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Biomedical subjects

P Vague

Publications and source records attributed to P Vague.

At least 109 records · Page 6Linked to original sources

Effect of nicotinamide treatment on the residual insulin secretion in type 1 (insulin-dependent) diabetic patients.

In vivo and in vitro experiments have shown that nicotinamide enhances the regeneration of rat B cells. Nicotinamide has been administered to human subjects at a dose of 3 g/day for more than one year without any serious side effects. A trial was conducted to study if nicotinamide could protect B cells in Type I (insulin-dependent) diabetic patients with established diabetes, but still with residual insulin secretion, the latter being evaluated throughout the study period. A randomized double-blind study was carried out on 26 Type I diabetic patients aged 15 to 40 years who had been treated with insulin for 1 to 5 years but who had a residual insulin secretion characterized by a glucagon stimulated C-peptide level higher than 0.1 nmol/l. They were given either 3 g/day of nicotinamide or a placebo for nine months. At baseline the treated and control groups did not differ according to age, diabetes duration, insulin dose, HbA1c or C-peptide levels. Three patients dropped out of the study. At 9 months there were no significant changes in the insulin doses required. However, HbA1c rose in the control group (8.1 +/- 0.4 vs 9.8 +/- 0.5%, p less than 0.05) but not in the nicotinamide treated group (7.5 +/- 0.5 vs 6.9 +/- 0.4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fat distribution and plasminogen activator inhibitor activity in nondiabetic obese women.

Epidemiologic data strongly suggest that upper distribution of body fat and high plasminogen activator inhibitor (PAI) activity are risk factors for cardiovascular disease. Therefore, a link between these two parameters was evaluated by studying 51 menstrually active nondiabetic obese women. In this group positive correlations were observed between body mass index (BMI), waist to hip circumference ratio (W/H ratio, which estimates body fat distribution), plasma insulin, and PAI activity. In addition, plasma triglycerides were related to the W/H ratio and insulin and PAI activity. Partial correlations revealed that BMI was independently and solely related to W/H ratio, which was also independently related to plasma insulin, which in turn related to PAI activity. These results suggest that upper body fat distribution acts as a risk factor of cardiovascular disease through its association with high PAI activity.

Adipose Tissue↗

High dose nicotinamide fails to prevent diabetes in BB rats.

Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.

Age Factors↗

[Sexual differentiation of the adipose tissue-muscle ratio. Its metabolic impact].

Muscle and fat development are regulated by opposite and also cooperating factors. Adipo-muscular ratio is the result of those forces. The need of a determined fat mass and of its corollary a determined muscle mass is an important physiologic parameter. Sexual differentiation is the main factor adipo-muscular ratio. Feminine fat is twice as big as masculine fat: it predominates in the lower body, masculine fat in the upper body. Brachio-femoral adipo-muscular ratio is, among others, a good index of fat sexual differentiation. Android obesity, predominating in both sexes in the upper body, is, with genetic predispositions, the main factor of non insulin dependent diabetes carbohydrate sensitive hyperlipoproteinemia, hyperuricemia, atherosclerosis. Easy determination on fat topography before the age of 30 is, particularly in women, the best tool for an efficacious prophylaxis of obesity's metabolic complications.

Adipose Tissue↗

Low acute insulin response to intravenous glucose. A sensitive but non-specific marker of early stages of type 1 (insulin-dependent) diabetes.

Preventive treatment of Type 1 (insulin-dependent) diabetes presupposes early and accurate diagnosis of prediabetic states. The low acute insulin response to intravenous glucose has been proposed as a marker of both pre-Type 1 and pre-Type 2 (non-insulin-dependent) diabetes. In order to test the reliability of this marker for clinical detection of Type 1 diabetes we looked for this anomaly in 150 first degree relatives of Type 1 diabetic patients, 31 relatives of Type 2 diabetic patients and 39 young non-obese diabetic patients with mild or transient hyperglycaemia. The low acute insulin response was defined by a peak insulin value (sum of plasma insulin at 2 and 5 min after glucose load, 0.3 g/kg body weight) below 50 microU/ml. It was observed in 12% of the relatives of Type 1 diabetic patients (2 of them became diabetic) and in 13% of the relatives of Type 2 diabetic patients. Reproducibility of the peak insulin value in 2 subsequent tests (r = 0.749) was inadequate to interpret small variations in one individual. In the population of 39 diabetic patients, 10 subsequently developed typical Type 1 diabetes, 9 were low insulin responders. In the 29 patients who are still non-insulin-dependent 3 years later, the anomaly was found in the 3 islet cell antibody-positive subjects and 11 out of 26 patients with no detectable antibodies. In conclusion, low acute insulin response to glucose is a sensitive but non-specific marker of early stages of Type 1 diabetes as this anomaly is shared by both Type 2 and Type 1 diabetes.

