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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]

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.

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]

Diabetes is associated with numerous comorbidities, one of which is increased vulnerability to infections. This review will focus on how diabetes mellitus (DM) affects the immune system and its various components, leading to the impaired proliferation of immune cells and the induction of senescence. We will explore how the pathology of diabetes-induced immune dysfunction may have similarities to the pathways of "inflammaging", a persistent low-grade inflammation common in the elderly. Inflammaging may increase the likelihood of conditions such as rheumatoid arthritis (RA) and periodontitis at a younger age. Diabetes affects bone marrow composition and cellular senescence, and in combination with advanced age also affects lymphopoiesis by increasing myeloid differentiation and reducing lymphoid differentiation. Consequently, this leads to a reduced immune system response in both the innate and adaptive phases, resulting in higher infection rates, reduced vaccine response, and increased immune cells' senescence in diabetics. We will also explore how some diabetes drugs induce immune senescence despite their benefits on glycemic control.

Introduction: We designed and implemented a patient-centered, data-driven, holistic care model with evaluation of its impacts on clinical outcomes in patients with young-onset type 2 diabetes (T2D) for which there is a lack of evidence-based practice guidelines., Research Design and Methods: In this 3-year Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial, we evaluate the effects of a multicomponent care model integrating use of information and communication technology (Joint Asia Diabetes Evaluation (JADE) platform), biogenetic markers and patient-reported outcome measures in patients with T2D diagnosed at ≤40 years of age and aged ≤50 years. The JADE-PRISM group received 1 year of specialist-led team-based management using treatment algorithms guided by biogenetic markers (genome-wide single-nucleotide polymorphism arrays, exome-sequencing of 34 monogenic diabetes genes, C-peptide, autoantibodies) to achieve multiple treatment goals (glycated hemoglobin (HbA1c) <6.2%, blood pressure <120/75 mm Hg, low-density lipoprotein-cholesterol <1.2 mmol/L, waist circumference <80 cm (women) or <85 cm (men)) in a diabetes center setting versus usual care (JADE-only). The primary outcome is incidence of all diabetes-related complications., Results: In 2020-2021, 884 patients (56.6% men, median (IQR) diabetes duration: 7 (3-12) years, current/ex-smokers: 32.5%, body mass index: 28.40±5.77 kg/m 2 , HbA1c: 7.52%±1.66%, insulin-treated: 27.7%) were assigned to JADE-only (n=443) or JADE-PRISM group (n=441). The profiles of the whole group included positive family history (74.7%), general obesity (51.4%), central obesity (79.2%), hypertension (66.7%), dyslipidemia (76.4%), albuminuria (35.4%), estimated glomerular filtration rate <60 mL/min/1.73 m 2 (4.0%), retinopathy (13.8%), atherosclerotic cardiovascular disease (5.2%), cancer (3.1%), emotional distress (26%-38%) and suboptimal adherence (54%) with 5-item EuroQol for Quality of Life index of 0.88 (0.87-0.96). Overall, 13.7% attained ≥3 metabolic targets defined in secondary outcomes. In the JADE-PRISM group, 4.5% had pathogenic/likely pathogenic variants of monogenic diabetes genes; 5% had autoantibodies and 8.4% had fasting C-peptide <0.2 nmol/L. Other significant events included low/large birth weight (33.4%), childhood obesity (50.7%), mental illness (10.3%) and previous suicide attempts (3.6%). Among the women, 17.3% had polycystic ovary syndrome, 44.8% required insulin treatment during pregnancy and 17.3% experienced adverse pregnancy outcomes., Conclusions: Young-onset diabetes is characterized by complex etiologies with comorbidities including mental illness and lifecourse events., Trial Registration Number: NCT04049149., Competing Interests: Competing interests: JCNC and RCWM hold patents for using genetic markers to predict diabetes and its complications for personalized care. JCNC, RCWM and CL are cofounders of a start-up biotech company partially supported by the Technology Start-up Support Scheme for Universities (TSSSU) of the Hong Kong Government Innovation and Technology Commission., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The applicability of a UK-validated genetic risk score (GRS) was assessed in 158 participants in the Fremantle Diabetes Study Phase II diagnosed between 20 and <40 years of age with type 1 or type 2 diabetes or latent autoimmune diabetes of adults (LADA). For type 1 versus type 2/LADA, the area under the receiver operating characteristic curve (AUC) was highest for serum C-peptide (0.93) and lowest for the GRS (0.66). Adding age at diagnosis and body mass index to C-peptide increased the AUC minimally (0.96). The GRS appears of modest diabetes diagnostic value in young Australians., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Aims/introduction: Different types of diabetes show distinct genetic characteristics, but the specific genetic susceptibility factors remain unclear. Our study aimed to explore the associations between the ribosomal protein S26 (RPS26) gene rs1131017 polymorphisms and susceptibility to type 1 diabetes mellitus, latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus in the Chinese Han population, and their correlations with clinical features., Materials and Methods: Genotyping of the rs1131017 variant was carried out for 1,006 type 1 diabetes mellitus patients, 210 LADA patients, 642 type 2 diabetes mellitus patients and 2,099 control individuals., Results: We found that the rs1131017 C allele was a risk locus for both type 1 diabetes mellitus and LADA (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.33-1.69, P < 0.001; OR 1.31, 95% CI 1.04-1.64, P = 0.021, respectively). Nevertheless, this association was not found for type 2 diabetes mellitus. Carrying the C allele genotype was associated with a lower postprandial C-peptide for type 1 diabetes mellitus (OR 1.41, 95% CI 1.11-1.80, P = 0.006) and lower fasting C-peptide for LADA (OR 1.55, 95% CI 1.01-2.38, P = 0.047). Interestingly, a lower GC frequency was noted for LADA than for type 1 diabetes mellitus, regardless of classification based on age at diagnosis, C-peptide or glutamic acid decarboxylase antibody positivity., Conclusions: The RPS26 polymorphism was associated with susceptibility and clinical characteristics of type 1 diabetes mellitus and LADA in the Chinese population, but was not related to type 2 diabetes mellitus. Thus, it might serve as a novel biomarker for particular types of diabetes., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Source Citation: Wei Y, Herzog K, Ahlqvist E, et al. All-cause mortality and cardiovascular and microvascular diseases in latent autoimmune diabetes in adults. Diabetes Care. 2023;46:1857-1865. 37635682., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0107.