VLDL TC/TG ratio and prevalence of ‘double pre-beta lipoproteinemia’. For these parameters no significant differences have been found between the two groups. The results of our study suggest that, provided metabolic control is good, the VLDL metabolism does not seem to be affected by the type of treatment.     

高血压病人颈动脉重构与脂蛋白(a)、氧化型低密度脂蛋白关系的探讨

目的 探讨高血压病人血清中氧化型低密度脂蛋白(ox-LDL)、脂蛋白(a)(Lp(a))的变化及其与高血压病人颈动脉重构的相互关系。方法 选取原发性高血压病人43例,健康自愿者40例作为观察对象。应用二维超声测定颈动脉结构与功能改变,应用酶联免疫吸附法测定ox-LDL及LP(a)。结果 原发性高血压组Lp(a)及ox-LDL较正常对照组显著升高(P<0.05)。直线相关分析显示,Lp(a)与原发性高血压组颈动脉内膜-中层厚度(IMT)呈正相关(r=0.204,P<0.01),与颈动脉扩张性(CD)无关。ox-LDL与原发性高血压组颈动脉IMT呈正相关(r=0.389,P<0.01),与CD呈负相关(r=-0.386,P<0.05)。结论 高血压病人血清中氧化型低密度脂蛋白及脂蛋白(a)水平较健康人增加。氧化型低密度脂蛋白与高血压病人颈动脉结构及功能改变相关,而脂蛋白(a)仅与颈动脉结构改变有关,可能与颈动脉功能改变无关。     

Are the binding and degradation of low density lipoprotein altered in type 2 (non-insulin-dependent) diabetes mellitus?

Summary Studies in vitro have shown that glycosylation of low density lipoprotein (LDL) will decrease its ability to bind to its receptor. We have evaluated the possibility that such an event might occur in vivo in diabetes by comparing the binding and degradation by normal fibroblasts and mouse peritoneal macrophages of LDL obtained from normal control subjects and patients with Type 2 (non-insulin-dependent) diabetes mellitus. When compared with control subjects, Type 2 diabetic patients had elevated fasting glucose (increased by 160%), haemoglobin A_1c (increased by 75%), triglyceride (increased by 550%), and cholesterol (increased by 48%) levels. LDL from Type 2 diabetic patients displayed populations of particles with more heterogeneous hydrated densities than LDL from control subjects, with enrichment in the triglyceride content of the lighter population. ¹²⁵I-LDL from normal and Type 2 diabetic subjects bound to fibroblasts with similar binding affinities and binding capacities. The kinetics of degradation of LDL from normal and Type 2 diabetic subjects by fibroblasts were also similar. Furthermore, all populations of LDL particles from Type 2 diabetic patients were bound and degraded by normal fibroblasts in identical fashions. In addition, ¹²⁵I-LDL from normal and Type 2 diabetic subjects were not bound or degraded by mouse peritoneal macrophages. It is concluded that the LDL of patients with Type 2 diabetes with moderate hyperglycaemia are not modified sufficiently to alter their normal binding and degradation by human fibroblasts or to cause their uptake by mouse peritoneal macrophages.     

Metabolism by human endothelial cells of very low density lipoprotein subfractions isolated from Type 1 (insulin-dependent) diabetic patients

Summary The very low density lipoprotein (VLDL) fraction was isolated from 11 normolipidaemic Type 1 (insulin-dependent) diabetic patients in good to fair glycaemic control and from 11 age-, sex- and race-matched, non-diabetic, control subjects. The rate of receptor-mediated degradation by human endothelial cells was significantly greater (p<0.02) for the total VLDL fraction isolated from diabetic patients compared to control subjects and averaged 1008±300 and 717±150 ng·mg cell protein^–1·16 h^–1, respectively. The total VLDL fraction was separated into three subfractions: VLDL-I, S_f 100–400 (S_f = Svedberg units); VLDL-II, S_f 60–100; VLDL-III, S_f20–60. Rates of receptor-mediated degradation of VLDL-I and VLDL-II isolated from diabetic patients were significantly greater than the comparable subfraction isolated from control subjects and averaged 1023±279 vs 361±122 (p<0.01) and 433±70 vs 294±70 ng·mg cell protein^–1·16 h^–1 (p<0.03), respectively. Rates of receptor-mediated degradation of the V-III subfraction isolated from the two groups did not differ significantly. There were no significant differences in the chemical composition or in the plasma concentrations of the VLDL subfractions isolated from diabetic patients compared to control subjects. There was a significant increase in the apoprotein E content of VLDL-I (p<0.01) and VLDL-II (p<0.05) isolated from diabetic patients. There was a significant increase in the ratio of apoprotein C compared to apoprotein E (p<0.03) in VLDL-I isolated from control subjects compared to the diabetic patients. There were no significant differences in the apoprotein composition of VLDL-III isolated from the two groups.     