Adolescent↗

[The effect of pentoxifylline and propentofylline on the membrane fluidity of red blood cells in uncontrolled insulin-dependent (type 1) diabetic patients].

Fluorescence polarization of red blood cell (RBC) membranes evaluated using DPH was measured in patients with uncontrolled insulin-dependent diabetes mellitus and in controls. The effect of in vitro addition of pentoxifylline and propentofylline (10(-5) and 10(-4) M) was studied. The fluorescence polarization parameter (P) was lower in the diabetic patients (p = 0.20 +/- 0.03, n = 8) as compared to the controls (p = 0.28 +/- 0.02), n = 8), reflecting an increase in probe mobility in the hydrophobic environment in the depth of the double lipid layer. In vitro addition of pentoxifylline had no effect on the fluorescence parameter of RBC membranes from controls, whereas both concentrations of pentoxifylline studied (p = 0.24 +/- 0.03) significantly increased the fluorescence parameter of RBC membranes from diabetics. Propentofylline had no effect. These findings suggest that the active site responsible for improved membrane fluidity of RBC from diabetics is located on the methyl radical present in the pentoxifylline molecule but not in the propentofylline molecule.

Diabetes Mellitus, Type 1↗

Increased prevalence of neurologic complications among insulin dependent diabetic patients of Algerian origin.

This study was undertaken to ascertain a clinical impression that the prevalence of complications is higher in insulin-dependent Algerian diabetics than in their European counterparts. Forty-one Algerian patients under regular follow-up for 2 years or more were closely matched to 41 French insulin dependent diabetics with regard to sex (34M/7F) and duration of disease (10.5 +/- 1 year; range 2 -32 years). Insulin dose, number of injections, arterial blood pressure, glycemia, glycosylated haemoglobin, cholesterolemia and triglyceridemia were similar in the two groups. The age at the time of diagnosis of diabetes was higher in the Algerian group (28.7 +/- 1.9 vs 21.4 +/- 1.7) as was the number of smokers (23/41 vs 12/41). No difference was noted between the two groups with respect to the prevalence of retinopathy (absent, simple, proliferative): 25, 12, and 4 vs 29, 9, and 3 or nephropathy (absent, incipiens, patent): 30, 6, 5 for the Algerians and 35, 3, 2 for the French. This suggest that long term metabolic control was relatively identical in the two groups. The incidence of neuropathy rated as absent, moderate (abolished reflexes, impaired pallesthesia, cardiac neuropathy) or severe was significantly higher in the Algerians (13, 16 and 12) as compared to the French (28, 10 and 3) p less than 0.01. Severe neuropathy in the Algerian group was often multiple (8/12), serious and early. The only difference between the neuropathic and non-neuropathic Algerian subgroups was the duration of disease (13.2 +/- 2.2 vs 7.3 +/- 0.01; p less than 0.01). Since there were apparently no acquired nutritional factors, an ethnic predisposition of Algerians to develop neuropathy seems likely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Metformin decreases the high plasminogen activator inhibition capacity, plasma insulin and triglyceride levels in non-diabetic obese subjects.

We have previously observed a positive correlation between Plasminogen Activator Inhibition capacity (PA Inhibition), Body Mass Index (BMI) and plasma insulin levels in a population of non diabetic subjects. The anti diabetic biguanide Metformin which decreases insulin resistance has been reported to increase the blood fibrinolytic activity. Therefore we have studied the effect of Metformin on PA Inhibition levels in obese subjects with normal glucose tolerance. Eighteen obese women (O) (BMI: 31.4 +/- 1.13, m +/- S.E.M.) were compared to age matched controls (C) (BMI: 20.2 +/- 0.8) and randomized to a 15 days treatment by Metformin (M) (1.7 g/day) or placebo (P) in a double blind study while on a weight maintaining diet. O compared to C had higher levels (m +/- S.E.M.) of PA Inhibition (9 +/- 1.8 IU/ml, versus 2.88 +/- 0.29 p less than 0.01), lower euglobulin fibrinolytic activity (EFA) (4.95 +/- 1.17 mm versus 9 +/- 0.29 p less than 0.05), higher plasma insulin (24.1 +/- 2.1. uU/ml), versus 12 +/- 1 p less than 0.01) and triglyceride (1.32 +/- 0.16 mmol/l, versus 0.8 +/- 0.08 p less than 0.05). After 15 days of treatment, in group M a significant decrease in PA Inhibition (5.51 +/- 1.4, versus 9.48 +/- 2.1 p less than 0.05) in plasma insulin (18.5 +/- 0.1, versus 24.5 +/- 3.5, p less than 0.05) and plasma triglyceride (1.08 +/- 0.1, versus 1.47 +/- 0.3 p less than 0.05) and an increase in EFA (6.50 +/- 0.28, versus 5.25 +/- 0.35 p less than 0.05) were observed. No significant variation was observed in group P.

