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Query: UMLS:C0011849 (diabetes)
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Autoimmune recurrence and subsequent diabetes after pancreas transplantation has been described. In this cross-sectional study 91 type 1 diabetic patients were examined after successful pancreas/kidney transplantation (SPK). We studied the prevalence of autoantibodies to insulin (IAA), glutamate decarboxylase (GAD) and tyrosine phosphatase (IA-2) as well as parameters of pancreas graft function. Graft recipients were grouped according to immunoreactivity: group 1: no immunoreactivity; group 2: immunoreactivity to one antigen; group 3: immunoreactivity to two or three antigens. Twenty-five percent of graft recipients displayed no immunoreactivity, 39% displayed positivity for one antigen and 36% were positive for two or three antigens. There were no significant differences concerning fasting glucose, HbA1(c), glucose tolerance and renal function between the groups. Patients with cyclosporine (n = 42) as first-line immunosuppression displayed more often immunoreactivity to IA-2 and IAA than patients treated with tacrolimus (n = 49) (31% vs. 14%, P = 0.04; 67% vs. 47%, P = 0.04). In addition methylprednisolone therapy was related to less immunoreactivity to IA-2. Immunological markers for type 1 diabetes can be determined in the majority of pancreas graft recipients despite adequate immunosuppression. However, immunoreactivity was not associated with impaired graft function. Patients with cyclosporine for immunosuppression and withdrawal of glucocorticoids therapy were more often immunoreactive to IAA and IA-2.
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PMID:Insulin and islet autoantibodies after pancreas transplantation. 1629 55

We underwent a project aimed to define the clinical and immunological characteristics of type 1 diabetes (T1D) in a Colombian population. This was a multicenter and cross-sectional study. Patients were systematically interviewed and their medical records reviewed, using a questionnaire that sought information about demographic, clinical and immunological characteristics. Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase antibodies (IA-2A) and insulin antibodies (IAA) were examined by radioimmunoassay. There were 107 patients with T1D. Male:female ratio was 1:1. Half of the patients developed diabetes ketoacidosis at onset. GADA, IA-2A, and IAA were detected in 45%, 40%, and 69% of the cases, respectively. GADA positive patients were older and had a less duration of disease than patients without these autoantibodies (p<0.01). Association between breast feeding with the presence of antibodies or clinical characteristics was not observed. The results highlight some differences of T1D expression according to geographic location and ethnicity. Differences in age at onset and clinical variables may point to an environmental factor or deficient access to health care system. Genetic studies underway will provide important information in this population. These results might help to define public health policies in our population to improve T1D diagnosis, patients' quality of life and their outcome.
Diabetes Res Clin Pract 2006 May
PMID:Clinical and immunological characteristics of type 1 diabetes mellitus in a northwestern Colombian population. 1632 57

Haemolytic-uraemic syndrome (HUS) is a rare cause of insulin-dependent diabetes mellitus during the acute stage. We previously reported the case of a 3-year-old girl having presented with typical HUS with diarrhea, microangiopathic anaemia, thrombocytopenia and acute renal failure (17 days of anuria). Transient hyperglycaemia (highest level: 513 mg/dl) was observed, requiring continuous intravenous insulin infusion for 9 days. Subcutaneous insulin injections were stopped after 24 days. Oral glucose tolerance test performed 4 months after normalization of blood glucose was normal. HLA DQ genotype (DQA1-DQB1.AZH/DQA3-DQB3.1) was not at risk for type 1 diabetes and there were no auto-antibodies (ICA and IAA). The 3-years follow-up was marked by persistent arterial hypertension, proteinuria and slight renal insufficiency despite angiotensin-converting enzyme inhibitor treatment. Ten years after HUS occurred (the patient had been lost to follow-up for 7 years), she came back with complaints of headache but neither polyurodipsia nor weight loss. She was found to have arterial hypertension. Chronic renal impairment had moderately progressed with decreased glomerular filtration rate (63 ml/min/1.73 m2) and proteinuria (2 g/24 hours). Fasting blood glucose was 189 mg/dl and reached 315 mg/dl during an oral glucose tolerance test. HbA1c level was 8.2% (N<6.2%) and diabetes mellitus was diagnosed without any signs of autoimmunity (IAA, ICA, GADA and IA2B were negative). Good glycaemic control was obtained with 0.5 U/kg/day of insulin. In conclusion, transient beta-cell dysfunction complicating HUS acute stage may evolve to overt non-autoimmune diabetes mellitus (microangiopathic process?), even after a long free interval. This case emphasizes the need for a long-term follow-up of patients with HUS.
Diabetes Metab 2006 Jun
PMID:Insulin-dependent diabetes mellitus as long term complication of haemolytic-uraemic syndrome. 1679 6

