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Ito J, Hagi K, Kochi K, Ueki K, Watada H, Kaku K. Gastrointestinal symptoms in patients receiving imeglimin in combination with metformin: A post-hoc analysis of imeglimin clinical trial data. J Diabetes Investig 2025; 16:629-638. [PMID: 39723797 PMCID: PMC11970294 DOI: 10.1111/jdi.14396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 11/06/2024] [Accepted: 12/14/2024] [Indexed: 12/28/2024] Open
Abstract
INTRODUCTION An increased rate of gastrointestinal (GI) symptoms is reported in patients with type 2 diabetes receiving imeglimin plus metformin vs monotherapy or in combination with other antidiabetic drugs. This post-hoc analysis explored GI symptom incidence, risk factors for their occurrence, and the impact on therapeutic efficacy during imeglimin and metformin combination therapy. MATERIALS AND METHODS Data were derived from the 52-week, open-label, phase 3 TIMES-2 trial in Japanese type 2 diabetes patients. Patients in the imeglimin plus metformin group were divided into two subgroups based on the presence of GI symptoms and diarrhea, with efficacy and safety assessed. Factors associated with their occurrence were explored using multivariate logistic regression analysis. RESULTS Of 64 patients analyzed, GI symptoms and diarrhea occurred in 40.6% (n = 26) and 17.2% (n = 11) of patients, respectively. Metformin dose and patient age did not significantly affect their incidence. Events occurred more frequently within the first 4 months of treatment. Approximately half resolved within 1 week, and most were mild. Type 2 diabetes duration <5 years was significantly associated with diarrhea (odds ratio = 5.979; P = 0.039). Significant hypoglycemic effects were observed from baseline, irrespective of GI symptoms or diarrhea. However, the degree of HbA1c improvement tended to be greater in patients with GI symptoms and diarrhea. CONCLUSIONS Increased awareness regarding the potential for GI symptoms, including diarrhea, during imeglimin plus metformin combination therapy is warranted. This data will provide clinicians with useful information regarding symptomatic treatment when it occurs and help determine whether to continue treatment administration and is expected to improve patient adherence.
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Affiliation(s)
- Jumpei Ito
- Medical Science, Sumitomo Pharma Co., Ltd.TokyoJapan
- Present address:
Rare Disease Business UnitAmgen K.K.TokyoJapan
| | | | - Kenji Kochi
- Data Science, Sumitomo Pharma Co., Ltd.TokyoJapan
| | - Kohjiro Ueki
- Department of Diabetes, Endocrinology and MetabolismNational Center for Global Health and MedicineTokyoJapan
| | - Hirotaka Watada
- Department of Metabolism and EndocrinologyJuntendo University Graduate School of MedicineTokyoJapan
| | - Kohei Kaku
- Department of MedicineKawasaki Medical SchoolOkayamaJapan
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Duan DF, Liu M, Ma DY, Yan LJ, Huang YY, Chen Y, Jiang W, Tang X, Xiong AQ, Shi YY. Exploring Symptom Clusters in Chinese Patients with Diabetic Kidney Disease: A Network Analysis. Int J Gen Med 2024; 17:871-884. [PMID: 38468820 PMCID: PMC10926920 DOI: 10.2147/ijgm.s447921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/26/2024] [Indexed: 03/13/2024] Open
Abstract
Purpose The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients. Methods 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters. Results Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction. Conclusion This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.
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Affiliation(s)
- Di-Fei Duan
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Min Liu
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Deng-Yan Ma
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Lin-Jia Yan
- The Nethersole School of Nursing Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
| | - Yue-Yang Huang
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Yi Chen
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Wei Jiang
- West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - Xi Tang
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
| | - An-Qi Xiong
- Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China
| | - Yun-Ying Shi
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
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Chandra P, Kaleem M, Sachan N, Pathak R, Alanazi AS, Alsaif NA, Alsanea S, Alsuwayt B, Alanazi MM, Kabra A. Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats. Saudi Pharm J 2023; 31:101815. [PMID: 37860685 PMCID: PMC10582054 DOI: 10.1016/j.jsps.2023.101815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 10/01/2023] [Indexed: 10/21/2023] Open
Abstract
Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.
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Affiliation(s)
- Phool Chandra
- Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, U.P. 244001, India
| | - Mohammad Kaleem
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput, Delhi Road (NH-24), Moradabad 244 102, U.P., India
| | - Neetu Sachan
- Maharana Pratap College of Pharmacy, Mandhana, Kanpur 209217, U.P., India
| | - Rashmi Pathak
- Department of Pharmacy, Invertis University, Bareilly 243123, U.P., India
| | - Ashwag S. Alanazi
- Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
| | - Nawaf A. Alsaif
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Sary Alsanea
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Bader Alsuwayt
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Hafr Al-Batin 31991, Saudi Arabia
| | - Mohammed M. Alanazi
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Atul Kabra
- University Institute of Pharma Sciences, Chandigarh University, Mohali 140301, Punjab, India
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Wei L, Ji L, Miao Y, Han X, Li Y, Wang Z, Fu J, Guo L, Su Y, Zhang Y. Constipation in DM are associated with both poor glycemic control and diabetic complications: Current status and future directions. Biomed Pharmacother 2023; 165:115202. [PMID: 37506579 DOI: 10.1016/j.biopha.2023.115202] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/15/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.
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Affiliation(s)
- Luge Wei
- Tianjin University of Traditional Chinese Medicine, China.
| | - Lanqi Ji
- Tianjin University of Traditional Chinese Medicine, China
| | - Yulu Miao
- Tianjin University of Traditional Chinese Medicine, China
| | - Xu Han
- Tianjin University of Traditional Chinese Medicine, China
| | - Ying Li
- Tianjin University of Traditional Chinese Medicine, China
| | - Zhe Wang
- Tianjin University of Traditional Chinese Medicine, China
| | - Jiafeng Fu
- Tianjin University of Traditional Chinese Medicine, China
| | - Liuli Guo
- Tianjin University of Traditional Chinese Medicine, China
| | - Yuanyuan Su
- Tianjin University of Traditional Chinese Medicine, China
| | - Yanjun Zhang
- Tianjin University of Traditional Chinese Medicine, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China
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Ud-Din M, Karout B, Torbé WM, Lunding J, Wegeberg AM, Drewes AM, Brock C, Hellström PM. DIgestive COmplications in DIabetes - the DICODI population study. Scand J Gastroenterol 2023; 58:3-6. [PMID: 35961288 DOI: 10.1080/00365521.2022.2106149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Diabetes type 1 and type 2 may develop gastrointestinal complications e.g., gastroparesis and gastroenteropathy. Concomitant celiac disease and pancreatic exocrine insufficiency occur with high prevalence in diabetes and with symptomatic overlap. Consequently, it is a challenge to disentangle symptoms of these conditions and separate them from functional dyspepsia. We aim to develop a clinical decision-support tool to differentiate the underlying disease in a plethora of gastrointestinal symptoms. METHODS An internet-based computerized survey will collect basic characteristics (diabetes type, age, gender, duration, HbA1c, treatment) and patient reported outcomes by validated questionnaires focusing on (1) gastroparesis using Gastroparesis Cardinal Symptom Index; (2) gastroenteropathy using Gastrointestinal Symptom Rating Scale; (3) celiac disease using Celiac Symptom Index and (4) pancreatic exocrine insufficiency with Pancreatic Exocrine Insufficiency Questionnaire. Logistic regression and multiple regression analyses will identify risk factors and gastrointestinal complications. Cluster analyses and machine learning will classify different symptoms and co-existing presentations, into a likely diagnosis. We seek biomarkers for autonomic neuropathy by characterizing development of retinopathy using the Visual Function Questionnaire-25 and peripheral neuropathy by the Michigan neuropathy questionnaire. Participants are re-examined yearly for disease progression over time. RESULTS From focus group studies gastrointestinal symptoms are of major concern in diabetes. Potentially, estimates of symptom prevalence, risk factor identification and classifications of gastrointestinal complications can be unraveled for feedback to health care providers. CONCLUSION The web-based DICODI project will open up possibilities to detect gastrointestinal complications of diabetes in a societal setting, benefitting people living with diabetes, health care professionals, and society.
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Affiliation(s)
- Moeen Ud-Din
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | | | - Johan Lunding
- Diakonhjemmet Hospital, Oslo University, Oslo, Norway
| | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Per M Hellström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Portincasa P, Bonfrate L, Wang DQH, Frühbeck G, Garruti G, Di Ciaula A. Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract. Eur J Clin Invest 2022; 52:e13846. [PMID: 35904418 DOI: 10.1111/eci.13846] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022]
Abstract
Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - David Q-H Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Gabriella Garruti
- Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
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Sang M, Wu T, Zhou X, Horowitz M, Jones KL, Qiu S, Guo H, Wang B, Wang D, Rayner CK, Sun Z. Prevalence of Gastrointestinal Symptoms in Chinese Community-Dwelling Adults with and without Diabetes. Nutrients 2022; 14:3506. [PMID: 36079764 PMCID: PMC9459935 DOI: 10.3390/nu14173506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Gastrointestinal symptoms have been reported to occur frequently in diabetes, but their prevalence in Chinese community-dwelling individuals with diabetes is unknown. The present study aimed to address this issue and explore the risk factors for gastrointestinal symptoms. METHODS A total of 1304 community-dwelling participants (214 with diabetes, 360 with prediabetes and 730 with normoglycemia) were surveyed for gastrointestinal symptoms using the Diabetes Bowel Symptom Questionnaire. Logistic regression analyses were applied to identify risk factors for gastrointestinal symptoms. RESULTS Of the overall study population, 18.6% reported at least one gastrointestinal symptom, without a significant difference between subjects with normoglycemia (17.7%), prediabetes (19.7%) and diabetes (20.1%). In all three groups, lower gastrointestinal symptoms, particularly diarrhea and constipation, were the most frequent. There was an interaction between age (≥65 years) and diabetes on the prevalence of at least one gastrointestinal symptom (p = 0.01) and of constipation (p = 0.004), with these being most frequent in subjects with diabetes aged ≥ 65 years. After multivariable adjustment, female gender and older age were associated with increased odds of at least one gastrointestinal symptom, specifically lower gastrointestinal symptoms. Older age was also associated with an increase in upper gastrointestinal symptoms. CONCLUSIONS Gastrointestinal symptoms are common in Chinese community-dwelling adults with and without diabetes. Females, and the elderly with diabetes, are at an increased risk of symptoms.
