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

This paper presents a hypothesis of the aetiology of the increasing incidence of type 1 diabetes (T1D). This together with the global increased incidence of celiac disease (CD) and that these increases cannot be explained by genetic factors suggest a common environmental factor for these two diseases. Even though enterovirus (EV) infections are believed to trigger T1D and gluten is the trigger of CD, the increasing intake of gluten containing products all over the world could be the trigger for both diseases directly and indirectly. It has been shown that the duration of exposure to gluten is related to the prevalence of T1D. It has also been shown that T1D patients at onset have an inflammatory reaction in the gut. Hence, early diagnose of CD followed by elimination of dietary gluten will lead to a decreased incidence of T1D.
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PMID:A unifying hypothesis on the development of type 1 diabetes and celiac disease: gluten consumption may be a shared causative factor. 1824 99

The increased prevalence of coeliac disease (CD) among children with type 1 diabetes mellitus (DM1) implies that there is more than a simple association. A link between the gut immune system and DM1 has been suggested both in animal models and in humans. We review the literature on the epidemiology and genetic and clinical aspects shared by these two diseases and speculate on the role of gluten on the possible relationship between CD and DM1, on the basis of recent animal and human studies. The data suggest a failure in oral tolerance mechanisms in DM1 other than that in CD. It remains to be understood why only a small proportion of patients with DM1 proceed to the production of coeliac-associated antibodies and to overt enteropathy.
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PMID:Update on coeliac disease and type 1 diabetes mellitus in childhood. 1834 Oct 84

Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone with the potential to change diabetes. The physiological effects of GLP-1 are multiple, and many seem to ameliorate the different conditions defining the diverse physiopathology seen in type 2 diabetes. In animal studies, GLP-1 stimulates beta-cell proliferation and neogenesis and inhibits beta-cell apoptosis. In humans, GLP-1 stimulates insulin secretion and inhibits glucagon and gastrointestinal secretions and motility. It enhances satiety and reduces food intake and has beneficial effects on cardiovascular function and endothelial dysfunction. Enhancing incretin action for therapeutic use includes GLP-1 receptor agonists resistant to degradation (incretin mimetics) and dipeptidyl peptidase (DPP)-4 inhibitors. In clinical trials with type 2 diabetic patients on various oral antidiabetic regimes, both treatment modalities efficaciously improve glycaemic control and beta-cell function. Whereas the incretin mimetics induce weight loss, the DPP-4 inhibitors are considered weight neutral. In type 1 diabetes, treatment with GLP-1 shows promising effects. However, several areas need clinical confirmation: the durability of the weight loss, the ability to preserve functional beta-cell mass and the applicability in other than type 2 diabetes. As such, long-term studies and studies with cardiovascular end-points are needed to confirm the true benefits of these new classes of antidiabetic drugs in the treatment of diabetes mellitus.
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PMID:GLP-1: physiological effects and potential therapeutic applications. 1843 75

Because the role of regulatory T cells in the intestinal inflammation is unknown in coeliac disease (CD) and type 1 diabetes (T1D), the expression of forkhead box P3 (FoxP3), CD25, transforming growth factor-beta, interferon (IFN)-gamma, interleukin (IL)-4, IL-8, IL-10, IL-15 and IL-18 was measured by quantitative reverse transcription-polymerase chain reaction in the small intestinal biopsies from paediatric patients with active or potential CD, T1D and control patients. The numbers of FoxP3- and CD25-expressing cells were studied with immunohistochemistry. Enhanced intestinal expressions of FoxP3, IL-10 and IFN-gamma mRNAs were found in active CD when compared with controls (P-values < 0.001, 0.004, <0.001). In potential CD, only the expression of IFN-gamma mRNA was increased. The numbers of FoxP3-expressing cells were higher in active and potential CD (P < 0.001, P = 0.05), and the ratio of FoxP3 mRNA to the number of FoxP3-positive cells was decreased in potential CD when compared with controls (P = 0.007). The ratio of IFN-gamma to FoxP3-specific mRNA was increased in active and potential CD (P = 0.001 and P = 0.002). Patients with T1D had no changes in regulatory T cell markers, but showed increased expression of IL-18 mRNA. The impaired up-regulation of FoxP3 transcripts despite the infiltration of FoxP3-positive cells in potential CD may contribute to the persistence of inflammation. The increased ratio of IFN-gamma to FoxP3 mRNA in active and potential CD suggests an imbalance between regulatory and effector mechanisms. The increased intestinal expression of IL-18 mRNA in patients with T1D adds evidence in favour of the hypothesis that T1D is associated with derangements in the gut immune system.
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PMID:Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes. 1843 1

