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Zhang Y, Tang YW, Zhou J, Wei YR, Peng YT, Yan Z, Yue ZH. Electroacupuncture at ST36 ameliorates gastric dysmotility in rats with diabetic gastroparesis via the nucleus tractus solitarius-vagal axis. World J Gastroenterol 2025; 31:107395. [DOI: 10.3748/wjg.v31.i21.107395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2025] [Revised: 04/11/2025] [Accepted: 05/23/2025] [Indexed: 06/06/2025] Open
Abstract
BACKGROUND Diabetic gastroparesis (DGP), characterized by delayed gastric emptying and impaired motility, poses significant therapeutic challenges due to its complex neural and molecular pathophysiology. Emerging evidence suggests that electroacupuncture (EA) at ST36 modulates gastrointestinal function; however, the precise neuromolecular pathways underlying its efficacy in DGP remain incompletely defined.
AIM To elucidate the neural mechanisms underlying EA at ST36 improving DGP gastric motility through the nucleus tractus solitarius (NTS)-vagal axis.
METHODS The DGP model was established via a single high-dose intraperitoneal injection of 2% streptozotocin combined with an 8-week high-sugar/high-fat diet. Interventions included EA at ST36, pharmacological modulation [choline acetyltransferase (ChAT) agonist polygalacic acid (PA) and inhibitor antagonist alpha-NETA], and subdiaphragmatic vagotomy. Post-intervention observations included body weight and blood glucose levels. Gastric emptying was evaluated using phenol red assays, gastric slow-wave recordings, and dynamic positron emission tomography-computed tomography imaging. Histopathological analysis (hematoxylin-eosin staining) and molecular assessments (Western blot, immunofluorescence) were performed to quantify gastric smooth muscle-associated factors [neuronal nitric oxide synthase (nNOS), cluster of differentiation 117 (C-kit), stem cell factor (SCF)] and vagal targets [ChAT, α7 nicotinic acetylcholine receptor (α7nAChR)] in the ST36 acupoint region, L4-L6 spinal segments, and NTS. Gastrointestinal peptides [gastrin (Gas), motilin (MLT) and vasoactive intestinal peptide (VIP)] were measured via enzyme-linked immunosorbent assay.
RESULTS The study found that EA significantly increased the rate of gastric emptying, restored the slow-wave rhythms of the stomach, and improved the architecture of the smooth muscles in the stomach. This was evidenced by a reduction in inflammatory infiltration and an increase in the expression of nNOS, C-kit, and SCF. Mechanistically, EA activated vagal targets (ChAT and α7nAChR) at ST36, transmitting signals via spinal segments L4-L6 to the NTS, subsequently regulating gastrointestinal peptides (Gas, MLT, VIP) and restoring interstitial cells of Cajal (ICCs) function via subdiaphragmatic vagal efferent pathways. It is crucial to note that subdiaphragmatic vagotomy led to the abrogation of EA-induced enhancements in gastric motility and ICC recovery, thereby confirming the indispensable role of vagal efferent signalling.
CONCLUSION EA provides a novel molecular mechanism for improving gastrointestinal motility in DGP via a peripheral stimulation (ST36), spinal afferent (L4-L6), brainstem integration (NTS), vagal efferent (gastric) circuit.
