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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We explored the importance of the genetic markers microsatellite TNFa, HLA-DR3-DQ2, and DR4-DQ8 in diabetes mellitus. The studied groups comprised autoimmune type 1 (n = 63), nonautoimmune type 1 (n = 35), latent autoimmune diabetes in adults (LADA; n = 54), and nonautoimmune type 2 (n = 340) and these patients were compared to 117 healthy controls. HLA genotyping was done with polymerase chain reaction and sequence-specific oligonucleotides. TNFa microsatellites were determined with polymerase chain reaction and fragment size determination. Univariate analysis of these genetic risk factors demonstrated that homozygosity for TNFa2/2 was a significant risk factor for autoimmune type 1 diabetes (odds ratio (OR) = 5.82; 95% confidence interval (95%CI) 1.97-17.2), for autoimmune negative type 1 diabetes (OR = 4.63; 95%CI 1.32-16.2), and for LADA (OR = 3.90; 95%CI 1.21-12.5). Moreover, heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was an important risk factor for autoimmune type 1 diabetes (OR = 16.4; 95%CI 3.60-75) as was DR4-DQ8/x (OR = 2.52; 95%CI 1.27-4.98). Heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was a risk factor also for LADA (OR = 10.0; 95%CI 2.05-48.9). Neither HLA-DR3-DQ2 nor DR4-DQ8 were risk factors for nonautoimmune type 1 or type 2 diabetes. We concluded that heterozygosity for DR3-DQ2/DR4-DQ8 and to some extent homozygosity for TNFa2/2 were risk factors for autoimmune diabetes irrespective of the clinical classification.
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PMID:Polymorphisms of TNF microsatellite marker a and HLA-DR-DQ in diabetes mellitus-a study in 609 Swedish subjects. 1682 7

Type 1 diabetes may occur at any age, in young individuals before or after adolescence, during middle age life, or even in the elderly. When diagnosed in adults it is characterized by the presence of islet cell-related autoantibodies (ICA), in particular GAD and IA2 (less common) and very rarely insulin autoantibodies (IAA). Baseline C-peptide at diagnosis of type 1 diabetes can identify different patient populations according to when the disease is diagnosed depending on age. A key question is whether the process of beta cell destruction follows the same pattern in patients diagnosed in young age, soon after adolescence, or in adult age. The terms SPIDDM--slowly progressive insulin-dependent diabetes mellitus, and LADA--latent autoimmune diabetes in adults, have been considered synonymous on most grounds based on the fact that with this form of diabetes we intend a form of diabetes that has an autoimmune basis that eventually will require insulin for its treatment sometime after diagnosis. Therapeutic approaches are similar for prevention and treatment of SPIDDM or LADA, including both specific and nonspecific immunomodulation. For specific immunomodulation the attention is focused on DiaPep277, GAD, and insulin, and for nonspecific immunomodulation on 1,25 dihydroxy-vitamin D3 (calcitriol) and thiazolidinediones. Current trials in SPIDDM/LADA with both specific and nonspecific immunomodulation seem promising. Response to therapy varies according to age and residual beta cell function at diagnosis of SPIDMM/LADA. Results in beta cell protection with different agents can also help to identify differences, if any, between SPIDMM and LADA.
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PMID:Immunomodulation for the prevention of SPIDDM and LADA. 1713 May 36

The authors have summarized literature data and results of own studies on autoantibodies and beta-cells of Langergan's islands of the pancreas (ICA, GADA, IA-2A and IAA). It may help predicting the development of I type diabetes mellitus even in practically healthy individuals before they present clinically evident disease. The history of the discovery of these autoantibodies, their immunological properties, comparative characteristics, sensibility and specificity and their application in clinical practice to forecast the development of I type diabetes mellitus in different populations of children and adolescents as well as to more exactly carry out differential diagnostics of DM type I and DM type II in difficult cases in adults is presented in the article. Having diabetes-associated autoantibodies as a diagnostic tool allows to diagnose a separate subtype of diabetes mellitus--autoimmune diabetes mellitus of adults (LADA) and it is very important to choose a right way of the treatment.
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PMID:[Discovery of autoantibodies to Langergan's islands of the pancreas is a prominent achievement in the field of forecasting the development and diagnostics of diabetes mellitus in clinics]. 1731 77

