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Context: The role of circular RNAs (circRNAs) in type 1 diabetes (T1D) is largely unknown., Objective: We aimed to identify some circRNAs as differential diagnostic biomarkers for T1D to distinguish between patients with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D)., Methods: The circRNA expression profiles were determined by Arraystar human circRNA microarray in T1D compared to controls (n = 6 each). The differentially expressed circRNAs were validated by real-time quantitative polymerase chain reaction using a validation cohort with 20 T1D and 20 controls. The diagnostic performances of the candidate circRNAs and the clinical parameters were assessed using the logistic least absolute shrinkage and selection operator (LASSO) regression model in a larger cohort with 457 individuals, including patients with T1D, T2D, and LADA, and controls., Results: We identified 110 differentially expressed circular transcripts (53 upregulated and 57 downregulated) in T1D patients compared with controls. Further analysis showed that the levels of hsa&#95;circRNA&#95;405498 and hsa&#95;circRNA&#95;100033 were significantly downregulated in T1D compared to controls (both P < .05). Moreover, the expression levels of these 2 circRNAs showed sequential downregulation from controls, patients with T2D, LADA, to T1D (P < .05). The area under the curve (AUC) of receiver operating characteristic plots in logistic LASSO regression model showed high diagnostic accuracy for combination model with the 2 circRNAs and some clinical parameters in distinguishing T1D from LADA (AUC = 0.915), T2D (AUC = 0.993), and controls (AUC = 0.992)., Conclusion: Our study demonstrated that hsa&#95;circRNA&#95;405498 and hsa&#95;circRNA&#95;100033 are promising novel differential diagnostic biomarkers for T1D., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Autoimmune polyendocrine syndromes (APS) encompass m ultiple e ndocrin e gland ins ufficiencies asso ci ated wit h auto immune disease. This c as e report underscores the importance of recognising the association between latent auto immune di a betes of ad ults (LADA) and type 3 polyglandular syndrome. A 42-year-old man belonging to R awalpi ndi, Pakistan, p resented to th e out patient department (OPD) of Ali Medi cal Centre, Islamab ad, i n Januar y 2023 with the complaints o f e xtreme thirs t and frequent urination. The patient reported consistently raised app etite an d eating four to five meals a day along with abrupt weight loss, dry mouth, fatigue occasional dizziness, an d dyspnoea. He was diagno s ed with type 3 polygla ndular syndrome w ith associat io n of LADA. Daily administration of 10 units of glargine insulin, along with six units of rapid-acting insulin, was prescribed. The patient's H bA1c level reduce d in a few months afte r succe ssive follow-up. Patients who exhi bit uncontrol led diabe tes despite dietar y and oral hypoglycaemic management should be further investigated for multiple au toimmune endocrine disorders.

