Gene/Protein Disease Symptom Drug Enzyme Compound
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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 allele and genotype frequency distributions of polymorphic markers of genes coding for antioxidant enzymes were compared for type 1 diabetes mellitus patients with or without diabetic polyneuropathy (DPN). The groups (total 180 patients) had nonoverlapping (polar) phenotypes. Group DPN+ included 86 patients with DPN and diabetic record no more than 5 years. Control group DPN- included patients without DPN and diabetic record of at least 10 years. Comparative analysis with Fisher's exact test revealed a significant difference in allele and genotype frequency distributions of the T(-262)C polymorphic marker of the CAT gene. Polymorphic markers C1167T of the CAT gene, Pro/Leu of the GPX1 gene, 0/+ of the GSTT1 gene, and 0/+ of the GSTM1 gene showed no significant difference in allele or genotype frequency distribution. On this evidence, these markers were not associated with DPN in the sample examined.
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PMID:[Search for the association of polymorphic markers for genes coding for antioxidant defense enzymes, with development of diabetic polyneuropathies in patients with type 1 diabetes mellitus]. 1512 29

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucose-independent effects. Preclinical studies have demonstrated dose-dependent effects on Na+,K(+)-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.
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PMID:Type 1 diabetic neuropathy and C-peptide. 1519 72

The aim of this study was the search of association with diabetic polyneuropathy of the polymorphic markers epsilon2/epsilon3/epsilon4 of apolipoprotein E (APOE) and I/D of apolipoprotein B (APOB) genes in groups of type 1 diabetes patients with diabetic polyneuropathy (n = 86) and without its clinical signs (n = 94). We have not found significant association with diabetic polyneuropathy (DPN) of epsilon2/epsilon3/epsilon4 marker of APOE gene. However the comparison of allele and genotype frequencies of I/D marker of APOB gene showed that the carriers of I allele and II genotype had higher risk (OR = 1.66 and 2.01, relatively; p < 0.027), whereas the carriers of D allele had lower risk of DPN (OR = 0.60; p < 0.018). Our findings show that APOB gene, encoding one of the main components of lipid metabolism system, is involved into the diabetic polyneuropathy development in type 1 diabetes mellitus.
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PMID:[Association of polymorphic markers of lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus]. 1585 46

Diabetic neuropathy is a debilitating disorder that occurs in nearly 50 percent of patients with diabetes. It is a late finding in type 1 diabetes but can be an early finding in type 2 diabetes. The primary types of diabetic neuropathy are sensorimotor and autonomic. Patients may present with only one type of diabetic neuropathy or may develop combinations of neuropathies (e.g., distal symmetric polyneuropathy and autonomic neuropathy). Distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Diabetic neuropathy also can cause motor deficits, silent cardiac ischemia, orthostatic hypotension, vasomotor instability, hyperhidrosis, gastroparesis, bladder dysfunction, and sexual dysfunction. Strict glycemic control and good daily foot care are key to preventing complications of diabetic neuropathy.
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PMID:Evaluation and prevention of diabetic neuropathy. 1595 41

The levels and types of immune responses are determined dependent on the extent of pathogen invasion, reactions to antigens mediated by macrophage-dendritic cells, T cells and antibodies. Recently, accumulating evidence suggests that B cells also play an important role in the regulation of immune responses. Here we have made a review to present a role of B cells in determining the level of immune responses and discussed about the clinical significance of B cell-targeted therapy in patients with autoimmune diseases. Type 1 diabetes is a T cell-mediated autoimmune disease characterized by the destruction of insulin-producing pancreatic beta cells. We and other groups have elucidated that B cells play a critical role in the development of insulitis and diabetes, as B-cell-deficient NOD mice are protected from developing type 1 diabetes. B cells are essential for the T cell receptor clonotype spreading of islet-infiltrating T cells, indicating that B cells may play a role in determining the level of immune responses by antigen presentation to antigen specific T cells. There are now numerous case reports and small series of clinical trials regarding rituximab therapy in autoimmune diseases, such as refractory autoimmune hemolytic anemia, IgM antibody-associated polyneuropathy, systemic lupus erythematosus and rheumatoid arthritis. Rituximab is a genetically engineered chimeric anti-CD 20 monoclonal antibody that is approved for the treatment of lymphoma. CD20 is a B-cell surface antigen that is expressed only on pre- B and mature B cells. Thus, rituximab causes a selective transient depletion of the CD20+ B -cell subpopulation. Rationale and strategy for targeting B cells in the treatment of autoimmune diseases consist of the inhibition of antigen-presentation and co-stimulation that induces T cell expansion and activation. Further careful mechanistic studies are required to develop therapies in patients with autoimmune diseases.
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PMID:[B cells as key contributors in determining the level of immune responses -B-cell-targeted therapy in patients with autoimmune diseases]. 1599 5

The Fas death receptor is expressed by activated lymphocytes and is involved in switching-off the immune response. Its inherited defects cause auto-immune lymphoproliferative syndrome. Impaired Fas function may also play a role in other auto-immune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The aim of this work was to evaluate Fas function in T cells from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated Fas-induced apoptosis in T-cell lines from 27 patients with CIDP, 12 patients with acute inflammatory demyelinating polyneuropathy (AIDP), and 110 controls. CIDP patients displayed lower Fas function than both AIDP patients and controls, whereas no statistically significant difference was found between AIDP patients and controls. Moreover, Fas function was lower in CIDP patients with progressive course than in those with relapsing-remitting course and lower in CIDP patients with axonal damage than in those with pure demyelination. These data suggest that defective Fas function favours CIDP development and aggressive evolution.
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PMID:Fas-mediated T-cell apoptosis is impaired in patients with chronic inflammatory demyelinating polyneuropathy. 1651 82