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Affiliation(s)
- You Zhang
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Yi-Wen Tang
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Jin Zhou
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Yan-Rong Wei
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Yu-Ting Peng
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Zi Yan
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Zeng-Hui Yue
- College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
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Wang X, Ma L, Jiang M, Zhu H, Ni C, Yang X, Hu J, Zhang HH. Analysis of gastric electrical rhythm in patients with type 2 diabetes mellitus. Endocrine 2024; 86:612-619. [PMID: 38861116 PMCID: PMC11489290 DOI: 10.1007/s12020-024-03908-y] [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: 04/01/2024] [Accepted: 05/30/2024] [Indexed: 06/12/2024]
Abstract
AIM To analysis the change of electrogastrogram (EGG) in patients with type 2 diabetes mellitus (T2DM), and evaluate the prevalence of abnormal gastric electrical rhythm (AGER) and its relative influencing factors. METHODS A total of 65 patients with T2DM hospitalized at the Second Affiliated Hospital of Soochow University from Dec. 2020 to Dec. 2021 were included in the cross-sectional study. General information, clinical data, and medical history data of all study subjects, including name, gender, body mass index (BMI), duration of diabetes, anti-diabetic therapies, high blood pressure (HBP) history, smoking history, and medication history, were completely collected. The results of laboratory tests, including biochemical parameters, glycosylated hemoglobin (HbA1c), fasting C-peptide, 2 h postprandial C-peptide, 24 h urine total protein (24 hUTP), urine microalbumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were recorded. EGG, Gastroparesis Cardinal Symptom Index (GCSI), gastric emptying ultrasound, fundus examination, carotid artery ultrasonography, cardiac autonomic function test, heart rate variability (HRV) were all examined and recorded as well. According to the results of EGG, the subjects were divided into normal gastric electrical rhythm (NGER) group and abnormal gastric electrical rhythm (AGER) group. RESULTS (1) Fasting blood glucose (FBG), HbA1c, the presence of diabetic peripheral neuropathy (DPN) and diabetic cardiac autonomic neuropathy (DCAN) were significantly higher in the AGER group (p < 0.05). Low frequency (LF) and high frequency (HF), the indicators of HRV, were significantly lower in the AGER group (p < 0.05). In addition, the prevalence of feeling excessively full after meals, loss of appetite, and stomach or belly visibly larger after meals of gastrointestinal symptoms of gastroparesis were significantly higher in the AGER group (p < 0.05). Multiple logistic regression analysis showed that FBG and the prevalence of DCAN were the independent risk factors. CONCLUSION AGER was associated with high FBG and the presence of DCAN. EGG examination is recommended for patients with gastrointestinal symptoms and clues of DCAN.
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Affiliation(s)
- Xixi Wang
- The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Lianhua Ma
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Miao Jiang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- NO.2 People's Hospital of Fuyang City, Fuyang, China
| | - Hong Zhu
- The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China
| | - Chendong Ni
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | | | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
| | - Hong-Hong Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
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Lee J, Park HL, Park SY, Lim CH, Kim MH, Lee JM, Chang SA, Oh JH. Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study. BMC Gastroenterol 2024; 24:30. [PMID: 38212710 PMCID: PMC10782575 DOI: 10.1186/s12876-023-03106-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/25/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.
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Affiliation(s)
- Jeongmin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Hye Lim Park
- Division of Nuclear medicine, Department of Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Su Young Park
- Division of Nuclear medicine, Department of Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea
| | - Min-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Jung Min Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Sang-Ah Chang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Jung-Hwan Oh
- Division of Gastroenterology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea.
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Li M, Gao N, Wang S, Guo Y, Liu Z. A global bibliometric and visualized analysis of the status and trends of gastroparesis research. Eur J Med Res 2023; 28:543. [PMID: 38017518 PMCID: PMC10683151 DOI: 10.1186/s40001-023-01537-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 11/17/2023] [Indexed: 11/30/2023] Open
Abstract
BACKGROUND Gastroparesis has a substantial impact on the quality of life but has limited treatment options, which makes it a public health concern. No bibliometric studies on gastroparesis have been published thus far. Thus, this article aims to summarize and analyze research hotspots to provide a reference for clinical researchers. MATERIALS AND METHODS Gastroparesis-related research articles were searched in the Web of Science Core Collection (WOSCC), and relevant information was extracted after screening. A total of 1033 documents were analyzed with the bibliometric method using Microsoft Excel, Citespace, and VOSviewer. RESULTS Overall, our search retrieved 1033 papers contributed by 966 research institutions from 53 countries. Since 1980, publications in this field have increased rapidly. United States (n = 645) and Temple University (n = 122) were the most productive country and institution, respectively. Parkman, with 96 publications, was the most prominent author. CONCLUSIONS Research hotspots in gastroparesis can be summarized into four domains: innovation in diagnostic modalities, change of oral therapeutic agents, choice of surgical interventions, and pathological mechanisms. Future research on gastroparesis should focus on the quality of life of patients, diagnostic techniques, pyloromyotomy, and transpyloric stent placement.
