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

Administration of insulin by a variety of routes can prevent the onset of diabetes and the destruction of pancreatic beta-cells in prediabetic animals. Moreover, intensive insulin therapy improves beta-cell function in patients with recent-onset type 1 diabetes. Preliminary trials have suggested that treatment of high-risk prediabetic patients with insulin can prevent the onset of diabetes. In addition, long-term insulin treatment appears to have no significant side-effects in non-diabetics. However, the mechanism of the protective action of insulin is not yet understood. Several large-scale controlled trials have been organized (e.g. the Diabetes Prevention Trial 1, DPT-1, and the European Paediatric Prediabetes Subcutaneous Insulin Trial, EPP-SCIT), to evaluate the effect of prophylactic insulin therapy in the prevention or delay of diabetes in high-risk paediatric individuals.
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PMID:Treatment of prediabetic patients with insulin: experience and future. European Prediabetes Study Group. 880 30

Now that prediction of type I diabetes mellitus has markedly improved, worldwide attempts to prevent the disease are under way (e.g., DPT-1, ENDIT, and TRIGR). Subjects are being recruited and families of children or parents with diabetes should be informed about the availability of such studies and given the option to participate. The creation of a network of study sites or cooperative groups will allow for the implementation of new protocols aimed at preventing the disease. The greatest barrier to the prevention of diabetes is the lack of proven effective interventional agents. The journey toward prevention of type I diabetes mellitus has only just begun.
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PMID:The prevention of type I diabetes mellitus. 1049

The general population risk of developing type 1 diabetes mellitus (DM), 1/300, is magnified 15-20 fold in first-degree relatives of affected individuals. Because a combination of immunologic, metabolic, and genetic markers can be used to predict the disease, multicenter prevention trials in the US (DPT-1) and Europe (ENDIT) were initiated in relatives. In the DPT-1 over 80,000 relatives under 45 years of age will be screened for ICA and then 'staged' to assess risk. High-risk subjects (>50% over 5 yr) are randomized either to 4 days intravenous insulin infusion annually followed by b.i.d. low doses of subcutaneous ultralente insulin, or to close observation. To date (September 2000), 331/340 (97%) high-risk subjects have been enrolled with the intention of detecting a 35% decrease in disease over 5 years (80% power). 280/490 (57%) of intermediate risk subjects (25-50% over 5 yr) have been randomized to oral insulin or placebo. A 50% treatment difference is sought. Anticipated enrolment for the high-risk arm will be completed by year 2001, and by 2003 for the oral arm. The ENDIT study will prospectively address whether nicotinamide will reduce the rate of progression to DM in relatives. 40,000 first-degree relatives (5-40 yr) have been screened with 552 subjects (ICA titers > or = 20 JDF U) randomized to nicotinamide or placebo. This study is designed with 90% power to detect a 35% reduction in disease (placebo group estimated at 40% risk over 5 years). Analysis of data is expected in 2003.
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PMID:Update on major trials for the prevention of type 1 diabetes mellitus: the American Diabetes Prevention Trial (DPT-1) and the European Nicotinamide Diabetes Intervention Trial (ENDIT). 1139 53

The Diabetes Prevention Trial Type 1 (DPT-1) has recruited relatives of patients with type 1 diabetes throughout the United States and Canada. Of the group screened before June 30, 2000, 71,148 initial screening samples of DPT-1 subjects were tested for GAD65 autoantibodies (GAA) and ICA512 (IA-2) autoantibodies (ICA512AA). Of 71,148 relatives screened, first-degree relatives (4.63%, n = 59,752) had a significantly higher prevalence of autoantibodies than did second-degree relatives (2.61%, n = 9,856) (P < 0.0001 for both autoantibodies). Among first-degree relatives, siblings (5.47%, n = 27,128) had a significantly higher prevalence of autoantibodies than did offspring (3.98%, n = 17,063) and parents (3.88%, n = 15,561) (P < 0.0001 for both autoantibodies). Among offspring, the offspring (n = 105) of both parents with diabetes had twice (8.57%) the prevalence of autoantibodies than did the offspring (n = 16,901) of a single diabetic parent (3.96%). Interestingly, the offspring (n = 8,777) of diabetic fathers had a significantly higher prevalence of autoantibodies than did the offspring (n = 8,124) of diabetic mothers, but only among those aged 10-30 years (P < 0.0001). We conclude that the prevalence of anti-islet cell autoantibodies is affected by multiple levels of relationship to the proband.
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PMID:Diabetes Prevention Trial 1: prevalence of GAD and ICA512 (IA-2) autoantibodies by relationship to proband. 1202 Nov 18

