Autoimmune Diabetes In Adults Research Articles

Sex-driven factors associated with anxiety and depression in autoimmune diabetes.

To analyze the prevalence of anxiety and depression in a large cohort of adults with autoimmune diabetes, identifying sex-driven associated factors. In this cross-sectional study, we enrolled 553 consecutive adults with Type 1 diabetes mellitus or latent autoimmune diabetes in adults who came to the Division of Endocrinology of the S.Orsola-Malpighi Polyclinic, Bologna (Italy),to receive their second dose of SARS-CoV-2 vaccine. We administered the questionnaires: Hospital Anxiety and Depression Scale, Diabetes Distress Scale, Diabetes-related Quality of Life, Diabetes Treatment Satisfaction Questionnaire. We collected clinical and biochemical data and 14 days glucose metrics in patients with sensor use > 70% in a time span of ± 4months from the questionnaires' administration. We excluded 119 patients from our analyses with missing data (final cohort n = 434: 79% of those enrolled). Anxiety and depression prevalence was respectively 30.4% and 10.8%. According to the multivariate analysis, higher diabete-related emotional burden, lower treatment satisfaction, but not physician-related distress, were risk factors for anxiety and depression; female sex was associated with anxiety (OR 0.51, 95% 0.31-0.81; p = 0.005); in women, depression was associated with increasing age (males vs. females OR 0.96 per 1year increase, 95% CI 0.92-1.00; p = 0.036), whilst in men with HbA1c (OR 1.08 per 1mmol/mol increase, 95% CI 1.03-1.13; p = 0.002). Nearly 1/3 of patients with autoimmune diabetes suffers from anxiety and 1/10 from depression. These conditions are associated with independent modifiable and non-modifiable characteristics. For depression, these characteristics differ between males and females.

The association between serum cholecalciferol level and lipid profile in patients with latent autoimmune diabetes in adults

The association between serum cholecalciferol level and lipid profile in patients with latent autoimmune diabetes in adults

The dependence of anxiety and depression indicators on serum cholecalciferol level in patients with latent autoimmune diabetes in adults

The dependence of anxiety and depression indicators on serum cholecalciferol level in patients with latent autoimmune diabetes in adults

Autoimmune polyglandular syndrome type 2: a clinical case of a rare combination of primary adrenal insufficiency and latent autoimmune diabetes in adults

Autoimmune polyglandular syndrome type 2: a clinical case of a rare combination of primary adrenal insufficiency and latent autoimmune diabetes in adults

Characterization of the gut bacterial and viral microbiota in latent autoimmune diabetes in adults

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced. Amplicon sequence variants (ASVs) were generated with DADA2 and annotated to the SILVA database. The gut virome was sequenced, using a viral particle enrichment and metagenomics approach, assembled, and quantified to describe the composition of the viral community. Comparison of the bacterial alpha- and beta-diversity measures revealed that the gut bacteriome of individuals with LADA resembled that of individuals with T2D. Yet, specific genera were found to differ in abundance in individuals with LADA compared with T1D and T2D, indicating that LADA has unique taxonomical features. The virome composition reflected the stability of the most dominant order Caudovirales and the families Siphoviridae, Podoviridae, and Inoviridae, and the dominant family Microviridae. Further studies are needed to confirm these findings.

Safety of native glucose-dependent insulinotropic polypeptide in humans

In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1-42) in human studies with administration of synthetic human GIP. We searched the PubMed database for all trials investigating synthetic human GIP(1-42) administration. A total of 67 studies were included. Study duration ranged from 30minutes to 6 days. In addition to healthy individuals, the studies included individuals with impaired glucose tolerance, type 2 diabetes, type 1 diabetes, chronic pancreatitis and secondary diabetes, latent autoimmune diabetes in adults, diabetes caused by a mutation in the hepatocyte nuclear factor 1-alpha gene, end-stage renal disease, chronic renal insufficiency, critical illness, hypoparathyroidism, or cystic fibrosis-related diabetes. Of the included studies, 78% did not mention safety events, 10% of the studies reported that no safety events were observed in relation to GIP administration, and 15% of the studies reported safety events in relation to GIP administration with most frequently reported event being a moderate and transient increased heart rate. Gastrointestinal safety events, and changes in blood pressure were also reported. Plasma concentration of active GIP(1-42) increased linearly with dose independent of participant phenotype. There was no significant correlation between achieved maximal concentration of GIP(1-42) and reported safety events. Clearance rates of GIP(1-42) were similar between participant groups. In conclusion, the available data indicate that GIP(1-42) in short-term (up to 6 days) infusion studies is generally well-tolerated. The long-term safety of continuous GIP(1-42) administration is unknown.

