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A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation
  1. Adil E Bharucha1,
  2. Phillip Low2,
  3. Michael Camilleri1,
  4. Erica Veil1,
  5. Duane Burton1,
  6. Yogish Kudva3,
  7. Pankaj Shah3,
  8. Tonette Gehrking2,
  9. Alan R Zinsmeister4
  1. 1Clinical and Enteric Neuroscience Translational and Epidemiological Research Program (C.E.N.T.E.R.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
  2. 2Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
  3. 3Department of Medicine, Division of Endocrinology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
  4. 4Department of Health Sciences Research, Division of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
  1. Correspondence to Dr Adil E Bharucha, Clinical and Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA; bharucha.adil{at}


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).

  • Constipation
  • treatment
  • autonomic disorders
  • colon
  • gastrointestinal transit
  • pyridostigmine
  • cholinesterase inhibitor
  • diabetes mellitus
  • constipation
  • autonomic nervous system
  • pelvic floor disorders
  • pelvic floor physiology
  • fecal incontinence
  • pharmacogenetics
  • inflammatory bowel syndrome
  • dyspepsia
  • pharmacotherapy

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  • Funding This study was supported by USPHS NIH Grant P01 DK068055 and UL1 RR024150-01* from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. PL's contribution was supported in part by the NIH (NS 44233). The contents of this article are solely the responsibility of the author(s) and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at Information on Reengineering the Clinical Research Enterprise can be obtained from

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the Mayo Clinic Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed