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For many autoimmune diseases, including type 1 diabetes mellitus (T1DM), efforts have been made to modify the disease process through pharmacotherapy. The ultimate goal must be to develop therapies with curative potential by achieving an organ without signs of parenchymal cell destruction and without signs of immune cell infiltration. In the case of the pancreas, this means regenerated and well-preserved beta cells in the islets without activated infiltrating immune cells. Recent research has opened up the prospect of successful antibody combination therapy for autoimmune diabetes with curative potential. This goal cannot be achieved with monotherapies. The requirements for the implementation of such a therapy with curative potential for the benefit of patients with T1DM and LADA (latent autoimmune diabetes in adults) are considered. [ABSTRACT FROM AUTHOR]

Latent Autoimmune Diabetes in Adults (LADA) is a type of diabetes mellitus often overlooked in clinical practice for its dual resemblance to Type 1 Diabetes Mellitus (T1DM) in pathogenesis and to Type 2 Diabetes Mellitus (T2DM) in clinical presentation. To better understand LADA's distinctiveness from T1DM and T2DM, we conducted a comprehensive review encompassing etiology, pathology, clinical features, treatment modalities, and prognostic outcomes. With this comparative lens, we propose that LADA defies simple classification as either T1DM or T2DM. The specific treatments for the disease are limited and should be based on the therapies of T1DM or T2DM that address specific clinical issues at different stages of the disease. It is crucial to identify LADA cases potentially misdiagnosed as T2DM, warranting prompt screening for poor blood sugar control, short-term blood sugar deterioration, and other conditions. If the prognosis for LADA is similar to T2DM, it can be managed as T2DM. However, if the prognosis fundamentally differs, early LADA screening is crucial to optimize patient outcomes and enhance research on tailored treatments. The pathogenesis of LADA is clear, so the prognosis may be the key to determining whether it can be classified as T2DM, which is also the direction of future research. On the one hand, this paper aims to provide suggestions for the clinical screening and treatment of LADA based on the latest progress and provide worthy directions for future research on LADA. [ABSTRACT FROM AUTHOR]

Abstract Latent Autoimmune Diabetes in Adults (LADA) is a type of diabetes mellitus often overlooked in clinical practice for its dual resemblance to Type 1 Diabetes Mellitus (T1DM) in pathogenesis and to Type 2 Diabetes Mellitus (T2DM) in clinical presentation. To better understand LADA’s distinctiveness from T1DM and T2DM, we conducted a comprehensive review encompassing etiology, pathology, clinical features, treatment modalities, and prognostic outcomes. With this comparative lens, we propose that LADA defies simple classification as either T1DM or T2DM. The specific treatments for the disease are limited and should be based on the therapies of T1DM or T2DM that address specific clinical issues at different stages of the disease. It is crucial to identify LADA cases potentially misdiagnosed as T2DM, warranting prompt screening for poor blood sugar control, short-term blood sugar deterioration, and other conditions. If the prognosis for LADA is similar to T2DM, it can be managed as T2DM. However, if the prognosis fundamentally differs, early LADA screening is crucial to optimize patient outcomes and enhance research on tailored treatments. The pathogenesis of LADA is clear, so the prognosis may be the key to determining whether it can be classified as T2DM, which is also the direction of future research. On the one hand, this paper aims to provide suggestions for the clinical screening and treatment of LADA based on the latest progress and provide worthy directions for future research on LADA.

Background. Among the heterogeneous types of diabetes, latent autoimmune diabetes in adults (LADA) attracts the most attention today. Despite the large number of studies on dyslipidemia in diabetes and its relationship with vitamin D deficiency, data on the course of these conditions in patients with LADA are practically absent. The purpose of our study was to determine the characteristics of lipid metabolism in patients with LADA and its phenotypes compared to classical type 1 diabetes mellitus (T1DM) depending on vitamin D status. Materials and methods. We study 56 patients with DM: 34 individuals with LADA and 22 with classical T1DM. They underwent a number of general clinical laboratory tests, study of carbohydrate metabolism, liver function, the blood lipid spectrum, vitamin D status. Results. Analysis of the lipid metabolism indicators in patients with LADA compared to data of patients with classical T1DM showed that dyslipidemia was observed in all experimental groups. In the LADA group, the degree of dyslipidemia according to indicators of lipid metabolism (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), atherogenic index) was higher than in T1DM, which indicates a higher frequency of dyslipidemia in this subtype of autoimmune diabetes in particular and, accordingly, the metabolic syndrome in general. These changes, in our opinion, are caused by the heterogeneous nature of LADA with the involvement of mechanisms of insulin resistance in its development and course. Conclusions. Vitamin D deficiency is associated with lipid metabolism disorders, in particular, with an increase in TG and a decrease in HDL-C, as well as with LADA decompensation, which indicates the need for its normalization in this type of diabetes regardless of the phenotype.

Objective: Acute worsening of glycemic control in diabetic patients and new–onset type I diabetes were reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Latent autoimmune diabetes in adults (LADA) is defined as a slowly evolving immune–mediated diabetes. A few cases of LADA diagnosed after SARS-CoV-2 vaccination have been reported in the literature. This study aims to report LADA after mRNA-based SARS-CoV-2 vaccinations in subjects with a history of well-controlled type 2 diabetes. Methods: We report four cases with LADA diagnosed after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, all subjects had well-controlled type 2 diabetes with oral anti-diabetic medication. One case had autoimmune thyroid disease. One subject was presented with diabetic ketoacidosis. Results: Glycemic control of the presented cases had deteriorated 6–10 weeks after BNT162b2 vaccination. All patients were male and had high levels of glutamic acid decarboxylase 65 antibody (GAD65ab). An intensive insulin regimen was initiated at the time of diagnosis. The need for insulin therapy in two patients disappeared during follow-up. Two subjects were managed with basal insulin and oral antidiabetics. GAD65ab disappeared just 1 year after the diagnosis of LADA in a subject. Conclusion: In case of impaired glycemic control after SARS-CoV-2 vaccination in a well-controlled diabetic patient, LADA should be considered. [ABSTRACT FROM AUTHOR]

