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

Latent autoimmune diabetes in adults (LADA) is characterized by clinical presentation as type 2 diabetes after 25 years of age, initial control achieved with diet or oral hypoglycaemic agents during at least 6 months, presence of autoantibodies (first of all GADA) and some immunogenetic features of diabetes mellitus type 1. In patients with an autoimmune endocrine disease, which could be also autoimmune diabetes, there is a high risk of development of another autoimmune endocrine disorder. The coexistence of two or more autoimmune endocrine diseases is pathognomonic for autoimmune polyglandular syndrome. Autoimmune thyroiditis and type 1 diabetes mellitus are the most common combination of autoimmune endocrine diseases reported. Most studies reported the prevalence of autoimmune thyroiditis in "typical" type 1 adult diabetic subjects about 20 - 40%. Little is known about the prevalence of autoimmune thyroiditis in subjects with LADA. Only a few studies confirmed a high prevalence of thyroid autoantibodies in type 2 diabetic subjects with GADA compared to type 2 diabetic subjects without GADA and compared to non-diabetic population too.
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PMID:Latent autoimmune diabetes in adults (LADA) and autoimmune thyroiditis. 1167 44

Latent autoimmune diabetes in adults (LADA) is a special form of diabetes that is clinically similar to type 2 diabetes but with positivity for pancreatic autoantibodies. The frequency of LADA patients among all patients diagnosed as type 2 varies between 6-50% in various populations. The frequency is higher in younger age groups. It is clear, however, that the frequency of autoimmune diabetes among adults is underestimated. Clinical features such as age and severity of symptoms are of no help in identifying these patients. Body mass index and C peptide levels in the general population increase with age, and these parameters are of limited use in identifying LADA patients. Determination of autoantibodies is necessary in order to correctly classify the type of diabetes. Among antibodies, GADA is the most frequently occurring autoantibody, followed by ICA. The natural course of these patients shows that C peptide will decrease with time in parallel with the curve for C peptide in classical type 1 diabetic patients. Most of the LADA patients will require insulin within three years. Our recommendation is that all patients be tested for pancreatic islet autoantibodies at diagnosis of diabetes to enable correct diagnosis and to avoid future failure of hypoglycemic agents and risk of complications due to hyperglycemia. It is still unclear whether early treatment with insulin is beneficial for the remaining beta cells.
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PMID:Latent autoimmune diabetes in adults. 1202 Oct 90

Latent autoimmune diabetes in adults (LADA) is identified by the presence of GAD65 autoantibodies in diabetic patients who do not require insulin treatment for at least six months after the diagnosis. Previous studies have shown that the risk for LADA, similarly to type 1 diabetes mellitus (T1DM), is increased in subjects carrying the HLA-DRB1*03-DQA1*0501-DQB1*0201 and/or HLA-DRB1*04-DQA1*0301-DQB1*0302 haplotypes. In the present study, we investigated the association between LADA and the CTLA-4 A/G polymorphism, another gene polymorphism associated with T1DM and other autoimmune diseases. The heterozygous A/G genotype was significantly more frequent among 80 LADA (69%) than among 85 healthy subjects of similar age and geographical provenience (47%) (OR = 2.47, corrected P = 0.023). Conversely, the homozygous A/A genotype was significantly less frequent in LADA subjects than in healthy controls (26% vs. 47%, OR = 0.4, corrected P = 0.028). The results of our study show that LADA is positively associated with the CTLA-4 A/G genotype, similarly to T1DM, thus providing further supporting evidence of the autoimmune origin of this form of diabetes mellitus of the adult.
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PMID:CTLA-4 gene polymorphism contributes to the genetic risk for latent autoimmune diabetes in adults. 1202 Nov 37

