Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus

Background and Aims: Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). Methods: Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. Results: Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean±SEM) was higher (9.3±1.0 vs 4.6±0.6; P=0.002), and ejection fraction was lower (57.4±4.0 vs 74.2±2.4; P=0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6±2.4 vs 20.0±1.4; P=0.034 and 9.3±1.0 vs 5.9±1.1; P=0.00003, respectively), and an improvement in ejection fraction (57.4±4.0 vs 72.6±3.8; P=0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n=13) (57.3±5.4 vs 80.4±2.9; P=0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5±6.1 vs 65.4±6.5; P=NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. Conclusion: Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.