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Query: UMLS:C0011849 (diabetes)
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In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria, and assays for the detection of autoantibodies are not available. In consequence, slowly progressive autoimmune diabetes or LADA is likely to be missed. Antibodies to GAD65 and IA-2 are the major immunological markers in autoimmune diabetes. Recently, a new beta cell antigen, called ICA12, has been identified, which has a homology to the SOX family of transcription factors. The aim of the study was to analyze the prevalence of ICA12 antibodies in diabetes mellitus patients and controls from Latvia and to see whether this antigen is important in revealing autoimmunity when antibodies against major antigens are not present. We studied 88 IDDM patients and 100 NIDDM patients as well as controls for the prevalence of GAD65, IA-2, and ICA12 antibodies by radioligand binding assay (RIA) using (35)S-labeled islet antigens. We found ICA12Abs in 26 of 88 IDDM patients (30%) vs. 4% in healthy controls (4/100) and in 9 of 100 NIDDM patients (9%) vs. 2% controls (2/100). ICA12Abs alone are present in only 3% (3/88) of the patients with IDDM and 1% (1/100) of the NIDDM patients. We conclude that ICA12 represents the minor antigens in autoimmune diabetes and that, as a minor antigen, ICA12 alone does not contribute significantly in revealing new cases of autoimmunity.
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PMID:Antibodies to new beta cell antigen ICA12 in Latvian diabetes patients. 1202 Nov 28

Right classification of diabetes is important clinical issue. The aim of present study was to compare clinical, biochemical and immunological features, to analyze their practical use and to establish new decision tree which make the distinction between diabetes type 1, LADA, diabetes type 2 and MODY. We studied 97 not obese (mean BMI 26.3 +/- 4.9 kg/m2) patients aged 14 to 70 years, mean age 43 +/- 11.7 years, 53 women, 44 men. Mean duration of diabetes--2.3 +/- 4.3 years. We measured basal and stimulated C-peptide (6 minutes after 1 mg i.v. glucagon) (ELISA) and antibodies titers to glutamic acid decarboxylase--antiGAD65, tyrosine phosphatase-like molecule--IA2 and insulin--IAA (RIA). Autoimmune diabetes (LADA, type 1) was diagnosed with presence of one or more islet antigen antibodies. The highest frequencies had anti-GAD antibodies 33/97 (34%). The most complicated was to sort out group of patients with LADA. Comparison between this group and patients with diabetes type 2 have shown that BMI, co-existence of autoimmune disease, autoimmune markers and basal and stimulated C-peptide level measured at entry for the classification were useful in differentiation. Moreover we observed significantly lower C-peptide basal, stimulated and over basal level in group with MODY diabetes in comparison to diabetes type 2 patients. In the studied group were 5 patients with diabetes type 2 and obesity, in relatively young age. At the end there was one case of ADM (atypical diabetes mellitus). Clinical criteria for the classification of diabetes not always correlated with diagnosis. Autoimmune markers, basal and stimulated C-peptide were useful specially in differentiation between LADA and diabetes type 2 or diabetes type 1. Autoimmune diabetes co-existe with autoimmune disease. Proposed diagnostic scheme take for consideration presence of autoantibodies as well as C-peptide criteria.
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PMID:[Clinical, biochemical and immunological characteristic of diabetes type I, LADA, diabetes type II, and MODY patients]. 1268 30

Major histocompatibility complex class I chain-related gene A (MICA) encodes polymorphic, stress-inducible antigens recognized by gammadelta T cells within the intestinal epithelium. MICA microsatellite polymorphism has been implicated to be related to different autoimmune diseases. Ninety-eight patients with type 1 diabetes (median age, 35 years; range, 9-89 years and 51 patients with latent autoimmune diabetes (LADA; median age, 48 years; range, 19-79 years) were compared with 113 healthy control patients (median age, 35 years; range, 19-65 years) to study the importance of MICA-microsatellite polymorphism and HLA-DR-DQ as genetic risk factors for diabetes. The different factors were compared univariately and by logistic regression analysis. In the logistic regression model, heterozygosity for MICA5.0/5.1 was a significant risk factor for LADA (odds ratio [OR] = 12; 95% confidence interval [95%CI], 2.5-59) as well as heterozygosity for HLA-DR3-DQ2/DR4-DQ8 (OR = 15; 95%CI, 2.7-84). None of the MICA polymorphisms were related to type 1 diabetes. Heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was a risk factor for type 1 diabetes (OR = 14; 95%CI, 2.9-66) as well as DR4-DQ8/x (OR = 2.8; 95%CI, 1.4-5.9). HLA-DR15-DQ6 was protective for type 1 diabetes (OR = 0.12; 95%CI, 0.015-0.96). We concluded that both heterozygosity for MICA5.0/5.1 and HLA-DR3-DQ2/DR4-DQ8 are separate risk factors for LADA, but that heterozygosity for HLA-DR3-DQ2/DR4-DQ8 and DR4-DQ8 alone are most important for type 1 diabetes.
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PMID:Heterozygosity for MICA5.0/MICA5.1 and HLA-DR3-DQ2/DR4-DQ8 are independent genetic risk factors for latent autoimmune diabetes in adults. 1294 47