The authors hypothesized that genetic predisposition to diabetes complications would be more evident among low-risk individuals and aimed to identify genes related to developing complications (confirmed distal symmetric polyneuropathy, overt nephropathy, or coronary artery disease) in low-risk groups. Participants in the Pittsburgh, Pennsylvania, Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes, first seen in 1986-1988 (mean age, 28 years; diabetes duration, 19 years), were reexamined biennially for 10 years. For each complication, subgroups with the lowest disease risk were identified by using tree-structured survival analysis, and 15 candidate genes were compared between subjects with and without complications. In the group with the lowest incidence of confirmed distal symmetric polyneuropathy (n = 123), confirmed distal symmetric polyneuropathy risk increased fivefold for those with the eNOS GG genotype (p < 0.05). In the group with the lowest risk of overt nephropathy (n = 340), the ACE D polymorphism increased overt nephropathy risk twofold (p = 0.05), whereas a protective effect was observed for the LIPC CC genotype (p < 0.05). In the group with the lowest incidence of coronary artery disease (n = 331), the MTHFR CC genotype increased coronary artery disease risk threefold (p < 0.05). Tree-structured survival analysis may help identify genetic predispositions among individuals who, despite low risk, develop diabetes-related complications.
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PMID:Identifying genetic susceptibilities to diabetes-related complications among individuals at low risk of complications: An application of tree-structured survival analysis. 1692 30

In this article we describe differences in early metabolic abnormalities between type 1 and type 2 diabetic polyneuropathy (DPN), and how these differences lead to milder initial functional defects in type 2 diabetes, despite the same hyperglycemic exposures. This early reversible metabolic phase is progressively overshadowed by structural degenerative changes eventually resulting in nerve fiber loss. In comparison, the late structural phase of DPN affects type 1 diabetes more severely. Progressive axonal atrophy and loss is hence expressed to a larger extent in type 1 diabetes. In addition, type 1 DPN is characterized by paranodal degenerative changes not seen in type 2 DPN. These differences can be related to the differences in insulin action and signal transduction affecting the expression of neurotrophic factors and their receptors in type 1 diabetes. Downstream effects on neuroskeletal and adhesive proteins, their posttranslational modifications, and nociceptive peptides underlie the more severe resultant pathology in type 1 DPN. These differences in underlying mechanisms should be seriously considered in the future design of interventional paradigms to combat these common conditions.
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PMID:Diabetic neuropathy differs in type 1 and type 2 diabetes. 1715 5

In this review we will describe the interaction between insulin and C-peptide which enhances and attenuates insulin-signaling functions. We will describe how replenishment of C-peptide prevents and reverses the early metabolic abnormalities in type 1 diabetic polyneuropathy, such as Na(+)/K(+)-ATPase activity and endoneurial vascular NO release, resulting in prevention and reversal of early nerve dysfunction. The effects on expression of neurotrophic factors and their receptors, mediated by corrections of early gene responses and transcription factors, have downstream beneficial effects on cytoskeletal protein mRNAs and protein expression. Similar effects probably underlie corrections of cell adhesive molecules. The end-effects are prevention and reversal of myelinated and unmyelinated axonal degeneration, atrophy, and loss. Similarly, progressive degeneration of the node and paranode is prevented and repaired by C-peptide replacement with normalization of the molecular constituents of these functionally important structures. Cognitive dysfunction is now recognized as a complication of type 1 diabetes. Experimentally it is linked to impaired synaptic plasticity and eventually apoptotic neuronal loss caused by impaired insulin action and neurotrophic support. C-peptide replacement partially prevents hippocampal neuronal apoptosis and cognitive deficits. It is therefore becoming increasingly clear that C-peptide has major functions in supporting insulin action with a multitude of beneficial effects on diabetic polyneuropathy and primary diabetic encephalopathy in type 1 diabetes.
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PMID:Is C-peptide replacement the missing link for successful treatment of neurological complications in type 1 diabetes? 1822 Jul 11

The aim of this study was the search of association of polymorphous markers Pro72Arg and C(-594)CC of TP53 gene with diabetic polyneuropathy (DPN) in patients with type 1 diabetes mellitus with or without clinical signs of DPN. We have found that polymorphous marker Pro72Arg of TP53 gene was associated with DPN in Russian patients with type 1 diabetes mellitus living in Moscow. The carriers of Arg allele and Arg/Arg genotype had higher risk of DPN development (OR = 1.96; CI = 1.32-2.90; and OR = 2.14; CI = 1.23-3.73; relatively). On the contrary, the carriage of Pro allele was associated with the lower risk of DPN development (OR = 0.51; CI = 0.34-0.76). We have not found any association of polymorphous marker C(-594)CC of TP53 gene with DPN in Russian patients with type 1 diabetes mellitus living in Moscow.
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PMID:[Association of polymorphous markers Pro72Arg and C(-594)CC OF TP53 gene with diabetic polyneuropathy in patients with type 1 diabetes mellitus living in Moscow]. 1831 16


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