Identification of autoimmune type 1 diabetes and multiple organ‐specific autoantibodies in adult‐onset non‐insulin‐requiring diabetes in China: A population‐based multicentre nationwide survey

2019 ◽  
Vol 21 (4) ◽  
pp. 893-902 ◽  
Author(s):  
Yufei Xiang ◽  
Gan Huang ◽  
Yaxi Zhu ◽  
Xuan Zuo ◽  
Xinyuan Liu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nationwide Survey ◽  
Population Based ◽  
Multiple Organ ◽  
Adult Onset ◽  
Organ Specific

Type 1 Diabetes-related Autoantibodies in Different Forms of Diabetes

2019 ◽  
Vol 15 (3) ◽  
pp. 199-204 ◽  
Author(s):  
Elin Pettersen Sørgjerd
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Autoimmune Diabetes ◽  
Acid Decarboxylase ◽  
Adult Onset ◽  
Latent Autoimmune Diabetes ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type

Autoantibodies against Glutamic Acid Decarboxylase (GADA), insulinoma antigen-2 (IA- 2A), insulin (IAA) and the most recently Zinc Transporter 8 (ZnT8A) are one of the most reliable biomarkers for autoimmune diabetes in both children and adults. They are today the only biomarkers that can distinguish Latent Autoimmune Diabetes in Adults (LADA) from phenotypically type 2 diabetes. As the frequency of autoantibodies at diagnosis in childhood type 1 diabetes depends on age, GADA is by far the most common in adult onset autoimmune diabetes, especially LADA. Being multiple autoantibody positive have also shown to be more common in childhood diabetes compared to adult onset diabetes, and multiple autoantibody positivity have a high predictive value of childhood type 1 diabetes. Autoantibodies have shown inconsistent results to predict diabetes in adults. Levels of autoantibodies are reported to cause heterogeneity in LADA. Reports indicate that individuals with high levels of autoantibodies have a more type 1 diabetes like phenotype and individuals with low levels of autoantibody positivity have a more type 2 diabetes like phenotype. It is also well known that autoantibody levels can fluctuate and transient autoantibody positivity in adult onset autoimmune diabetes have been reported to affect the phenotype.

scholarly journals One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Lu ◽  
Shan-mei Shen ◽  
Qing Ling ◽  
Bin Wang ◽  
Li-rong Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stromal Cells ◽  
Treated Group ◽  
Control Group ◽  
Adult Onset ◽  
Β Cell ◽  
Juvenile Onset ◽  
C Peptide

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

scholarly journals DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life

Diabetologia ◽  
2021 ◽  
Author(s):  
Nicholas J. Thomas ◽  
John M. Dennis ◽  
Seth A. Sharp ◽  
Akaal Kaur ◽  
Shivani Misra ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Major Type ◽  
Diabetes Incidence ◽  
Diabetes Diagnosis ◽  
Risk Haplotype ◽  
Adult Onset ◽  
Uk Biobank ◽  
Onset Type ◽  
Increased Risk

Abstract Aims/hypothesis Among white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased. Methods In two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years. Results DR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, all p < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes. Conclusions/interpretation HLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life. Graphical abstract

scholarly journals Clinical and demographic features among patients with type 1 diabetes mellitus in Henan, China

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liguo Yang ◽  
Guangxing Yang ◽  
Xialian Li
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Retinopathy ◽  
Blood Glucose Control ◽  
Disease Onset ◽  
Overweight And Obesity ◽  
Adult Onset ◽  
C Peptide ◽  
Young Onset ◽  
Onset Group

Abstract Background The hallmark of type 1 diabetes (T1D) is an absolute lack of insulin. However, many studies showed a tendency to heterogeneity in TID. We aimed to investigate the demographic and clinical characteristics in T1D and the differences in young-onset and adult-onset patients. Methods This retrospective study was conducted among 1943 patients with clinically diagnosed T1D. Medical records on patients’ demographics, anthropometric measurements, and clinical manifestation were collected. According to the age at onset, the newly diagnosed patients were divided into the young-onset group (< 18 years, 234 patients, mean age 11 years) and adult-onset group (≥ 18 years, 219 patients, mean age 27 years). Pancreatic β-cell function was assessed by fasting C-peptide (FCP) and 2-h C-peptide (2-h CP). Results The median age of patients at disease onset was 22 years. The median duration of patients was 3 years. The overall median glycated hemoglobin (HbA1c) value was 10.3 % [89(mmol/mol)]. The prevalence of diabetic retinopathy was 25.1 %. The overall rate of DKA at onset in the new-onset patients was 59.6 %. The frequency of overall dyslipidemia was 37.8 %. The most frequent dyslipidemia was low high-density lipoprotein-cholesterol (HDL) (29 %). The proportion of patients with anti-glutamic acid decarboxylase (GADA), insulin antibody (IAA) and islet cell antibody (ICA) were 28.1 %, 6.4 % and 21.6 %, respectively. The mean HbA1c showed a downward trend with age. Increasing or decreasing trends of overweight and obesity in this population during the period 2012 to 2018 was not found. Compared with young-onset T1D, adult-onset patients comprised better islet function (FCP: 0.4 vs. 0.3 ng/ml, P < 0.001; 2-h CP: 0.9 vs. 0.7 ng/ml P < 0.001, respectively) and glycemic control [12.9 % (117mmol/mol) vs. 11.7 % (104mmol/mol), P < 0.001], higher prevalence of diabetes condition in the male gender (64.4 % vs. 51.3 %, P = 0.006), higher proportion of obesity or overweight (24.6 % vs. 9.5 %, P = 0.002), higher frequency of GADA (33.7 % vs. 23.3 %, P = 0.025), and lower frequency of diabetic ketoacidosis at disease onset (64.5 % vs. 43.5 %, P < 0.001). Conclusions This population was characterized by poor overall blood glucose control, high prevalence of DKA, dyslipidemia and diabetic retinopathy, and low prevalence of islet-related antibodies, and overweight or obesity. Adult-onset patients with T1D were not uncommon and had better clinical manifestations than young-onset patients. Any findings related to body mass index (BMI) and autoantibodies should be considered strictly exploratory due to excessive missing data.

