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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]

Objective: To analyze the degree of control based on classical glucometric parameters and Glycemia Risk Index (GRI) in real-life conditions in a cohort of patients with type 1 Diabetes Mellitus (DM) and Latent Autoimmune Diabetes in Adults (LADA) and to assess the factors that are associated with GRI. Patients and methods: Cross-sectional study. 447 adult patients with type 1 DM and LADA users of Intermittent Continuous Glucose Monitoring (iCGM) with an adherence ≥ 70% were included. GRI was calculated with its Hypoglycemia (CHypo) and Hyperglycemia (CHyper) Components. Multivariate linear regression analysis was performed to evaluate the factors associated with GRI. Results: Mean age 44.6 years (SD 13.7); 57.7% men; 83.9% type 1 DM; 16.1% LADA; time of evolution 20.6 years (SD 12.3). In patients with type 1 DM vs. LADA, differences were observed in relation to age [−11.1 years (SD 1.7)], age of onset [−21.9 years (DE 1.5)], time of evolution [11.7 years (DE 1.5)], treatment modality (p < 0.001), Time in Range (TIR) [−6.3% (SD 2.2)], Time Below Range (TBR) [1.9% (SD 0.6)], TBR level 1 (TBR1) [1.4% (SD 0.5)], Time Above Range (TAR) level 2 (TAR2) [4.7% (SD 1.3)], Coefficient of Variation (CV) [4.6% (SD 0.9)], GRI [11.3% (SD 2.8)], CHypo [1.3% (SD 0.5)] and CHyper [4.8% (SD 1.7)]. The variables that were independently associated with GRI were TIR (β = −1.34; CI 95% −1.43 to −1.25; p < 0.001), Glucose Management Indicator (GMI) (β = −5.82; CI 95% −7.59 to −4.05; p < 0.001), CV (β = 0.67; CI 95% 0.57 to 0.77; p < 0.001) and adherence to sensor usage (β = −0.16; CI 95% −1.27 to −0.06; p < 0.002). Conclusions: LADA present better control according to some glucometric parameters and a low GRI. However, the type of DM is not a factor that is independently associated with GRI. [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.

Aim: To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). Methods: In this phase 2b multicentre, open‐label, comparator‐controlled, parallel‐group, non‐inferiority study, we randomly assigned 33 people with LADA who had a fasting C‐peptide concentration ≥0.2 nmol/L (0.6 ng/mL) to receive 1‐year daily treatment with either the combination of saxagliptin (5 mg) plus dapagliflozin (10 mg) or insulin glargine (starting dose: 10 IU), both on top of metformin. The primary outcome was the 2‐h mixed meal‐stimulated C‐peptide area under the curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change in body mass index (BMI), and hypoglycaemic events. Results: In the modified intention‐to‐treat analysis, the primary outcome was similar in participants assigned to saxagliptin/dapagliflozin or to insulin glargine (median C‐peptide AUC: 152.0 ng*min/mL [95% confidence interval {CI} 68.2; 357.4] vs. 122.2 ng*min/mL [95% CI 84.3; 255.8]; p for noninferiority = 0.0087). Participants randomized to saxagliptin/dapagliflozin lost more weight than those randomized to insulin glargine (median BMI change at the end of the study: −0.4 kg/m2 [95% CI −1.6; −0.3] vs. +0.4 kg/m2 [95% CI −0.3; +1.1]; p = 0.0076). No differences in HbA1c or in the number of participants experiencing hypoglycaemic events were found. Conclusions: Saxagliptin/dapagliflozin was non‐inferior to glargine in terms of β‐cell function in this 12‐month, small, phase 2b study, enrolling people with LADA with still viable endogenous insulin production. Weight loss was greater with saxagliptin/dapagliflozin, with no differences in glycaemic control or hypoglycaemic risk. [ABSTRACT FROM AUTHOR]

This article explores the topic of Latent Autoimmune Diabetes in Adults (LADA), a form of diabetes that combines characteristics of both type 1 and type 2 diabetes. The article emphasizes the need for standardized diagnostic criteria and recommends autoantibody testing for newly diagnosed type 2 diabetes patients. The management of LADA is still uncertain, and further research is necessary to determine the most effective interventions. The article also acknowledges the variability in the progression and long-term outcomes of LADA patients. The authors call for more scientific research and international collaborations to address the unanswered questions surrounding LADA and ultimately benefit those affected by the condition. [Extracted from the article]

