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Biomedical subjects

P Vague

Publications and source records attributed to P Vague.

At least 19 recordsLinked to original sources
PubMed1997

[Nutrition in patients treated with antilipemic agents. Survey of 337 patients].

OBJECTIVE: Assess eating habits in patients with dyslipidemia taking lipid-lowering drugs and compare the current situation with generally proposed counselling. METHODS: In the framework of a survey on the prevention of cardiovascular risk, we studied eating habits in 337 subjects. Food intake was recorded for 3 consecutive days and data compared among groups of subjects taking different classes of lipid-lowering drugs. RESULTS: Lipid-lowering therapy was relatively effective, giving satisfactory laboratory results. In general, patients followed general counselling concerning hyperlipidemia. However, for more specific aspects such as balanced fatty acid intake, and elements aimed at mid-term prevention, results could still be improved by further explaining desirable eating habits. CONCLUSION: For patients with hyperlipidemia, it is clear that personalized counseling management, in a structured health care unit, is certainly the best way to help these patients and optimize therapeutic results.

Cardiovascular Diseases↗
PubMed1997

Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats.

Diabetic cardiomyopathy has been associated with a decrease in Na,K-ATPase activity and expression, as well as alterations in membrane lipid composition. The aim of this study was twofold: 1) to document in rats the effect of streptozotocin-induced diabetes on myocardial Na,K-ATPase and fatty acids, and 2) to evaluate the potential effect of a dietary supplementation with fish oil (n-3 fatty acids) on the streptozotocin-induced changes. Assays were performed in purified cardiac plasma membranes to determine Na,K-ATPase activity, expression of the different alpha- and beta-subunits of Na,K-ATPase, and the fatty acid content of total phospholipids. Relative abundance of the mRNAs encoding the alpha 1, alpha 2 and beta 1 isoforms was studied by Northern blot analysis. Results demonstrated that diabetes significantly decreased activities of alpha 1 and alpha 2 isoforms and mRNA levels of alpha 2 and beta 1 isoforms, and, at the protein level, increased alpha 1-isoforms and decreased both alpha 2- and beta 1-isoforms. Changes in fatty acid content of the membrane were consistent with inhibition of desaturase. Fish-oil supplementation produced an increase in membrane incorporation of eicosapentaenoic acid. It also increased the level of beta 1-isoforms and restored the activity of the alpha 2-isoenzyme without significant changes in the level of alpha 1- and alpha 2-isoforms. Northern blot analysis showed no effect of fish oil supplementation. Experimental diabetes and prevention by the fish oil rich (n-3 fatty acids) diet induced specific effects on the activity and expression of alpha and beta Na,K-ATPase subunit isoforms. These studies suggest that fish oil therapy may be effective in preventing some of the adverse consequences of diabetes.

Analysis of Variance↗
PubMed1997

Association of diabetic neuropathy with Na/K ATPase gene polymorphism.

Diabetes mellitus induces a decrease in Na/K ATPase activity in man and animals, and this decrease plays a role in the development of diabetic neuropathy. Na/K ATPase is encoded by various genes, of which the ATP1 A1 gene is expressed predominantly in peripheral nerves and in erythrocytes. To investigate whether a polymorphism in the Na/K ATPase genes could explain the predisposition of some patients with insulin-dependent diabetes mellitus (IDDM) to develop polyneuropathy, a restriction fragment length polymorphism (RFLP) of the ATP1 A1 gene was studied together with erythrocyte Na/K ATPase activity in 81 Caucasian patients with more than 10 years' duration of IDDM. Associations with diabetic neuropathy, retinopathy and nephropathy were sought. Digestion of the first intron of the ATP1 A1 gene by the Bgl II restriction enzyme revealed a dimorphic allelism. Frequency of the restricted allele was 0.18 in this selected series (however, it was 0.10 in representative samples of IDDM patients and of normal subjects in our area). Mean erythrocyte Na/K ATPase activity was lower in diabetic patients than in 42 control subjects (292 +/- 10, vs 402 +/- 13 nmol Pi.mg protein-1.h-1, p < 0.0001) and was not related to HbA1c value or to diabetes duration. It was lower in the group of the 28 patients bearing the restricted allele (241 +/- 10 vs 319 +/- 11 nmol Pi.mg protein-1.h-1, p < 0.0001). Neuropathy was absent in 50 patients, mild in 15 and severe in 16. When classified accordingly the three groups of patients did not differ with respect to sex, age and duration of diabetes. The respective frequency of the restricted allele among the groups was 10, 73 and 81%, (p < 0.0001) and mean erythrocyte Na/K ATPase activity was respectively: 322 +/- 10.7 nmol Pi.mg protein-1.h-1, 268 +/- 15 and 229 +/- 17, (p < 0.001). A borderline association between renal status or retinal status and repartition of polymorphism and a borderline correlation between renal status and Na/K ATPase activity were found, but significance disappeared after checking for the presence or absence of neuropathy. IDDM patients bearing the ATP1 A1 variant detected by Bgl II RFLP are much more frequently affected by neuropathy (relative risk 6.5, with 95% CI 3.3-13). Identification of this risk factor may help to prevent this complication. It is suggested that the restricted allele is in linkage disequilibrium with a genomic mutation allowing diabetes to induce a greater impairment of Na/K ATPase activity which could in turn favour the development of neuropathy.