Enhancing outcome prediction by applying the 2019 WHO DM classification to adults with hyperglycemic crises: A single-center cohort in Thailand

Background and aimsHyperglycemic crisis is a metabolic catastrophe which can occur in any type of diabetes. In 2019, the World Health Organization (WHO) revised the classification of diabetes mellitus (DM) and established two new hybrid forms, latent autoimmune diabetes in adults (LADA) and ketosis-prone type 2 diabetes (T2D). This study aimed to determine clinical outcomes after a hyperglycemic crisis event in people with diabetes classified subtypes by 2019 WHO DM classification. MethodsA five-year (2015–2019) retrospective study of adult patients admitted with hyperglycemic crises was conducted. Types of diabetes were recategorized based on the 2019 WHO DM classification. Clinical characteristics, in-admission treatment and complications, long-term follow-up outcomes, and mortality were collected, analyzed, and compared. ResultsA total of 185 admissions occurred in 136 patients. The mean age was 50.6 ± 18.4 years (49.3 % men). The annual average incidence of hyperglycemic crises was 5.2 events/1000 persons. The proportion of type 1 diabetes, T2D, LADA, ketosis-prone T2D, and pancreatic DM were 15.4 %, 69.1 %, 2.2 %, 11 %, and 2.2 %, respectively. In-hospital mortality was 3.7 % while cumulative mortality totaled 19.1 %. During the 24-month follow-up, ketosis-prone T2D had the highest success of insulin discontinuation (HR 6.59; 95 % CI 6.69–319.4; p < 0.001), while T2D demonstrated the highest mortality compared to others (HR, 2.89; 95%CI 1.15–6.27; p = 0.02). ConclusionThe reclassification of diabetes based on 2019 WHO DM classification helped elucidate differences in long-term outcomes and mortality among DM types. The new classification, which separates ketosis-prone T2D from standard T2D, should be encouraged in clinical practice for precise and individualized management.

An Overview of Differential miRNA Profile of Patients with Latent Autoimmune Diabetes in Adults (LADA)

Diabetes mellitus (DM) is a metabolic and chronic disease characterized by hyperglycemia developing with impaired pancreatic beta cell activity, decreased insulin secretion, icreased insulin resistance, and accordingly impaired carbohydrate, protein and lipid metabolism. DM is classified as type 1, type 2, gestational and other forms of diabetes according to the characteristic properties such as age of onset, insulin dependency, micro- and macrovascular complications. Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes that begins in adulthood without insulin dependency for glycemic control at least in the first six months after diagnosis. Owing to the common genetic, immunologic, and metabolic features LADA is misdiagnosed with type 1 or type 2 diabetes. Therefore, it is need a biomarkers that ease the diagnosis of LADA. MicroRNAs are small non-coding RNAs involved in biological processes and regulate the response of target tissues to insulin as well as insulin production, signaling and release, insulin resistance, and glucose homeostasis. Dysregulation in miRNA expression can lead to impairment of glucose metabolism. Circulating miRNA are associated with different types of diabetes and have a potential to discriminate them. So, we reviewed the miRNAs that gene expressions levels which change in LADA compared to type 1 and type 2 diabetes.

A novel subpopulation of monocytes with a strong interferon signature indicated by SIGLEC-1 is present in patients with in recent-onset type 1 diabetes.

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. 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. 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 (cluster4) 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. 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. RNA-seq data have been deposited in the GSA human database ( https://ngdc.cncb.ac.cn/gsa-human/ ) under accession number HRA003649.

Multifaceted nature of young-onset diabetes - can genomic medicine improve the precision of diagnosis and management?

Young-onset type 2 diabetes (YOD), defined as diabetes diagnosis before age 40, has an aggressive clinical course with premature mortality, in part due to long disease duration and lack of evidence to guide diagnosis and management. Autoimmune type 1 diabetes, maturity-onset diabetes of the young (MODY), and latent autoimmune diabetes in adults (LADA) are subtypes of diabetes in young people, which, however, cannot fully explain their complex clinical course. Similarly, family members carrying the same rare genetic variant of monogenic diabetes can have different presentations and outcomes. Ancestral heterogeneity, ecological transition, inter-ethnic differences in genomic architecture, and variations in living environment, lifestyles, access to care, and timeliness of diagnosis and treatment can influence the age of diagnosis and exposure to these cardiometabolic-renal risk factors. Despite the wealth of literature on genetic associations with diabetes, the familial cosegregation of rare variants and their relevance to YOD remains uncertain. This perspective was motivated by decades of clinical observations and learnings from an ongoing randomized controlled trial that uses biogenetic markers to classify patients with YOD for improving outcomes. Apart from highlighting the need to use family-based studies to improve the precision of diagnosis, we discussed atypical causes for diabetic ketoacidosis and the importance of lifecourse and psychosocial-behavioral factors in patients with YOD. Apart from detailed clinical evaluation, we propose using plasma C peptide, homeostasis model of assessment (HOMA) indexes, autoantibodies, and polygenic risk scores to stratify risk, classify diabetes subtypes, and personalize treatment in YOD. To achieve these goals, we advocate changing the practice environment and team structure to enable physicians to use the insights they learn from patients and their family members to implement precision medicine and improve the outlook of these high-risk individuals.

