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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., (© 2022. The Author(s).)

Serum creatinine level begins to increase after a decrease in glomerular filtration rate (GFR) by 50% and more, so the question emerged about a more accurate method of determining GFR. The study aimed to determine the role of renal damage markers in the diagnosis of early-stage renal disease in patients with latent autoimmune diabetes in adults (LADA). We included 84 patients with diabetes mellitus (DM) and chronic kidney disease (CKD) caused by diabetic kidney disease (DKD), as well as 25 representatives of the control group. Patients were divided into three groups - 43 people with LADA, 21 with type 1 diabetes mellitus (T1DM), and 20 patients with type 2 diabetes mellitus (T2DM). GFR was assessed using six formulas after establishing the category of GFR and albuminuria. The GFR rate estimated by the CKD-EPI formula in patients with LADA and DKD did not significantly differ from that of CKD-EPI cysC, slightly different from MDRD GFR (10.6% higher, respectively) but 21.9% lower compared to CG formula. In patients with LADA and T1DM, GFR was higher in cases with existing albuminuria, regardless of the formulas used. Thus, the non albuminuria phenotype is accompanied by a greater degree of renal impairment, which indicates the need to determine serum cystatin C in the early stages of LADA. Cystatin C levels are the most accurate, early, and independent predictor of the development and progression of CKD in patients with DM, including LADA., Competing Interests: The authors declare no conflict of interest., (©2022 JOURNAL of MEDICINE and LIFE.)

Objectives: This study aimed to compare the prevalence of hypogonadism between male patients with latent autoimmune diabetes (LADA) and type 2 diabetes (T2DM) and investigate the risk factors for hypogonadism in these patients., Methods: This cross-sectional study evaluated 367 male patients with LADA (n=73) and T2DM (n=294) who visited the endocrinology department of Shanghai Tenth People's Hospital between January 2016 and October 2019 for diabetes management. Sex hormones, lipid profiles, sex hormone-binding globulin (SHBG), glycosylated hemoglobin A1c, beta-cell function, uric acid, and osteocalcin were determined in serum samples. Hypogonadism was defined as calculated free testosterone (cFT) less than 220 pmol/L along with the presence of symptoms (positive ADAM score)., Results: The rate of hypogonadism in the LADA and T2DM group were 8.2, and 21.7%, respectively (p=0.017). After adjusting possible confounders, the rate of hypogonadism in the LADA group was comparable to those of the T2DM group. Univariate logistic regressions demonstrated that age, BMI, fasting C-peptide, triglycerides, total cholesterol and uric acid were associated with hypogonadism in men with diabetes, BMI, triglycerides and estradiol were independent risk for hypogonadism in men with diabetes., Conclusion: This is the first evidence to explore the rate of hypogonadism in male patients with latent autoimmune diabetes (LADA). In the population requiring admission to a large urban hospital in China, the rate of hypogonadism was comparable to those of the T2DM group after adjusting for possible confounders. BMI, triglycerides and estradiol were independently associated with the presence of HH in male diabetic patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cai, Cui, Yang, Gao, Cheng, Sheng, Li, Sheng, Qu and Zhang.)

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/m 2 , 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/m 2 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2020 Diabetes UK.)

Objective: We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes., Methods: We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI ≥ 25 kg/m2) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP)., Results: The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO., Conclusions: Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA., (Copyright © 2019 Endocrine Society.)

Aim: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy., Methods: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy., Results: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA 1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters., Conclusions: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes., (© 2018 Diabetes UK.)

Aims: Latent autoimmune diabetes in adults (LADA) is diagnosed in up to 12% of adults with clinically diagnosed type 2 diabetes (T2D). LADA tends to have healthier cardiovascular (CV) risk profiles than T2D, but it remains uncertain whether the risk of CV events differs between the two. We examined the risk of CV events in patients enrolled in the United Kingdom Prospective Diabetes Study (UKPDS) according to LADA status., Materials and Methods: Diabetes autoantibodies (AAb) were measured in 5062 UKPDS participants. The incidence of major adverse CV events (MACE), defined as CV death, non-fatal myocardial infarction or non-fatal stroke, was compared in those with LADA (≥1 AAb test positive) and those without LADA (AAb negative)., Results: There were 567 participants (11.2%) with LADA. Compared with participants with T2D, they were younger, with higher mean HbA1c and HDL-cholesterol values, and with lower body mass index and total cholesterol and systolic blood pressure values (all P < 0.01). After a median (25th, 75th percentile) 17.3 (12.6-20.7) years of follow-up, MACE occurred in 157 (17.4 per 1000 person-years) participants with LADA and in 1544 (23.5 per 1000 person-years) participants with T2D (HR, 0.73; 95% confidence interval [CI], 0.62-0.86; P < 0.001). However, after adjustment for confounders, this difference was no longer significant (HR adj , 0.90; 95% CI, 0.76-1.07; P = 0.22)., Conclusions: In adults thought to have newly diagnosed T2D, the long-term risk of MACE was lower in those with LADA. However, this did not differ after adjustment for traditional CV risk factors, suggesting that measurement of AAb in addition to traditional CV risk factors will not aid in stratification of CV risk in clinically diagnosed T2D., (© 2019 John Wiley & Sons Ltd.)

