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

Partial recovery of beta-cell function in type 1 diabetes is common after diagnosis by intensive insulin therapy. Residual beta-cell function can be improved by other therapies. Cyclosporin (CyA) and nicotinamide (NA), alone or in combination, can preserve this function, as indicated by the parameters of metabolic control (insulin dose, HbA1C). After suspension of CyA, insulin requirement returns to control values, suggesting loss of residual beta-cell function. The effects induced by withdrawal of NA after 1 year are not known. For the first time, we studied 27 type 1 diabetes patients treated with NA for 12 months and then followed up for 1 year after discontinuance of NA. Another 25 patients treated with NA + CyA and 28 control patients were followed up similarly. Insulin requirement doubled 12 months after discontinuance of NA or NA + CyA, becoming identical to that of controls. As patients showed HbA1C values similar to control subjects, it is likely that beta-cell function deteriorated after discontinuance of therapy. As NA is safer than other agents and its effects are beneficial, longer studies are warranted to investigate NA in prolonged treatments since this compound is also being considered for prevention of type 1 diabetes.
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PMID:Adjuvant therapy in recent onset type 1 diabetes at diagnosis and insulin requirement after 2 years. 778 43

Nicotinamide was shown to prevent damage and to stimulate B cell regeneration in experimental diabetes but in humans results are still controversial. To ascertain if long term nicotinamide treatment can induce and/or prolong remission of the disease, 21 type 1 (insulin-dependent) recently diagnosed subjects entered a controlled study and randomly divided in two groups comparable for age, genetic and immunologic patterns: group 1 (11 subjects) received insulin and nicotinamide (3 g/day for 1 year) and group 2 (10 subjects) insulin alone. Bimonthly insulin requirement and HbA1c, and every 6 months C-peptide response to glucagon were registered for 2 years. No significant difference was observed between the two groups in the monitored parameters, including rates of clinical remission, along this time period. In conclusion nicotinamide, when employed after the clinical onset of the disease, has no additional effect on natural history of newly diagnosed type 1 diabetes mellitus, besides results obtained by insulin alone.
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PMID:Residual B cell activity and insulin requirements in insulin-dependent diabetic patients treated from the beginning with high doses of nicotinamide. A two-year follow-up. 785 83

IDDM is caused by an immune-mediated destruction of the insulin-producing beta cells. Beta cells are destroyed by induction of oxygen-derived free radicals (FR) and nitric oxide (NO), which results in perturbation of the mitochondrial respiratory system and DNA strand breaks. As a result of beta cell destruction, islet cell antibodies (ICA) can be demonstrated in the circulation. These antibodies can be detected up to eight years prior to overt IDDM. Nicotinamide, a vitamin B3 derivative, interferes with the immune mediated beta-cell destruction by reducing the content of FR and NO and thereby reducing their deleterious effects. At the same time, nicotinamide increases the intracellular NAD pool, thus increasing the energy supply of the cell. Nicotinamide protects against chemically induced as well as spontaneous diabetes in animal models of the disease. Recently, open clinical studies have suggested that nicotinamide when administered to humans can prevent or delay clinical onset of IDDM. To test the possible preventive effect of nicotinamide in IDDM, a prospective, randomized, placebo-controlled study is needed. A multicentre study including 18 European countries, Israel and Canada is planned to start during 1993.
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PMID:[Nicotinamide and prevention of insulin-dependent diabetes mellitus. Rationale, effects, toxicology and clinical experiences. ENDIT Group]. 814 Jun 61

A 1-year open randomized controlled multicentre trial was carried out on 90 patients with recent onset (< 4 weeks) insulin-dependent diabetes (IDDM) to compare the effect of nicotinamide (NCT) with the combination NCT and low dose cyclosporin (CyA) on clinical remission and optimization of metabolic control during the first year from diagnosis. Three groups of patients were randomly assigned to receive for 12 months either NCT 25 mg kg-1 day-1 (n = 30) or NCT 25 mg kg-1 day-1 + CyA 5 mg kg-1 day-1 (n = 30), the latter adjusted to maintain 12 whole blood trough levels of 83 nmol l-1; a third group of patients (n = 30) receiving insulin only acted as a control group for spontaneous remission and metabolic control. Clinical remission (i.e. suspension of insulin therapy with normal metabolic parameters for more than 2 weeks according to the International Diabetes Immunotherapy Group) was achieved at 3 months in 6/30 NCT treated patients and in 1/30 NCT + CyA treated patient (p = 0.05); no remission was observed in control patients. At 6 months the number of patients achieving remission in each group was 4/29, 3/27, and 1/29, respectively (p = NS). One year after diagnosis 4/27 NCT treated, 2/25 NCT+CyA treated but 0/28 of the control patients were in remission (NCT vs control p = 0.05). Clinical remission lasted longer (7 +/- 3 SD months) in NCT treated patients than in NCT+CyA treated or control patients (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Randomized trial comparing nicotinamide and nicotinamide plus cyclosporin in recent onset insulin-dependent diabetes (IMDIAB 1). The IMDIAB Study Group. 818 Dec 61

