scholarly journals Blood Co-Circulating Extracellular microRNAs and Immune Cell Subsets Associate with Type 1 Diabetes Severity

2020 ◽  
Vol 21 (2) ◽  
pp. 477 ◽  
Author(s):  
Silvia Garavelli ◽  
Sara Bruzzaniti ◽  
Elena Tagliabue ◽  
Francesco Prattichizzo ◽  
Dario Di Silvestre ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Cell ◽  
Disease Onset ◽  
Cell Subset ◽  
Healthy Controls ◽  
Cell Frequency ◽  
Logistic Regression Models ◽  
Immune Cell Subsets ◽  
Diabetes Severity

Immune cell subsets and microRNAs have been independently proposed as type 1 diabetes (T1D) diagnostic and/or prognostic biomarkers. Here, we aimed to analyze the relationships between peripheral blood circulating immune cell subsets, plasmatic microRNAs, and T1D. Blood samples were obtained from both children with T1D at diagnosis and age-sex matched healthy controls. Then, immunophenotype assessed by flow cytometry was coupled with the quantification of 60 plasmatic microRNAs by quantitative RT-PCR. The associations between immune cell frequency, plasmatic microRNAs, and the parameters of pancreatic loss, glycemic control, and diabetic ketoacidosis were assessed by logistic regression models and correlation analyses. We found that the increase in specific plasmatic microRNAs was associated with T1D disease onset (let-7c-5p, let-7d-5p, let-7f-5p, let-7i-5p, miR-146a-5p, miR-423-3p, and miR-423-5p), serum C-peptide concentration (miR-142-5p and miR-29c-3p), glycated hemoglobin (miR-26a-5p and miR-223-3p) and the presence of ketoacidosis (miR-29c-3p) more strongly than the evaluated immune cell subset frequency. Some of these plasmatic microRNAs were shown to positively correlate with numbers of blood circulating B lymphocytes (miR-142-5p) and CD4+CD45RO+ (miR-146a-5p and miR-223-3p) and CD4+CD25+ cells (miR-423-3p and miR-223-3p) in children with T1D but not in healthy controls, suggesting a disease-specific microRNA association with immune dysregulation in T1D. In conclusion, our results suggest that, while blood co-circulating extracellular microRNAs and immune cell subsets may be biologically linked, microRNAs may better provide powerful information about T1D onset and severity.

Methylation Analysis in Distinct Immune Cell Subsets in Type 1 Diabetes

2015 ◽  
pp. 143-151 ◽  
Author(s):  
Mary N. Dang ◽  
Claire M. Bradford ◽  
Paolo Pozzilli ◽  
R. David Leslie
Keyword(s):  
Type 1 Diabetes ◽  
Immune Cell ◽  
Methylation Analysis ◽  
Immune Cell Subsets

scholarly journals Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size

2021 ◽  
Author(s):  
James J. Ross ◽  
Clive H. Wasserfall ◽  
Rhonda Bacher ◽  
Daniel J. Perry ◽  
Kieran McGrail ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Onset ◽  
Serum Samples ◽  
Serum Lipase ◽  
Logistic Regression Models ◽  
Recent Onset ◽  
Pancreas Volume ◽  
Serum Trypsinogen ◽  
Serological Biomarkers

Exocrine pancreas abnormalities are increasingly recognized as features of type 1 diabetes. We previously reported reduced serum trypsinogen levels and in a separate study, smaller pancreata at and prior to disease onset. We hypothesized that three pancreas enzymes (amylase, lipase and trypsinogen) might serve as serological biomarkers of pancreas volume and risk for type 1 diabetes. Amylase, lipase, and trypsinogen were measured from two independent cohorts, together comprising 800 serum samples from single-autoantibody positive (1AAb+) and multiple-AAb+ (≥2AAb+) subjects, individuals with recent-onset or established type 1 diabetes, their AAb negative (AAb-) first-degree relatives, and AAb- controls. Lipase and trypsinogen were significantly reduced in ≥2AAb+, recent-onset, and established type 1 diabetes subjects versus controls and 1AAb+, while amylase was reduced only in established type 1 diabetes. Logistic regression models demonstrated trypsinogen plus lipase (AUROC=81.4%) performed equivalently to all three enzymes (AUROC=81.4%) in categorizing ≥2AAb+ versus 1AAb+ subjects. For Cohort 2 (n=246), linear regression demonstrated lipase and trypsinogen levels could individually and collectively serve as indicators of BMI-normalized relative pancreas volume (RPV<sub>BMI</sub>, <i>P</i><0.001), previously measured by magnetic resonance imaging. Serum lipase and trypsinogen levels together provide the most sensitive serological biomarker of RPV<sub>BMI</sub> and may improve disease staging in pre-type 1 diabetes.

