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.

AIMS: This 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). METHODS: This 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. RESULTS: HCV 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). CONCLUSIONS: LADA 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.

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

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.

The worldwide prevalence of latent autoimmune diabetes of adults among adult-onset diabetic individuals: a systematic review and meta-analysis.

PURPOSE: The actual global burden of Latent Autoimmune Diabetes of Adults (LADA) remains unknown even though its prevalence is almost equal to the type 1 form of diabetes. Hence the present systematic review and meta-analysis were performed to estimate the prevalence of LADA among diabetic individuals using the studies published at global levels. METHODS: A comprehensive literature revival was performed to identify articles on the prevalence of LADA published till 2023. The prevalence estimates were calculated using DerSimonian and Laird random-effects models with a heterogeneity measure by Cochrane Q and I2 statistics. Publication bias was assessed by the Doi plot and Luis Furuya-Kanamori asymmetry index (LFKindex). P < 0.05 was considered statistically significant. RESULTS: The overall pooled prevalence of LADA obtained from a total of 51,725 diabetic individuals was found to be 8.9% (95%CI 7.5-10.4, P < 0.001) with a prevalence range of 2.3% in to 18.9% in United Arab Emirates and Bahrain respectively. Subgroup analysis of LADA in the context of the IDF geographic regions showed a higher prevalence in North America (13.5%), 9.5% in Middle East and North Africa, 9.4% in Africa, 9.2% in South East Asia, 8.3% in Western Pacific and the lowest prevalence of 7.0% in Europe. CONCLUSION: The Meta-analysis revealed a worldwide prevalence of LADA as 8.9%, with the highest prevalence in Bahrain and the lowest in United Arab Emirates. Further, the higher prevalence in some IDF regions and the inconsistent association between socioeconomic status and LADA recommend more research in the future.

Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis.

Antioxidant vitamins C and E are inversely associated with type 1 diabetes (T1D). We investigated if antioxidants are also associated with latent autoimmune diabetes in adults (LADA), with low (LADAlow) and high (LADAhigh) autoantibody levels, type 2 diabetes (T2D), and estimates of beta cell function (HOMA-B) and insulin resistance (HOMA-IR). We used Swedish case-control data with incident cases of LADA (n = 584) and T2D (n = 1989) and matched population-based controls (n = 2276). Odds ratios (OR) and 95% confidence intervals (CI) were calculated per one standard deviation higher beta-carotene, vitamin C, vitamin E, selenium, and zinc intakes. Two-sample Mendelian randomization (MR) analyses assessed causality between genetically predicted circulating antioxidants and LADA, T1D, and T2D, using summary statistics from genome-wide association studies. Among the antioxidants, vitamins C and E were inversely associated with LADAhigh (OR 0.84, CI 0.73, 0.98 and OR 0.80, CI 0.69, 0.94 respectively), but not with LADAlow or T2D. Vitamin E was also associated with higher HOMA-B and lower HOMA-IR. MR analyses estimated an OR of 0.50 (CI 0.20, 1.25) for the effect of vitamin E on T1D, but did not support causal relationships between antioxidants and either LADA or T2D. In conclusion, vitamin E may have a protective effect on autoimmune diabetes, possibly through preserved beta cell function and less insulin resistance.

Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults.

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 ).

Latent autoimmune diabetes in adults in China.

Latent autoimmune diabetes in adults (LADA) is a type of diabetes caused by slow progression of autoimmune damage to pancreatic beta cells. According to the etiological classification, LADA should belong to the autoimmune subtype of type 1 diabetes (T1D). Previous studies have found general immune genetic effects associated with LADA, but there are also some racial differences. Multicenter studies have been conducted in different countries worldwide, but it is still unclear how the Chinese and Caucasian populations differ. The epidemiology and phenotypic characteristics of LADA may vary between Caucasian and Chinese diabetic patients as lifestyle, food habits, and body mass index differ between these two populations. The prevalence of LADA in China has reached a high level compared to other countries. The prevalence of LADA in China has reached a high level compared to other countries, and the number of patients with LADA ranks first in the world. Previous studies have found general immune genetic effects associated with LADA, but some racial differences also exist. The prevalence of LADA among newly diagnosed type 2 diabetes patients over the age of 30 years in China is 5.9%, and LADA patients account for 65% of the newly diagnosed T1D patients in the country. As a country with a large population, China has many people with LADA. A summary and analysis of these studies will enhance further understanding of LADA in China. In addition, comparing the similarities and differences between the Chinese and the Caucasian population from the perspectives of epidemiology, clinical, immunology and genetics will help to improve the understanding of LADA, and then promote LADA studies in individual populations.