Retracted: Oxidative Stress and Its Related Factors in Latent Autoimmune Diabetes in Adults.

[This retracts the article DOI: 10.1155/2021/5676363.].

In latent autoimmune diabetes in adults, mortality was similar to T2DM but retinopathy was higher at 5.9 y.

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.

Hsa_circRNA_405498 and hsa_circRNA_100033 serve as potential biomarkers for differential diagnosis of type 1 diabetes.

The role of circular RNAs (circRNAs) in type 1 diabetes (T1D) is largely unknown. We aimed to identify some circRNAs as differential diagnostic biomarkers for T1D to discriminate patients with latent autoimmune diabetes in adults (LADA), and type 2 diabetes (T2D). The circRNA expression profiles were determined by Arraystar human circRNA microarray in T1D compared to controls (n = 6 each). The differentially expressed circRNAs were validated by RT-qPCR using a validation cohort with 20 T1D and 20 controls. The diagnostic performances of the candidate circRNAs and the clinical parameters were assessed using the logistic least absolute shrinkage and selection operator (LASSO) regression model in a larger cohort with 457 subjects including patients with T1D, T2D and LADA, and controls. We identified 110 differentially expressed circular transcripts (53 upregulated and 57 downregulated) in T1D patients compared with controls. Further analysis showed that the levels of hsa_circRNA_405498 and hsa_circRNA_100033 were significantly downregulated in T1D compared to controls (both P < 0.05). Moreover, the expression levels of these two circRNAs showed sequential downregulation from controls, patients with T2D, LADA, to T1D (P < 0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) plots in logistic LASSO regression model showed high diagnostic accuracy for combination model with the two circRNAs and some clinical parameters in discriminating T1D from LADA (AUC = 0.915), T2D (AUC = 0.993), and controls (AUC = 0.992). Our study demonstrated that hsa_circRNA_405498 and hsa_circRNA_100033 are promising novel differential diagnostic biomarkers for T1D.

Association of human leukocyte antigen (HLA) footprints with the comorbidity of latent autoimmune diabetes in adults (LADA) and hepatitis C virus (HCV) infection: A multicenter cross-sectional study

AimsThis study aims to investigate the interplay between hepatitis C virus (HCV) infection and major forms of diabetes: type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). MethodsThis multicenter study analyzed a cohort of 2699 diabetic and 7344 non-diabetic subjects who visited medical centers in China from 2014 to 2021. T1D, T2D, LADA, and HCV were diagnosed using standard procedures. High-throughput sequencing was conducted to identify genetic footprints of human leukocyte antigen (HLA) alleles and haplotypes at the DRB1, DQA1, and DQB1 loci. ResultsHCV infection was detected in 3 % (23/766) of LADA patients, followed by 1.5 % (15/977) of T2D patients, 1.4 % (13/926) of T1D patients, and 0.5 % (38/7344) of non-diabetic individuals. HCV prevalence was significantly higher in people with diabetes than in non-diabetic individuals (p < 0.01). HLA alleles (DQB1*060101, DQB1*040101) and haplotypes (DRB1*080302-DQA1*010301-DQB1*060101) in LADA patients with HCV revealed higher frequencies than in LADA patients without HCV (adjusted p < 0.03). Furthermore, a higher risk of diabetes complications was found among LADA patients with HCV infection (p < 0.001). ConclusionsLADA patients are susceptible to HCV infection, potentially associated with certain HLA alleles/haplotypes. Early diagnosis and treatment of HCV infection among people with diabetes are important for the management of severe complications.

Prevalence and Metabolic Characteristics of Patients with Latent Autoimmune Diabetes in Adults: A Cross-Sectional Study

Prevalence and Metabolic Characteristics of Patients with Latent Autoimmune Diabetes in Adults: A Cross-Sectional Study

Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?

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). 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 5-10years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Individuals who developed LADA did not have a higher prevalence of infectious disease 1-10years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1-3years. 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]). 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.

Association of RPS26 gene polymorphism with different types of diabetes in Chinese individuals.

