CLINICAL AND IMMUNOLOGICAL ASPECTS OF VERIFICATION OF LATENT AUTOIMMUNE DIABETES IN ADULTS AT EARLY STAGES OF DISEASE MANIFESTATION

The aim: To establish diagnostic markers of LADA at the stage of manifestation based on the analysis of clinical and anamnestic data, the results of immunological examination of patients with different types of DM. Materials and methods: Study included 121 patients with LADA (1st (main) group), 60 patients with type 1 DM (2nd group), 81 patients with type 2 DM (3d group). The examination included analysis of complaints, medical history, determination of anthropometric data, studies of the level of antibodies to glutamic acid decarboxylase (GAD ab), cytoplasmic antigen (ICA ab), tyrosine phosphatase (IA-2 ab). Results: Criteria of LADA diagnosis included slow nature of DM course, the average age of the disease onset (45,02±9,96) years, combination of diabetic complaints with gradual weight loss, frequent detection of DM (64,46%) on request, fairly high level of glycemia at diagnosis ((14,12±4,57) mmol/l)), the possibility of ketonuria episodes in a certain amount (23,14%) of cases in the absence of acute ketoacidotic states. The presence of excess body weight and even obesity is not a criterion for excluding LADA. Conclusions: To verify the diagnosis of LADA it is necessary to study of at least two types of antibodies. The most conclusive is the determination of GAD ab and IA-2 ab.

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Latent autoimmune diabetes of adults (LADA): The informative value of autoantibodies

Terapevticheskii arkhiv ◽

10.17116/terarkh2016881042-45 ◽

2016 ◽

Vol 88 (10) ◽

pp. 42-45 ◽

Cited By ~ 1

Author(s):

Yu V Silko ◽

T V Nikonova ◽

O N Ivanova ◽

S M Stepanova ◽

M V Shestakova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Islet Cell ◽

Autoimmune Diabetes ◽

Acid Decarboxylase ◽

Latent Autoimmune Diabetes ◽

Immunological Examination ◽

The Russian Federation ◽

Islet Antigen

Aim. To investigate the prevalence of autoantibodies (autoAbs) associated with the development of type 1 diabetes mellitus (T1DM) in latent autoimmune diabetes of adults (LADA) in the Russian Federation. Subjects and methods. A total of 96 patients (46 women and 50 men) with LADA were examined. All the patients underwent an immunological examination including the determination of autoAbs, such as glutamic acid decarboxylase autoAbs (GADA), islet antigen-2 auto-Abs (IA-2A), islet cell cytoplasmic auto-Abs (ICA), zinc transporter 8 auto-Abs (ZnT8A), and insulin auto-Abs (IAA). Results. GADAs were found in 61.5% of the examinees. ICAs were detected in 24%, IA-2As were observed in 57.3%. AutoAbs were more frequently observed in combination than alone. IAAs were least commonly seen in 8.3% and only in combinations. ZnT8As were found in 52.1% of the examinees and they were present alone in 5.2%. Conclusion. The antibodies that are most frequently observed in LADA are GADAs, IA-2As and ZnT8As. It is insufficient to identify only GADAs, as the latter are found in only 61.5% of the patients. IA-2As and ZnT8As, which are present in 57.3% and 52.1% of the patients, respectively, should also be used in the diagnosis of LADA. ICAs are much less commonly seen and along with IAAs may be additional markers for LADA.

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Evaluation of Two Nonisotopic Immunoassays for Determination of Glutamic Acid Decarboxylase and Tyrosine Phosphatase Autoantibodies in Serum

Clinical Chemistry ◽

10.1373/clinchem.2004.031799 ◽

2004 ◽

Vol 50 (8) ◽

pp. 1378-1382 ◽

Cited By ~ 12

Author(s):

Xavier Palomer ◽

Dídac Mauricio ◽

José Rodríguez-Espinosa ◽

Edgar Zapico ◽

Carme Mayoral ◽

...

