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Biomedical subjects

O Ziegler

Publications and source records attributed to O Ziegler.

At least 55 records · Page 3Linked to original sources
PubMed1998

Protease inhibitors, diabetes mellitus and blood lipids.

We report the case of a patient with human immunodeficiency virus (HIV) and no familial or personal history of metabolic disease, who experienced two diabetes decompensations (severe hyperglycaemia without ketonuria) associated with severe hypertriglyceridaemia, after the introduction of protease inhibitors. Initial insulin therapy at high doses (2 IU/kg/day) was required, and metabolic control was restored within several weeks without treatment after withdrawal of protease inhibitors. This case confirms that due attention must be paid to both blood glucose and plasma triglyceride levels in HIV-infected patients treated with protease inhibitors.

Adult↗
PubMed1997

Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes.

Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity.

Catecholamines↗
PubMed1996

Role of albumin glycation on the erythrocyte aggregation: an in vitro study.

The increased erythrocyte aggregation observed in diabetes mellitus is mainly due to changes in the balance between aggregating factors and anti-aggregating ones, like albumin. Since chronic hyperglycaemia results in protein glycation, we examined the effect of in vitro glycation of albumin on its anti-aggregating role with blood from 29 Type 1 diabetic patients and 29 healthy controls. After the addition of glycated and unglycated albumin, samples had a glycation level of 24% for healthy controls and 28% for diabetic patients. Erythrocyte aggregation was determined by the analysis of the light backscattered by a blood suspension. Erythrocytes from healthy controls suspended in glycated albumin had significantly higher rates of rouleaux formation (p < 0.01) than in unglycated albumin and increased cohesion of rouleaux (p < 0.05). The erythrocyte aggregation in diabetic patients underwent similar changes (p < 0.01). The time-resolved fluorescence of the single tryptophan residue was monitored to describe the changes in the conformational equilibrium of albumin. The lifetime data showed that the increases in the two lifetime components and in the relative proportion of the major lifetime are in agreement with a conformational change in albumin after glycation. Thus, the changes in albumin conformation could be responsible for the smaller hypoaggregating effect of glycated albumin.

Adult↗
PubMed1996

Intraperitoneal insulin infusion improves the depletion in choline-containing phospholipids of lipoprotein B particles in type I diabetic patients.

Insulin-dependent diabetes mellitus (IDDM) is characterized by altered composition of atherogenic lipoproteins, especially a depletion in choline-containing phospholipids (PL) of apolipoprotein (apo) B lipoproteins (LpB). To determine the effects of continuous intraperitoneal (IP) insulin infusion (CIPII) on this qualitative lipoprotein abnormality, we compared lipoprotein profiles of 14 IDDM patients treated by continuous subcutaneous insulin infusion (CSII) and at 2 and 4 months after treatment with CIPII using an implantable pump. IDDM patients were in fair metabolic control and were compared with 14 healthy control subjects matched for sex, age, body mass index, and plasma lipids. The following parameters were studies: hemoglobin A1c (HbA1c), monthly blood glucose, daily insulin dose (units per kilogram per day), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, apo A-I, and apo B. Choline-containing PL were assessed in plasma and in apo B- and no-apo B-containing lipoprotein particles (LpB and Lp no B). As compared with the control group, plasma PL and LpB-PL were significantly lower in IDDM patients treated by CSII (2.95 +/- 0.26 v 3.30 +/- 0.45 mmol/L,P<.05, and 1.09 +/- 0.45 v 1.68 +/- 0.33 mmol/L,P<.01, respectively). No significant differences were observed for Lp no B lipid determinations between both groups. After initiation of CIPII, IDDM patients did not experience any significant changes in mean values for body mass index, HbA1c, and monthly blood glucose throughout the study. Daily insulin doses were identical to those observed before IP therapy. Lipid parameters remained unchanged in IDDM patients (TC, TG, HDL and LDL cholesterol, apo A-I, and apo B). A moderate but progressive elevation of plasma PL was noted, and after 4 months of CIPII, PL and LpB-PL levels were no longer significantly different between IDDM patients and controls. The increase in plasma and LpB choline-containing PL observed after 2 and 4 months of CIPII is not linked to changes in blood glucose control, body weight or daily insulin requirements. These changes may be related to the route of insulin administration, which may be accompanied by a reduction of lipoprotein lipase (LPL) activity and consequently a reduction of phospholipase activity. These results suggest that IP insulin delivery may be a more physiological route that increases the choline-containing PL content of LpB particles.