冠心病患者血清铜蓝蛋白与血浆氧化低密度脂蛋白水平的测？…

目的：探讨冠心病患血清铜蓝蛋白与血浆氧化低密度脂蛋白水平之间的关系。方法：测定６０例冠心病患及３６例正常人血浆氧化低密度脂蛋白（ＯＸ－ＬＤＬ）和血清铜蓝蛋白（ＣＰ）水平,并与ＯＸ－ＬＤＬ进行直线相关分析。结果：冠心病组血浆ＯＸ－ＬＤＬ及血清铜蓝蛋白水平显高于正常对照组,直线相关分析表明血清铜蓝蛋白与ＯＸ－ＬＤＬ水平呈显正相关。结论：作为铜的载体,铜蓝蛋白可能促进体内ＯＸ－ＬＤＬ的形成。     

绝经后妇女尿脱氧吡啶酚和骨密度的关系

目的探讨绝经后妇女尿脱氧吡啶酚（Ｄ－Ｐｙｒ）的变化及其与骨密度（ＢＭＤ）的关系。方法４０例绝经早期健康妇女平均年龄５０．９５±２．８６岁，平均绝经年限１．８３±０．９７年，３９例老年妇女平均年龄７０．６４±４．１２岁，平均绝经年限２２．５２±６．３４年。留取空腹第二次晨尿１０ｍｌ，采用酶免法测定尿脱氧吡啶酚，批内、批间差异分别为１０％、１５％。采用双能量Ｘ线骨密度仪测定腰椎２～４（Ｌ２～Ｌ４）和左髋骨ＢＭＤ。结果老年组ＢＭＤ明显低于绝经早期组，２组妇女尿Ｄ－Ｐｙｒ水平均增高，且绝经早期组高于老年组，尿Ｄ－Ｐｙｒ与腰椎ＢＭＤ呈负相关，表明２组妇女骨吸收均增加，绝经早期妇女更明显。结论老年人骨量大量丢失，脊柱部位骨吸收活跃，脊柱ＢＭＤ评价骨丢失优于股骨。     

Extending the limits of transcatheter closure of atrial septal defects with the double umbrella device (CardioSEAL)

Objective—To report initial findings from a selected group of patients with morphological variations of the atrial septal defect who underwent transcatheter closure with a second generation redesigned double umbrella device.
Patients—Two patients with abnormal location of the oval fossa and partial deficiency of the septal rim, three patients with multiple defects, and two patients with a multiperforated aneurysm of the interatrial septum (age range, 3.6-25.5 years).
Methods—Defects were closed with the double umbrella device (CardioSEAL) consisting of two sets of flexible arms (with central and two mid-arm hinges) covered with sewn Dacron patches. The implantation procedure was monitored by transoesophageal echocardiography.
Results—The diameter of the defect measured during transoesophageal echocardiography ranged from 7-18 mm and the balloon stretched diameter ranged from 13-21 mm. The size of the devices varied from 28-33 mm and the ratio of device size to defect size varied from 1.6-2.1. Two devices (23 and 28 mm) were chosen in a patient with two separated defects. No complications or serious arrhythmias were observed during implantation or follow up (median, 1.8 months). Residual shunting was trivial in three patients and mild in one patient (inferiorly located additional defect).
Conclusions—To extend the selection critera of an isolated central interatrial defect for transcatheter closure, some modifications of the implantation technique are needed. Using the redesigned double umbrella device, effective closure in patients with multiple or irregularly shaped atrial septal defects was achieved, indicating a broadening of the spectrum of transcatheter closure.

