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

Cow's milk beta-casein has been proposed as a candidate trigger of autoimmunity associated with type 1 diabetes. In this study, cellular and humoral immunity against beta-casein was compared to that against other major cow's milk proteins in patients with recent onset type 1 diabetes and control subjects. T cell responses were found against alpha-casein, beta-casein, beta-lactoglobulin and bovine serum albumin in both patients with type 1 diabetes (stimulation index: 0.2-22.8, n=23) and control subjects (stimulation index: 0.1-18.2, n=22), with no significant differences between groups. Twelve (52%) patients and nine (41%) control subjects had stimulation indices >3 to at least one protein, including 9 (39%) patients and 4 (18%) control subjects against beta-casein, all but one of these also having elevated responses to alpha-casein. The highest responses (stimulation index >9) were against alpha- and beta-casein in some patients and control subjects who had the HLA DR3 allele. Antibody levels against alpha-casein, beta-casein and beta-lactoglobulin were low in both patients (n=59) and control subjects (n=52). Nevertheless, significantly higher IgG binding to both alpha-casein in ELISA (P=0.02) and beta-casein using ELISA (P=0.02) and RIA (P=0.04) was observed in patients aged <15 years compared to control subjects of similar age. No relationship was found between cellular and humoral immunity against individual antigens. These data show that immune responses to cow's milk are not limited to patients with diabetes and not solely against beta-casein.
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PMID:Cellular and humoral immunity against cow's milk proteins in type 1 diabetes. 1055 Feb 24

Type 1 diabetes is based on autoimmunity, and its development is in part determined by environmental factors. Among those, milk intake is discussed as playing a pathogenic role. Geographical and temporal relations between type 1 diabetes prevalence and cow's milk consumption have been found in ecological studies. Several case-control studies found a negative correlation between frequency and/or duration of breast-feeding and diabetes, but this was not confirmed by all authors. T-cell and humoral responses related to cow's milk proteins were suggested to trigger diabetes. The different findings of studies in animals and humans as well as the potential underlying mechanisms with regard to single milk proteins (bovine serum albumin, beta-lactoglobulin, casein) are discussed in this review. In contrast to type 1 diabetes, the etiology of type 2 diabetes, characterized by insulin resistance is still unclear. In a population with a high prevalence of type 2 diabetes, the Pima Indians, people who were exclusively breastfed had significantly lower rates of type 2 diabetes than those who were exclusively bottlefed. Studies in lactovegetarians imply that consumption of low fat dairy products is associated with lower incidence and mortality of diabetes and lower blood pressures. In contrast, preference for a diet high in animal fat could be a pathogenic factor, and milk and high fat dairy products contribute considerably to dietary fat intake. Concerning milk fat composition, the opposite effects of various fatty acids (saturated fatty acids, trans-fatty acids, conjugated linoleic acid) in vitro, in animals and in humans have to be considered.
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PMID:Milk and diabetes. 1075 42

As the study of type 1 diabetes moves towards preventive therapy, the role of adjuvants needs to be addressed. Incomplete Freund's adjuvant (IFA) is thought of as "immunologically inert" as, unlike complete FA (CFA), it has no components designed to provoke an immune response. We investigated the effect of IFA as an immunomodulator on the disease process leading to type 1 diabetes in the non-obese diabetic (NOD) mouse. 24 NOD mice were injected intradermally (i.d.) at 8 and 12 weeks of age with a 1:1 mixture of IFA and saline; 24 controls received saline alone. Splenocytes were tested against antigens thought to be involved in the disease process, namely insulin, a GAD peptide, a beta-casein peptide, a Glut-2 peptide and concanavalin A (ConA) as a non-specific antigen. In the IFA experiment diabetes incidence was 13% compared to 38% in the controls (p < 0.05). In vitro, splenocytes from IFA treated animals showed non-specific immunosuppression with ConA (p < 0.01), whereas the response to 1-casein and Glut-2 was raised in IFA treated animals with respect to controls. ELISA using supernatants from IFA treated animals, showed a typical Th2 cytokine pattern, whereas controls showed a Th1 pattern. In conclusion, IFA alone can reduce diabetes incidence in the NOD mouse apparently by modulating the immune response towards beta-cell related specific antigens. As IFA has been adopted as an adjuvant in preventive trials in the NOD mouse, this might have implications for the interpretation of previous and future results.
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PMID:Incomplete Freund's adjuvant reduces diabetes in the non-obese diabetic mouse. 1089 48

