Indian J Gastroenterol DOI 10.1007/s12664-016-0724-2 REVIEW ARTICLE Management of chronic constipation in patients with diabetes mellitus V. G. M. Prasad1 & Philip Abraham2 Received: 26 July 2016 /Accepted: 27 November 2016 # Indian Society of Gastroenterology 2016 Abstract are indicated if osmotic laxatives are not effective. Newer Aim The aim of this review is to provide an overview of the agents such as chloride-channel activators and 5-HT4 agonist clinical assessment and evidence-based treatment options for can be considered for severe or resistant cases. managing diabetes-associated chronic constipation. Conclusion The primary aim of intervention in diabetic pa- Methods A literature search of published medical reports in tients with chronic constipation is to better manage the diabe- English language was performed using the OVID Portal, from tes along with management of constipation. The physician PUBMED and the Cochrane Database of Systematic should explain the rationale for prescribing laxatives and ed- Reviews, from inception to October 2015. A total of 145 ab- ucate patients about the potential drawbacks of long-term use stracts were identified; duplicate publications were removed of laxatives. They should contact their physician if short-term and 95 relevant full-text articles were retrieved for potential use of prescribed laxative fails to provide relief. inclusion. Results Chronic constipation is one of the most common gas- Keywords Chronic constipation . Diabetes mellitus . trointestinal symptoms in patients with diabetes, and occurs Laxatives more frequently than in healthy individuals. Treatment goals include improving symptoms and restoring bowel function by accelerating colonic transit and facilitating defecation. Based Introduction on guidelines and data from published literature, food and dietary change with exercise and lifestyle change should be The prevalence of diabetes mellitus has reached epidemic pro- the first step in management. For patients recalcitrant to these portions in both developed and developing countries, affect- changes, laxatives should be the next step of treatment. ing more than 366 million people worldwide [1]. This number Treatment should begin with bulking agents such as psyllium, is likely to increase in the coming years as a result of an ageing bran or methylcellulose followed by osmotic laxatives if re- global population, urbanization, rising prevalence of obesity sponse is poor. Lactulose, polyethylene glycol and lactitol are and sedentary lifestyles [2]. Diabetes is on the verge of gaining the most frequently prescribed osmotic agents. Lactulose has a the status of an epidemic in India. As per the 2011 estimate, prebiotic effect and a carry-over effect (continued laxative India is home to 62 million diabetics, with an increase of effect for at least 6 to 7 days, post cessation of treatment). nearly two million each year. India is expected to cross the Stimulants such as bisacodyl, sodium picosulphate and senna 100 million mark by 2030 [3]. Several gastrointestinal (GI) symptoms such as diarrhea, chronic constipation and fecal incontinence are often observed * V. G. M. Prasad in patients with diabetes mellitus [4–6]; among these, chronic [email protected] constipation is the most commonly reported [7]. The preva- lence of chronic constipation in the general population is re- 1 VGM Hospital, 2100, Trichy Road, Coimbatore 641 005, India ported as around 14% [8]. A recent cross-sectional study with 2 P D Hinduja National Hospital and Medical Research Centre, Veer 372 diabetic patients treated at an outpatient clinic reported Savarkar Marg, Mahim, Mumbai 400 016, India that about 31% of patients had chronic constipation. Indian J Gastroenterol Prevalence studies conducted in the US, Europe and Hong Table 1 Rome IV diagnostic criteria for functional constipation Kong report the rate of chronic constipation in diabetic pa- Following criteria should be present for at least 3 months with symptom tients to be 10%, 13% to 22% and 27.5%, respectively, indi- onset at least 6 months prior to diagnosis cating that chronic constipation is a very common GI symp- a tom in diabetics [9–12]. In another cross-sectional study, 1 Presence of ≥2 of the following symptoms : •Lumpyorhardstools(Bristolstoolformscale1–2) in >25% of 13.9% of 224 Indian patients with functional constipation defecations had diabetes [13]. •Straining during >25% of defecations Poor dietary habits, less fluid intake and low physical ac- •Sensation of incomplete evacuation for >25% of defecations tivity are significant factors leading to chronic constipation. •Sensation of anorectal obstruction/blockage for >25% of defecations •Manual maneuvers to facilitate >25% of defecations (digital The prevalence of chronic