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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary antigens are candidate environmental factors in the pathogenesis of type 1 diabetes. In the non-obese diabetic (NOD) mouse, an animal model of type 1 diabetes, cereal-based diets promote disease development, whereas the diets based on hydrolysed proteins or non-diabetogenic proteins are protective. The hypothesis that diabetogenic diets modulate the cytokine balance in the gut was tested. NOD mice were fed with NTP-2000 (mainly a wheat-based milk-free diet) or Prosobee (a semi-purified hypoallergenic diet based on soy protein isolate) or Prosobee plus casein (milk protein fraction). The mRNA levels of IFN-gamma, IL-10, TNF-alpha, TGF-beta, and inducible NO synthase in the small intestine and the Peyer's patches were determined by semi-quantitative RT-PCR. Mice fed on the cereal-based NTP-2000 diet expressed higher levels of the Th1-type and pro-inflammatory markers IFN-gamma, TNF-alpha, and inducible NO synthase mRNA compared to the Prosobee-fed animals. The expression of the counterregulatory cytokines IL-10 and TGF-beta was unaffected. This resulted in a significant bias of the intestinal cytokine balance towards T helper cell type 1 after feeding NTP-2000. The cytokine mRNA levels in the gut-associated Peyer's patches were not affected. Thus, modulation of gut immunoreactivity by diet may contribute to disease development in NOD mice.
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PMID:A wheat-based, diabetes-promoting diet induces a Th1-type cytokine bias in the gut of NOD mice. 1269 53

Involvement of gut immune system has been implicated in the pathogenesis of type 1 diabetes. However, few studies have been performed on the gut mucosa from patients with type 1 diabetes. Thus, we characterized the stage of immune activation in jejunal biopsy samples from 31 children with type 1 diabetes by immunohistochemistry, in situ hybridization, and RT-PCR. We found enhanced expressions of HLA-DR, HLA-DP, and intercellular adhesion molecule-1 by immunohistochemistry even on structurally normal intestine of patients with type 1 diabetes and no signs of celiac disease. In addition, the densities of IL-1 alpha- and IL-4-positive cells detected by immunohistochemistry and IL-4 mRNA-expressing cells evaluated by in situ hybridization were increased in the lamina propria in patients with type 1 diabetes and normal mucosa. Instead, the densities of IL-2, gamma-interferon (IFN-gamma), and tumor necrosis factor alpha-positive cells, the density of IFN-gamma mRNA positive cells, and the amounts of IFN-gamma mRNA detected by RT-PCR correlated with the degree of celiac disease in patients with type 1 diabetes. Our study supports the hypothesis that a link exists between the gut immune system and type 1 diabetes.
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PMID:Immunologic activity in the small intestinal mucosa of pediatric patients with type 1 diabetes. 1294 68

Although controversial, exclusive breast milk feeding was shown to exert a protective effect in preventing type 1 diabetes. In contrast, an early introduction of cow's milk-based formula in young infants may enhance the risk of disease, especially in genetically susceptible children, presumably by an increase of intestinal permeability to macromolecules such as bovine serum albumin and beta-casein, which may arouse autoimmunity. We have shown that human milk contains insulin in substantial concentrations, while insulin is barely detectable (if at all) in infant formulas. Orally administered insulin was demonstrated to promote gut maturation and to reduce intestinal permeability to macromolecules. Furthermore, oral insulin may induce tolerance to insulin and protect against the development of type 1 diabetes. We herewith raise a hypothesis that human milk is protective against the development of type 1 diabetes by virtue of the effects of its substantial content of insulin.
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PMID:Insulin in human milk and the prevention of type 1 diabetes. 1501 83