Aim: To characterize the exosomal miRNA profiles of latent autoimmune diabetes in adults (LADA) and evaluate the biomarker potential of selected miRNAs to distinguish LADA from type 2 diabetes (T2D)., Methods: Plasma-derived exosomal miRNA expression profiles were measured in patients with LADA (N = 5) and control subjects (N = 5). Five differentially expressed miRNAs were selected to validate their expression levels and assess their diagnostic potential by quantitative real-time PCR (qRT-PCR) in a larger cohort., Results: Seventy-five differentially expressed plasma-derived exosomal miRNAs were identified in LADA patients compared to healthy subjects. The expression levels of three exosomal miRNAs (hsa-miR-146a-5p, hsa-miR-223-3p and hsa-miR-21-5p) were significantly different between the LADA group and the T2D group. The three miRNAs exhibited areas under the receiver operating characteristic curves of 0.978, 0.96 and 0.809, respectively., Conclusions: This study uncovers the miRNA profiles of plasma-derived exosomes from LADA patients and identifies exosomal miRNAs as potential biomarkers to discriminate LADA from T2D for the first time. Our data demonstrate the function of exosomal miRNAs in the development of LADA and contribute to an in-depth understanding of the precise mechanisms underlying the pathogenesis of LADA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Latent autoimmune diabetes in adults (LADA) is a type of diabetes mellitus showing overlapping characteristics between type 1 Diabetes Mellitus and type 2 Diabetes Mellitus (T2DM), and autoimmunity against insulin-producing pancreatic cells. For its diagnosis, at least one type of anti-pancreatic islet antibody (GADAb is the most common) is required. Many authors recommend performing this measure in all newly diagnosed patients with DM, but it is not possible in Primary Health Care (PHC) due to its high cost. Currently, a relevant proportion of patients diagnosed as T2DM could be LADA. Confusing LADA with T2DM has clinical and safety implications, given its different therapeutic approach. The main objective of the study is to develop and validate a clinical score for identifying adult patients with DM at high risk of LADA in PHC., Methods: This is an observational, descriptive, cross-sectional study carried out in Primary Care Health Centers with a centralized laboratory. All people over 30 years of age diagnosed with diabetes within a minimum of 6 months and a maximum of 4 years before the start of the study will be recruited. Individuals will be recruited by consecutive sampling. The study variables will be obtained through clinical interviews, physical examinations, and electronic medical records. The following variables will be recorded: those related to Diabetes Mellitus, sociodemographic, anthropometric, lifestyle habits, laboratory parameters, presence of comorbidities, additional treatments, personal or family autoimmune disorders, self-perceived health status, Fourlanos criteria, and LADA diagnosis (as main variable) according to current criteria., Discussion: The study will provide an effective method for identifying patients at increased risk of LADA and, therefore, candidates for antibody testing. However, a slight participation bias is to be expected. Differences between participants and non-participants will be studied to quantify this potential bias., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vich-Pérez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Latent Onset Autoimmune Diabetes in Adults (LADA) is an autoimmune disorder between T1DM and T2DM and is often misdiagnosed as T2DM due to its late-onset. The disease is characterized by β-cell failure and slow progression to insulin dependence. Early diagnosis is significant in limiting disease progression. C-peptide levels and autoantibodies against β-cells are the most critical diagnostic biomarkers in LADA. The review aims to provide an overview of the biomarkers used to diagnose LADA, and the following treatment approaches. We have summarized LADA's pathophysiology and the autoantibodies involved in the condition, diagnostic approaches, and challenges. There are clear shortcomings concerning the feasibility of autoantibody testing. Finally, we have explored the treatment strategies involved in the management of LADA. In conclusion, the usual management includes treatment with metformin and the addition of low doses of insulin. Newer oral hypoglycaemic agents, such as GLP-1RA and DPP-4 inhibitors, have been brought into use. Since the disease is not entirely understood at the research level and in clinical practice, we hope to encourage further research in this field to assess its prevalence. Large randomized controlled trials are required to compare the efficacy of different available treatment options., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: We aimed to explore the performance of detrended fluctuation function (DFF) in distinguishing patients with latent autoimmune diabetes in adults (LADA) from type 2 diabetes mellitus (T2DM) with glucose data derived from continuous glucose monitoring., Methods: In total, 71 LADA and 152 T2DM patients were enrolled. Correlations between glucose parameters including time in range (TIR), mean glucose, standard deviation (SD), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV), DFF and fasting and 2-hour postprandial C-peptide (FCP, 2hCP) were analyzed and compared. Receiver operating characteristics curve (ROC) analysis and 10-fold cross-validation were employed to explore and validate the performance of DFF in diabetes classification respectively., Results: Patients with LADA had a higher mean glucose, lower TIR, greater SD, MAGE and CV than those of T2DM ( P <0.001). DFF achieved the strongest correlation with FCP (r = -0.705, P <0.001) as compared with TIR (r = 0.485, P <0.001), mean glucose (r = -0.337, P <0.001), SD (r = -0.645, P <0.001), MAGE (r = -0.663, P <0.001) and CV (r = -0.639, P <0.001). ROC analysis showed that DFF yielded the greatest area under the curve (AUC) of 0.862 (sensitivity: 71.2%, specificity: 84.9%) in differentiating LADA from T2DM as compared with TIR, mean glucose, SD, MAGE and CV (AUC: 0.722, 0.650, 0.800, 0.820 and 0.807, sensitivity: 71.8%, 47.9%, 63.6%, 72.7% and 78.8%, specificity: 67.8%, 83.6%, 80.9%, 80.3% and 72.4%, respectively). The kappa test indicated a good consistency between DFF and the actual diagnosis (kappa = 0.551, P <0.001). Ten-fold cross-validation showed a stable performance of DFF with a mean AUC of 0.863 (sensitivity: 78.8%, specificity: 77.8%) in 10 training sets and a mean AUC of 0.866 (sensitivity: 80.9%, specificity: 84.1%) in 10 test sets., Conclusions: A more violent glucose fluctuation pattern was marked in patients with LADA than T2DM. We first proposed the possible role of DFF in distinguishing patients with LADA from T2DM in our study population, which may assist in diabetes classification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Tian, Guo, Wu, Ye, Ding, Zhou, Huang, Li, Zhou and Yang.)

Background: Latent autoimmune diabetes in adults is an infrequent form of autoimmune diabetes mellitus, while Hashimoto's thyroiditis, the most common thyroid disease in adults, rarely manifests as thyrotoxicosis. The concurrent initial presentation of these two autoimmune disorders is extremely rare., Case Presentation: A 29-year-old male of Albanian descent presented after being hospitalized owing to diabetic ketoacidosis. The diagnosis of type 1 diabetes mellitus was placed, and intensified insulin therapy was initiated. Medical history was not of significance except a 5 kg weight loss within 2 months. The patient presented with recurrent episodes of hypoglycemia, and the doses of preprandial and basal insulin were reduced. The differential diagnosis included type 1 diabetes mellitus "honeymoon" period or another type of diabetes mellitus. His serological tests only revealed positive autoantibodies against glutamic acid decarboxylase 65 and C-peptide. The diagnosis leaned toward latent autoimmune diabetes in adults, and the therapeutic approach involved cessation of preprandial insulin therapy, regulation, and subsequent discontinuation of basal insulin and introduction of metformin. Two years later, basal insulin was reintroduced along with a glucagon-like peptide-receptor agonist and metformin. Further physical examination during the initial visit disclosed upper limb tremor, lid lag, excessive sweating, increased sensitivity to heat, and tachycardia. Laboratory tests were indicative of hashitoxicosis (suppressed level of thyroid-stimulating hormone, high levels of total and free thyroid hormones, positive anti-thyroglobulin and anti-thyroid peroxidase, and negative anti-thyroid-stimulating hormone receptor). Thyroid-stimulating hormone level was spontaneously restored, but an increase was observed during follow-up. Levothyroxine was administrated for 2 years until the patient had normal thyroid function., Conclusions: The prevalence of thyroid autoantibodies in patients with latent autoimmune diabetes in adults ranges from 20% to 30%. This correlation can be attributed to genetic involvement as well as disorders of immune tolerance to autoantigens. Hence, this report gives prominence to the holistic approach and consideration of comorbidities in patients with diabetes mellitus., (© 2022. The Author(s).)

