The polymorphism in the 3′ untranslated region of IL12B has a negligible effect on the susceptibility to develop type 1 diabetes in Norway

2001 ◽  
Vol 53 (7) ◽  
pp. 603-605 ◽  
Author(s):  
Stefan Johansson ◽  
Benedicte A. Lie ◽  
Erik Thorsby ◽  
Dag E. Undlien
Keyword(s):  
Type 1 Diabetes ◽  
Untranslated Region ◽  
Negligible Effect ◽  
Develop Type

scholarly journals Umbilical Cord Blood DNA Methylation in Children Who Later Develop Type 1 Diabetes

2021 ◽  
Author(s):  
Essi Laajala ◽  
Ubaid Ullah ◽  
Toni Grönroos ◽  
Omid Rasool ◽  
Viivi Halla-aho ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Type 1 Diabetes ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Reduced Representation ◽  
Prediction And Prevention ◽  
Develop Type ◽  
Methylation Patterns

Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine, whether perinatal DNA methylation could be associated with later progression to type 1 diabetes. Reduced representation bisulfite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Type 1 Diabetes Prediction and Prevention (DIPP) study. Children later diagnosed with type 1 diabetes and/or testing positive for multiple islet autoantibodies (N=43) were compared to control individuals (N=79), who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis. No differences in the cord blood methylation patterns were observed between these cases and controls.

scholarly journals Immunoreactive Trypsinogen and Free Carnitine Changes on Newborn Screening after Birth in Patients Who Develop Type 1 Diabetes

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3669
Author(s):  
Jane Frances Grace Lustre Estrella ◽  
Veronica C. Wiley ◽  
David Simmons
Keyword(s):  
Type 1 Diabetes ◽  
Newborn Screening ◽  
Conditional Logistic Regression ◽  
Free Carnitine ◽  
Parameter Estimates ◽  
Reference Ranges ◽  
Develop Type ◽  
Post Hoc ◽  
Immunoreactive Trypsinogen

Are free carnitine concentrations on newborn screening (NBS) 48–72 h after birth lower in patients who develop type 1 diabetes than in controls? A retrospective case-control study of patients with type 1 diabetes was conducted. NBS results of patients from a Sydney hospital were compared against matched controls from the same hospital (1:5). Multiple imputation was performed for estimating missing data (gestational age) using gender and birthweight. Conditional logistic regression was used to control for confounding and to generate parameter estimates (α = 0.05). The Hommel approach was used for post-hoc analyses. Results are reported as medians and interquartile ranges. A total of 159 patients were eligible (80 females). Antibodies were detectable in 86. Median age at diagnosis was 8 years. Free carnitine concentrations were lower in patients than controls (25.50 µmol/L;18.98–33.61 vs. 27.26; 21.22–34.86 respectively) (p = 0.018). Immunoreactive trypsinogen was higher in this group (20.24 µg/L;16.15–29–52 vs. 18.71; 13.96–26.92) (p = 0.045), which did not persist in the post-hoc analysis. Carnitine levels are lower and immunoreactive trypsinogen might be higher, within 2–3 days of birth and years before development of type 1 diabetes as compared to controls, although the differences were well within reference ranges and provide insight into the pathogenesis into neonatal onset of type 1 diabetes development rather than use as a diagnostic tool. Given trypsinogen’s use for evaluation of new-onset type 1 diabetes, larger studies are warranted.

scholarly journals Functional genetic polymorphisms in cytokines and metabolic genes as additional genetic markers for susceptibility to develop type 1 diabetes

2004 ◽  
Vol 5 (1) ◽  
pp. 36-40 ◽  
Author(s):  
P Eerligh ◽  
B P C Koeleman ◽  
F Dudbridge ◽  
G Jan Bruining ◽  
B O Roep ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Polymorphisms ◽  
Genetic Markers ◽  
Metabolic Genes ◽  
Develop Type

scholarly journals Diabetes mellitus secondary to treatment with immune checkpoint inhibitors

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
V. Venetsanaki ◽  
A. Boutis ◽  
A. Chrisoulidou ◽  
P. Papakotoulas
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Adverse Events ◽  
Type 1 Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Positive Outcome ◽  
Develop Type

Cancer immunotherapy has been one of the highlights in the advancement of cancer care. Certain immune checkpoint inhibitors bind to PD-1 on T cells and mediate an antitumour immune response. Given that immune checkpoint inhibitors are becoming part of standard care, a new class of adverse events—immune-related adverse events—has emerged.  Among them is endocrine toxicity, most commonly targeting the thyroid, pituitary, or adrenal glands. New-onset diabetes mellitus has been reported in fewer than 1% of patients. We present a patient with type 1 diabetes mellitus secondary to immunotherapy, together with an overview of the associated literature. Patients who develop type 1 diabetes mellitus experience a rapid course, and diabetic ketoacidosis is commonly the presenting symptom. Insulin is currently the treatment of choice; oral antidiabetics or corticosteroids do not assist in management. Several predictive factors are under investigation, but physician awareness and prompt management are key to a positive outcome.

