{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T22:42:54Z","timestamp":1781649774186,"version":"3.54.5"},"reference-count":117,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Chronic constipation is a prevalent gastrointestinal (GI) disorder among individuals with diabetes mellitus (DM), occurring more often than in healthy subjects. This review provides a systematic overview of this often-underestimated clinical condition in people with DM. Methods: A narrative review of literature up to 30 May 2025 was conducted, focusing on studies regarding the pathogenesis of constipation in DM, the correlation with GLP-1 RAs treatment, and the diagnostic-therapeutic framework. Results: The mechanisms underlying constipation in DM remain largely unclear; however, a multifactorial etiology has been proposed, involving structural changes in various tissues within the GI tract wall, as well as functional abnormalities, often secondary to hyperglycemia. It is noteworthy that the use of GLP-1 RAs, a class of medications crucial for managing glycemic control and reducing cardiovascular and renal risk in type 2 DM, is another cause of constipation. The diagnosis of constipation is typically based on clinical evaluation, as validated methods for assessing colonic transit are invasive and available only in specialized centers. Treatment objectives include alleviating symptoms and restoring bowel function. The primary strategy for management involves dietary changes and physical activity. If the clinical response is inadequate, the use of laxatives is recommended. Finally, newer agents and mechanical methods may be considered for scenarios that are particularly severe. Conclusions: Given the increasing global prevalence of DM, healthcare professionals must recognize the clinical problem constituted by the occurrence of chronic constipation, especially considering the use of medications such as GLP-1 RAs that may induce this clinical condition.<\/jats:p>","DOI":"10.3390\/nu17193038","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:19:45Z","timestamp":1758701985000},"page":"3038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Sweet Side of Constipation: Colonic Motor Dysfunction in Diabetes Mellitus"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-5991","authenticated-orcid":false,"given":"Michelantonio","family":"De Fano","sequence":"first","affiliation":[{"name":"Endocrine and Metabolic Sciences Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Baluganti","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4207-5340","authenticated-orcid":false,"given":"Marcello","family":"Manco","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Sciences Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-6734","authenticated-orcid":false,"given":"Francesca","family":"Porcellati","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Sciences Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4063-158X","authenticated-orcid":false,"given":"Carmine G.","family":"Fanelli","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Sciences Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-1812","authenticated-orcid":false,"given":"Gabrio","family":"Bassotti","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108839","DOI":"10.1016\/j.diabres.2021.108839","article-title":"The physiological basis of insulin therapy in people with diabetes mellitus","volume":"175","author":"Bolli","year":"2021","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"G645","DOI":"10.1152\/ajpgi.00015.2016","article-title":"Glucosensing in the gastrointestinal tract: Impact on glucose metabolism","volume":"310","author":"Fournel","year":"2016","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_3","first-page":"334","article-title":"Diabetes and gastrointestinal motor activity","volume":"82","author":"Bassotti","year":"1991","journal-title":"Recent. Prog. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1756284819852047","DOI":"10.1177\/1756284819852047","article-title":"Pathophysiology and management of diabetic gastroenteropathy","volume":"12","author":"Meldgaard","year":"2019","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13846","DOI":"10.1111\/eci.13846","article-title":"Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract","volume":"52","author":"Portincasa","year":"2022","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1046\/j.1365-2036.1997.00177.x","article-title":"Cisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin-dependent) diabetes mellitus","volume":"11","author":"Annese","year":"1997","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.3748\/wjg.v26.i19.2333","article-title":"Gastroparesis: New insights into an old disease","volume":"26","author":"Bellini","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1007\/s11938-017-0151-1","article-title":"Diabetes mellitus and the colon","volume":"15","author":"Piper","year":"2017","journal-title":"Curr. Treat. Options Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","article-title":"Bowel disorders","volume":"150","author":"Lacy","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bpg.2010.12.010","article-title":"Epidemiology of constipation in children and adults: A systematic review","volume":"25","author":"Mugie","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/ajg.2013.73","article-title":"Association of low dietary intake of fiber and liquids with constipation: Evidence from the National Health and Nutrition Examination Survey","volume":"108","author":"Markland","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1053\/j.gastro.2012.10.028","article-title":"American Gastroenterological Association technical review on constipation","volume":"144","author":"Bharucha","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"378","DOI":"10.7326\/0003-4819-98-3-378","article-title":"Disorders of gastrointestinal motility associated with diabetes mellitus","volume":"98","author":"Feldman","year":"1983","journal-title":"Ann. Intern. Med."