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

Cell mediated immune response in vitro to a number of antigens has been reported in patients with Type 1 diabetes. The aim of the present study was to develop an in vivo intradermal (delayed type hypersensitivity) skin test using antigens known to be recognized by lymphocytes of patients with Type 1 diabetes and to compare, where possible, the in vivo response to the in vitro T cell proliferation to the same antigens. The skin test was performed in the following group of patients: 55 with recent onset Type 1 diabetes; 16 patients with Type 1 diabetes of longer duration; 10 patients with autoimmune thyroid disease and 20 patients with Latent Autoimmune Diabetes in Adults (LADA). Type 1 diabetes specific antigens for the skin test included glutamic acid decarboxilase (GAD65), insulin and beta casein, whereas diabetes non specific antigens included tetanus toxoid, diphteria, proteus, tubercolin, streptococcus, and glycerol as control. A multitest device consisting of heads delivering intradermally 10 microl of solution containing the antigens was applied to the forearms; the specific antigens were injected in one forearm whereas the non specific antigens were injected in the other forearm. Reading of the reaction, which was considered positive in the presence of a nodule of 2 mm diameter was performed 48 h after the multitest application. The in vitro T cell response to diabetes specific antigens used in the multitest was studied using conventional proliferation assays in patients with recent onset Type 1 diabetes and in age matched normal subjects. Only recent onset Type 1 diabetes patients showed an in vivo positive response to GAD65, such response being detectable in 10 patients (18%). Two patients reacted also to beta casein and insulin, all other patient groups resulted negative but 2 patients with longer duration of Type 1 diabetes. There was no apparent link between the in vivo skin test and in vitro T cell proliferation to GAD65. We conclude that in vivo cell mediated immune reaction to GAD65, insulin and beta casein can be visualized in a minority of patients with recent onset Type 1 diabetes. Further studies are required to determine specificity and whether altering the dose can improve the sensitivity of the test.
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PMID:Intradermal skin test with diabetes specific antigens in patients with type 1 diabetes. 1129 23

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

The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 microg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 microg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 microg dose group. GADA log levels clearly increased (P=.0002) in response to 500 microg Diamyd. The (CD4+)(CD25+)/(CD4+)(CD25-) cell ratio increased (P=.0128) at 24 weeks in the 20 microg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.
J Diabetes Complications
PMID:Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes. 1599 59

Type 1 diabetes mellitus (T1DM) is one of the long-time studied autoimmune disorders. The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family. In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested. Patients were divided into the subgroups in relation to the disease type: T1DM in children, T1DM in adults, and Latent Autoimmune Diabetes in Adults (LADA). HLA-DRB1 (*)04 and HLA-DQB1 (*)0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively). HLA-DRB1 (*)03 has been found as a single risk factor for LADA (P<0.0001, OR=4.9). We detected 15 alleles for the NFKB1 gene polymorphism (CA-repeats) in the Czech population. The alleles were ranging in size from 114-142 bp corresponding to 10-25 CA repeats. Frequency of the A7 allele of NFKB1 gene has been significantly increased in T1DM adults (P<0.01). There was no difference in A and a G allele frequency of NFKBIA gene between the control group and patients, but the association of the AA genotype of NFKBIA gene has been found for LADA (P<0.05). Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course. Due to the results obtained in the epidemiological study we have been looking also for the function significance of the genetic predisposition. No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background.
Exp Clin Endocrinol Diabetes 2007 Feb
PMID:HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients. 1731 73

Latent Autoimmune Diabetes In Adults (LADA) is a form of autoimmune-mediated diabetes in adults. The progression of beta-cell failure is slower than in childhood type 1 diabetes. Patients with LADA present with more preserved beta-cell function than those with classic type 1 diabetes. The diagnosis of LADA according to Immunology of Diabetes Society is based on three features: age over 35 years, the presence at least one of four circulating autoantibodies to pancreatic islet cell antigens and lack of requirement for insulin at least 6 month after diagnosis. The level of C-peptide secretion after stimulation with intravenous glucagon helped to diagnosis. There are different opinions in relation to treatment of LADA. Some studies suggest, that insulin treatment is indicated at the time of diagnosis LADA, some of them--when patients upon failure of oral hypoglycemic treatment.
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PMID:[LADA--latent autoimmune diabetes in adults]. 1794 Sep 91