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Affiliation(s)
- Miaomiao Sang
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing 210009, China
| | - Tongzhi Wu
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
| | - Xiaoying Zhou
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing 210009, China
| | - Michael Horowitz
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
| | - Karen L. Jones
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
| | - Shanhu Qiu
- Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing 210009, China
| | - Haijian Guo
- Department of Integrated Services, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China
| | - Bei Wang
- Key Laboratory of Environmental Medicine and Engineering Ministry of Education, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China
| | - Donglei Wang
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing 210009, China
| | - Christopher K. Rayner
- Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
| | - Zilin Sun
- Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing 210009, China
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Tseng PH, Hung CS, Tu CH, Chen CC, Liao WC, Lee YC, Chiu HM, Yang WS, Wu MS. Association of Incidence of Acid-related Upper Gastrointestinal Disorders With Glycated Hemoglobin Level. J Clin Endocrinol Metab 2022; 107:e2563-e2571. [PMID: 35134176 DOI: 10.1210/clinem/dgac062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Previous cross-sectional studies show diabetes and higher levels of plasma hemoglobin A1c (HbA1c) are associated with a higher prevalence of gastrointestinal (GI) complications. However, whether the glycemic status is associated with incident acid-related upper GI disorders remains unclear. OBJECTIVE We aimed to determine the effect of hyperglycemia per se, in terms of HbA1c, on the incidence of acid-related disorders. METHODS We analyzed consecutive subjects who had undergone repeated upper endoscopies as part of the health examinations at the National Taiwan University Hospital from 2005 to 2011. Acid-related endoscopic abnormalities were defined as erosive esophagitis (EE), Barrett's esophagus (BE), and peptic ulcer disease (PUD), which included gastric ulcers (GUs) and duodenal ulcers (DUs). All subjects were categorized by 3 tertiles of HbA1c levels. We analyzed the occurrence of respective acid-related disorders during the follow-up period. RESULTS A total of 11 391 participants (mean HbA1c level 5.6 ± 0.7%) were enrolled in this longitudinal study. During the 38 426.3 person-years of follow-up (mean duration 3.37 ± 1.59 years), the incidence of EE, BE, GU, DU, PUD, and any acid-related disorders were 22.1%, 0.5%, 4.5%, 8.6%, 12.3%, and 30.3%, respectively. The higher HbA1c level was associated with higher risk of disease incidents, except BE, during the follow-up (all log-rank P < .001). In the Cox regression analyses with confounding factors fully adjusted, the hazard ratios for EE, GU, DU, PUD, and acid-related disorders were 1.174, 1.339, 1.24, 1.24, and 1.186, respectively, for the third tertile of HbA1c (all P < .05). CONCLUSION Higher HbA1c level was associated with a higher risk of acid-related upper GI endoscopic abnormalities. Efforts toward better glycemic control may help to prevent the development of late GI complications.
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Affiliation(s)
- Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Sheng Hung
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hung Tu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Chung Liao
- Health Management Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Shiung Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Kazeminia M, Salari N, Shohaimi S, Akbari H, Mohammadi M. Prevalence of gastrointestinal complications in patients with type 2 diabetes mellitus in Iran: a systematic review and meta-analysis. J Diabetes Metab Disord 2022; 21:1029-1036. [PMID: 35673410 PMCID: PMC9167313 DOI: 10.1007/s40200-022-00974-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 01/03/2022] [Indexed: 01/16/2023]
Abstract
Background Type 2 diabetes is the most common diabetes in the world and constitutes a high percentage of diabetes cases. This study aims to determine the overall prevalence of gastrointestinal complaints in Iranian patients with type 2 diabetes. Methods The articles were extracted based on entry and exit criteria by searching the Cochrane (Embase), ScienceDirect databases. Scopus PubMed; And Web of Science (WoS), based on PRISMA 2009. To evaluate the studies, a 22-item STROBE checklist was selected and related items were used. Results The probability of publication bias in reporting the results was examined by the Egger test (P = 0.891). The prevalence rate of gastrointestinal complaints in patients with type 2 diabetes in Iran in 10 studies was 52.3% (95% CI: 33.4-70.7%). The results of metargression showed a significant difference between the sample size and the prevalence of gastrointestinal complaints in patients with type 2 diabetes (P < 0.05). and the prevalence of gastrointestinal complaints in patients with type 2 diabetes. Conclusion The results of this study report that, the prevalence of gastrointestinal complications in type 2 diabetes patients was high. As a result, appropriate measures should be taken to improve the condition of diabetic patients through appropriate policy-making and providing feedback to hospitals and patients.
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Affiliation(s)
- Mohsen Kazeminia
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nader Salari
- Department of Biostatistics, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shamarina Shohaimi
- Department of Biology, Faculty of Science, University Putra Malaysia, Serdang, Selangor Malaysia
| | - Hakimeh Akbari
- Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran
| | - Masoud Mohammadi
- Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran
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10
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Yan H, An Y, Zhang T, Zhao J, Yan J. The efficacy and safety of Tuina for diabetic gastroparesis: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e27964. [PMID: 34964787 PMCID: PMC8615438 DOI: 10.1097/md.0000000000027964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 11/09/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Diabetic gastroparesis (DGP) is one of the most common complication of diabetes. At present, despite the increasing number of clinical researches of treatment with Tuina have been reported, there are no systematic reviews of Tuina therapy for DGP. Therefore, it is of great significance to evaluate its safety and efficacy as a complementary and alternative therapy. METHODS AND ANALYSIS Randomized controlled trials (RCTs) of Tuina therapy in the treatment of DGP will be retrieved from PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP), Medline, and Clinical Trial Register (CTR). We will consider articles published in English or Chinese between database initiation and October 2021. Research selection, data extraction, risk of bias assessment, and meta-analyses will be independently completed by 2 researchers. Our researchers will use Revman 5.3 software, provided by the Cochrane Collaborative Network for conducting systematic reviews and meta-analysis. RESULTS This systematic review provides a high-quality synthesis to assess the effectiveness and safety of Tuina therapy for treating DGP. CONCLUSION The conclusions of our study will provide evidence to determine whether Tuina therapy is an effective and safe intervention for patients with DGP. SYSTEMATIC REVIEW REGISTRATION : INPLASY2021110019.
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The prevalence of disorders of the gut-brain axis in type 2 diabetes mellitus patients with metabolic dysfunction-associated fatty liver disease: an observational study. Acta Gastroenterol Belg 2021; 84:541-547. [PMID: 34965034 DOI: 10.51821/84.4.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND AND STUDY AIM Disorders of the gut-brain axis (DGBI) and metabolic dysfunction-associated liver disease (MAFLD) are frequently diagnosed and exhibit pathophysiological similarities. This study aimed to estimate the prevalence of DGBI in type 2 diabetes mellitus (T2DM) patients with MAFLD. PATIENTS AND METHODS In this single center, observational study, in adults with T2DM demographics, diabetes-related parameters and liver tests were recorded. MAFLD was defined by the presence of hepatic steatosis on imaging. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed based on Rome IV criteria. Quality of life (QOL), anxiety levels and depression levels were documented by validated questionnaires. RESULTS We included 77 patients, 44 with and 33 without steatosis. There were no significant differences in age, body mass index (BMI), waist circumference, HbA1c levels or metformin use between groups. IBS was significantly more prevalent in the liver steatosis group (9/44 vs. 2/33, p = .037), while a similar trend was observed for FD (9/35 vs. 2/31, p = .103). No differences were found in anxiety, depression and overall QOL. However, QOL subscales for health worry, food avoidance and social reaction were significantly higher in the liver steatosis group. CONCLUSIONS In otherwise comparable T2DM patients, DGBI, and especially IBS, are more prevalent in the presence of MAFLD. This difference could not be attributed to increased levels of anxiety or depression. Future research should target the underlying pathophysiological mechanisms.
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Sommers T, Mitsuhashi S, Singh P, Hirsch W, Katon J, Ballou S, Rangan V, Cheng V, Friedlander D, Iturrino J, Lembo A, Nee J. Prevalence of Chronic Constipation and Chronic Diarrhea in Diabetic Individuals in the United States. Am J Gastroenterol 2019; 114:135-142. [PMID: 30410038 DOI: 10.1038/s41395-018-0418-8] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Diabetic individuals commonly report disordered bowel habits. This study aims to report the prevalence and associated factors of chronic diarrhea (CD) and chronic constipation (CC) in diabetics using a nationally representative sample of US adults. METHODS Analyses were performed using data from subjects in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) dataset who completed the Bowel Health Questionnaire. The NHANES dataset provides medical comorbidities, demographics, and dietary habits of a nationally representative group of adult survey participants in the United States. CC and CD were defined by Bristol Stool Form Scale (BSFS) Types 1 & 2 and BSFS Types 6 & 7 as the "usual or most common stool type," respectively, and frequent laxative users were also defined as having CC. Co-variables for all subjects included demographic and lifestyle factors, and co-variables evaluated only in diabetics included treatment and severity markers for diabetes. RESULTS We identified 661 diabetic subjects and 4488 non-diabetic subjects. Diabetic subjects (25.8%) reported disordered bowel habits. In unadjusted analysis, CD was more prevalent in diabetics than in non-diabetics (11.2% vs. 6.0%; p < 0.0001); however, the prevalence of CC was not significantly different between groups (14.6% vs. 11.2%; p = 0.126). When adjusting for covariates (e.g., BMI, gender, age, race/ethnicity, education level, etc.), diabetes itself remained associated with CD. Diabetic individuals with CD more frequently used drugs to lower blood sugar, and diabetic subjects with CC more frequently had poor kidney function. CONCLUSIONS CD is significantly more prevalent in diabetics than in non-diabetics, whereas CC is not, and the association between CD and diabetes remains significant when adjusting for covariates. Use of medications that lower blood sugar is associated with CD in diabetic individuals, whereas poor kidney function is associated with CC in diabetics.