We describe here the unusual aggregation of diabetes cases in a family of 10 subjects. Among them, three adult siblings presented with LADA and one child presented with juvenile type 1 diabetes. Although the exact pathogenesis of LADA is unknown and questions the role of autoimmunity in beta cell failure, the familial aggregation of these two forms of diabetes underlines the existence of common roots, i.e. immune mechanisms and genetic susceptibility. This report clearly illustrates the differences in terms of autoimmunity (prevalence and titer of GAD and IA2 antibodies) and HLA class II genotype between patients with LADA and those with juvenile type 1 diabetes.
Diabetes Metab 2007 Apr
PMID:Familial aggregation of LADA and juvenile type 1 diabetes in a French Caucasian family. 1739 15

In this work, we studied the association of the E23K polymorphism of the Kir6.2 ATP-sensitive potassium channels in 212 Czech patients with diabetes mellitus who were diagnosed after the age of 35. Patients were classified into T1DM, LADA and T2DM groups based on C-peptide and GADA levels. Carriers of the predisposing Kir6.2 E23K K allele showed no increased risk of either type of diabetes mellitus development. On the other hand, we found a correlation between E23K SNP of the KCNJ11 gene and C-peptide levels, which may be considered a measure of pancreatic beta-cell activity, although this correlation was not statistically significant. In conclusion, we failed to confirm the Kir6.2 E23K as a genetic marker for T1DM, LADA and T2DM in the Central Bohemian population of the Czech Republic.
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PMID:KCNJ11 E23K polymorphism and diabetes mellitus with adult onset in Czech patients. 1797 7

Autoimmune diabetes mellitus, called type 1 diabetes mellitus (T1DM), is caused by autoimmune destruction of islet beta cells in the pancreas. T1DM susceptibility loci mapped by different genome screening are IDDM1-IDDM18. It has been estimated that HLA (IDDM1) provides up to 40-50 % of the familial clustering of T1DM (LOD score of 65.8). Many studies have verified that DQB1*0302 is a strong susceptibility gene and that the heterozygous combination of DQA1*0301-DQB1*0302 on the HLA-DR4 haplotype and DQA1*0501-DQB1*0201 on the HLA-DR3 haplotype results in a synergistically increased risk of T1DM. The presence of predisposing genes in autoimmune diabetes decreases with age, probably due to increasing influence of environmental factors. Autoimmune diabetes with manifestation in adults may have partly different immunogenetic etiopathogenesis than autoimmune diabetes with manifestation in childhood. Compared to fast progressing adult-onset T1DM, slowly progressing adult-onset type 1 diabetes (LADA) might involve genes leading to a slow progressive beta-cells destruction.
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PMID:Genetics of autoimmune diabetes mellitus. 1828 44

Diabetes mellitus, especially when complicated with decline of renal function due to diabetic nephropathy (DN), is associated with accumulation of advanced glycation end products (AGEs) exerting their adverse effects via receptor of AGE (RAGE). Soluble RAGE (sRAGE) is a truncated form of RAGE functioning as an inhibitor of AGE-mediated signalling. We studied relationships between sRAGE, renal function and genetic variability in the AGER gene in diabetic subjects. Study comprised a total of 265 diabetics (type 1 or 2 or LADA) with normoalbuminuria (n = 94) or DN (n = 171). sRAGE (assessed by ELISA) was significantly higher in DN than normoalbuminuria subjects (P = 0.007) and positively correlated with age, S-urea, S-creatinine and albuminuria and AGEs (determined spectrofluorimetrically), negatively with GFR (all P < 0.05); however, multivariate regression revealed that GFR was the only independent variable associated with sRAGE (P = 0.047). sRAGE did not correspond with carrier state of risk-haplotype copies (RAGE2) (P > 0.05). In conclusion, GFR is a principal determinant of sRAGE concentration and gradual sRAGE increase in subjects with advancing impairment of renal function is paralleled by AGEs.
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PMID:Soluble RAGE, diabetic nephropathy and genetic variability in the AGER gene. 1861