Aim: To investigate the prevalence and clinical features of latent autoimmune diabetes in youth (LADY) diagnosed between 15 and 29 years old as a component of an age-related autoimmune diabetes spectrum., Research Design and Methods: This nationwide, multicenter, cross-sectional study continuously included 19,100 newly diagnosed diabetes patients over 15 years old across China. LADY patients were screened from 1803 subjects aged between 15 and 29 years old, with the type 2 diabetes (T2D) phenotype and positive autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated-2 (IA-2A) or zinc transporter-8 (ZnT8A). The clinical features of LADY, including metabolic status, β-cell function and insulin resistance, were investigated and compared with those of latent autoimmune diabetes in adults (LADA) identified from 17,297 other subjects over 30 years old. The age-related characteristics of the latent autoimmune diabetes spectrum were explored., Results: A total of 135 subjects were diagnosed as LADY, accounting for 9.0% of the T2D phenotypic youth. Compared with autoantibody-negative T2D patients, LADY patients had fewer metabolic syndrome, less insulin resistance and poorer β-cell function, which were closely related to their autoantibody status (all p < 0.05). After stratifying LADA according to age, the GADA titer decreased across the LADY, "Y-LADA" (young LADA, onset age < 60 years old) and "E-LADA" (elderly LADA, onset age ≥ 60 years old) groups, while the prevalence of metabolic syndrome and level of β-cell function increased (all p < 0.05)., Conclusions: A high prevalence of LADY exists in youth with T2D phenotype. Latent autoimmune diabetes forms a continuous age-related spectrum from LADY to LADA, in which LADY shows greater autoimmunity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressive Type 1 diabetes subgroup with onset during middle age. Studies report that about 10% of adults initially diagnosed with clinical Type 2 diabetes (T2D) have LADA. Inappropriate diagnosis and mismanagement of the LADA can increase the risk of diabetic complications, which affect the quality of life and is the cause of increased mortality. In low-income countries setting, data regarding the magnitude of LADA is limited. We carried out this study to estimate the burden of misdiagnosed LADA among T2D patients in selected health facilities in Dar es Salaam and to bring awareness to the use of Glutamic Acid Decarboxylase (GAD) autoantibody in screening for LADA., Methodology: We enrolled 186 phenotypically T2D patients in this cross-sectional study, through a standardized data collection tool we obtained participants' demographic and clinical information. For testing GAD levels, we used a double-antibody Enzyme-Linked Immunosorbent Assay (ELISA). The Fisher's Exact and student t-tests were used to test the significance of the statistical associations of the glycaemic control and diabetes complications between T2D and LADA., Results: Out of 186 patients, 156 gave conclusive GAD Ab ELISA reading with LADA accounting for 5.1% (95% CI: 2.5 - 10.0). The mean age of subjects was 54.3 years (Range: 33-85 years). The parameters such as mean age, family history of diabetes mellitus status, Fasting Blood Glucose, clinical characteristics, and complications did not show significant statistical differences between patients with LADA and Type 2 diabetes. However, all LADA- Human Immunodeficiency Virus (HIV) comorbid patients had retinopathy, which was statistically insignificant in 20 (87%) T2D-HIV comorbid patients (p = 0.669). Neither neuropathy, nephropathy, nor Diabetic Mellitus (D.M.) foot syndrome was observed among LADA-HIV comorbid patients. Nevertheless, 22 (95.7%), 3 (13%), and 2 (8.7%) of T2D-HIV comorbidity had neuropathy, nephropathy, or D.M. foot syndrome, respectively., Conclusions: The study established a LADA prevalence of 5.1% among T2D patients and has shown the role of GAD autoantibody in the screening for LADA. The study calls for a well- designed larger longitudinal study to generate strong evidence on the association of risk factors and complications associated with the LADA. This will develop robust evidence on the association of risk factors and complications associated with the LADA and T2D., (© 2022. The Author(s).)