Adult↗
PubMed1996

Insulin kinetics in type I diabetic patients treated by continuous intraperitoneal insulin infusion: influence of anti-insulin antibodies.

Continuous intraperitoneal insulin infusion (CIPII) is a promising therapy of patients with Type 1 (insulin-dependent) diabetes mellitus (IDDM), since it improves metabolic control and decreases frequency of severe hypoglycaemia. This could be due to more appropriate insulin kinetics. Our aim, therefore, was to compare plasma free insulin levels achieved in patients with Type 1 diabetes chronically treated with CSII or CIPII. Furthermore, as anti-insulin antibodies increase with this treatment, we wanted to assess their influence upon insulin kinetics. Plasma free insulin profiles were obtained during the night and then after the bolus for breakfast and the bolus for lunch in 11 patients with Type 1 diabetes treated successively by CSII and CIPII. In another group of 16 patients with long-term Type 1 diabetes, treated by CIPII, we examined the influence of anti-insulin antibody level on insulin kinetics after a bolus. During the night, plasma free insulin levels were lower with CIPII than with CSII (12:00 am: 10.1 +/- 1.7 vs 18.5 +/- 2.6 mU l-1; 4:00 am: 9.1 +/- 2 vs 15 +/- 3 mU l-1), p < 0.01. After the bolus, CIPII lead to an earlier (1h vs 3h) and higher (25.8 +/- 3.3 vs 18 +/- 2.7, p < 0.05) plasma free insulin peak than CSII. With CIPII, the return to baseline level was observed within 3 h. Conversely, during CSII, insulin levels did not return to baseline until the next meal. After the bolus, high insulin-antibody levels were associated with a reduced maximal value of plasma free insulin peak. Taken together, these findings suggest that CIPII provides plasma free insulin profiles which are much closer to physiology than CSII. This could explain the lower rate of severe hypoglycaemia observed with this type of treatment. But in long-term CIPII treated patients with high anti-insulin antibody level, insulin profile could be moderately modified. This emphasizes the need for a less immunogenic insulin preparation.

Adult↗
PubMed1996

Decreased Na/K ATPase ouabain binding sites in red blood cells of patients with insulin-dependent diabetes and healthy north African control subjects: relationship with diabetic neuropathy.

Like other degenerative complications occurring during diabetes, development of neuropathy is determined mainly by the duration of disease and quality of control. However, there may be some predisposing factors. Activity of Na/K ATPase has been implicated in the pathophysiology of diabetic neuropathy. A decrease in the activity of this enzyme has been observed in red blood cells of poorly controlled diabetic patients and healthy North African subjects who are predisposed to diabetic neuropathy. This study was performed to characterize abnormalities of Na/K ATPase activity in these two populations. For this purpose we measured enzyme activity (hydrolysis of ATP) and the number of enzyme units (number of binding sites for ouabain) in the red blood cells of three groups of men, i.e., healthy Caucasian subjects, healthy North African subjects and Caucasian insulin-dependent diabetic patients. The level of Na/K ATPase activity and the number of enzyme units were about 30% lower in the red blood cells of diabetic patients and North African subjects, than in healthy Caucasian controls. In healthy North African subjects predisposed to neuropathy in case of development of diabetes, the decrease in enzymatic activity was correlated with a decrease in the number of enzyme units. This correlation was not observed in diabetic patients. We speculate that the constitutional decrease in Na/K ATPase activity in healthy North African subjects corresponds to a quantitative defect, whereas the acquired decrease in diabetic patients corresponds to a qualitative defect probably related to the structure of the lipid membrane.

Adult↗
PubMed1996

Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes.

OBJECTIVE: To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS: An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied. RESULTS: The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone. CONCLUSIONS: In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.

Adipocytes↗
PubMed1996

Erythrocyte Na(+)-K(+)-ATPase activity, metabolic control, and neuropathy in IDDM patients.

