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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Preexisting insulin autoantibodies predict efficacy of otelixizumab in preserving residual b-Cell function in recent-onset type 1 diabetes
Diabetes Care, Volume 38, No. 4, Year 2015
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Description
OBJECTIVE Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose. RESEARCH DESIGN AND METHODS In the included patients (n = 40 otelixizumab, n = 40 placebo), b-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid-phase radiobinding assay. RESULTS At baseline, only better preserved AUC C-peptide release and higher levels of IAA were associated with better preservation of b-cell function and lower insulin needs under anti-CD3 treatment. In multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P = 0.013) independently predicted outcome together with treatment. During follow-up, good responders to anti-CD3 treatment (i.e., IAA+ participants with relatively preserved b-cell function [‡25% of healthy control subjects]) experienced a less pronounced insulin-induced rise in I(A)A and lower insulin needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment, and their changes showed no relation to functional outcome. CONCLUSIONS There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional b-cell mass and presence of IAA as inclusion criteria. © 2015 by the American Diabetes Association.
Authors & Co-Authors
Keymeulen, Bart
Belgium, Brussels
Vrije Universiteit Brussel
Kaufman, Léonard
Belgium, Brussels
Vrije Universiteit Brussel
Balti Vounsia, Eric
Belgium, Brussels
Vrije Universiteit Brussel
Goubert, Patrick
Belgium, Brussels
Vrije Universiteit Brussel
Verhaeghen, Katrijn
Belgium, Brussels
Vrije Universiteit Brussel
Wenzlau, Janet M.
United States, Aurora
University of Colorado Anschutz Medical Campus
Weets, Ilse
Belgium, Brussels
Vrije Universiteit Brussel
Pipeleers, Daniël G.
Belgium, Brussels
Vrije Universiteit Brussel
Gorus, Frans K.
Belgium, Brussels
Vrije Universiteit Brussel
Statistics
Citations: 18
Authors: 9
Affiliations: 2
Identifiers
Doi:
10.2337/dc14-1575
ISSN:
01495992
Research Areas
Noncommunicable Diseases
Study Design
Randomised Control Trial
Cohort Study