},{"key":"ref_14","first-page":"637","article-title":"Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic subjects","volume":"32","author":"Enck","year":"1994","journal-title":"Z. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1001\/archinte.160.18.2808","article-title":"Gastrointestinal tract symptoms among persons with diabetes mellitus in the community","volume":"160","author":"Maleki","year":"2000","journal-title":"Arch. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1177\/2050640614528175","article-title":"Constipation severity is associated with productivity losses and healthcare utilization in patients with chronic constipation","volume":"2","author":"Neri","year":"2014","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1111\/j.1365-2036.2010.04273.x","article-title":"Systematic review: Impact of constipation on quality of life in adults and children","volume":"31","author":"Belsey","year":"2010","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.atherosclerosis.2018.12.021","article-title":"Constipation and risk of death and cardiovascular events","volume":"281","author":"Sumida","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1023\/A:1026657426396","article-title":"Pilot study of pathophysiology of constipation among community diabetics","volume":"43","author":"Maleki","year":"1998","journal-title":"Dig. Dis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4239\/wjd.v8.i6.249","article-title":"Diabetes-induced mechanophysiological changes in the small intestine and colon","volume":"8","author":"Zhao","year":"2017","journal-title":"World J. Diabetes"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.3748\/wjg.v12.i18.2846","article-title":"Upper gastrointestinal sensory-motor dysfunction in diabetes mellitus","volume":"12","author":"Zhao","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4239\/wjd.v7.i2.14","article-title":"Brain changes in diabetes mellitus patients with gastrointestinal symptoms","volume":"7","author":"Drewes","year":"2016","journal-title":"World J. Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/nmo.12330","article-title":"Diabetic gastrointestinal motility disorders and the role of enteric nervous system: Current status and future directions","volume":"26","author":"Yarandi","year":"2014","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1007\/s00125-015-3831-1","article-title":"Diabetic neuropathy in the gut: Pathogenesis and diagnosis","volume":"59","author":"Azpiroz","year":"2016","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.pain.2007.04.009","article-title":"Gut sensations in diabetic autonomic neuropathy","volume":"131","author":"Andersen","year":"2007","journal-title":"Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1113\/jphysiol.2006.117390","article-title":"Involvement of intramuscular interstitial cells of Cajal in neuroeffector transmission in the gastrointestinal tract","volume":"576","author":"Ward","year":"2006","journal-title":"J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s12013-014-0365-y","article-title":"The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients","volume":"71","author":"Babizhayev","year":"2015","journal-title":"Cell Biochem. Biophys."},{"key":"ref_28","first-page":"37","article-title":"C-peptide, Na+, K(+)-ATPase, and diabetes","volume":"5","author":"Vague","year":"2004","journal-title":"Exp. Diabesity Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1007\/s00125-014-3461-z","article-title":"The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy","volume":"58","author":"Finnerup","year":"2015","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0168-8227(92)90159-O","article-title":"Segmental gut transit in diabetes mellitus: Effect of cisapride","volume":"17","author":"Kawagishi","year":"1992","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2982.2010.01611.x","article-title":"Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress","volume":"23","author":"Chandrasekharan","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/BF01296772","article-title":"Relation of symptoms to impaired stomach, small bowel, and colon motility in long-standing diabetes","volume":"38","author":"Iber","year":"1993","journal-title":"Dig. Dis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/gut.28.1.17","article-title":"Twenty-four-hour manometric recording of colonic motor activity in a healthy man","volume":"28","author":"Narducci","year":"1987","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1080\/07420528.2021.1890761","article-title":"The day-night pattern of colonic contractility is not impaired in type 1 diabetes and distal symmetric polyneuropathy","volume":"38","author":"Jensen","year":"2021","journal-title":"Chronobiol. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.1007\/s10620-021-07346-y","article-title":"Gastrocolic reflex is delayed and diminished in adults with type 1 diabetes","volume":"67","author":"Wegeberg","year":"2022","journal-title":"Dig. Dis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"118","DOI":"10.4321\/S1130-01082012000300003","article-title":"Transit of radiopaque particles through the gastrointestinal tract: Comparison between type 2 diabetes patients and healthy individuals","volume":"104","author":"Jorge","year":"2012","journal-title":"Rev. Esp. Enferm. Dig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1136\/gutjnl-2012-302483","article-title":"A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation","volume":"62","author":"Bharucha","year":"2013","journal-title":"Gut"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/j.1440-1746.2008.05326.x","article-title":"Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in diabetic db\/db mice","volume":"23","author":"Yamamoto","year":"2008","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e14647","DOI":"10.1111\/nmo.14647","article-title":"Downregulation of BDNF-TrkB signaling may contribute to the colonic motility disorders in mice with streptozocin-induced diabetes","volume":"7","author":"Quan","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.regpep.2014.11.005","article-title":"Insulin-like growth factor-1 inhibits colonic smooth muscle cell apoptosis in diabetic rats with colonic dysmotility","volume":"194\u2013195","author":"Sun","year":"2014","journal-title":"Regul. Pept."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1053\/j.gastro.2021.04.040","article-title":"Colonic Motility Is Improved by the Activation of 5-HT2B Receptors on Interstitial Cells of Cajal in Diabetic Mice","volume":"161","author":"Jin","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"G315","DOI":"10.1152\/ajpgi.00196.2007","article-title":"Increase in stretch-induced rhythmic motor activity in the diabetic rat colon is associated with loss of ICC of the submuscular plexus","volume":"294","author":"Forrest","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0016-5085(97)70080-5","article-title":"Physiological hyperglycemia slows gastric emptying in normal subjects and patients with Insulin-Dependent Diabetes Mellitus","volume":"113","author":"Schvarcz","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_44","first-page":"G859","article-title":"Effect of acute hyperglycemia on colorectal motor and sensory function in humans","volume":"273","author":"Maleki","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107751","DOI":"10.1016\/j.jdiacomp.2020.107751","article-title":"Defecation frequency and glycemic control in patients with diabetes: The Fukuoka Diabetes Registry","volume":"35","author":"Ohkuma","year":"2020","journal-title":"J. Diabetes Complicat."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1001\/archinte.161.16.1989","article-title":"Prevalence of gastro-intestinal symptoms associated with diabetes mellitus: A population-based survey of 15,000 adults","volume":"161","author":"Bytzer","year":"2001","journal-title":"Arch. Intern. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3252","DOI":"10.3748\/wjg.v22.i11.3252","article-title":"Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors","volume":"22","author":"Nagata","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2337\/diacare.24.2.371","article-title":"Relationships of upper gastrointestinal motor and sensory function with glycemic control","volume":"24","author":"Rayner","year":"2001","journal-title":"Diabetes Care"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"107799","DOI":"10.1016\/j.jdiacomp.2020.107799","article-title":"Constipation and glycemic control","volume":"35","author":"Conway","year":"2021","journal-title":"J. Diabetes Complicat."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1111\/nmo.12630","article-title":"Association of high dietary saturated fat intake and uncontrolled diabetes with constipation: Evidence from the National Health and Nutrition Examination Survey (NHANES)","volume":"27","author":"Vakili","year":"2015","journal-title":"Neurogastroentereol. Motil."},{"key":"ref_51","first-page":"14","article-title":"Effect of high fat-diet and obesity on gastrointestinal motility","volume":"1","author":"Mushref","year":"2013","journal-title":"Ann. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110828","DOI":"10.1016\/j.diabres.2023.110828","article-title":"The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime?","volume":"203","author":"Porcellati","year":"2023","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"G424","DOI":"10.1152\/ajpgi.00048.2012","article-title":"Serotonin availability in rat colon is reduced during a Western diet model of obesity","volume":"303","author":"Bertrand","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"473 e3","DOI":"10.1053\/j.gastro.2013.10.053","article-title":"MicroRNA 375 mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice","volume":"146","author":"Nezami","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1046\/j.1464-5491.1999.00135.x","article-title":"Gastrointestinal symptoms in Chinese patients with Type 2 diabetes mellitus","volume":"16","author":"Ko","year":"1999","journal-title":"Diabet. Med."