Objective: Diabetes is a heterogeneous disease and a precise diagnosis of diabetes subgroups is necessary to initiate proper early treatment and clinical management of the disease. Circulating small RNAs (sRNAs) are potentially diagnostic biomarkers in diseases, including diabetes. Here we aimed to examine whether profiles of circulating sRNAs differed between patients with autoimmune and non-autoimmune diabetes and non-diabetic controls., Design: This cross-sectional case-control study included participants from the third survey of the HUNT study., Methods: We performed sRNA sequencing in serum from adult-onset type 1 diabetes (n = 51), type 2 diabetes (n = 50) and latent autoimmune diabetes in adult (LADA, n = 51), as well as non-diabetic HUNT3 participants as control group (n = 51). Differential expression analysis of the sRNAs was performed in R using limma-voom., Results: We identified differences in sRNA expression between autoimmune (type 1 diabetes and LADA) and non-autoimmune diabetes (type 2 diabetes) and between patients with diabetes and non-diabetic controls. Focusing on miRNA, we identified 10 differentially expressed mature miRNAs and 30 differentially expressed miRNA variants (isomiRs). We also identified significant changes within other sRNA classes, including a pronounced downregulation of a tRNA fragment in patients with diabetes compared to non-diabetic controls. We created cross-validated sRNA signatures based on the significant sRNAs that distinguished patients with diabetes from non-diabetic controls, and autoimmune from non-autoimmune diabetes, with high specificity and sensitivity. sRNA profiles did not distinguish between type 1 diabetes and LADA., Conclusions: Circulating sRNAs are differentially expressed between patients with diabetes and non-diabetic controls and between autoimmune and non-autoimmune diabetes.

Aim: To search for risk factors that could predict progression in latent autoimmune diabetes in adults (LADA) and compare them with those for type 2 diabetes., Materials and Methods: This study included 175 participants with LADA (autoantibody positive, without insulin treatment ≥1 year after diagnosis) and 2331 participants with type 2 diabetes (autoantibody negative, without insulin treatment ≥1 year after diagnosis) from the HUNT2 and HUNT3 surveys. We used Cox regression models and receiver operating characteristic curve analysis to identify predictive factors for progression to insulin dependency within 10 years., Results: Low C-peptide levels (<0.3 nmol/L) predicted progression to insulin dependency within 10 years in both LADA (hazard ratio [HR] 6.40 [95% CI, 2.02-20.3]) and type 2 diabetes (HR 5.01 [95% CI, 3.53-7.10]). In addition, a high glutamic acid decarboxylase autoantibody (GADA) level (HR 5.37 [95% CI, 1.17-24.6]) predicted progression in LADA. Together, these two factors had a discriminatory power between non-progressors and progressors of area under the curve (AUC) of 0.86 (95% CI, 0.80-0.93). In type 2 diabetes, younger age at diagnosis (<50 years: HR 2.83 [95% CI, 1.56-5.15]; 50-69 years: HR 2.11 [95% CI, 1.19-3.74]), high HbA1c levels (≥53 mmol/mol, HR 2.44 [95% CI, 1.72-3.46]), central obesity (HR 1.65 [95% CI, 1.06-2.55]) and a body mass index of more than 30 kg/m 2 (HR 1.73 [95% CI, 1.23-2.41]) were independent predictors. Together with C-peptide they reached an AUC of 0.79 (95% CI, 0.76-0.82)., Conclusion: Factors predicting progression to insulin dependence are partly similar and partly dissimilar between LADA and type 2 diabetes. A constellation of low C-peptide and high GADA levels identifies LADA patients who are probable to progress to insulin dependence., (© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

BACKGROUND We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The study recruited 930 patients aged ≥18 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298). RESULTS Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving b cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=-8.249-0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)-0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%). CONCLUSIONS This model can be applied to people newly diagnosed with T2DM. When Y ≥0.0472, total autoantibody screening is recommended to assess LADA.

Aims: This study aimed to compare the bone mineral densities (BMDs) among male patients with latent autoimmune diabetes in adults (LADA), classical type 1 diabetes (T1DM), and type 2 diabetes (T2DM), and to examine the risk factors for developing low BMD in these patients., Patients and Methods: Between January 2017 and October 2020, a total of 57, 67, and 223 male patients with LADA, classical T1DM, and T2DM, respectively, were recruited from the endocrinology department of Shanghai Tenth People's Hospital. Hormonal markers of bone metabolism, lipid profiles, uric acid, glycosylated hemoglobin A1c (HbA1c), and beta-cell function were measured using blood samples. BMD was measured at the lumbar spine, femoral neck, and right hip by dual-energy X-ray absorptiometry., Results: The mean BMD values from all three skeletal sites in male patients with LADA were comparable to those with classical T1DM but were much lower than those with T2DM. After adjusting for confounding factors, multiple linear regression analysis demonstrated that in all male patients with diabetes, body mass index (BMI), uric acid, and fasting C-peptide showed significant positive associations with BMD at all three skeletal sites; however, osteocalcin showed a negative association at all three sites., Conclusions: Compared with male patients with T2DM, lower BMDs were observed in patients with LADA and T1DM. Low BMI, uric acid, C-peptide levels, and high osteocalcin levels are risk factors for developing low BMD in male patients with diabetes., (© 2021. Italian Society of Endocrinology (SIE).)