Background. Among the heterogeneous types of diabetes, latent autoimmune diabetes in adults (LADA) attracts the most attention today. Despite the large number of studies on dyslipidemia in diabetes and its relationship with vitamin D deficiency, data on the course of these conditions in patients with LADA are practically absent. The purpose of our study was to determine the characteristics of lipid metabolism in patients with LADA and its phenotypes compared to classical type 1 diabetes mellitus (T1DM) depending on vitamin D status. Materials and methods. We study 56 patients with DM: 34 individuals with LADA and 22 with classical T1DM. They underwent a number of general clinical laboratory tests, study of carbohydrate metabolism, liver function, the blood lipid spectrum, vitamin D status. Results. Analysis of the lipid metabolism indicators in patients with LADA compared to data of patients with classical T1DM showed that dyslipidemia was observed in all experimental groups. In the LADA group, the degree of dyslipidemia according to indicators of lipid metabolism (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), atherogenic index) was higher than in T1DM, which indicates a higher frequency of dyslipidemia in this subtype of autoimmune diabetes in particular and, accordingly, the metabolic syndrome in general. These changes, in our opinion, are caused by the heterogeneous nature of LADA with the involvement of mechanisms of insulin resistance in its development and course. Conclusions. Vitamin D deficiency is associated with lipid metabolism disorders, in particular, with an increase in TG and a decrease in HDL-C, as well as with LADA decompensation, which indicates the need for its normalization in this type of diabetes regardless of the phenotype. [ABSTRACT FROM AUTHOR]

The article provides up-to-date information on latent autoimmune diabetes in adults (LADA), presents data on epidemiology, factors and mechanisms of development, clinical features of this disease. The phenotypic variants of the course of LADA are described, the issues of diagnostic features and differential diagnosis are revealed. LADA is a form of diabetes characterized by a less intense autoimmune process and a wide range of clinical signs compared to classical type 1 diabetes mellitus (T1DM) and can have features of both major types of diabetes. Based on the results of epidemiological studies, the prevalence of LADA is approximately 12 % of all cases of diabetes, it is the second most common form of diabetes after type 2 diabetes mellitus (T2DM) and is the most common type of autoimmune diabetes in adults. According to the modern classification, LADA belongs to the autoimmune subtype of T1DM. Since patients do not need insulin at the beginning of the disease, the course of LADA is similar to T2DM, which is the cause of diagnostic errors. The literature data and the results of the conducted research have shown that, in addition to autoimmune damage to pancreatic beta cells, insulin resistance plays a key role in the mechanisms of LADA development, with an increase in the frequency and degree of abdominal obesity, which not only worsens metabolic control and increases the risk of metabolic syndrome, but also causes a decrease in insulin secretion and progression of the autoimmune process. In patients with LADA, the prevalence and degree of obesity, hypertension and dyslipidemia occupy an intermediate position between the classical types of diabetes. Despite having fewer metabolic risk factors compared to T2DM, patients with LADA have the same or even higher risk of death and cardiovascular diseases. The most important diagnostic markers of LADA are levels of C-peptide and autoantibodies against islet antigens. The possibility of a clear diagnosis of LADA is limited due to the significant heterogeneity of the disease due to an overlap of T1DM and T2DM symptoms. According to modern guidelines, therapeutic approaches to LADA, which are based on insulin therapy and metformin, depend on the level of C-peptide. More research is needed to improve personalized approaches to the treatment of this disease.

The article provides up-to-date information on latent autoimmune diabetes in adults (LADA), presents data on epidemiology, factors and mechanisms of development, clinical features of this disease. The phenotypic variants of the course of LADA are described, the issues of diagnostic features and differential diagnosis are revealed. LADA is a form of diabetes characterized by a less intense autoimmune process and a wide range of clinical signs compared to classical type 1 diabetes mellitus (T1DM) and can have features of both major types of diabetes. Based on the results of epidemiological studies, the prevalence of LADA is approximately 12 % of all cases of diabetes, it is the second most common form of diabetes after type 2 diabetes mellitus (T2DM) and is the most common type of autoimmune diabetes in adults. According to the modern classification, LADA belongs to the autoimmune subtype of T1DM. Since patients do not need insulin at the beginning of the disease, the course of LADA is similar to T2DM, which is the cause of diagnostic errors. The literature data and the results of the conducted research have shown that, in addition to autoimmune damage to pancreatic beta cells, insulin resistance plays a key role in the mechanisms of LADA development, with an increase in the frequency and degree of abdominal obesity, which not only worsens metabolic control and increases the risk of metabolic syndrome, but also causes a decrease in insulin secretion and progression of the autoimmune process. In patients with LADA, the prevalence and degree of obesity, hypertension and dyslipidemia occupy an intermediate position between the classical types of diabetes. Despite having fewer metabolic risk factors compared to T2DM, patients with LADA have the same or even higher risk of death and cardiovascular diseases. The most important diagnostic markers of LADA are levels of C-peptide and autoantibodies against islet antigens. The possibility of a clear diagnosis of LADA is limited due to the significant heterogeneity of the disease due to an overlap of T1DM and T2DM symptoms. According to modern guidelines, therapeutic approaches to LADA, which are based on insulin therapy and metformin, depend on the level of C-peptide. More research is needed to improve personalized approaches to the treatment of this disease. [ABSTRACT FROM AUTHOR]

Latent autoimmune diabetes in adults is a form of diabetes that progresses slowly and is controlled by diet and oral glucose-lowering medications before insulin is required. The aim of the present study was to evaluate the prevalence of latent autoimmune diabetes in adults. The present study was conducted based on PRISMA 2020-27-item checklist. To find the studies conducted in line with the purpose of the study, PubMed, Web of Science, Scopus, Science Direct, Web of Knowledge, EBSCO, Wiley, ISI, Elsevier, Embase databases and Google Scholar search engine were reviewed from 2013 to August 2023. Meta-analysis was performed using effect size with 95% confidence interval. Data analysis was done using STATA/MP. v17 software. The present study was carried out based on the PRISMA 2020 27-point checklist. To find out which studies were carried out in accordance with the purpose of the study, from 2013 to August, the databases PubMed, Web of Science, Scopus, Science Direct, Web of Knowledge, EBSCO, Wiley, ISI, Elsevier, Embase and the search engine Google Scholar reviewed 2023. Meta-analysis was performed using effect size with 95% confidence interval. Data analysis was carried out using STATA/MP. v17 software. The overall prevalence of Latent autoimmune diabetes of adults was found to be 7% (95%CI 0–20). Subgroup analysis of Latent autoimmune diabetes of adults in the context of geographic regions showed a higher prevalence in North America (15%) and South East Asia (5%). Since the identification of Latent autoimmune diabetes of adult patients with other forms of diabetes is misdiagnosed due to the combination of phenotypic features with T1D and T2D, studying its prevalence is of great importance.

