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Biomedical subjects

B Vialettes

Publications and source records attributed to B Vialettes.

At least 91 records · Page 5Linked to original sources

Pharmacological approach in the treatment of insulin resistance.

Insulin resistance syndromes are heterogeneous in either severity or mechanism. Many drugs have been shown to counteract various elements of insulin resistance. Some of them, by normalization of metabolic parameters, decrease insulin resistance induced by chronic hyperglycemia in diabetes. Insulin and, to some extent, sulfonylureas are in this group, but these drugs are not stricto sensu medication of insulin resistance. Some drugs sensitize peripheral tissues to the action of insulin. For instance, biguanides and thiazolidine-dione facilitate translocation to the membrane of glucose transporter in presence of insulin. Other compounds as vanadate or IGF-1 mimic some peripheral action of insulin. Finally, blockade of FFA oxidation by specific inhibitors (methylpalmoxyrate) can limit insulin resistance. In 1992, among these compounds, specific of insulin resistance, biguanides are mostly used. However, the efficacy of these drugs is moderate and limited to type 2 diabetes.

Diabetes Mellitus, Type 2↗

[Mediterranean nutrition: a model for the world?].

The protection of Mediterranean populations against ischaemic heart disease has been recognised ever since the "Seven Countries" Study by Keys. It is probably related to the life style and, in particular, to the dietary habits of these populations. The Mediterranean diet is characterised by a certain frugality, a low intake of saturated animal fats contrasting with a high but reasonable intake of mono or polyunsaturated fatty acids, slow carbohydrates, fresh vegetables rich in antioxidating vitamins, fish and wine. These dietary habits have been shown to improve the lipid profile (not only lowering LDL-cholesterol but also raising the HDL-cholesterol), platelet activity and to reduce the phenomena of lipoperoxidation. The roles played by garlic and onions are controversial. Nevertheless, at pharmacological dosages, they have cholesterol lowering, fibrinolytic and antiaggregant effects. These dietary habits, which have been proved to be beneficial, should therefore be preserved in our country.

Allium↗

Autoantibody formation after bone marrow transplantation: a comparison between autologous and allogeneic grafts.

Various autoantibodies were screened in 11 allogeneic, 14 autologous bone marrow transplanted patients and 11 healthy controls. Except anti-mitochondria antibodies, autoantibodies were found with similar frequencies after allogeneic and autologous transplantation. Moreover, 50% of autoantibodies were already present before transplantation. These results suggest that factors other than allogeneic reaction could be responsible for autoantibody formation after bone marrow transplantation, in particular, pre-graft conditioning treatment and/or viral and bacterial infection. Nevertheless, the number of patients with 2 or more autoantibodies was significantly higher after allogeneic than after autologous grafting (respectively, 82% and 36.7%; p less than 0.05). Forty percent of allografted but none of autografted patients were still positive at 12 months post graft. So, allogeneic reaction could play a role in intensity of humoral response and its maintenance for a long period.

Adolescent↗

The soluble receptor of interleukin 2 is not a serum marker of the autoimmune activity in type I diabetes mellitus.

In order to determine if soluble interleukin 2 receptor (IL2R) was useful as a marker in screening for early Type 1 diabetes and in monitoring immunological treatment, we assayed serum IL2R levels in 67 controls, 43 patients with newly diagnosed diabetes and 28 first degree relatives of diabetic patients (5 subjects were islet cell antibody positive). In 23 diabetes, specimens were analysed at 3 and 6 months after diagnosis whether or not cyclosporin A was administered. Seven patients were in a clinical trial using anti IL2R monoclonal antibody and cyclosporin A. Since IL2R level in the normal population is elevated in the first 5 years of life then decreases until adulthood (age:IL2R correlation between 0 and 15 years: r = -0.42, P less than 0.05), subjects were carefully matched in age. In recent onset diabetes, this negative correlation disappeared and IL2R levels tended to decrease particularly in younger subjects. In Type 1 prediabetic subjects presenting persistent islet-cell antibody serum IL2R was not elevated. During immunological treatment of recent onset diabetes, serum IL2R remained stable and was not modified by cyclosporin A. As expected IL2R became undetectable during treatment with anti IL2R MC Ab. But it rebounded when treatment was stopped with no effect on remission. We concluded that IL2R levels in Type 1 diabetic patients is not useful in screening autoimmune activity or in evaluating the effectiveness of immunosuppressors.