},{"key":"ref_56","first-page":"277","article-title":"Disorders of colonic motility in patients with diabetes mellitus","volume":"56","author":"Battle","year":"1983","journal-title":"Yale J. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.3748\/wjg.v16.i14.1782","article-title":"Diabetic factors associated with gastrointestinal symptoms in patients with type 2 diabetes","volume":"16","author":"Kim","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3904\/kjim.2009.24.4.309","article-title":"The prevalence of gastrointestinal symptoms in patients with Non-Insulin Dependent Diabetes Mellitus","volume":"24","author":"Oh","year":"2009","journal-title":"Korean J. Intern. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jdiacomp.2012.09.009","article-title":"Recto-anal manometric characteristic of type 2 diabetes patients who have sensation of incomplete defecation","volume":"27","author":"Jorge","year":"2013","journal-title":"J. Diabetes Complicat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2982.2006.00803.x","article-title":"Pelvic floor anatomy and function","volume":"18","author":"Bharucha","year":"2006","journal-title":"Neurogastroenetrol. Motil."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Reszczy\u0144ska, M., and Kempi\u0144ski, R. (2021). The Prevalence of Enteropathy Symptoms from the Lower Gastrointestinal Tract and the Evaluation of Anorectal Function in Diabetes Mellitus Patients. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030415"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e000514","DOI":"10.1136\/bmjdrc-2018-000514","article-title":"Lower gastrointestinal symptoms are associated with worse glycemic control and quality of life in type 1 diabetes mellitus","volume":"6","author":"Leeds","year":"2018","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/jgh.14022","article-title":"Clinical factors associated with the symptoms of constipation in patients with diabetes mellitus: A multicenter study","volume":"33","author":"Yamada","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.2169\/internalmedicine.7676-21","article-title":"Constipation is a frequent problem associated with vascular complications in patients with type 2 diabetes: A cross-sectional study","volume":"61","author":"Ito","year":"2022","journal-title":"Intern. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s10157-021-02105-9","article-title":"Constipation and diabetic kidney disease: The Fukuoka Diabetes Registry","volume":"25","author":"Ohkuma","year":"2021","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101102","DOI":"10.1016\/j.molmet.2020.101102","article-title":"GLP-1 receptor agonists in the treatment of type 2 diabetes-state-of-the-art","volume":"46","author":"Nauck","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1056\/NEJMoa2501006","article-title":"Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes","volume":"392","author":"McGuire","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1056\/NEJMoa2403347","article-title":"Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes","volume":"391","author":"Perkovic","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1172\/JCI75276","article-title":"The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss","volume":"124","author":"Secher","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e133429","DOI":"10.1172\/jci.insight.133429","article-title":"Semaglutide lowers body weight in rodents via distributed neural pathways","volume":"5","author":"Gabery","year":"2020","journal-title":"JCI Insight"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Liu, L., Chen, J., Wang, L., Chen, C., and Chen, L. (2022). Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1043789"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Aldhaleei, W.A., Abegaz, T.M., and Bhagavathula, A.S. (2024). Glucagon-like Peptide-1 Receptor Agonists Associated Gastrointestinal Adverse Events: A Cross-Sectional Analysis of the National Institutes of Health All of Us Cohort. Pharmaceuticals, 17.","DOI":"10.3390\/ph17020199"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102181","DOI":"10.1016\/j.eclinm.2023.102181","article-title":"Glucometabolic outcomes of GLP-1 receptor agonist-based therapies in patients with type 2 diabetes: A systematic review and network meta-analysis","volume":"64","author":"Caruso","year":"2023","journal-title":"eClinicalMedicine"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/dom.14496","article-title":"The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update","volume":"23","author":"Nauck","year":"2021","journal-title":"Diabetes Obes. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1007\/s40618-024-02441-z","article-title":"The real-world safety profile of tirzepatide: Pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database","volume":"47","author":"Caruso","year":"2024","journal-title":"J. Endocrinol. