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Biomedical subjects

U Julius

Publications and source records attributed to U Julius.

At least 19 recordsLinked to original sources
PubMed2003

[Significance of triglycerides for other metabolic parameters in the familial metabolic syndrome].

BACKGROUND: The relationship between the various degrees of glucose tolerance and metabolic parameters have already been examined in various studies. Whether and to what extent the triglycerides (TG) affect other metabolic parameters in the different degrees of glucose tolerance is not certain. We therefore studied the importance of the triglycerides within a defined glycemic state in patients with an elevated familial risk for metabolic diseases. METHODS: We examined 866 patients (380 men, 486 women, mean age 44,4 years) in the "Familial Metabolic Syndrome Study" (FAMES). The patients were assigned to various degrees of glucose tolerance, according to the result of an oral glucose tolerance test. All degrees were divided into subgroups in respect of the triglyceride level (TG < 1,7 or TG >/= 1,7 mmol/l). In these subgroups we measured various metabolic parameters like fasting glucose, insulin resistance, insulin and proinsulin levels, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), uric acid, HbA (1c), and free fatty acids (FFA). RESULTS: In patients with normal glucose tolerance the hypertriglyceridemia is already associated with other components of the metabolic syndrome like elevated HbA (1c), free fatty acids, proinsulin and insulin levels, worsened insulin sensitivity, elevated uric acid and LDL-C levels as well as a lowered HDL-C level. The patients with diabetes and hypertriglyceridemia also showed higher levels of FFA, proinsulin and insulin, a lower HDL-C level and a more prominent insulin resistance. CONCLUSION: Hypertriglyceridemia is an indicator for insulin resistance and elevated levels of other components of the metabolic syndrome within the various degrees of glucose tolerance.

Adult↗
PubMed2003

Lipid-lowering therapy and cholesterol levels following acute myocardial infarction: a German study of 5361 patients.

BACKGROUND: Current studies on secondary prevention of cardiovascular events (CARE, LIPID, 4S) illustrate the necessity of an effective lipid-lowering therapy. An important part of secondary prevention is the prompt measurement of lipids following an infarct, to be able to start therapy as quickly as possible. AIMS: This study should show the general situation in the prescription of lipid-lowering drugs in patients with acute myocardial infarction (MI) and if there are gender differences in therapy and in the lipid parameters. The second aim was to determine the therapeutical conclusions for secondary prevention made in-hospital in patients with heart attacks. METHODS: Post-infarct lipid parameters (total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) were examined in 5361 patients within 24 hours following an acute MI. Lipid parameters from 576 patients were measured again after 1 week. RESULTS: 80.1% of men under examination and 81.9% of the women had suffered from their first MI. Only 9% of all patients were already under lipid-lowering therapy before the MI. After the MI TC and LDL-C levels decreased significantly in a time-dependent manner. Around 50% of patients received lipid-lowering drug, or the recommendation of one, during their hospital stay. CONCLUSION: The range of TC values of the patients examined was comparable to those in the CARE and the 4S secondary prevention studies. It can therefore be assumed that the results of these studies are also applicable to Germany. Nevertheless, according to existing data, therapy with lipid-lowering drugs is currently unsatisfactory, even in secondary prevention.

Aged↗
PubMed2003

Fat modification in the diabetes diet.

The modification of dietary fat in the diet of diabetic patients is of interest with respect to metabolic and other consequences of this modification. To begin with the data are reviewed for the use of monounsaturated fatty acids (MUFA) in the diabetes diet. Compared to a carbohydrate-rich diet, glucose concentrations are lower. Blood pressure was also found to be lower. There were no major differences with respect to lipid concentrations. HDL-cholesterol levels tended to be higher after a MUFA-rich diet. In type-1 diabetic patients, the number of circulating big VLDL particles was greater after a MUFA diet than after a carbohydrate-rich diet. Comparisons were also made between diets enriched with MUFA and with polyunsaturated fatty acids (PUFA). With respect to lipid concentrations, different groups observed different effects. While one group saw no differences in fasting lipids, they measured a higher remnant-like particle cholesterol after a diet enriched with MUFA. Another group found higher total and LDL-cholesterol levels after a PUFA-rich diet than after a MUFA-diet. In their study, fasting glucose, insulin and fasting chylomicrons and postprandial chylomicrons and VLDL were higher following the PUFA diet. A MUFA-rich diet increased endothelium-dependent flow-mediated dilatation in the superficial femoral artery. Alpha-linolenic acid appears to be a precursor of eicospentaenoic and docosahexaenoic fatty acids. As a diet rich in n-6 PUFA reduces this conversion, a n-6/n-3 PUFA ratio not exceeding 4 - 6 should be observed. No prospective data are available for alpha-linolenic acid in diabetic patients. The review summarizes the results of the Lyon Diet Heart Study and the Nurses' Health Study. Both studies saw a reduced cardiovascular risk associated with a higher intake of alpha-linolenic acid. Finally, data on the effects of fish oil are given. The latter has a clearly expressed triglyceride-lowering effect. Data with respect to glucose control are heterogeneous. Major studies did not find any influence in glucose concentrations. Hepatic glucose production and peripheral insulin sensitivity remained constant. Evidently, nerve function can be improved by fish oil. Data have been compiled comparing the effects of fish oil with those of olive oil, linseed oil and sunflower oil.

