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.