OBJECTIVE: To study the relationship among red blood cell Na(+)-K(+)-ATPase activity, metabolic control, and diabetic neuropathy. RESEARCH DESIGN AND METHODS: Na(+)-K(+)-ATPase activity has been measured in the red cell membrane of 43 long-standing IDDM patients (duration of diabetes 17.5 +/- 2 years, mean +/- SE), with 20 of the patients presenting with peripheral neuropathy. There were 23 healthy subjects serving as the control group. RESULTS: Na(+)-K(+)-ATPase activity was significantly lower in diabetic patients than in healthy subjects (236.5 +/- 7.5 vs. 294 +/- 10 nmol P1 . mg protein-1 . h-1, P < 0.05). Among diabetic patients, Na+/K(+)-ATPase activity was not dependent on the degree of diabetic control, nor was it correlated with either fasting blood glucose (r = 0.16, NS) or HbA1 (r = 0.01, NS). Na(+)-K(+)-ATPase activity was lower in patients with neuropathy than in those without it (212 +/- 8.5 vs. 261 +/- 6.6, P < 0.05). Furthermore, in a subgroup of 20 patients, a positive correlation was observed between erythrocyte Na(+)-K(+)-ATPase activity and nerve conduction velocity in the peroneal (r = 0.558, P < 0.02) and tibial nerve (r = 0.528, P < 0.05). CONCLUSIONS: These results suggest that diabetes-induced Na(+)-K(+)-ATPase activity dysfunction could be implicated in the pathogenesis of human diabetic neuropathy and the electrophysiological abnormalities observed in these patients.

Adult↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗
PubMed1996

Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus.

Disturbances of the haemostatic system may favour the development of vascular damage and the final occlusion events in the progress of coronary heart disease (CHD). It has been shown recently in epidemiological studies, that increased concentration of several factors, mainly fibrinogen, factor VII, von Willebrand factor (vWF), and the fibrinolytic variables plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA), can be considered as risk factors for CHD. As morbidity and mortality through coronary atherosclerosis are higher in type 2 diabetic patients than in nondiabetic subjects and as insulin resistance represents a situation which favours the development of atherothrombosis, evaluation of the haemostatic factors which are recognized as risk factors may be interesting to consider in these situations. In fact, it has been shown that the fibrinolytic parameters PAI-1 and t-PA antigen are strongly related to the metabolic disorder of insulin resistance, whereas the link with fibrinogen, factor VII, and vWF remains weak. Many cross-sectional studies conducted in different populations have shown that PAI-1 and t-PA antigen (which represents t-PA/PAI-1 complexes) are strongly correlated with insulin, triglyceride, high-density lipoprotein (HDL) cholesterol, body mass index, walst-to-hip ratio and blood pressure, and that the improvement of insulin resistance improves in parallel the metabolic abnormalities and the concentration of the fibrinolytic parameters. Attempts at explaining the elevated PAI-1 and t-PA antigen levels in the insulin resistance syndrome have involved many clinical and in vitro studies, in which the role of insulin, insulin propeptides, very-low-density lipoprotein (VLDL) triglyceride, insulin resistance per se, glucose, and adipose tissue have successively been analysed and the main results of these studies are presented in this review. Due to recent experimental data from animal models of thrombosis, a pathogenic role of decreased fibrinolytic activity or increased PAI-1 levels can be proposed and could play a role in the development of vascular disease in subjects with Type 2 diabetes or insulin resistance.

Blood Coagulation Factors↗
PubMed1996

[The implantable insulin pump in the treatment of diabetes. Hopes and reality?].

Advantages and drawbacks of the treatment of insulin-dependent diabetes by intra-peritoneal administration of insulin through an implanted infusion system are presented. This review is based upon our personal studies and the french experience centralized by the EVADIAC group. Between 1989 and 1994, 312 insulin-dependent patients were implanted in France. The mean followed up was 36 +/- 1 months, allowing an experience of 660 patients years. The main benefit is an important reduction in the incidence of severe hypoglycemia falling down from 15 per cent patient years before implantation to 2.5 per cent after. Although the patients were previously treated by intensive insulin treatment and well controlled, mean glycated hemoglobin was slightly improved and the glycemic stability increased as evidenced by the reduction of standard deviation of glycemia. Life duration of the implanted system averaged 38 months excepted for incidents requiring an explantation. Although the frequency of incidents was non negligible, they were acceptable. Vigilance, as performed by EVADIAC group is still necessary. This point can be illustrated by a technical problem which appeared recently and was due to a poor compatibility between a new preparation of insulin and the ejection chamber of the pump. Intraperitoneal administration of insulin allows to obtain plasma insulin concentration through the day closer to the physiology than that obtained with subcutaneous insulin infusion. Blood levels of some proteins, mainly SHBG and IGF1, return to normal values. However, this mode of administration is associated in some cases with an important increase of the insulin antibody levels, increase which does not seem to have a deleterious metabolic effect, but has to be carefully evaluated on the long term.