Diet, Diabetic↗
PubMed2003

Influence of plasma free fatty acids on lipoprotein synthesis and diabetic dyslipidemia.

The regulation of hepatic VLDL secretion mainly depends on apolipoprotein (apo) B synthesis, on microsomal triglyceride transfer protein, insulin and the availability of triglycerides, free fatty acids (FFA) and cholesteryl ester. Four sources of fatty acids are used for lipoprotein synthesis: de-novo lipogenesis, cytoplasmic triglyceride stores, fatty acids derived from lipoproteins taken up directly by the liver and plasma FFA. Quantitatively, de-novo lipogenesis plays a minor role in regulating VLDL synthesis, but evidently it is elevated under conditions of high carbohydrate feeding. Cytoplasmic triglyceride stores appear to essentially contribute to VLDL triglycerides. Plasma FFA enter the hepatocytes and are either oxidized or esterified. The relationship between oxidation and esterification appears to be important in regulating the VLDL synthesis. An enhanced esterification is accompanied by increased VLDL secretion. The addition of oleic acid to hepatocytes has been shown to stimulate production of VLDL triglyceride and apoB. In human beings, an acute experimental elevation of plasma FFA stimulates VLDL production. In healthy men strong positive relations were found between the late increases in large triglyceride-rich lipoproteins and plasma FFA concentrations after 6 h following a mixed meal. In contrast, n-3 fatty acids impair VLDL assembly and secretion. Chronic hyperinsulinemia seems to stimulate VLDL production. On the other hand, the short-term addition of insulin has been shown to inhibit VLDL-triglyceride and apoB production in vitro. There is in vivo evidence that acute hyperinsulinemia suppresses VLDL-apoB and VLDL-triglyceride production in insulin-sensitive humans. Part of this action is due to suppression of plasma FFA. In patients with impaired glucose tolerance (IGT), VLDL production was increased when compared with subjects with normal glucose (NGT). When infusing a lipid emulsion, VLDL production could not be further stimulated in IGT patients in contrast to NGT persons. Hypertriglyceridemia in type 2 diabetes mellitus is usually the consequence of a VLDL overproduction. In type 2 diabetic patients, in contrast to normal men, insulin failed to suppress VLDL1 particle release. In normal men, an elevation of blood glucose led to a decrease in fatty acid oxidation and an increase in hepatic triglyceride secretion. Under these conditions, approximately 30% of total VLDL triglycerides coming out of the liver did not originate from plasma FFA. In conclusion, plasma FFA seem to play an important role in stimulating hepatic VLDL production. Other factors such as chronic hyperinsulinemia or nutrition modify this effect.

Diabetes Complications↗
PubMed2002

Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass.

In obese people, an increase of plasma leptin levels is well-known and is seen as a consequence of the increased body fat mass. Moreover, a relationship between fasting concentrations of leptin and insulin has been described. Hyperinsulinemia is considered to be indicative of insulin resistance. We aimed at elucidating the interrelations between leptin, insulin and insulin resistance in type 2 diabetic patients. Under metabolic ward conditions, we investigated 21 moderately overweight men with type 2 diabetes. The patients had a mean age of 49.1 years, a mean body mass index (BMI) of 26.8 kg/m(2), and a mean diabetes duration of 82.5 months. All patients were treated with diet alone. We measured fasting leptin and insulin levels, body composition by determination of total body water, and insulin resistance by euglycemic hyperinsulinemic clamp technique. At univariate analysis, fasting leptin level significantly and positively correlated with BMI (r=0.49, p=0.02) and with fasting insulin (r=0.69, p=0.001), while it negatively correlated with the glucose disposal rate (r=-0.62, p=0.002). Furthermore, leptin was inversely correlated with HDL-cholesterol (r=-0.45, p=0.04). When excluding the influence of body fat mass or of BMI in partial correlation analysis, the correlations between leptin and insulin or insulin sensitivity remained significant. The relationship between insulin resistance (as measured directly in the clamp experiments) and leptin concentrations was also shown by subdividing the diabetic patients according to tertiles of insulin sensitivity. The highest fasting leptin levels were observed in those patients with the most expressed insulin resistance. Our data point to a functional relationship between insulin resistance and leptin concentrations in insulin-resistant type 2 diabetic men, independently of body composition. This relationship is believed to be mediated by insulin.