Immune-mediated cerebellar ataxias (IMCAs) have diverse etiologies. Patients with IMCAs develop cerebellar symptoms, characterized mainly by gait ataxia, showing an acute or subacute clinical course. We present a novel concept of latent autoimmune cerebellar ataxia (LACA), analogous to latent autoimmune diabetes in adults (LADA). LADA is a slowly progressive form of autoimmune diabetes where patients are often initially diagnosed with type 2 diabetes. The sole biomarker (serum anti-GAD antibody) is not always present or can fluctuate. However, the disease progresses to pancreatic beta-cell failure and insulin dependency within about 5 years. Due to the unclear autoimmune profile, clinicians often struggle to reach an early diagnosis during the period when insulin production is not severely compromised. LACA is also characterized by a slowly progressive course, lack of obvious autoimmune background, and difficulties in reaching a diagnosis in the absence of clear markers for IMCAs. The authors discuss two aspects of LACA: (1) the not manifestly evident autoimmunity and (2) the prodromal stage of IMCA's characterized by a period of partial neuronal dysfunction where non-specific symptoms may occur. In order to achieve an early intervention and prevent cell death in the cerebellum, identification of the time-window before irreversible neuronal loss is critical. LACA occurs during this time-window when possible preservation of neural plasticity exists. Efforts should be devoted to the early identification of biological, neurophysiological, neuropsychological, morphological (brain morphometry), and multimodal biomarkers allowing early diagnosis and therapeutic intervention and to avoid irreversible neuronal loss. [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. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by pancreatic beta cell destruction. In this study, we explored the pathogenic immune responses in initiation of type 1 diabetes and new immunological targets for type 1 diabetes prevention and treatment. Methods: We obtained peripheral blood samples from four individuals with newly diagnosed latent autoimmune diabetes in adults (LADA) and from four healthy control participants. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells to uncover transcriptomic profiles of early LADA. Validation was performed through flow cytometry in a cohort comprising 54 LADA, 17 adult-onset type 2 diabetes, and 26 healthy adults, matched using propensity score matching (PSM) based on age and sex. A similar PSM method matched 15 paediatric type 1 diabetes patients with 15 healthy children. Further flow cytometry analysis was performed in both peripheral blood and pancreatic tissues of non-obese diabetic (NOD) mice. Additionally, cell adoptive transfer and clearance assays were performed in NOD mice to explore the role of this monocyte subset in islet inflammation and onset of type 1 diabetes. Results: The scRNA-seq data showed that upregulated genes in peripheral T cells and monocytes from early-onset LADA patients were primarily enriched in the IFN signalling pathway. A new cluster of classical monocytes (cluster 4) was identified, and the proportion of this cluster was significantly increased in individuals with LADA compared with healthy control individuals (11.93% vs 5.93%, p=0.017) and that exhibited a strong IFN signature marked by SIGLEC-1 (encoding sialoadhesin). These SIGLEC-1+ monocytes expressed high levels of genes encoding C-C chemokine receptors 1 or 2, as well as genes for chemoattractants for T cells and natural killer cells. They also showed relatively low levels of genes for co-stimulatory and HLA molecules. Flow cytometry analysis verified the elevated levels of SIGLEC-1+ monocytes in the peripheral blood of participants with LADA and paediatric type 1 diabetes compared with healthy control participants and those with type 2 diabetes. Interestingly, the proportion of SIGLEC-1+ monocytes positively correlated with disease activity and negatively with disease duration in the LADA patients. In NOD mice, the proportion of SIGLEC-1+ monocytes in the peripheral blood was highest at the age of 6 weeks (16.88%), while the peak occurred at 12 weeks in pancreatic tissues (23.65%). Adoptive transfer experiments revealed a significant acceleration in diabetes onset in the SIGLEC-1+ group compared with the SIGLEC-1− or saline control group. Conclusions/interpretation: Our study identified a novel group of SIGLEC-1+ monocytes that may serve as an important indicator for early diagnosis, activity assessment and monitoring of therapeutic efficacy in type 1 diabetes, and may also be a novel target for preventing and treating type 1 diabetes. Data availability: RNA-seq data have been deposited in the GSA human database (https://ngdc.cncb.ac.cn/gsa-human/) under accession number HRA003649. [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

