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 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 Pancreas Volume Declines During the First Year After Diagnosis of Type 1 Diabetes and Exhibits Altered Diffusion at Disease Onset

Diabetes Care ◽  
2018 ◽  
Vol 42 (2) ◽  
pp. 248-257 ◽  
Author(s):  
John Virostko ◽  
Jon Williams ◽  
Melissa Hilmes ◽  
Chris Bowman ◽  
Jordan J. Wright ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Disease Onset ◽  
First Year ◽  
Pancreas Volume

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.

scholarly journals Characterization of the endocrine pancreas in Type 1 Diabetes: islet size is maintained but islet number is markedly reduced

2018 ◽  
Author(s):  
Peter Seiron ◽  
Anna Wiberg ◽  
Lars Krogvold ◽  
Frode Lars Jahnsen ◽  
Knut Dahl-Jørgensen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Cell Loss ◽  
Recent Onset ◽  
Islet Size ◽  
Pancreas Volume

AbstractInsulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of specific beta-cell loss. Since healthy pancreatic islets consist of ~65% beta cells, this would lead to reduced islet size if the beta cells are not replaced by other cells or tissue. The number of islets per pancreas volume (islet density) would not be affected.In this study, we compared the islet density, size, and size distribution in subjects with recent-onset or long-standing T1D, with that in matched non-diabetic subjects. Results show that subjects with T1D, regardless of disease duration, had a dramatically reduced islet number per mm2, while the islet size was similar in all groups. Insulin-negative islets in T1D subjects were dominated by glucagon-positive cells that frequently had lost the alpha-cell transcription factor ARX while instead expressing PDX1, normally expressed in beta cells.Based on our findings, we propose that failure during childhood to establish a sufficient islet number to reach the beta-cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta-cell dedifferentiation to alpha-cells, explaining the preserved islet size observed in T1D compared to controls.

scholarly journals Elevated Biomarkers of NETosis in the Serum of Pediatric Patients With Type 1 Diabetes and Their First-Degree Relatives

2021 ◽  
Vol 12 ◽  
Author(s):  
Adam Klocperk ◽  
Jana Vcelakova ◽  
Petra Vrabcova ◽  
Irena Zentsova ◽  
Lenka Petruzelkova ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Clinical Manifestation ◽  
Pediatric Patients ◽  
Disease Onset ◽  
Cell Free Dna ◽  
Recent Onset ◽  
First Degree Relatives ◽  
Free Dna

Type 1 diabetes (T1D) is an autoimmune disorder with unambiguous involvement of both innate and adaptive immune mechanisms in the destruction of pancreatic beta cells. Recent evidence demonstrated that neutrophils infiltrate the pancreas prior to disease onset and therein extrude neutrophil extracellular traps (NETs), web-like structures of DNA and nuclear proteins with a strong pro-inflammatory biologic activity. Our previous work showed that T1D NETs activate dendritic cells, which consequently induce IFNγ-producing Th1 lymphocytes. The aim of this study was to assess direct ex vivo biomarkers of NETosis in the serum of recent onset and long-term pediatric T1D patients, their first-degree relatives and healthy controls. To this end we evaluated serum levels of myeloperoxidase (MPO), neutrophil elastase (NE), proteinase 3 (PR3), protein arginine deiminase 4 (PAD4), LL37 and cell-free DNA-histone complexes in sex- and age-matched cohorts of T1D first-degree relatives, recent-onset T1D patients, and in patients 12 months after clinical manifestation of the disease. Our data shows that disease onset is accompanied by peripheral neutrophilia and significant elevation of MPO, NE, PR3, PAD4 and cell-free DNA-histone complexes. Most biomarkers subsequently decrease but do not always normalize in long-term patients. First-degree relatives displayed an intermediate phenotype, except for remarkably high levels of LL37. Together, this report provides evidence for the presence of ongoing NETosis in pediatric patients with T1D at time of clinical manifestation of the disease, which partly subsides in subsequent years.

Alpha-1 Antitrypsin Therapy in Recent-Onset Type 1 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 235-OR
Author(s):  
YAEL LEBENTHAL ◽  
AVIVIT BRENER ◽  
ELI HERSHKOVITZ ◽  
NAIM SHEHADEH ◽  
SHLOMIT SHALITIN ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Recent Onset ◽  
Onset Type ◽  
Alpha 1 Antitrypsin
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