Latent autoimmune diabetes of adults (LADA) is typically defined as a new diabetes diagnosis after 35 years of age, presenting with clinical features of type 2 diabetes, in whom a type 1 diabetes-associated islet autoantibody is detected. Identifying autoimmune diabetes is important since the prognosis and optimal therapy differ. However, the existing LADA definition identifies a group with clinical and genetic features intermediate between typical type 1 and type 2 diabetes. It is unclear whether this is due to 1 ) true autoimmune diabetes with a milder phenotype at older onset ages that initially appears similar to type 2 diabetes but later requires insulin, 2 ) a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or 3 ) a heterogeneous group resulting from difficulties in classification. Herein, we suggest that difficulties in classification are a major component resulting from defining LADA using a diagnostic test-islet autoantibody measurement-with imperfect specificity applied in low-prevalence populations. This yields a heterogeneous group of true positives (autoimmune type 1 diabetes) and false positives (nonautoimmune type 2 diabetes). For clinicians, this means that islet autoantibody testing should not be undertaken in patients who do not have clinical features suggestive of autoimmune diabetes: in an adult without clinical features of type 1 diabetes, it is likely that a single positive antibody will represent a false-positive result. This is in contrast to patients with features suggestive of type 1 diabetes, where false-positive results will be rare. For researchers, this means that current definitions of LADA are not appropriate for the study of autoimmune diabetes in later life. Approaches that increase test specificity, or prior likelihood of autoimmune diabetes, are needed to avoid inclusion of participants who have nonautoimmune (type 2) diabetes. Improved classification will allow improved assignment of prognosis and therapy as well as an improved cohort in which to analyze and better understand the detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes., (© 2021 by the American Diabetes Association.)

Latent Autoimmune Diabetes in Adults (LADA) is an autoimmune disease arising at adulthood. LADA is characterized by a less intensive autoimmune process, slower progression and a mild metabolic decompensation at onset compared with young-onset type 1 diabetes mellitus. The onset of LADA is usually in non-obese patients over 30, without prominent features of metabolic syndrome and insulin resistance. Nevertheless it may be falsely classified as type 2 diabetes, especially, when diagnosed in older age and for the possibility of non-insulin treatment for at least 6 months after diagnosis. LADA is treated early with insulin and combined with metformin in patients with a higher level of insulin resistance. Clinical studies suggested also effectivity of other oral antidiabetics enabling preservation of residual &#946;-cell function, such as particularly incretines.

Latent autoimmune diabetes in adults (LADA) is still a poorly characterized entity. However, its prevalence may be higher than that of classical type 1 diabetes. Patients with LADA are often misclassified as type 2 diabetes. The underlying autoimmune process against β-cell has important consequences for the prognosis, comorbidities, treatment choices and even patient-reported outcomes with this diabetes subtype. However, there is still an important gap of knowledge in many areas of clinical relevance. We are herein focusing on the state of knowledge of relevant clinical issues than may help in the diagnosis and management of subjects with LADA.

Objective: 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., Patients and Methods: 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: 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., Conclusion: 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.

Objective: Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of β-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA., Methods: Peripheral blood neutrophils were isolated from newly diagnosed LADA patients (n = 5) and age-and sex-matched healthy controls (n = 5). The Transcriptomic signature was determined by RNA sequencing (RNA-seq). Differentially expressed genes (DEG) were screened, followed by analyzing downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Real-time polymerase chain reaction (qPCR) was applied for validation in LADA patients (n = 9) and age-and sex-matched healthy controls (n = 18), including sequencing samples., Results: Compared with controls, 4105 DEG were screened in LADA patients, including 2661 upregulated and 1444 downregulated DEG. In GO analysis, DEG are mainly involved in leukocyte degranulation, myeloid cell differentiation, and immune response-regulating signaling. The top enriched KEGG pathways included cytokine-cytokine receptor interaction, adhesion molecule signaling, nuclear factor-κB (NF-κB) signaling and Th17 cell differentiation. Consistent with RNA-seq results, SELL , ITGA4 , ITGAM , NCF4 , ARHGAP3 , and CLDN15 are upregulated in neutrophils by qPCR., Conclusion: The present study results provided a profile of DEG in the newly diagnosed LADA of south China. Our study reveals an abnormality in neutrophil disposition at the transcriptional level in LADA. Several essential genes may be involved in of LADA's pathological process, which may be useful to guide prediction for LADA and further investigation into the pathogenesis for this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Xing, Lin, Tong, Zhou, Huang, Wang, Huang, Li, Xiang, Zhou, Li and Xiao.)

Background: Extracts from Boswellia serrata gum resin have anti-inflammatory effect and are used for treatment of a variety of chronic inflammatory diseases. It was previously demonstrated that the treatment with Boswellia serrata gum resin of LADA (Latent Autoimmune Diabetes in Adults) patients decreased blood levels of IA2 antibodies, one of the markers associated with LADA autoimmune diabetes., Primary Study Objective: The purpose of this study was to test whether Boswellia serrata gum resin also influences GAD65 autoantibodies as the other marker associated with LADA., Methods/design: We report a case study of male patient diagnosed with LADA with positive GAD65 autoantibodies who was treated with extract from Boswellia serrata gum resin, during 9 months. Blood levels of GAD65 autoantibodies, fasting blood glucose levels and HbA1c were measured before the treatment and periodically during the treatment., Results: Over the observed period, the blood levels of GAD65 autoantibodies linearly decreased about 25%., Conclusion: The study confirms that extract of Boswellia serrata gum resin seems to prevent insulitis in patients with LADA, as indicated by its action on both markers of autoimmune diabetes, i.e., GAD65 and IA2 autoantibodies. The possibility that the treatment with boswellic acids of LADA patients with positive autoantibodies could be beneficial on the course of the disease, calls for further investigation and a clinical study.