Purpose: Developmental abnormalities in B cells is one of the key players in autoimmune diabetes, but little is known about its role in latent autoimmune diabetes in adults (LADA). This study aimed to investigate the distribution of B cell subsets in different types of diabetes and to analyze their correlations with other biochemical parameters. Methods: A total of 140 participants were prospectively enrolled from January 2021 to December 2022. Diabetes-related autoantibodies and laboratory indicators were tested. Flow cytometry was used to analyze the percentage of circulating B cell subsets and T follicular cells. The correlation of B cell subsets with different indicators was assessed by Spearman's correlation method. Results: We observed that the Naïve phenotype cells tended to be less frequent in patients with diabetes than in healthy controls. The frequency of plasmablasts (PB) and Breg cell-related phenotype (B10) were significantly higher in LADA. Notably, the percentage of PB was positively associated with levels of islet cell antibody (ICA) and insulin autoantibody (IAA), but inversely associated with fasting C-peptide (FCP), further indicating that PB may promote the destruction of β-cell in patients with diabetes. Conclusions: This study showed that patients with LADA had significantly altered frequencies of B cell subsets, particularly in the naïve to memory B cell ratio. Our study provided valuable information on the distribution characteristics of B cell subsets in LADA and suggested the feasibility of B-cell targeted therapy in LADA patients. [ABSTRACT FROM AUTHOR]

Aims: Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods: We used data from a population‐based Swedish case‐control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results: Individuals who developed LADA did not have a higher prevalence of infectious disease 1–10 years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1–3 years. Similar results were seen for LADA with high‐risk HLA genotypes (OR 0.95 [0.64, 1.42]) or high GADA levels (OR 1.10 [0.79, 1.55]), ≥2 episodes (OR 0.89 [0.56, 1.40]), and in infections treated using antibiotics (OR 1.03 [0.73, 1.45]). The only significant association was observed with lower respiratory disease the year preceding LADA diagnosis (OR 1.67 [1.06, 2.64]). Conclusions: Our findings do not support the idea that exposure to infections increases the risk of LADA. A higher prevalence of respiratory infection in the year before LADA diagnosis could reflect increased susceptibility to infections due to hyperglycemia. [ABSTRACT FROM AUTHOR]

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]

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 of 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 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 the only (1) and (2), but not (3), he/she is diagnosed with "SPIDDM (probable)" because the diabetes is non-insulin-dependent state. [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]

Objective To investigate the effect of metformin plus insulin on β-cell function in non-obese patients with latent autoimmune diabetes in adults (LADA). Methods　 A LADA cohort established between 2008 and 2012 was studied retrospectively. Ten non-obese patients with LADA treated with insulin plus metformin (500-850 mg, twice daily) were screened from the cohort and matched 1∶1 with the insulin-treated control group. The retrospective cohort was followed up for a total of 3 years. Height, weight, waist and hip circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and body mass index (BMI) and waist-hip ratio (WHR) were calculated. Glycated hemoglobin A1C (HbA1c), fasting plasma glucose, 1 h postprandial plasma glucose, 2 h postprandial plasma glucose, blood lipids were measured at baseline and during follow-up. A mixed meal tolerance test was performed and C-peptide was measured. β-cell function was evaluated with fasting C-peptide (FCP), 1 h postprandial C-peptide (1hCP), 2 h postprandial C-peptide (2hCP), peak C-peptide (CPmax), variation in C-peptide (ΔCP) and area under the curve of C-peptide (AUCC). Insulin regimen and insulin dose were documented at each visit, and total daily insulin dose per kg was calculated. Differences in metabolic profiles and β-cell function during follow-up between the two groups were analyzed by repeated-measures analysis of covariance. Results　At the end of the three-year follow-up, the metformin group had an increase in SBP compared with baseline [(123±6) vs. (114±11) mmHg (1 mmHg=0.133 kPa), P= 0.043], and there were no significant differences in BMI, waist circumference, WHR, blood glucose, blood lipids and other metabolic profiles, or insulin dose between the two groups compared with the baseline, nor were there any significant difference between the two groups at any time point (all P> 0.05). 1hCP in the control group was significantly reduced from baseline [(462.1±378.9) vs. (923.6± 895.7) pmol/L, P=0.039] at the 6th month, with a significant decline in islet function at follow-ups. Notably, a significant difference in FCP from baseline was observed only in the metformin group after 24 months of follow-up [(296.0±264.2) vs. (463.9±304.3) pmol/L, P=0.017], and other parameters of β-cell function decreased significantly from baseline at the end of follow-up (P<0.05). At the 12th month of follow-up, the metformin group had significantly better islet function than that of the control group (P<0.05). However, at the 24th and the 36th months of follow-up, there was no significant difference in comparison of C-peptide between the two groups (P>0.05). Conclusion　 This small retrospective study suggests that the combination of metformin and insulin may help slow down the decay rate of islet function in non-obese LADA patients, but larger-scale clinical trials are needed to confirm this. [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]