Adult↗
PubMed1996

Hyperinsulinemia is related to erythrocyte phospholipid composition and membrane fluidity changes in obese nondiabetic women.

It has been suggested that changes in the properties of cell membranes are involved in an altered insulin action. However, the influence of changes in the distribution of phospholipid classes has not been explored. We investigated 69 obese nondiabetic normoglycemic women (17 patients with impaired glucose tolerance) with varying degrees of insulin sensitivity to determine the phospholipid composition and fluid state of their erythrocyte plasma membranes. The fasting plasma insulin, the homeostasis model analysis of insulin resistance (HOMA), and the integrated area under the insulin curve (AUC-I) after an oral glucose challenge were used as markers of insulin resistance. Results were divided into normal glucose tolerance (NGT) and impaired glucose tolerance. There was a positive correlation in NGT group between the membrane sphingomyelin (SM) content and the fasting plasma insulin (r = 0.523; P < 0.0001), HOMA value (r = 0.483; P < 0.0005), and AUC-I (r = 0.352; P < 0.05) and negative correlations between membrane fluidity determined with two fluorescent probes and plasma fasting insulin (r = 0.320; r = -0.365; P < 0.05) and HOMA value (r = 0.321; r = -0.382; P < 0.05). There were also correlations between SM and the three markers of insulin resistance in the impaired glucose tolerance group. There was no correlation between insulin resistance and other membrane components. Stepwise multiple regression analysis in the NGT group confirmed that the membrane SM content was an independent predictor of plasma fasting insulin, HOMA values, and AUC-I variations. Sphingomyelin could be one of the membrane parameters contributing to insulin resistance.

Administration, Oral↗
PubMed1996

Accessibility of human apolipoprotein B-100 epitopes in insulin-dependent diabetes: relation with the surface lipid environment of atherogenic particles.

The physicochemical modifications (composition and conformation) of lipoproteins containing apolipoprotein B-100 (apo B-100) were studied in normocholesterolaemic adequately controlled Type 1 insulin-dependent diabetic patients. Thirty-one normocholesterolaemic (serum cholesterol < 6.50 mmol/l) diabetic male patients and 31 age-and body mass index-adjusted healthy normolipaemic male controls were studied. Cholesterol and choline-containing phospholipids were measured in total serum and in two lipoprotein subfractions containing or not apo B (LpB and LpnoB respectively). These subfractions were separated by precipitation with concanavalin A. Total apo B-100 and two lipoprotein particles defined according to their apo B-100 epitope accessibility were determined using respectively anti-apo B polyclonal and two monoclonal antibodies that reacted with specific epitopes on the apo B molecule. Despite a classical lipid profile (cholesterol and triglyceride levels), which was quite normal in plasma from patients as compared to controls, a depletion of choline-containing phospholipid content in serum and more specifically in LpB particles was observed in diabetic patients. Decreased cholesterol content was also observed in LpB particles. Immunological analysis demonstrated an increased number of lipoprotein particles (a condition previously related to coronary artery disease) and decreased immunoaccessibility of a conformationally expressed apo B-100 epitope. These conformational changes were correlated with modifications of the surface phospholipid environment of LpB particles. It is concluded that subtle abnormalities in the composition and conformation of atherogenic apo-B-containing lipoproteins occur in Type 1 diabetes mellitus. These structural modifications may be one factor accounting for the increased rate of atherosclerosis in diabetes, despite the existence of a normal classical lipid profile.

Adult↗
PubMed1995

Decreased erythrocyte membrane fluidity in poorly controlled IDDM. Influence of ketone bodies.

OBJECTIVE: To examine the factors that might alter the fluidity of erythrocyte membrane in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: The subjects were 10 health men and 30 IDDM mem: 10 with good blood glucose (BG) control (HbA1c 5.88 +/- 0.60% [mean +/- SD]), 10 with poor BG control (HbA1C 9.48 +/- 1.05%), and 10 with poor BG control and mild to moderate diabetic ketoacidosis (DKA) (HbA1C 9.12 +/-2.25%, strongly positive ketonuria 3+ and elevated plasma beta-hydroxybutyrate). Erythrocyte membrane fluidity was determined by fluorescence polarization using 6-(9-anthroyloxy stearic acid as fluorescent probe. RESULTS: Membrane fluidity was normal in the diabetic patients with good BG control but significantly lower in the two groups of patients with poor BG control than in the healthy subjects (P < 0.01). The membrane fluidity in the poor BG control groups was also lower in the patients with DKA than in those without DKA (P < 0.01). CONCLUSIONS: The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.