scholarly journals NK Cell Subsets Changes in Partial Remission and Early Stages of Pediatric Type 1 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Laia Gomez-Muñoz ◽  
David Perna-Barrull ◽  
Adrian Villalba ◽  
Silvia Rodriguez-Fernandez ◽  
Rosa-Maria Ampudia ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nk Cells ◽  
Partial Remission ◽  
Immune Cell ◽  
Nk Cell ◽  
Disease Onset ◽  
Potential Candidate ◽  
Early Stages ◽  
Cd16 Expression

Type 1 diabetes (T1D) is a chronic metabolic disease characterized by the autoimmune destruction of β-cells in the pancreatic islets. T1D is preceded by islet-specific inflammation led by several immune cells. Among them, natural killer (NK) cells are emerging as important players in T1D development. Human NK cells are characterized by CD56 and CD16 expression, which allows classifying NK cells into four subsets: 1) CD56dimCD16+ or effector NK cells (NKeff); 2) CD56brightCD16− or regulatory NK cells (NKreg); 3) intermediate CD56brightCD16+ NK cells; and 4) CD56dimCD16− NK cells, whose function is not well determined. Since many studies have shown that T1D progression is associated with changes in various immune cell types, we hypothesize that the kinetics of NK cell subsets in the blood could correlate with different stages of T1D. To that aim, pediatric patients newly diagnosed with T1D were recruited, and peripheral NK cell subsets were analyzed by flow cytometry at several disease checkpoints: disease onset, partial remission (PR), 8 months (for non-remitters), and 12 months of progression. Our results showed that total NK cells and their four subsets are altered at the early stages of T1D. A decrease in the counts and percentage of total NK cells and NKeff cells at the different disease stages was found when compared to controls. These results suggest the extravasation of these cells into the islets at disease onset, which is maintained throughout the follow-up. By contrast, NKreg cells increased during the early stages after T1D onset, and both intermediate NK cells and CD56dimCD16- NK cells diminished at the PR stage, which might reflect the immunoregulatory attempts and could be candidate biomarkers for this stage. Also, CD56dimCD16- NK cells increased during T1D progression. Finally, changes in CD16 expression were identified in the different T1D stages, highlighting a CD16 expression reduction in total NK cells and NKeff cells 1 year after diagnosis. That may reflect a state of exhaustion after multiple cell-to-cell interactions. Altogether, our preliminary data provide a longitudinal picture of peripheral NK cell subpopulations during the different T1D stages, which could be potential candidate biomarkers indicators of disease progression.

scholarly journals Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size

2021 ◽  
Author(s):  
James J. Ross ◽  
Clive H. Wasserfall ◽  
Rhonda Bacher ◽  
Daniel J. Perry ◽  
Kieran McGrail ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Onset ◽  
Serum Samples ◽  
Serum Lipase ◽  
Logistic Regression Models ◽  
Recent Onset ◽  
Pancreas Volume ◽  
Serum Trypsinogen ◽  
Serological Biomarkers

Exocrine pancreas abnormalities are increasingly recognized as features of type 1 diabetes. We previously reported reduced serum trypsinogen levels and in a separate study, smaller pancreata at and prior to disease onset. We hypothesized that three pancreas enzymes (amylase, lipase and trypsinogen) might serve as serological biomarkers of pancreas volume and risk for type 1 diabetes. Amylase, lipase, and trypsinogen were measured from two independent cohorts, together comprising 800 serum samples from single-autoantibody positive (1AAb+) and multiple-AAb+ (≥2AAb+) subjects, individuals with recent-onset or established type 1 diabetes, their AAb negative (AAb-) first-degree relatives, and AAb- controls. Lipase and trypsinogen were significantly reduced in ≥2AAb+, recent-onset, and established type 1 diabetes subjects versus controls and 1AAb+, while amylase was reduced only in established type 1 diabetes. Logistic regression models demonstrated trypsinogen plus lipase (AUROC=81.4%) performed equivalently to all three enzymes (AUROC=81.4%) in categorizing ≥2AAb+ versus 1AAb+ subjects. For Cohort 2 (n=246), linear regression demonstrated lipase and trypsinogen levels could individually and collectively serve as indicators of BMI-normalized relative pancreas volume (RPV<sub>BMI</sub>, <i>P</i><0.001), previously measured by magnetic resonance imaging. Serum lipase and trypsinogen levels together provide the most sensitive serological biomarker of RPV<sub>BMI</sub> and may improve disease staging in pre-type 1 diabetes.