Adipose Tissue↗
PubMed2002

Intraindividual comparison of two extracorporeal LDL apheresis methods: lipidfiltration and HELP.

Low density lipoprotein (LDL) apheresis is an effective treatment option for patients with severe hypercholesterolemia not adequately responding to diet and drug therapy. Membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP), here named Lipidfiltration, and heparin-induced extracorporeal LDL-precipitation (HELP) are two of the five methods available for extracorporeal LDL apheresis. In this prospective investigation 6 patients with severe LDL-hypercholesterolemia and CAD were treated in a cross-over design with Lipidfiltration at two stages of technical development and HELP to compare the efficacy of these two LDL apheresis methods with respect to lowering and modifying plasma lipids and rheologically relevant plasma proteins, especially fibrinogen. In total, 44 LDL apheresis sessions were investigated. In weekly intervals, patients were treated with consecutive LDL apheresis sessions with either Lipidfiltration and HELP, treating identical plasma volumes. In one part of the investigation Lipidfiltration was performed with the novel Lipidfilter EC-50, combined with a newly developed blood and plasma therapy machine allowing optimized plasma heating. The results showed that the reduction rates of LDL-cholesterol, lipoprotein(a) and triglycerides were essentially identical for both methods. Also pretreatment levels of total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were not significantly different in both treatment groups. Both methods lead to a significant reduction of serum lipoproteins, especially for LDL-cholesterol, which was decreased by 61.4% with Lipidfiltration (treated plasma volume: 2998 ml) and 61.3% with HELP (treated plasma volume: 3013 ml). With respect to Lipidfiltration LDL-cholesterol reduction was more efficient with the novel Lipidfilter EC-50. Mean pretreatment HDL cholesterol concentrations remained unchanged. Comparing Cascadeflo AC-1770 with the novel Lipidfilter EC-50 reduction rates of HDL-cholesterol (17.4% versus 6.4%) and total protein (17.9% versus 7.8%) were significantly reduced. Lipidfiltration and HELP both resulted in a reduction of plasma viscosity and hemorheologically relevant plasma proteins, like fibrinogen.

Blood Component Removal↗
PubMed2001

Different susceptibility to oxidation of proline and arginine residues of apolipoprotein B-100 among subspecies of low density lipoproteins.

gamma-Glutamyl semialdehyde is a primary oxidation product of apolipoprotein (apo) B-100 proline (Pro) and arginine (Arg) side chain residues. By reduction gamma-glutamyl semialdehyde forms 5-hydroxy-2-aminovaleric acid (HAVA). Here we describe the application of sensitive and specific HAVA measurement to characterize the formation of gamma-glutamyl semialdehyde in several domains of apoB-100 in LDL(1) (S(f) 7-12) and LDL(2) (S(f) 0-7) subfractions subjected to oxidative damage in the presence of iron in vitro. Results suggest that susceptibility of apoB-100 Pro and Arg residues toward oxygen radicals drastically changes along the lipoprotein metabolic cascade.

Adult↗
PubMed2001

Eight novel LDL receptor gene mutations among patients under LDL apheresis in Dresden and Leipzig.

LDL apheresis is highly efficient in reducing elevated plasma cholesterol. Due to strict indications only patients with severe, refractory hypercholesterolemia are treated with this method. Mutations in the LDL receptor gene are major genetic causes for severe hypercholesterolemia. Screening the entire gene in LDL apheresis patients from Saxony should determine whether an increased frequency of defined mutations is responsible for the atherogenic hypercholesterolemia in this group. 31 unrelated patients (15 male, 16 female, age 33-71 yrs.) were included in the analysis. The LDL-R gene was screened using SSCP and/or automated sequencing. The familial defective apolipoprotein B-100 (FDB) mutation was genotyped using established PCR techniques. Nineteen of 31 patients were carriers of an LDL-R mutation. Ten missense and two nonsense mutations, three insertions and two deletions were detected. The mutations C74S, C74R, T87M, 660delC, 662insCCCCG, 680insGGACAAATCTGA, 1428insC and 2167delG have not been previously described. One patient was compound heterozygous for two missense mutations. Two further patients were heterozygous for FDB. No mutations were found among controls. A genetic background for hypercholesterolemia in the LDL-R could be established in about 61% of the patients examined. Therefore, methods of DNA analysis allow to recognize and adequately treat a large portion of high-risk individuals at an early stage.