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are increasingly used for the treatment of type 2 diabetes, but have been associated with ketoacidosis., Methods/results: We report a case series of three patients with latent autoimmune diabetes of the adult who presented with ketoacidosis, including one case with normal blood glucose levels, in the context of SGLT2 inhibitor use., Conclusions: Sodium-glucose co-transporter-2 inhibitors should be used with caution and close clinical monitoring in patients with latent autoimmune diabetes of the adult. A clinical risk score permits targeted autoantibody testing and should be undertaken prior to commencement of SGLT2 inhibitors or cessation of insulin., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

The classification of diabetes mellitus in 2020 still starts with 2 major types, ie, type 1 and type 2, but each of these now includes a few uncommon variants. Understanding the many faces of the diabetes syndrome can make a difference in how clinicians select glucose-lowering therapy., Competing Interests: Dr. Hoogwerf has disclosed formerly being an employee of and currently owning stock in Eli Lilly and consulting for Mannkind Corp., (Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.)

Objective: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region., Research Design and Methods: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects ( n = 1,985) and control subjects ( n = 2,219). The same approach was applied to a LADA cohort ( n = 1,428) using population-based control subjects ( n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects)., Results: The strongest associations in the MHC class II region (rs3957146, β [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (β [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, β [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA., Conclusions: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes., (© 2019 by the American Diabetes Association.)

Aim: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy., Methods: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy., Results: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA 1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters., Conclusions: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes., (© 2018 Diabetes UK.)

LADA (latent autoimmune diabetes in adults), a special subtype of type 1 diabetes, turns out to exhibit phenotypes mimicking the type 2 diabetes, which results in serious misdiagnosis issues. In order to better distinguish LADA from other diabetes subtypes, specific diagnostic and prognostic biomarkers of LADA are required. Circulating microRNAs (miRNAs) are recently shown to be promising biomarkers for disease diagnosis and subtyping. In this study, serum samples from LADA patients and type 2 diabetes patients were collected during the first diagnosis of diabetes and the miRNA transcriptomes of these patients and healthy individuals were profiled. Comparative analysis shows that the differentially expressed miRNAs between groups and their predicted target genes are enriched for several functions including immune regulation. Besides, a few miRNAs showing distinct expression pattern in LADA patients could discriminate LADA from type 2 diabetes, as validated by further qRT-PCR assay. In all, our study implies potential miRNA biomarkers which would be investigated in further clinical researches.

Background: Latent autoimmune diabetes in adults (LADA) is determined by both a noninsulin-dependent clinical presentation and an autoimmune pathogenic process. Glutamic acid decarboxylase antibody (GADA) constitutes the most important marker, although IA-2A and ZnT8A also define LADA presentation. Type 2 diabetes mellitus (T2DM) is the most prevalent type particularly over 65 years old. Studies about autoimmunity in this age group are scarce., Objective: The aim of this work was to determine whether three autoantibodies for diabetes autoimmunity were present in elderly T2DM patients, and to assess the distinctive clinical features of autoantibody-positive patients., Research Design and Methods: We recruited 153 patients with diabetes with onset of diabetes after 65 years of age and a BMI under 30 kg/m 2 ., Results: The prevalence of at least one of the autoantibodies was 15.68% (24/153). The most prevalent autoantibody was GADA with 8.49% (13/153), followed by ZnT8A with 6.50% (10/153) and IA2A with 1.96% (3/153). The autoimmunity-positive group presented higher HbA1c (7.01 ± 1.98 vs 6.35 ± 1.01; P = 0.007) and more prevalent insulin therapy (25% vs 10.85%; P = 0.047). GADA-positive patients with diabetes presented higher FPG (7.79 ± 3.79 mmol/L vs 6.43 ± 1.6 mmol/L; P = 0.014) and insulin therapy more frequently (46% vs 10.71%; p = 0.015). GADA titre levels in the individuals with BMI under 27 kg/m 2 were higher (35.00 ± 4.20) than those in the group with BMI over 27 kg/m 2 (8.83 ± 3.041; P = 0.0005)., Conclusion: Autoantibodies GADA and Znt8A may be useful markers in identifying a subgroup of older patients with a clinical presentation of diabetes which could be characterized as latent autoimmune diabetes in the elderly., (© 2019 John Wiley & Sons, Ltd.)

