Physicians may want to rethink the role of chronic constipation in diabetes management, say experts calling for more research in this area. Constipation has long been thought of as a benign condition and one better suited for self-management. It affects approximately 60% of patients with diabetes, up to 34% of the elderly in the general population, and 16% of adults overall.
Chronic constipation may be due to a number of factors, such as medications, metabolic abnormalities, and comorbidities, but also diet, a gut microbiota imbalance, or physiological factors such as anxiety.
But for patients with chronic medical conditions, such as diabetes, gastrointestinal complications can lead to more stress for individuals who are already managing a complicated condition. Constipation can be long-lasting, possibly leading to hemorrhoids, fecal impaction, bowel incontinence, and gastrointestinal complications, such as diverticulitis, perforation, and peritonitis. Diabetes patients are at high risk for developing other colonic disorders beyond chronic constipation. These include enteropathic diarrhea, colorectal cancer, inflammatory bowel disease, microscopic colitis, and Clostridioides difficile (C diff).
Beyond the discomfort of constipation, new evidence shows an independent association with end-stage renal disease (ESRD), cardiovascular disease, Parkinson disease, and mortality.3-7
A 2011 study published in the American Journal of Medicine by Elena Salmoirago-Blotcher, MD, of the University of Massachusetts Medical School, Worcester, found that of 93,676 postmenopausal women enrolled in the Women’s Health Initiative study, women with severe constipation had a 23% higher risk of cardiovascular events.7 Other studies have confirmed those findings, while a Japanese study by Honkura et al8 documented a 21 to 39% increase higher mortality associated with having only 1 to 2 bowel movements each week.
Constipation Has Been Overlooked and Understudied
The gut plays an important role in eliminating uremic toxins that are excreted by the kidneys to help regulate pH, but constipation may complicate and impede that process leading to excess morbidity and mortality, write the study authors of a review published in February 2020 in Kidney International Reports.
Led by Csaba P. Kovesdy, MD, FASN, a nephrologist and director of the Clinical Outcomes and Clinical Trials Program at the University of Tennessee Health Science Center, Memphis, the study authors say that constipation has been overlooked and understudied, particularly as a complication of chronic kidney disease.2
“In an ongoing quest to improve outcomes in chronic kidney disease, the time has come to advance our understanding of this overlooked, unpleasant, and hazardous gastrointestinal condition and to explore its therapeutic potential beyond conventional constipation management,” Kovesdy et al wrote.
The Problem With Diagnosing Constipation
Kovesdy et al suggests that constipation could be far more common among patients than physicians realize because instead of using subjective diagnostic tools, such as the Rome criteria and the Bristol Stool Form Scale, physicians may be relying on patients to self-report. Whereas diagnostic assessment tools can establish a baseline status and more details necessary for creating a comprehensive treatment plan.
Here’s a glimpse of the 2 most commonly used diagnostic tools for constipation:
· The Rome IV diagnostic criteria for functional constipation includes at least 2 of the following: straining during 25% of defecations; 25% of stools are lumpy or hard; feeling of incomplete evacuation 25% of the time; and a feeling of anorectal obstruction or blockage at least 25% of the time. The criteria also includes the absence of loose stools obtained only with the use of laxative.
· The Bristol Stool Form Scale includes 7 stool types: type 1, separate hard lumps; type 2, sausage-shaped with lumps; type 3, resembling sausage or snake, but with surface cracks; type 4, smooth or soft sausage or snake; type 5, soft blobs with clear-cut edges; type 6, a mushy stool with fluffy pieces and ragged edges; and type 7, watery with no solid pieces.
Constipation can vary from normal-transit in which there is some straining and abdominal discomfort in the presence of an adequate bowel movement or slow-transit in which the bowels move, but slowly. There is a physiological explanation for slow bowel movements, per Kovesdy et al.
“Structurally, patients with slow-transit constipation have been shown to have reduced numbers of interstitial cells of Cajal (ICC) and myenteric plexus neurons expressing the excitatory neurotransmitter substance P54 and abnormalities in the inhibitory transmitters vasoactive intestinal peptide and nitric oxide,” the study authors wrote.
Treatments for Constipation From Selective Serotonin 5-HT4 Receptor Agonists to Acupuncture
There is no one size fits all approach for relieving chronic constipation because the medical and environmental conditions associated with the condition are vast and complex.
Achieving optimal blood sugar levels can relieve mild cases of constipation in some patients with diabetes, but for secondary constipation, which is drug-induced, the patient’s medications should be adjusted if necessary.
Other considerations should be made as well. In diabetes patients, anorectal disorders are prevalent and the patient should be screened for pelvic floor muscle dysfunction, according to Marc S. Piper, MD, and Richard J. Saad, MD, writing in the December 2017 issue of Current Treatment Options in Gastroenterology. They recommend colonic transit testing for patients who fail to respond to laxative therapies.
Kovesdy et al write that the fundamental key to properly managing the condition is to identify and address the etiologic, pathophysiologic, and symptomatic factors associated with the condition in each patient.
Non-pharmacological modifications, such as changes in diet, exercise, and the use of fiber supplements, are more effective for patients with primary constipation. But for secondary constipation, which is drug-induced, pharmacological interventions will most likely be required.
