Plasma-derived exosomal miRNAs as potentially novel biomarkers for latent autoimmune diabetes in adults.

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.

Development and validation of a clinical score for identifying patients with high risk of latent autoimmune adult diabetes (LADA): The LADA primary care-protocol study.

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.

Diagnostic Dilemmas and Current Treatment Approaches in Latent Onset Autoimmune Diabetes in Adults: A Concise Review.

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 ß-cell failure and slow progression to insulin dependence. Early diagnosis is significant in limiting disease progression. C-peptide levels and autoantibodies against ß-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.

Analysis of detrended fluctuation function derived from continuous glucose monitoring may assist in distinguishing latent autoimmune diabetes in adults from T2DM.

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.

Diabetic ketoacidosis as first presentation of latent autoimmune diabetes in adults in a patient with hashitoxicosis as first presentation of Hashimoto's thyroiditis: a case report.

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.

Prevalence and factors associated with latent autoimmune diabetes in adults (LADA): a cross-sectional study.

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.

Small RNAs are differentially expressed in autoimmune and non-autoimmune diabetes and controls.

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.

Latent autoimmune diabetes in youth shows greater autoimmunity than latent autoimmune diabetes in adults: Evidence from a nationwide, multicenter, cross-sectional study.

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, ß-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 ß-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 ß-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.

Case Report: A Rare Case of Coexisting of Autoimmune Polyglandular Syndrome Type 3 and Isolated Gonadotropin-Releasing Hormone Deficiency.

APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison's disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. We recently received a 43-year-old woman with a one-year history of Graves' disease (GD) and a four-month history of type 1 diabetes presented with hyperthyroidism and hyperglycemia. After the GnRH stimulation test, she was diagnosed with secondary amenorrhea attributed to suspected autoimmune Hypothalamitis and APS type 3 associated with Graves' disease and Latent Autoimmune Diabetes (LADA). According to this case, the hypothalamus cannot be spared from the general autoimmune process. It is recommended to carry out the GnRH stimulation test when encountering APS patients combined with secondary amenorrhea.

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM).

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.

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

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.

A Case Report of Latent Autoimmune Diabetes Arising After Isotretinoin Treatment: Real Association or Coincidence? A Hypothesis on Pathophysiology.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is the most common form of adult-onset autoimmune diabetes. Isotretinoin is a very effective treatment for severe acne. There are various reports on the effect of isotretinoin on autoimmunity. We present a case of LADA, probably related to isotretinoin treatment. To the best of our knowledge, this case was the second case of LADA that occurred after isotretinoin treatment. Here we discuss a hypothesis on the pathophysiology of how isotretinoin can induce LADA. CASE PRESENTATION: A 55-year-old female was diagnosed with type 2 diabetes mellitus (T2DM) one month after the end of a nine-month isotretinoin treatment period. At the time of diagnosis, the patient's fasting blood glucose level was 257 mg/dL and HbA1c level was 10.3%. Then, she was followed-up for T2DM for two years. Since the patient did not comply with classical T2DM characteristics and C-peptide level was 0.4 ng/ml (0.78-5.18), autoantibody test was performed. The patient was found positive for anti-glutamic acid decarboxylase antibody (>2000 IU/mL). Her oral antidiabetic drug treatment was discontinued and insulin degludec and insulin aspart therapy was started. Three months after this adjustment, HbA1c level decreased to 7.2%. Except 25-hydroxycholecalciferol which was low (10.9 ng/mL), all other laboratory parameters were within normal range. CONCLUSION: Isotretinoin is known to have some immunomodulating effects. There are some case reports on the relationship between isotretinoin and autoimmune diseases. The negative immune environment that developed due to the long-standing moderate-severe VitD deficiency may have taken a turn toward autoimmunity upon isotretinoin treatment. This hypothesis on how isotretinoin can cause autoimmune diabetes needs to be validated.

Low C-peptide together with a high glutamic acid decarboxylase autoantibody level predicts progression to insulin dependence in latent autoimmune diabetes in adults: The HUNT study.

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/m2 (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.

Current view of diagnosis and treatment of latent autoimmune diabetes in adults.

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 β-cell function, such as particularly incretines.

Latent Autoimmune Diabetes of Adults (LADA) Is Likely to Represent a Mixed Population of Autoimmune (Type 1) and Nonautoimmune (Type 2) Diabetes.

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.

Comparing the bone mineral density among male patients with latent autoimmune diabetes and classical type 1 and type 2 diabetes, and exploring risk factors for osteoporosis.

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.

Latent Autoimmune Diabetes in Adults: A Review of Clinically Relevant Issues.

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 ß-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.

Disseminated gonococcal infection and the inaugural diagnosis of latent autoimmune diabetes in a young adult

Disseminated gonococcal infection (DGI) is a rare and emerging disease that should be considered in individuals who present with acute polyarthralgias, skin lesions and/or tenosynovitis, even in the absence of genitourinary symptoms.We describe a 29 years old man presenting with fever, arthralgias, skin lesions and signs of tenosynovitis. The diagnostic approach identified a disseminated gonococcal infection and an unrecognized and latent autoimmune diabetes.We emphasize not only the particularities of diagnostic and treatment approach currently required by this emergent infection, but also the importance of investigation of rare risk factors associated with an underlying immunosuppression. In latent autoimmune diabetes of adults a timely recognition and individualized treatment are fundamental for prognostic

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