We describe a 37 year-old woman case of latent autoimmune diabetes in adults (LADA). She was presented with unfounded weight loss. The diagnosis of diabetes mellitus was established on twice plasma glucose measurements above 200 mg/dl. In other routine biochemical examinations we did not observe dehydratation, electrolyte depletion, acidosis. However plasma level of C peptide basal and after stimulation with glucagon was reduced. Initially, the patient responded well to sulphonylurea treatment. To test immunological pathogenesis we examine autoimmune markers of diabetes type 1. Autoimmune antibodies (GAD, IAA) were found in patients and her parents, which were until now diabetic type 2. We report this case because incidence of latent autoimmune diabetes in adults is underestimate and rarely diagnosed in clinical practice.
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PMID:[Family incidence of latent autoimmune diabetes in adults--case report]. 1683 90

Type 1 diabetes results from the autoimmune destruction of the insulin producing pancreatic beta-cells. For years, the notion that T-lymphocytes played a crucial role in the disorder's formation was considered such sound dogma, that interest in B-lymphocytes and autoantibodies as pathogenic variables was largely relegated to second-class status. However, much of our knowledge regarding the pathogenesis and natural history of this disease has been afforded by analysis of subjects having type 1 diabetes associated autoantibodies. While autoantibodies to more than two dozen autoantigens have been associated with this disease, a majority of interest has been directed at four autoantibodies; islet cell cytoplasmic (ICA), insulin (IAA), glutamic acid decarboxylase (GADA), and IA2/ICA512 autoantigen (IA2A). These autoantibodies, combined with other metabolic and genetic markers, are extremely effective for predicting eventual development of type 1 diabetes in otherwise healthy individuals. These autoantibodies have also aided in our understanding of disease heterogeneity and suggest that the autoimmune processes underlying type 1 diabetes initiate in the earliest stages of life (e.g., initial autoantibody formation at 9-18 months of age). Additional improvements are needed to more accurately define the time to disease onset, response to therapeutic intervention, the pathogenic features of the autoimmune response, and perhaps even the quantity of residual beta cell function.
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PMID:Autoantibody markers for the diagnosis and prediction of type 1 diabetes. 1689 Aug 98

The purpose of the study was to investigate the condition of immunity (blood lymphocyte immune phenotype and ultrastructure) in healthy children with a family background of type 1 diabetes mellitus (DM 1) having or not having diabetes-associated autoantibodies (DAAB). The subjects of the study were divided into three groups. Group 1 consisted of 90 children with a family background of DM 1 (first line relatives had DM 1), DAAB- (GADA, IA-2A, and IAA) positive or negative; group 2 consisted of 51 children with newly revealed DM 1; group 3 included 45 healthy controls, normoglycemic DAAB-negative children with no family background of DM 1. GADA, IA-2A, and IAA titers were measured using radioimmunoassay. The immune phenotype of lymphocytes (CD3+, CD4+, CDr8, CD20+, and CD56+ cells) were studied using flow cytometry (FACS-analysis); their ultrastructure was studied by means of electron microscopy. The study found a significantly lower total number of T-lymphocytes (CD3+ cells), T-helpers/inductors (CD4+ cells), and natural killer cells (CD56+ cells and large granule-containing lymphocytes) in the DAAB-positive children vs. the DAAB-negative ones and especially the controls. In the DAAB-positive children, electron microscopy found distinct changes in the ultrastructure of CD4+ lymphocytes and large granule-containing lymphocytes (CD56+ cells), which evidences changes in the secretory and cytostatic function. Such changes in the number and ultrastructure of these lymphocyte subpopulations are found in patients with newly revealed DM 1. Thus, immune changes happen in the organism of a healthy person a long time before clinical manifestations of DM 1 develop; these changes reflect a concealed autoimmune process in Langerhans islets. Detection of DAAB plays a significant role not only in studying poorly understood pre-diabetes nature, but also in the development of new, scientifically based methods of its prevention and treatment.
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PMID:[The immunity during the pre-clinical period of type I diabetes mellitus]. 1708 89