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Affiliation(s)
- Thomas Sommers
- Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
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Ghadiri-Anari A, Gholami S, Zolfaghari F, Namiranian N. Prediabetes and gastrointestinal (GI) symptoms; a cross-sectional study. Diabetes Metab Syndr 2019; 13:844-846. [PMID: 30641819 DOI: 10.1016/j.dsx.2018.12.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 12/07/2018] [Indexed: 12/19/2022]
Abstract
AIMS Prediabetes associate with known micro and macrovascular complications of diabetes. Also gastrointestinal symptoms are present in diabetics higher than general population. The aim of this study was evaluation of gastrointestinal symptoms in subjects with prediabetes. METHODS This analytical cross-sectional study was conducted on 130 persons 30-65 years old, 65 pre-diabetic patients and 65 persons without glucose disorders from 2014 to 2015 in YAZD province. FBS and HbA1c used for diagnosis prediabetes. Demographic and medical history were collected. A questionnaire according to Rome III Criteria was used to collect digestive information (diarrhea, abdominal pain, constipation, abdominal bloating, heartburn, increased gas passing, nausea, intermittent diarrhea and constipation in the last 6 months ago). Frequency of GI symptoms in subjects with and without glucose disorders were compared. Data were analyzed by SPSS software Version 20. Data were reported as mean ± standard deviation or frequency and T-test, Chi Square and Spearman correlation coefficient tests were used. P-value less than 0.05 were considered statistically significant. RESULTS Higher frequency of bloating, early satiety, nausea, heartburn, gas passing and constipation are seen in the pre-diabetes group than in the control group; (p-value 0.0001, 0.0001, 0.0001, 0.0001, 0.001 and 0.0001 respectively). 96.9% in prediabetics had at least one gastrointestinal symptom, while in the normal groups 50% had at least one GI symptom (p-value: 0.0001). CONCLUSIONS Gastrointestinal symptoms were seen in prediabetics higher than healthy persons. So, prediabetes can not be considered an entirely benign and asymptomatic condition. Lifestyle interventions maybe necessary at this state.
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Affiliation(s)
- Akram Ghadiri-Anari
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Somaye Gholami
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Fariba Zolfaghari
- Medical Student, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasim Namiranian
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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AlOlaiwi LA, AlHarbi TJ, Tourkmani AM. Prevalence of cardiovascular autonomic neuropathy and gastroparesis symptoms among patients with type 2 diabetes who attend a primary health care center. PLoS One 2018; 13:e0209500. [PMID: 30576362 PMCID: PMC6303088 DOI: 10.1371/journal.pone.0209500] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Accepted: 12/06/2018] [Indexed: 12/27/2022] Open
Abstract
Introduction Cardiovascular autonomic neuropathy (CAN) and gastroparesis are two types of diabetic autonomic neuropathy which could affect patients' quality of life and carry significant morbidity and mortality outcomes. The aim of this study was to estimate the prevalence and risk factors of both CAN and gastroparesis symptoms among patients with type 2 diabetes mellitus (T2DM) at primary health care level. Methods A cross-sectional study was conducted among 400 adults with T2DM from April 1, 2017 to March 20, 2018. CAN was defined by the presence of any of the followings: resting tachycardia, orthostatic hypotension or prolonged corrected QT interval in the electrocardiogram. Gastroparesis symptoms were assessed using a validated questionnaire: the Gastroparesis Cardinal Symptom Index. Results The mean age of study participants and disease duration were 55.26 ± 10.65 years and 10.77 ± 6.89 years, respectively. CAN was present in 15.3% of the participants. Hypertension, smoking, antihypertensive use, body mass index, dyslipidemia and albuminuria were significantly higher in participants with CAN than those without CAN (p<0.05). Prolonged disease duration (p = 0.007) and hypertension (p = 0.004) were independently associated with CAN. Gastroparesis symptoms were present in 6.3% of study participants and were significantly associated with those of female gender (P<0.05). Metformin use emerged as an independent predictor of the presence of at least one symptom (p = 0.001). Conclusion Among Saudi adults with T2DM at primary care level, the prevalence of CAN is significant and is independently related to disease duration and hypertension, indicating the importance of CAN screening, especially for those with prolonged disease duration, and the importance of controlling blood pressure in order to prevent CAN or its consequences. The prevalence of gastroparesis symptoms is 6% and is independently related to metformin use, and therefore, symptomatic screening is required to decide which patients need further evaluation.
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Affiliation(s)
- Lina A. AlOlaiwi
- Family and Community Medicine Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Turki J. AlHarbi
- Family and Community Medicine Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
- * E-mail: ,
| | - Ayla M. Tourkmani
- Family and Community Medicine Department, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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Abstract
This article is a comprehensive review of diabetic gastroparesis, defined as delayed or disordered gastric emptying, including basic principles and current trends in management. This review includes sections on anatomy and physiology, diagnosis and differential diagnosis as well as management and current guidelines for treatment of diabetic gastroparesis. Diabetic gastroparesis (DGp) is a component of autonomic neuropathy resulting from long-standing poorly controlled type 1 and type 2 diabetes. The diagnostic workup of DGp first excludes obstruction and other causes including medications that may mimic delayed/disordered gastric emptying. Targeting nutrition, hydration, symptomatic relief and glycemic control are mainstays of treatment for DGp. Additionally, optimal treatment of DGp includes good glycemic management, often involving customizing insulin delivery using basal-bolus insulin and technology, including sensor-augmented pumps and continuous glucose monitoring systems. Prokinetic medications may be helpful in DGp symptoms, although only limited number of medications is currently available in the USA. Selected medication-refractory patients with DGp may benefit from gastric neuromodulation, and some from surgical interventions including pyloric therapies that can also be done endoscopically. As is true of any of the diabetic complications, prevention of DGp by early and optimal glycemic control is more cost-effective.Funding: Hansa Medcell, India.
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Affiliation(s)
- Sathya Krishnasamy
- Division of Endocrinology, Metabolism, and Diabetes, University of Louisville, Louisville, KY, USA
| | - Thomas L Abell
- Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY, USA.
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Zhao D, Zhao JB. Comparison of Chang Run Tong and Forlaxin Treatment of Constipation in Elderly Diabetic Patients. J Altern Complement Med 2018; 24:472-480. [PMID: 29698053 DOI: 10.1089/acm.2018.0052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Dong Zhao
- Department of Chinese Medicine Geriatrics, China-Japan Hospital, Beijing, China
| | - Jing-Bo Zhao
- Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
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17
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Yamada E, Namiki Y, Takano Y, Takamine H, Inazumi K, Sasaki H, Yamada M, Ito S, Iwasaki T, Mantani N, Minami T, Osada UN, Terauchi Y, Nakajima A. Clinical factors associated with the symptoms of constipation in patients with diabetes mellitus: A multicenter study. J Gastroenterol Hepatol 2018; 33:863-868. [PMID: 29048762 DOI: 10.1111/jgh.14022] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 09/13/2017] [Accepted: 10/11/2017] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND AIM Changes in treatment protocols for patients with diabetes mellitus (DM) may influence the functions of the digestive tract. This study examined possible clinical factors associated with the symptoms of constipation in patients with DM. METHODS This was a multicenter study. Participants were consecutive Japanese patients undergoing treatment for type 1 or type 2 DM. Constipation was evaluated using the gastrointestinal symptom rating scale. Diabetic neuropathy was evaluated by the presence or absence of peripheral neuropathy of the lower limbs. RESULTS Of 419 participants, 258 were men and 161 women (ratio: 1.6:1), with a mean age of 63.6 ± 12.5 years. In multivariate analysis, symptoms of constipation were significantly associated with age (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.01-1.04, P = 0.032), lower mental component summary (OR = 3.31, 95% CI: 1.69-6.48, P < 0.001), diabetic retinopathy (OR = 1.99, 95% CI: 1.14-3.45, P = 0.015), and diabetic neuropathy (OR = 1.86, 95% CI: 1.10-3.16, P = 0.021). In patients with peripheral neuropathy of the lower limbs, regardless of the presence of other complications (diabetic nephropathy and diabetic retinopathy), the prevalence of symptoms of constipation was twice that of patients without peripheral neuropathy (40.0-49.1% vs 22.0%). Diabetic drugs were not associated with symptoms of constipation. CONCLUSIONS Diabetic neuropathy, defined as peripheral neuropathy of the lower limbs, was significantly associated with symptoms of constipation. Peripheral neuropathy of the lower limbs is not a direct risk factor for constipation but may be a useful criterion when assessing whether constipation is associated with DM.
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Affiliation(s)
- Eiji Yamada
- Gastroenterology Division, National Hospital Organization Yokohama Medical Center, Yokohama, Japan
| | - Yulia Namiki
- Diabetes and Endocrinology Division, Saiseikai Yokohama-shi Nanbu Hospital, Yokohama, Japan
| | - Yuya Takano
- Diabetes and Endocrinology Division, Saiseikai Yokohama-shi Nanbu Hospital, Yokohama, Japan
| | - Hikaru Takamine
- Diabetes and Endocrinology Division, Saiseikai Yokohama-shi Nanbu Hospital, Yokohama, Japan
| | - Koji Inazumi
- Endocrinology and Diabetes Division, Yokosuka Kyosai Hospital, Yokosuka, Japan
| | - Hiroto Sasaki
- Endocrinology and Metabolism Division, Yokohama Sakae Kyosai Hospital, Yokohama, Japan
| | - Masayo Yamada
- Endocrinology and Metabolism Division, Yokohama Sakae Kyosai Hospital, Yokohama, Japan
| | - Satoshi Ito
- Diabetes and Endocrinology Division, Machida Municipal Hospital, Machida, Japan
| | | | | | - Taichi Minami
- Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Uru Nezu Osada
- Diabetes and Endocrinology Division, Saiseikai Yokohama-shi Nanbu Hospital, Yokohama, Japan.,Bayside Clinic, Yokohama, Japan
| | - Yasuo Terauchi
- Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Atsushi Nakajima
- Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
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Du YT, Rayner CK, Jones KL, Talley NJ, Horowitz M. Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management. Diabetes Care 2018; 41:627-637. [PMID: 29463666 DOI: 10.2337/dc17-1536] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 12/07/2017] [Indexed: 02/05/2023]
Abstract
If you haven't measured something, you really don't know much about it.-Karl Pearson (attributed)Gastrointestinal (GI) symptoms represent an important and often unappreciated cause of morbidity in diabetes, although the significance of this burden across the spectrum of patients and the underlying pathophysiology, including the relationship of symptoms with glycemic control, remain poorly defined. The relevance of GI symptoms and the necessity for their accurate assessment have increased with the greater focus on the gut as a therapeutic target for glucose lowering. This review addresses the prevalence, assessment, pathogenesis, and management of GI symptoms in diabetes, beginning with broad principles and then focusing on specific segments of the GI tract. We initially performed a literature search of PubMed by using synonyms and combinations of the following search terms: "gastrointestinal symptoms", "diabetes", "prevalence", "pathogenesis", "diagnosis", and "management". We restricted the search results to English only. Review papers and meta-analyses are presented as the highest level of evidence where possible followed by randomized controlled trials, uncontrolled trials, retrospective and observational data, and expert opinion.
