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

The authors described a case of acute miopericarditis with evolution towards dilated cardiomiopathy, secondary to Coxsackie B4 infection, in a patient developing a concomitant insulin dependent diabetes (DIDM), admitted to be also an expression of this infection. The pathogenesis and the immunological basis of this aggression is discussed and some therapeutic considerations made.
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PMID:[Coxsackie B4 infection, myopericarditis and diabetes mellitus]. 165 Oct 46

Insulin-dependent diabetes mellitus (IDDM) is characterized by a progressive autoimmune destruction of the pancreatic beta-cells. One of the best-suited animal models for IDDM is the nonobese diabetic (NOD) mouse. In this investigation pancreatic islets were isolated from female NOD mice aged 5-7, 8-11, and 12-13 wk and examined immediately (day 0) or after 7 d of culture (day 7). The mice showed a progressive disturbance in glucose tolerance with age, and a correspondingly increased frequency of pancreatic insulitis. Islets isolated from the oldest mice often contained inflammatory cells on day 0, which resulted in an elevated islet DNA content. During culture these islets became depleted of infiltrating cells and the DNA content of the islets decreased on day 7. Islets of the eldest mice failed to respond with insulin secretion to high glucose, whereas a response was observed in the other groups. After culture all groups of islets showed a markedly improved insulin secretion. Islets from the 12-13-wk-old mice displayed a lower glucose oxidation rate at 16.7 mM glucose on day 0 compared with day 7. Islet (pro)insulin and total protein biosynthesis was essentially unaffected. In conclusion, islets obtained from 12-13-wk-old NOD mice exhibit an impaired glucose metabolism, which may explain the suppressed insulin secretion observed immediately after isolation. This inhibition of beta-cell function can be reversed in vitro. Thus, there may be a stage during development of IDDM when beta-cell destruction can be counteracted and beta-cell function restored, provided the immune aggression is arrested.
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PMID:Reversal of beta-cell suppression in vitro in pancreatic islets isolated from nonobese diabetic mice during the phase preceding insulin-dependent diabetes mellitus. 218 96

Experimental results and therapeutic strategies. Insulin-dependent diabetes mellitus (IDDM) results from an autoimmune aggression toward beta cells in genetically predisposed individuals. Examination of the frequency of the different antigens coded by the major histocompatibility complex reveals an increased proportion of DR3-DQ2 and DR4-DQ8 haplotypes in IDDM subjects. Sequencing DQ-beta chains in such patients indicates the absence of aspartate in position 57 when compared to control individuals. Islet cell cytoplasmic autoantibodies are early markers of ongoing autoimmunity in addition to insulin autoantibodies before administration of exogenous insulin. Experimental models of autoimmune diabetes like the NOD (NonObese Diabetes) mouse underline the predominant role of T lymphocytes in the constitution of both insulitis and beta cell destruction. In humans, an increased proportion of activated T lymphocytes can be observed but is not specific of the disease. This underlines the need for new cellular markers of the autoimmune process. Transgenic mice allow studies on the consequences of abnormal expression of new molecules on beta cell surface like cytokines or MHC class II molecules which represent a new field of investigation on the pathogenesis of IDDM. Prospective studies in first degree relatives of type I diabetic patients indicate the existence of an asymptomatic phase of beta cell destruction where specific autoimmune markers can be individualized. In some individuals abnormal insulin response to glucose--loss of first phase insulin release during intravenous glucose tolerance test--precedes insulin deficiency. The identification of an autoimmune process leading to beta cell destruction allows new therapeutic approaches with immunointervention at early stages of the disease.
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PMID:[Autoimmunity and insulin-dependent diabetes mellitus. Experimental data and therapeutic prospects]. 267 68

In most of the cases, once a given endocrine gland is involved, the corresponding specific autoantibody may be detected; for example, anti-islet cell antibodies are produced within the first few years, after onset of symptoms in insulin-dependent diabetes (DID). Accompanying autoantibodies are quite frequently found in the patient himself. In Schmidt's syndrome (thyroid and adrenal glands are involved and associated to IDD in 30% of the cases) thyroid microsomal antibodies are found in 38% of the cases, thyroglobulin antibodies in 11% of the cases, islet-cell antibodies in 7% of the cases and steroid cell antibodies in 17% of the cases. Associations are also possible in patient family members. Aberrant expression of HLA-DR molecules at the membrane of follicular thyroid cells (as of any other endocrine gland), following a viral aggression, could well account for the endocrinopathy combinations, but alternative mechanisms should be discussed.
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PMID:[Autoimmune polyendocrinopathies. Pathogenic hypotheses]. 382 97