Autoantibodies (Abs) directed against L-type voltage-gated calcium channels (VGCCs) have been shown to contribute to autonomic dysfunction of the gastrointestinal tract and bladder in patients with Type 1 diabetes mellitus (T1D). We used a passive transfer model to determine whether the functional activity of the Ab requires crosslinking of channels in colon and bladder and can be neutralized by intravenous immunoglobulin (IVIg). Mice were injected with mono- and divalent F(ab) fragments of patient IgG with anti-VGCC activity and tested for gut and bladder function using a colonic migrating motor complex (MMC) assay and bladder-filling cystometry. The ability of IVIg to neutralize anti-VGCC IgG-mediated autonomic dysfunction was investigated by injection of mice with an equimolar concentration of IVIg prior to T1D IgG injection, or by injection with T1D IgG passed over a sepharose 4B column coupled with F(ab')(2) from IVIg. Passive transfer of T1D IgG and its F(ab')(2) or F(ab) fragments reduced the amplitude of spontaneous colonic motility. In contrast, intact IgG and F(ab')(2,) but not F(ab), produced the urodynamics features of an overactive bladder. T1D IgG-mediated colonic and bladder dysfunction was neutralized in vivo by prior injection of animals with equimolar IVIg. Moreover, anti-VGCC activity was depleted by preabsorption of patient IgG on a IVIg F(ab')(2) column. The activity of anti-VGCC IgG is mediated by the antigen-binding site consistent with a true functional Ab. The pathogenic effect on the bladder requires crosslinking of the channel, whereas monovalent binding of Ab is sufficient for disruption of colon motility. The anti-VGCC Abs are neutralized by antiidiotypic antibodies present in IVIg that may prevent the emergence of these Abs in healthy individuals.
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PMID:Autoantibodies to calcium channels in type 1 diabetes mediate autonomic dysfunction by different mechanisms in colon and bladder and are neutralized by antiidiotypic antibodies. 1847 96

It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a "perfect storm" critical to the development of type 1 diabetes. This trio of factors includes an aberrant intestinal microbiota, a "leaky" intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss the complex interplay between these factors and raise testable hypotheses that form a fertile area for future investigations as to the role of the gut in the pathogenesis and prevention of type 1 diabetes.
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PMID:The "perfect storm" for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. 1882 Feb 10

The development of type 1 diabetes (T1D) has been linked to environmental factors and dietary components. Increasing evidence indicates that the integrity of the gut mucosa plays a role in the development of autoimmune diseases, and evidence from both preclinical and clinical studies demonstrates that increased leakiness of the intestinal epithelium precedes the development of type 1 diabetes. However, there is limited information on modulation of gut barrier function and its relationship to diabetes development. Here we show that the nonobese diabetic (NOD) mouse, a model of T1D, exhibits enhanced intestinal transcellular permeability before the development of autoimmune diabetes. Treatment of NOD mice with a glucagon-like peptide 2 (GLP-2) analog, synthetic human [Gly(2)] glucagon-like peptide-2 (h[Gly(2)]GLP-2, increased the length and weight of the small bowel and significantly improved jejunal transepithelial resistance. However, chronic administration of once daily h[Gly(2)]GLP-2 failed to delay or reverse the onset of T1D when treatment was initiated in young, normoglycemic female NOD mice. Furthermore, h[Gly(2)]GLP-2 administration had no significant effect on lymphocyte subpopulations in NOD mice. These findings demonstrate that h[Gly(2)]GLP-2-mediated enhancement of gut barrier function in normoglycemic NOD mice disease is not sufficient to prevent or delay the development of experimental T1D.
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PMID:Glucagon-like peptide-2 reduces intestinal permeability but does not modify the onset of type 1 diabetes in the nonobese diabetic mouse. 1884 25