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

BACKGROUND: The Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressive Type 1 diabetes subgroup with onset during middle age. Studies report that about 10% of adults initially diagnosed with clinical Type 2 diabetes (T2D) have LADA. Inappropriate diagnosis and mismanagement of the LADA can increase the risk of diabetic complications, which affect the quality of life and is the cause of increased mortality. In low-income countries setting, data regarding the magnitude of LADA is limited. We carried out this study to estimate the burden of misdiagnosed LADA among T2D patients in selected health facilities in Dar es Salaam and to bring awareness to the use of Glutamic Acid Decarboxylase (GAD) autoantibody in screening for LADA. METHODOLOGY: We enrolled 186 phenotypically T2D patients in this cross-sectional study, through a standardized data collection tool we obtained participants' demographic and clinical information. For testing GAD levels, we used a double-antibody Enzyme-Linked Immunosorbent Assay (ELISA). The Fisher's Exact and student t-tests were used to test the significance of the statistical associations of the glycaemic control and diabetes complications between T2D and LADA. RESULTS: Out of 186 patients, 156 gave conclusive GAD Ab ELISA reading with LADA accounting for 5.1% (95% CI: 2.5 - 10.0). The mean age of subjects was 54.3 years (Range: 33-85 years). The parameters such as mean age, family history of diabetes mellitus status, Fasting Blood Glucose, clinical characteristics, and complications did not show significant statistical differences between patients with LADA and Type 2 diabetes. However, all LADA- Human Immunodeficiency Virus (HIV) comorbid patients had retinopathy, which was statistically insignificant in 20 (87%) T2D-HIV comorbid patients (p = 0.669). Neither neuropathy, nephropathy, nor Diabetic Mellitus (D.M.) foot syndrome was observed among LADA-HIV comorbid patients. Nevertheless, 22 (95.7%), 3 (13%), and 2 (8.7%) of T2D-HIV comorbidity had neuropathy, nephropathy, or D.M. foot syndrome, respectively. CONCLUSIONS: The study established a LADA prevalence of 5.1% among T2D patients and has shown the role of GAD autoantibody in the screening for LADA. The study calls for a well- designed larger longitudinal study to generate strong evidence on the association of risk factors and complications associated with the LADA. This will develop robust evidence on the association of risk factors and complications associated with the LADA and T2D.

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

AIM: To investigate the prevalence and clinical features of latent autoimmune diabetes in youth (LADY) diagnosed between 15 and 29 years old as a component of an age-related autoimmune diabetes spectrum. RESEARCH DESIGN AND METHODS: This nationwide, multicenter, cross-sectional study continuously included 19,100 newly diagnosed diabetes patients over 15 years old across China. LADY patients were screened from 1803 subjects aged between 15 and 29 years old, with the type 2 diabetes (T2D) phenotype and positive autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated-2 (IA-2A) or zinc transporter-8 (ZnT8A). The clinical features of LADY, including metabolic status, ß-cell function and insulin resistance, were investigated and compared with those of latent autoimmune diabetes in adults (LADA) identified from 17,297 other subjects over 30 years old. The age-related characteristics of the latent autoimmune diabetes spectrum were explored. RESULTS: A total of 135 subjects were diagnosed as LADY, accounting for 9.0% of the T2D phenotypic youth. Compared with autoantibody-negative T2D patients, LADY patients had fewer metabolic syndrome, less insulin resistance and poorer ß-cell function, which were closely related to their autoantibody status (all p < 0.05). After stratifying LADA according to age, the GADA titer decreased across the LADY, "Y-LADA" (young LADA, onset age < 60 years old) and "E-LADA" (elderly LADA, onset age ≥ 60 years old) groups, while the prevalence of metabolic syndrome and level of ß-cell function increased (all p < 0.05). CONCLUSIONS: A high prevalence of LADY exists in youth with T2D phenotype. Latent autoimmune diabetes forms a continuous age-related spectrum from LADY to LADA, in which LADY shows greater autoimmunity.