Abstract The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin‐dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for ‘a definitive diagnosis of SPIDDM’: (1) presence of anti‐islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C‐peptide immunoreactivity

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin‐dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for 'a definitive diagnosis of SPIDDM': (1) presence of anti‐islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C‐peptide immunoreactivity <0.6 ng/mL) at the last observed point in time. When a patient fulfills only (1) and (2), but not (3), he/she is diagnosed with 'SPIDDM (probable)' because the diabetes is non‐insulin‐dependent type. [ABSTRACT FROM AUTHOR]

Abstract Background The prevalence of diabetes mellitus (DM) is dramatically increasing around the world, and patients are getting younger with changes in living standards and lifestyle. This study summarized and analyzed the clinical characteristics of different types of newly diagnosed diabetes mellitus patients with an onset age between 18 and 40 years to provide clinical evidence for the early diagnosis and treatment of diabetes, reduce short-term and long-term complications and offer scientific and personalized management strategies. Methods A total of 655 patients newly diagnosed with early-onset diabetes mellitus in the Department of Endocrinology, the First Medical Center of PLA General Hospital from January 2012 to December 2022 were retrospectively enrolled in this study, with an onset age of 18–40 years. Their clinical data were collected and investigated. All patients were divided into two groups according to whether they presented with diabetic microangiopathy. Similarly, patients with early-onset type-2 diabetes were grouped in accordance with whether they had ketosis at the time of diagnosis. Binary logistic regression analysis was performed to analyze risk factors, and receiver-operating characteristic (ROC) analysis was used to explore the predictive value of significant risk factors. Results The findings were as follows: (1) Of 655 enrolled patients, 477 (72.8%) were male and 178 (27.1%) were female, with a mean age of onset of was 29.73 years ± 0.24 SD. (2) The prevalence of early-onset diabetes was gradually increasing. Type-2 diabetes was the most common type of early-onset diabetes (491, 75.0%). The ages of onset of early-onset type-1 diabetes, type-2 diabetes and LADA were mainly 18–24 years, 25–40 years and 33–40 years, respectively. (3) Initial clinical manifestations of early-onset diabetes were classic diabetes symptoms (361, 55.1%), followed by elevated blood glucose detected through medical examination (207, 31.6%). (4) Binary logistic regression analysis suggested that high serum uric acid (UA), a high urinary albumin-to-creatinine ratio (UACR) and diabetic peripheral neuropathy (DPN) were risk factors for microangiopathy in early-onset diabetes patients (P

Abstract Background Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride–glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA). Methods This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed. Results A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all P

Abstract Aims The objective of this study is to explore the relationship between red blood cell distribution and islet β-cell function indexes in patients with Latent Autoimmune Diabetes in Adults. Methods A total of 487 LADA patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and laboratory measurements of age, height, weight, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and blood lipids were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCP). Correlations and multiple linear regressions were implemented to determine the association of RDW and islet function indexes. Results As the increase of serum RDW level, the presence of β-cell secretion increased(P

Latent autoimmune diabetes in adults (LADA) according to various sources is from 4 to 12% of all cases of type 2 diabetes mellitus (T2DM). Its uniqueness lies in the simultaneous combination of autoantibodies to β-cells (characteristic of T1DM) and the possibility of treatment with oral hypoglycemic drugs (characteristic of T2DM) for at least 6 months. This is based on the pathogenesis common for T1DM and T2DM — the presence of an autoimmune reaction with the simultaneous involvement of adaptive and innate immunity, as well as, to a lesser extent, insulin resistance and a number of components of the metabolic syndrome. LADA has more in common with T1DM — the same stages in the development of the disease, from genetic predisposition to the undoubted development of insulin dependence, the difference lies in the duration of each of the periods and the age of manifestation. LADA is characterized by an older age of manifestation of 30–35 years and a slower rate of destruction of β-cells. This article presents data on the diagnosis, progress of LADA, its similarities and differences with other types of DM, and immunological features. The article also analyzes the modern approach to the treatment of patients with LADA and promising methods of treatment. The search for information was processing in published sources attached to the search engines PubMed, Google Scholar, Scopus, Web of Science, eLibrary.ru over the past 10 years. The following medical subject headings were used: latent autoimmune diabetes in adults, diabetes mellitus type 1 and 2, immunology, pancreas, genetic, treatment in various combinations using OR and AND logical operators.

Latent autoimmune diabetes in adults (LADA) is a slow progressive autoimmune destruction of pancreatic beta cells. This condition tends to manifest during adulthood, often around 35 years of age. While LADA can initially be managed by oral medications, eventually the patient will require insulin. We report a case of a 34-year-old woman who was initially treated for type 2 diabetes mellitus but was later diagnosed with LADA.

Objective: To evaluate the frequency of autoantibodies to glutamic acid decarboxylase-65 (GADA) and tyrosine phosphatase (IA-2A) in adult patients diagnosed with type 2 diabetes (T2D) and its associated characteristics, in particular those that related to metabolic syndrome. Materials and methods: In this cross-sectional study, autoantibodies to GADA and IA-2A were measured in 384 adult patients with T2D. Assays for autoantibodies were conducted using ELISA kits. The sociodemographic, clinical, and metabolic characteristics of islet autoantibody-positive and negative participants were then compared. SPSS software was used for data analysis and p < 0.05 was selected as a significant level. Results: Thirty two (8.3%) participants were positive for at least one islet autoantibody. The prevalence of GADA and IA-2A were reported 6.3% and 2.3% respectively, and one patient had both antibodies together. Autoantibody-positive patients were significantly younger (p < 0.001), had lower median age at diagnosis (p = 0.010), mean body mass index (BMI) (p = 0.004), waist circumference (WC) (p = 0.033), total cholesterol (p = 0.020), triglycerides (p = 0.041), C-peptide (p < 0.001) and prevalence of metabolic syndrome (p < 0.001) and higher fasting blood glucose (FBG) (p = 0.046), glycated hemoglobin (HbA1c) levels (p = 0.035) and need for insulin therapy (p < 0.001) than patients with T2D. Sex distribution, blood pressure levels and family history of diabetes were similar in the two groups. Conclusions: The prevalence of LADA in the studied population was 8.3%. LADA should be suspected in leaner patients with T2D with worse glycemic control, low C-peptide level and without metabolic syndrome. Antibody screening is recommended to discriminate of LADA and to help better control of glycemic profile. [ABSTRACT FROM AUTHOR]