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Affiliation(s)
- Meng Li
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China
| | - Ning Gao
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China
| | - Shaoli Wang
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China
| | - Yufeng Guo
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China.
| | - Zhen Liu
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China.
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Xu W, Gharibans AA, Calder S, Schamberg G, Walters A, Jang J, Varghese C, Carson D, Daker C, Waite S, Andrews CN, Cundy T, O’Grady G. Defining and Phenotyping Gastric Abnormalities in Long-Term Type 1 Diabetes Using a Novel Body Surface Gastric Mapping Device. GASTRO HEP ADVANCES 2023; 2:1120-1132. [PMID: 39131562 PMCID: PMC11307485 DOI: 10.1016/j.gastha.2023.08.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/04/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims Diabetic gastroenteropathy is associated with poor glycemic control and morbidity in people with type 1 diabetes (T1D). There is a lack of noninvasive techniques to assess and monitor gastric abnormalities. We aimed to define phenotypes of gastric myoelectrical abnormalities in people with longstanding T1D with and without symptoms using a novel noninvasive body surface gastric mapping (BSGM) device. Methods BSGM was performed on people with T1D of >10 years duration and matched controls, employing Gastric Alimetry (Alimetry, New Zealand), comprising of a high-resolution 64-channel array, validated symptom-logging App, and wearable reader. Results Thirty-two people with T1D were recruited (15 with a high symptom burden), and 32 controls. Those with symptoms showed more unstable gastric myoelectrical activity (Gastric Alimetry Rhythm Index 0.39 vs 0.51, P = .017; and lower average spatial covariance 0.48 vs 0.51, P = .009) compared with controls. Symptomatic patients also had a higher prevalence of peripheral neuropathy (67% vs 6%, P = .001), anxiety/depression diagnoses (27% vs 0%, P = .001), and higher mean hemoglobin A1C levels (76 vs 56 mmol/mol, P < .001). BSGM defined distinct phenotypes in T1D participants including those with markedly unstable gastric rhythms (4/32, 12.5%) and abnormally high gastric frequencies (9/32, 28%). Deviation in gastric frequency was positively correlated with symptoms of bloating, upper gut pain, nausea and vomiting, and fullness (R > 0.35, P < .05). Conclusion Gastric symptoms in people with longstanding T1D correlate with myoelectrical abnormalities on BSGM evaluation, in addition to glycemic control, psychological comorbidities, and peripheral neuropathy. BSGM using Gastric Alimetry identified a range of myoelectrical phenotypes, presenting targets for diagnosis, monitoring, and therapy.