Keyword(s):

Glutamic Acid ◽

Glutamic Acid Decarboxylase ◽

Clinical Laboratory ◽

Autoimmune Diabetes ◽

Tyrosine Phosphatase ◽

Acid Decarboxylase ◽

Time Resolved ◽

Radiobinding Assay

Abstract Background: Autoantibodies for the 65-kDa form of glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase-like protein (IA-2) are measured for risk prediction and diagnosis of autoimmune diabetes mellitus. There is a lack of adequate nonisotopic alternatives to the most widely used method for both autoantibodies, which is a radiobinding assay (RBA). Methods: We compared two commercially available immunoassays, an ELISA and a time-resolved immunofluorometric assay (TR-IFMA), with RBA. Results: We found excellent agreement between the RBA and ELISA for measurement of GAD65 autoantibodies (GADAs); they showed comparable analytical precision in the cutoff range and achieved similar diagnostic specificity. The ELISA identified more GADA-positive individuals among patients with new-onset type 1 diabetes than did the RBA [89% (95% confidence interval, 78–95%), vs 71% (58–82%); P <0.03]. For IA-2 autoantibodies (IA-2As), only the TR-IFMA achieved analytical performance and diagnostic accuracy comparable to that of the RBA. These results with the GADA ELISA and IA-2A TR-IFMA were consistent with those obtained blindly in the Diabetes Antibody Standardization Program 2003. The performance of the GADA TR-IFMA and IA-2A ELISA was unsatisfactory, and these tests were not subjected to clinical evaluation. Conclusions: The GADA ELISA and IA-2A TR-IFMA behave comparably with RBA and are thus suitable for use in the clinical laboratory.

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Number of autoantibodies and HLA genotype, more than high titers of glutamic acid decarboxylase autoantibodies, predict insulin dependence in latent autoimmune diabetes of adults

Acta Endocrinologica ◽

10.1530/eje-10-0427 ◽

2010 ◽

Vol 163 (4) ◽

pp. 541-549 ◽

Cited By ~ 47

Author(s):

M Maioli ◽

G M Pes ◽

G Delitala ◽

L Puddu ◽

A Falorni ◽

...

Keyword(s):

Glutamic Acid ◽

Disease Progression ◽

Glutamic Acid Decarboxylase ◽

Autoimmune Diabetes ◽

Tyrosine Phosphatase ◽

Female Gender ◽

Acid Decarboxylase ◽

Latent Autoimmune Diabetes ◽

Insulin Dependence ◽

Glutamic Acid Decarboxylase Autoantibodies

ObjectiveIn latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence.DesignThe screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed.ResultsFour years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020).ConclusionsHigh GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.

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Slowly evolving, immune-mediated diabetes in 14-year-old patient: a case report

Diabetes Mellitus ◽

10.14341/dm12397 ◽

2021 ◽

Vol 24 (1) ◽

pp. 70-73

Author(s):

M. R. Ragimov ◽

D. D. Omelchuk ◽

L. I. Ibragimova ◽

O. S. Derevyanko ◽

T. V. Nikonova

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Insulin Therapy ◽

Type 1 Diabetes Mellitus ◽

Autoimmune Diabetes ◽

Tyrosine Phosphatase ◽

Acid Decarboxylase ◽

Latent Autoimmune Diabetes ◽

Immune Mediated

Slowly developing immune-mediated diabetes, often called latent autoimmune diabetes in adults, is characterized by the presence of autoantibodies (ATs) to glutamic acid decarboxylase (GADA), the patient's age at the onset over 35 years, and the absence of the need for insulin therapy for 6-12 months to 6 years from the moment of diagnosis, according to the WHO classification of 2019, refers to hybrid forms of diabetes mellitus (DM). In this article, we present a case history of slowly developing immune-mediated diabetes in a 14-year-old boy who was transferred from metformin monotherapy and a diet with restriction of digestible carbohydrates to the intensified insulin therapy only 4 years after the onset of diabetes mellitus with a glycated hemoglobin (HbA1c) level of less than 6.5% throughout the disease. As a result of the studies, the patient was found to have a homozygous genotype highly predisposing to the development of Type 1 Diabetes Mellitus (T1DM), as well as increased levels of ATs to GADA and tyrosine phosphatase (IA-2A). The initially preserved level of basal C-peptide and the clinical course of the disease in this patient do not allow us to classify this case as a classic variant of the course of Type 1 Diabetes Mellitus.