Context: We aimed to investigate whether human leukocyte antigen (HLA) Class I loci differentially modulated the risk for and clinical features of Chinese people with classic type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). Methods: In this case-control study, genotypes of HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 loci were obtained from 1067 cases with classic T1D, 1062 cases with LADA, and 1107 normal controls using next-generation sequencing. Results: Despite 4 alleles shared between classic T1D and LADA (protective: A*02:07 and B*46:01; susceptible: B*54:01 and C*08:01), 7 Class I alleles conferred risk exclusively for classic T1D (A*24:02, B*15:02, B*15:18, B*39:01, B*40:06, B*48:01, and C*07:02) whereas only A*02:01 was an additional risk factor for LADA. Class I alleles affected a wide spectrum of T1D clinical features, including positive rate of protein tyrosine phosphatase autoantibody and zinc transporter 8 autoantibody (A*24:02), C-peptide levels (A*24:02), and age at diagnosis (B*46:01, C*01:02, B*15:02, C*07:02, and C*08:01). By contrast, except for the detrimental effect of C*08:01 on C-peptide concentrations in LADA, no other Class I associations with clinical characteristics of LADA could be reported. The addition of Class I alleles refined the risk model consisting only of DR-DQ data in classic T1D while the overall predictive value of the LADA risk model comprising both Class I and II information was relatively low. Conclusion: The attenuated HLA Class I susceptibility to LADA was indicative of a less deleterious immunogenetic nature compared with classic T1D. These autoimmune diabetes-related Class I variants might serve as additional markers in future screening among Chinese people. [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]

Aims: To investigate glycaemic variability (GV) patterns in patients with type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). Materials and Methods: A total of 842 subjects (510 T1D, 105 LADA, 227 T2D) were enrolled and underwent 1 week of continuous glucose monitoring (CGM). Clinical characteristics and CGM parameters were compared among T1D, LADA, and T2D. LADA patients were divided into two subgroups based on glutamic acid decarboxylase autoantibody titres (≥180 U/mL [LADA‐1], <180 U/mL [LADA‐2]) and compared. The C‐peptide cut‐offs for predicting a coefficient of variation (CV) of glucose ≥36% and a time in range (TIR) > 70% were determined using receiver operating characteristic analysis. Results: Twenty‐seven patients (9 T1D, 18 T2D) were excluded due to insufficient CGM data. Sex, diabetes duration and HbA1c were comparable among the three groups. Fasting and 2‐h postprandial C‐peptide (FCP, 2hCP) increased sequentially across T1D, LADA, and T2D. T1D and LADA patients had comparable TIR and GV, whereas those with T2D had much higher TIR and lower GV (p < 0.001). The GV of LADA‐1 was close to that of T1D, while the GV of LADA‐2 was close to that of T2D. CP exhibited the strongest negative correlation with GV. The cut‐offs of FCP/2hCP for predicting a CV ≥ 36% and TIR >70% were 121.6/243.1 and 128.9/252.8 pmol/L, respectively. Conclusions: GV presented a continuous spectrum across T1D, LADA‐1, LADA‐2, and T2D. More frequent glucose monitoring is suggested for patients with impaired insulin secretion. Clinical Trail Registration: Chinese Clinical Trial Registration (ChiCTR) website approved by WHO; http://www.chictr.org.cn/ ‐ ChiCTR2200065036 [ABSTRACT FROM AUTHOR]