Adult↗
PubMed2001

Homocysteine levels in patients treated with lipid apheresis: effect of a vitamin therapy.

BACKGROUND: Patients treated with lipid apheresis already suffer from familial hypercholesterolemia and severe coronary heart disease: any additional risk factor is dangerous for these patients. Hyperhomocysteinemia has been recognized as an independent risk factor for atherosclerotic disease. We checked the frequency of hyperhomocysteinemia in lipid apheresis patients and measured the effect of a vitamin therapy. MATERIALS AND METHODS: Sixteen heterozygous patients (10 males, 6 females) were studied, who were being treated by three different apheresis procedures. Homocysteine was measured using an enzyme conversion immunoassay. Cystathionine and methylmalonic acid were assessed by gas chromatography/mass spectrometry. Serum levels of folic acid, vitamin B12, and vitamin B6 were also determined. The patients received a vitamin therapy (3 mg folate, 60 microg cyanocobalamine, 10 mg pyridoxine hydrochloride daily) for 12 weeks. RESULTS: In 9 out of 16 patients, plasma homocysteine levels were found to be elevated (> 12 micromol L(-1)). Cystathionine concentrations were also increased, especially in those patients with elevated homocysteine. Methylmalonic acid levels were not elevated. Serum folic acid, vitamin B6, and vitamin B12 concentrations were initially in the normal range and not correlated to plasma homocysteine. The vitamin therapy reduced the plasma homocysteine concentrations in all patients significantly by 33%. Among those patients with elevated homocysteine levels, the optimal range < 12 micromol L(-1) for homocysteine was rarely reached. CONCLUSIONS: In patients treated with lipid apheresis, a hyperhomocysteinemia can be frequently seen. The constellation of both elevated homocysteine and cystathionine levels points to the existence of tissue vitamin deficiencies, folate and vitamin B-6, which were improved by vitamin supplements. Because methylmalonic acid was mostly normal, a vitamin B-12 deficiency was not proven.

Adult↗
PubMed2001

Estimation of the heritability of latent variables which are included in a structural model for metabolic syndrome.

In a study looking for risk factors of atherosclerosis in families with combined hyperlipidemia and hypertension, clinical and biochemical data of 1,149 persons were analyzed to develop two hypothetical multivariate scores concerning the degree to which a patient is affected by the metabolic syndrome. The scores are based on a structural model for low-density cholesterol (LDL) and high-density cholesterol (HDL), triglycerides, uric acid, creatinine, glucose, insulin, systolic blood pressure and waist-to-hip ratio. Age, gender and body mass index were used for adjusting all variables. In segregation analyses of 42 pedigrees without using genotype information, estimations of the heritabilities and environmentally caused variance and covariance components were computed for the individual score values of the two latent factors. The first score shows a heritability of 42%; the environment component disappeared. The score mainly reflects the HDL, LDL and triglyceride levels. The second score shows a heritability of 16% with an environment component of 7%. It includes mainly insulin, uric acid and creatinine. In the search for genetic causes, both scores could be a basis for further phenotypic classification of the metabolic syndrome.

Arteriosclerosis↗
PubMed2000

Distinct effects of LDL apheresis by hemoperfusion (DALI) and heparin-induced extracorporeal precipitation (HELP) on leukocyte respiratory burst activity of patients with familial hypercholesterolemia.

Hypercholesterolemia and oxidative stress are major risk factors in atherogenesis. In the last years, lipid apheresis has been established as an effective clinical therapy by lowering not only elevated plasma low-density lipoprotein (LDL) levels but also by reducing the incidence of cardiovascular events. The aim of the present study was to investigate peripheral leukocyte oxidant generation in patients with familial hypercholesterolemia (FH) undergoing regular LDL apheresis. The activity state of leukocytes was estimated prior to, immediately after, and 2 days after LDL apheresis carried out by two distinct techniques: hemoperfusion with the DALI system and heparin-induced extracorporeal LDL precipitation (HELP). Oxidant generating activity was measured by chemiluminescence (CL) in whole blood and isolated polymorphonuclear leukocytes (PMNL). The results of our study show increased baseline respiratory burst activities in FH patients as compared to healthy controls. Apheresis with the HELP system was followed by increases in leukocyte count, zymosan-induced whole blood CL, and plasma PMNL elastase levels. The DALI technique caused no changes in leukocyte count and elastase levels and decreased whole blood CL activity. Two days after lipid removal the observed changes returned to pre-apheresis levels. Leukocyte activity parameters before and after apheresis did not correlate with the corresponding plasma levels of triglycerides, total cholesterol, and LDL cholesterol, suggesting that different handling in the framework of both apheresis techniques rather than lipid profile changes during therapy accounted for leukocyte activity modulation.

