Diabetic gastroenteropathy: a pan-alimentary complication
Open accessAbstract
Autonomic neuropathy contributes to the pathophysiology of diabetic gastroenteropathy, which impacts the entire gastrointestinal tract alongside pancreatic and gallbladder functions. This is evident in the widespread morphological remodelling of the enteric nervous system, smooth muscle cells, interstitial cells of Cajal and vascular supply, causing pan-enteric motor, sensory and secretory disturbances. The gastrointestinal symptoms caused by these changes are often burdensome and non-specific and frequently coexist with poor glycaemic management and even malnutrition, impacting quality of life negatively. The Gastroparesis Cardinal Symptom Index and the Gastrointestinal Symptom Rating Scale are validated questionnaires for assessing gastrointestinal symptoms. However, clinical supplementary objective measures are essential. Transit time assessments are frequently used and typically evaluated using gastric emptying scintigraphy, breath tests or colonic radiopaque markers, but they cannot measure contractile activity or fluid transport. The primary treatment goals are to prevent further disease progression and to obtain symptomatic relief. Treatments include improved glycaemic management and dietary modifications, while pharmacological treatments target gastrointestinal symptoms, small intestinal bacterial overgrowth and exocrine pancreatic insufficiency. Invasive interventions may involve gastric peroral pyloromyotomy or the implantation of a gastric neurostimulator to manage pharmacologically refractory gastroparesis. This review describes the prevalence, pathophysiology, clinical presentation, assessment and treatment of diabetic gastrointestinal dysfunction within each segment of the gastrointestinal tract and directly connected exocrine organs.
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The selective 5‐HT4 receptor agonist prucalopride may improve nausea, early satiety, bloating, and quality of life in selected patients, though it carries gastrointestinal side effects and requires individualization.
“The selective 5‑HT4 receptor agonist prucalopride may improve nausea, early satiety, bloating, and quality of life in selected patients, though it carries gastrointestinal side effects and requires individualization [49, 124, 125].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [49]
Table 1 (Gastric complications of diabetes; page not provided) identifies prucalopride as a 5-HT4 receptor agonist, reports improved quality of life in chronic idiopathic constipation, and lists abdominal pain, nausea and diarrhoea as side effects. The Colonic complications section says it may help constipated individuals with gastroparesis, while the Gastric complications section recommends individualised treatment generally. Neither passage says prucalopride improves nausea, early satiety or bloating. (LLM, conf=0.88)
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Daly, A., Hartnell, S., Boughton, C. K., & Evans, M. (2021) · Journal of Diabetes Science and Technology · doi:10.1177/19322968211035447 · Cited by 23 · cited 1× · see citing works
“There have been few investigations of hybrid closed-loop systems in diabetic gastroparesis, but smaller studies have indicated improved glycaemic management and quality of life [48].”
The ultrasound meal accommodation test in 509 patients with functional gastrointestinal disorders
Steinsvik, E. K., Hausken, T., & Gilja, O. H. (2016) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2016.1153138 · Cited by 22 · cited 1× · see citing works
“Contractile activity can be evaluated using antroduodenal manometry and cine-MRI, while accommodation and sensory function can be assessed with ultrasound, MRI and a barostat [29, 45, 46].”
The association between diabetes and gallstones: a nationwide population-based cohort study
Ratheesh, R., Ulrich, M. T., Ghozy, S. A., Al-Jaboori, M., & Nayak, S. S. (2023) · Gastroenterology Review · doi:10.5114/pg.2023.131395 · Cited by 22 · see citing works
Ambulatory long‐term jejunal manometry in diabetic patients with cardiac autonomic neuropathy
Hackelsberger, N., Schmidt, T., Renner, R., Widmer, R., Pfeiffer, A., & Kaess, H. (1997) · Neurogastroenterology & Motility · doi:10.1046/j.1365-2982.1997.d01-23.x · Cited by 20 · cited 2× · see citing works
“Manometry has confirmed the presence of postprandial hypomotility alongside other abnormal motor patterns in symptomatic individuals [35, 66].”
