Insulitis and β-cell mass in the natural history of type 1 diabetes

Martha Campbell-Thompson, Ann Fu, John S. Kaddis, Clive Wasserfall, Desmond A. Schatz, Alberto Pugliese, Mark A. Atkinson

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Abstract

Descriptions of insulitis in human islets throughout the natural history of type 1 diabetes are limited. We determined insulitis frequency (the percent of islets displaying insulitis to total islets), infiltrating leukocyte subtypes, and β-cell and α-cell mass in pancreata recovered from organ donors with type 1 diabetes (n = 80), as well as from donors without diabetes, both with islet autoantibodies (AAb+, n = 18) and without islet autoantibodies (AAb2, n = 61). Insulitis was observed in four of four donors (100%) with type 1 diabetes duration of ≤1 year and two AAb+ donors (2 of 18 donors, 11%). Insulitis frequency showed a significant but limited inverse correlation with diabetes duration (r = 20.58, P = 0.01) but not with age at disease onset. Residual β-cells were observed in all type 1 diabetes donors with insulitis, while β-cell area and mass were significantly higher in type 1 diabetes donors with insulitis compared with those without insulitis. Insulitis affected 33% of insulin+ islets compared with 2% of insulin2 islets in donors with type 1 diabetes. A significant correlation was observed between insulitis frequency and CD45+, CD3+, CD4+, CD8+, and CD20+ cell numbers within the insulitis (r = 0.53-0.73, P = 0.004-0.04), but not CD68+ or CD11c+ cells. The presence of β-cells as well as insulitis several years after diagnosis in children and young adults suggests that the chronicity of islet autoimmunity extends well into the postdiagnosis period. This information should aid considerations of therapeutic strategies seeking type 1 diabetes prevention and reversal.

Original languageEnglish (US)
Pages (from-to)719-731
Number of pages13
JournalDiabetes
Volume65
Issue number3
DOIs
StatePublished - Mar 1 2016

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Type 1 Diabetes Mellitus
Tissue Donors
Autoantibodies
Autoimmunity
Age of Onset
Young Adult
Pancreas
Leukocytes
Cell Count
Insulin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Campbell-Thompson, M., Fu, A., Kaddis, J. S., Wasserfall, C., Schatz, D. A., Pugliese, A., & Atkinson, M. A. (2016). Insulitis and β-cell mass in the natural history of type 1 diabetes. Diabetes, 65(3), 719-731. https://doi.org/10.2337/db15-0779

Insulitis and β-cell mass in the natural history of type 1 diabetes. / Campbell-Thompson, Martha; Fu, Ann; Kaddis, John S.; Wasserfall, Clive; Schatz, Desmond A.; Pugliese, Alberto; Atkinson, Mark A.

In: Diabetes, Vol. 65, No. 3, 01.03.2016, p. 719-731.

Research output: Contribution to journalArticle

Campbell-Thompson, M, Fu, A, Kaddis, JS, Wasserfall, C, Schatz, DA, Pugliese, A & Atkinson, MA 2016, 'Insulitis and β-cell mass in the natural history of type 1 diabetes', Diabetes, vol. 65, no. 3, pp. 719-731. https://doi.org/10.2337/db15-0779
Campbell-Thompson M, Fu A, Kaddis JS, Wasserfall C, Schatz DA, Pugliese A et al. Insulitis and β-cell mass in the natural history of type 1 diabetes. Diabetes. 2016 Mar 1;65(3):719-731. https://doi.org/10.2337/db15-0779
Campbell-Thompson, Martha ; Fu, Ann ; Kaddis, John S. ; Wasserfall, Clive ; Schatz, Desmond A. ; Pugliese, Alberto ; Atkinson, Mark A. / Insulitis and β-cell mass in the natural history of type 1 diabetes. In: Diabetes. 2016 ; Vol. 65, No. 3. pp. 719-731.
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