Background: The prevalence of diabetes mellitus (DM) is dramatically increasing around the world, and patients are getting younger with changes in living standards and lifestyle. This study summarized and analyzed the clinical characteristics of different types of newly diagnosed diabetes mellitus patients with an onset age between 18 and 40 years to provide clinical evidence for the early diagnosis and treatment of diabetes, reduce short-term and long-term complications and offer scientific and personalized management strategies. Methods: A total of 655 patients newly diagnosed with early-onset diabetes mellitus in the Department of Endocrinology, the First Medical Center of PLA General Hospital from January 2012 to December 2022 were retrospectively enrolled in this study, with an onset age of 18–40 years. Their clinical data were collected and investigated. All patients were divided into two groups according to whether they presented with diabetic microangiopathy. Similarly, patients with early-onset type-2 diabetes were grouped in accordance with whether they had ketosis at the time of diagnosis. Binary logistic regression analysis was performed to analyze risk factors, and receiver-operating characteristic (ROC) analysis was used to explore the predictive value of significant risk factors. Results: The findings were as follows: (1) Of 655 enrolled patients, 477 (72.8%) were male and 178 (27.1%) were female, with a mean age of onset of was 29.73 years ± 0.24 SD. (2) The prevalence of early-onset diabetes was gradually increasing. Type-2 diabetes was the most common type of early-onset diabetes (491, 75.0%). The ages of onset of early-onset type-1 diabetes, type-2 diabetes and LADA were mainly 18–24 years, 25–40 years and 33–40 years, respectively. (3) Initial clinical manifestations of early-onset diabetes were classic diabetes symptoms (361, 55.1%), followed by elevated blood glucose detected through medical examination (207, 31.6%). (4) Binary logistic regression analysis suggested that high serum uric acid (UA), a high urinary albumin-to-creatinine ratio (UACR) and diabetic peripheral neuropathy (DPN) were risk factors for microangiopathy in early-onset diabetes patients (P < 0.05). The area under the curve (AUC) on ROC analysis of the combination of UA, UACR and DPN was 0.848, 95% CI was 0.818 ~ 0.875, sensitivity was 73.8% and specificity was 85.9%, which had higher predictive value than those of UA, UACR and DPN separately. (5) Weight loss, high glycosylated hemoglobin (HbA1c) and young onset age were risk factors for ketosis in patients with early-onset type-2 diabetes (P < 0.05). Conclusion: (1) Men were more likely to have early-onset diabetes than women. (2) Early-onset diabetes patients with high serum uric acid levels, high UACRs and peripheral neuropathy were prone to microangiopathy. Comprehensive evaluation of these risk factors could have higher predictive value in the prediction, diagnosis and treatment of microvascular lesions. (3) Patients with weight loss at onset, high HbA1c and young onset age were more likely to develop ketosis. Attention should be given to the metabolic disorders of these patients. [ABSTRACT FROM AUTHOR]

Introduction: Latent autoimmune diabetes in adults (LADA) is a highly heterogeneous autoimmune condition with clinical and genetic characteristics that fall between those of type 1 diabetes mellitus and type 2 diabetes mellitus; therefore, there are no uniform criteria for the selection of therapeutic agents. We conducted a network meta-analysis to evaluate the efficacy of various therapeutic agents for LADA by comparing their effects on various indicators used to reflect LADA. Methods: We searched the PubMed, Cochrane Library, Embase and Web of Science databases from their inception to March 2023 and collected data from 14 randomized controlled trials on glucose-lowering drugs for LADA, including 23 studies and 15 treatment regimens. The effectiveness of drugs was ranked and evaluated by combining surface under the cumulative ranking (SUCRA) plots and forest plots. Factors that may influence study heterogeneity were also searched and analyzed by combining subgroup analysis, publication bias, funnel plots and sensitivity analysis. Results: The results of the network meta-analysis showed that insulin had the most significant effect on the control of change from baseline in glycosylated hemoglobin, type A1 (ΔHbA1c). Insulin combined with dipeptidyl peptidase-4 (DPP-4) inhibitors performed the best in reducing fasting blood glucose and body mass index. Treatment regimens involving thiazolidinediones were the most advantageous in HbA1c, fasting C-peptide and postprandial C-peptide control. Longer dosing may be more beneficial in maintaining islet β-cell function in the LADA population. Conclusion: LADA is an immune condition with high heterogeneity, and treatment should be administered according to the C-peptide level of the LADA population. For this population with LADA with a certain level of β-cell function, combinations of insulin with DPP-4 inhibitors or thiazolidinediones probably can be more effective treatment options to maintain islet function and normal blood glucose. Trial Registration: PROSPERO CRD42023410795. [ABSTRACT FROM AUTHOR]

Background. Recently, a lot of information has appeared on the role of cholecalciferol deficiency in the development of the mechanisms of classical types of diabetes mellitus (DM) and its complications. However, there are currently almost no data regarding latent autoimmune diabetes in adults (LADA). The purpose of this study was to determine the effect of vitamin D deficiency on the compensation of carbohydrate metabolism in LADA. Materials and methods. The study included 56 patients with DM: 34 with LADA and 22 with classical type 1 DM (DM1), as well as 20 practically healthy individuals of the control group. According to the main phenotypes, patients with LADA were divided into 2 groups: LADA1 and LADA2. Cholecalciferol status was determined by the immunochemiluminescence method. Results. The fasting blood glucose level in LADA and DM1 group was significantly higher than in the controls, by 63.9 and 91.1 % (p < 0.001), respectively, and was also 16.6 % higher when comparing DM1/LADA groups (p < 0.05). The level of HbA1c in 66.1 % of patients of the experimental groups was more than 7 %, which indicates insufficient compensation of the disease. The content of vitamin D was significantly lower in the experimental groups compared to the controls; when comparing LADA/DM1 — by 43.7 % lower in case of classical DM1 (p < 0.05). Compensation of carbohydrate metabolism is worse in patients with LADA1 than in LADA2, and the lowest level of vitamin D was recorded in LADA1. According to the linear regression analysis of correlations in patients with LADA, negative correlations of medium strength were recorded between the level of cholecalciferol and fasting blood glucose (r = 0.487; p < 0.05), HbA1c (r = –0.593; p < 0.05); positive — between cholecalciferol and C-peptide (r = 0.412; p < 0.05). Conclusions. In patients with autoimmune diabetes, there is an insufficient supply of cholecalciferol. Low cholecalciferol content is observed in both groups of patients with LADA regardless of the disease phenotype and is associated with worse compensation of DM.