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

BACKGROUND We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS The study recruited 930 patients aged ≥18 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298). RESULTS Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving b cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=-8.249-0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)-0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%). CONCLUSIONS This model can be applied to people newly diagnosed with T2DM. When Y ≥0.0472, total autoantibody screening is recommended to assess LADA.

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

AIM: To search for risk factors that could predict progression in latent autoimmune diabetes in adults (LADA) and compare them with those for type 2 diabetes. MATERIALS AND METHODS: This study included 175 participants with LADA (autoantibody positive, without insulin treatment ≥1 year after diagnosis) and 2331 participants with type 2 diabetes (autoantibody negative, without insulin treatment ≥1 year after diagnosis) from the HUNT2 and HUNT3 surveys. We used Cox regression models and receiver operating characteristic curve analysis to identify predictive factors for progression to insulin dependency within 10 years. RESULTS: Low C-peptide levels (<0.3 nmol/L) predicted progression to insulin dependency within 10 years in both LADA (hazard ratio [HR] 6.40 [95% CI, 2.02-20.3]) and type 2 diabetes (HR 5.01 [95% CI, 3.53-7.10]). In addition, a high glutamic acid decarboxylase autoantibody (GADA) level (HR 5.37 [95% CI, 1.17-24.6]) predicted progression in LADA. Together, these two factors had a discriminatory power between non-progressors and progressors of area under the curve (AUC) of 0.86 (95% CI, 0.80-0.93). In type 2 diabetes, younger age at diagnosis (<50 years: HR 2.83 [95% CI, 1.56-5.15]; 50-69 years: HR 2.11 [95% CI, 1.19-3.74]), high HbA1c levels (≥53 mmol/mol, HR 2.44 [95% CI, 1.72-3.46]), central obesity (HR 1.65 [95% CI, 1.06-2.55]) and a body mass index of more than 30 kg/m2 (HR 1.73 [95% CI, 1.23-2.41]) were independent predictors. Together with C-peptide they reached an AUC of 0.79 (95% CI, 0.76-0.82). CONCLUSION: Factors predicting progression to insulin dependence are partly similar and partly dissimilar between LADA and type 2 diabetes. A constellation of low C-peptide and high GADA levels identifies LADA patients who are probable to progress to insulin dependence.

Critical Amino Acid Variants in HLA-DRB1 and -DQB1 Allotypes in the Development of Classical Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Japanese Population.

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

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

Latent autoimmune diabetes of adults (LADA) is typically defined as a new diabetes diagnosis after 35 years of age, presenting with clinical features of type 2 diabetes, in whom a type 1 diabetes-associated islet autoantibody is detected. Identifying autoimmune diabetes is important since the prognosis and optimal therapy differ. However, the existing LADA definition identifies a group with clinical and genetic features intermediate between typical type 1 and type 2 diabetes. It is unclear whether this is due to 1) true autoimmune diabetes with a milder phenotype at older onset ages that initially appears similar to type 2 diabetes but later requires insulin, 2) a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or 3) a heterogeneous group resulting from difficulties in classification. Herein, we suggest that difficulties in classification are a major component resulting from defining LADA using a diagnostic test-islet autoantibody measurement-with imperfect specificity applied in low-prevalence populations. This yields a heterogeneous group of true positives (autoimmune type 1 diabetes) and false positives (nonautoimmune type 2 diabetes). For clinicians, this means that islet autoantibody testing should not be undertaken in patients who do not have clinical features suggestive of autoimmune diabetes: in an adult without clinical features of type 1 diabetes, it is likely that a single positive antibody will represent a false-positive result. This is in contrast to patients with features suggestive of type 1 diabetes, where false-positive results will be rare. For researchers, this means that current definitions of LADA are not appropriate for the study of autoimmune diabetes in later life. Approaches that increase test specificity, or prior likelihood of autoimmune diabetes, are needed to avoid inclusion of participants who have nonautoimmune (type 2) diabetes. Improved classification will allow improved assignment of prognosis and therapy as well as an improved cohort in which to analyze and better understand the detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes.

Low rate of latent autoimmune diabetes in adults (LADA) in patients followed for type 2 diabetes: A single center's experience in Turkey.

