Journal Article

A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation

Bharucha, Adil E, Camilleri, Michael, Low, Phillip, Zinsmeister, Alan R, Veil, Erica, Burton, Duane, Shah, Pankaj, Gehrking, Tonette, Kudva, Yogish

2013

Overview

Objectives Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. Design After a 9-day baseline period, 30 patients (mean±SEM age 50±2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. Results 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean±SEM 1.98±0.17 (baseline), 1.84±0.16 (treatment)), pyridostigmine accelerated (1.96±0.18 (baseline), 2.45±0.2 units (treatment), p<0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p≤0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. Conclusions Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation. Clinical trial registration number TrialRegNo (NCT 00276406).

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
• Subject: Administration, Oral / Adolescent / Adult / Aged / Algorithms / autonomic disorders / autonomic nervous system / cholinesterase inhibitor / Cholinesterase Inhibitors - administration & dosage / Cholinesterase Inhibitors - adverse effects / Cholinesterase Inhibitors - therapeutic use / Clinical trials / Colon / Constipation / Constipation - drug therapy / Constipation - etiology / Defecation - drug effects / Diabetes / diabetes mellitus / Diabetes Mellitus - drug therapy / Diabetes Mellitus, Type 1 - complications / Diabetes Mellitus, Type 1 - drug therapy / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Dose-Response Relationship, Drug / Double-Blind Method / Drug dosages / dyspepsia / fecal incontinence / Female / Gastrointestinal Motility - drug effects / gastrointestinal transit / Gastrointestinal Transit - drug effects / Humans / inflammatory bowel syndrome / Laxatives / Male / Middle Aged / pelvic floor disorders / pelvic floor physiology / pharmacogenetics / pharmacotherapy / Pharmacy / pyridostigmine / Pyridostigmine Bromide - administration & dosage / Pyridostigmine Bromide - adverse effects / Pyridostigmine Bromide - therapeutic use / Rodents / Studies / treatment / Treatment Outcome