This paper summarized nursing measures of skin and soft-tissue infections(SSTIs) complicated with allergic dermatitis caused by catheter insertion during continuous subcutaneous insulin infusion (CSII) in a patient with latent autoimmune diabetes in adults (LADA). Key issues of nursing were as follows: debridement, drainage, systemic and local anti-infection in the early stage of skin care, and negative-pressure wound therapy to improve the wound healing in the later stage of skin care; comprehensive blood glucose management including standardized self-management of insulin pump and monitoring on adverse reactions of clindamycin hydrochloride, levofloxacin and clindamycin; enhancement on psychological nursing and health education. The patient was discharged form hospital and the follow-up results showed that the wound was healed and the blood glucose was well-controlled. (总结1例胰岛素泵导管致皮肤软组织感染伴过敏性皮炎的成人隐匿性自身免疫糖尿病患者的皮肤及伤口护理经验。护理要点包括: 针对伤口护理, 前期给予以清创、引流、全身及局部抗感染, 后期应用负压伤口疗法, 促进伤口愈合; 实施腹针联合激光疗法治疗过敏性皮炎的护理经验; 根据病情全方位血糖管理, 指导患者胰岛素泵规范化自我管理, 监测盐酸克林霉素、左氧氟沙星、克林霉素等消炎药物的不良反应, 预防并发症; 加强心理护理和健康教育。患者经治疗护理16 d后好转出院, 糖尿病足伤口门诊及微信随访, 出院3 d后伤口愈合良好, 血糖控制稳定。)

Latent autoimmune diabetes in adults (LADA) is a slow progressive autoimmune destruction of pancreatic beta cells. This condition tends to manifest during adulthood, often around 35 years of age. While LADA can initially be managed by oral medications, eventually the patient will require insulin. We report a case of a 34-year-old woman who was initially treated for type 2 diabetes mellitus but was later diagnosed with LADA. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride–glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA). Methods: This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed. Results: A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all P < 0.05). The positive relationship between the TyG index and the urinary albumin/creatinine ratio was significant (r = 0.249, P = 0.010). There was also a significant correlation between the TyG index and the eGFR (r = − 0.211, P = 0.034) after adjusting for confounding factors. The area-under-the-curve value of the TyG index was 0.708 (95% confidence interval: 0.61–0.81, P < 0.001). Conclusions: The TyG index is significantly associated with the severity of CKD in patients with LADA. This conclusion supports the clinical application of the TyG index for the assessment of kidney disease in patients with LADA. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study is to explore the relationship between red blood cell distribution and islet β-cell function indexes in patients with Latent Autoimmune Diabetes in Adults. Methods: A total of 487 LADA patients were enrolled in this cross-sectional study. Patients were divided into three groups according to RDW tertiles. Clinical and laboratory measurements of age, height, weight, duration of diabetes, blood pressure, RDW, glycosylated hemoglobin A1c (HbA1c), C-peptide and blood lipids were performed. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were assessed using homeostasis model assessment (HOMA) based on fasting blood glucose (FBG) and fasting C-peptide index (FCP). Correlations and multiple linear regressions were implemented to determine the association of RDW and islet function indexes. Results: As the increase of serum RDW level, the presence of β-cell secretion increased(P < 0.05). Correlation analysis indicated that there were significant correlations between RDW and male sex, age, duration, TG, Cr, FCP, and HOMA-β in all subjects. Multiple linear regressions indicated that RDW was significantly correlated with HOMA-β in the total population in both unadjusted and adjusted analysis. This finding could be reproduced in the subgroup of low GAD titers for HOMA-β. RDW were significantly associated with HbA1c in LADA patients with high GAD titers, but the correlation was not found in subgroup with low GAD titers in either unadjusted analyses or adjusted analysis. Conclusions: RDW is associated with β-cell function assessed by HOMA-β after adjusting for covariates in LADA patients with low GAD titers. [ABSTRACT FROM AUTHOR]

In clinical practice, the distinction between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) can be challenging, leaving patients with “ambiguous” diabetes type. Insulin-treated patients (n=115) previously diagnosed with T2DM had to be re-classified based on clinical phenotype and laboratory results, and were operationally defined as having an ambiguous diabetes type. They were compared against patients with definite T1DM and T2DM regarding 12 clinical and laboratory features typically different between diabetes types. Characteristics of patients with ambiguous diabetes type, representing approximately 6% of all patients with T1DM or T2DM seen at our specialized clinic, fell in between those of patients with definite T1DM and T2DM, both regarding individual features and with respect to a novel classification based on multi-variable regression analysis (P

Background: Latent autoimmune diabetes in adults (LADA) and maturity onset diabetes of the young (MODY) are two forms of diabetes with varied disease symptoms. The prevalence of LADA is higher in adults than MODY. Both diseases contribute to the general burden of diabetes globally. While LADA is a sporadic autoimmune disorder, MODY is a heritable genetic disorder. The prevalence of LADA and MODY has not been fully documented in Africa due to the lack of robust diagnostic tools and the exorbitantly high cost of the available diagnostic tools. Methods: To understand the prevalence landscape of LADA and MODY in Africa, we conducted an extensive scoping review and mapped the various studies performed in Africa. We adopted the Joanna Briggs Institute literature review framework to conduct the scoping review of literature. Results: Research articles were included in the review analysis following exhaustive inclusion criteria to ensure that only qualified articles were included in the final analysis. Overall, 16 research articles met the inclusion criteria and were critically analyzed. An in-house data extraction sheet was used for data extraction from all the shortlisted articles. Information about the sample size, inclusion criteria, age, gender, and study design extracted from all the articles and analyzed. Majority of the studies adopted cross-sectional study design. In terms of sample sizes, the studies used relatively smaller sample sizes due to the high cost of the diagnosis and nature of the diseases. The prevalence rates of LADA and MODY varied in various countries ranging from 1.8 to 18%. Conclusion: African countries are significantly under-represented. The scarcity of research on LADA and MODY research in Africa is evidence of the urgent need to invest more resources in this area. This would guide future research and shape the road towards understanding diabetes in Africa.

