Abstract
Aim:Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D).Methods64 patients (T1D since <4 months, age 10–17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1–90 400 mg/day Ibuprofen, D1–450 vitamin D 2000 IU/day, D15, 45 sc. 20 μg GAD-alum; as A but placebo instead of Ibuprofen; as B but 40 μg GAD-alum D15, 45; placebo.Results:Treatment was safe and tolerable. No C-peptide preservation was observed. We observed a linear correlation of baseline C-peptide, HbA1c and insulin/per kilogram/24 h with change in C-peptide AUC at 15 months (r = -0.776, p < 0.0001).Conclusion:Ibuprofen, vitamin D + GAD-alum did not preserve C-peptide. Treatment efficacy was influenced by baseline clinical and immunological factors and vitamin D concentration. Clinical Trial Registration: NCT01785108 (ClinicalTrials.gov).
Highlights
It is reasonable to include vitamin D in further studies of GAD-alum trials with the aim to reach relevant serum concentrations, but we find no real support for further use of Ibuprofen, which, beside some immunological effects, did not contribute to β-cell preservation
As Type I diabetes is heterogenous, we need to learn how to select the right patients for adequate therapies based on both genetic, clinical and immunological characteristics
Type I diabetes is heterogenous and our results underline the importance of basal clinical and immunological picture for treatment results
Summary
It is reasonable to include vitamin D in further studies of GAD-alum trials with the aim to reach relevant serum concentrations, but we find no real support for further use of Ibuprofen, which, beside some immunological effects, did not contribute to β-cell preservation. Baseline clinical and immunological data should be considered in the design and evaluation of future immune interventions. As Type I diabetes is heterogenous, we need to learn how to select the right patients for adequate therapies based on both genetic, clinical and immunological characteristics.
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