The origin of autoimmunity leading to the destruction of insulin-producing beta-cells is not known. Several studies suggest that a link exists between the gut immune system and the islets infiltrating lymphocytes. Inflamed pancreatic islets express the same adhesion molecules involved with the homing of gut-associated lymphocytes. The manifestation of autoimmune diabetes in the animal models can be modified by dietary factors, which cause changes in the cytokine production by islet-infiltrating lymphocytes. Increased risk of type 1 diabetes has been associated with an early introduction of cows' milk formula in infancy, indicating that triggering of the gut immune system in early infancy may contribute to the later development of beta-cell autoimmunity. Enhanced immune reactivity to cow milk (CM) proteins in the patients with type 1 diabetes suggests aberrant regulation of the gut immune system in this disease. In the patients with newly diagnosed type 1 diabetes, anti-glutamate decarboxylase (GAD)-reactivity was found in the subpopulation of lymphocytes expressing gut-associated homing receptor alpha 4 beta 7. Based on these findings, the hypothesis that aberrant function of the gut immune system would lead to the development of beta-cell autoimmunity and type 1 diabetes has recently received a lot of attention. The possibility that regulation of the gut immune system is not normal in subjects at risk of autoimmune diabetes should be considered when treatments interfering with mucosal immunity for the prevention of type 1 diabetes are planned.
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PMID:The role of the gut in beta-cell autoimmunity and type 1 diabetes: a hypothesis. 1501 19

Defects in the intestinal immune system may contribute to the pathogenesis of autoimmune diseases. Intraepithelial lymphocytes represent a substantial fraction of gut-associated lymphocytes, but their function in mucosal immunity is unclear. A newly described population of NK cells that spontaneously secrete IL-4 and IFN-gamma is present in the intraepithelial lymphocyte compartment of the rat. We hypothesized that defects in the number or function of these cells would be present in rats susceptible to autoimmunity. We report that the number of NKR-P1A(+)CD3(-) intraepithelial NK (IENK) cells is deficient before onset of spontaneous autoimmune diabetes in diabetes-prone BB (BBDP) rats. The absolute number of recoverable IENK cells was only approximately 8% of that observed in WF rats. Bone marrow transplantation from histocompatible WF donors reversed the IENK cell deficiency (and prevented diabetes) in these animals, suggesting a hemopoietic origin for their IENK cell defect. Analysis of diabetes-resistant BB rats, which develop autoimmune diabetes only after perturbation of the immune system, revealed IENK cell numbers intermediate between that of BBDP and WF rats. IENK cells were selectively depleted during treatment to induce diabetes. Prediabetic BBDP and diabetes-resistant BB animals also exhibited defective IENK cell function, including decreased NK cell cytotoxicity and reduced secretion of IL-4 and IFN-gamma. IENK functional defects were also observed in LEW and BN rats, which are susceptible to induced autoimmunity, but not in WF, DA, or F344 rats, which are resistant. Defects in IENK cell number and function may contribute to the pathogenesis of autoimmune diseases including type 1 diabetes.
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PMID:Deficiencies in gut NK cell number and function precede diabetes onset in BB rats. 1510 Feb 75

Celiac disease (CD) is a complex inflammatory disorder of the small intestine, induced by dietary gluten in genetically susceptible individuals. CD is strongly associated with HLA-DQ2 and it has recently been established that gut-derived DQ2-restricted T cells from patients with CD predominantly recognize gluten-derived peptides in which specific glutamine residues are deamidated to glutamic acid by tissue transglutaminase. Recently, intestinally expressed human genes with high homology to DQ2-gliadin celiac T-cell epitopes have been identified. Single or double point mutations which would increase the celiac T-cell epitope homology, and mutation in these genes, leading to the expression of glutamic acid at particular positions, could hypothetically be involved in the initiation of CD in HLA-DQ2-positive children. Six gene regions with high celiac T-cell epitope homology were investigated for single-nucleotide polymorphisms using direct sequencing of DNA from 20 CD patients, 27 type 1 diabetes mellitus (T1DM) patients with associated CD, 24 patients with T1DM without CD and 110 healthy controls, all of Caucasian origin. No variants in any of these genes in any of the investigated groups were found. We conclude that gut-expressed human celiac epitope homologous peptides are unlikely to represent non-HLA risk factors in the development of celiac disease in Caucasians.
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PMID:No allelic variation in genes with high gliadin homology in patients with celiac disease and type 1 diabetes. 1530 43