Objective: Young-onset diabetes is heterogeneous in etiology and disease progression. We compared the incidence of diabetes-related complications and mortality in patients with young-onset type 2 diabetes with or without anti-GAD antibodies and patients with type 1 diabetes. We determined changes in glycemic control before and after commencement of insulin therapy stratified by antibody status., Research Design and Methods: Between 1994 and 2012, 1,504 consecutively enrolled patients with type 2 diabetes who had received a diagnosis at <40 years of age and had available anti-GAD antibody status and 251 patients with type 1 diabetes from the Hong Kong Diabetes Register were followed for incident cardiovascular disease (CVD), end-stage renal disease (ESRD), severe hypoglycemia, and all-cause mortality until June 2015. Information on insulin use and HbA 1c levels during follow-up was obtained., Results: Anti-GAD antibodies were positive in 8.1% of patients with type 2 diabetes (GAD + ). By multivariate Cox regression, patients with GAD + had a lower hazard of CVD (hazard ratio [HR] 0.43, P = 0.048), a higher hazard of severe hypoglycemia (HR 1.63, P = 0.032), and a similar hazard of ESRD and mortality compared with counterparts without anti-GAD antibodies (GAD - ). Compared with patients with type 1 diabetes, ESRD was more likely to develop (HR 2.91, P = 0.043) in patients with GAD + , but no differences were detected in the hazards of severe hypoglycemia, CVD, and mortality. Among new insulin users ( n = 304), patients with GAD + had larger reductions in HbA 1c than patients with GAD - after 12 months of insulin use (-2.30 ± 3.80% [25 ± 42 mmol/mol] vs -0.72 ± 1.86% [8 ± 20 mmol/mol], P = 0.05)., Conclusions: Anti-GAD positivity identifies a group of patients with a different prognosis compared with patients without antibodies and those with type 1 diabetes. Patients with GAD + responded differently to insulin compared with patients with GAD - ., (© 2019 by the American Diabetes Association.)

Aims/hypothesis: Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies., Methods: Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs with 95% CI., Results: In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA;

Background: Latent Autoimmune Diabetes in Adults (LADA) is the second most common form of diabetes, but data on its clinical course and prognosis are scarce. We compared long-term risk of mortality and cardiovascular outcomes in patients with LADA, type 2 diabetes mellitus (T2D), and insulin deficient diabetes (IDD)., Methods: We conducted a cohort study of 4368 adults with diabetes referred to the Department of Endocrinology, Odense University Hospital, Denmark, between 1997 and 2012. Data on comorbidity, cardiovascular outcomes and death were obtained from prospective medical databases. We compared adjusted hazard ratios (HRs) of mortality and cardiovascular outcomes for patients with LADA, T2D and IDD, respectively., Results: We included 327 patients with LADA, 3539 with T2D and 502 with IDD. At diagnosis, patients with LADA were older (50 years (IQR 37-59)) than IDD patients (40 years (IQR 28-52)), but younger than patients with T2D (55 years (IQR 45-64)). During a median follow-up period of 6.6 years (IQR 3.4-9.4), patients with IDD had higher mortality than patients with LADA, age- and gender-adjusted HR 2.2 (95% CI, 1.5-3.2). T2D also conferred higher mortality than LADA, HR 1.4 (95% CI, 1.0-1.9). Compared with LADA patients, cardiovascular outcome rates were increased both with IDD, HR 1.2 (95% CI, 0.7-2.0) and T2D, HR 1.2 (95% CI, 0.8-1.8), with the strongest association observed for T2D vs. LADA and acute myocardial infarction HR 1.7 (95% CI, 0.8-3.5)., Conclusion: LADA seems to be associated with lower mortality and lower risk of cardiovascular events, compared with both T2D and IDD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: LADA is probably the most prevalent form of autoimmune diabetes. Nevertheless, there are few data about cardiovascular disease in this group of patients. The aim of this study was to investigate the frequency of carotid atherosclerotic plaques in patients with LADA as compared with patients with classic type 1 diabetes and type 2 diabetes., Methods: Patients with LADA were matched for age and gender in different proportions to patients with type 2 diabetes, and classic type 1 diabetes. None of the patients had clinical cardiovascular disease. All subjects underwent B-mode carotid ultrasound to detect atheroma plaques. Demographics were obtained from all subjects., Results: We included 71 patients with LADA, 191 patients with type 2 diabetes and 116 patients with type 1 diabetes. Carotid atherosclerosis was more frequent in patients with LADA compared with type 2 diabetes (73.2% vs. 56.9%, P = 0.0018) and classic type 1 diabetes (57.1%, P = 0.026); these changes occurred despite healthier macrovascular risk profiles in the former. Age (P < 0.001), smoking (P = 0.003) and hypertension (P = 0.019) were independently associated with carotid atherosclerosis. Multiple plaques were also more frequent in patients with LADA as compared with classic type 1 diabetes and type 2 diabetes (45.1% and 33.6% vs. 27.2%, respectively, P = 0.022). The frequency of carotid plaques increased with increasing diabetes duration in LADA patients compared with type 2 diabetes (85.7% vs. 58.8%, inverse OR 5.72 [1.5-21.8]; P = 0.009)., Conclusions: LADA patients do not present with less carotid atherosclerosis than patients with type 1 and type 2 diabetes. Their macrovascular risk occurs despite a healthier macrovascular risk profile than those patients with type 2 diabetes.

