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E Larger

Publications and source records attributed to E Larger.

At least 37 records · Page 2Linked to original sources
PubMed1998

Major histocompatibility class II genes polymorphism in insulin dependent diabetes mellitus with or without associated thyroid autoimmunity.

Insulin dependent diabetes mellitus (IDDM) is sometimes associated with extrapancreatic organ-specific autoimmune diseases, but whether this phenotype results from a peculiar genetic profile is still unclear. The allelic distribution of the major histocompatibility complex (MHC) class II genes (HLA-DRB1, DQA1, DQB1 and TAP) was analysed in 143 patients with IDDM alone by comparison with 82 IDDM patients with autoimmune thyroid disease (IDDM/AITD). The frequency of the DQB1*0301 IDDM-protective phenotype seemed to be lower in IDDM than in IDDM/AITD patients (16.8% vs 30.5% respectively, p = 0.02). By contrast, the frequency of the DRB1*04-DQB1*0302 IDDM-predisposing phenotype was higher in IDDM than in IDDM/AITD patients (91.3% vs 76.1% of DR4-positive patients respectively, p = 0.007), but these differences were not significant after correcting the p values, except in the case of the DRB1*0405-DQB1*0302 combination (21.3% vs 2.4% of DR4-positive patients, Pc = 0.05). Furthermore, all differences disappeared when patients were matched for age at IDDM-onset. Our data do not long give support for a particular role of MHC class II genes in favouring the occurrence of thyroid autoimmunity in IDDM patients, but rather suggest that some class II alleles or residues might determine the rapidity of progression to IDDM in genetically susceptible individuals. The involvement of non-MHC genes and/or environmental factors remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Acute renal failure in a diabetic patient.

We report the case of a young insulin-dependent diabetic patient in whom acute renal failure led to detection of ureterohydronephrosis secondary to neurogenic bladder. The persistence of a high daily urine volume revealed diabetes insipidus, suggesting Wolfram syndrome, which was confirmed by the diagnosis of optic atrophy. The main features of Wolfram syndrome, particularly urologic ones, and their treatment are discussed in the light of our findings in this patient.

Acute Kidney Injury↗
PubMed1997

Immune mechanisms leading to type 1 insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) results from the autoimmune destruction of the endocrine (beta) cells responsible for the secretion of insulin. Experimental and human studies have resulted in unpredicted developments over the past ten years. Against most predictions, a long list of possible autoantigens has been defined, most of which are not beta-cell specific. Seemingly, up to 10 to 20 genetic regions, rather than 2 to 3 as initially predicted, carry markers that associate them with IDDM. Finally, there is accumulating evidence that beta cells are not a passive bystander in the event that leads to the activation of the diabetes autoimmune reaction. Whether the immune system or the islet, or both, are at the initiation of the disease process is a challenge for the near future.

Animals↗
PubMed1996

[Immunological prospects in the treatment of type 1 diabetes mellitus].

The first therapeutical trials using conventional immunosuppressive agents in recent onset type-1 diabetes mellitus have shown that such an approach can be efficient. However, remissions have remained inconstant and, when induced, transient. New approaches are being developed in experimental models in animals. Some, especially attempts to induce immune tolerance per os, could find rapid applications in the human.

Animals↗
PubMed1995

Pancreatic islet beta cells drive T cell-immune responses in the nonobese diabetic mouse model.

The role of autoantigens and that of target organs in which tissue lesions develop remains elusive in most spontaneous models of autoimmune diseases. Whether the presence of target autoantigens is required for the recruitment of autoreactive lymphocytes is unknown in most cases. To evaluate the importance of islet cells in the development of autoimmunity in the nonobese diabetic (NOD) mouse, we generated beta cell-deprived mice by injecting a high dose of alloxan, a toxic agent specific for beta cells. In contrast with spleen cells from 6-mo-old naive NOD mice which transfer diabetes in irradiated 8-mo-old male recipients, spleen cells from age-matched NOD mice which received a single injection of alloxan at 3 wk of age did not transfer diabetes. With the exception of the ability to transfer diabetes, beta cell-deprived NOD mice showed maintained immune competence. Furthermore, sialitis developed with the expected intensity and prevalence in beta cell-deprived mice. Already committed "diabetogenic" spleen cells collected from spontaneously diabetic mice also showed a reduced capacity to transfer diabetes after their removal from the diabetic mice and transient "parking" in beta cell-deprived mice. Taken together, our data bring evidence that involvement of autoreactive T cells detected by the capacity to transfer diabetes requires the presence of target beta cells.

Animals↗
PubMed1995

Anti-bovine serum albumin antibodies: genetic heterogeneity and clinical relevance in adult-onset IDDM.