Insulin-Dependent Diabetes Mellitus (IDDM) is a chronic disease characterized by the inability of the pancreas to produce sufficient amounts of insulin. Daily compensation of the deficiency requires 4-6 insulin injections to be taken daily, the aim of this insulin therapy being to maintain normoglycemia - i.e., a blood glucose level between 4 and 7mmol/l. To determine the quantity and timing of these injections, various different approaches are used. Currently, mostly qualitative and semi-quantitative models and reasoning are used to design such a therapy. Here, an attempt is made to show how system identification and control may be used to estimate predictive quantitative models to be used in design of optimal insulin regimens. The system was divided into three subsystems, the insulin subsystem, the glucose subsystem and the insulin-glucose interaction. The insulin subsystem aims to describe the absorption of injected insulin from the subcutaneous depots and the glucose subsystem the absorption of glucose from the gut following a meal. These subsystems were modeled using compartment models and proposed models found in the literature. Several black-box models and grey-box models describing the insulin/glucose interaction were developed and analyzed. These models were fitted to real data monitored by an IDDM patient. Many difficulties were encountered, typical of biomedical systems: Non-uniform and scarce sampling, time-varying dynamics and severe nonlinearities were some of the difficulties encountered during the modeling. None of the proposed models were able to describe the system accurately in all aspects during all conditions. However, all the linear models shared some dynamics. Based on the estimated models, short-term blood glucose predictors for up to two-hour-ahead blood glucose prediction were designed. Furthermore, we explored the issues that arise when applying prediction theory and control to short-term blood glucose prediction.
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PMID:Diabetes mellitus modeling and short-term prediction based on blood glucose measurements. 1902 64

Insulin Dependent Diabetes Mellitus (IDDM) is a chronic disease characterized by the inability of the pancreas to produce sufficient amounts of insulin. Daily compensation of the deficiency requires 4-6 insulin injections to be taken daily, the aim of this insulin therapy being to maintain normoglycemia--i.e., a blood glucose level between 4-7 mmol/L. To determine the quantity and timing of these injections, various different approaches are used. Currently, mostly qualitative and semi-quantitative models and reasoning are used to design such a therapy. Here, an attempt is made to show how system identification and control may be used to estimate predictive quantitative models to be used in design of optimal insulin regimens. The system was divided into three subsystems, the insulin subsystem, the glucose subsystem and the insulin-glucose interaction. The insulin subsystem aims to describe the absorbtion of injected insulin from the subcutaneous depots and the glucose subsystem the absorbtion of glucose from the gut following a meal. These subsystems were modeled using compartment models and proposed models found in the literature. Several black-box models and grey-box models describing the insulin/glucose interaction were developed and analysed. These models were fitted to real data monitored by a IDDM patient. Many difficulties were encountered, typical of biomedical systems: Non-uniform and scarce sampling, time-varying dynamics and severe nonlinearities were some of the difficulties encountered during the modeling. None of the proposed models were able to describe the system accurately in all aspects during all conditions. However, all the linear models shared some dynamics. Based on the estimated models, short-term blood glucose predictors for up to two-hour-ahead blood glucose prediction were investigated.
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PMID:Short-term diabetes blood glucose prediction based on blood glucose measurements. 1916 50

Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity-such as found in the intestinal microflora-and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease-to cite but a few-the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.
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PMID:Intestinal microflora and metabolic diseases. 1941 95


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