The enzyme glutamic acid decarboxylase (GAD) is of great importance for the neurotransmission in the central nervous system, and therefore of interest for treatment of pain and neurological disease. However, it is also released in pancreas although its role is not quite clear. GAD is a major auto-antigen in the process leading to type 1 diabetes with both a clear cell-mediated immune response to GAD and auto-antibodies to GAD (GADA), which can be used as a predictor of diabetes. Administration of the isoform GAD65 can prevent autoimmune destruction of pancreatic beta cells in non-obese diabetic (NOD) mice and the subsequent need for exogenous insulin replacement. In Phase I and II studies an alum-formulated vaccine (Diamyd) has shown to be safe, and in a dose-finding study in Latent Autoimmune Diabetes in Adults (LADA) patients 20-microg was given subcutaneously one month apart indicating preservation of residual insulin secretion. A double-blind randomized Phase II trial in 70 patients (10-18 years old) with recent-onset type 1 diabetes showed significant preservation of residual insulin secretion and a GAD-specific immune response, both humoral and cell-mediated, but no treatment-related adverse events. With this promising background further studies are on their way, both intervention in newly diagnosed type 1 diabetic patients, and trials to prevent the disease.
Diabetes Metab Res Rev 2009 May
PMID:Therapy with GAD in diabetes. 1926 32

Latent Autoimmune Diabetes in Adults (LADA) is an autoimmune endocrine disorder in which despite the presence of antipancreatic islets antibodies in the moment of diagnostics, the progression to beta-cell secretory insufficiency is slow. It is often confused with others types of diabetes and therefore the management is frequently inadequate. We report a clinical case of a 23-year-old man with diagnosis of type 2 diabetes since 6 months ago, poorly controlled with a sulfonylurea, who initially presented 2 months ago from polyuria, polydipsia, and asthenia and 6 kg weight loss. History of past illness was negative, however, his mother relates exclusive breastfeeding during the first 15 days of life and later (until the 6 months) he was fed with infant formula (S-26). Family history revealed a first-degree relative (father) with diabetes mellitus secondary to steroid administration due to diagnosis of bone marrow hypoplasia. Also presents second-degree family history (uncle and grandfather) of type 2 diabetes mellitus. There were no pathologic findings at the physical examination. Anthropometry and laboratory tests were as follows: body mass index (BMI) = 19.66 kg/m, basal and postprandial glycemia = 108, and 276 mg/dL respectively, glycated haemoglobin = 8.9%, basal and postprandial C-peptide (2 hours) = 1.9, and 3.2 ng/mL, homeostasis model assessment of beta cell function: 87.5%, homeostasis model assessment of insulin resistance: 1.6. LADA presumptive diagnosis was confirmed with presence of autoantibodies anti-tyrosin-phosphatase and GAD65. At the time of diagnosis, individuals with LADA present an onset age <50, BMI <25 kg/m2, low magnitude postprandial and basal hyperglycemia, normal or close to normal C-peptide values, and thus not occur with acute hyperglycemic crises. Insulin therapy preserves pancreatic b-cell function, at the point that eventually prescribed insulin doses need to be reduced.
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PMID:Latent Autoimmune Diabetes in Adults: a case report. 2022 23

Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) are connected with autoimmune insulitis (associated with islet cell autoantibodies) and the specific high-risk HLA class II genotype. The study was aimed at analyzing time and clinical characteristics of the diabetics with an onset of the disease after 35 y. (T1D and LADA). Main target of the study was to assess possible role of the old age onset and compare it with diabetics with the onset in the middle age (incl. analyzing HLA-DRB1 genotype). In the study, we included 103 diabetics with an onset of autoimmune diabetes at 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. 46 men and 57 women of the average age 65.7 +/- 13.8 y. (range 35-93 y.) were out of this number. 41 were assessed as the T1D patients and 61 as the LADA ones. As a control group we used 99 healthy individuals. Patients of the T1D subgroup developed diabetes in the age of 50.8 +/- 15.1 y. and of the LADA subgroup in the age of 52.6 +/- 12.8 y. Its duration in the time of this study was 10.7 +/- 11.6 y.; respectively 5.3 +/- 7.1 y. Fasting and postprandial C-peptide levels were statistically higher (p < 0.01) in the LADA subgroup vs. T1D. Obesity 1st and 2nd grade were present together only in 12.6%. BMI was not statistically significantly different between both groups. We found in our diabetic patients the predisposition alleles HLA-DRB1*03, HLA-DRB1*04 and particularly their combination. The occurrence of these HLA alleles is significantly higher in T1D patients in comparison to control groups (p = 0.01, OR = 4.0). In our study, the occurrence of the susceptible HLA-DRB1*03 and HLA-DRB1*04 alleles in T1D patients is higher than in LADA. The presence of these alleles identifies patients of high risk and requirement of insulin therapy. Since risk alleles are similarly present in middle and old age, environmental factors probably play similar role in these onsets of autoimmune diabetes.
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PMID:Type 1 diabetes and LADA--occurrence of HLA-DRB1 *03 and DRB1 *04 alleles in two age different groups of diabetics. 2103 93

