Effect of clonidine on gallbladder contraction and small bowel transit time in insulin-treated diabetics

Cholelithiasis is more prevalent in diabetics than in nondiabetics. Gallbladder dysmotility is supposed to be one of the causative factors. Reduced alpha-adrenergic tone has been demonstrated in the enterocytes of diabetic rats, and its correction by clonidine might explain the beneficial effect that the drug has on diabetic diarrhea. We therefore surmised that diabetic cholecystoparesis could also be due to alpha-adrenergic alterations. To test this hypothesis, we studied gallbladder contractions by real time ultrasonography, and small bowel transit time by lactulose hydrogen breath test, in 13 insulin-requiring diabetics before and after administration of the alpha-adrenergic stimulant clonidine (0.3 mg orally). That plasma levels were sufficient was evidenced indirectly by a fall in blood pressure. Clonidine significantly improved the rate of emptying (0.0193 +/- 0.00057/min vs. 0.0318 +/- 0.0027/min; p less than 0.005), but not the fasting and residual gallbladder volumes. Small bowel transit time was significantly prolonged after clonidine (169 +/- 17 min vs. 208 +/- 17; p less than 0.05). These results suggest that 1) reduced alpha-adrenergic tone corrected by clonidine may be present in the diabetic gallbladder, and 2) clonidine's antidiarrheal effect might be explained, at least in part, by a prolongation of the small bowel transit time.