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Title
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Baseline plasma proinsulin response to glucose for predicting therapeutic response to otelixizumab in recent-onset type 1 diabetes
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Author
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Abstract
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| Aims: In recent-onset type 1 diabetes, clamp-derived C-peptide predicts good response to anti-CD3. Elevated proinsulin and proinsulin/C-peptide ratio (PI/CP) suggest increased metabolic/inflammatory beta cell burden. We reanalyzed trial data to compare the ability of baseline acutely glucose-stimulated proinsulin, C-peptide and PI/CP to predict functional outcome.Methods: Eighty recent-onset type 1 diabetes patients participated in the placebo-controlled otelixizumab (GSK; NCT00627146) trial. Hyperglycemic clamps were performed at baseline, 6, 12 and 18 months, involving 3 h of induced euglycemia, followed by acutely raising and maintaining glycemia to >= 10 mmol/l for 140 min. Plasma proinsulin, C-peptide and PI/CP were determined after acute (minute 0 at 10 mmol/l; PI0, CP0, PI/CP0) and sustained glucose stimulation (AUC between minutes 60-140). Outcome was assessed as change in AUC(60-140) C-peptide from baseline.Results: In multiple linear regression, higher baseline (>= median [P50]) PI0 independently predicted preservation of beta cell function in response to anti-CD3 and interacted significantly with IAA. During follow-up, anti-CD3 tempered a further increase in PI/CP0, but not in PI0. CP0 outperformed PI0 and PI/CP0 for post-treatment monitoring.Conclusions: In recent-onset type 1 diabetes, elevated acutely glucose-stimulated proinsulin may complement or replace acutely or sustainedly stimulated C-peptide release for identifying good responders to anti-CD3, but not as outcome measure. |
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Language
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English
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Source (journal)
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Diabetes research and clinical practice. - Amsterdam
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Publication
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Amsterdam
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2023
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ISSN
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0168-8227
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DOI
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10.1016/J.DIABRES.2023.110974
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Volume/pages
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205
(2023)
, p. 1-7
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Article Reference
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110974
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ISI
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001107300400001
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Pubmed ID
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37884063
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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