Background. Recently, a lot of information has appeared on the role of cholecalciferol deficiency in the development of the mechanisms of classical types of diabetes mellitus (DM) and its complications. However, there are currently almost no data regarding latent autoimmune diabetes in adults (LADA). The purpose of this study was to determine the effect of vitamin D deficiency on the compensation of carbohydrate metabolism in LADA. Materials and methods. The study included 56 patients with DM: 34 with LADA and 22 with classical type 1 DM (DM1), as well as 20 practically healthy individuals of the control group. According to the main phenotypes, patients with LADA were divided into 2 groups: LADA1 and LADA2. Cholecalciferol status was determined by the immunochemiluminescence method. Results. The fasting blood glucose level in LADA and DM1 group was significantly higher than in the controls, by 63.9 and 91.1 % (p < 0.001), respectively, and was also 16.6 % higher when comparing DM1/ LADA groups (p < 0.05). The level of HbA1c in 66.1 % of patients of the experimental groups was more than 7 %, which indicates insufficient compensation of the disease. The content of vitamin D was significantly lower in the experimental groups compared to the controls; when comparing LADA/DM1 - by 43.7 % lower in case of classical DM1 (p < 0.05). Compensation of carbohydrate metabolism is worse in patients with LADA1 than in LADA2, and the lowest level of vitamin D was recorded in LADA1. According to the linear regression analysis of correlations in patients with LADA, negative correlations of medium strength were recorded between the level of cholecalciferol and fasting blood glucose (r = 0.487; p < 0.05), HbA1c (r = -0.593; p < 0.05); positive - between cholecalciferol and C-peptide (r = 0.412; p < 0.05). Conclusions. In patients with autoimmune diabetes, there is an insufficient supply of cholecalciferol. Low cholecalciferol content is observed in both groups of patients with LADA regardless of the disease phenotype and is associated with worse compensation of DM. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta‐analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients. Materials and Methods We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β‐cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis. Results Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference −0.36, 95% confidence interval −0.61 to −0.10, I2 = 91.6%), increased fasting C‐peptide (weighted mean difference 0.08, 95% confidence interval −0.02 to 0.17, I2 = 88.8%) and had fewer adverse events compared with insulin alone. The inter‐study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C‐peptide, regardless of the duration of intervention and sample size. Conclusions Sitagliptin combined with insulin can achieve better glycemic control and improve islet β‐cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well‐designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.

Background. IDM/LADA is late-manifesting immune-mediated diabetes diagnosed in patients over 30 years of age. It is estimated to account for 5–10% of diabetes cases in adults. Objectives. The aim of the study was to identify the parameters implying the diagnosis of immune-mediated diabetes among adults with new-onset diabetes. Material and methods. Study included patients 30–50 years of age with new-onset diabetes, hospitalised between 2014 and 2019 in the Diabetology Department. Medical history, hyperglycaemia symptoms, comorbidities, anthropometric measurements and laboratory tests were analysed. The exclusion criterion was a history of pancreatitis. Results. We analysed a group of 182 patients (mean age 38.1 ± 5.1). IDM/LADA was diagnosed in 78 (43%) patients. In the subgroup of subjects 30–35 years of age, IDM/LADA patients constituted 50.08%, whereas in the 36–50 years of age group, this constituted 38.65% of all the patients. The IDM/LADA patients were younger, had a lower body mass and BMI, noticed symptoms of diabetes before hospitalisation and more often had other autoimmune disorders. Thier C-peptide concentrations were nearly three times lower, while T2DM patients had a higher concentration of total cholesterol and triglycerides and more frequently had arterial hypertension (all p < 0.05). Testing for one antibody (GADA) allows one to diagnose 83% of IDM/LADA cases. Furthermore, determination of both GADA and ICA resulted in diagnosing autoimmune diabetes in 97% of all the patients. Conclusions. With a measurement of C-peptide concentration and GADA detection, we could diagnose IDM/LADA with 89% sensitivity. Moreover, the inclusion of clinical features increased the sensitivity up to 93.5%. Considering the age criterion, there was no significant difference between the groups of patients with IDM/LADA. [ABSTRACT FROM AUTHOR]

In clinical practice, the distinction between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) can be challenging, leaving patients with "ambiguous" diabetes type. Insulin-treated patients (n=115) previously diagnosed with T2DM had to be re-classified based on clinical phenotype and laboratory results, and were operationally defined as having an ambiguous diabetes type. They were compared against patients with definite T1DM and T2DM regarding 12 clinical and laboratory features typically different between diabetes types. Characteristics of patients with ambiguous diabetes type, representing approximately 6% of all patients with T1DM or T2DM seen at our specialized clinic, fell in between those of patients with definite T1DM and T2DM, both regarding individual features and with respect to a novel classification based on multi-variable regression analysis (P<0.0001). In conclusion, a substantial proportion of diabetes patients in a tertiary care centre presented with an "ambiguous" diabetes type. Their clinical characteristics fall in between those of definite T1DM or T2DM patients. [ABSTRACT FROM AUTHOR]

Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results: Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. Data availability: Analysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA). [ABSTRACT FROM AUTHOR]

Thekra Al-Zubairi, Molham AL-Habori, Riyadh Saif-Ali Department of Biochemistry and Molecular Biology, Faculty of Medicine and Health Sciences, University of Sana`a, Sana`a, YemenCorrespondence: Molham AL-Habori Email malhabori@hotmail.comPurpose: Although there is ample data about the prevalence of diabetes in the Middle East, little is known about the prevalence and features of autoimmune diabetes in this region. The aim of this study was to investigate the prevalence and metabolic characteristics of latent autoimmune diabetes in adults (LADA) amongst Yemeni Type 2 DM patients.Patients and Methods: In this cross-section study, 270 Type 2 DM patients aged 30– 70 years were recruited from the National Diabetes Center, Al-Thowra Hospital, Sana’a city, during the period November 2015 to August 2016. All Type 2 DM patients were diagnosed within 5 years and who did not require insulin for a minimum of 6 months following diagnosis. Levels of glutamic acid decarboxylase autoantibodies (GADA) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Further, biochemical analysis was carried out including fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, and lipid profile. Insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were calculated.Results: The prevalence of LADA, as defined by GADA-positive, amongst patient with Type 2 DM was 4.4%; with no significant difference in the prevalence between male (5.8%) and female (3.4%). LADA patients were younger than GADA-negative Type 2 DM. Body mass index, waist circumference, insulin and HOMA-β were significantly lower in LADA patients, whereas triglyceride, cholesterol, HDL-c and HOMA-IR were non-significantly lower with respect to Type 2 DM. In contrast, FBG and HbA1c were significantly higher in LADA patients. Moreover, the prevalence of metabolic syndrome was significantly lower in LADA as compared with Type 2 DM. Only 2 out of the 12 GADA-positive (16.7%) were on insulin treatment at the time of the study.Conclusion: The prevalence of LADA in Yemeni Type 2 DM is lower than many of those reported in the literature, with no gender preference. Metabolic syndrome was significantly lower in LADA patients. Patients with LADA share insulin resistance with Type 2 DM but display a more severe defect in β-cell function, thus highlighting the importance of an early diagnosis of LADA, to correctly treat LADA patients, allowing safe and effective therapies.Keywords: latent autoimmune diabetes in adults, Type 2 DM, metabolic syndrome, insulin resistance, glutamic acid decarboxylase antibody

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. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta‐analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients. Materials and Methods: We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, β‐cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis. Results: Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference −0.36, 95% confidence interval −0.61 to −0.10, I2 = 91.6%), increased fasting C‐peptide (weighted mean difference 0.08, 95% confidence interval −0.02 to 0.17, I2 = 88.8%) and had fewer adverse events compared with insulin alone. The inter‐study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C‐peptide, regardless of the duration of intervention and sample size. Conclusions: Sitagliptin combined with insulin can achieve better glycemic control and improve islet β‐cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well‐designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials. [ABSTRACT FROM AUTHOR]

Latent autoimmune diabetes in adults (LADA) is a type of diabetes characterized by slow autoimmune damage of pancreatic b cells without insulin treatment in the early clinical stage. There are differences between LADA and classical type 1 diabetes (T1D) and type 2 diabetes (T2D) in genetic background, autoimmune response, rate of islet function decline, clinical metabolic characteristics, and so on. The disease progression and drug response of patients with LADA are closely related to the level of islet autoimmunity, thus exploring the pathogenesis of LADA is of great significance for its prevention and treatment. Previous studies reported that adaptive immunity and innate immunity play a critical role in the etiology of LADA. Recent studies have shown that the intestinal microbiota which impacts host immunity hugely, participates in the pathogenesis of LADA. In addition, the progression of autoimmune pancreatic b cell destruction in LADA is slower than in classical T1D, providing a wider window of opportunities for intervention. Therefore, therapies including antidiabetic drugs with immune-regulation effects and immunomodulators could contribute to promising interventions for LADA. We also shed light on potential interventions targeting the gut microbiota and gut-associated immunity, which may be envisaged to halt or delay the process of autoimmunity in LADA. [ABSTRACT FROM AUTHOR]

Background: Latent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to insulin dependency. In a recent trial BALAD (Behandling Av LADa) early insulin treatment compared with sitagliptin failed to preserve insulin secretion, which deteriorated in individuals displaying high levels of antibodies to GAD (GADA). These findings prompted us to evaluate a treatment that directly affects autoimmunity. Intra-lymphatic GAD-alum treatment has shown encouraging results in Type 1 diabetes patients. We therefore tested the feasibility of such therapy in LADA-patients (the GADinLADA pilot study). Material and Methods: Fourteen GADA-positive (>190 RU/ml), insulin-independent patients 30-70 years old, with LADA diagnosed within < 36 months were included in an open-label feasibility trial. They received an intra-nodal injection of 4 mg GAD-alum at Day 1, 30 and 60 plus oral Vitamin D 2000 U/d from screening 30 days before (Day-30) for 4 months if the vitamin D serum levels were below 100 nmol/L (40 µg/ml). Primary objective is to evaluate safety and feasibility. Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test at baseline and after 5 and 12 months are used for estimation of beta cell function. Results will be compared with those of the recent BALAD study with comparable patient population. Immunological response is followed. Results: Preliminary results show feasibility and safety, with almost stable beta cell function and metabolic control during follow-up so far (5 months). Conclusions: Intra-lymphatic GAD-alum treatment is an option to preserve beta cell function in LADA-patients. An ongoing trial in 14 LADA-patients show feasibility and safety. Clinical and immunological responses will determine how to proceed with future trials. [ABSTRACT FROM AUTHOR]

BackgroundLatent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to insulin dependency. In a recent trial BALAD (Behandling Av LADa) early insulin treatment compared with sitagliptin failed to preserve insulin secretion, which deteriorated in individuals displaying high levels of antibodies to GAD (GADA). These findings prompted us to evaluate a treatment that directly affects autoimmunity. Intra-lymphatic GAD-alum treatment has shown encouraging results in Type 1 diabetes patients. We therefore tested the feasibility of such therapy in LADA-patients (the GADinLADA pilot study).Material and MethodsFourteen GADA-positive (>190 RU/ml), insulin-independent patients 30-70 years old, with LADA diagnosed within < 36 months were included in an open-label feasibility trial. They received an intra-nodal injection of 4 μg GAD-alum at Day 1, 30 and 60 plus oral Vitamin D 2000 U/d from screening 30 days before (Day -30) for 4 months if the vitamin D serum levels were below 100 nmol/L (40 ng/ml). Primary objective is to evaluate safety and feasibility. Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test at baseline and after 5 and 12 months are used for estimation of beta cell function. Results will be compared with those of the recent BALAD study with comparable patient population. Immunological response is followed.ResultsPreliminary results show feasibility and safety, with almost stable beta cell function and metabolic control during follow-up so far (5 months).ConclusionsIntra-lymphatic GAD-alum treatment is an option to preserve beta cell function in LADA-patients. An ongoing trial in 14 LADA-patients show feasibility and safety. Clinical and immunological responses will determine how to proceed with future trials.

The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous subtype of diabetes characterized by islet cell destruction mediated by islet autoimmunity and insulin resistance. Metabolic syndrome (MetS) is a state in which many risk factors for metabolic and cardiovascular diseases accumulate in an individual. Based on clinical data, this review covers the prevalence of MetS in LADA, focusing on the risk associated with and the role of insulin resistance in the development of LADA from the perspective of inflammatory factors, environmental factors, and the gut microbiota, aiming to improve our understanding of this condition. [ABSTRACT FROM AUTHOR]