scholarly journals HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression1

2018 ◽  
Author(s):  
Jennifer Schloss ◽  
Riyasat Ali ◽  
Jeremy J. Racine ◽  
Harold D. Chapman ◽  
David V. Serreze ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Mouse Model ◽  
Disease Onset ◽  
Cell Subset ◽  
Class I ◽  
Class I Mhc ◽  
Insulin Expression

ABSTRACTType 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing βcells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared to littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, indicating that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, we propose that it allows the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage, which may contribute to varying diabetogenic CD8 T cell repertoires in the presence of different HLA class I alleles.

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.

Decreased Flow-Mediated Dilatation in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis

Angiology ◽  
2021 ◽  
pp. 000331972110100
Author(s):  
Lei Cao ◽  
Miao Hou ◽  
Wanping Zhou ◽  
Ling Sun ◽  
Jie Shen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Endothelial Function ◽  
Meta Analysis ◽  
Quality Data ◽  
Cochrane Library ◽  
Healthy Children ◽  
Healthy Controls ◽  
Flow Mediated Dilatation

Type 1 diabetes (T1DM) is a strong risk factor for the development of cardiovascular disease. Flow-mediated dilatation (FMD) is an early noninvasive marker of endothelial function and it predicts future cardiovascular disease. However, the changes in FMD among T1DM children are still controversial. The present meta-analysis aimed to investigate whether FMD is impaired in children with T1DM. PubMed, EMBASE, Cochrane library, and Web of Science were searched for studies comparing FMD in children with T1DM and healthy controls. The Newcastle-Ottawa quality assessment scale for case–control studies was used to assess study quality. Data were pooled using a random effects models to obtain the weighted mean differences (WMD) in FMD and 95% CIs. Overall, 19 studies with 1245 patients and 872 healthy controls were included in this meta-analysis. Children with T1DM had significantly lower FMDs compared with healthy controls (WMD: −2.58; 95% CI: −3.36 to −1.81; P < .001). Meta-regression analysis revealed that low-density lipoprotein cholesterol levels impacted the observed difference in FMD between T1DM and healthy children. This meta-analysis showed that T1DM children have impaired endothelial function, which indicates they are at higher risk of developing cardiovascular disease in later life.

scholarly journals Gender-Specific Risk Factors for the Development of Retinal Changes in Children with Type 1 Diabetes

2021 ◽  
Vol 11 (6) ◽  
pp. 588
Author(s):  
Marta Wysocka-Mincewicz ◽  
Joanna Gołębiewska ◽  
Marta Baszyńska-Wilk ◽  
Andrzej Olechowski
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Uric Acid ◽  
Serum Creatinine ◽  
Regression Models ◽  
Retinal Thickness ◽  
Disease Onset ◽  
Specific Risk ◽  
Gender Specific

The aim of the study was to determine gender-specific risk factor sets which could influence optical coherence tomography (OCT) results in children with type 1 diabetes (T1D). Material and Methods: 175 children with T1D without symptoms of diabetic retinopathy were enrolled, but 330 eyes were used for the final analysis (168 children, mean age 12.81 ± 3.63 years, diabetes duration 4.59 ± 3.71 years). The multivariate regression models for retinal thickness (foveal FT, and parafoveal PFT) and vascular densities (superficial and deep) were carried out separately for both genders using all metabolic and demographic parameters. Results: In the statistically significant multiple regression models for all analyzed OCT parameters for both genders, pH at the onset of diabetes were in existence, as well as for retinal thickness current HbA1c. Duration of continuous insulin infusion (CSII) was an important factor in all parameters, except PFT. For the girls, the most significant factors were daily insulin dose, uric acid, and triglycerides, but for the boys, it was serum creatinine, systolic pressure, and free thyroxine level. Conclusions: We detected significant risk factors set for development of OCT parameters changes, and they were not identical for both genders. Current metabolic control, diabetic ketoacidosis at the disease onset, serum creatinine and longer use of CSII are the most important factors for retinal thickness and vessel densities in both genders in children with type 1 diabetes. For the girls, elements of metabolic syndrome (uric acid and triglycerides) and parameters of insulin amount were more pronounced.

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