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Affiliation(s)
- Yang T Du
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
- National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
- National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
- Karolinska Institute, Stockholm, Sweden
| | - Michael Horowitz
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
- National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
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Meldgaard T, Olesen SS, Farmer AD, Krogh K, Wendel AA, Brock B, Drewes AM, Brock C. Diabetic Enteropathy: From Molecule to Mechanism-Based Treatment. J Diabetes Res 2018; 2018:3827301. [PMID: 30306092 PMCID: PMC6165592 DOI: 10.1155/2018/3827301] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 08/13/2018] [Indexed: 12/19/2022] Open
Abstract
The incidence of the micro- and macrovascular complications of diabetes is rising, mirroring the increase in the worldwide prevalence. Arguably, the most common microvascular complication is neuropathy, leading to deleterious changes in both the structure and function of neurons. Amongst the various neuropathies with the highest symptom burden are those associated with alterations in the enteric nervous system, referred to as diabetic enteropathy. The primary aim of this review is to provide a contemporaneous summary of pathophysiology of diabetic enteropathy thereby allowing a "molecule to mechanism" approach to treatment, which will include 4 distinct aspects. Firstly, the aim is to provide an overview of the diabetes-induced structural remodelling, biochemical dysfunction, immune-mediated alterations, and inflammatory properties of the enteric nervous system and associated structures. Secondly, the aim is to provide a synopsis of the clinical relevance of diabetic enteropathy. Thirdly, the aim is to discuss the various patient-reported outcome measures and the objective modalities for evaluating dysmotility, and finally, the aim is to outline the clinical management and different treatment options that are available. Given the burden of disease that diabetic enteropathy causes, earlier recognition is needed allowing prompt investigation and intervention, which may lead to improvements in quality of life for sufferers.
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Affiliation(s)
- Theresa Meldgaard
- Mech-Sense, Department of Clinical Medicine, Aalborg University, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
| | - Søren Schou Olesen
- Mech-Sense, Department of Clinical Medicine, Aalborg University, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
| | - Adam D. Farmer
- Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, 4 Newark Street, London E1 2AT, UK
- Department of Gastroenterology, University Hospitals of North Midlands, Stoke-on-Trent, Staffordshire ST4 6QJ, UK
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul Jensens Boulevard, 8200 Aarhus N, Denmark
| | - Anne Astrid Wendel
- Mech-Sense, Department of Clinical Medicine, Aalborg University, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
| | - Birgitte Brock
- Steno Diabetes Center Copenhagen, The Capital Region of Denmark, Niels Steensens Vej 2-4, Building: NSK, 2820 Gentofte, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Clinical Medicine, Aalborg University, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Clinical Medicine, Aalborg University, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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Huang Y, Zhang H, Zhang M, Li W, Wang J, Hu J. The Association Between Fasting C-peptide and Gastrointestinal Symptoms of Gastroparesis in Type 2 Diabetic Patients. J Neurogastroenterol Motil 2017; 23:254-261. [PMID: 27820956 PMCID: PMC5383120 DOI: 10.5056/jnm16091] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 10/05/2016] [Accepted: 10/09/2016] [Indexed: 12/24/2022] Open
Abstract
Background/Aims The relationship between C-peptide levels and gastrointestinal (GI) symptoms in type 2 diabetic patients is not clear. The purpose of this study is to examine the association between fasting C-peptide and GI symptoms of gastroparesis in type 2 diabetic patients. Methods We recruited 333 type 2 diabetic patients into the present study. All patients filled out questionnaires of gastroparesis cardinal symptom index (GCSI) to evaluate GI symptoms. Hospital anxiety and depression scale were adopted to define anxiety and depression. Patients with GCSI scores ≥ 1.9 were regarded as having symptoms of gastroparesis. Results In our study, 71 (21.3%) type 2 diabetic patients had GCSI scores ≥ 1.9. In comparison to patients with scores < 1.9, those with scores ≥ 1.9 had significantly lower fasting c-peptide levels (1.49 ng/mL vs 1.94 ng/mL, P < 0.001), higher prevalence of depression (40.9% vs 18.3%, P < 0.001) and anxiety (28.2% vs 13.0%, P = 0.002). Multivariate logistic regression revealed that fasting C-peptide was still significantly associated with symptoms of gastroparesis (odds ratio, 0.67; 95% confidence intervals, 0.48–0.94; P = 0.021), even after adjustments for age, sex, body mass index, HbA1c, current smoking and drinking status, anxiety, and depression. Furthermore, linear regressions showed that fasting C-peptide was independently and negatively related to GCSI scores (standardized regression coefficient, −0.29; P < 0.001) in patients with at least one GI symptom. Conclusion GI symptoms of diabetic gastroparesis affect approximately 20% of type 2 diabetes patients and are associated with lower fasting C-peptide levels independent of depression and anxiety status.
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Affiliation(s)
- Yun Huang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Honghong Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Minxia Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wenya Li
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jinhua Wang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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Ravages of Diabetes on Gastrointestinal Sensory-Motor Function: Implications for Pathophysiology and Treatment. Curr Gastroenterol Rep 2016; 18:6. [PMID: 26768896 DOI: 10.1007/s11894-015-0481-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Symptoms related to functional and sensory abnormalities are frequently encountered in patients with diabetes mellitus. Most symptoms are associated with impaired gastric and intestinal function. In this review, we discuss basic concepts of sensory-motor dysfunction and how they relate to clinical findings and gastrointestinal abnormalities that are commonly seen in diabetes. In addition, we review techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of sensory-motor function. Such technological advances, while not readily available in the clinical setting, may facilitate stratification and individualization of therapy in diabetic patients in the future. Unraveling the structural, mechanical, and sensory remodeling in diabetes disease is based on a multidisciplinary approach that can bridge the knowledge from a variety of scientific disciplines. The final goal is to increase the understanding of the damage to GI structures and to sensory processing of symptoms, in order to assist clinicians with developing an optimal mechanics based treatment.
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Tao W, Dong X, Kong G, Fang P, Huang X, Bo P. Elevated Circulating hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b in Type 2 Diabetes Mellitus with Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterol Res Pract 2016; 2016:9256209. [PMID: 27635130 PMCID: PMC5011218 DOI: 10.1155/2016/9256209] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 04/26/2016] [Indexed: 12/15/2022] Open
Abstract
Background and Aims. Although the differential expression of microRNA (miRNA) genes has been identified in many diseases, little information exists concerning the miRNA expression profile in type 2 diabetes mellitus (T2DM) with diarrhea-predominant irritable bowel syndrome (D-IBS). Therefore, the specific expression of miRNAs in diabetes with D-IBS is identified in the study. Materials and Methods. 201 patients with IBS and 220 matched healthy controls were included in the study. Microarray technology and real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) were taken to examine the miRNA expression profiles of T2DM patients with diarrhea-predominant irritable bowel syndrome (D-IBS) compared with patients with T2DM, patients with D-IBS, and control subjects. Results. We have found that 35 miRNAs were differentially expressed in T2DM with D-IBS, in which three representative miRNAs, hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b, were found to be significantly elevated in T2DM with D-IBS by RT-PCR. Conclusions. Our study has indicated that hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b were elevated in T2DM with D-IBS, which may be the potential biomarkers of T2DM with D-IBS. To obtain a better understanding of the biological functions of these miRNAs in T2DM with D-IBS, functional annotation analysis suggested that the MAPK pathway may be responsible for T2DM with D-IBS.
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Affiliation(s)
- Wenhua Tao
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Xiaoyun Dong
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Guimei Kong
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Penghua Fang
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Xiaoli Huang
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Ping Bo
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
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D'Addio F, Fiorina P. Type 1 Diabetes and Dysfunctional Intestinal Homeostasis. Trends Endocrinol Metab 2016; 27:493-503. [PMID: 27185326 DOI: 10.1016/j.tem.2016.04.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2016] [Revised: 04/09/2016] [Accepted: 04/13/2016] [Indexed: 12/11/2022]
Abstract
Despite the relatively high frequency of gastrointestinal (GI) disorders in individuals with type 1 diabetes (T1D), termed diabetic enteropathy (DE), the pathogenic mechanisms of these disorders remain to be elucidated. While previous studies have assumed that DE is a manifestation of diabetic autonomic neuropathy, other contributing factors such as enteric hormones, inflammation, and microbiota were later recognized. More recently, the emerging role of intestinal stem cells (ISCs) in several GI diseases has led to a new understanding of DE. Given the absence of diagnostic methods and the lack of broadly efficacious therapeutic remedies in DE, targeting factors and pathways that control ISC homeostasis and are dysfunctional in DE may represent a new path for the detection and cure of DE.
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Affiliation(s)
- Francesca D'Addio
- Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Transplant Medicine, IRCCS Ospedale San Raffaele, Milan 20132, Italy
| | - Paolo Fiorina
- Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Transplant Medicine, IRCCS Ospedale San Raffaele, Milan 20132, Italy.