Human CD38 is a protein which catalyzes the synthesis of nicotinic acid adenine dinucleotide (NAADP+) and the conversion of NAD+ to cADPR. Both cADPR and NAADP+ are powerful intracellular Ca2+ ([Ca2+]i) mobilizers in different cell types. Recently, the presence of CD38 autoantibodies has been found in a significant number (9-15%) of patients with Type 2 or long-standing Type 1 diabetes. These autoantibodies are biologically active, the majority of them (-60%) displaying agonistic properties, i.e., [Ca2+]i mobilization in lymphocytic cell lines and in pancreatic islets. In cultured rat pancreatic islets, the human autoantibodies inhibit glucose-induced insulin release, whereas, in human pancreatic islets CD38 autoantibodies stimulate glucose-mediated insulin secretion. The clinical phenotype of anti-CD38-positive Type 2 diabetes differs from the LADA (latent autoimmune diabetes of adults) phenotype. When accurately matched for age and obesity, only LADA patients with anti-GAD antibodies, but not GAD-negative/ CD38-positive patients, have reduced in vivo beta-cell function in comparison to antibody-negative patients. Transgenic mice overexpressing CD38 show enhanced glucose-induced insulin release, whereas, conversely, CD38 knockout mice display a severe impairment in beta-cell function. Few Japanese diabetic patients carry a missense mutation in the CD38 gene; in Caucasian patients mutations in the CD38 gene have not been found. Collectively, these findings suggest that activation of CD38 represents an alternative signaling pathway for glucose-induced insulin secretion in human beta-cells. More information, however, is necessary to gauge the role of CD38 autoimmunity in the context of the natural history of human Type 1 or Type 2 diabetes.
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PMID:CD38 autoimmunity: recent advances and relevance to human diabetes. 1550 98

Type 1 and type 2 diabetes have different clinical presentations in their common forms. The absence of biological tests for diagnosis of type 2 diabetes, for reliable evaluation of insulin secretion and, beta-cell mass or for diagnosis of insulitis and the limited sensitivity of antibody tests in type 1 diabetes explain the difficulty of classifying a large number of cases of diabetes and the identification of questionable clinical entities: LADA (Latent Autoimmune Diabetes in Adult), non-insulin dependant diabetes in coloured people. Hyperglycaemia may also be observed in genetic diseases affecting insulin secretion (MODY, mutations of mitochondrial DNA), complex genetic diseases, pancreatic, endocrine and iatrogenic affections. Type 1 diabetes is characterised by the destruction of, beta-cells while type 2 diabetes combines abnormal insulin secretion and insulin resistance. The reduction of the beta-cell mass in type 2 diabetes remains controversial. These different conditions are examples of multifactorial diseases during which several physiopathological processes are disturbed in association with the expression of multiple genes, of normal structure and function, but variants of which copy for a number of partial phenotypes the association of which causes the disease. Some hypotheses suggest that type 2 diabetes is the consequence of the selection of variants of genes involved in energetic storing and responsible for defence against infection and of the recent very rapid changes in the environment.
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PMID:[Physiopathological mechanisms in type 1 and type 2 diabetes]. 1566 75

During the 1997-2002 period, 48 eyes of 41 patients of the mean age 58 years were operated on because of complications of proliferative diabetic retinopathy. In the cohort of operated patients, the type I diabetes mellitus was determined in 10 (21%) cases, the type II diabetes mellitus in 36 (75%) cases, and in two cases (4%), another type of diabetes was detected. One patient of those two had LADA type diabetes and the second one had secondary diabetes due to chronic pancreatitis. In the early postoperative period, or during first three months postoperatively, after the pars plana vitrectomy, the visual acuity (VA) in 28 (59%) eyes improved, in 16 (33%) eyes remained the same, and in 4 eyes (8%) worsened. VA 1/60 (0.017 or 3/200) and better had 37 (77%) eyes, VA 6/60 (0.1 or 20/200) and better had 17 (37%) eyes, and VA 6/12 and better (0.5 or 20/40) had 3 (6%) eyes only. VA worse than 1/60 (0.017 or 3/200) had 11 (23%) eyes. Authors emphasize the importance of regular and detailed ophthalmologic examinations with early diagnosis of pathological changes and early start of adequate treatment.
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PMID:[Early functional effect of the pars plana vitrectomy in complications of the proliferative diabetic retinopathy]. 1578 55

