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

Abstract

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.

Figure 1

Study design. Bowel habits and gastrointestinal (GI) transit was recorded during the baseline (B) and medication (M) phases. tid, three times a day.

Figure 2

Consort diagram. All randomised patients completed studies and were included in the analysis.

Figure 3

Effects of pyridostigmine on gastric emptying (GE) and small intestinal transit in diabetes mellitus and constipation. While the gastric emptying half time was shorter after pyridostigmine, differences versus placebo were not significant.

Figure 4

Effects of pyridostigmine on colonic transit in diabetes mellitus and constipation. Pyridostigmine accelerated (p<0.01) GC24 (geometric centre for colonic transit at 24 h) relative to placebo.

Figure 5

Scintigraphic images comparing colonic transit before (GC24 (geometric centre for colonic transit at 24 h) Pre) and after (GC24 Post) placebo or pyridostigmine in diabetes mellitus and constipation.

Figure 6

Effects of pyridostigmine on bowel symptoms in diabetes mellitus and constipation. Pyridostigmine improved stool frequency, consistency and ease of passage compared with placebo.