Temporary Preservation of β-Cell Function by Diazoxide Treatment in Childhood Type 1 Diabetes

  1. Eva Örtqvist, MD, PHD1,
  2. Elisabeth Björk, MD, PHD2,
  3. Måna Wallensteen, MD, PHD1,
  4. Johnny Ludvigsson, MD, PHD3,
  5. Jan Åman, MD, PHD4,
  6. Calle Johansson, MD5,
  7. Gun Forsander, MD, PHD6,
  8. Fredrik Lindgren, MD, PHD7,
  9. Lars Berglund, PHD8,
  10. Mats Bengtsson, MD, PHD9,
  11. Christian Berne, MD, PHD2,
  12. Bengt Persson, MD, PHD1 and
  13. F. Anders Karlsson, MD, PHD2
  1. 1Department of Woman and Child Health, Astrid Lindgrens Children’s Hospital, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Medicine, University Hospital, Uppsala, Sweden
  3. 3Department of Pediatrics, University of Linköping, Linköping, Sweden
  4. 4Department of Pediatrics, Örebro, Sweden
  5. 5Department of Pediatrics, Jönköping, Sweden
  6. 6Department of Pediatrics, Falun, Sweden
  7. 7Department of Woman and Child Health, Sachs’ Children’s Hospital, Stockholm, Sweden
  8. 8Uppsala Clinical Research Centre, University of Uppsala, Uppsala, Sweden
  9. 9Department of Clinical Immunology, University of Uppsala, Uppsala, Sweden
  1. 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

  • 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.

    • Accepted May 31, 2004.
    • Received February 1, 2004.
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