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Ihana-Sugiyama N, Nagata N, Yamamoto-Honda R, Izawa E, Kajio H, Shimbo T, Kakei M, Uemura N, Akiyama J, Noda M. Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors. World J Gastroenterol 2016; 22:3252-3260. [PMID: 27004003 PMCID: PMC4790001 DOI: 10.3748/wjg.v22.i11.3252] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 12/12/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases.
METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated.
RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P < 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P < 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c ≥ 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) < 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI < 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI < 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38).
CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms.
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Thiruppathy K, Bajwa A, Kuan KG, Murray C, Cohen R, Emmanuel A. Gut symptoms in diabetics correlate with components of the rectoanal inhibitory reflex, but not with pudendal nerve motor latencies or systemic autonomic neuropathy. J Dig Dis 2015; 16:342-9. [PMID: 25761939 DOI: 10.1111/1751-2980.12244] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Fecal incontinence (FI) occurs in up to 20% of diabetes mellitus (DM) patients. Rectoanal inhibitory reflex (RAIR) is an enteric anorectal reflex that reflects the integrity of mechanisms in the physiology of FI. We aimed to investigate whether diabetic patients with FI, not constipation, had prolongation of RAIR and altered gut-specific autonomic tone. METHODS In this prospective case-matched study 31 type I DM (19 FI and 12 constipation) and 42 type II DM (26 FI and 16 constipation). Another 21 participants were included as controls. Patients underwent the following assessments: cardiovagal autonomic tone (Modified Mayo Clinic composite autonomic severity score), rectal mucosal blood flow (RMBF) (assessment of gut-specific autonomic tone) and RAIR. Three phases of RAIR and the amplitude of maximal reflex relaxation were compared between groups. All participants completed symptom scores for FI and constipation. RESULTS RAIR recovery time back to resting pressure was slower in diabetic patients with FI than controls (8.7 s vs 3.6 s, P < 0.05) and was an independent variable correlating with symptoms of FI (P < 0.05). RAIR recovery time was correlated with RMBF (r = 0.58, P = 0.04). CONCLUSION RAIR is correlated with anorectal symptoms of FI and was associated with gut-specific autonomic neuropathy.
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Affiliation(s)
- Kumaran Thiruppathy
- Physiology Unit, Department of Gastroenterology, University College Hospital London, London, UK.,Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia
| | - Adeel Bajwa
- Physiology Unit, Department of Gastroenterology, University College Hospital London, London, UK
| | - Kean Guan Kuan
- Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia
| | - Charles Murray
- Department of Gastroenterology, Royal Free Hospital, London, UK
| | - Richard Cohen
- Physiology Unit, Department of Gastroenterology, University College Hospital London, London, UK
| | - Anton Emmanuel
- Physiology Unit, Department of Gastroenterology, University College Hospital London, London, UK
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Fujiwara M, Miwa T, Kawai T, Odawara M. Gastroesophageal reflux disease in patients with diabetes: preliminary study. J Gastroenterol Hepatol 2015; 30 Suppl 1:31-5. [PMID: 25827801 DOI: 10.1111/jgh.12777] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIM Some studies report that complications of gastroesophageal reflux disease (GERD) occur more frequently in patients with diabetes mellitus (DM) than in non-diabetic patients. This study used transnasal endoscopy to elucidate the current status of concurrent GERD in patients with type 2 diabetes mellitus, and to examine the associations between intraesophageal pressure and GERD, as well as other neuropathic conditions. METHODS The study included 57 outpatients with type 2 diabetes mellitus. The mean age was 67 years and the duration of DM was 13 years. The mean hemoglobin A1c was 6.8%. Transnasal endoscopic evaluation items were (i) the presence or absence of esophagitis and its severity; (ii) intraesophageal pressure; and (iii) Helicobacter pylori status, which was evaluated by endoscopic findings, such as the presence or absence of gastritis and peptic ulcer, and by urea breath test. RESULTS Of 57 patients, 24 (42.1%) were given a diagnosis of GERD based on endoscopy. Patients with concurrent GERD were younger, had shorter duration of DM, and were taller and heavier. Interestingly, no difference in body mass index was observed. There was no significant association between the presence of concurrent GERD and diabetic complications, including peripheral neuropathy, and infection or non-infection with H. pylori. Although there was no significant association between the presence of concurrent GERD and intraesophageal pressure values, we found aging, reduced estimated glomerular filtration rate, and the presence of autonomic nerve symptoms to correlate with reduced intraesophageal pressure. CONCLUSION The results of this study could be used to answer the question of whether or not endoscopic GERD is a diabetic complication; however, further study is required.
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Affiliation(s)
- Mariko Fujiwara
- Department of Diabetes, Endocrinology and Metabolism, Tokyo Medical University Hospital, Tokyo, Japan
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Huang Y, Sun J, Wang X, Tao X, Wang H, Tan W. Helicobacter pylori infection decreases metformin tolerance in patients with type 2 diabetes mellitus. Diabetes Technol Ther 2015; 17:128-33. [PMID: 25391019 DOI: 10.1089/dia.2014.0203] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM This study assessed whether Helicobacter pylori infection could influence metformin tolerance in patients with type 2 diabetes mellitus. SUBJECTS AND METHODS Demographic, anthropometric, ultrasound, and laboratory data were obtained from 415 metformin-naive patients with diabetes. H. pylori infection was assessed based on the (13)C-labeled urea breath test ((13)C-UBT). The study duration was 4 weeks, and all subjects started metformin from 500 mg/day to 1,500 mg/day progressively. Gastrointestinal side effects were assessed each week, and the metformin doses were adjusted by the compliance. Gastrointestinal side effects were compared between H. pylori-positive and -negative groups. RESULTS According to the (13)C-UBT results, 220 patients were categorized as H. pylori negative versus 195 as H. pylori positive. At baseline, the scoring of gastrointestinal symptoms showed no statistical difference between the two groups. After 4 weeks, for gastrointestinal symptoms such as abdominal pain, nausea, bloating, and anorexia, the respective percentages in H. pylori-positive and -negative subjects were 44.6% versus 21.8% (P < 0.01), 20.0% versus 9.6% (P < 0.01), 47.7% versus 23.2% (P < 0.01), and 32.8% versus 12.3% (P < 0.01). The final metformin dose was 951.28 ± 661.1 mg in H. pylori-positive subjects, significantly less than that in H. pylori-negative subjects (1,209.09 ± 522.91 mg) (P < 0.01). On multivariate analysis, female gender, H. pylori infection, body mass index, triglycerides, age, and low-density lipoprotein-cholesterol were the independent parameters associated with any gastrointestinal symptoms. CONCLUSIONS Patients with diabetes having H. pylori infection demonstrated more gastrointestinal side effects than those without H. pylori infection after taking metformin. Furthermore, female gender, H. pylori infection, body mass index, triglycerides, age, and low-density lipoprotein-cholesterol are independent determinants of metformin's side effects.
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Affiliation(s)
- Yuxin Huang
- Department of Endocrinology, Shanghai Huadong Hospital affiliated with Fudan University , Shanghai, People's Republic of China
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Søfteland E, Brock C, Frøkjær JB, Brøgger J, Madácsy L, Gilja OH, Arendt-Nielsen L, Simrén M, Drewes AM, Dimcevski G. Association between visceral, cardiac and sensorimotor polyneuropathies in diabetes mellitus. J Diabetes Complications 2014; 28:370-7. [PMID: 24355661 DOI: 10.1016/j.jdiacomp.2013.10.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2013] [Revised: 09/13/2013] [Accepted: 10/21/2013] [Indexed: 12/13/2022]
Abstract
AIMS Gastrointestinal complaints are common in diabetes mellitus. However, its association to peripheral sensorimotor and autonomic neuropathies is not well investigated. The aim was to assess skin, muscle, bone and visceral sensitivity in diabetes patients with sensorimotor neuropathy, and correlate these with gastrointestinal symptoms and degree of cardiac autonomic neuropathy. METHODS Twenty patients with sensorimotor neuropathy (65% type 2 diabetes, aged 58.3±12.0 years, diabetes duration 15.8±10.0 years) and 16 healthy controls were recruited. Cutaneous sensitivity to von Frey filaments, mechanical allodynia, muscle/bone/rectosigmoid sensitivities, and heart rate variability were examined. Gastrointestinal symptom scores (PAGI-SYM) and health-related quality of life (SF-36) were also recorded. RESULTS Patients displayed hypesthesia to von Frey filaments (p=0.028), but no difference to muscle and bone pain sensitivities. Also, patients were hyposensitive to multimodal rectal stimulations (all p<0.05), although they suffered more gastrointestinal complaints. Heart rate variability was reduced in the patient cohort. Rectal mechanical and cutaneous sensitivities correlated (p<0.001), and both were associated with heart rate variability as well as PAGI-SYM and SF-36 scores (p<0.01). CONCLUSIONS In diabetic sensorimotor neuropathy there is substantial evidence of concomitant cutaneous, cardiac and visceral autonomic neuropathies. The neuropathy may reduce quality of life and explain the higher prevalence of gastrointestinal complaints.
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Affiliation(s)
- Eirik Søfteland
- Department of Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Jens B Frøkjær
- Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Jan Brøgger
- Section for Clinical Neurophysiology, Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - László Madácsy
- 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
| | - Odd H Gilja
- Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Lars Arendt-Nielsen
- Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Magnus Simrén
- Institute of Medicine, Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark; Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway; National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Søfteland E, Brock C, Frøkjær JB, Simrén M, Drewes AM, Dimcevski G. Rectal sensitivity in diabetes patients with symptoms of gastroparesis. J Diabetes Res 2014; 2014:784841. [PMID: 25136644 PMCID: PMC4130227 DOI: 10.1155/2014/784841] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 07/07/2014] [Indexed: 02/07/2023] Open
Abstract
In a clinical setting, diabetic autonomic complications (cardiac, gastrointestinal, urogenital, etc.) are often handled as separate entities. We investigated rectal sensitivity to heat, mechanical distension, and electrical stimulations in 20 patients with diabetes and symptoms of gastroparesis, to evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the relation between the nervous structures we examined gastric emptying and cardiac autonomic function with the hypothesis being an association between these. We found that 60% of patients had delayed gastric empting. Rectal hyposensitivity was a general finding as they tolerated 67% higher thermal, 42% more mechanical, and 33% higher electrical current intensity compared to healthy controls. In patients, most heart rate variability parameters were reduced; they reported significantly more gastrointestinal symptoms and a reduced quality of life in all SF-36 domains. Shortened RR interval correlated with reduced rectal temperature sensitivity, and gastric retention rate was negatively associated with symptoms of nausea and vomiting. To conclude, in these patients with signs and symptoms of diabetic gastroparesis, rectal sensitivity was reduced, and heart rate variability was impaired. Thus, we suggest regarding diabetic autonomic neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction and sensory disorders should be expected and treated in these patients.
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Affiliation(s)
- Eirik Søfteland
- Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
- Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- *Eirik Søfteland:
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, 9000 Aalborg, Denmark
| | - Jens B. Frøkjær
- Mech-Sense, Department of Radiology, Aalborg University Hospital, 9000 Aalborg, Denmark
| | - Magnus Simrén
- Institute of Medicine, Department of Internal Medicine & Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Asbjørn M. Drewes
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, 9000 Aalborg, Denmark
- Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University, 9000 Aalborg, Denmark
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
- National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, 5020 Bergen, Norway
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Hamdan AL, Jabbour J, Barazi R, Korban Z, Azar ST. Prevalence of laryngopharyngeal reflux disease in patients with diabetes mellitus. J Voice 2013; 27:495-9. [PMID: 23602088 DOI: 10.1016/j.jvoice.2012.07.010] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2012] [Accepted: 07/12/2012] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To study the prevalence of laryngopharyngeal reflux disease (LPRD) in patients with type 2 diabetes mellitus (T2DM) and report the correlation between LPRD and glycemic control, duration of the disease, and presence of neuropathy. MATERIALS AND METHODS This is a cross-sectional study of 100 patients with T2DM and 33 controls matched according to age and gender. The reflux symptom index (RSI) was used to assess the presence of LPRD. A score greater than 10 was considered diagnostic of LPRD. RESULTS Twenty-two percent of patients with T2DM had RSI above 10 versus 9.1% of controls. The difference was not statistically different (P value of 0.100). The average score of all symptoms of LPRD was higher in the diabetic group compared with the control group. There was a significant increase in the average score of "throat clearing" and "lump sensation in throat," with a borderline significant increase in "annoying cough" in patients with diabetes versus controls (respective P values of 0.03, 0.025, and 0.066). There was no correlation between LPRD and any of the demographic variables except neuropathy. CONCLUSION Patients with T2DM are more likely to have LPRD compared with controls. However, the prevalence of LPRD is not significantly higher in diabetic patients compared with controls. When present, LPRD correlates with neuropathy. LEVEL OF EVIDENCE 2c.
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Affiliation(s)
- Abdul-latif Hamdan
- Department of Otolaryngology and Head and Neck Surgery, American University of Beirut Medical Center, New York, NY 10017, USA
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Frøkjær JB, Andersen LW, Brock C, Simrén M, Ljungberg M, Søfteland E, Dimcevski G, Yavarian Y, Gregersen H, Drewes AM. Altered brain microstructure assessed by diffusion tensor imaging in patients with diabetes and gastrointestinal symptoms. Diabetes Care 2013; 36:662-8. [PMID: 23139372 PMCID: PMC3579353 DOI: 10.2337/dc12-1131] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE In patients with long-standing diabetes mellitus (DM), there is increasing evidence for abnormal processing of gastrointestinal sensations in the central nervous system. Using magnetic resonance diffusion tensor imaging, we characterized brain microstructure in areas involved in visceral sensory processing and correlated these findings to clinical parameters. RESEARCH DESIGN AND METHODS Twenty-six patients with DM and gastrointestinal symptoms and 23 healthy control subjects were studied in a 3T scanner. The apparent diffusion coefficient (i.e., diffusivity of water) and fractional anisotropy (FA) (i.e., organization of fibers) were assessed in the "sensory matrix" (cingulate cortex, insula, prefrontal and secondary sensory cortex, amygdala, and corona radiata) and in corpus callosum. RESULTS Patients had decreased FA values compared with control subjects in 1) all areas (P = 0.025); 2) anterior (P < 0.001), mid- (P = 0.001), and posterior (P < 0.001) cingulate cortex; 3) prefrontal cortex gray matter (P < 0.001); 4) corona radiata (P < 0.001); 5) secondary sensory cortex (P = 0.008); and 6) anterior white matter (P = 0.045), anterior gray matter (P = 0.002), and posterior gray matter (P = 0.002) insula. No difference was found in corpus callosum (P > 0.05). The microstructural changes in some areas correlated with clinical parameters such as bloating (anterior insula), mental well-being (anterior insula, prefrontal cortex, and mid-cingulated and corona radiata), autonomic function based on electrocardiographic results (posterior insula and anterior cingulate), and presence of gastroparesis (anterior insula). CONCLUSIONS The findings of this explorative study indicate that microstructural changes of brain areas involved in visceral sensory processing are associated with autonomic dysfunction and therefore may be involved in the pathogenesis of gastrointestinal symptoms in DM patients.
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Affiliation(s)
- Jens Brøndum Frøkjær
- Department of Radiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
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Sun F, Yu K, Yang Z, Wu S, Zhang Y, Shi L, Ji L, Zhan S. Impact of GLP-1 receptor agonists on major gastrointestinal disorders for type 2 diabetes mellitus: a mixed treatment comparison meta-analysis. EXPERIMENTAL DIABETES RESEARCH 2012; 2012:230624. [PMID: 23365557 PMCID: PMC3540917 DOI: 10.1155/2012/230624] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2012] [Accepted: 10/01/2012] [Indexed: 12/16/2022]
Abstract
AIM We aimed to integrate evidence from all randomized controlled trials (RCTs) and assess the impact of different doses of exenatide or liraglutide on major gastrointestinal adverse events (GIAEs) in type 2 diabetes (T2DM). METHODS RCTs evaluating different doses of exenatide and liraglutide against placebo or an active comparator with treatment duration ≥4 weeks were searched and reviewed. A total of 35, 32 and 28 RCTs met the selection criteria evaluated for nausea, vomiting, and diarrhea, respectively. Pairwise random-effects meta-analyses and mixed treatment comparisons (MTC) of all RCTs were performed. RESULTS All GLP-1 dose groups significantly increased the probability of nausea, vomiting and diarrhea relative to placebo and conventional treatment. MTC meta-analysis showed that there was 99.2% and 85.0% probability, respectively, that people with exenatide 10 μg twice daily (EX10BID) was more vulnerable to nausea and vomiting than those with other treatments. There was a 78.90% probability that liraglutide 1.2 mg once daily (LIR1.2) has a higher risk of diarrhea than other groups. A dose-dependent relationship of exenatide and liraglutide on GIAEs was observed. CONCLUSIONS Our MTC meta-analysis suggests that patients should be warned about these GIAEs in early stage of treatment by GLP-1s, especially by EX10BID and LIR1.2, to promote treatment compliance.
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Affiliation(s)
- Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 100191, China
- International Research Center of Medicinal Administration, Peking University, Beijing 100191, China
- Department of Preventive Medicine, College of Medicine, Shihezi University, Shihezi 832002, China
| | - Kai Yu
- Department of Orthopedics, Tianjin Fifth Central Hospital, Tianjin 300450, China
| | - Zhirong Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 100191, China
| | - Shanshan Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 100191, China
| | - Yuan Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 100191, China
| | - Luwen Shi
- International Research Center of Medicinal Administration, Peking University, Beijing 100191, China
| | - Linong Ji
- Department of Endocrinology and Metabolism, People's Hospital, Peking University, Beijing 100044, China
| | - Siyan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing 100191, China
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Frøkjaer JB, Brock C, Brun J, Simren M, Dimcevski G, Funch-Jensen P, Drewes AM, Gregersen H. Esophageal distension parameters as potential biomarkers of impaired gastrointestinal function in diabetes patients. Neurogastroenterol Motil 2012; 24:1016-e544. [PMID: 22738347 DOI: 10.1111/j.1365-2982.2012.01966.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi-factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract. METHODS Seventeen patients with longstanding DM and GI symptoms and 13 healthy controls were studied using ultrasound monitored esophageal distension. The sensory response was recorded and their symptoms registered. Biomechanical parameters, such as compliance and stiffness were computed from luminal diameters during distension based on the ultrasound images and from pressure data. Biomechanical and sensory parameters were correlated with the clinical data. KEY RESULTS Diabetes patients had reduced esophageal sensitivity compared with controls (P = 0.046). The esophageal compliance was reduced (P = 0.004) and the esophageal stiffness was increased (P = 0.004) in the diabetes patients. Among patients, both postprandial fullness/early satiety and bloating correlated negatively to the esophageal compliance parameters (all P < 0.05). CONCLUSIONS & INFERENCES Patients with long-standing DM and GI symptoms had reduced esophageal sensitivity together with reduced compliance and increased stiffness, which were correlated to the patients' GI symptoms. Biomechanical parameters obtained during distension may serve as biomarker for similar pathophysiologic effects of diabetes in the stomach and small bowel. They may contribute to our understanding of the pathophysiology underlying GI dysfunction and symptoms in patients with longstanding DM.
