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)

Immune responses protect against infectious diseases and cancers. In normal circumstances, the immune system is tolerant to self. However, under certain conditions this tolerance is broken. The immune system attacks otherwise normal tissue. An autoimmune disease ensues. Strategies are now being sought that remove the pathogenic T cells without affecting other immune functions. "Classical" veto has been described as an immune suppressive mechanism able to remove T cells in a highly specific and effective manner. The present article briefly reviews the current knowledge on the development of autoreactive T cells and their regulation in the periphery. It describes "classical" veto, its mechanisms, and its novel applications. Finally, it argues that "classical" veto can be adapted to treat an autoimmune disease, such as type I diabetes mellitus.
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PMID:Treatment of an autoimmune disease with "classical" T cell veto: a proposal. 1047 73

A low cumulative incidence of IDDM was reported in Dutch males born in 1962 (Diabetologia 1992: 35: 139-142) compared to males born in previous or later years. The cause for the decreased risk has not been previously explained. We propose that children born in 1962 during an European smallpox epidemic may have received the smallpox vaccine in the first month of life and this may have attributed to the decreased risk of IDDM in these children. We have shown that immunization with several different vaccines starting in the first month of life prevents diabetes in NOD mice and BB rats (Autoimmunity 1996: 24: 137-145) while immunization at birth with the BCG vaccine is associated with an decreased risk of IDDM in humans (Infectious Diseases in Clinical Practice 1997: 6: 449-454). An even bigger decline in diabetes is seen in rodents and associated in humans when one compares immunization starting in the first month of life to immunization starting after 2 months, since the later has been associated with an increased risk of IDDM. Immunization studies in the past have typically followed patients for only several weeks to determine any unplanned affects on autoimmune disease. Due to the potential benefit of reducing the incidence of diabetes by 50% through age 18 we believe clinical trials are warranted to study the effect of timing of immunization on IDDM.
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PMID:Immunization in the first month of life may explain decline in incidence of IDDM in The Netherlands. 1059 68

The Asia-Pacific region is at the forefront of the current epidemic of diabetes. There are currently more than 30 million people with diabetes in the Western Pacific region alone. The World Health Organization predicts that this number will rise dramatically by the year 2025, by which time India and China may each face the problem of dealing with 50 million affected individuals. The problem in the region results from a combination of large population size with rapidly rising prevalence rates, particularly of type 2 diabetes mellitus. Although much heterogeneity exists, rising prevalence rates are being seen throughout the region and appear to be closely associated with westernisation, urbanisation, and mechanisation. The risk for diabetes appears to result from a combination of genetic predisposition and lifestyle change. The most important lifestyle changes relate to changes in dietary habits and physical activity and diabetes risk, particularly in younger individuals, is associated with the development of obesity and particularly central obesity. In some populations, for example Chinese, the relationship between diabetes and weight gain begins to appear at levels of body weight that would not be conventionally regarded as representing obesity. The increasing trend for type 2 diabetes to develop in young people is of particular concern. In children and adolescents in some parts of the region, type 2 diabetes now outnumbers type 1 diabetes by a ratio of 4:1. In view of the severity of the long-term complications of diabetes, the health consequences of this epidemic will become increasingly devastating and threaten to overwhelm the health care systems in the most vulnerable countries. There is an urgent need for prioritisation of diabetes as a key issue by governments throughout the region. Diabetes prevention programmes can be justified on economic, as well as humanitarian grounds. At the level of primary prevention, such programmes can be linked to other non-communicable disease prevention programmes which also target lifestyle-related issues.
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PMID:The epidemiology of diabetes mellitus in the Asia-Pacific region. 1079 2