Keywords: atrial septal defects;  transcatheter closure;  congenital heart disorders;  double umbrella device;  CardioSEAL     

Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins

Summary We have investigated whether and how the elevated glucose concentrations characteristic of diabetes may alter the interaction of endothelial cells with low-density lipoproteins (LDL). Protracted exposure of cultured human endothelial cells to 20 mmol/l glucose failed to affect either the relationship between the degree of confluency of the monolayer and the extent of LDL degradation or the dose-responses for LDL uptake and degradation. In contrast, non-enzymatic glycosylation of LDL by pre-incubation of LDL with glucose markedly inhibited their uptake and degradation by endothelial cells. Thus, at protein concentration of 5 g/ml, the amount of glycosylated ¹²⁵I-LDL associated with cells was decreased fourfold compared with native ¹²⁵I-LDL (47±3 versus 194±10 ng·mg cell protein^-1·24 h^-1, mean±SEM), and degradation was decreased twenty-fold (135±4 versus 2873±115 ng·mg cell protein^-1·24 h^-1). The degree of inhibition was proportional to the extent of glycosylation. At all concentrations studied, methylated LDL behaved similarly to glycosylated LDL. The decreased recognition of glycosylated LDL by the endothelial lining of small and large blood vessels may have an impact on tissue physiology and on the overall fate of the glycosylated molecules.     

Specific and global coagulation tests in patients with mild haemophilia A with a double mutation (Glu113Asp,Arg593Cys)

Background

Heterogeneous bleeding phenotypes are observed in haemophilia A patients with the same mutation in the F8 gene. Specific mutations in the A2 domain of factor VIII are associated with mild haemophilia and a higher risk of inhibitor development. Double mutations in mild haemophilia A are rarely reported. In this study, we investigated the in vitro function of factor VIII, performing different specific and global coagulation assays, observed clinical characteristics and assessed the possible predictive diagnostic value of the differences.

Materials and methods

The clinical features of haemophiliacs with a mild phenotype were reviewed. Blood samples were obtained and analysed for mutations and coagulation assays: activated partial thromboplastin time, one-stage and chromogenic factor VIII activity, factor VIII antigen and rotational thromboelastometry.

Results

We report on a cohort of 22 patients with double Glu113Asp, Arg593Cys mutations. All our patients have a quantitative defect of factor VIII and preserved similar functional activity. Factor VIII activities measured by the one-stage or chromogenic method were not discrepant, although the chromogenic assay resulted in 20% lower factor VIII activities. Waveform analysis showed a lower maximum value of the second derivative curve (Max2) of APTT with curve shape alternation, while thromboelastometry (INTEM) showed low sensitivity in comparison to results in a normal population.

Discussion

In genotyping, the coexistence of a second mutation should never be excluded, especially in cases of discordant clinical presentation. Waveform analysis correlates better with factor VIII activity than thromboelastometry and the Max2 parameter could provide additional information in managing haemophilia patients. The utility of specific factor activity and global haemostatic assays in general practice still needs to be investigated.     

Influence of lean and fat mass on bone mineral density (BMD) in postmenopausal women with osteoporosis

Despite known positive association between body mass and bone mineral density (BMD), relative contribution of fat and lean tissue to BMD remains under debate. We aimed at investigating the effect of selected anthropometric parameters, including fat content and lean body mass (LBM) on BMD in postmenopausal, osteoporotic women with body mass index (BMI) > 20 kg/m². The study involved 92 never-treated women (mean age 69.5 ± 7.3). L1-L4 and femoral neck (FN) BMD were measured by dual energy X-ray absorptiometry (DEXA). Absolute (kg) and relative (%) fat and LBM were assessed by means of electric bioimpedance method. We showed both FN and L1-L4 BMD were positively correlated with body mass, waist circumference (WC), hip circumference (HC) and LBM (kg). Fat content correlated with FN BMD (r = 0.36, p < 0.001). Regression analysis revealed the only predictor of L1-L4 BMD was LBM (R² = 0.18, p < 0.05), for FN - both LBM and fat (R² = 0.18, p < 0.05 and p < 0.001, respectively). Of the women, 44.5% were overweight, 18.4% obese. Obese women displayed the highest BMD. Both L1-L4 and FN BMD were higher in women with WC > 80 cm. In postmenopausal osteoporotic women with BMI > 20 kg/m² both fat and lean tissue might contribute to BMD. Positive association between body mass and BMD does not make obesity and osteoporosis mutually exclusive.     

Is age or the body mass index (BMI) more determinant of the bone mineral density (BMD) in geriatric women and men?