Pharmacological treatment options include laxative compounds such as bulk-forming and osmotic laxatives, stimulants, stool softeners, and lubricants. There are also newer agents of different mechanisms of action, such as chloride channel activators, guanylate cyclase C receptor agonists, selective serotonin 5-HT4 receptor agonists, and ileal bile acid transporter inhibitors.
The American College of Gastroenterology Evidence-Based Monograph and a practice guideline from the American Gastroenterological Association recommend bulk-forming and osmotic agents (such as psyllium and polyethylene glycol) supplemented by stimulant laxatives before using one of the newer agents.
“When there is failure of these agents to either individually, or as combination therapy, [relieve constipation], a variety of pro-secretory agents can be considered,” according to Marc S. Piper, MD, and Richard J. Saad, MD, writing in the December 2017 issue of Current Treatment Options in Gastroenterology.9 “All of these agents require a prescription. This includes the peripheral acting guanylate cyclase-C agonists, linaclotide, and plecanatide. Both agents have been shown to stimulate intestinal fluid secretion and transit.”
Lubiprostone, a peripheral-acting derivative from prostaglandin E1 that activates CIC-2 chloride channels stimulating intraluminal fluid secretion, was studied in a group of 76 patients with diabetes. In study results published in 2017 in the American Journal of Gastroenterology, researchers reported that after 4 weeks of treatment, patients who received lubiprostone had a 20.3 ± 7.3 h difference in colonic transit time than placebo.(9)
Observational studies have shown that nontraditional treatments, such as cannabidiol, can be effective in relieving constipation. And, small studies have shown that acupuncture can offer relief from constipation.
Guangju Zhou, PhD, of the Affiliated Hospital of North Sichuan Medical College, Sichuan, China, is currently conducting a review(1) of existing studies that show acupuncture is effective in relieving constipation. Small studies have shown that acupuncture with electrical stimulation of nerves in the stomach several times each week is also effective in treating chronic constipation.
An Overlooked Area of Study
Despite the increased presence of colonic conditions in diabetes patients, few clinical trials have been conducted, and there is limited evidence-based treatment for diabetes-related constipation, Piper et al wrote.
“Despite this increased risk for these oftentimes chronic colonic conditions, there are few clinical trials in diabetics. In most cases, treatment is extrapolated from studies in the general population or those with functional bowel disorders. It is important for the clinician to be aware of these associated conditions with diabetes mellitus as prevention, early detection, and treatment will improve outcomes. This also underscores the need for more clinical trials, especially treatment trials in the setting of constipation and diarrhea in diabetics,” the study authors wrote.
1. Sumida K, Molnar MZ, Potukuchi PK, et al. Constipation and incident CKD. J Am Soc Nephrol. 2017;28(4):1248-1258. doi:10.1681/ASN.2016060656
2. Kubota Y, Iso H, Tamakoshi A; JACC Study Group. Bowel movement frequency, laxative use, and mortality from coronary heart disease and stroke among japanese men and women: the Japan Collaborative Cohort (JACC) Study. J Epidemiol. 2016;26(5):242-248. doi:10.2188/jea.JE20150123
3. Honkura K, Tomata Y, Sugiyama K, et al. Defecation frequency and cardiovascular disease mortality in Japan: the Ohsaki cohort study. Atherosclerosis. 2016;246:251-256. doi:10.1016/j.atherosclerosis.2016.01.007
4. Sumida K, Molnar MZ, Potukuchi PK. Constipation and risk of death and cardiovascular events. Atherosclerosis. 2019;281:114-120. doi:10.1016/j.atherosclerosis.2018.12.021
5. Salmoirago-Blotcher E, Crawford S, Jackson E, Ockene J, Ockene I. Constipation and risk of cardiovascular disease among postmenopausal women. Am J Med. 2011;124:714-723. doi:10.1016/j.amjmed.2011.03.026
6. Honkura K, Tomata Y, Sugiyama K., et al. Defecation frequency and cardiovascular disease mortality in Japan: the Ohsaki cohort study. Atherosclerosis. 2016;246:251-256. doi:10.1016/j.atherosclerosis.2016.01.007
7. Sumida K, Yamagata K, Kovesdy C. Constipation in CKD. Kidney International Reports. 2020;5(2):121-134. doi:10.1016/j.ekir.2019.11.002
8. Piper M, Saad R. Diabetes mellitus and the colon. Curr Treat Options Gastroenterol.. 2017.15(4):460-474. doi:10.1007/s11938-017-0151-1
9. Christie J, Shroff S, Shahnavaz N, et al. A randomized, double-blind, placebo-controlled trial to examine the effectiveness of lubiprostone on constipation symptoms and colon transit time in diabetic patients. Am J Gastroenterol. 2017;112(2):356-364. doi:10.1038/ajg.2016.531
10. Cui S, Yang Q, Xie S, Liu Q, Zhou G. Acupuncture for chronic constipation in patients with diabetes mellitus: a protocol for systematic review. Medicine. 2021;100(9):e24886. doi:10.1097/MD.0000000000024886
This article originally appeared on Endocrinology Advisor