OBJECTIVE: In this study, we aimed to determine the frequency of and the clinical and metabolic features of patients with latent autoimmune diabetes in adults (LADA) at a single center in Turkey. METHODS: Patients over 30 years of age diagnosed with type 2 diabetes who did not require insulin for a minimum of 6 months following diagnosis were included. Data from 324 patients (163 women; 161 men), with a mean age of 54.97 ± 7.53 years, were analyzed in the study. Levels of antibodies to glutamate decarboxylase (anti-GAD) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. RESULTS: Anti-GAD positivity was identified in 5 patients (1.5%). Family history of diabetes, body mass index (BMI), age, sex distribution, insulin resistance, serum triglycerides, high-density lipoprotein, and low-density lipoprotein were similar in the LADA and type 2 diabetes patients. Median HbA1c was significantly higher (10.8% vs. 7.38%, p = 0.002) and fasting C-peptide was lower (0.75 ng/mL vs. 2.82 ng/mL, p = 0.009) in patients with LADA compared to in those with type 2 diabetes. Among the 5 patients with LADA, 4 were positive for antithyroid peroxidase antibodies. The median disease duration was relatively shorter among patients with LADA (4 years vs. 7 years, p = 0.105). CONCLUSION: We observed a LADA frequency of 1.5% among Turkish patients followed for type 2 diabetes. The presence of obesity and metabolic syndrome did not exclude LADA, and patients with LADA had worse glycemic control than patients with type 2 diabetes did.

Combined lifestyle factors and the risk of LADA and type 2 diabetes - Results from a Swedish population-based case-control study.

AIMS: We investigated the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes in relation to a healthy lifestyle, the proportion of patients attributable to an unhealthy lifestyle, and the influence of family history of diabetes (FHD) and genetic susceptibility. METHODS: The population-based study included incident LADA (n = 571), type 2 diabetes (n = 1962), and matched controls (n = 2217). A healthy lifestyle was defined by BMI < 25 kg/m2, moderate-to-high physical activity, a healthy diet, no smoking, and moderate alcohol consumption. We estimated odds ratios (OR) with 95% confidence intervals (CIs) adjusted for age, sex, education, and FHD. RESULTS: Compared to a poor/moderate lifestyle, a healthy lifestyle was associated with a reduced risk of LADA (OR 0.51, CI 0.34-0.77) and type 2 diabetes (OR 0.09, CI 0.05-0.15). A healthy lifestyle conferred a reduced risk irrespective of FHD and high-risk HLA genotypes. Having a BMI < 25 kg/m2 conferred the largest risk reduction for both LADA (OR 0.54, CI 0.43-0.66) and type 2 diabetes (OR 0.12, CI 0.10-0.15) out of the individual items. CONCLUSION: People with a healthy lifestyle, especially a healthy body weight, have a reduced risk of LADA including those with genetic susceptibility to diabetes.

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

Latent autoimmune diabetes in adults (LADA) is still a poorly characterized entity. However, its prevalence may be higher than that of classical type 1 diabetes. Patients with LADA are often misclassified as type 2 diabetes. The underlying autoimmune process against ß-cell has important consequences for the prognosis, comorbidities, treatment choices and even patient-reported outcomes with this diabetes subtype. However, there is still an important gap of knowledge in many areas of clinical relevance. We are herein focusing on the state of knowledge of relevant clinical issues than may help in the diagnosis and management of subjects with LADA.

Risk of cardiac autonomic neuropathy in latent autoimmune diabetes in adults is similar to type 1 diabetes and lower compared to type 2 diabetes: A cross-sectional study.