'Latent autoimmune diabetes in adults' (LADA) is the term coined to describe adults who have a slowly progressive form of autoimmune or type 1 diabetes that can be treated initially without insulin injections. The diagnosis of LADA is currently based on three clinical criteria: (1) adult age at onset of diabetes; (2) the presence of circulating islet autoantibodies, which distinguishes LADA from type 2 diabetes; and (3) insulin independence at diagnosis, which distinguishes LADA from classic type 1 diabetes. The prevalence of LADA in adults presenting with non-insulin-requiring diabetes is approximately 10%. Recognition of LADA expands the concept and prevalence of autoimmune diabetes, but LADA remains poorly understood at both a clinical and research level. In this perspective, we review the nomenclature, diagnostic criteria, genetics, pathology and therapy of LADA, to arrive at recommendations that might advance knowledge and management of this form of diabetes.
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PMID:Latent autoimmune diabetes in adults (LADA) should be less latent. 1619 87

Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune beta-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of beta-cell function show that LADA patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even though it may take up to 12 years until beta-cell failure occurs in some patients, impairments in the beta-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive beta-cell failure might be a more adequate concept. In agreement with proved impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of choice.
Diabetes 2005 Dec
PMID:Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment. 1630 43

Latent autoimmune diabetes in adults (LADA) is a disorder with onset after age 30, insulin independence for at least 6 months after diagnosis, and the presence of circulating pancreatic islet autoantibodies. The prevalence of LADA varies substantially across ethnic groups and ranges approximately from 1% to 10% among patients with type 2 diabetes. In this review we discuss the nomenclature, diagnostic criteria, immunologic and genetic markers, metabolic alterations and therapy of this form of diabetes.
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PMID:[Latent autoimmune diabetes in adults]. 1666 54

Small ubiquitin-related modifier (SUMO4), located in IDDM5, has been identified as a potential susceptibility gene for type 1 diabetes mellitus (T1DM). The novel polymorphism M55V, causing an amino acid change in the evolutionarily conserved met55 residue has been shown to activate the nuclear factor kappaB (NF-kappaB), hence the suspected role of SUMO4 in the pathogenicity of T1DM. The M55V polymorphism has been shown to be associated with susceptibility to T1DM in Asians, but not in Caucasians. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of T1DM and SUMO4 M55V has not been studied in LADA to date. The current study aims to test whether Latvians are similar to Caucasians in susceptibility to autoimmune diabetes (T1DM and LADA), with respect to SUMO4 M55V. We studied, age- and sex-matched, Latvian T1DM patients (n = 100) and healthy controls (n = 90) and LADA patients (n = 45) and healthy controls (n = 95). SUMO4 M55V polymorphism was analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The allelic frequencies of the A and G alleles were compared with HLA DR3-DR4-positive and HLA DR3-DR4-negative patients to identify any potential relation between HLA DR3-DR4 and SUMO4 M55V. We found no significant association between SUMO4 M55V and T1DM susceptibility in Latvians, the results being in concurrence with the previous studies in Caucasians of British and Canadian origin. Comparison of the A and G alleles with HLA DR3-DR4 did not result in any significant P values. No significant association was found between SUMO4 M55V and LADA. SUMO4 M55V is not associated with susceptibility to T1DM and LADA in Latvians, and Latvians exhibit similarity to other Caucasians with respect to association of SUMO4 M55V with autoimmune diabetes.
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PMID:Association of SUMO4 M55V polymorphism with autoimmune diabetes in Latvian patients. 1713 May 65