constipation has been reported to be manipulations, pelvic floor support) higher in women than in men, in older patients (≥50 years), in •<3 spontaneous bowel movements per week those with longer (≥10 years) duration of diabetes mellitus and 2 Loose stools rarely present without the use of laxatives in those who take concomitant medications such as calcium- 3 Insufficient criteria for irritable bowel syndrome channel blockers that promote chronic constipation [14]. The occurrence of chronic constipation is significantly higher in a In research studies, the patients with symptoms of opioid-induced con- diabetic patients with autonomic neuropathy compared to stipation should not be diagnosed as FC, since it is difficult to distinguish between opioid side-effects and other causes of constipation. However, those without neuropathy (22% vs. 9.2%, p <0.04)[15]. clinicians recognize that symptoms of the two conditions might overlap Measures of general health, social functioning and mental health are significantly impaired in patients suffering from chronic constipation and are comparable with those in other the criteria for irritable bowel syndrome, although abdominal conditions such as osteoarthritis, rheumatoid arthritis and pain and/or bloating may be present but are not predominant chronic allergies [16]. Given the growing prevalence of symptoms. Symptom onset should occur at least 6 months diabetes-associated chronic constipation, it is important to fo- before diagnosis, and symptoms should be present during cus attention on early identification and appropriate manage- the last 3 months [21]. ment of these complications for improving both diabetic care Functional constipation is divided into two subtypes: slow- and quality of life of the affected patient. transit constipation or colonic inertia is characterized by a There is no universally accepted definition of constipation. prolonged length of time for stool to pass through the entire In a real-world clinical setting, constipation tends to be a sub- colon [22]; obstructive defecation (also called pelvic floor jective diagnosis. Frequency of bowel movement is an impor- dyssynergia, dyssynergic defecation, anismus, or outlet ob- tant factor in the assessment of constipation, yet there is no struction) is characterized by difficulty in evacuation or a consensus on how often the ‘normal’ bowel opens. There is sense of incomplete evacuation after defecation. wide variation between individuals in ‘normal’ frequency of bowel movements, ranging from three times per day to three times per week, but many patients have expectations of a daily Pathophysiology bowel movement. In addition to frequency of stools, consis- tency of the stool is also important. The Bristol Stool Form The exact pathogenesis of chronic constipation in diabetes Scale is a useful visual aid that was designed to assist in the is not well understood. The autonomic nervous system is evaluation of patients with self-reported constipation who do intimately involved in the control of GI motility and sensi- not have infrequent bowel movements, to establish that hard tivity, and a disturbance of this system may be involved in or lumpy stools are indeed present [17]. the pathophysiology of constipation [15]. Autonomic dys- Based on definition, the prevalence of constipation varies function with a lack of synchronicity between the gut mus- between different populations across the world. The Rome culature and the sphincters is thought to be the major con- classification is widely recognized as a standardized tributing factor [23]. Battle et al. [24]intheirstudyofco- symptom-based classification of functional GI disorders, in- lonic myoelectric and motor activity, demonstrated that di- cluding functional constipation (Table 1)[18]. Other defini- abetic patients with chronic constipation had absent gastro- tions of constipation are consistent with the Rome criteria but colonic response to feeding, resulting in mild to moderate are less quantitative and more subjective [19]. The Rome constipation. High blood sugar levels in both types 1 and 2 criteria are however used principally for research purposes diabetes can lead to loss of interstitial cells of cajal (ICC) and are not widely applied in clinical practice [20]. The re- and diabetic neuropathy. Damage to the nerves controlling cently developed Rome IV classification defines functional the digestive tract motility can lead to chronic constipation constipation as a functional bowel disorder in which symp- and sometimes alternating bouts of diarrhea [25–28]. For toms of difficult, infrequent or incomplete defecation predom- many patients, this condition is chronic, with symptoms inate. Patients with functional constipation should not meet persisting 3 months