Adult↗
PubMed1995

[Lipoprotein (a) and diabetes mellitus].

Lp(a) has atherogenic and thrombotic properties and is considered to be a major risk factor for the development of atherosclerotic disease. The risk of cardiovascular disease is increased in both insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), and Lp(a) has attracted attention as a potential risk factor in diabetic patients. Lp(a) levels are "probably" elevated in IDDM patients and related to altered metabolic control and increased urinary albumin excretion rate or renal insufficiency, although results are controversial. There appears to be a real difference between the Lp(a) of patients with proliferative diabetic retinopathy and those with or without background retinopathy. The plasma Lp(a) level may therefore be associated with microangiopathy in some IDDM patients. However, data relating Lp(a) to complications of diabetes are limited, and the literature is conflicting. The few available data suggest that Lp(a) is not elevated in NIDDM patients and that there is no strong link between blood glucose control and plasma Lp(a). There is no clear evidence as to whether Lp(a) is related to microalbuminuria in NIDDM patients. There is little evidence for a correlation between increased risk of cardiovascular disease and plasma Lp(a) among diabetic patients. However, some diabetic patients with coronary heart disease have elevated plasma Lp(a), which seems to be correlated with genetic factors (especially the isoforms of apolipoprotein a) rather than to diabetes per se. Lp(a) synthesis and catabolism could be influenced by insulin or by diabetes and its metabolic concomitants. The atherogenic and thrombogenic potential of Lp(a) could also be increased in diabetic patients. Plasma Lp(a) should be measured for both IDDM and NIDDM patients. If the Lp(a) level is elevated, it seems reasonable to check the other major vascular risk factors.

Cardiovascular Diseases↗
PubMed1994

Minimal model for determination of insulin sensitivity: repeatability in control and obese subjects.

A mathematical model was recently developed (minimal model) to estimate insulin sensitivity from the analysis of blood glucose and insulin concentration after a modified intravenous glucose tolerance test. This approach was successfully compared with the euglycemic glucose clamp in humans. In this study, we have analysed the distribution and reproducibility of this method in 10 healthy subjects and seven obese patients. We have observed a lower insulin sensitivity (SI) in obese patients (1.96 +/- 0.38 x 10(-4)/min/microU/ml) than in healthy subjects (8.19 +/- 1.16 x 10(-4)/min/microU/ml) with a small overlap between the two groups. The test was repeated twice and good repeatability was found with the method of Blank and Altman when a log transformation was applied to the data.

Adult↗
PubMed1994

Insulin binding to human cultured lymphocytes measured by flow cytometry using three ligands.

The binding of insulin to cultured IM-9 human lymphocytes was studied by flow cytometry using FITC-insulin and biotinylated insulins coupled to streptavidin-phycoerythrin (N alpha beta 1-biotinylinsulin (B-insulin) and N alpha B1-(biotinyl-epsilon-aminocaproyl)insulin (NBC-insulin)). The reference methods were 125I-insulin binding and the insulin-antiinsulin antibody complexes for flow cytometry. There was a close correlation between 125I-insulin binding and increase in fluorescence for B-insulin, NBC-insulin, and insulin-anti-insulin antibody complexes, but not for FITC-insulin. NBC-insulin gave the largest increase in fluorescence (79 +/- 9 channels) and the the insulin-antiinsulin antibody complexes the smallest (34 +/- 2 channels) (P < 0.05). FITC-insulin and B-insulin gave similar results: 47 +/- 6 and 59 +/- 6 channels. The concentration reducing 125I-insulin binding by 50% was 1.1 x 10(-9) M for native insulin, 2.7 x 10(-9) M for B-insulin, 3.3 x 10(-9) M for NBC-insulin, and 6.6 x 10(-9) M for FITC-insulin (P < 0.05). Nonspecific binding was low for B-insulin and NBC-insulin but reached 75% for 10(-6) M FITC-insulin. These results suggest that B-insulin and NBC-insulin are suitable ligands for insulin binding studies using flow cytometry. This two-step procedure is easier than the insulin-antiinsulin antibody complex technique. Its poor affinity, specificity, and sensitivity make FITC-insulin less suitable.

Animals↗
PubMed1994

[Hyperlipidemia during diabetes mellitus. Recent developments].