Mandarino, F. V., Barchi, A., Salmeri, N., Azzolini, F., Fasulo, E., Dell’Anna, G., Vespa, E., Sinagra, E., Jacques, J., & Danese, S. (2024) · DEN Open · doi:10.1002/deo2.70021 · Cited by 19 · see citing works
Monreal‐Robles, R., & Remes-Troche, J. M. (2017) · Current Treatment Options in Gastroenterology · doi:10.1007/s11938-017-0153-z · Cited by 19 · cited 3× · see citing works
“If motility disturbances are associated with hypomotility, symptoms may be treated empirically with prokinetic drugs, such as metoclopramide, domperidone and erythromycin [19].”
InfluentialGlasbrenner, B., Dominguez-Munoz, E., Riepl, R. L., Vetsi, A., & Malfertheiner, P. (1995) · Digestive Diseases and Sciences · doi:10.1007/bf02065429 · Cited by 19 · cited 1× · see citing works
“At the same time, some studies have shown elevated levels of CCK in individuals with diabetes and autonomic neuropathy [33, 34].”
Klinge, M. W., Sutter, N., Mark, E. B., Haase, A., Borghammer, P., Schlageter, V., Lund, S. A., Fleischer, J., Knudsen, K., Drewes, A. M., et al. (2021) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm19195 · Cited by 19 · cited 1× · see citing works
“Small intestinal volume was increased in CT and MRI images of symptomatic individuals with diabetes, accompanied by small intestinal post-prandial hypomotility [44, 65].”
Self-citationDiabetes‐induced mechanophysiological changes in the esophagus
Zhao, J., & Gregersen, H. N. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13180 · Cited by 18 · see citing works
Ghrelin and Obestatin Levels in Type 2 Diabetic Patients With and Without Delayed Gastric Emptying
Harsch, I. A., Koebnick, C., Tasi, A. M., Hahn, E. G., & Konturek, P. C. (2008) · Digestive Diseases and Sciences · doi:10.1007/s10620-008-0622-2 · Cited by 18 · see citing works
Gregersen, H. N., Liao, D., Drewes, A. M., Drewes, A. M., & Zhao, J. (2016) · Current Gastroenterology Reports · doi:10.1007/s11894-015-0481-x · Cited by 15 · cited 6× · see citing works
“The underlying pathophysiological changes are complex, including autonomic neuropathy within the local enteric nervous system and the regulatory spinal and vagal afferents involved in gut–brain communication [1–3].”
InfluentialSelf-citationCassidy, D. J., Gerull, W. D., Zike, V. M., & Awad, M. M. (2024) · Journal of the American College of Surgeons · doi:10.1097/xcs.0000000000001105 · Cited by 15 · see citing works
Klinge, M. W., Borghammer, P., Lund, S. A., Fedorova, T. D., Knudsen, K., Haase, A., Christiansen, J. J., & Krogh, K. (2019) · Neurogastroenterology & Motility · doi:10.1111/nmo.13731 · Cited by 13 · cited 2× · see citing works
“The underlying pathophysiological changes are complex, including autonomic neuropathy within the local enteric nervous system and the regulatory spinal and vagal afferents involved in gut–brain communication [1–3].”
Self-citationHammersjö, R., Roth, B., Höglund, P., & Ohlsson, B. (2016) · The Review of Diabetic Studies · doi:10.1900/rds.2016.13.79 · Cited by 13 · cited 1× · see citing works
“Supporting this, individuals with GLP-1 [31, 32].”
Muroi, K., Miyahara, R., Funasaka, K., Furukawa, K., Sawada, T., Maeda, K., Yamamura, T., Ishikawa, T., Ohno, E., Nakamura, M., et al. (2020) · Digestion · doi:10.1159/000510081 · Cited by 13 · cited 2× · see citing works
“Mano-metric measures are relevant when suspecting motility disturbances in those presenting with dysphagia, with high-resolution manometry providing the most comprehensive and detailed evaluation [12].”