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Affiliation(s)
- William Xu
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Armen A. Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Anthony Walters
- Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Jia Jang
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Daniel Carson
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Alimetry Ltd, Auckland, New Zealand
- Department of Gastroenterology, North Shore Hospital, Te Whatu Ora Waitemata, New Zealand
| | | | - Christopher N. Andrews
- Alimetry Ltd, Auckland, New Zealand
- Department of Gastroenterology, University of Calgary, Calgary, Canada
| | - Tim Cundy
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Gregory O’Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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Ahmed MSO, Forde H, Smith D. Diabetic gastroparesis: clinical features, diagnosis and management. Ir J Med Sci 2023; 192:1687-1694. [PMID: 36266392 DOI: 10.1007/s11845-022-03191-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 10/09/2022] [Indexed: 11/07/2022]
Abstract
Diabetic gastroparesis carries a heavy burden on people with diabetes and the healthcare system. It remains underdiagnosed and represents challenges to treat. This article reviews the epidemiology, pathophysiology, clinical features, diagnosis and treatment of diabetic gastroparesis. The disorder is characterized by delayed gastric emptying without evidence of mechanical gastric outflow obstruction. It presents with upper gastrointestinal (GI) symptoms such as nausea, vomiting, early satiety, postprandial fullness, upper abdominal discomfort and or bloating. As the prevalence of diabetes has been growing over the last few decades, we would expect an increased incidence of delayed gastric emptying in poorly controlled diabetes and perhaps in line with the increasing use of medications that act on the GI tract such as incretin-based therapy. The disease results from multiple reversible and irreversible mechanisms. Diagnosing diabetic gastroparesis requires careful history, examination and investigations to exclude other disorders that could mimic its clinical presentation. Treatment involves a wide variety of options starting with optimization of glycaemic control, stopping any offending medications and lifestyle modifications followed by the introduction of medical therapeutics such as prokinetics. Then, surgical interventions are considered in refractory cases.
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Affiliation(s)
- Mohammed S O Ahmed
- Academic Department of Diabetes and Endocrinology, Beaumont Hospital, The Royal College of Surgeons in Ireland, Dublin, Ireland.
| | - Hannah Forde
- Academic Department of Diabetes and Endocrinology, Beaumont Hospital, The Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Diarmuid Smith
- Academic Department of Diabetes and Endocrinology, Beaumont Hospital, The Royal College of Surgeons in Ireland, Dublin, Ireland
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Zhang YX, Zhang YJ, Miao RY, Fang XY, Wei JH, Wei Y, Lin JR, Tian JX. Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis: A network meta-analysis. World J Diabetes 2023; 14:313-342. [PMID: 37035221 PMCID: PMC10075042 DOI: 10.4239/wjd.v14.i3.313] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/29/2022] [Accepted: 02/23/2023] [Indexed: 03/15/2023] Open
Abstract
BACKGROUND Diabetic gastroparesis (DGP) is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them. The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine (TCM) decoctions that have been shown to be effective in treating the disease. There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice.
AIM To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference.
METHODS PubMed, EMBASE, Cochrane Library, Web of Science, China National Kno-wledge Infrastructure, The China Biology Medicine DVD, Wanfang, and CQVIP were searched from inception to September 17, 2022, to collect randomized controlled trials (RCTs) about TCM decoctions for DGP. Clinical effects and symptom scores were the primary outcomes. Additionally, we assessed motilin (MOT), somatostatin (SS), gastrin (GAS), gastric emptying rate, gastric emptying time, and adverse drug events as secondary outcomes.
RESULTS A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included. The results of network meta-analysis (NMA) and surface under the cumulative ranking curve showed that with western medicine (WM) as a common control, the Banxia Xiexin Decoction (BXXD) + WM was most effective in clinical effects and enhancing early satiety scores; the Simo decoction (SMD) + WM was most effective in improving nausea and vomiting scores and anorexia scores, bloating scores; the Chaishao Liujunzi Decoction (CSLJD) was most effective in MOT, the Zhishi Xiaopi Decoction (ZSXPD) was most effective in SS and upgrading emptying rate; the Jianpi Xiaozhi Decoction was most effective in GAS; the CSLJD + WM was most effective in improving gastric emptying time.
CONCLUSION These NMA results suggest that the BXXD + WM and SMD + WM may be one of the potential optimal treatments. Due to various limitations, further large-sample, double-blind, multi-center randomized RCTs are needed.