Adolescent↗

Correction by pentoxifylline of the abnormal fluorescence polarization of erythrocyte membranes from diabetic patients.

Erythrocytes from diabetic patients show abnormal rheology. Pentoxifylline, a methylxanthine, improves the abnormal deformability of diabetic erythrocytes, but its mechanism of action remains unclear. We have studied the effect of pentoxifylline on the lipid order of erythrocyte membranes from controls and patients with Type I diabetes. We studied the structural organization of membrane lipids in individual erythrocyte ghosts by fluorescence polarization using a cell sorter. Fluorescence polarization values (P) for 17 controls (P = 0.244) and 20 diabetic patients (P = 0.215) were significantly different. Pentoxifylline added in vitro had no effect on normal membranes, but significantly increased at 10(-5) mol X l-1 (P = 0.233), and normalized at 10(-4) mol X l-1 (P = 0.243), the P value of membrane ghosts from diabetics.

Adult↗

In vivo insulin effect on ATPase activities in erythrocyte membrane from insulin-dependent diabetics.

Na+-K+-dependent ouabain-sensitive ATPase and Mg2+-ATPase have been assayed in the erythrocyte membranes of control subjects and in uncontrolled type I (insulin-dependent) diabetics. A decrease in Na+-K+-ATPase activity was observed in the patients that was significantly correlated with glycemia. The Mg2+-ATPase was increased moderately, and no correlation with glycemia was found. To study the in vivo effect of insulin, ATPase activities were measured in uncontrolled diabetics before and after a 24-h continuous insulin perfusion administered by means of an artificial pancreas. ATPase activities were corrected after normalization of glycemia. It therefore seems that glycemia and/or insulinemia are involved in the regulation of erythrocyte Na+-K+ ouabain-sensitive ATPase and to a lesser extent in that of Mg2+-dependent ATPase.

Adenosine Triphosphatases↗

Cold reacting antilymphocyte antibodies in type I (insulin dependent) diabetes.

Non HLA antilymphocyte antibodies have been detected in numerous auto-immune illnesses and notably in type I (insulin dependent) diabetes. In order to ascertain their role in this illness, the actual frequency of this phenomenon has been estimated. The privileged cellular target has been determined. Finally correlations with the other immunogenetic markers of diabetes have been investigated. Non HLA antilymphocyte antibodies are frequent, above all at the beginning of the illness (32.4% before 6 months, 10% after 5 years). The cellular target is mainly composed of B lymphocytes. B lymphocyte enrichment of cellular suspensions leads to better method sensitivity (70.3% positive reactions at the beginning of the illness). No correlation was found with presence of anti islet cell antibodies or anti coxsackie B virus antibodies (IgM). Association with the HLA DR3 phenotype is relatively frequent but does not attain statistical significance.

Adult↗

Relationships between plasma insulin triglyceride, body mass index, and plasminogen activator inhibitor 1.

Low fibrinolytic activity, as measured by euglobulin (EFA), has been observed in obese subjects, and hypofibrinolysis may play a role in the pathogenesis of atherosclerosis and its complications. Blood fibrinolytic activity is regulated through a complex system of activators and inhibitors, especially plasminogen activator inhibitors (PA Inhibitors). In a group of 35 non-diabetic subjects with a wide range of body mass index (BMI), EFA was negatively correlated, and PA Inhibitor activity positively correlated, with BMI and plasma insulin levels. In a population of 49 non-diabetic obese women (differing from a control group of normal weight by lower EFA and higher level, of PA Inhibitor activity, plasma insulin and triglyceride), the PA Inhibitor activity was positively correlated with BMI, insulin and triglyceride. The increase in PA Inhibitor activity was associated with a high value of PA Inhibitor 1 antigen measured by an immuno-radiometric assay, indicating that the increased activity was due to a high level of circulating PA Inhibitor 1. Plasma insulin was lowered in obese non-diabetic subjects, without modification of the body weight, by a 24 hour fast or by treatment with Metformin. After 24 hours' fast, ten obese subjects had lower levels of insulin and PA Inhibitor activity and an increase in EFA. Treatment for 15 days by 1.75 g Metformin (or placebo), on a weight maintaining diet, induced, in the Metformin group, a decrease in plasma insulin, triglyceride and PA Inhibitor activity and an increase in EFA, while no change was observed in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