Patients with diabetes mellitus are at increased risk of coronary, cerebral, and peripheral vascular disease, and frequently have abnormal plasma lipid levels. Glycaemic control, environmental factors and inherent genetic potential may affect lipoprotein metabolism. Quantitative alterations in the concentrations of major lipids and lipoproteins have been extensively studied in both insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus. However several recent findings indicate the possible presence of structural and functional abnormalities that may impair the lipid metabolism transport system in diabetic patients. These include glycation of several major or minor apolipoproteins, apo E phenotype frequency, free cholesterol or triglyceride enrichment of VLDL and LDL. Moreover lipoprotein (a) which is an independent risk factor for coronary heart disease may be increased in diabetic patients with poor glycaemic control or with microproteinuria. Patients with microalbuminuria or chronic renal failure show atherogenic changes of lipoprotein pattern. New epidemiological evidence indicates that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Postprandial lipaemia can increase the risk of cardiovascular disease potentially by low triglyceride metabolic capacity. The role of insulin must also be considered. Some lipoprotein abnormalities could be attributed to peripheral hyperinsulinaemia, insulin resistance or type of insulin infusion for insulin-dependent diabetes mellitus patients. In diabetes lipids and lipoproteins are potentially atherogenic although their concentrations may be strictly normal. The achievement of optimum lipid and lipoprotein levels as a goal of treatment for diabetic patients would reduce the current rates of morbidity and mortality from vascular disease.

Apolipoproteins E↗
PubMed1994

Increased erythrocyte aggregation in insulin-dependent diabetes mellitus and its relationship to plasma factors: a multivariate analysis.

Red blood cell aggregation in vitro (kinetics and shear resistance) was studied in 13 healthy controls and 13 type I (insulin-dependent) diabetic patients free of severe degenerative complications who were matched for age, sex, and body mass index. Measurements were performed with a device that analyzes the laser light backscattered by a blood suspension. Both the velocity of rouleau formation and the cohesion of the rouleau network were significantly increased in diabetic patients. Plasma viscosity and whole-blood viscosity measured at low shear rate (0.95 s-1) were also significantly elevated in the diabetic group. Multivariate analyses of the whole population sample and the diabetic patients confirmed the influence of plasma proteins on the kinetics of aggregation. Fibrinogen levels, which were close to normal, affected mainly the shear resistance of the aggregates. Triglyceride and apolipoprotein (apo) B levels and indexes of metabolic control or protein glycation (fasting blood glucose and fructosamine) also appeared to influence markedly both the kinetics of rouleau formation and the cohesion of the rouleau networks. These rheological abnormalities occurred in diabetic patients before the appearance of any severe degenerative complications. We suggest that these rheological abnormalities are linked to plasma or erythrocyte factors, and are not due to angiopathy.

Adult↗
PubMed1994

Improved visual evoked potential latencies in poorly controlled diabetic patients after short-term strict metabolic control.

OBJECTIVE: To determine whether short-term strict control of blood glucose can improve abnormal visual evoked potentials (VEPs) in poorly controlled diabetic patients with no overt diabetic complications. RESEARCH DESIGN AND METHODS: VEPs (P100 wave latencies) were recorded in 12 poorly controlled diabetic patients (7 with insulin-dependent diabetes mellitus and 5 with non-insulin-dependent diabetes mellitus) before and after at least 3 days of near normoglycemia obtained by continuous subcutaneous insulin infusion (CSII). Exclusion criteria were overt diabetic neuropathy or retinopathy. The control subjects were 12 healthy subjects matched for age and sex. Fifty-two other subjects formed a reference control population. The intra-individual coefficient of variation for P100 latency was < 3%. RESULTS: The P100 latencies were longer in diabetic patients than in control subjects (means of both eyes +/- SD: 116.8 +/- 10.1 vs. 106.2 +/- 4.5 ms, P < 0.01), and 4 of the 12 diabetic patients had abnormal VEPs. After 3 days of close blood glucose control (mean blood glucose profile fell from 13.7 +/- 2.2 mmol/l to 6.8 +/- 1.2 mmol/l, P < 0.01), the mean P100 latencies were significantly shorter (112.5 +/- 7.6 ms, P < 0.01) but were still significantly longer than control values. The longer the initial P100 latency, the greater the decrease after CSII. There was no correlation between the fall in blood glucose and improvement in VEPs. CONCLUSIONS: Short-term blood glucose normalization is associated with improved P100 wave latency in uncomplicated diabetic patients. These data suggest that abnormal VEPs are partly reversible and include functional disturbances related to glucose metabolism.

Adult↗