The 61st Annual Meeting and Scientific Sessions of the American Diabetes Association (ADA) in Philadelphia, PA, (June 22-26, 2001) presented many topics of interest to pediatric clinicians. Of particular interest were the results of the insulin injection arm of the Diabetes Prevention Trial for type 1 diabetes mellitus (DM) (DPT-1). Over 80,000 relatives of patients with type 1 DM were screened. Ultimately, 339 subjects were randomized either to active therapy (twice daily insulin injections plus an annual insulin infusion) or to close observation. Risk prediction algorithms appeared to be accurate. Unfortunately, however, insulin therapy did not decrease the risk of developing DM. Of note, this was primarily a pediatric study with most of those randomized under 21 years of age. As expected, young subjects (<12 years) progressed toward the development of DM at a faster rate than older subjects (>15 years). The second arm of the DPT-1 trial, testing oral insulin in those with intermediate risk (25-50%) for DM, is still recruiting subjects. The controversial topic of continuous subcutaneous insulin infusion (CSII) in young children was also addressed. Many investigators presented data strongly supporting the successful use of infusion pumps in young children. In general, glycemic control was improved or remained stable, the incidence of severe hypoglycemia was low, and families reported more flexibility in their lifestyle. Obesity, an increasing problem in pediatric patients, was also addressed.
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PMID:Progress in the treatment of childhood diabetes mellitus and obesity. 1209 89

The author comments on the DPT-1 Trial and why the observed negative outcome in preventing diabetes in first-degree relatives of type 1 diabetic patients by parenteral insulin administration may have occurred and what can be gathered from this large study. There were three main lessons to be learned from the DPT-1 Trial as follows. (1) Large preventive trials of type 1 diabetes are feasible in first-degree relatives of type 1 diabetic patients and other preventive approaches may be now envisaged. (2) The natural history of type 1 diabetes, at least in its final years before clinical onset, has been elucidated and reiterates the relevance of our present predictive tools (autoantibodies) for identifying individuals at risk for the disease. (3) Strict follow-up of enrolled subjects in trials permits an earlier diagnosis of the disease with less frequency of ketoacidosis and implementation of insulin therapy when higher C-peptide levels are present. DPT-1 has paved the way on how to proceed and new trials will be planned benefiting from such experience.
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PMID:The DPT-1 trial: a negative result with lessons for future type 1 diabetes prevention. 1220 41

The frequency of type 1 diabetes mellitus (T1DM)-associated HLA DQ alleles in the U.S. Pacific Northwest is as high as in Scandinavia, which has the highest T1DM incidence in the world. The high regional rate of islet autoimmunity observed among DPT-1 relatives supports this notion. Fortunately, Washington State archives dried blood spots after legislature-mandated newborn screening. The Diabetes Evaluation in Washington (DEW-IT) study aims to show that population-based prospective prediction of T1DM by HLA genotype screening followed by autoantibody surveillance can be performed within the public health infrastructure.
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PMID:Population-wide infant screening for HLA-based type 1 diabetes risk via dried blood spots from the public health infrastructure. 1467