Type 1 diabetes is considered to be a T-cell-mediated autoimmune disease in which insulin-producing beta-cells are destroyed. Immunity to insulin has been suggested to be one of the primary autoimmune mechanisms leading to islet cell destruction. We have previously shown that the first immunization to insulin occurs by exposure to bovine insulin (BI) in cow's milk (CM) formula. In this study, we analyzed the development of insulin-specific T-cell responses by proliferation test, emergence of insulin-binding antibodies by enzyme immunoassay, and insulin autoantibodies by radioimmunoassay in relation to CM exposure and family history of type 1 diabetes in infants with a first-degree relative with type 1 diabetes and increased genetic risk for the disease. The infants were randomized to receive either an adapted CM-based formula or a hydrolyzed casein (HC)-based formula after breast-feeding for the first 6-8 months of life. At the age of 3 months, both cellular and humoral responses to BI were higher in infants exposed to CM formula than in infants fully breast-fed (P = 0.015 and P = 0.007). IgG antibodies to BI were higher in infants who received CM formula than in infants who received HC formula at 3 months of age (P = 0.01), but no difference in T-cell responses was seen between the groups. T-cell responses to BI at 9 months of age (P = 0.05) and to human insulin at 12 (P = 0.014) and 24 months of age (P = 0.009) as well as IgG antibodies to BI at 24 months of age (P = 0.05) were lower in children with a diabetic mother than in children with a diabetic father or a sibling, suggesting possible tolerization to insulin by maternal insulin therapy. The priming of insulin-specific humoral and T-cell immunity occurs in early infancy by dietary insulin, and this phenomenon is influenced by maternal type 1 diabetes.
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PMID:Effect of cow's milk exposure and maternal type 1 diabetes on cellular and humoral immunization to dietary insulin in infants at genetic risk for type 1 diabetes. Finnish Trial to Reduce IDDM in the Genetically at Risk Study Group. 1101 49

The present studies were undertaken to examine concomitant diet-induced changes in pancreatic islets and cells of the gut immune system of diabetes-prone BB rats in the period before classic insulitis. Diabetes-prone (BBdp) and control nondiabetes prone (BBc) BB rats were fed for approximately 17 days either a mainly plant-based standard laboratory rodent diet associated with high diabetes frequency, NIH-07 (NIH) or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. By about 7 weeks of age, NIH-fed BBdp rats had lower plasma insulin and insulin/glucose ratio, lower insulin content of isolated islets, lower basal levels of NO but higher responsiveness of NO production to IL-1beta in cultured islets, and higher Con A response and biosynthetic activities in mesenteric lymphocytes than control rats fed the same diet. In control rats, the HC diet caused only minor changes in most variables, except for a decrease in oxidation of L-[U-14C]glutamine in Peyer's patch (PP) cells and an increase in protein biosynthesis in mesenteric lymphocytes. In BBdp rats, however, the HC diet increased plasma insulin concentration, islet insulin/protein ratio, and tended to normalize the basal and IL-1beta-stimulated NO production by cultured islets. The HC diet decreased oxidation of L[U-14C]glutamine in BBdp pancreatic islets, whereas oxidation of L-[U-14C]glutamine in PP cells was increased, and the basal [Methyl-3H]thymidine incorporation in mesenteric lymphocytes was decreased. These findings are compatible with the view that alteration of nutrient catabolism in islet cells as well as key cells of the gut immune system, particularly changes in mitotic and biosynthetic activities in mesenteric lymphocytes, as well as basal and IL-1beta stimulated NO production, participate in the sequence of events leading to autoimmune diabetes in BB rats. Thus, the protection afforded by feeding a hydrolysed casein-based diet derives from alterations in both the target islet tissue and key cells of the gut immune system in this animal model of type 1 diabetes.
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PMID:Feeding a protective hydrolysed casein diet to young diabetic-prone BB rats affects oxidation of L[U-14C]glutamine in islets and Peyer's patches, reduces abnormally high mitotic activity in mesenteric lymph nodes, enhances islet insulin and tends to normalize NO production. 1146 96