The objective was to determine the effect of the body mass index (BMI) and age on the bone mineral density (BMD) in geriatric women and men. 900 geriatric patients were included in the study. BMD was measured in the right femoral neck and the antero-posterior lumbar region. All geriatric patients were classified in 1 of 4 categories on the basis of their BMI, as underweight, ideal weight, overweight, and obese. They were separated into three groups, 65-74, 75-84 and 85 and older, according to age groups. While a significant relationship was only determined between the femoral BMD measurements and the BMI in men; significant relationship was shown between both the lumbar and the femoral BMD measurements and the BMI in women. Significant relationship was also determined between the femoral BMD measurements and the BMI and age among women. While the BMDs of those aged 65-74 years group were found to be high compared to those aged 75-84 years and those aged 85 years and older groups, no difference was found between the two groups. This study confirms the effect of a high BMI on femoral neck and L2-L4 BMD among older men and women, but the effect of age was not shown above 75 years of age.     

The metabolic fate of high density lipoprotein (HDL) in the diabetic rat

Summary Diabetic rats, pre-fed and maintained on a sucrose-rich diet, have marked hyperlipoproteinaemia, with an increase in both very low density (VLDL) and high density lipoproteins (HDL). HDL obtained from both diabetic and non-diabetic rats and labelled with ¹²⁵I or ¹³¹I was injected simultaneously into diabetic and non-diabetic rats. The half life of the two HDL preparations was similar in both diabetic and non-diabetic rats and ranged between 11.4 to 12.0 hours. A-I apolipoprotein had a disappearance rate parallel to the whole HDL, in contrast to the apo-C peptides which had a faster rate of removal. Although the fractional catabolic rate (FCR) of HDL preparations was slower in the diabetic rats, there was a 16% increase in the calculated synthetic rate (SR) of HDL-protein. These observations could explain the increased plasma HDL levels in the sucrose-fed, streptozotocin-induced diabetic rat.This work was presented in part at the 12th Annual Meeting of the European Association for the Study of Diabetes (EASD), Helsinki, Finland, September 1976     

代谢综合征并发冠心病患者氧化修饰型低密度脂蛋白与胰岛素抵抗的关系

目的:探讨代谢综合征(MS)及并发冠心病(CHD)患者氧化修饰型低密度脂蛋白(ox-LDL)水平和胰岛素抵抗及MS其他指标的关系。方法:用酶联免疫吸附法(ELISA)测定单纯MS组(17例)、MS并发CHD组(40例)和正常对照组(19例)ox-LDL水平和空腹血浆胰岛素水平,并收集MS的其他有关数据:腰围、体质指数、空腹血糖和血脂,计算胰岛素敏感指数(ISI)。结果:①ox-LDL水平在正常对照组为(5.97±5.18)μg/L,MS组为(24.68±12.00)μg/L,MS并发CHD组为(41.45±35.80)μg/L,3组间差异有统计学意义(F=11.48,P<0.05);②ox-LDL水平与ISI呈负相关(r=-0.472,P<0.05),与体质指数、腰围、LDL-C、空腹真胰岛素无明显相关性;③以ox-LDL水平为应变量的多元逐步回归分析提示,ISI(r2=0.224)与ox-LDL具有相关性,体质指数、腰围、LDL-C、空腹真胰岛素与ox-LDL无明显相关性。结论:MS患者的ox-LDL水平增加,并发CHD的MS患者更为明显,并与胰岛素抵抗相关,可能在MS发展为CHD中起一定作用。     

The efficacy and safety of the new heparin-induced extracorporeal low-density lipoprotein precipitation system (Plasmat Futura) in comparison with the currently used system (Plasmat Secura)

The aim of the present study was to examine whether the recently introduced heparin-mediated extra-corporeal low-density lipoprotein precipitation (HELP) apheresis system Plasmat Futura (since 2001) was comparable to Plasmat Secura system, used to date, in its efficiency to remove atherogenic components, its ease of handling and operating as well as clinical safety and patient compliance. Coronary heart disease (CHD) patients (N = 21) were first treated with Plasmat Secura system and 13 of them were then randomly switched over to the upgraded Plasmat Futura system. Eight patients remained on Secura system. All together, 40 Futura treatments and 40 Secura treatments were performed. Blood samples were collected immediately before and after each apheresis therapy. Our data showed no significant differences in the reduction of plasma low-density lipoprotein, lipoprotein (a) and fibrinogen by Plasmat Futura and Secura system (P > 0.05). However, the major advantages of Plasmat Futura system are the ready-to-use sterile dialysis solutions instead of reverse osmosis device in Plasmat Secura, which ensures flexibility and lower risk of cross infections. Long-term tolerance and safety parameters showed no significant difference (P > 0.05). On the basis of our studies. Plasmat Futura system is easy to use, shows no adverse events and is comparable to Plasmat Secura in its capacity to remove proatherogenic plasma factors.