Latent autoimmune diabetes in adults or type 1.5 diabetes is considered to be a T-cell-mediated autoimmune disease. However, identification of patients is based commonly on autoantibody (Ab) detection. To determine whether measuring T-cell reactivity to islet proteins compared with measuring Abs improves detection of autoimmune diabetes and how beta-cell function correlates with T-cell reactivity compared with Ab positivity, we assessed the T-cell proliferative responses and Ab responses (islet cell autoantibodies, insulin autoantibodies, insulinoma-associated protein-2 autoantibodies, and GAD Abs) to islet proteins of 36 phenotypic type 2 diabetic patients. To be considered Ab(+) or T-cell(+), patients were required to be positive for a minimum of two consecutive time points. beta-Cell function was measured with fasting and glucagon-stimulated C-peptide. Independent of T-cell reactivity, Ab(+) and Ab(-) patients had comparable fasting and glucagon-stimulated C-peptide. Independent of Ab status, T-cell(+) patients demonstrated significantly lower glucagon-stimulated (P < 0.003) C-peptide compared with T-cell(-) patients. These data suggest that measuring T-cell responses to multiple islet proteins in phenotypic type 2 diabetic patients improves identification of patients with autoimmune diabetes and delineates those who have a more severe beta-cell lesion compared with Ab assessment alone.
Diabetes 2007 Aug
PMID:T-cell responses to islet antigens improves detection of autoimmune diabetes and identifies patients with more severe beta-cell lesions in phenotypic type 2 diabetes. 1747 22

Latent autoimmune diabetes in adults (LADA) is characterised by a relatively mild diabetes onset, autoantibody positivity and eventual requirement for insulin therapy. Twelve per cent of newly diagnosed, UK Prospective Diabetes Study (UKPDS) patients were positive for autoantibodies to GAD65 (GADA) and/or insulinoma-associated antigen-2A (IA-2A) and managed as if they had Type 2 diabetes according to the UKPDS protocol. Here, we compare data from UKPDS LADA patients with that from other cohorts. In common with other groups, UKPDS LADA patients required insulin therapy earlier post-diagnosis than non-LADA patients. Reduction of islet function was similar in UKPDS LADA groups randomised to oral glucose-lowering agents or insulin replacement therapy, contesting the current hypothesis of reduced decline of insulin secretion in LADA by immediate insulin therapy. Disease progression was not predicted by post-diagnosis GADA levels or epitope specificities as has been suggested. Slowly progressing insulitis and pancreatic beta-cell loss at post-mortem are consistent with sustained retention of residual C-peptide secretion in LADA. Genetic association patterns at the human leucocyte antigen (HLA) and insulin gene (INS) regions are similar in UKPDS LADA patients and individuals with adult and childhood-onset Type 1 diabetes. The combined evidence suggests that LADA is an adult-onset form of Type 1 diabetes, rather than a separate condition or an intermediate state in a continuum of phenotype from Type 1 to Type 2 diabetes.
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PMID:Autoimmune diabetes in adults: lessons from the UKPDS. 1871 76

KIRs (killer Ig-like receptors) expressed on natural killer (NK) cells are an important component of innate (and adaptive) immunity. They are either activatory or inhibitory, and certain KIRs are known to interact with specific motifs of HLA Class I molecules, which is very crucial in determining whether a cell is targeted to lysis or otherwise. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes, with an adult onset (>30 years). Because autoantibodies and autoimmunity involved are involved in the etiology of LADA, KIRs might play an important role in conferring susceptibility to or protection against the disease. The purpose of this study was to identify killer immunoglobulin-like receptor (KIR) genes, which are associated with susceptibility to and protection against type 1 diabetes in Latvian and Asian Indian patients with LADA. KIR and HLA-C ligand genotyping was performed using PCR-SSP in LADA patients from Latvia (n= 45) with age- and sex-matched controls (n= 92) and from India (n= 86) with controls (n= 98). Results showed that in Latvian patients with LADA, KIRs 2DL1, 2DS2, and 2DS4 were associated with susceptibility and KIR 2DS5 with protection. In Asian Indian LADA patients, KIRs 2DL5 and 3DL1 were associated with susceptibility and KIRs 2DS1 and 2DS3 with protection. Stratification analyses for KIRs that bind to HLA-C1 and C2 were performed. We concluded that KIRs are important in conferring susceptibility (or protection) to adult patients with LADA in both our study populations. However the KIR genes (and their HLA-C ligands) conferring susceptibility or protection in these two populations differ, showing a role of ethnicity in disease susceptibility.
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PMID:Different KIRs confer susceptibility and protection to adults with latent autoimmune diabetes in Latvian and Asian Indian populations. 1912 Feb 81


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