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Affiliation(s)
- J B Frøkjaer
- Mech-Sense, Department of Radiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
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The relationship between type 2 diabetes mellitus and failure to proton pump inhibitor treatment in gastroesophageal reflux disease. J Clin Gastroenterol 2012; 46:662-8. [PMID: 22858518 DOI: 10.1097/mcg.0b013e31824e139b] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND There is limited information regarding the contribution of diabetes mellitus (DM) to proton pump inhibitor (PPI) failure in gastroesophageal reflux disease (GERD) patients. AIM To determine whether type 2 DM is a risk factor for PPI failure and the potential predictive factors for PPI failure among type 2 DM patients with GERD. DESIGN A case-control study was performed using hospital medical records of GERD patients treated with a PPI. The prevalence of type 2 DM and other risk factors (established >1 y before study enrollment) was determined in the PPI failure (treatment with more than once daily PPI) as compared with PPI responders. RESULTS A total of 732 GERD patients receiving PPI therapy, including 285 who failed PPI treatment, were included. The overall prevalence of PPI failure was significantly higher in diabetic versus nondiabetic patients. The relationship between PPI failure and type 2 DM depended on body mass index. Only in obese patients the odds ratio of PPI failure was significantly higher in type 2 DM as compared with non-DM patients. In the subgroup of GERD patients with type 2 DM (n=349), PPI failure was significantly associated with female sex, the presence of general comorbidities, and adequate DM control. Duration of DM, type of antidiabetic medication prescribed, and DM-associated complications were not associated with PPI failure. CONCLUSIONS PPI failure was significantly associated with type 2 DM in obese patients. Among GERD patients with type 2 DM, failure of PPI treatment was significantly associated with female sex and the presence of general comorbidities.
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Bener A, Ghuloum S, Al-Hamaq AO, Dafeeah EE. Association between psychological distress and gastrointestinal symptoms in diabetes mellitus. World J Diabetes 2012; 3:123-9. [PMID: 22737283 PMCID: PMC3382709 DOI: 10.4239/wjd.v3.i6.123] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2012] [Revised: 05/27/2012] [Accepted: 06/10/2012] [Indexed: 02/05/2023] Open
Abstract
AIM: To examine the possible association between gastrointestinal symptoms and anxiety and depression in type 2 diabetes mellitus (T2DM).
METHODS: The study was a matched case-control study based on a face to face interview with designed diagnostic screening questionnaires for gastrointestinal (GI) symptoms and T2DM, Patient Health Questionnaire (PHQ-9) for depression and General Anxiety Disorders (GAD-7) for anxiety. The questionnaire consisted of questions about symptoms and signs of anxiety and depression disorders. Also, socio-demographic characteristics, life style habits and the family history of patients were collected. It was carried out from June 2010 to May 2011 among Qatari and other Arab nationals over 20 years of age at Primary Health Care Centers of the Supreme Council of Health, Qatar, including patients with diabetes mellitus and healthy subjects over 20 years of age.
RESULTS: In the studied sample, most of the studied T2DM patients with GI symptoms (39.3%) and healthy subjects (33.3%) were in the age group 45-54 years (P < 0.001). The prevalence of severe depression (9.5% vs 4.4%, P < 0.001) and anxiety (26.3% vs 13.7%, P < 0.001) was significantly higher in T2DM patients with GI symptoms than in general population. Obesity (35.7% vs 31.2%) and being overweight (47.9% vs 42.8%) were significantly higher in T2DM patients with GI symptoms than in healthy subjects (P = 0.001). Mental health severity score was higher in T2DM patients with GI symptoms than in healthy subjects; depression (8.2 ± 3.7 vs 6.0 ± 3.6) and anxiety (7.6 ± 3.3 vs 6.0 ± 3.7). The most significant GI symptom which was considerably different from controls was early satiety [odds ratio (OR) = 10.8, P = 0.009] in depressed T2DM patients and loose/watery stools (OR = 2.79, P = 0.029) for severe anxiety. Anxiety was observed more than depression in T2DM patients with GI symptoms.
CONCLUSION: Gastrointestinal symptoms were significantly associated with depression and anxiety in T2DM patients, especially anxiety disorders.
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Affiliation(s)
- Abdulbari Bener
- Abdulbari Bener, Department of Medical Statistics and Epidemiology, Hamad Medical Corporation, Doha, PO Box 3050, Qatar
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de Kort S, Kruimel JW, Sels JP, Arts ICW, Schaper NC, Masclee AAM. Gastrointestinal symptoms in diabetes mellitus, and their relation to anxiety and depression. Diabetes Res Clin Pract 2012; 96:248-55. [PMID: 22325156 DOI: 10.1016/j.diabres.2012.01.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2010] [Revised: 01/11/2012] [Accepted: 01/16/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prevalence of gastrointestinal (GI) symptoms is increased in patients with diabetes mellitus. In general, GI symptoms are influenced by psychological factors such as anxiety and depression, but little is known about this association in diabetic patients. AIM We tested the hypothesis that anxiety and depression have major impact on GI symptoms in diabetic patients. METHODS 280 diabetic patients and 355 non-diabetic, age and sex matched controls were studied by validated questionnaires: (1) PAGI-SYM and GSRS for common GI symptoms and (2) HADS for anxiety and depression. Data were compared using logistic regression analysis. RESULTS Patients with diabetes scored significantly (p<0.05) higher on the symptoms diarrhea (OR 1.64, 95% CI 1.05-2.56), early satiety (OR 2.50, 95% CI 1.39-4.49) and bloating (OR 1.58, 95% CI 1.03-2.43), but not on other symptoms. Prevalence of anxiety and depression (HADS scores ≥ 8) in diabetics and controls was respectively 27.5% and 20.6% for anxiety (p<0.05), and 19.6% and 13.4% for depression (p<0.05). After adjusting for anxiety and depression only the GI symptom "early satiety" remained significantly more prevalent in the patients with diabetes. CONCLUSIONS The prevalence of the gastrointestinal symptoms diarrhea, bloating and early satiety, and of anxiety and depression is significantly increased in our cohort of predominantly patients with longstanding type 2 diabetes mellitus compared to controls. When adjusted for anxiety and depression, only the gastrointestinal symptom "early satiety" remained more prevalent in these diabetic patients, pointing to a somatic based origin. Thus, in our diabetic population psychological factors to a large extent are associated with gastrointestinal symptoms and should be taken into account when considering treatment of the gastrointestinal symptoms.
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Affiliation(s)
- Sander de Kort
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
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Tseng PH, Lee YC, Chiu HM, Chen CC, Liao WC, Tu CH, Yang WS, Wu MS. Association of diabetes and HbA1c levels with gastrointestinal manifestations. Diabetes Care 2012; 35:1053-1060. [PMID: 22410812 PMCID: PMC3329853 DOI: 10.2337/dc11-1596] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Accepted: 01/24/2012] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine the prevalence of gastrointestinal (GI) manifestations associated with diabetes mellitus (DM) in a Taiwanese population undergoing bidirectional endoscopies. RESEARCH DESIGN AND METHODS Subjects voluntarily undergoing upper endoscopy/colonoscopy as part of a medical examination at the National Taiwan University Hospital were recruited during 2009. Diagnosis of DM included past history of DM, fasting plasma glucose ≥ 126 mg/dL, or glycated hemoglobin (HbA(1c)) ≥ 6.5%. Comparisons were made between diabetic and nondiabetic subjects, subjects with lower and higher HbA(1c) levels, and diabetic subjects with and without complications, respectively, for their GI symptoms, noninvasive GI testing results, and endoscopic findings. RESULTS Among 7,770 study subjects, 722 (9.3%) were diagnosed with DM. The overall prevalence of GI symptoms was lower in DM subjects (30.3 vs. 35.4%, P = 0.006). In contrast, the prevalence of erosive esophagitis (34.3 vs. 28.6%, P = 0.002), Barrett's esophagus (0.6 vs. 0.1%, P = 0.001), peptic ulcer disease (14.8 vs. 8.5%, P < 0.001), gastric neoplasms (1.8 vs. 0.7%, P = 0.003), and colonic neoplasms (26.6 vs. 16.5%, P < 0.001) was higher in diabetic subjects. Diagnostic accuracy of immunochemical fecal occult blood test for colonic neoplasms was significantly decreased in DM (70.7 vs. 81.7%, P < 0.001). Higher HbA(1c) levels were associated with a decrease of GI symptoms and an increase of endoscopic abnormalities. Diabetic subjects with complications had a higher prevalence of colonic neoplasms (39.2 vs. 24.5%, P = 0.002) than those without. CONCLUSIONS DM and higher levels of HbA(1c) were associated with lower prevalence of GI symptoms but higher prevalence of endoscopic abnormalities.
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Affiliation(s)
- Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Biostatistics, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Chih Liao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hung Tu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Division of Biostatistics, Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Wei-Shiung Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Abstract
OBJECTIVES In patients with diabetes mellitus (DM) and upper gastrointestinal symptoms, a diagnosis of diabetic gastroparesis is often considered, but population-based data on the epidemiology of diabetic gastroparesis are lacking. We aimed to estimate the frequency of and risk factors for gastroparesis among community subjects with DM. METHODS In this population-based, historical cohort study, the medical records linkage system of the Rochester Epidemiology Project was used to identify 227 Olmsted County, MN residents with type 1 DM in 1995, a random sample of 360 residents with type 2 DM, and an age- and sex-stratified random sample of 639 nondiabetic residents. Using defined diagnostic criteria, we estimated the subsequent risk of developing gastroparesis in each group through 2006. The risk in DM, compared with frequency-matched community controls, was assessed by Cox proportional hazards modeling. RESULTS The cumulative proportions developing gastroparesis over a 10-year time period were 5.2% in type 1 DM, 1.0% in type 2 DM, and 0.2% in controls. The age- and gender-adjusted hazard ratios (HRs) for gastroparesis (relative to controls) was 33 (95% confidence interval (CI): 4.0, 274) in type 1 DM and 7.5 (95% CI: 0.8, 68) in type 2 DM. The risk of gastroparesis in type 1 DM was significantly greater than in type 2 DM (HR: 4.4 (1.1, 17)). Heartburn (HR: 6.6 (1.7, 25)) at baseline was associated with diabetic gastroparesis in type 1 DM. CONCLUSIONS Gastroparesis is relatively uncommon in patients with DM, although an increased risk for gastroparesis was observed in type 1 DM.