Enhanced cellular immune response to bovine beta-casein has been reported in patients with type 1 diabetes. In this study we aimed to establish beta-casein-specific T cell lines from newly diagnosed type 1 diabetic patients and to characterise these cell lines in terms of phenotype and epitope specificity. Furthermore, since sequence homologies exist between beta-casein and putative beta-cell autoantigens, reactivity to the latter was also investigated. T cell lines were generated from the peripheral blood of nine recent onset type 1 diabetic patients with different HLA-DQ and -DR genotypes, after stimulation with antigen pulsed autologous irradiated antigen presenting cells (APCs) and recombinant human interleukin-2 (rhIL-2). T cell line reactivity was evaluated in response to bovine beta-casein, to 18 overlapping peptides encompassing the whole sequence of beta-casein and to beta-cell antigens, including the human insulinoma cell line, CM, and a peptide from the beta-cell glucose transporter, GLUT-2. T cell lines specific to beta-casein could not be isolated from HLA-matched and -unmatched control subjects. beta-Casein T cell lines reacted to different sequences of the protein, however a higher frequency of T cell reactivity was observed towards the C-terminal portion (peptides B05-14, and B05-17 in 5/9 and 4/9 T cell lines respectively). Furthermore, we found that 1 out of 9 beta-casein-specific T cell lines reacted also to the homologous peptide from GLUT-2, and that 3 out of 4 of tested cell lines reacted also to extracts of the human insulinoma cell line, CM. We conclude that T cell lines specific to bovine beta-casein can be isolated from the peripheral blood of patients with type 1 diabetes; these cell lines react with multiple and different sequences of the protein particularly towards the C-terminal portion. In addition, reactivity of beta-casein T cell lines to human insulinoma extracts and GLUT-2 peptide was detected, suggesting that the potential cross-reactivity with beta-cell antigens deserves further investigation.
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PMID:Establishment of T cell lines to bovine beta-casein and beta-casein-derived epitopes in patients with type 1 diabetes. 1252 58

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

This study evaluated the possible role of enterovirus infections in the pathogenesis of type I (insulin-dependent) diabetes in a prospective dietary intervention trial. Children participated in the second pilot of the Trial to Reduce IDDM in Genetically at Risk (TRIGR) project. They were randomized into two groups receiving either a casein hydrolysed formula (Nutramigen) or a regular formula, whenever breast milk was not available over the first 6-8 months of life. Altogether 19 children who turned positive for autoantibodies associated with type I diabetes by 2 years of age and 84 matched control children were analysed for enterovirus antibodies and enterovirus RNA in serum. Enterovirus infections were common during the first 2 years of life and more frequent among boys than girls (P = 0.02). Autoantibody-positive children had more enterovirus infections than autoantibody-negative children before the appearance of autoantibodies (0.83 versus 0.29 infection per child, P = 0.01). The average levels of IgG antibodies to echovirus antigen were also higher in autoantibody-positive than in autoantibody-negative children (P = 0.0009). No difference was found in the frequency of enterovirus infections between children receiving the casein hydrolysed formula or regular formula. These results suggest that enterovirus infections are associated with the induction of beta-cell autoimmunity in young children with increased genetic susceptibility to type I diabetes.
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PMID:Enterovirus infections as a risk factor for type I diabetes: virus analyses in a dietary intervention trial. 1269 16

The purpose of this study was to assess the humoral immune response to cow's milk proteins in Iranian children with Type 1 diabetes mellitus (T1DM). Eighty children aged 4-17 yr with T1DM from two centres in Iran (the Iranian Association of Diabetes in Tehran and Center for Diabetes Research in Hamedan), 37 apparently healthy siblings of diabetic patients (related controls), 82 apparently healthy age- and sex- matched controls (unrelated controls), and 32 patients aged 11-15 yr with auto-immune thyroiditis were examined for specific whole antibodies (Igs), IgG, and IgM to the major proteins found in cow's milk or to ovo-albumin by enzyme-linked immunosorbent assay (ELISA). A crude extract was made from 2.5% fat pasteurized cow's milk. This extract, together with individual commercial major proteins of cow's milk, was then used as antigen to evaluate the humoral immune response of the subjects to the individual proteins found in cow's milk or to cow's milk as a whole. A questionnaire on medical history, duration of exclusive and non-exclusive breast-feeding and daily intake of dairy products was completed before blood sampling. Diabetic children had significantly higher serum levels of Igs, IgG and IgM to the proteins found in cow's milk than unrelated healthy controls (p<0.001). Healthy siblings of diabetic patients, compared to unrelated controls, had significantly higher levels of serum Igs and IgG to cow's milk proteins (p<0.05 and p<0.01, respectively). Serum levels of Igs and IgG to the cow's milk proteins showed a significantly negative correlation with duration of non-exclusive breast-feeding but positive correlation with daily intake of dairy products. These correlations were stronger when calculated just within the T1DM group. In this group, serum levels of IgM to cow's milk proteins also showed a positive correlation with daily intake of dairy products. Though serum levels of IgG to casein were insignificantly higher in diabetic children than in healthy controls, there was a significant negative correlation between serum levels of IgG to casein and duration of non-exclusive breast-feeding. Again in the T1DM group, this correlation was stronger. There was no significant difference in serum levels of Igs, IgG or IgM to other major proteins of cow's milk or to ovo-albumin between groups. It was concluded that though high levels of Igs or IgG were found to cow's milk proteins, especially casein, it seems unrelated to the early introduction of cow's milk into an infant diet and the onset of T1DM in Iranian subjects.
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PMID:Serum antibodies to the major proteins found in cow's milk of Iranian patients with Type 1 diabetes mellitus. 1524 98

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


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