The clinical characteristics of 132 diabetic patients referred for treatment of foot lesions were surveyed. One hundred and sixty three lesions (n=163) concerned 88 men and 44 women during a five-year period (from January 1989 to December 1993). Hospitalisation rate equalled 9.16%, i.e. 11.17% for men and 6.82% for women (p <0.001); the men/women ratio was 1.64. Eighty nine per cent (89%) of patients presented type 2 diabetes and 11% of patients type 1 diabetes. Mean age at the first foot lesion was 59.64 +/- 11.74 years. The mean duration of diabetes was 10.95 +/- 6.80 years. The patients had a high prevalence of diabetic complications, particularly peripheral neuropathy (84.85%) and obvious peripheral arteriopathy (78.78%). Infection was almost constant. There was no significant difference between men and women as far as the prevalence of complications was concerned. Smoking habits were noticed only in men. Inadequate footwear was considered as the major exogenous risk factor leading to a foot lesion. The definitive results 6 months after hospitalisation were as follows: the death rate was 9.09% (n=2; 11 men and 1 women, NS); 15.90% of patients (n=12) underwent a major amputation (4 at the level of the thigh, 17 at the level of the leg), 14.39% of patients (n=19) underwent a minor amputation; in 59.09% of patients (n=78) there was no amputation. Two patients (1.51%) underwent two consecutive amputations, left hospital against medical advice during their second hospitalisation, and then were lost sight. The prevalence of foot lesions was more important in men. Moreover, seriousness of the lesions and consequently the rate of amputations were important in men; this was probably due to smoking habits. The factors that influence the outcome seem to be: male gender, delay of management, quality of medical treatment, surgical attitude, inadequate level of amputation and finally lack of structured prevention. Prevention then should be based on the patient's education, general practitioners' training and a better and more efficient cooperation between surgeons and diabetologists.
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PMID:Diabetic foot lesions: etiologic and prognostic factors. 1080 25

Major life events, recent life stressors, and childhood diseases were examined among children and adolescents who were offspring, siblings, or other relatives of persons with type 1 diabetes mellitus (DM). All youth were recruited as part of a multi-site nationwide trial on the prevention of type 1 DM; parents of 347 children (4 to 18 yr) completed measures that asked about children's life events, recent stressors, and childhood illnesses. Analyses compared age groups (young child, preadolescent, adolescent) and relative type (offspring, sibling, other relative). Findings revealed offspring and siblings did not differ from "other relatives" in terms of life events, recent life stress, and disease/illness variables. However, siblings were reported to have fewer major life events and fewer life stressors in the past 12 months than offspring; siblings also had fewer infectious diseases during the first two years of life compared to offspring. Few age-related differences were found. Overall, results suggest that offspring and siblings of persons with type 1 DM are not at a disadvantage in terms of early life stress or disease in comparison to youth who have other family members with diabetes. However, siblings may have some advantages relative to children who are offspring. The mechanisms underlying these relationships require further elucidation and study.
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PMID:Early life stress and disease among offspring and siblings of individuals with type 1 diabetes mellitus. 1139 60

The Middle East is perhaps the world's best laboratory for learning more about iron and zinc deficiencies, and their widespread prevalence contributes much to constraining the quality of life for a large share of the population. Always, in the context of endemic IDD, countries in the region need to make sure that the programs are in place to consign this still-serious problem to the history books. Research is not required so much in relation to IDD, but clearly applications need to be monitored. Vitamin A deficiency is probably widespread at mild to moderate levels, and should be addressed by a combination of appropriate case management for infectious disease, breastfeeding promotion, and dietary diversification/nutrition education. Iron deficiency is the most prevalent, and so far the most intractable, micronutrient problem. It probably will not yield to less than a multipronged strategy including fortification of the food supply with iron. Several other micronutrient deficiencies require our eventual attention as well, and looking forward to their solution should be part of the research agenda.
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PMID:Micronutrient deficiency conditions in the Middle East region: an overview. 1141 Dec 62

To investigate the possible involvement of IDDMK1,2 22/HERV-K18 in childhood type I diabetes mellitus, we identified two nonsynonymous A/G polymorphisms in the superantigen-coding region of IDDMK1,2 22 at the 290- and 461-nucleotide (nt) positions from the initial methionine codon and compared their frequencies in 74 Japanese patients with type 1 diabetes and in 54 nondiabetic controls. Although the G substitution was observed more frequently at either site in the patients than it was in the controls (7% vs. 4% at 290 nt, and 29% vs. 20% at 461 nt), the differences were not statistically significant. A weak significance of difference in the frequency of 461G was obtained only in an early-onset group of patients manifesting the disease at 5 years of age or less (n = 24) when compared with controls (38% vs. 20%; P = 0.03). However, in addition to the common absence of a particular allele among the expected four alleles, remarkable differences in allele frequencies were present between Japanese and European populations. This first trial investigating the association of IDDMK1,12 22 with type 1 diabetes presents intriguing suggestions for the role of this region in the etiology of autoimmune and infectious diseases.
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PMID:Identification of nonsynonymous polymorphisms in the superantigen-coding region of IDDMK1,2 22 and a pilot study on the association between IDDMK1,2 22 and type 1 diabetes. 1177 84