Background: Latent autoimmune diabetes in adults (LADA) exhibits significant clinical heterogeneity, but the underlying causes remain unclear. The aim of this study was to investigate whether age of onset of LADA contributes to the observed clinical heterogeneity by comparing the clinical, metabolic, and immunogenetic characteristics between elderly and young LADA patients., Methods: The cross-sectional study included a total of 579 patients with LADA which was further divided into elderly LADA (E-LADA) group (n = 135, age of onset ≥60 years) and young LADA (Y-LADA) group (n = 444, age of onset <60 years). Age-matched subjects with type 2 diabetes were served as control (E-T2D group, n = 622). Clinical characteristics, serum autoantibodies, and HLA-DQ haplotypes were compared among these groups., Results: Compared with patients with Y-LADA, patients with E-LADA have better residual beta-cell function and higher level of insulin resistance (both P < .01), more metabolic syndrome characteristics, similar proportion of islet autoantibody positivity, and strikingly different HLA-DQ genetic background. In comparison with E-T2D patients, E-LADA patients tend to have similar metabolic syndrome prevalence, comparable C-peptide levels, and insulin resistance levels and share similar HLA-DQ genetic characteristics., Conclusions: Elderly LADA differs phenotypically and genetically from Y-LADA but has a clinical and genetic profile more similar to that of E-T2D. These distinct phenotypes could potentially help physicians better manage patients with E-LADA., (© 2018 John Wiley & Sons, Ltd.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than "classical" type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis has been challenged. Despite the absence of a genetic background that is exclusive to LADA, this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems as to therapy and follow-up perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The study of the sociomedical problems of diabetes mellitus led to the discovery of latent autoimmune diabetes in adults (LADA), a special form of the disease. The slow onset of the disease, the clinical signs of type 2 diabetes mellitus concurrent with the autoantibody pancreatic β-cell destruction mechanism that is characteristic of type 1 diabetes. Genetic factors play an important role in the genesis of the disease. Insulitis concurrent with intact or hypertrophic islets of the gland originally develops morphologically. Subsequently, the phenomena of islet atrophy and sclerosis are progressive. The disease is typical for young people (generally those aged 25-35 years) with normal body mass index, low blood C-peptide levels, with antibodies against β-cells, primarily to glutamate decarboxylase, being detected. Insulin preparations should be used to treat these patients.

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than "classical" type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis have been challenged. Despite the absence of a genetic background that is exclusive for LADA this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems to therapy and follow-up, perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Latent autoimmune diabetes in adults (LADA) is characterized by the presence of islet autoantibodies and initial insulin independence, which can lead to misdiagnosis of type 2 diabetes (T2D). As such, understanding the genetic etiology of LADA could aid in more accurate diagnosis. However, there is ongoing debate regarding the exact definition of LADA, so understanding its impact in different populations when contrasted with type 1 diabetes (T1D) and T2D is one potential strategy to gain insight into its etiology. Unfortunately, the lack of consistent and thorough autoantibody screening around the world has hampered well-powered genetic studies of LADA. This review highlights recent genetic and epidemiological studies of LADA in diverse populations as well as the importance of autoantibody screening in facilitating future research., (Copyright © 2018. Published by Elsevier Ltd.)

Aims/hypothesis: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies., Methods: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs with 95% CI., Results: In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA;

Latent Autoimmune Diabetes in Adults (LADA) is often misdiagnosed because it lacks both awareness and standardized diagnostic criteria. A 30-year-old patient with high blood glucose, HbA1c level 10.1% and positive GAD antibodies was diagnosed with type 1 diabetes but LADA was not ruled out. Patient refused to receive insulin therapy. He chose to follow the dietary restrictions and therapy with sulfonylurea, initiated by another physician. Following 7 months the patient's HbA1c values decreased, but never achieved the goal. Furthermore, after the first year of diagnosis his glycemic values rapidly worsened. The similarities between type 1 diabetes, type 2 diabetes, and LADA can make diagnosis difficult. The Immunology of Diabetes Society (IDS) has proposed three criteria to standardize the definition of LADA. 1) age usually ≥25 years 2) positive titer for at least one of the four antibodies, and 3) no treatment with insulin was needed in the first 6 months after diagnosis. The patient in this case closely fits the proposed IDS criteria for diagnosing LADA. Making the right diagnosis at the right time is crucial for patients with diabetes. Patients with LADA are often misdiagnosed due to the use of arbitrary screening criteria such as age. Health care providers must learn to recognize the characteristics of LADA, in order to improve the treatment options, glycemic control and potentially decrease the risk of long-term complications.

Objective: To test whether differences in serum concentrations of adiposity-related low-grade inflammatory mediators could help to differentiate patients with latent autoimmune diabetes in adults (LADA), classic adult-onset type 1 diabetes, and type 2 diabetes., Research Design and Methods: This cross-sectional study involved 75 patients with LADA, 67 with classic adult-onset type 1 diabetes, and 390 with type 2 diabetes. Serum concentrations of adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFRII), interleukin-6, hs-CRP, and total leukocyte number were measured. To evaluate the differences of these markers among diabetes types, we performed logistic regression models and evaluated area under the receiver-operating characteristic curve (AUC ROC ) values., Results: The profile of innate immunity-related inflammatory markers correlated with metabolic syndrome components. LADA versus classic adult-onset type 1 diabetes was independently related to sTNFRII (odds ratio [OR] 1.9 [95% CI 1.01-3.97]; P = 0.047) and hs-CRP levels (OR 0.78 [95% CI 0.62-0.96]; P = 0.019), and a higher number of total leukocytes lowered the risk of LADA compared with type 2 diabetes (OR 0.98 [95% CI 0.97-0.99]; P = 0.036). The logistic regression model including explanatory biomarkers explained 35% of the variation for LADA versus classic adult-onset type 1 diabetes (AUC ROC 0.83 [95% CI 0.74-0.92]; P < 0.001) and 15% of the variation for LADA versus type 2 diabetes (AUC ROC 0.73 [95% CI 0.70-0.80]; P < 0.001)., Conclusions: Inflammatory, adiposity, and immune-related markers could help to differentiate a LADA diagnosis from that of classic adult-onset type 1 diabetes, and also LADA from that of type 2 diabetes, along with islet autoantibody positivity., (© 2018 by the American Diabetes Association.)