The newly developed insulin sensitizer-thiazolidinediones have the potential to downregulate inflammation and autoimmune response. The objective of this study was to observe the beneficial effects on beta-cell function in the LADA patients treated with rosiglitazone. 54 LADA patients were assigned to oral hypoglycemic agents group (GAD-Ab<175 U/mL and FCP>0.3 nmol/L) or early insulin administration group (GAD-Ab>or=175 U/mL or GAD-Ab<175 U/mL and FCP<or=0.3 nmol/L). Then, those patients were randomly assigned to receive sulfonylureas (SUs group) or rosiglitazone (RSG group) therapy, or to receive insulin alone (INS group) or rosiglitazone plus insulin (INS+RSG group). Plasma glucose, HbA1c, fasting C-peptide (FCP) and C-peptide after 2h 75-g glucose load (PCP) were determined every 6 months. The levels of PCP and delta CP were higher in RSG group compared with those in SUs group after the 18th month. The PCP level (after the 12th month) and delta CP level (after the 18th month) in INS+/-RSG group were higher than those in INS group. Rosiglitazone combined with insulin wherever or not preserved beta-cell function in LADA patients after 3 years.
Diabetes Res Clin Pract 2009 Jan
PMID:Rosiglitazone preserves islet beta-cell function of adult-onset latent autoimmune diabetes in 3 years follow-up study. 1900 7

This study aims to explore whether diabetes mellitus from T1DM, through LADA, to T2DM presents a continuous spectrum in terms of HLA-DQ genetic background. We recruited 223 patients with autoimmune T1DM, 215 with LADA, 206 with T2DM, and 228 nondiabetic controls, and then defined their HLA-DQA1 and -DQB1 genotypes and haplotypes. T1DM patients were divided into two groups depending on age of onset of disease: juvenile-onset (JO; before the age of 20) and adult-onset (AO; after the age of 20). LADA patients were sorted according to the GADA titer: the LADA1 group had titers higher than 175 U/mL, whereas the LADA2 group had lower titers. The susceptible haplotypes of T1DM were DQA1*03-DQB1*0303, DQA1*03-DQB1*0401, and DQA1*05-DQB1*0201. The protective haplotype was DQA1*0102-DQB1*0602. The frequency of DQA1*03-DQB1*0303 in JO, AO, LADA1, LADA2, T2DM, and control groups were 38.2%, 34.2%, 25.3%, 18.9%, 17.5%, and 16.5%, respectively. The frequencies of DQA1*05-DQB1*0201 were 21.2%, 15.0%, 12.7%, 4.6%, 3.6% and 3.3%; the frequencies of DQA1*03-DQB1*0401 were 11.3%, 9.4%, 11.3%, 5.4%, 4.4% and 3.3%; and the frequencies of DQA1*0102-DQB1*0602 were 1.4%, 1.7%, 0.7%, 4.6%, 7.0%, and 5.3%. The linear-by-linear association showed that the frequency of DQA1*03-DQB1*0303, DQA1*05-DQB1*0201, and DQA1*03-DQB1*0401 presented a decremental tendency in JO, AO, LADA1, LADA2, T2DM, and control groups. The preliminary data demonstrated that the susceptible haplotypes of the HLA-DQ gene present a continuous spectrum from typical T1DM, through LADA, to T2DM, which deserves further investigation.
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PMID:From Type 1, through LADA, to type 2 diabetes: a continuous spectrum? 1912 Feb 76

Practitioners can be faced with cases of diabetes that do not clearly correspond to the clinical characteristics of type 1 or type 2 diabetes. They should take into account forms of diabetes such as MODY or LADA, which often go unrecognised in spite of significant prevalence. Various tests can be conducted to measure insulin secretion and resistance, and to check whether the disease is auto-immune. This makes for correct diagnosis and prescription of the appropriate course of treatment.
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PMID:[Type 1 or 2 diabetes? Or other?]. 1957 19


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