The determination of GADA may be useful for clinical classification of diabetes mellitus (DM) in clinically unclear cases. This GADA positivity may persist in any diabetics Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) many years after appearance of DM. The study was aimed at comparing the levels of GADA between both diabetic subsets with their clinical parameters, age of onset DM, period of insulin need, body mass index, HbA1C, fasting and postprandial C-peptide, risky HLA-DRB1* alleles, occurrence of micro- and macrovascular diabetic complications. Further analysis of GADA titers in different time consequences to the development of DM and relations to IA-2 were made. In the study, we included 130 diabetics with an onset of diabetes (T1D or LADA) 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. Out of this number there were 62 men and 68 women of the average age 65.5 +/- 14.0 y. (range 35-93 y.). 54 were assessed as the T1D patients and 76 as the LADA ones. Patients of the T1D subgroup were GADA positive 22 times and of the LADA subgroup 21 times. LADA 2 patients that were GADA negative were more obese than GADA positive LADA diabetics (p < 0.01). Also postprandial C-peptide was higher in LADA patients GADA negative (p < 0.05). Other clinical characteristics were without statistically significant differences. We found in our diabetic patients a relation between alleles HLA-DRB1*03 and particularly combination with HLA-DRB1*04 with positive GADA levels. In the GADA negative group obesity, coronary heart disease, hypertension, syndrome of diabetic foot and dyslipidaemia appeared more frequently (OR = 2.8; 3.1; 6.2 and 2.4). We found no significant differences in observed parameters--comparison GADA positivity and negativity according to the duration of DM. GADA positive were even 10 y. duration 16 times and after 20 y. even 6 times. Recent DM had positive GADA in 11 cases and 13 cases of recent DM had GADA negative. IA-2 antibodies were positive (> 1.0 U/ml) 18 times altogether and always with positive GADA, but only 7 times in recent DM. The presence of elevated GADA identifies patients unequivocally suitable for early insulin therapy. Our observations and experiences confirm that GADA can be found increased after more than 10-20 years duration of DM, although in decreasing trend.
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PMID:GAD antibodies in T1D and LADA--relations to age, BMI, c-peptide, IA-2 and HLA-DRB1*03 and DRB1*04 alleles. 2195 94

Diabetes, one of the most commonly seen metabolic disorders, is affecting a major area of population in many developing as well as most of the developed countries and is becoming an alarming concern for the rising cost of the healthcare system. Latent Autoimmune Diabetes in Adults (LADA) is a form of diabetes which is less recognized and underdiagnosed type of diabetes which appears to have characteristics of both type 1 (autoimmune in nature) and type 2 diabetes (adult age at onset and initial response to oral hypoglycemic agents). An epidemiological study was carried out on 500 patients in the western region of India. Various parameters such as age at onset, duration of diabetes, gender, basal metabolic index (BMI), type of diabetes, family history, HbA1c levels, cholesterol levels, and current treatment regimen were evaluated and correlated with type 1 and type 2 diabetes. Moreover, diagnostic markers for LADA, namely, GAD autoantibodies and C-peptide levels, were determined for 80 patients selected from the epidemiological study. Some of the results obtained were found to be consistent with the literature whereas some results were found to be contradictory to the existing data.
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PMID:Characteristics and Prevalence of Latent Autoimmune Diabetes in Adults (LADA). 2257 77


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