OBJECTIVE: To evaluate the prevalence of anti-bovine serum albumin (BSA) antibodies in patients with adult-onset insulin-dependent diabetes mellitus (IDDM) and investigate a possible link between their presence and genetic susceptibility or resistance determined by human leukocyte antigen (HLA) complex. RESEARCH DESIGN AND METHODS: Sera from 60 recent-onset diabetic patients, 5 prediabetic subjects, and 102 healthy control subjects were tested using a radioimmunoprecipitation assay. HLA-DRB and -DQB alleles were determined by means of allele-specific oligonucleotide typing. Islet cell antibodies (ICAs) were assayed by indirect immunofluorescence. RESULTS: Levels of anti-BSA antibodies were significantly higher in IDDM patients (18.1 +/- 3.5%, n = 60) than in healthy control subjects (7.5 +/- 1.2%, n = 102) (P < 0.001), but in only 16.6% of IDDM patients (10 of 60) were the titers above the 95th percentile of control values. Anti-BSA antibody titers were higher in HLA-DR3 and/or -DR4 patients (23.4 +/- 4.9%, n = 41) compared with DR3 and/or DR4 control subjects (3.1 +/- 1.0%, n = 10) (P < 0.001). DR3 IDDM patients showed higher levels of anti-BSA antibodies (26.3 +/- 6.3%, n = 30) than non-DR3 patients (9.9 +/- 2.6%, n = 30) (P < 0.01) and healthy control subjects. Only two out of five prediabetic subjects had significant anti-BSA levels before clinical onset of diabetes. CONCLUSIONS: Our data confirm that antibodies to BSA are present in adult-onset IDDM patients, particularly in HLA-DR3-positive patients. However, the prevalence of anti-BSA antibodies was lower than previously reported in children, and there was a considerable overlap with healthy control subjects. Only two out of the five prediabetic patients demonstrated anti-BSA antibodies. Taken together, these results do not bring strong support to the clinical usefulness of anti-BSA antibodies as a relevant marker in diabetes prediction or diagnosis.

Adolescent↗
PubMed1995

Mefloquine-associated hypoglycaemia in a cachectic AIDS patient.

Quinine and its isomer quinidine are well-known causes of iatrogenic hypoglycaemia, due to excessive insulin secretion. The situation is less clear regarding other anti-malarial quinine analogues. In particular, this adverse effect has never been described with mefloquine (Lariam). We report a case of hypoglycaemia after mefloquine therapy (1,500 mg over two days) for severe gastrointestinal cryptosporidiasis in a cachectic AIDS patient with protracted diarrhoea. Blood glucose levels, which were normal before treatment, dropped to 2.3 mmol/l within a few hours and were corrected by i.v. glucose infusion. Hypoglycaemia did not recur despite continued treatment. Rat islets of Langerhans exposed to mefloquine in vitro (10(-8) mol/l to 10(-3) mol/l) secreted significantly more insulin than control islets (up to 980 +/- 180 microU/ml/5 islets incubated with mefloquine 10(-3) mol/l, vs 20 +/- 4 microU/ml/5 untreated islets). Mechanisms and triggering factors of hypoglycaemia induced by mefloquine and some other anti-malarial quinine analogues are discussed. Clinicians who manage cachectic patients, particularly those with protracted diarrhoea and/or receiving anti-malarial drugs including mefloquine, should be aware of the risk of severe hypoglycaemia.

Acquired Immunodeficiency Syndrome↗
PubMed1994

IDDM: an islet or an immune disease?

Insulin-dependent diabetes develops as a consequence of the selective destruction of insulin-producing cells by an autoimmune reaction. However, the precise series of events which trigger anti-islet autoreactive T cells is still being investigated. Major issues will need to be raised before a comprehensive view of the anti-islet autoimmune reaction can be delineated. These include defining the primary site of activation of autoreactive lymphocytes and exploring hypotheses to explain the chronicity of the diabetes process. These issues all relate with the more general dilemma of the actual role of the islets of Langerhans in breaking self tolerance to beta-cell antigens. By studying non-obese diabetic mice deprived of beta cells following a single injection of a high dose of alloxan at 3 weeks of age, we recently obtained evidence that the activation of autoreactive T cells requires the presence of target islet cells in order to develop.

Animals↗
PubMed1994

[Is a gene therapy for diabetic syndromes foreseeable?].

The concepts and methods of gene therapy are summarized in order to assess a possible implication in the treatment of diabetes mellitus. Gene therapy requires identification of the critical genetic defect and then the preparation and introduction of the therapeutic transgene, with an appropriate targeting and a strong regulated expression. The bases of the different human diabetic syndromes are reviewed in their present state of knowledge: they are mostly clarified in the case of MODY, extreme insulin resistance syndromes, and some mitochondrial diabetic syndromes; but still obscure in the case of Type 2 and Type 1 diabetic syndromes. Substantial contributions to the understanding of the pathophysiology of diabetes have been brought by transgenic animal models. Gene therapy of human diabetic syndromes may become available, in an undetermined future, particularly under the forms of insulin secreting transgenic "organoïds". Such treatments should be proportionate to the intrinsic severity of the candidate diseases and carefully screened for safety.

Animals↗