Prevention of type 1 diabetes in high risk individuals presents with both positive and negative aspects. On one hand, the availability of reliable and convenient screening tools (antibodies) allows us to quantify the risk of diabetes in the short term. Large randomised studies have provided indisputable answers regarding the efficiency of selection of at risk patients. Unfortunately, both DPT-1 study (using insulin) and ENDIT trial (with nicotinamide) ruined the hopes raised from solid experimental data. These studies have also demonstrated the huge costs in terms of number of subjects, time for follow-up, and financial burden, requiring an international collaboration. Finally, only a small number of such studies can be conducted simultaneously. Progress and obstacles paving this research area must be explained to diabetic patients and their family. Current mitigated results should not drive us to give up screening campaigns. Rather, these results should prompt diabetes centers and families to participate in the selection of high risk individuals in order to explore new therapeutic options within future prevention trials.
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PMID:[Prevention of type 1 diabetes: what have we achieved? What should we say and propose next to families?]. 1470 96

Type 1 diabetes begins with the progressive autoimmune mediated destruction of the insulin-producing beta cells. When sufficient beta cell function is lost, the endocrine phase, characterized by insulin deficiency and hyperglycemia, supervenes. While a genetic predisposition to diabetes is an important precondition, most believe an environmental factor or factors serve as the trigger for initiating this process. In this paper we review trials designed to prevent or delay the clinical onset of diabetes. In these studies, high-risk individuals are identified by their genetic predisposition to diabetes, and/or by the presence of immune markers indicating activation of the autoimmune process directed against islet cells. The Deutsche Nicotinamide Intervention Study (DENIS) randomized 55 high-risk subjects to either nicotinamide or placebo and found no significant benefit. The European Nicotinamide Diabetes Intervention Trial (ENDIT) completed enrollment in May 1998. ENDIT screened over 40 000 relatives, randomizing 552 to either nicotinamide or placebo. Results are expected in May of 2003. Designed to test if avoidance of cow's milk in infancy will decrease the incidence of diabetes, the Trial to Reduce Type I Diabetes in the Genetically at Risk (TRIGR). High-risk infants are randomly assigned to different supplemental formulas in the first 6 months of life. Initial results suggest that removing cow's milk has a protective effect. The ongoing, NIH funded, multicenter Diabetes Prevention Trial-Type 1 (DPT-1) is testing two antigen-based (insulin) interventions in relatives at high risk for diabetes. Now in its sixth year, the DPT-1 study group has screened over 84,000 individuals. As of November 2000, 339 subjects have been randomized in the parenteral insulin study, completing the enrollment phase. Enrollment continues in the oral insulin study. Results of this trial are not yet available. Different epitopes of insulin and its analogs, monoclonal antibodies, and cytokine-based therapy, among others, have all been proposed as potential new interventional agents. While a great deal of effort will be required to test these approaches, the potential benefits of prevention justify these research efforts.
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PMID:Prevention of type 1a diabetes mellitus*. 1501 6

The pathogenesis of type 1 diabetes is multifactorial, involving genetic susceptibility, autoimmune mechanisms, and environmental factors. This article will focus on two main strategies for altering the underlying disease process in type 1 diabetes. The first strategy is to identify individuals at risk for the development of diabetes and to halt the immune process before it leads to overt clinical disease, Promising in vitro and animal studies with nicotinamide, parenteral insulin, and oral insulin led to large clinical prevention studies, such as the European Nicotinamide Diabetes Intervention Trial and the Diabetes Prevention Trial (DPT-1). These studies failed to show that nicotinamide and insulin prevented the disease in at risk relatives of patients with type 1 diabetes and left many questions unanswered. The second strategy focuses on intervention shortly after diagnosis in order to arrest the destruction of beta cells and to preserve residual beta-cell function as long as possible. Cyclosporin was an effective immunosuppressive but was rejected as a potential treatment for type 1 diabetes because of its renal toxicity. Recently, more attention has been focused on an anti-CD3 antibody, on DiaPep277, and on glutamic acid decarboxylase (GAD). Animal studies and small short-term human trials with these compounds have suggested that they may be effective interventions in patients recently diagnosed with type 1 diabetes.
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PMID:Therapeutic targets for the prevention of type 1 diabetes mellitus. 1608 57


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