Background: A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22., Methods: We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA., Results: We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes)., Conclusions: The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood., (© 2018 S. Karger AG, Basel.)

Background: LADA is probably the most prevalent form of autoimmune diabetes. Nevertheless, there are few data about cardiovascular disease in this group of patients. The aim of this study was to investigate the frequency of carotid atherosclerotic plaques in patients with LADA as compared with patients with classic type 1 diabetes and type 2 diabetes., Methods: Patients with LADA were matched for age and gender in different proportions to patients with type 2 diabetes, and classic type 1 diabetes. None of the patients had clinical cardiovascular disease. All subjects underwent B-mode carotid ultrasound to detect atheroma plaques. Demographics were obtained from all subjects., Results: We included 71 patients with LADA, 191 patients with type 2 diabetes and 116 patients with type 1 diabetes. Carotid atherosclerosis was more frequent in patients with LADA compared with type 2 diabetes (73.2% vs. 56.9%, P = 0.0018) and classic type 1 diabetes (57.1%, P = 0.026); these changes occurred despite healthier macrovascular risk profiles in the former. Age (P < 0.001), smoking (P = 0.003) and hypertension (P = 0.019) were independently associated with carotid atherosclerosis. Multiple plaques were also more frequent in patients with LADA as compared with classic type 1 diabetes and type 2 diabetes (45.1% and 33.6% vs. 27.2%, respectively, P = 0.022). The frequency of carotid plaques increased with increasing diabetes duration in LADA patients compared with type 2 diabetes (85.7% vs. 58.8%, inverse OR 5.72 [1.5-21.8]; P = 0.009)., Conclusions: LADA patients do not present with less carotid atherosclerosis than patients with type 1 and type 2 diabetes. Their macrovascular risk occurs despite a healthier macrovascular risk profile than those patients with type 2 diabetes.

Rationale: Latent autoimmune diabetes in adults (LADA) refers to an autoimmune disorder characterized with detectable islets antibodies in the early diagnosis and increased autoimmune beta-cell failure progression. Notably, this kind of diabetes seems to be confused with other phenotypic diabetes., Patient Concerns: A young woman suffered an emotional exhaustion-induced LADA, showing asthenia, polydipsia, polyuria, and visible weight loss. The patient emotionally ended a 14-year romantic relationship, leading to the emotional flooding., Diagnoses: The data from physical examination and laboratory tests exhibited as follows: glutamic acid decarboxylase antibody (GADA) = 63.83 U/mL, the fasting blood glucose (FBG) = 13.3 mmol/L, and glycated haemoglobin (HbA1c) = 10.9%. According to levels of GADA, the patient was diagnosed as LADA., Interventions: The patient was clinically treated with insulin for 3-month. Then, running, diet-control, and emotional treatment were combined, such as the patient started a new relationship., Outcomes: An emotional recovery initiated from a new romantic relationship and a baby, showing normal levels of GAD65 (27.007 IU/mL) and FBG (5.46) mmol/L., Lessons: The emotional exhaustion might play a significant role in induction of LADA. It is important that individuals should maintain optimism, cheer, and a positive attitude.

Objective: Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes., Design/methods: Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression., Results: Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11-3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02-1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00-1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95-1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07-1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA., Conclusions: High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance., (© 2016 European Society of Endocrinology.)

Latent autoimmune diabetes in adults (LADA) is a subtype of autoimmune diabetes, which shares characteristics of both Type 1 and 2 diabetes (T1D and T2D), and for this reason, it is often confused with other types of diabetes, misdiagnosed, and inappropriately treated. Two cases were presented (41-year-old and 50-year-old females), one occasionally diagnosed during routine health checkup, the other one identified as having T2D, and as far as misclassified and not optimally treated. Now, after approximately 9 months of LADA diagnosis, the first patient has an optimal metabolic control while maintaining the values of glycated hemoglobin to around 7% with small doses of analogue insulin (lispro 4-6 UI) before meals and long acting insulin (glargine 4-6 UI) at bedtime. The second patient, after approximately 2 years from the LADA diagnosis, has an optimal metabolic control, with maintenance of glycated hemoglobin to around 6.5%, and stable C-peptide level (around 1.5 ng/mL), only with dietary and exercise habits. To avoid misclassification, any patient who does not fit the typical T2D profile, or with poor glycemic control, and who does not follow the expected clinical course, as become insulin dependent sooner than expected, should be investigated to exclude LADA. To define the best therapeutic approach, each patient must be evaluated and therapy tailored on his/her specific profile, considering as very low insulin doses may be effective to maintain a successful metabolic control and the only dietary approach may be sufficient until the insulin-secretory capacity remains good.

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.