EFFECT OF ERYTHROMYCIN ON GALLBLADDER EMPTYING IN DIABETIC-PATIENTS WITH AND WITHOUT AUTONOMIC NEUROPATHY AND HIGH-LEVELS OF MOTILIN

A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine-sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 mug/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean +/- SE) of 45.3 +/- 8.2% and 37.3 +/- 5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 11 1.5 +/- 14.5 pmol/liter in diabetic patients and 63.3 +/- 6.0 pmol/liter in healthy subjects (P < 0.01). However, patients with AN had higher (130.0 +/- 11.9 pmol/liter) motilin plasma levels than patients without (74.0 +/- 9.4 pmol/liter, P < 0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients without AN, but did not stimulate motilin release in neuropathic patients. A negative correlation (r = -0.75, P < 0.01) was found between basal plasma levels of motilin and peak of gallbladder emptying induced by erythromycin. Atropine completely inhibited the effects of erythromycin on gallbladder emptying and motilin release (P < 0.001 by ANOVA). A negative correlation (r = -0.52, P < 0.05) was also found between plasma glucose concentrations and peak of gallbladder emptying. Present results demonstrate that erythromycin could be used for treating alterations of gallbladder emptying in diabetic patients with or without AN.