Örtqvist E, Björk E, Wallensteen M, Ludvigsson J, Åman J, Johansson C, Forsander G, Lindgren F, Berglund L, Bengtsson M, Berne C, Persson B, Karisson FA, Ortqvist, Eva, Björk, Elisabeth, Wallensteen, Måna, Ludvigsson, Johnny, Aman, Jan, Johansson, Calle, and Forsander, Gun
Objective: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-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 approximately 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 beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest. [ABSTRACT FROM AUTHOR]