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Features of chronic complications in latent autoimmune diabetes in adults

Clinical endocrinology and endocrine surgery ◽

10.30978/cees-2021-1-45 ◽

2021 ◽

pp. 45-51

Author(s):

I. O. Tsaryk ◽

N. V. Pashkovska

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Autoimmune Diabetes ◽

Tyrosine Phosphatase ◽

Acid Decarboxylase ◽

Latent Autoimmune Diabetes ◽

Patients With Diabetes ◽

Type 1 Dm

Purpose of the work. To find out the features of the course of chronic kidney disease in patients with latent autoimmune diabetes in adults (LADA) compared with the classic types of diabetes. Materials and methods. 145 patients with diabetes mellitus (DM) were examined (70 patients with LADA, 40 with type 1 DM — T1DM, 35 with type 2 DM — T2DM. Antibodies to glutamic acid decarboxylase and to tyrosine phosphatase were determined in all patients. Features of chronic kidney disease (CKD) were studied on the basis of anamnesis, clinical examination, glomerular filtration rate, microalbuminuria and the of albumin-creatinine ratio in urine. Results and discussion. According to the anamnesis, the diagnosis of CKD in patients with LADA was established on average up to 3 years from the manifestation of diabetes (in 30 % — already in the onset of the disease), while in T1DM — after 7.2 years, in T2DM — after 1.9 years. The most common stage of CKD in LADA patients was III (in 49 % of people). At the same time, the majority of patients had a nonalbuminuric phenotype of diabetic kidney disease (NARI). In terms of the characteristics of the course of CKD, LADA occupied an intermediate position, combining the signs of both main types of diabetes. Conclusions. The diagnosis of CKD in patients with LADA was established much earlier than in T1DM which indicates the incorrect use of the same recommendations for screening this complication in these patients. There was a predominance of NARI in patients with LADA. CKD in LADA requires the development of special approaches to screening, diagnosis and treatment.

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Autoimmune diagnostics in diabetes mellitus

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2006.025 ◽

2006 ◽

Vol 44 (2) ◽

Cited By ~ 7

Author(s):

Jochen Seissler ◽

Werner A. Scherbaum

Keyword(s):

Type 1 Diabetes ◽

Islet Cell ◽

Autoimmune Diabetes ◽

Tyrosine Phosphatase ◽

Islet Cell Antibodies ◽

Acid Decarboxylase ◽

Latent Autoimmune Diabetes ◽

Islet Cell Antigens

AbstractType 1 diabetes results from a specific destruction of the insulin-producing β-cells of the pancreas. The disease is characterized by the appearance of specific autoantibodies against islet cell antigens. Autoantibodies to insulin, glutamic acid decarboxylase, tyrosine phosphatase IA-2 and cytoplasmic islet cell antibodies are useful markers for the differential diagnosis of type 1 diabetes when clinical and metabolic criteria alone do not allow definite classification. Autoimmune diagnostics is of particular importance in adults to discriminate between type 1 and type 2 diabetes and to assess the diagnosis of latent autoimmune diabetes in adults.

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Type 1 Diabetes-related Autoantibodies in Different Forms of Diabetes

Current Diabetes Reviews ◽

10.2174/1573399814666180730105351 ◽

2019 ◽

Vol 15 (3) ◽

pp. 199-204 ◽

Cited By ~ 7

Author(s):

Elin Pettersen Sørgjerd

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Autoimmune Diabetes ◽

Acid Decarboxylase ◽

Adult Onset ◽

Latent Autoimmune Diabetes ◽

Childhood Type 1 Diabetes ◽

Childhood Type

Autoantibodies against Glutamic Acid Decarboxylase (GADA), insulinoma antigen-2 (IA- 2A), insulin (IAA) and the most recently Zinc Transporter 8 (ZnT8A) are one of the most reliable biomarkers for autoimmune diabetes in both children and adults. They are today the only biomarkers that can distinguish Latent Autoimmune Diabetes in Adults (LADA) from phenotypically type 2 diabetes. As the frequency of autoantibodies at diagnosis in childhood type 1 diabetes depends on age, GADA is by far the most common in adult onset autoimmune diabetes, especially LADA. Being multiple autoantibody positive have also shown to be more common in childhood diabetes compared to adult onset diabetes, and multiple autoantibody positivity have a high predictive value of childhood type 1 diabetes. Autoantibodies have shown inconsistent results to predict diabetes in adults. Levels of autoantibodies are reported to cause heterogeneity in LADA. Reports indicate that individuals with high levels of autoantibodies have a more type 1 diabetes like phenotype and individuals with low levels of autoantibody positivity have a more type 2 diabetes like phenotype. It is also well known that autoantibody levels can fluctuate and transient autoantibody positivity in adult onset autoimmune diabetes have been reported to affect the phenotype.

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