Most studies dealing with the pathogenesis of IDDM have emphasized the immune assault against beta-cells. In this perspective, we review the data that suggest that the beta-cell destruction of IDDM depends on a balance between beta-cell damage and repair. The progressive beta-cell damage leading to IDDM seems to follow markedly different temporal courses in individual patients. Some individuals at high risk for developing IDDM, and presenting with impaired beta-cell function, appear to recover beta-cell function when followed prospectively. Moreover, after the clinical onset of IDDM, most patients experience a transitory period of improved insulin secretion. In vitro and in vivo experimental data suggest that beta-cells are indeed able to repair themselves after damage. Dispersed beta-cells or whole islets can survive and regain their function after a toxic assault. Furthermore, the abnormal insulin release and glucose oxidation of islets isolated from NOD mice during the prediabetic period is completely restored after 1 wk in tissue culture. Finally, treatment of NOD mice with monoclonal antibodies directed against infiltrating T-cells reverses the altered glucose metabolism of beta-cells. Note that beta-cell repair after exposure to different toxic agents can be enhanced both in vivo and in vitro. Potential enhancers of beta-cell repair are nicotinamide, glucose, protein-rich diets, and branched chain amino acids. A basic question that remains to be answered is the nature of the repair mechanisms triggered by beta-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Repair of pancreatic beta-cells. A relevant phenomenon in early IDDM? 837 80

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

Nitric oxide (NO) has been proposed as a possible mediator of beta-cell damage in human IDDM. This hypothesis is based on in vitro studies with rodent pancreatic islets. In the present study we examined whether human beta-cells are affected by NO. In view of species differences in beta-cell sensitivity to damaging agents, rat islets were investigated in parallel. Isolated islets were exposed for 90 min to different concentrations of three chemically unrelated NO donors, SIN-1, GSNO or RBS. At the end of this incubation, human insulin release was mostly similar in control and NO-treated islets but, 48 h later, islet retrieval, islet DNA and insulin content, and glucose-induced insulin release were markedly lower in islets exposed to NO donors. Rat islets were already inhibited during the initial 90 min; 48 h later their loss in beta-cell function was similar to that in human islets. Nicotinamide or succinic acid monomethyl ester partially protected against SIN-1 induced islet cell loss, but not against the functional inhibition of human pancreatic islets. Exposure of human or rat islets to RBS was associated with significant DNA strand breakage, as judged by the comet assay (single cell gel electrophoresis) and by ultrastructural signs of cell damage. DNA damage was more severe in rat islet cells exposed to similar amounts of RBS. It is concluded that NO donors can damage human pancreatic islets, an effect paralleled by induction of nuclear DNA strand breaks.
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PMID:Nitric oxide donors decrease the function and survival of human pancreatic islets. 873 93

Beta-cell regeneration in adult pancreas is usually considered to be limited. However, various animal models suggest that this tissue is still capable of regeneration under certain conditions. Reg protein could be responsible for this replicative process. The reg gene codes for a 166 amino-acid protein usually synthesized and secreted by pancreatic acinar cells but expressed in islet beta cells during experimental regenerative processes in animals (90% pancreatectomy + nicotinamide, or insulinoma tumor removal in rats, or the "wrapping pancreas model" in the hamster). In addition, recombinant rat reg protein can stimulate beta-cell replication in vivo and in vitro. In animal models of Type 1 diabetes mellitus, reg gene overexpression occurs during active phases of diabetogenesis and could be a defence mechanism. During human pancreatic development, reg gene is expressed at an early stage but is not associated with the expression of other pancreatic genes. Conversely, gene expression for reg and insulin are correlated in adult pancreas. Accordingly, reg protein could be a beta-cell-specific growth factor implicated in the maintenance of beta-cell mass, especially in adult pancreas.
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PMID:Reg protein: a potential beta-cell-specific growth factor? 876 67

Type I diabetes mellitus is a chronic autoimmune disease in which there is T cell-mediated destruction of the pancreatic beta cells. Susceptibility to the disease is determined by several genes, with HLA genes having the strongest effect. The onset of the disease is predictable, at least in the relatives of affected persons, using a combination of autoantibody measurements, intravenous glucose tolerance testing, and genetic typing. The disease may be preventable, and several large clinical trials are now underway to test whether interventions such as administering low-dose insulin or the use of nicotinamide can prevent the onset of diabetes in at-risk relatives.
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PMID:Strategies for preventing type I diabetes mellitus. 877 49

Autoimmune processes are involved in pancreatic beta-cell destruction in type 1 diabetes. Autoantibodies including islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA), and antibodies directed against the 37/ 40 K antigen appear in the circulation years before clinical onset and permit increasingly precise disease prediction. A cellular immune response causes pancreatic infiltration, while macrophages and Th-cells appear to be implicated-via local release of cytokines-in beta-cell destruction. Generation of free radicals, DNA strand breaks, activation of the enzyme poly (ADP-ribose) polymerase (PARP), and depletion of intracellular nicotinamide adenine dinucleotide (NAD) appear to be common factors in beta-cell death, whether mediated by oxygen radicals, nitric oxide, or streptozotocin. Nicotinamide, a soluble B group vitamin which offers protection against these toxic stimuli, is at high doses a free radical scavenger, a potent inhibitor of PARP, and protects against depletion of intracellular NAD. A sound scientific rationale therefore exists for its use in human prediabetes, and promising pilot studies have been performed in ICA-positive first-degree relatives and school children. No serious side effects have been reported from its use at the doses proposed in man or other species. There is therefore a sound case for submitting this agent to a controlled clinical trial.
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PMID:Molecular mechanisms of beta-cell destruction in IDDM: the role of nicotinamide. 880 29


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