In order to elucidate the possible relationship between insulin autoantibodies (IAA), conventional (ICA-IgG) and complement-fixing (CF-ICA) islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies (IgG, IgM and IgA classes), we studied 194 children and adolescents with newly diagnosed Type 1 (insulin-dependent) diabetes. Sixty-one (31.4%) of the subjects were IAA-positive at diagnosis and 73.8% (45/61) of these also had ICA-IgG compared to 51.1% (68/113, p less than 0.01) of IAA-negative children. CF-ICA showed no significant association with IAA. The levels of IAA were significantly higher in the patients with ICA-IgG compared to those without [5.9 +/- 1.6% (SEM) vs 2.5 +/- 0.3%, p less than 0.01]. The patients positive for IAA were younger at diagnosis than the IAA-negative ones; (7.1 +/- 0.5 vs 9.3 +/- 0.3 years, p less than 0.001) and this was also true for ICA-IgG-positive children (8.1 +/- 0.4 vs 9.4 +/- 0.5 years, p less than 0.05) in comparison to ICA-IgG-negative subjects. No significant associations were found between IAA or ICA on the one hand and a positive family history of Type 1 diabetes or metabolic derangements at diagnosis on the other. Subjects negative for ICA were more frequently positive for mumps virus specific IgG antibodies than the ICA-positive patients (50/80 vs 53/111, p less than 0.05), and Coxsackie-B4 virus-specific IgA antibodies were more common in the CF-ICA-negative than the CF-ICA-positive children (53/111 vs 29/80, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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Hormones (Athens)
January 2025
Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can give rise to immune-related adverse events such as ICI-related diabetes mellitus (DM).
Case Presentation: We herein present the case of a 59-year-old Japanese man with malignant melanoma who developed ICI-related DM after 18 months of nivolumab treatment. He experienced marked hyperglycemia and diabetic ketoacidosis without a personal or family history of diabetes.
Endocrinology
January 2025
Thyroid Research Unit, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
The pathogenesis of Thyroid Eye Disease (TED) has been suggested as due to signal enhancement in orbital fibroblasts as a result of autoantibody-induced, synergistic, interaction between the TSH receptor (TSHR) and the IGF-1 receptor (IGF-1R). This interaction has been explained by a "receptor cross talk", mediated via β-arrestin binding. Here, we have examined if this interaction can be mediated via direct receptor contact using modeling and experimental approaches.
View Article and Find Full Text PDFDiabetes
January 2025
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado.
Type 1 Diabetes (T1D) is an autoimmune disease mediated by autoreactive T cells. Our studies indicate that CD4 T cells reactive to Hybrid Insulin Peptides (HIPs) play a critical role in T cell-mediated beta-cell destruction. We have shown that HIPs form in human islets between fragments of the C-peptide and cleavage products of secretory granule proteins.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Protein citrullination modification plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and anti-citrullinated protein antibodies (ACPAs) are extensively employed for clinical diagnosis of RA. However, there remains limited understanding regarding specific citrullinated proteins and their implications in the progression of RA. In this study, we screen and verify insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) as a novel citrullinated protein with significantly elevated citrullinated level in RA.
View Article and Find Full Text PDFSci Rep
January 2025
Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
Correct classification of type 1 (T1D) and type 2 diabetes (T2D) is challenging due to overlapping clinical features and the increasingly early onset of T2D, particularly in South Asians. Polygenic risk scores (PRSs) for T1D and T2D have been shown to work relatively well in South Asians, despite being derived from largely European-ancestry samples. Here we used PRSs to investigate the rate of potential misclassification of diabetes amongst British Bangladeshis and Pakistanis.
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