Diabetic diarrhoea: A study on gastrointestinal motility, pH levels and autonomic function
Sangnes, D. A., Dimcevski, G. G., Frey, J., & Søfteland, E. W. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13340 · Cited by 13 · cited 2× · see citing works
“However, accelerated colonic transit time is often detected in individuals with predominant diarrhoea [57].”
Bertoli, D., Mark, E. B., Liao, D., Okdahl, T., Nauser, S., Daugberg, L., Brock, C., Brock, B., Knop, F. K., Krogh, K., et al. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12185968 · Cited by 12 · see citing works
Self-citationThe antroduodenal transition time is prolonged in adults with type 1 diabetes
Brock, C., Liao, D., Wegeberg, A., & Drewes, A. M. (2021) · Neurogastroenterology & Motility · doi:10.1111/nmo.14144 · Cited by 11 · cited 2× · see citing works
“Involvement of the distal stomach is characterised by antral hypomotility, increased pyloric pressure, prolonged antroduodenal transition and dyscoordinated activity between the stomach and the small intestine [22, 25, 28].”
Self-citationChen, L., Peng, Y., Chen, F., & Tung, T. (2015) · World Journal of Clinical Cases · doi:10.12998/wjcc.v3.i7.599 · Cited by 9 · cited 2× · see citing works
“Ultrasonography has proven effective as a primary diagnostic tool, but endoscopic ultrasound, computed tomography or magnetic resonance cholangiopancreatography may be used consecutively when ultrasonography is inconclusive [96].”
Thiruppathy, K., Bajwa, A., Kuan, K. G., Murray, C. D., Cohen, R., & Emmanuel, A. V. (2015) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12244 · Cited by 9 · cited 1× · see citing works
“Rectal hyposensitivity has been observed in both long-term and early diabetes [84, 85] and is most frequently observed combined with dysfunctional sphincters in those with faecal incontinence [83, 86].”
Kornum, D. S., Brock, C., Okdahl, T., Bertoli, D., Kufaishi, H., Wegeberg, A., Høyer, K. L., Mark, E. B., Brock, B., Hansen, C. S., et al. (2024) · Neurogastroenterology & Motility · doi:10.1111/nmo.14956 · Cited by 9 · see citing works
Self-citationGastrocolic Reflex Is Delayed and Diminished in Adults with Type 1 Diabetes
Wegeberg, A., Liao, D., Jensen, S. L., Sørensen, P. S., Wigh, I. M. N., Zaugg, V. S., & Brock, C. (2022) · Digestive Diseases and Sciences · doi:10.1007/s10620-021-07346-y · Cited by 9 · see citing works
Self-citationSmall intestinal bacterial overgrowth in diabetic gastroenteropathy
Varma, R., Chakraborty, S., Burton, D. D., Bailey, K. R., & Bharucha, A. E. (2024) · Neurogastroenterology & Motility · doi:10.1111/nmo.14798 · Cited by 8 · see citing works
Medical Management of Fecal Incontinence in Challenging Populations: A Review
Lee, D. C., & Arora, G. (2014) · Clinics in Colon and Rectal Surgery · doi:10.1055/s-0034-1384661 · Cited by 8 · cited 3× · see citing works
“The treat-ment of faecal incontinence in diabetes has been little investigated and standard treatment regimens are generally used [87, 88].”
Pancreatic exocrine insufficiency in diabetes is associated with autonomic dysfunction
Sangnes, D. A., Bergmann, E. S., Moss, R. M., Engjom, T., & Søfteland, E. W. (2021) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2021.1957496 · Cited by 8 · cited 2× · see citing works
“This extends beyond the stomach and intestines by affecting pancreatic and gallbladder functions [5, 6].”