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Jun JY. The important roles of interstitial cells of cajal and cholinergic receptors on diabetes related dysfunction of colon. J Neurogastroenterol Motil 2011; 17:333-4. [PMID: 22148100 PMCID: PMC3228971 DOI: 10.5056/jnm.2011.17.4.333] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2011] [Revised: 08/30/2011] [Accepted: 09/02/2011] [Indexed: 01/27/2023] Open
Affiliation(s)
- Jae Yeoul Jun
- Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
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How Is the Autonomic Nerve Function Different Between Gastroesophageal Reflux Disease Alone and Gastroesophageal Reflux Disease With Diabetes Mellitus Neuropathy?: Author's Reply. J Neurogastroenterol Motil 2011. [PMCID: PMC3228989 DOI: 10.5056/jnm.2011.17.4.432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Kim SJ, Park JH, Song DK, Park KS, Lee JE, Kim ES, Cho KB, Jang BK, Chung WJ, Hwang JS, Kwon JG, Kim TW. Alterations of colonic contractility in long-term diabetic rat model. J Neurogastroenterol Motil 2011; 17:372-80. [PMID: 22148106 PMCID: PMC3228977 DOI: 10.5056/jnm.2011.17.4.372] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2011] [Revised: 07/28/2011] [Accepted: 08/06/2011] [Indexed: 12/28/2022] Open
Abstract
Background/Aims Dysfunction of the gastrointestinal tract occurs in about 76% of patients who are diabetic for more than 10 years. Although diabetes-related dysfunctions of the stomach such as gastroparesis have been extensively studied over the recent years, studies about the mechanism underlying colonic symptoms in long-term diabetes models are rare. Therefore, the goal of our study was to clarify the nature of colonic dysfunction in a long-term diabetic rat model. Methods The characteristics of colonic smooth muscle were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. These results were compared to those obtained from Long-Evans Tokushima Otsuka (LETO) control rats. Results Spontaneous contractility of the proximal colon was significantly decreased in the diabetic rats compared to the controls, while the spontaneous contractility of the distal colon was not. The number of interstitial cells of Cajal networks in the proximal colon was greatly decreased in diabetic rats compared to the controls. Contractility of the proximal colon in response to carbachol, an acetylcholine receptor agonist, was significantly weaker in the diabetic rats. In addition, the degree of relaxation in response to nitric oxide in the proximal colon of diabetic rats also appeared to be attenuated. Conclusions The results from our study suggest that the decrease of interstitial cells of Cajal network, cholinergic receptors, and neuronal nitric oxide synthase in the proximal colon plays important roles in diabetes-related dysfunction of colon.
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Affiliation(s)
- Sun Joo Kim
- Department of Physiology, Keimyung University School of Medicine, Daegu, Korea
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Boaz M, Kislov J, Dickman R, Wainstein J. Obesity and symptoms suggestive of gastroparesis in patients with type 2 diabetes and neuropathy. J Diabetes Complications 2011; 25:325-8. [PMID: 21813291 DOI: 10.1016/j.jdiacomp.2011.06.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Revised: 05/22/2011] [Accepted: 06/20/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND Associated with neuropathy, symptoms suggestive of gastroparesis are common in patients with type 2 diabetes mellitus (T2DM) and include nausea, vomiting, bloating and early satiety. Gastric motor abnormalities have been reported in obese patients, and obesity is associated with T2DM. An association between obesity and gastroparesis symptoms in diabetic patients with neuropathy has not been investigated. METHODS In this nested case-control study, 161 patients with neuropathy were identified from within a cross-sectional survey of 380 T2DM patients. Of these, 134 (83.2%, "cases") had at least one cardinal symptom suggestive of gastroparesis. The remaining symptom-free subjects served as controls. Logistic and general linear modeling was used to assess associations between obesity and the presence and number of symptoms. RESULTS Subjects were 66.6±10 years of age. Cases were significantly more likely than controls to be obese (89% vs. 77%, P=.04), female (55.6% vs. 33.3%) and hypertensive (90.2% vs. 63%, P=.001) and to report adherence to diet (87.4% vs. 66.7%, P=.007). In a logistic regression model including sex, hypertension, antiaggregant therapy, adherence to diet therapy and an obesity-by-sex interaction term, obesity emerged as a significant independent predictor of any cardinal symptom suggestive of gastroparesis (odds ratio 9.86, 95% confidence interval 1.4-69.2, P=.02). Obesity was also identified as a significant independent predictor of number of cardinal symptoms suggestive of gastroparesis in the general linear model. Obese subjects reported significantly more early satiety (61.5% vs. 35.2%, P=.001), fullness (63.7% vs. 40.8%, P=.004), bloating (70.3% vs. 49.3%, P=.006) and abdominal distention (71.4 vs. 50.7%, P=.007) than nonobese subjects. Further, obese subjects reported more cardinal symptoms suggestive of gastroparesis symptoms (4.2±2.4 vs. 3.1±2.5, P=.01). CONCLUSIONS Obesity emerged as a significant independent predictor of cardinal symptoms suggestive of gastroparesis in patients with T2DM and neuropathy. This finding suggests that mechanisms in addition to neuropathy play a role in the generation of symptoms suggestive of gastroparesis in this patient population.
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Affiliation(s)
- Mona Boaz
- Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel.
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Bolin P, Gohh R, Kandaswamy R, Shihab FS, Wiland A, Akhlaghi F, Melancon K. Mycophenolic acid in kidney transplant patients with diabetes mellitus: does the formulation matter? Transplant Rev (Orlando) 2011; 25:117-23. [DOI: 10.1016/j.trre.2010.12.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2010] [Revised: 11/18/2010] [Accepted: 12/21/2010] [Indexed: 10/18/2022]
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Jaursch-Hancke C. Gastrointestinale Probleme bei Diabetes. DER GASTROENTEROLOGE 2011; 6:300-306. [DOI: 10.1007/s11377-010-0505-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Karayiannakis AJ, Bolanaki H, Kouklakis G, Dimakis K, Memet I, Simopoulos C. Ischemic colitis of the left colon in a diabetic patient. Case Rep Gastroenterol 2011; 5:239-45. [PMID: 21552382 PMCID: PMC3088756 DOI: 10.1159/000327981] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Diabetes mellitus may affect the gastrointestinal tract possibly as a result of autonomic neuropathy. Here we present a 68-year-old male with non-insulin-dependent diabetes mellitus who presented with prolonged watery diarrhea and in whom imaging studies demonstrated ischemic colitis of the left colon. Resection of the affected colon resulted in sustained disappearance of symptoms.
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Eldesoky A, El-Hafez AA. Oesophageal dysmotility in diabetic patients with varices. Arab J Gastroenterol 2010. [DOI: 10.1016/j.ajg.2010.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Kim JH, Park HS, Ko SY, Hong SN, Sung IK, Shim CS, Song KH, Kim DL, Kim SK, Oh J. Diabetic factors associated with gastrointestinal symptoms in patients with type 2 diabetes. World J Gastroenterol 2010; 16:1782-7. [PMID: 20380013 PMCID: PMC2852829 DOI: 10.3748/wjg.v16.i14.1782] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether gastrointestinal (GI) symptoms are more frequent in type 2 diabetic patients and to examine which diabetic factors are associated with the symptoms.
METHODS: Consecutive subjects with diabetes and age-/gender-matched normal controls were recruited for this study. GI symptoms were assessed using a structured questionnaire divided into two GI symptom categories (upper and lower GI symptoms), and consisting of 11 individual symptoms. In the diabetic patient group, diabetic complications including peripheral neuropathy, nephropathy and retinopathy, glycosylated hemoglobin (HbA1c) level and diabetes duration were evaluated.
RESULTS: Among the total 190 diabetic patients and 190 controls enrolled, 137 (72%) of the diabetic patients and 116 (62%) of the controls had GI symptoms. In the diabetic patient group, 83 (43%) had upper GI symptoms and 110 (58%) lower GI symptoms; in the control group, 59 (31%) had upper GI symptoms and 104 (55%) lower GI symptoms. This difference between the two groups was significant for only the upper GI symptoms (P = 0.02). Among the diabetic factors, the HbA1c level was the only independent risk factor for upper GI symptoms in the multiple logistic regression analysis (odds ratio = 2.01, 95% confidence interval: 1.02-3.95).
CONCLUSION: Type 2 diabetes was associated with an increased prevalence of upper GI symptoms and these symptoms appeared to be independently linked to poor glycemic control, as measured by the HbA1c levels.
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Oh JH, Choi MG, Kang MI, Lee KM, Kim JI, Kim BW, Lee DS, Kim SS, Choi H, Han SW, Choi KY, Son HY, Chung IS. The prevalence of gastrointestinal symptoms in patients with non-insulin dependent diabetes mellitus. Korean J Intern Med 2009; 24:309-317. [PMID: 19949728 PMCID: PMC2784973 DOI: 10.3904/kjim.2009.24.4.309] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2008] [Accepted: 01/21/2009] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND/AIMS Gastrointestinal (GI) symptoms are common among patients with non-insulin dependent diabetes mellitus (NIDDM). Our aim was to investigate the frequency of chronic GI symptoms in Korean patients with NIDDM. METHODS A cross-sectional survey, using a reliable and valid questionnaire, was performed in diabetes clinics from seven hospitals of the Catholic University of Korea. RESULTS A total of 608 patients (249 males and 359 females, mean age 53.7+/-10.9 years) were investigated. The frequencies of weekly heartburn and acid regurgitation (esophageal symptoms) were 7.1% (95% confidence interval [CI], 5.0 to 9.2) and 4.4% (95% CI, 2.8 to 6.1), respectively. The frequency of dyspepsia was 13.2% (95% CI, 10.5 to 15.8). The frequencies of constipation and diarrhea were 15.0% (95% CI, 12.2 to 18.0) and 5.3% (95% CI, 3.5 to 7.1), respectively. Nausea and the use of manual maneuvers to facilitate defecation were more prevalent in women than in men. Constipation and fecal incontinence were more common in diabetes patients with long duration (>10 years). Fecal incontinence and using laxatives were more frequent in the complicated diabetes group. Using laxatives was more frequent in the uncontrolled diabetes group. CONCLUSIONS Two-thirds of diabetic patients experienced GI symptoms. The prevalence of GI symptoms was more common in patients who had diabetic complications and a long duration of diabetes.
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Affiliation(s)
- Jung-Hwan Oh
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Moo-Il Kang
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Kang-Moon Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Jin Il Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Byung-Wook Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Dong-Soo Lee
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sung-Soo Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Hwang Choi
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Sok-Won Han
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Kyu-Yong Choi
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - Ho-Young Son
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
| | - In-Sik Chung
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea
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