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Integrated Analysis of the Pancreas and Islets Reveals Unexpected Findings in Human Male With Type 1 Diabetes. | LitMetric

AI Article Synopsis

  • - Recent research reveals significant variability in type 1 diabetes, emphasizing unexpected results in a 22-year-old male patient who had been diagnosed for 8 years, showing a negative for islet autoantibodies and high hemoglobin A1c levels.
  • - Examination of pancreatic tissue from the donor indicated reduced but still present β-cell mass, with some islets lacking β cells entirely, while others retained functional β cells that secreted insulin, which is atypical for long-term type 1 diabetes.
  • - Genetic analysis pointed to a predisposition for type 1 diabetes through specific high-risk genetic markers, and overall findings suggest that the patient’s insulin deficiency stemmed from autoimmune β-cell loss, highlighting the complex and diverse characteristics

Article Abstract

Clinical and pathologic heterogeneity in type 1 diabetes is increasingly being recognized. Findings in the islets and pancreas of a 22-year-old male with 8 years of type 1 diabetes were discordant with expected results and clinical history (islet autoantibodies negative, hemoglobin A1c 11.9%) and led to comprehensive investigation to define the functional, molecular, genetic, and architectural features of the islets and pancreas to understand the cause of the donor's diabetes. Examination of the donor's pancreatic tissue found substantial but reduced β-cell mass with some islets devoid of β cells (29.3% of 311 islets) while other islets had many β cells. Surprisingly, isolated islets from the donor pancreas had substantial insulin secretion, which is uncommon for type 1 diabetes of this duration. Targeted and whole-genome sequencing and analysis did not uncover monogenic causes of diabetes but did identify high-risk human leukocyte antigen haplotypes and a genetic risk score suggestive of type 1 diabetes. Further review of pancreatic tissue found islet inflammation and some previously described α-cell molecular features seen in type 1 diabetes. By integrating analysis of isolated islets, histological evaluation of the pancreas, and genetic information, we concluded that the donor's clinical insulin deficiency was most likely the result autoimmune-mediated β-cell loss but that the constellation of findings was not typical for type 1 diabetes. This report highlights the pathologic and functional heterogeneity that can be present in type 1 diabetes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633619PMC
http://dx.doi.org/10.1210/jendso/bvab162DOI Listing

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