Background: To investigate the association of both latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2DM) with muscle mass and function (sarcopenia)., Methods: Japanese patients with LADA (N=20), T2DM (N=208), and control subjects (N=41) were included in this cross-sectional study. The definition of LADA was based on age of onset (≥30), positive glutamic acid decarboxylase autoantibodies, and insulin requirement within the first 6months after diagnosis. Sarcopenia was diagnosed by the criteria for Asians, using skeletal muscle index (male <7.0 and female <5.4) and grip strength (male <26.0kg and female <18.0kg). The odds ratio (OR) with a 95% confidence interval (CI) was estimated using logistic regression., Results: The prevalence of sarcopenia was higher in LADA (35.0%) than in either T2DM (13.3%) or control subjects (9.8%). LADA was significantly associated with an increased risk for sarcopenia in a multivariate model in which age and body mass index were incorporated (OR: 9.57, 95% CI: 1.86-49.27). In contrast, T2DM tended to be associated with an increased risk for sarcopenia (OR: 2.99, 95% CI: 0.83-10.80)., Conclusions: This study provides evidence that patients with LADA are at a high risk for sarcopenia compared to those with T2DM or to control subjects., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Latent autoimmune diabetes in adults (LADA) is autoimmune diabetes with a slow progression characterized by the presence of antibodies associated with Type I diabetes. The present study aimed to assess autoimmune characteristics in patients with LADA in Iran. We attempted to obtain a clear view of autoimmune conditions in LADA among our population., Methods: This study was sourced from the population-based survey of KERCARDS aiming assessment of cardiovascular risk factors among a great sample of Iranian population who were resident in Kerman, a great province in southern Iran. Among all diabetic patients who were negative for Anti Glutamic Acid Decarboxylase (GAD) antibody test, 120 were selected as the controls and among 80 patients who were positive for this test diagnosed as LADA, the recorded files of 57 patients were complete considered as the cases., Results: The level of thyroxin is significantly lower in patients with LADA compared with the controls so 73.7% and 45% of patients had normal level of thyroxin, respectively. Also, those with LADA had considerably lower levels of both thyroid peroxydaseantibody (TPO-Ab) and C-peptide when compared with non-LADA group. Using multivariate analyses and with the presence of baseline variables including gender, age, and duration of disease, the diagnosis of LADA was associated with lower serum levels of Anti-TPO, C-peptide, and thyroxin, but not associated with the level of Anti-TTG in serum., Conclusion: LADA patients may face with lower serum levels of C-peptide and thyroid-specific antibodies indicating insulin therapy requirement and authoimmune fundaments of the disease, respectively., (Copyright © 2016. Published by Elsevier Ltd.)

Introduction: Latent autoimmune diabetes in adults (LADA) is a slow-developing form of autoimmune diabetes, characterised by the presence of type 1 diabetes-associated autoantibody and presentation at diagnosis similar to patients with type 2 diabetes. The aim of this study was to determine the prevalence of auto-antibodies related to endocrine autoimmune diseases in patients with LADA and to assess their association with HLA genotype., Material and Methods: We evaluated the presence of anti-thyroglobulin (ATG), anti-thyroid peroxidase (ATPO), anti-tissue transglutaminase IgA (ATTA), and anti 21 hydroxylase (A21H) in 70 patients with LADA, 69 with Type 2 diabetes, and in 50 healthy controls HLA genotype was assed in subpopulation of sluclied subjects., Results: The presence of ATPO (28.6 vs. 10%); ATG (28.6 vs. 14%) was higher in patients with LADA in comparison to healthy controls and ATPO in comparison to patients with type 2 diabetes (38.6 vs. 17.4 %). In patients with LADA the presence of autoimmune thyroid autoantibodies was associated with newly diagnosed subclinical hypothyroidism; almost 7% of patients presented with high TSH. The presence of A21H (2.86 vs. 5.8 vs. 6.1%) and ATTA (2.86 vs. 4.3 vs. 6.0%) was not different between groups. Patients with high TSH level were positive for DQA1*0301 and DRB1*04 HLA genotype: DQB1*0201 and DQB1*02 were higher in patients positive for ATTA., Conclusions: Patients with LADA have higher prevalence of thyroid autoimmune diseases. In patients with LADA similarly to type 1 genotype DQA1*0301 seems to CONFER susceptibility to thyroid autoimmunity, and DQB1*0201 to celiac disease.