Serum creatinine level begins to increase after a decrease in glomerular filtration rate (GFR) by 50% and more, so the question emerged about a more accurate method of determining GFR. The study aimed to determine the role of renal damage markers in the diagnosis of early-stage renal disease in patients with latent autoimmune diabetes in adults (LADA). We included 84 patients with diabetes mellitus (DM) and chronic kidney disease (CKD) caused by diabetic kidney disease (DKD), as well as 25 representatives of the control group. Patients were divided into three groups - 43 people with LADA, 21 with type 1 diabetes mellitus (T1DM), and 20 patients with type 2 diabetes mellitus (T2DM). GFR was assessed using six formulas after establishing the category of GFR and albuminuria. The GFR rate estimated by the CKD-EPI formula in patients with LADA and DKD did not significantly differ from that of CKD-EPI cysC, slightly different from MDRD GFR (10.6% higher, respectively) but 21.9% lower compared to CG formula. In patients with LADA and T1DM, GFR was higher in cases with existing albuminuria, regardless of the formulas used. Thus, the non albuminuria phenotype is accompanied by a greater degree of renal impairment, which indicates the need to determine serum cystatin C in the early stages of LADA. Cystatin C levels are the most accurate, early, and independent predictor of the development and progression of CKD in patients with DM, including LADA. [ABSTRACT FROM AUTHOR]

Jing Li,1 Songbai Lin,1 Chuiwen Deng,2 Tengda Xu1 1Department of Health Management, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 2Rheumatology and Immunology Department, Peking Union Medical College Hospital, Beijing, People’s Republic of ChinaCorrespondence: Tengda XuDepartment of Health Management, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of ChinaTel/Fax +86 10 6915 9866Email xutd@pumch.cnPurpose: To investigate the prevalence of GAD antibody (GADA) in the general adult population and to evaluate its predictive value for diabetes in China.Patients and Methods: We searched the PUMCH-HM database and identified 36,731 adult subjects with GADA test results from 2012 to 2015. We then established a retrospective cohort of 4835 nondiabetic subjects at baseline with complete annual health evaluation records through 2019. The median follow-up time was 4.8 (3.0– 7.3) years.Results: The overall prevalence of GADA was 0.53% and was higher in diabetic subjects (1.25%) than in nondiabetic subjects (0.47%). We found a decrease in baseline body mass index (BMI) from the GADA- to GADAhigh subgroups among baseline diabetic and prediabetic patients and also those who developed diabetes later in the cohort study. A total of 136 subjects (2.8%) developed diabetes after a median follow-up of 3.5 years. For GADA+ participants, BMI was not associated with the risk for diabetes. In the Cox regression model, the GADAlow and GADAhigh exhibited 2.63-fold and 4.16-fold increased risk for diabetes, respectively. This increased risk for diabetes by GADA-positivity is only found in male adults (HR 4.55, 95% CI 2.25– 9.23).Conclusion: GADA has a low prevalence in China but is associated with a 2.63– 4.16-fold increased risk for diabetes.Keywords: autoimmune diabetes, glutamic acid decarboxylase antibody, latent autoimmune diabetes in adults, obesity, prevention

Latent autoimmune diabetes in adults (LADA) is a heterogeneous subtype of diabetes characterized by islet cell destruction mediated by islet autoimmunity and insulin resistance. Metabolic syndrome (MetS) is a state in which many risk factors for metabolic and cardiovascular diseases accumulate in an individual. Based on clinical data, this review covers the prevalence of MetS in LADA, focusing on the risk associated with and the role of insulin resistance in the development of LADA from the perspective of inflammatory factors, environmental factors, and the gut microbiota, aiming to improve our understanding of this condition.

Introduction: We report a case series of severe ketoacidosis after COVID-19 vaccination in a type 1 diabetes patients treated with insulin and an SGLT-2 inhibitor. Case Report: We present two cases of type 1 diabetes mellitus. One patient was treated with insulin therapy and an SGLT-2 inhibitor, and the other patient was treated with insulin therapy alone. Both patients became ill after coronavirus disease-2019 vaccination, making it difficult to continue their diet or insulin injections. On admission, they developed severe diabetic ketoacidosis. This is the first report of ketoacidosis after coronavirus disease-2019 vaccination. Conclusion: The vaccine should be carefully administered to type 1 diabetes patients receiving intensive insulin therapy and a sodium-glucose transporter due to the high risk ketoacidosis. It is important to instruct patients to drink sufficient fluids and to continue insulin injections when they become sick. [ABSTRACT FROM AUTHOR]

Abstract Introduction Adult-onset autoimmune diabetes (AID) has two different phenotypes: classic type 1 diabetes mellitus (T1DM), with insulin requirement just after diagnosis, and latent autoimmune diabetes in adults (LADA). The purpose of this study is to characterize patients with AID followed on a tertiary centre, comparing classic T1DM and LADA. Methods We collected data from patients with diabetes and positive islet autoantibodies, aged 30 years old and over at diagnosis. Patients who started insulin in the first 6 months were classified as T1DM and patients with no insulin requirements in the first 6 months were classified as LADA. Data regarding clinical presentation, autoantibodies, A1C and C-peptide at diagnosis, pharmacologic treatment and complications were analysed. Results We included 92 patients, 46 with classic T1DM and 46 with LADA. The percentage of females was 50% in T1DM group and 52.1% in LADA group. The median age at diagnosis was 38 years (IQR–15) for T1DM and 42 years (IQR–15) for LADA (p = 0.057). The median time between diagnosis of diabetes and diagnosis of autoimmune aetiology was 0 months in T1DM group and 60 months in LADA group (p

Abstract Background A growing body of evidence supports neutrophils as having an active role in the development of diabetic kidney disease (DKD). However, the clinical relevance of neutrophils and DKD in autoimmune diabetes remains unknown. This study aimed to investigate the relationship between circulating neutrophils and DKD in autoimmune diabetes. Methods Patients with type 1 diabetes (T1D, n = 226) and latent autoimmune diabetes in adults (LADA, n = 79) were enrolled and stratified according to the urinary albumin to creatinine ratio (ACR). Circulating levels of white blood cells (WBCs), including neutrophils, were measured in a central laboratory, and the neutrophil-to-lymphocyte ratio (NLR) was calculated. The risk factors associated with DKD were analysed by logistic regression. Results In T1D and LADA patients, the peripheral neutrophil counts increased in parallel with DKD advancement. The neutrophil counts in the patients with macroalbuminuria were significantly higher than those in the patients with normoalbuminuria for each type of diabetes. Furthermore, neutrophil counts positively correlated with ACR in T1D. In addition, neutrophils were independently associated with DKD in T1D in the logistic regression analysis, when various well-known risk factors, including age, gender, disease duration, hypertension, dyslipidemia and smoking status, were adjusted. Conclusions Neutrophil counts are closely associated with DKD in patients with autoimmune diabetes, suggesting that neutrophil-mediated inflammation may be involved in the pathogenesis of DKD in patients with autoimmune diabetes.