Medicinal grade opium tincture for severe diarrhea: effect revisited in observational study
Dahlgren, D., & Hellström, P. M. (2023) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000985 · Cited by 7 · see citing works
Yuan, S., Leffler, D., Lebwohl, B., Green, P. H. R., Sun, J., Carlsson, S., Larsson, S. C., & Ludvigsson, J. F. (2024) · Diabetologia · doi:10.1007/s00125-024-06175-8 · Cited by 7 · see citing works
Meling, S., Tjora, E., Eichele, H., Nedergaard, R. B., Ejskjær, N., Brock, C., & Søfteland, E. W. (2023) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2023.108452 · Cited by 4 · see citing works
Self-citationDefecatory disorders in patients with type 1 diabetes and chronic constipation
Xiao, A. H., Ramu, S. K., Gautam, M., & Bharucha, A. E. (2023) · Neurogastroenterology & Motility · doi:10.1111/nmo.14599 · Cited by 3 · see citing works
Debourdeau, A., Gonzalez, J., Mathias, F., Prost, C., Barthet, M. A., & Vitton, V. (2023) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2023.2279928 · Cited by 3 · see citing works
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12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2026
Bajaj, M. S., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Early, K. B., Callaghan, B. C., ChallaSivaKanaka, S., et al. (2025) · Diabetes Care · doi:10.2337/dc26-s012 · Cited by 143 · see citing works
Diabetes mellitus: Complications, emerging therapeutic targets, and evolving treatment approaches
Mohd, S., Kumar, L. L., Harish, V., Kumar, R., Chaudhary, A., & Sharma, V. (2025) · Obesity Medicine · doi:10.1016/j.obmed.2025.100652 · Cited by 15 · see citing works
Zhou, M., Zhao, Y., Chu, C.-L., Behera, T. R., Shen, Q., & Xing, Y.-B. (2025) · World Journal of Diabetes · doi:10.4239/wjd.v16.i9.110053 · Cited by 6 · see citing works
Høyer, K. L., Kornum, D. S., Baunwall, S. M. D., Klinge, M. W., Drewes, A. M., Yderstræde, K. B., Mikkelsen, S., Erikstrup, C., Krogh, K., & Hvas, C. L. (2025) · Diabetologia · doi:10.1007/s00125-025-06544-x · Cited by 6 · see citing works
Self-citationWang, X., Yan, C., Wang, S., Zhu, H., Cao, C., Wu, L., Wang, S., Hu, J., & Zhang, H. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i7.109067 · Cited by 5 · see citing works
The association of ZJU index with bowel health in US participants: a cross-sectional study
An, J., Jiao, C., Guo, J., Zhang, L., Li, Z., Liu, G., Zhang, Y., & Liu, W. (2025) · European journal of medical research · doi:10.1186/s40001-025-03452-z · Cited by 1 · see citing works
“Additionally, the incidence of diarrhea is elevated in diabetic patients and often alternates with constipation [28].”
Ying, H., Wang, Q., He, Q., Cao, Y., Wei, G., Xiao, Z., & Luo, X. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1834999 · Cited by 1 · see citing works
“Long-term hyperglycemia may induce diabetic autonomic neuropathy, impair intestinal motility and rhythmicity, and thereby promote pathogenic bacterial overgrowth and further deterioration of gut microbiota structure (Kornum et al., 2025).”
Liu, L., Zhao, Y., Xi, X., Hou, G., Liu, Y., Wang, Y., & Zhang, D. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1841622 · Cited by 1 · see citing works
Diabetic gastroparesis: pathophysiology and impact on insulin timing choices
Galeano, F., Tumminia, A., Oteri, V., Le Moli, R., Piticchio, T., Scilletta, S., Di Marco, M., Di Pino, A., & Frasca, F. (2026) · Endocrine · doi:10.1007/s12020-026-04693-6
“Antiemetics such as 5-HT3 receptor antagonists (e.g., ondansetron) and dopamine-D2/D3 antagonists (e.g., pro-chlorperazine) are commonly used to control nausea and vomiting, often in combination with prokinetics [49, 61, 124].”
