We studied the effect of the acute administration of gliclazide at 160 mg o
n insulin release during hyperglycaemic clamps in 12 type 2 diabetes patien
ts, age 50 +/- 9.0 years, diabetes duration 55 +/- 4.8 years, fasting blood
glucose 9.6 +/- 2.1 mmol/L (means +/- SD). After a 210 min of hyperinsulin
aemic euglycaemic clamp (blood glucose 4.6 +/- 0.14 mmol/L), gliclazide or
placebo (randomised, double-blind, cross-over) was administered; 60 minutes
later, a hyperglycaemic clamp (4hr) at 8mmol/L was started. Plasma C-pepti
de levels increased significantly after the administration of gliclazide (i
ncrement 0.17 +/- 0.15 vs. 0.04 +/- 0.07 nmol/L, p = 0.024) before the clam
p. After the start of the hyperglycaemic clamp, the areas under the curve (
AUC) for insulin and C-peptide did not differ from 0-10 min (first phase) w
ith gliclazide. However, second-phase insulin release (30-240 min) was mark
edly enhanced by gliclazide. AUC plasma insulin (30 to 240 min) was statist
ically significantly higher after gliclazide (72.3 +/- 13.9 vs. -0.56 +/- 9
.4 nmol/l x 210 min, p = 0.022); similarly, AUC plasma C-peptide (30 to 240
min) was also higher: 128 +/- 62 vs. 63 +/- 50 nmol/L x 210 min, p = 0.002
). In conclusion, in long-standing type 2 diabetes the acute administration
of gliclazide significantly enhances second phase insulin release at a mod
erately elevated blood glucose level. In contrast to previous findings in m
ildly diabetic subjects, these 12 type 2 diabetes patients who had an incon
siderable first phase insulin release on the placebo day, only showed an in
significant increase in first phase with gliclazide.