A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation
Adil E Bharucha, Phillip Low, Michael Camilleri, Erica Veil, Duane Burton, Yogish Kudva, Pankaj Shah, Tonette Gehrking, Alan R Zinsmeister, Adil E Bharucha, Phillip Low, Michael Camilleri, Erica Veil, Duane Burton, Yogish Kudva, Pankaj Shah, Tonette Gehrking, Alan R Zinsmeister
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.
Conflict of interest statement
Competing interests None.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3924965/bin/nihms553236f1.jpg)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3924965/bin/nihms553236f2.jpg)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3924965/bin/nihms553236f3.jpg)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3924965/bin/nihms553236f4.jpg)
Figure 5
Scintigraphic images comparing colonic transit…
Figure 5
Scintigraphic images comparing colonic transit before (GC24 (geometric centre for colonic transit at…
Figure 6
Effects of pyridostigmine on bowel…
Figure 6
Effects of pyridostigmine on bowel symptoms in diabetes mellitus and constipation. Pyridostigmine improved…
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3924965/bin/nihms553236f5.jpg)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3924965/bin/nihms553236f6.jpg)
Source: PubMed