AIMS: Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life-threatening complication of diabetes, also varies depending on diabetes type. METHODS: In this cross-sectional study, 43 adults with LADA, 80 with type 1 diabetes and 61 with type 2 diabetes were screened for cardiac autonomic neuropathy with recommended tests. Logistic regression models were used to test differences between diabetes types adjusting for confounders. RESULTS: Cardiac autonomic neuropathy was diagnosed in 17 (40%) participants with LADA, 21 (26%) participants with type 1 diabetes and 39 (64%) participants with type 2 diabetes (p < 0.001). The odds ratio (OR) for cardiac autonomic neuropathy in type 1 diabetes and in type 2 diabetes compared to LADA were 0.54 (95% CI: 0.25-1.20, p-value: 0.13) and 2.71 (95% CI: 1.21-6.06, p-value 0.015) respectively. Smoking (adj OR 3.09, 95% CI: 1.40-6.82, p-value: 0.005), HDL cholesterol (adj OR 0.29, 95% CI: 0.09-0.93, p-value: 0.037) and hypertension (adj OR 2.11, 95% CI: 1.05-4.24, p-value: 0.037) were independent modifiable risk factors for cardiac autonomic neuropathy. Differences among diabetes types did not change after correction for confounders. CONCLUSIONS: This is the first study offering a comparative evaluation of cardiac autonomic neuropathy among LADA, type 1 and type 2 diabetes, showing a lower risk of cardiac autonomic neuropathy in LADA compared to type 2 diabetes and similar compared to type 1 diabetes. This disparity was not due to differences in age, metabolic control or cardiovascular risk factors.

Low rate of latent autoimmune diabetes in adults (LADA) in patients followed for type 2 diabetes: A single centers experience in Turkey

ABSTRACT Objective In this study, we aimed to determine the frequency of and the clinical and metabolic features of patients with latent autoimmune diabetes in adults (LADA) at a single center in Turkey. Subjects and methods Patients over 30 years of age diagnosed with type 2 diabetes who did not require insulin for a minimum of 6 months following diagnosis were included. Data from 324 patients (163 women; 161 men), with a mean age of 54.97 ± 7.53 years, were analyzed in the study. Levels of antibodies to glutamate decarboxylase (anti-GAD) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Results Anti-GAD positivity was identified in 5 patients (1.5%). Family history of diabetes, body mass index (BMI), age, sex distribution, insulin resistance, serum triglycerides, high-density lipoprotein, and low-density lipoprotein were similar in the LADA and type 2 diabetes patients. Median HbA1c was significantly higher (10.8% vs. 7.38%, p = 0.002) and fasting C-peptide was lower (0.75 ng/mL vs. 2.82 ng/mL, p = 0.009) in patients with LADA compared to in those with type 2 diabetes. Among the 5 patients with LADA, 4 were positive for antithyroid peroxidase antibodies. The median disease duration was relatively shorter among patients with LADA (4 years vs. 7 years, p = 0.105). Conclusion We observed a LADA frequency of 1.5% among Turkish patients followed for type 2 diabetes. The presence of obesity and metabolic syndrome did not exclude LADA, and patients with LADA had worse glycemic control than patients with type 2 diabetes did.

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

PURPOSE: Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 (TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609. METHODS: We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (≥ 30 minutes of moderate activity 3 times/week) self-reported leisure time PA, compared to sedentariness. RESULTS: High PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype. MAIN CONCLUSIONS: Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.

Abnormal Neutrophil Transcriptional Signature May Predict Newly Diagnosed Latent Autoimmune Diabetes in Adults of South China.

Objective: Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of ß-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA. Methods: Peripheral blood neutrophils were isolated from newly diagnosed LADA patients (n = 5) and age-and sex-matched healthy controls (n = 5). The Transcriptomic signature was determined by RNA sequencing (RNA-seq). Differentially expressed genes (DEG) were screened, followed by analyzing downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Real-time polymerase chain reaction (qPCR) was applied for validation in LADA patients (n = 9) and age-and sex-matched healthy controls (n = 18), including sequencing samples. Results: Compared with controls, 4105 DEG were screened in LADA patients, including 2661 upregulated and 1444 downregulated DEG. In GO analysis, DEG are mainly involved in leukocyte degranulation, myeloid cell differentiation, and immune response-regulating signaling. The top enriched KEGG pathways included cytokine-cytokine receptor interaction, adhesion molecule signaling, nuclear factor-κB (NF-κB) signaling and Th17 cell differentiation. Consistent with RNA-seq results, SELL, ITGA4, ITGAM, NCF4, ARHGAP3, and CLDN15 are upregulated in neutrophils by qPCR. Conclusion: The present study results provided a profile of DEG in the newly diagnosed LADA of south China. Our study reveals an abnormality in neutrophil disposition at the transcriptional level in LADA. Several essential genes may be involved in of LADA's pathological process, which may be useful to guide prediction for LADA and further investigation into the pathogenesis for this disease.