Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes

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Abstract

Background: Interleukin-1β (IL-1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL-1β in patients with this disorder. We characterized the effects of IL-1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL-1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. Methods: PBMC from healthy adult volunteers were exposed to IL-1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Results: Although in vitro exposure to IL-1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra-treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin-dose-adjusted A1c 1 month after diagnosis. Conclusions: Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.

Original languageEnglish (US)
Pages (from-to)656-667
Number of pages12
JournalPediatric Diabetes
Volume12
Issue number7
DOIs
StatePublished - Nov 2011

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Interleukin 1 Receptor Antagonist Protein
Type 1 Diabetes Mellitus
Interleukin-1
Gene Expression
Insulin
Blood Cells
Therapeutics
Meals
Hemoglobins
Microarray Analysis
Recombinant Proteins
Healthy Volunteers
Control Groups

Keywords

  • CDNA microarray analysis
  • Gene expression
  • Immunomodulatory therapy

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes",
abstract = "Background: Interleukin-1β (IL-1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL-1β in patients with this disorder. We characterized the effects of IL-1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL-1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. Methods: PBMC from healthy adult volunteers were exposed to IL-1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Results: Although in vitro exposure to IL-1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra-treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin-dose-adjusted A1c 1 month after diagnosis. Conclusions: Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.",
keywords = "CDNA microarray analysis, Gene expression, Immunomodulatory therapy",
author = "Sumpter, {Kathryn M.} and Soumya Adhikari and Grishman, {Ellen K.} and White, {Perrin C.}",
year = "2011",
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language = "English (US)",
volume = "12",
pages = "656--667",
journal = "Pediatric Diabetes",
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T1 - Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes

AU - Sumpter, Kathryn M.

AU - Adhikari, Soumya

AU - Grishman, Ellen K.

AU - White, Perrin C.

PY - 2011/11

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N2 - Background: Interleukin-1β (IL-1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL-1β in patients with this disorder. We characterized the effects of IL-1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL-1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. Methods: PBMC from healthy adult volunteers were exposed to IL-1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Results: Although in vitro exposure to IL-1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra-treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin-dose-adjusted A1c 1 month after diagnosis. Conclusions: Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.

AB - Background: Interleukin-1β (IL-1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL-1β in patients with this disorder. We characterized the effects of IL-1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL-1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. Methods: PBMC from healthy adult volunteers were exposed to IL-1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Results: Although in vitro exposure to IL-1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra-treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin-dose-adjusted A1c 1 month after diagnosis. Conclusions: Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.

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