A nonlinear model predictive controller has been developed to maintain normoglycemia in subjects with type 1 diabetes during fasting conditions such as during overnight fast. The controller employs a compartment model, which represents the glucoregulatory system and includes submodels representing absorption of subcutaneously administered short-acting insulin Lispro and gut absorption. The controller uses Bayesian parameter estimation to determine time-varying model parameters. Moving target trajectory facilitates slow, controlled normalization of elevated glucose levels and faster normalization of low glucose values. The predictive capabilities of the model have been evaluated using data from 15 clinical experiments in subjects with type 1 diabetes. The experiments employed intravenous glucose sampling (every 15 min) and subcutaneous infusion of insulin Lispro by insulin pump (modified also every 15 min). The model gave glucose predictions with a mean square error proportionally related to the prediction horizon with the value of 0.2 mmol L(-1) per 15 min. The assessment of clinical utility of model-based glucose predictions using Clarke error grid analysis gave 95% of values in zone A and the remaining 5% of values in zone B for glucose predictions up to 60 min (n = 1674). In conclusion, adaptive nonlinear model predictive control is promising for the control of glucose concentration during fasting conditions in subjects with type 1 diabetes.
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PMID:Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes. 1538 30

Accumulating data indicate that intestinal dysfunction and dysregulation of the gut immune system may play a role in the development of type 1 diabetes. This review deals with the occurrence of gut damage and dysfunction in BB rats, an animal model of spontaneous immune type 1 diabetes, placing special emphasis on the effect of diet on the incidence of diabetes in BB rats, the identification of a type 1 diabetes-related protein from wheat, and preliminary observations documenting anomalies in the inductive tissues of the gut immune system (Peyer's patch cells and mesenteric lymph node cells) and pancreatic lymph node cells of diabetes-prone BB rats. In addition to histological evidence of gut damage, the review will also draw attention to altered intestinal disaccharidase activity, changes in intestinal peroxidase activity, glucagon-like peptide 1 anomalies, and perturbation of both intestinal permeability and mucin content in BB rats. In all these cases, the findings in rats fed a diabetes-promoting diet are compared to those collected in animals receiving a protective diabetes-retardant diet.
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PMID:Insulin-dependent diabetes and gut dysfunction: the BB rat model. 1548 8

In diabetes-prone BioBreeding rats, an enteropathy often precedes the onset of auto-immune insulitis. The present study draws attention to quantitative and qualitative alterations of intestinal mucins in this animal model of type 1 diabetes mellitus. Male and female diabetes-resistant (BBc) and diabetes-prone (BBdp) BioBreeding rats fed, from one to two weeks after weaning onwards, either a plant-based diabetes-promoting diet (NTP) or a hydrolysed casein diabetes-protective diet (HC), were sacrificed at 11-14 weeks of age. Proteins and total mucins, as well as acid and neutral mucins, were measured in a segment of the intestinal tract, located 25-30 cm below the pylorus. No significant difference between BBc and BBdp rats was found when fed the HC diet. However, the NTP diet lowered both total and neutral mucins, whilst failing to affect significantly acidic mucins. The effects of the NTP diet were more pronounced in BBdp rats than in BBc rats. It is speculated that the quantitative and qualitative changes evoked by the NTP diet in BBdp rats may play a role in the alteration of gut permeability found under the same experimental conditions.
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PMID:Quantitative and qualitative alterations of intestinal mucins in BioBreeding rats. 1558 35

Newer insulins and easier blood glucose monitoring have greatly improved the ability to obtain excellent control of blood glucose levels with less risk of hypoglycemia. In type 1 diabetes, insulin pump therapy remains the optimal approach with the most flexibility, especially with the ultra-fast-acting analogs lispro or aspart. Otherwise, once- or twice-daily dosing with the long-acting analog glargine provides excellent basal coverage, and lispro or aspart at meals provides bolus coverage, all in the attempt to mimic physiological insulin secretion. For type 2 diabetes, although oral agents continue to be a mainstay of therapy, it is clear that many patients require insulin to attain the goal A1c of < 6.5%. Once-daily glargine is now used more commonly after 1-2 oral agents have failed, and it typically takes the place of sulfonylureas. The future will likely have better systems for continuous glucose monitoring and novel therapies to control glucose through agents that affect gut hormones.
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PMID:Advances in diabetes for the millennium: insulin treatment and glucose monitoring. 1636 48


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