Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes.
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.


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.
Ortqvist
Eva
E
Department of Woman and Child Health, Astrid Lindgrens Children's Hospital, Karolinska Institutet, Stockholm, Sweden. eva.ortqvist@kbh.ki.se
Björk
Elisabeth
E
Wallensteen
Måna
M
Ludvigsson
Johnny
J
Aman
Jan
J
Johansson
Calle
C
Forsander
Gun
G
Lindgren
Fredrik
F
Berglund
Lars
L
Bengtsson
Mats
M
Berne
Christian
C
Persson
Bengt
B
Karlsson
F Anders
FA
D000293:Adolescent; D002096:C-Peptide / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D003981:Diazoxide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D014665:Vasodilator Agents / Q000627:therapeutic use*
D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D014665:Vasodilator Agents; D003981:Diazoxide