Chronic abdominal pain: Budd-Chiari syndrome with converging pathologies
DeVries, J. J., Myers, H. A., Buffington, J., & Brant, A. (2025) · Journal of Vascular Nursing · doi:10.1016/j.jvn.2025.08.007
Drug Repurposing Patent Applications July–September 2025
Mucke, H. A. (2025) · Drug repurposing · doi:10.58647/drugrepo.25.1.0009
“38 Although all components of the renin-angiotensin system are expressed in the gastrointestinal tract, there is limited information on its alterations in the intestine of diabetic individuals.”
Shi, H., Yao, H., Liu, Y., Fan, M., Cai, S., Xu, S., Jiang, C., Zhang, Y., Jiang, W., Qian, W., et al. (2026) · Journal of Clinical Investigation · doi:10.1172/jci192437
Chen, S., & Lu, M. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1739521
“…manifestations — such as early satiety, bloating, nausea, and delayed gastric emptying — have also been documented in subsets of patients with diabetes and may further impair nutrient intake and absorption, potentially exacerbating glycemic variability and protein – energy de fi ciency (22 – 26).”
Chmelir, T., Jarkovská, D., Šmrhová, T., Dvořáková, M. C., & Pandey, S. (2026) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2026.112792
Expanding the Scope of Ama: A Systems Biology Framework for Metabolic and Immune Disorders
Kolatkar, A. S., & Nakanekar, A. V. (2026) · Journal of Research in Ayurvedic Sciences · doi:10.4103/jras.jras_80_25
Chen, S., Xu, W., Xu, S., & Yao, H. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1777356
“Chronic hyperglycemia can lead to autonomic neuropathy affecting the gastrointestinal tract, resulting in delayed gastric emptying and dysmotility (32, 33).”
Yin, R.-Y., Liu, Z.-J., Yao, Y.-Q., Miao, R.-Y., Guan, H.-F., Zhang, Y., Fang, X.-Y., Zhang, Y.-J., & Tian, J.-X. (2026) · World Journal of Diabetes · doi:10.4239/wjd.115749
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“Hyperactive gastric cholinergic myenteric neurons in mice receiving T2D PSFs suggest dysregulated Ca 2+ dynamics and neuronal activity that may disrupt rhythmicity and peristalsis, mirroring early diabetic enteropathy [4, 9].”
Li, P., Wang, S., Wang, Y., Rao, X., & Dong, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1886576
“…lower esophageal sphincter function, esophageal clearance, and gastric emptying, thereby increasing re fl ux exposure and mucosal vulnerability (2, 3) Functional studies using impedance-pH monitoring, esophageal manometry, heart rate variability, and high-resolution manometry further indicate…”
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Diabetes mellitus and atrophic gastritis: progress in the study of interactive pathogenesis
Zhu, Z., Wang, L., Zhou, T., Che, Y., Shi, Y., Song, J., Zhang, Z., Xu, J., Tian, S., Qu, N., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1955709
- Authors
- Kornum, D. S., Krogh, K., Keller, J., Malagelada, C., Drewes, A. M., & Brock, C.
- Affiliations
- Aarhus University (DK)
- Universität Hamburg (DE)
- Universitat Autònoma de Barcelona (ES)
- Aalborg University Hospital (DK)
- Corresponding author
- Brock, Christina
- ORCID
- Venue
- Diabetologia
- Published
- 2025-02-11
- Volume
- 68
- Issue
- 5
- Pages
- 905-919
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC12021976
- OpenAlex
- W4407356611
- Cited by
- 23
- References
- 97
- Citations by year
- 2026: 15 · 2025: 8
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetologia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
- Keywords
- autonomic neuropathy, interstitial cells of Cajal, gastrointestinal motility disorders, gastric emptying, small intestinal bacterial overgrowth, exocrine pancreatic insufficiency, gastroparesis, glycemic control, malnutrition, quality of life
- MeSH terms
- Diabetic Neuropathies, Gastric Emptying, Gastrointestinal Diseases, Humans, Gastroparesis, Diabetes Complications
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