Almost all major causes of ill-health and premature death in human societies worldwide - including cancer, cardiovascular disease, diabetes and many infectious diseases - are, at least in part, genetically determined. Typically, risk of succumbing to one of these illnesses is thought to depend on both the individual repertoire of variation within a number of key susceptibility genes and the history of exposure to relevant environmental factors. For many of these conditions, the molecular basis of disease pathogenesis remains obscure. This represents a major obstacle to development of improved, rational strategies for disease treatment, prevention and eradication. It is easy therefore to appreciate the importance attached to efforts to deliver more comprehensive understanding of the molecular basis of disease pathogenesis. Nor is it hard to understand that identification of major susceptibility genes should highlight those components of molecular machinery that are critical for the preservation of normal health. The benefits promised are great, but progress to gene identification in multifactorial traits has been rather disappointing to date. Why is this? This review aims to answer this question by describing current and future approaches to gene discovery in multifactorial traits. The examples quoted will mostly relate to type 2 diabetes, but the issues and approaches are generic, and apply equally to other multifactorial traits in the endocrine and metabolic arena - type 1 diabetes; obesity; hyperlipidaemia; autoimmune thyroid disease; polycystic ovarian syndrome - and beyond.
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PMID:Susceptibility gene discovery for common metabolic and endocrine traits. 1185 95

Insulin-dependent diabetes mellitus (IDDM) is one of the most common chronic diseases. It is an autoimmune disease. Genes contributing the most for development of IDDM are located on chromosome 6p21.3 in the region called the major histocompatibility complex (MHC). HLA-DQ8/DR4 and DQ2/DR3 have shown positive association with IDDM, while DQ6 has negative association with IDDM in most Caucasian populations. The location of the tumor necrosis factor alpha (TNF-alpha) gene in the MHC suggests the role of TNF in the etiology of IDDM as an autoimmune disease. The TNF region contains several polymorphisms that are associated with different levels of TNF-alpha production and susceptibility to autoimmune and infectious diseases. Ninety-two Latvian IDDM patients corresponding to WHO diagnostic criteria and 107 unrelated age- and sex-matched healthy controls were analyzed for the frequency of TNF-alpha alleles to test the hypothesis that TNF-alpha is associated with IDDM. We found that TNF-alpha microsatellite allele 2 is associated with IDDM, 29/92 (32%), versus 14/107 (13%) in healthy controls. The test of the strongest association of the MICA A5 allele and TNF-alpha allele 2 with IDDM showed that both are independently associated with the disease.
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PMID:Tumor necrosis factor-alpha allele 2 shows an association with insulin-dependent diabetes mellitus in Latvians. 1202 Nov 42

We have developed a method to genotype variable number of tandem repeats (VNTRs) and insertion/deletion polymorphisms using an integrated microfluidic chip-based system. We used this method to analyze a) a highly polymorphic pentanucleotide repeat (CCTTT)(n) locus within the 5'-putative promoter region of the human inducible nitric oxide synthase gene (iNOS5) which is associated with diabetic complications and infectious diseases; b) a bi-allelic 27 bp VNTR region within intron 4 of endothelial nitric oxide gene (eNOS27) which is associated with hypertension in type 2 diabetes patients with coronary heart disease and excess risk of advanced diabetic nephropathy in type 1 diabetes patients and c) an insertion/deletion polymorphism within the gene encoding angiotensin-converting enzyme (ACE/ID) which is associated with cardiovascular pathology and nitric oxide activity, and is in strong linkage disequilibrium with functional variants. Following amplifications, samples were mixed with gel-dye and markers and loaded into commercially available microfluidic chips designed for DNA sizing applications. In the study (N = 230), 95 (41%) of the DNA samples were homozygous and 135 (59%) were heterozygous for the iNOS5 repeats. For eNOS27, 173 (75%) of the genotyped DNA samples were homozygous for the larger 4b allele and the remaining 57 samples (25%) were heterozygous (4b/4a). No DNA samples were homozygous for the shorter 4a allele with four 27 bp repeats. In case of ACE/ID, 47 (20%) of the DNA samples were homozygous for the insertion, 65 (28%) were homozygous for the deletion and the remaining 118 (51%) were heterozygous. The results obtained were verified by analyzing random amplicons using bi-directional sequencing and GeneScan 3.0 analyses with 100% concordance being observed. Using the microfluidic chip-based method, separation and DNA sizing and genotyping are rapidly accomplished. The DNA fragments are resolved clearly and the system allows quantitation. Finally, the microfluidic chip-based method may be used for both large- and small-scale genotyping studies.
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PMID:Microfluidic chip-based method for genotyping microsatellites, VNTRs and insertion/deletion polymorphisms. 1255 58


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