The diagnosis of diabetes mellitus would appear a simple matter. However, potential pitfalls in clinical practice need to be avoided, and this requires knowledge and attention. An initially pathological oral glucose tolerance test should be repeated before establishing a final diagnosis, since such necessary preconditions as a 10 to 16 hours fast, or alcohol abstinence, are difficult to monitor in the clinical setting. Accurate glucose testing requires appropriate sample preparation and handling. Further pitfalls may be encountered during treatment: HbA1c assessment is associated with certain limitations and does not permit the estimation of glucose variations. To establish a differential diagnoses between type 1 (LADA) and type 2 diabetes in older patients GAD must be measured. New biochemical markers such as adiponectin and intact proinsulin may facilitate treatment decisions and monitoring in patients with type 2 diabetes.
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PMID:[Pitfalls in the diagnosis and treatment optimization of type 2 diabetes]. 1583 93

Autoimmune diabetes is a complex, multifactorial disease caused by the interaction of genetic and environmental factors. This autoimmune diabetes is commonly manifested in childhood and adolescence with a fast onset (type 1 diabetes, IDDM) and it can occur in adult patients with a slow onset with delayed insulin requirement, (latent autoimmune diabetes in adults, LADA ). Autoimmune diabetes has strong class II HLA association mainly with DQB gene which constitutes the first susceptibility locus. However, association with the 5'INS- VNTR and CTLA-4 genes has been established. In this study, we analysed the polimorphic allele frequencies of DQB HLA gene in 63 LADA patients, 70 IDDM and 79 control subjects. The HLA DQB1 alleles typing was detected through Olerup SSP DQ kit using sequence specific primers. We observed a positive association of *0201-*0302 and *0201-*0201 genotypes in both types of diabetic patients compared to the control group (p < 0.05). Moreover, *0201-*0302 genotype was higher in IDDM than in LADA (p < 0.05). On the other hand, the *0602 protective allele analysis showed a high prevalence in the normal group compared to the diabetic population. In Argentina, the most frequent allele of susceptibility in LADA and IDDM patients was the *0201. Summing up, the finding of an increase in the *0201 allele, both in allelic and genotypic frequencies, allows the characterisation of our population of patients, LADA and IDDM, unlike other populations, in which the most frequent allele is *0302.
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PMID:[HLA DQB1 genotyping in latent autoimmune diabetes of adults (LADA)]. 1604 35

Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus. Some recently published papers confirm similarly high prevalence of autoimmune thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune thyroiditis is the most frequent form of autoimmune thyropathies. Authors examined 79 accidentally selected diabetics (38 women and 41 men, x = 55.4 +/- 2.8). Diabetic patients were divided into three groups. 20 patients with type 1 diabetes mellitus - classical form were the first group, 12 patients with LADA were the second group and 47 patients with type 2 diabetes mellitus constituted the third group. Authors diagnosed chronic autoimmune thyroiditis in 8 (40 %) patients in the group of patients with type 1 diabetes mellitus, in 6 (50%) in the group of patients with LADA and in 20 (43%) of patients with type 2 diabetes mellitus. They didn't find out statistically more frequent prevalence of chronic autoimmune thyroiditis in all groups of patients with diabetes (patients with type 1 diabetes mellitus, patients with LADA, patients with type 2 diabetes mellitus) in comparison with control group of non-diabetic subjects. They found out statistically significant more frequent prevalence of chronic autoimmune thyroiditis in diabetics of woman gender and in diabetics with positive family history of thyropathies. Results of paper confirm recommendation of examining once or twice a year autoantibodies against thyroid gland and level of thyrotropin (TSH) with the aim of early finding of laboratory manifestation of thyroidal autoimmunity or developing functional disorder.
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PMID:[Autoimmune thyropathies in diabetics]. 1662 76

Differentiation of the various forms of diabetes is necessary for therapeutic reasons. Typical signs of type 2 diabetes are age over 40, obesity, and other markers for metabolic syndrome, a positive famitory, gradual development of the classical symptoms, and no evidence of ketosis. It is important to distinguish this from LADA (latent autoimmune diabetes of adulthood), a form of type 1 diabetes mellitus. To establish this differential diagnosis antibody testing is employed. Antibody tests in patients with newly manifest diabetes make good sense when the clinical diagnosis is not unequivocal, that is, to distinguish it from type 2 diabetes, MODY diabetes, hereditary and secondary forms. At present, immunodiagnosis is used too often in unambiguous cases of type 1 diabetes, but too rarely in supposed type 2 diabetes. As a rule, LADA patients are GADA-positive. If MODY diabetes is suspected, a genetic examination is indicated. In patients with GDM, antibody testing with GADA makes sense, in particular in slim patients receiving insulin treatment, since these patients have a high risk for developing a postpartum diabetes already in the first years.
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PMID:[Diabetes mellitus--differential diagnosis]. 1680 91


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