Adolescent↗

Paradoxical lessening of autoimmune processes in non-obese diabetic mice after infection with the diabetogenic variant of encephalomyocarditis virus.

In order to gain insight into the interaction between autoimmunity and viral infection in the onset of insulin-dependent diabetes, non-obese diabetic (NOD) mice which spontaneously develop autoimmune diabetes were inoculated with the diabetogenic variant of the encephalomyocarditis virus (EMCV-D) before the onset of the disease. The pre-diabetic period was divided into two phases: the early phase (days 88 to 116) during which development of spontaneous diabetes is rare and the late phase (day 123 to 200) during which the incidence of spontaneous diabetes is high. As controls ICR mice of common ancestry were also inoculated. During the early phase diabetes was observed in 4/10 inoculated, 0/13 control NOD and 7/13 inoculated ICR males vs. 6/12 inoculated, 1/11 control NOD and 0/15 inoculated ICR females. However, in NOD female, virus-induced diabetes prevalence was variable from one experiment to another. In parallel the flow cytometric analysis showed a high percentage of L3T4+ T lymphocytes in the pancreas of inoculated female NOD mice 10 days after the infection. At this time a large proportion of both L3T4+ and Ly-2+ cells expressed the interleukin 2 receptor. During the late phase no new case of diabetes occurred in inoculated NOD mice but one case was observed in control NOD males and five in control NOD females. This prevention of autoimmune diabetes was constantly found in other experiments. Insulitis was milder in inoculated NOD mice of both sexes than in control NOD. Adoptive transfer of diabetes into irradiated 8-week-old males by splenocytes from 28-week-old females was successful in five out seven attempts with control splenocytes and in zero out of six attempts with splenocytes from inoculated mice. This immunosuppression was specific as the ability of lymphocytes to respond to soluble or allogeneic antigens was preserved. In the early phase EMCV-D precipitated the onset of diabetes in females NOD mice by amplifying L3T4+ T lymphocyte-mediated immune mechanisms. During the late phase viral infection had lessened immune processes in animals which had resisted or recovered from virus-induced diabetes.

Animals↗

Autoantibodies to the insulin receptor are infrequent findings in type 1 (insulin-dependent) diabetes mellitus of recent onset.

To determine whether autoantibodies to the insulin receptor may represent markers of Type 1 (insulin-dependent) diabetes, the prevalence of such antibodies was investigated in sera of 60 newly diagnosed untreated Type 1 diabetic patients. A sensitive assay, based on enzyme linked immunosorbent assay has been set up which detects antibodies to the insulin receptor irrespective of their potentially inhibiting effect on insulin binding. Moreover, this method allows easy determination of the immunoglobulin class involved in the anti-receptor activity. Among the 60 sera examined, only one was found to contain anti-insulin receptor autoantibodies (IgG class). In view of our data, we conclude that autoantibodies to the insulin receptor are infrequent findings in Type 1 diabetes of recent onset.

Adolescent↗

[Gestational diabetes].

Gestational diabetes defined by either glucose intolerance or overt diabetes discovered during pregnancy is a real nosologic entity which is associated with risks for both foetus and mother. Unfortunately biological definition of gestational diabetes remains controversial. In North America it is defined by O'Sullivan's criteria (OGTT with 100 g of glucose for 3 hours), in Europe it is defined by WHO's criteria (OGTT with 75 g of glucose for 2 hours). Strategy for selection of high risk women who have to be submitted to OGTT is also matter of debate. Despite these uncertainties, everybody agrees that gestational diabetes is associated with high risk of foetal macrosomia and high rate of cesarean section. For the mother, gestational diabetes is a marker of future development of diabetes. Most of gestational diabetes are related to type II diabetes but some cases of type I diabetes are preceded by gestational diabetes. The treatment of gestational diabetes depends upon the severity of glucose intolerance. It is resumed by dietetic intervention associated, if necessary, with insulin therapy.

Blood Glucose↗

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↗

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↗

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↗

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↗

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↗