Six months of diazoxide treatment at bedtime in newly diagnosed subjects with type 1 diabetes does not influence parameters of β-cell function and autoimmunity, but improves glycemic control.

  1. Maria Anita Radtke, M.D. (maria.radtke{at}ntnu.no)1,2,
  2. Ingrid Nermoen, M.D.3,
  3. Magnus Kollind, PhD4,
  4. Svein Skeie, PhD5,
  5. Jan Inge Sørheim, M.D.6,
  6. Johan Svartberg, PhD7,8,
  7. Ingrid Hals, M.Sc1,
  8. Torolf Moen, PhD9,
  9. Gry Høst Dørflinger, M.D.1 and
  10. Valdemar Grill, PhD1,2
  1. 1 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim
  2. 2 Department of Endocrinology, St.Olavs Hospital/University Hospital of Trondheim
  3. 3 Department of Endocrinology, Akershus University Hospital, Lørenskog
  4. 4 Endocrinology unit, Department of Internal Medicine, Levanger Hospital
  5. 5 Section of Endocrinology, Division of Medicine, Stavanger University Hospital
  6. 6 Section of Endocrinology, Department of Medicine, Haukeland University Hospital, Bergen
  7. 7 Section of Endocrinology, Division of Internal Medicine, University Hospital of North Norway; Tromsø
  8. 8 Institute of Clinical Medicine, University of Tromsø
  9. 9 Department of Laboratory Medicine,Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim

Abstract

Objective: Continuous β-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side-effects have hampered therapeutic usefulness. In a double blind study we tested whether lower, intermittent dosing of diazoxide had beneficial effects on insulin production, metabolic control and autoimmunity markers in the absence of side-effects.

Research Design and Methods: Forty-one newly diagnosed type 1 diabetes patients were randomized to 6 months treatment with placebo or diazoxide, 100 mg at bedtime. HbA1c, C-peptide (fasting and glucagon-stimulated) and FoxP3+ regulatory T-cells (Tregs) were measured. Patients were followed for 6 months after intervention.

Results: Of six drop-outs, three were due to perceived side effects: one subject in the diazoxide group experienced rash, another dizziness, and one in the placebo group sleep disturbance. Adverse effects in others were absent.

Diazoxide treatment reduced HbA1c from 8.6% at baseline to 6.0% at 6 and 6.5% at 12 months. Corresponding HbA1c in the placebo arm were 8.3%, 7.3% and 7.5% (p < 0.05 for stronger reduction in the diazoxide group). Fasting and stimulated C-peptide decreased during 12 months similarly in both arms (mean −0.30 and −0.18 nmol/l in the diazoxide, −0.08 and −0.09 nmol/l in the placebo arm). The proportion of Tregs was similar in both arms, and remained stable during intervention, but was significantly lower compared to non-diabetic subjects.

Conclusion: Six months of low-dose diazoxide was without the side-effects, did not measurably affect insulin production, but was associated with improved metabolic control.

Footnotes

    • Received August 3, 2009.
    • Accepted December 10, 2009.

This Article

  1. Diabetes Care
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