Adult↗
PubMed1995

[Bradycardia during treatments of weight loss].

Sinus bradycardia was observed in 10 adolescents participating in a weight loss diet conducted in a health centre. The precise cause was assessed. The subject's age ranged from 10 to 15 years and weight loss ranged from 8 to 24 kg over a period ranging from 8 to 23 weeks. None of the subjects had taken drugs with a bradycardic effect and search for toxic agents in the blood and urine was negative in all cases. Infection was suggested since 8 of the 10 adolescents had a rhinopharyngitis a few weeks before the discovery of bradycardia. This cause was not retained due to the lack of any signs of infection or inflammation and negative virus serology. Nutritional status was therefore retained as the most likely cause in these adolescents who were eating a diet containing < or = 1350 kcal/day. This hypothesis was supported by the results of work reported in 1970 showing arrhythmia in very low calorie diets. The effect is essentially related to the biological value of proteins in the diet, its duration and the initial weight of the subjects. In addition bradycardia is frequently seen in subjects taking hypocaloric diets or with anorexia nervosa and should be considered as an adaptation to hypometabolism rather than a true heart disorder. Thus the biological value of the proteins and the mineral status should be taken into consideration during the course of low calorie diets, even though bradycardia is frequent and does not require a specific treatment. Therefore heart rate and decreasing rate of weight loss should be carefully followed during the course of low calorie diets.

Adolescent↗
PubMed1995

Immunogenicity of long-term intraperitoneal insulin administration with implantable programmable pumps. Metabolic consequences.

OBJECTIVE: To assess immunogenicity of intraperitoneal insulin infusion via implanted pumps by two methods and to evaluate the possible influence of an increased antibody level on metabolic and clinical parameters. RESEARCH DESIGN AND METHODS: We studied insulin antibody levels in 17 type I diabetic patients before and until 24 months after implantation of a programmable pump delivering insulin intraperitoneally. Antibody levels were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). They were correlated with HbA1c, insulin requirements, free insulin, and the incidence of hypoglycemia. RESULTS: Insulin antibodies increased as soon as the 3rd month after implantation. This increase was sustained throughout the study period (month 0, 25.4 +/- 16.2%; month 3, 41.2 +/- 23.5%; month 12, 45.9 +/- 26%; month 24, 48.7 +/- 25%). The data was correlated with the two assay methods (RIA and ELISA). Postimplantation level was correlated with preimplantation level, which could indicate a predictive value of the latter . No correlation was observed with any metabolic parameters, particularly the number of hypoglycemic episodes. CONCLUSIONS: Our results indicate that intraperitoneal insulin administration by implantable programmable pumps leads to an increase of insulin antibodies, which are probably high-affinity antibodies (recognized by both RIA and ELISA). This increase in insulin immunogenicity did not induce significant metabolic consequences, which is reassuring for the future of programmable insulin pumps.

Adult↗
PubMed1995

Hypofibrinolysis and the insulin resistance syndrome.

Atherothrombosis seems now to be the most appropriate term to describe the pathogenic events leading to the development of cardiovascular disease. An impaired fibrinolysis may not only contribute to and aggravate the tendency to thrombosis but fibrin deposit may also play a role in the development of the atherosclerotic plaque. Hypofibrinolysis is observed among obese subjects and it has been shown that an excess of plasminogen activator inhibitor 1 (PAI 1) the main regulator of the fibrinolytic system, is closely associated to other components of the insulin resistance syndrome, namely, excessive body weight, high waist to hip ratio, elevated blood pressure, hyperinsulinemia and hypertriglyceridemia. PAI 1 levels decrease with measures attempting at decreasing insulin resistance. However, the mechanisms leading to increased PAI 1 levels are still unknown. On the basis of epidemiological studies, and in vitro studies with PAI secreting cells such as hepatocytes or endothelial cells, insulin, insulin precursors, and lipoproteins, mainly VLDL, appear candidates for triggering this excessive secretion, but no definite answer has yet been found.

Coronary Disease↗
PubMed1995

[Evaluation of assay methods of glycohemoglobin: reference method and parameter].

In this paper, the characteristics of the analytical procedures allowing the measurement of glycated hemoglobin products are presented. With respect to their respective performances, the authors recommend the specific measurement of HbA1c and the more reliable procedure, high pressure liquid chromatography (HPLC).

Chemistry Techniques, Analytical↗