The aim was to estimate the prevalence of the serological markers of pancreatic autoimmunity in a cohort of Italian patients with type 1 diabetes mellitus occurring after 20 years of age in order to determine the prevalence of autoimmune diabetes and the most sensitive autoantibody combination to be employed for the diagnosis. We investigated 57 patients (31 males and 26 females) at clinical diagnosis of type 1 diabetes. 35 patients were 21-40 years and 22 were 41-72 years of age. Autoantibodies to islet-cells (ICA) were detected by indirect immunofluorescence, while those against glutamic acid decarboxylase (GADA), tyrosine-phosphatase (IA2A) and insulin (IAA) were detected by radiobinding assays. A positive test for at least one of the pancreatic autoantibodies was found in 45 of the 57 patients (78.9%). Coupling two antibody tests, GADA and/or IAA were found in 73.7%, ICA and/or GADA in 71.9%, while GADA and/or IA2A were found in 70.2% of the patients. The most frequently positive test was for GADA (66.7%). In general, the frequency of diabetes-related antibodies was higher in the 21-40-year-old group compared to the 41-72-year-old group and in females than males. Based on the detection of pancreatic autoantibodies determination, the great majority of the adult patients with recent onset type 1 diabetes were found to be autoimmune in nature. The best cost/benefit combination is provided by coupling the detection of GADA and ICA.
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PMID:Pancreatic autoantibodies in Italian patients with newly diagnosed type 1 diabetes mellitus over the age of 20 years. 1714 85

Insulin resistance is a primary component in the pathophysiology of type 2 diabetes. In latent autoimmune diabetes in adults (LADA), insulin resistance has been reported to be significantly lower than in autoantibody-negative type 2 diabetes (T2DM), but whether this might be related to differences in body mass index (BMI) has not been excluded. Furthermore, previous studies have used limiting inclusive criteria for LADA, requiring only the presence of GADA or IA-2A. To apply more inclusive criteria for LADA, consistent with recent recommendations, we defined LADA by clinical manifestations characteristic of T2DM, but with the presence of any combination of GADA, IA-2A, ICA, or IAA. We recruited 43 LADA patients, 70 T2DM patients, and 150 non-diabetic controls. Insulin resistance was assessed by both the homeostasis model assessment and the quantitative insulin sensitivity check index, and BMI was calculated. We found that insulin resistance in LADA is equivalent to that of T2DM. When insulin resistance is assessed as a function of BMI, both diabetic populations demonstrated an insulin resistance equally greater than normal controls. The interaction between insulin resistance and BMI in the two diabetic groups was significantly different from that demonstrated in non-diabetic controls. In summary, LADA demonstrates insulin resistance of similar magnitude to T2DM, but with the concurrent component of an immune attack against the pancreatic beta-cells. LADA patients may be at significant risk for metabolic consequences of insulin resistance other than glucose metabolism, such as those described in the metabolic syndrome. As complications and treatment regimens specific to LADA are realized, improved means of identification of LADA will become increasingly important.
Diabetes Res Clin Pract 2007 Aug
PMID:Equivalent insulin resistance in latent autoimmune diabetes in adults (LADA) and type 2 diabetic patients. 1723 96

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

Japan is one of the countries with lowest incidence rate of childhood type 1 diabetes in the world, averaging 2.4 cases/100,000/year. However, it appears that the prevalence of type 1 diabetes in adulthood is more than twice compared to childhood patients. There are at least three clinical subtypes of type 1 diabetes in Japan, i.e. acute-onset, slow-onset, and fulminant type 1 diabetes. Fulminant type 1 diabetes is a unique subtype of type 1 diabetes that accounts for about 20% of acute-onset type 1 diabetes, and is rare in childhood in Japan. Furthermore, the slow-onset form of type 1 diabetes might be a major subtype of disease in adulthood. In patients with acute-onset type 1 diabetes, about 90% of patients express at least one of GADAbs, IAA, and IA-2Abs at disease onset. Slow-onset form of type 1 diabetes is diagnosed as having type 2 diabetes at disease onset, which is referred as "latent autoimmune diabetes in adults (LADA)", "GADAb(+) type 2 diabetes", or "slowly progressive type 1 diabetes". The prevalence of GADAbs in adulthood patients with type 2 diabetes without insulin therapy is 3-4%, and is higher in the patients with shorter duration of diabetes. Although high levels of GADAbs are one of the predictive markers for future insulin requirement, there are a certain number of patients with high titer of GADAbs who do not progress to insulin dependency for many years, and the predictive value of GADAbs positivity for future insulin requirement is estimated about 67% by Baye's theory. Thus, accurate predictive strategies of future insulin deficiency in LADA patients using autoantibody epitope analysis, genetic determination, or T cell assay are needed for the effective immune intervention.
Diabetes Res Clin Pract 2007 Sep
PMID:Current aspects on the clinical immunology and genetics of autoimmune diabetes in Japan. 1746 4


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