scholarly journals Association of HLA-G 3′ untranslated region variants with type 1 diabetes mellitus

2016 ◽  
Vol 77 (4) ◽  
pp. 358-364 ◽  
Author(s):  
Rafael S. de Albuquerque ◽  
Celso Teixeira Mendes-Junior ◽  
Norma Lucena-Silva ◽  
Camila Leal Lopes da Silva ◽  
Diane Meire Rassi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Untranslated Region

scholarly journals Enhanced levels of cow’s milk antibodies in infancy in children who develop type 1 diabetes later in childhood

2008 ◽  
Vol 9 (5) ◽  
pp. 434-441 ◽  
Author(s):  
Kristiina Luopajärvi ◽  
Erkki Savilahti ◽  
Suvi M Virtanen ◽  
Jorma Ilonen ◽  
Mikael Knip ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cow’S Milk ◽  
Cow's Milk ◽  
Develop Type ◽  
Milk Antibodies

scholarly journals The IL12B 3′ untranslated region DNA polymorphism is not associated with early-onset type 1 diabetes

2002 ◽  
Vol 3 (7) ◽  
pp. 433-435 ◽  
Author(s):  
R M McCormack ◽  
A P Maxwell ◽  
D J Carson ◽  
C C Patterson ◽  
D Middleton ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Early Onset ◽  
Untranslated Region ◽  
Dna Polymorphism ◽  
Onset Type

scholarly journals Maintenance of Pdx1 mRNA Translation in Islet β-Cells During the Unfolded Protein Response

2014 ◽  
Vol 28 (11) ◽  
pp. 1820-1830 ◽  
Author(s):  
Andrew T. Templin ◽  
Bernhard Maier ◽  
Sarah A. Tersey ◽  
Masayuki Hatanaka ◽  
Raghavendra G. Mirmira
Keyword(s):  
Type 1 Diabetes ◽  
Unfolded Protein Response ◽  
Proinflammatory Cytokines ◽  
Untranslated Region ◽  
Mrna Translation ◽  
Β Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

In type 1 diabetes, proinflammatory cytokines secreted by infiltrating immune cells activate the unfolded protein response (UPR) in islet β-cells, which leads to attenuation of global mRNA translation. Under such conditions, privileged mRNAs required for adaptation to the prevailing stress are maintained in an actively translated state. Pdx1 is a β-cell transcription factor that is required for the adaptive UPR, but it is not known how translation of its mRNA is maintained under these conditions. To study translation, we established conditions in vitro with MIN6 cells and mouse islets and a mixture of proinflammatory cytokines (IL-1β, TNF-α, and IFN-γ) that mimicked the UPR conditions seen in type 1 diabetes. Cell extracts were then subjected to polyribosome profiling to monitor changes to mRNA occupancy by ribosomes. Similar to other privileged mRNAs (Atf4 and Chop), Pdx1 mRNA remained partitioned in actively translating polyribosomes under the UPR, whereas the mRNA encoding a proinsulin-processing enzyme (Cpe) and others partitioned into inactively translating monoribosomes. Bicistronic luciferase reporter analyses revealed that the distal portion of the 5′-untranslated region of mouse Pdx1 (between bp −105 to −280) contained elements that promoted translation under both normal and UPR conditions, and this region exhibited conserved sequences and secondary structure similar to those of other known internal ribosome entry sites. Our findings suggest that Pdx1 protein levels are maintained in the setting of the UPR, in part, through elements in the 5′-untranslated region that confer privileged mRNA translation in a 5′-7-methylguanylate cap–independent manner.

scholarly journals The Role of β Cell Stress and Neo-Epitopes in the Immunopathology of Type 1 Diabetes

2021 ◽  
Vol 11 ◽  
Author(s):  
Jon D. Piganelli ◽  
Mark J. Mamula ◽  
Eddie A. James
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cell Types ◽  
Human Islets ◽  
Β Cells ◽  
Β Cell ◽  
Autoimmune Attack ◽  
Develop Type ◽  
Induced Changes

Due to their secretory function, β cells are predisposed to higher levels of endoplasmic reticulum (ER) stress and greater sensitivity to inflammation than other cell types. These stresses elicit changes in β cells that alter their function and immunogenicity, including defective ribosomal initiation, post-translational modifications (PTMs) of endogenous β cell proteins, and alternative splicing. Multiple published reports confirm the presence of not only CD8+ T cells, but also autoreactive CD4+ T cells within pancreatic islets. Although the specificities of T cells that infiltrate human islets are incompletely characterized, they have been confirmed to include neo-epitopes that are formed through stress-related enzymatic modifications of β cell proteins. This article summarizes emerging knowledge about stress-induced changes in β cells and data supporting a role for neo-antigen formation and cross-talk between immune cells and β cells that provokes autoimmune attack - leading to a breakdown in tissue-specific tolerance in subjects who develop type 1 diabetes.

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