We studied the effect of peripheral blood mononuclear cells (PBMNC) from insulin-dependent diabetic (IDDM) children on the insulin secretion pattern of the pancreas from recipient athymic mice. PBMNC from healthy controls or IDDM patients in different stages of disease were injected into athymic mice. PBMNC from newly diagnosed IDDM children elicited basal nonfasting hyperglycemia and in vitro inhibition of the first and second phases of glucose-stimulated insulin secretion in recipient mice. Animals injected with cells from chronically IDDM children showed normoglycemia, abnormal tolerance to glucose, and inhibition of first-phase insulin secretion. Mitomycin C treatment of MNC from IDDM patients abolished insulin secretion inhibition in recipient mice. PBMNC from newly diagnosed and chronically IDDM patients showed positive anti-beta-cell cellular immune aggression. Mice injected with cells from patients during the remission period showed normoglycemia and no alteration of insulin secretion patterns. When relapsed to their former clinical stage, injection of the cells significantly inhibited first-phase glucose-induced insulin secretion in recipients. PBMNC from newly diagnosed IDDM patients were found to migrate to the pancreas of recipient mice preferably as compared with cells from controls. Cells from chronically IDDM patients cultured with concanavalin A (Con A) increased insulin secretion inhibition; despite this, cells from children during the remission period cultured with Con A failed to modify insulin secretion in recipients. These results show that injection of PBMNC from diabetic patients leads to insulin secretion impairment in recipient mice pancreas, and provide a basis for the study of mechanisms involved in the onset and modulation of anti-beta-cell cellular immune aggression induced by human PBMNC.
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PMID:Insulin secretion by pancreas of athymic mice injected with peripheral mononuclear cells from insulin-dependent diabetic patients. 747 31

A better knowledge of the pathogenesis of type 1 diabetes (IDDM) may open the road to the prevention of the diseases. Primary prevention is meant to identify susceptible subjects, either soon after birth or before the immunological aggression of beta cells. The practical approach in this respect is very difficult because multiple obstacles must be overcome. Secondary prevention involves subjects who already show immunological or metabolic alterations, as the presence of ICA, antiinsulin antibodies, GAD antibodies and a defect of the first phase of insulin secretion. Most authors attach great interest to trials with insulin and nicotinamide. Insulin seems to reduce antigen expression when beta cells are damaged. Nicotinamide exerts a protection toward diabetes in animals, and, as scavanger of free radicals, facilitates beta cell regeneration. Research is going on, all over the world, and special multicenter trials are in progress both in the USA and Europe.
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PMID:[Prevention of juvenile diabetes (type 1): reality or fiction?]. 856 82

The importance of islet cell antibodies (ICA) as a predictor of insulin dependent diabetes mellitus (IDDM) has been emphasized by several investigators since 1974. The ICA was also detected in patients with various immune-mediated diseases such as auto-immune thyroiditis. Schistosomiasis is a wide-spread helminthic disease which affects more than 200 million patients all over the world. Immunological abnormalities and pancreatic affection are features of the disease. We studied the prevalence of ICA in 40 children with schistosomiasis (20 males and 20 females), 14 children with IDDM, and 30 of the non-diabetic siblings of patients with IDDM, and evaluated the oral glucose tolerance and early release of insulin after an i.v. load of glucose in children with schistosomiasis, diabetics' siblings, and 10 normal age-matched controls. The age of onset of IDDM and duration of the disease were 6.5 +/- 2.3 and 4.1 +/- 1.2, respectively, and the age of onset and duration of schistosomiasis were 8.3 +/- 2.7 and 2.5 +/- 1.5 years, respectively. Sex, consanguinity, history of previous virus diseases (mumps, measles and rubella), and sex maturity rating did not differ among the three study groups; however, children with schistosomiasis were significantly older. The prevalence of ICA was 50 per cent in children with IDDM, 13 per cent in the diabetics' siblings, and 25 per cent of children with schistosomiasis. Glucose tolerance was normal in children with schistosomiasis and diabetics' siblings. Early release of insulin after i.v. glucose load was significantly lower in children with schistosomiasis compared to the other two groups. In conclusion, the high prevalence of ICA and the decreased early release of insulin in response to an i.v. glucose load in children with schistosomiasis suggest that auto-immune aggression against the islet cells contributes in the pathogenesis of pancreatic disease in these patients, and might increase the risk for developing glucose intolerance and diabetes.
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PMID:High prevalence of islet cell antibody and defective insulin release in children with schistosomiasis. 882 Jun 21

