Temporary Preservation of β-Cell Function by Diazoxide Treatment in Childhood Type 1 Diabetes
- Eva Örtqvist, MD, PHD1,
- Elisabeth Björk, MD, PHD2,
- Måna Wallensteen, MD, PHD1,
- Johnny Ludvigsson, MD, PHD3,
- Jan Åman, MD, PHD4,
- Calle Johansson, MD5,
- Gun Forsander, MD, PHD6,
- Fredrik Lindgren, MD, PHD7,
- Lars Berglund, PHD8,
- Mats Bengtsson, MD, PHD9,
- Christian Berne, MD, PHD2,
- Bengt Persson, MD, PHD1 and
- F. Anders Karlsson, MD, PHD2
- 1Department of Woman and Child Health, Astrid Lindgrens Children’s Hospital, Karolinska Institutet, Stockholm, Sweden
- 2Department of Medicine, University Hospital, Uppsala, Sweden
- 3Department of Pediatrics, University of Linköping, Linköping, Sweden
- 4Department of Pediatrics, Örebro, Sweden
- 5Department of Pediatrics, Jönköping, Sweden
- 6Department of Pediatrics, Falun, Sweden
- 7Department of Woman and Child Health, Sachs’ Children’s Hospital, Stockholm, Sweden
- 8Uppsala Clinical Research Centre, University of Uppsala, Uppsala, Sweden
- 9Department of Clinical Immunology, University of Uppsala, Uppsala, Sweden
- Address correspondence and reprint requests to Eva Örtqvist, Astrid Lindgrens Children’s Hospital, Q2:05, Karolinska Hospital, S-171 77 Stockholm, Sweden. E-mail: eva.ortqvist{at}kbh.ki.se
Abstract
OBJECTIVE—We examined the effect of diazoxide, an ATP-sensitive K+ channel opener and inhibitor of insulin secretion, on β-cell function and remission in children at clinical onset of type 1 diabetes.
RESEARCH DESIGN AND METHODS—A total of 56 subjects (21 girls and 35 boys, age 7–17 years) were randomized to 3 months of active treatment (diazoxide 5–7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years.
RESULTS—Diazoxide decreased circulating C-peptide concentrations by ∼50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 ± 0.22 vs. 0.31 ± 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (−0.05 ± 0.24 vs. −0.18 ± 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 ± 0.20 and 0.20 ± 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent.
CONCLUSIONS—This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of β-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.
Footnotes
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J.L. has been a member of an advisory panel for Novo Nordisk.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted May 31, 2004.
- Received February 1, 2004.
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