Adult↗
PubMed2000

Impaired glucose tolerance (IGT) is not associated with disturbed homocysteine metabolism.

Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly diagnosed T2D, and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 +/- 4.6; T2D, 12.8 +/- 4.0; NGT, 10.7 +/- 4.4 micromol/L) and PML-tHcy (IGT, 46.5 +/-17.39; T2D, 41.1 +/- 6.8; NGT, 38.0 +/- 9.7 micromol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association between tHcy and renal function in these subjects.

Blood Glucose↗
PubMed2000

Oxidation of apolipoprotein B-100 in circulating LDL is related to LDL residence time. In vivo insights from stable-isotope studies.

5-Hydroxy-2-aminovaleric acid (HAVA) has been suggested to be a specific marker of oxidation of apolipoprotein (apo) B-100 proline (Pro) and arginine (Arg) side-chain residues in low density lipoprotein (LDL) in vitro. Here we describe the application of sensitive mass spectrometric techniques to the characterization of Pro/Arg-modified apoB-100 in LDL(1) (S(f) 7 to 12) and LDL(2) (S(f) 0 to 7) in vivo. We studied 7 subjects with familial defective apoB-100 (FDB) and 8 normolipidemic controls. In FDB subjects, the presence of a mutant apoB-100 (FDB(3500Q)) in LDL markedly reduced its affinity for the LDL receptor, leading to increased residence times (RTs) of LDL(1) (65+/-21 versus 32+/-12 hours, P<0.005) and LDL(2) (230+/-40 versus 53+/-7 hours, P:<0.001) when compared with controls, as determined by stable-isotope turnover studies. LDL(1) HAVA content was not different between the groups (FDB, 0.004+/-0. 001 mol/mol apoB-100 versus controls, 0.003+/-0.001 mol/mol apoB-100, P=0.200). LDL(2) HAVA content was higher in FDB subjects (0. 374+/-0.088 versus 0.013+/-0.002 mol/mol apoB-100, P<0.001). In both groups, LDL(2) HAVA was positively associated with LDL(2) RT (FDB, r=0.893, P:=0.003; controls, r=0.976, P=0.000) and negatively correlated with LDL(2) alpha-tocopherol content (FDB, r=-0.929, P=0. 003; controls, r=-0.903, P=0.002). No significant correlations could be found between LDL(1) HAVA, LDL(1) RT, and alpha-tocopherol, respectively. The low LDL(1) HAVA content observed in both FDB and control groups was thought to be due to the relatively lower RT as well as the higher alpha-tocopherol content of these lipoproteins. In contrast, LDL(2) seemed to be strongly prone to direct oxidation of apoB-100 in vivo. The longer these particles linger in the circulation, the more apoB-100 Pro/Arg residues become modified.

Adult↗
PubMed2000

Intraindividual comparison of the impact of two selective apheresis methods (DALI and HELP) on the coagulation system.

We performed an intraindividual comparison of the effect on the coagulation system of two selective apheresis procedures: Direct Adsorption of Lipoproteins (DALI) and Heparin-induced Lipoprotein Fibrinogen Precipitation (HELP). Six patients suffering from heterozygous familial hypercholesterolemia have been treated with 2 sessions of each procedure. Anticoagulation was carried out according to usual recommendations. Blood samples were taken before, immediately after and on the second day after the sessions. We assessed global coagulation tests (prothrombin time, activated partial thromboplastin time), fibrinogen, prothrombin fragment F 1 + 2 and a variety of factors (Factors II, V, VII, XIII, IX, X, XI, XII, XIIa; von Willebrand Factor; collagen-binding activity, prekallikrein, high-molecular weight kininogen) and antagonists (antithrombin III, protein S activity, free protein S). In fact, all parameters measured have been influenced by the apheresis treatment. Fibrinogen is lowered more by HELP which also has a more definite impact on factors belonging to the prothrombin complex (II, VII, X). In contrast, the major effects of the DALI system have been seen on the intrinsic pathway of the coagulation system (IX, XI, prekallikrein, high-molecular-weight kininogen). With both systems, no increases in activated Factor XII or in prothrombin fragment F 1 + 2 have been observed. These data provide a solid basis for individual adaptations of anticoagulant doses.

Adult↗