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.2337\/db21-0459","article-title":"GIP receptor agonism attenuates GLP-1 receptor agonist-induced nausea and emesis in preclinical models","volume":"70","author":"Borner","year":"2021","journal-title":"Diabetes"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"American College of Gastroenterology Chronic Constipation Task Force (2005). An evidence-based approach to the management of chronic constipation in North America. Am. J. Gastroenterol., 100, S1\u2013S4.","DOI":"10.14309\/00000434-200507001-00001"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41395-018-0286-2","article-title":"Digital Rectal Examination: The Whole World is a Country!","volume":"114","author":"Bellini","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"413","DOI":"10.2147\/CEG.S256364","article-title":"Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options","volume":"14","author":"Bassotti","year":"2021","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/ajg.2010.70","article-title":"Anorectal disorders","volume":"105","author":"Bharucha","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_81","first-page":"424","article-title":"The pathophysiology, diagnosis and treatment of constipation","volume":"106","year":"2009","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrgastro.2018.7","article-title":"International Working Group for Disorders of Gastrointestinal Motility and Function. Expert consensus document: Advances in the diagnosis and classification of gastric and intestinal motility disorders","volume":"15","author":"Keller","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Lambiase, C., D\u2019Alba, L., Galeazzi, F., Bassotti, G., Consalvo, D., Battaglia, E., Cataudella, G., Neri, M.C., Londoni, C., and Rossitti, P. (2024). The Diagnosis and Management of Chronic Constipation in Italy: Results from a Survey Conducted among Italian Gastroenterologists. J. Clin. Med., 13.","DOI":"10.3390\/jcm13206047"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/apt.18100","article-title":"Editorial: Sonographic assessment of colonic content-A new tool for constipation?","volume":"60","author":"Maconi","year":"2024","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s12664-016-0724-2","article-title":"Management of chronic constipation in patients with diabetes mellitus","volume":"36","author":"Prasad","year":"2017","journal-title":"Indian J. Gastroenterol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s11739-011-0698-0","article-title":"A practical approach to diagnosis and management of functional constipation in adults","volume":"8","author":"Bassotti","year":"2013","journal-title":"Intern. Emerg. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/284283a0","article-title":"Mechanism of action of dietary fibre in the human colon","volume":"284","author":"Stephen","year":"1980","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5056\/jnm.2013.19.2.149","article-title":"Primary care management of chronic constipation in Asia: The ANMA chronic constipation tool","volume":"19","author":"Gwee","year":"2013","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/BF02065421","article-title":"Effect of wheat bran in treatment of chronic nonorganic constipation. A double-blind controlled trial","volume":"40","author":"Badiali","year":"1995","journal-title":"Dig. Dis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0140-6736(94)91055-3","article-title":"Bran and irritable bowel syndrome: Time for reappraisal","volume":"344","author":"Francis","year":"1994","journal-title":"Lancet"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). Facilitating positive health behaviors and well-being to improve health outcomes: Standards of Care in diabetes-2025. Diabetes Care, 48, S86\u2013S127.","DOI":"10.2337\/dc25-S005"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1365-2982.2011.01709.x","article-title":"Diagnosis and treatment of chronic constipation-a European perspective","volume":"23","author":"Tack","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1046\/j.1365-2036.1998.00336.x","article-title":"Psyllium is superior to docusate sodium for treatment of chronic constipation","volume":"12","author":"McRorie","year":"1998","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/j.1532-5415.1995.tb07203.x","article-title":"Mechanisms of constipation in older persons and effects of fiber compared with placebo","volume":"43","author":"Cheskin","year":"1995","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ctim.2018.07.004","article-title":"Effects of psyllium vs. placebo on constipation, weight, glycemia, and lipids: A randomized trial in patients with type 2 diabetes and chronic constipation","volume":"40","author":"Soltanian","year":"2018","journal-title":"Complement. Ther. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.clnesp.2018.11.002","article-title":"Effect of flaxseed or psyllium vs. placebo on management of constipation, weight, glycemia, and lipids: A randomized trial in constipated patients with type 2 diabetes","volume":"29","author":"Soltanian","year":"2019","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/sj.ejcn.1601398","article-title":"Therapeutic effects of psyllium in type 2 diabetic patients","volume":"56","author":"Sierra","year":"2002","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1177\/1756283X10384173","article-title":"Current management of strategies and therapeutic targets in chronic constipation","volume":"4","author":"Emmanuel","year":"2011","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/j.1552-4604.1997.tb04264.x","article-title":"Tolerance and efficacy of polyethylene glycol 3350\/electrolyte solution versus lactulose in relieving opiate induced constipa-tion: A double-blinded placebo-controlled trial","volume":"37","author":"Freedman","year":"1997","journal-title":"J. Clin. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1111\/j.1365-2036.2004.01918.x","article-title":"Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation","volume":"19","author":"Bouhnik","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/ajcn\/45.5.1243","article-title":"Fermentation in the human large intestine and the available substrates","volume":"45","author":"Cummings","year":"1987","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_102","first-page":"321","article-title":"Constipation in elderly long-stay patients: Its treatment by magnesium hydroxide and bulk-laxative","volume":"19","author":"Kinnunen","year":"1987","journal-title":"Ann. Clin. Res."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Larsen, N., Vogensen, F.K., van den Berg, F.W., Nielsen, D.S., Andreasen, A.S., Pedersen, B.K., Al-Soud, W.A., S\u00f8rensen, S.J., Hansen, L.H., and Jakobsen, M. (2010). Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009085"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1365-2036.2008.03884.x","article-title":"Clinical trial: The efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation\u2014A 12-week, randomized, double-blind, placebo-controlled study","volume":"29","author":"Quigley","year":"2009","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1056\/NEJMoa0800670","article-title":"A placebo-controlled trial of prucalopride for severe chronic constipation","volume":"358","author":"Camilleri","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/17474124.2019.1568238","article-title":"Prucalopride for the treatment of constipation: A view from 2015 and beyond","volume":"13","author":"Bassotti","year":"2019","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/j.1572-0241.2007.01524.x","article-title":"Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation","volume":"103","author":"Johanson","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1111\/j.1365-2036.2007.03320.x","article-title":"Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: A double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety","volume":"25","author":"Johanson","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1007\/s10620-009-1068-x","article-title":"Efficacy and safety of lubiprostone in patients with chronic constipation","volume":"55","author":"Barish","year":"2010","journal-title":"Dig. Dis. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1080\/14656566.2018.1494728","article-title":"Linaclotide for the treatment of chronic constipation","volume":"19","author":"Bassotti","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1177\/1756283X14528269","article-title":"Elobixibat and its potential role in chronic idiopathic constipation","volume":"7","author":"Acosta","year":"2014","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1007\/s12325-022-02243-w","article-title":"Effects of elobixibat in patients with diabetes and concomitant chronic constipation: An 8-week, prospective, single-center, single-arm study","volume":"39","author":"Hishida","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1016\/j.clinthera.2022.08.009","article-title":"Effects of elobixibat, an inhibitor of ileal bile acid transporter, on glucose and lipid metabolism: A single-arm pilot study in patients with T2DM","volume":"44","author":"Yoshinobu","year":"2022","journal-title":"Clin. Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1080\/17474124.2018.1522248","article-title":"Elobixibat for the treatment of constipation","volume":"12","author":"Chedid","year":"2018","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Rudling, M., Camilleri, M., Graffner, H., Holst, J.J., and Rikner, L. (2015). Specific inhibition of bile acid transport alters plasma lipids and GLP-1. BMC Cardiovasc. Disord., 15.","DOI":"10.1186\/s12872-015-0070-9"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1080\/17474124.2023.2267968","article-title":"Relief from behind: Enemas, the back door enforcement to help treating chronic constipation in adults","volume":"17","author":"Bassotti","year":"2023","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1080\/17425255.2023.2193326","article-title":"Considerations for laxatives in terms of their interactions with other drugs","volume":"19","author":"Bassotti","year":"2023","journal-title":"Expert Opin. Drug Metab. Toxicol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3038\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:40Z","timestamp":1760035720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/19\/3038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":117,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["nu17193038"],"URL":"https:\/\/doi.org\/10.3390\/nu17193038","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}