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Oral Insulin Delay ...
Oral Insulin Delay of Stage 3 Type 1 Diabetes Revisited in HLA DR4-DQ8 Participants in the TrialNet Oral Insulin Prevention Trial (TN07)
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- Zhao, Lue Ping (author)
- Fred Hutchinson Cancer Research Center
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- Papadopoulos, George K (author)
- Technological Educational Institute of Epirus
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- Skyler, Jay S (author)
- University of Miami
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- Parikh, Hemang M (author)
- University of South Florida
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- Kwok, William W (author)
- Benaroya Research Institute
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- Bondinas, George P (author)
- Ionian University
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- Moustakas, Antonis K (author)
- Ionian University
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- Wang, Ruihan (author)
- Fred Hutchinson Cancer Research Center
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- Pyo, Chul-Woo (author)
- Fred Hutchinson Cancer Research Center
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- Nelson, Wyatt C (author)
- Fred Hutchinson Cancer Research Center
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- Geraghty, Daniel E (author)
- Fred Hutchinson Cancer Research Center
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- Lernmark, Åke (author)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- English.
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In: Diabetes Care. - 1935-5548. ; , s. 1-9
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.2...
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Abstract
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- OBJECTIVE: To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As).RESEARCH AND METHODS: Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin.RESULTS: Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028).CONCLUSIONS: These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Zhao, Lue Ping
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Papadopoulos, Ge ...
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Skyler, Jay S
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Parikh, Hemang M
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Kwok, William W
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Bondinas, George ...
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show more...
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Moustakas, Anton ...
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Wang, Ruihan
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Pyo, Chul-Woo
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Nelson, Wyatt C
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Geraghty, Daniel ...
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Lernmark, Åke
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Diabetes Care
- By the university
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Lund University