scholarly journals CTLA-4 (+49A/G) Polymorphism in Type 1 Diabetes Children of Sudanese Population

2021 ◽  
Vol 08 (01) ◽  
pp. 011-018
Author(s):  
Khalid E. Khalid Kheiralla
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Ethylenediaminetetraacetic Acid ◽  
Negative Regulator ◽  
Cytotoxic Lymphocyte ◽  
Pediatric Clinic ◽  
Homozygous Genotype ◽  
Organ Specific ◽  
Α Helix

Abstract Background Type 1 diabetes mellitus (T1DM) is an organ-specific T cell-mediated autoimmune disease, characterized by destruction of pancreatic islets. Cytotoxic lymphocyte antigen-4 (CTLA-4) is a negative regulator of T cell proliferation, thus conferring susceptibility to autoimmunity. Aims This study aimed to investigate the association of CTLA-4 +49A/G (rs231775) polymorphism with a risk of T1DM in Sudanese children. Methods This a case–control study included 100 children with T1DM, referred to the pediatric clinic at referral pediatric teaching hospital in Gezira State-Sudan. Hundred unrelated healthy controls were recruited from departments in the same hospital. Genomic deoxyribonucleic acid (DNA) was extracted from Ethylenediaminetetraacetic Acid (EDTA)-preserved blood using QIAamp DNA Blood Mini Kit (QIAamp Blood) (QIAGEN; Valencia, CA). The polymerase chain reaction PCR restriction fragment length polymorphism (PCR-RFLP) and sequencing were applied for the CTLA-4 (+49A/G) genotyping. The changes accompanied the polymorphism were evaluated using relevant bioinformatics tools. Results The genotype and allele frequencies of the CTLA-4 (+49A/G) polymorphism were significantly different between the patients and controls (p = 0.00013 and 0.0002, respectively). In particular, the frequency of the G allele, GG homozygous genotype, and AG heterozygous genotype were significantly increased in patients than in controls ([28% versus 7%, odds ratio (OR) = 5.16, 95% confidence interval [CI] = 2.77–9.65, p = 0.00] [12% versus 2%, OR = 6.68, CI = 1.46–30.69, p = 0.01] [32% versus 10%, OR = 4.24, CI = 1.95–9.21, p = 0.00], respectively). The presence of the G allele (homozygous) showed an influence on the signal peptide polarity, hydrophobicity, and α-helix propensity of the CTLA-protein. Conclusion The results further support the association of CTLA-4 (+49A/G) polymorphism and the risk of T1DM in our study population.

Excess mortality in Type 1 diabetes diagnosed in childhood and adolescence: a systematic review of population-based cohorts

2015 ◽  
Vol 52 (4) ◽  
pp. 801-807 ◽  
Author(s):  
Eileen Morgan ◽  
Christopher R. Cardwell ◽  
Catherine J. Black ◽  
David R. McCance ◽  
Christopher C. Patterson
Keyword(s):  
Systematic Review ◽  
Type 1 Diabetes ◽  
Excess Mortality ◽  
Population Based ◽  
Childhood And Adolescence

scholarly journals Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrzej S. Januszewski ◽  
Yoon Hi Cho ◽  
Mugdha V. Joglekar ◽  
Ryan J. Farr ◽  
Emma S. Scott ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cross Sectional Study ◽  
Diabetes Duration ◽  
Adult Onset ◽  
Sectional Study ◽  
Childhood Onset ◽  
Cross Sectional ◽  
C Peptide ◽  
Adult Onset Diabetes

AbstractThe aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood (< 18 y.o.), and diabetes duration was stratified as ≤ 10 years, 10–20 years and > 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n = 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend < 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.

244-OR: Toward Improved Identification of Adult-Onset Type 1 Diabetes (T1D): Clinical Characteristics Associated with T1D Polygenic Risk Scores in the Million Veteran Program (MVP)

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 244-OR
Author(s):  
PETER K. YANG ◽  
SANDRA JACKSON ◽  
BRIAN R. CHAREST ◽  
MICHAEL N. WEEDON ◽  
YILING J. CHENG ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Characteristics ◽  
Risk Scores ◽  
Adult Onset ◽  
Polygenic Risk ◽  
Onset Type
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