The purpose of this pilot study was to identify the coping strategies used by children, adolescents and youths with insulin dependent diabetes mellitus (IDDM) attending a camp for IDDM patients near Ryosen town, Fukushima Prefecture, Japan. Forty-three IDDM patients (24 females and 19 males) were studied, divided into two age groups. The first group included children (seven males and 10 females). The second group included adolescents and youths (12 males and 14 females). For the child group a projective drawing method was used for study and for the older group, an open questionnaire was used. Ryan-Wenger's taxonomy of children's coping strategies and Band's coding systems and classification were used for the content analysis. 'Instrumental action', 'Emotional expression' and 'Catastrophizing thinking' were the coping strategies, represented in the child group. Gender differences in coping strategies were found in the group of adolescents and youths. The most often represented and most important coping category for the male subgroup was 'Behavioral avoidance'. Next in frequency of representation for the male subgroup were 'Cognitive distraction' and 'Behavioral distraction'. The coping categories 'Seeking social support' and 'Behavioral distraction' were represented with equal frequency in the female subgroup and the next was 'Aggressive activities'. The most important coping strategy for the female group was 'Talking to peers' from the seeking social support category. The study also helped to identify several children and adolescents who might need special psychological support.
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PMID:Psychosocial problems of children and adolescents with a chronic disease: coping strategies. 899 58

Nonobese diabetic (NOD) mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human type 1 diabetes. Since prophylactic insulin injections reduced the incidence of diabetes in NOD mice, we tested a new prophylactic strategy to prevent diabetes in NOD mice consisting of oral administration of insulin, protected in polyalkylcyanoacrylate nanocapsules from degradation in the gastrointestinal tract. In humans, this form of prophylactic insulin administration would be less constraining than insulin injections. Ninety female NOD mice were randomized at weaning and fed once a week (from 60 to 300 days of age) with insulin nanocapsules (100 U/kg) or empty nanocapsules. Within the group fed with insulin nanocapsules, the incidence of diabetes was reduced (38% vs 75%; P < 0.02), the onset of disease was delayed (P < 0.02), and the severity of lymphocytic inflammation of endogenous islets was reduced (P < 0.03). Although the oral treatment was stopped at 300 days of age, the incidence of diabetes at 360 days remained lower in mice previously fed insulin nanocapsules (P < 0.02). Previous feedings with insulin nanocapsules did not protect against cyclophosphamide-induced diabetes, since final incidence of diabetes (sum of the incidence during the initial 360 days and the further CY-induced incidence) reached the final incidence obtained in mice previously fed empty nanocapsules and treated with cyclophosphamide. Intestinal absorption of insulin nanocapsules was evidenced by HPLC separation of human insulin in NOD sera. During cotransfer, T splenocytes from mice fed insulin nanocapsules were able to reduce the capacity of T cells from diabetic donors to adoptively transfer the disease (P < 0.01). Antigens for islet-cell autoantibodies (ICA) in pancreata from both NOD groups were compared by immunofluorescence with the same ICA-positive human sera to ensure that differences were due to quantitative changes in antigen. These antigens, which could serve as an index of a possibly more extended antigen beta-cell rest, were decreased (P < 0.02) and pancreatic insulin content was reduced (P < 0.05) in mice fed with insulin nanocapsules, suggesting a mechanism of 'beta cell rest'. To summarize, early feeding with insulin nanocapsules reduces diabetes and insulitis in the NOD mouse model that mimics human type 1 diabetes. This may be due both to generation of cellular mechanisms that actively suppress disease and a decrease in antigens which makes beta cells less vulnerable to autoimmune aggression.
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PMID:Prophylactic oral administration of metabolically active insulin entrapped in isobutylcyanoacrylate nanocapsules reduces the incidence of diabetes in nonobese diabetic mice. 911 73

Diabetic nephropathy accounts for almost a third of all causes of ESRD. Microalbuminuria screening among diabetics can offer early detection of incipient nephropathy. Aggressive treatment with ACE inhibitors may delay the onset of overt renal failure or delay its progression. Furthermore, intensive control of blood glucose has also been proven to prevent the microvascular complications of diabetes and should be pursued in both IDDM and NIDDM. The high association of diabetes mellitus with hypertension presents another problem to the clinician. It is necessary to control blood pressure to prevent further progression of renal failure. The choice of antihypertensive medications, however, becomes a therapeutic dilemma because of the metabolic and lipid disturbances that some drugs can cause. ACE inhibitors, CCBs, alpha-agonists, and low-dose diuretics, alone or in combination, may be tried to normalize blood pressures. Although beta-blockers are widely used and effective in nondiabetics, these agents should be considered the drugs of last resort because of their adverse effects, which are particularly troublesome for diabetics. Moderate protein restriction should also be advocated as a helpful adjunct to therapy.
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PMID:Diabetic nephropathy. 916 51


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