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. 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. 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. 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.

Clinical value of lymphocyte count in autoimmune diabetic nephropathy.

In recent years, the prevalence of diabetic nephropathy (DN) has increased significantly. An increasing number of studies have shown that lymphocyte-associated inflammatory responses play a role in DN. This study aims to investigate the relationship between lymphocytes and DN in patients with autoimmune diabetes. The clinical data of 226 patients with Type 1 diabetes (T1D) and 79 patients with latent autoimmune diabetes in adults (LADA) were retrospectively studied and stratified according to the urinary albumin to creatinine ratio (ACR). Risk factors associated with DN were analyzed using correlation analysis and logistic regression. In T1D and LADA patients, systolic blood pressure (SBP), uric acid duration, and diabetes duration in patients with normoalbuminuria were lower or shorter than those in patients with macroalbuminuria (P<0.05). The lymphocyte count of T1D patients was significantly higher than that in LADA patients (P<0.05), while the neutrophil to lymphocyte ratio (NLR) of T1D patients was significantly lower than that in LADA patients (P<0.05). The lymphocyte count in the T1D patients with normoalbuminuria was lower than that those with macroalbuminuria (P<0.05). The NLR was lower in the T1D patients with macroalbuminuria than those with microalbuminuria and normoproteinuria (all P<0.01). Based on logistic regression analysis, lymphocytes were independently associated with DN in T1D after adjusting for various known risk factors such as course of disease, age, gender, dyslipidemia, hypertension, and smoking status. Analysis of the receiver operating characteristic curve of subjects predicting lymphocytes in normoalbuminuria showed that the area under the curve was 0.601 (95% CI 0.510 to 0.693, P=0.039), and when the cutoff value of lymphocytes was 2.332, the sensitivity was 37.0%, and the specificity was 82.5%. Lymphocyte counts in autoimmune diabetic patients are closely associated with DN, suggesting that lymphocyte-mediated inflammation may be involved in the pathogenesis of DN in autoimmune diabetic patients. This study provides a possible perspective for using lymphocytes as a potential biomarker for the early identification of individuals at risk for DN and potential therapeutic targets for DN.

Abstract 15063: Incidence and Risk Factors for Heart Failure in 20 000 Newly Diagnosed Diabetes Patients

Introduction: Heart Failure (HF) is a diabetes complication causing high mortality and morbidity but has received relatively limited attention compared to other complications such as acute myocardial infarction (AMI). Substantial residual HF risk remains after achieving current treatment targets, suggesting important additional pathophysiological mechanisms beyond conventional risk factors. Aim: to study the incidence and risk factors for HF in newly diagnosed diabetes patients. Methods: We used a contemporary, regional inception cohort (n=19,938) from Scania County in Sweden, to study the incidence and risk factors for HF from initial diabetes diagnosis. Biochemical and questionnaire data were collected within 1 year from initial diagnosis in newly diagnosed diabetes patients (&gt;90% participation rate). We combined baseline data with information on incident HF and AMI diagnoses from a nationwide patient register, and applied Cox-regression models for analysis. Results: A total of 819 patients (4%) had been diagnosed with HF before diabetes diagnosis (median 3 years earlier) and 1245 (6%) with AMI. The cumulative incidence of HF in patients free from HF at diabetes diagnosis was 5%, similar to AMI (3%), during up to 13 years follow-up (median 5 years). Of patients with incident HF, 27% had a prior AMI. No type 1 diabetes (T1D) patient had incident HF, while HF risk was similar in type 2 diabetes, latent autoimmune diabetes in adults (LADA) and secondary diabetes. In non-T1D diabetes patients, male sex (HR 1.52) and higher age at onset (HR 1.08), BMI (HR 1.04), and insulin resistance (HR 1.17) were independently associated with higher incidence of all-cause HF and HF without prior AMI (p&lt;0.05). Baseline fasting glucose, HbA1c and autoantibodies were not associated with HF. Conclusions: Our findings demonstrate high incidence of HF over the decade after initial diabetes diagnosis, comparable to AMI. We further identify insulin resistance, but not hyperglycemia or autoantibodies, as risk factor for HF.

L’eterogeneità del diabete autoimmune

Autoimmune diabetes is a heterogeneous disease, encompassing both type 1 diabetes, characterized by fast progression towards an insulin-dependent state, and latent autoimmune diabetes in adults (LADA), considered a less severe form of autoimmune diabetes with a mild metabolic decompensation. An extensive genetic, phenotypic, and humoral heterogeneity is recognized even within the group of people with LADA. In this review, we discuss the pathological and clinical heterogeneity of autoimmune diabetes, highlighting the current understanding and gaps in knowledge.