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Affiliation(s)
- Yu-Xin Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jiao Zhang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Run-Yu Miao
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Graduate College, Beijing University of Chinese Medicine, Graduate College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xin-Yi Fang
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Graduate College, Beijing University of Chinese Medicine, Graduate College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jia-Hua Wei
- Graduate College, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
| | - Yu Wei
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Graduate College, Beijing University of Chinese Medicine, Graduate College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jia-Ran Lin
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
- Graduate College, Beijing University of Chinese Medicine, Graduate College, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jia-Xing Tian
- Institute of Metabolic Diseases, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Gastroparesis: An Evidence-Based Review for the Bariatric and Foregut Surgeon. Surg Obes Relat Dis 2023; 19:403-420. [PMID: 37080885 DOI: 10.1016/j.soard.2023.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023]
Abstract
Gastroparesis is a gastric motility disorder characterized by delayed gastric emptying. It is a rare disease and difficult to treat effectively; management is a dilemma for gastroenterologists and surgeons alike. We conducted a systematic review of the literature to evaluate current diagnostic tools as well as treatment options. We describe key elements in the pathophysiology of the disease, in addition to current evidence on treatment alternatives, including nutritional considerations, medical and surgical options, and related outcomes.
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9
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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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Dahiya DS, Inamdar S, Perisetti A, Goyal H, Singh A, Garg R, Cheng CI, Kichloo A, Al-Haddad M, Sharma N. The Conundrum of Obesity and Gastroparesis Hospitalizations: A Retrospective Comparative Analysis of Hospitalization Characteristics and Disparities Amongst Socioeconomic and Racial Backgrounds in the United States. J Neurogastroenterol Motil 2022; 28:655-663. [PMID: 36250372 PMCID: PMC9577565 DOI: 10.5056/jnm21232] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 04/10/2022] [Accepted: 04/12/2022] [Indexed: 12/24/2022] Open
Abstract
Background/Aims We aim to assess the influence of obesity on gastroparesis (GP) hospitalizations in the United States (US). Methods The National Inpatient Sample was analyzed from 2007-2017 to identify all adult hospitalizations with a primary discharge diagnosis of GP. They were subdivided based on the presence or absence of obesity (body mass index > 30). Hospitalization characteristics, procedural differences, all-cause inpatient mortality, mean length of stay (LOS), and mean total hospital charge (THC) were identified and compared. Results From 2007-2017, there were 140 293 obese GP hospitalizations accounting for 13.75% of all GP hospitalizations in the US. Obese GP hospitalizations were predominantly female (76.11% vs 64.36%, P < 0.001) and slightly older (51.9 years vs 50.8 years, P < 0.001) compared to the non-obese cohort. Racial disparities were noted as Blacks (25.49% vs 22%, P < 0.001) had higher proportions of GP hospitalizations with obesity compared to the non-obese cohort. Furthermore, we noted higher rates of inpatient upper endoscopy utilization (6.05% vs 5.42%, P < 0.001), longer mean LOS (5.71 days vs 5.32 days, P < 0.001), and higher mean THC ($53 373 vs $45 040, P < 0.001) for obese GP hospitalizations compared to the non-obese group. However, obese GP hospitalizations had lower rates of inpatient mortality (0.92% vs 1.33%, P < 0.001), and need for nutritional support with endoscopic jejunostomy (0.25 vs 0.56%, P < 0.001) and total parenteral nutrition (1.46% vs 2.33%, P < 0.001) compared to the non-obese cohort. Conclusions In the US, compared to non-obese, a higher proportion of obese GP hospitalizations were female and Blacks. Obese GP hospitalizations also had higher THC, LOS, and rates of upper endoscopy.
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Affiliation(s)
- Dushyant S Dahiya
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Sumant Inamdar
- Department of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | | | - Hemant Goyal
- The Wright Center for Graduate Medical Education, Scranton, PA, USA.,Department of Internal Medicine, Mercer University School of Medicine, Macon, GA, USA
| | - Amandeep Singh
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Rajat Garg
- Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Chin-I Cheng
- Central Michigan University College of Science and Engineering, Mt Pleasant, MI, USA
| | - Asim Kichloo
- Department of Internal Medicine, Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Neil Sharma
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN, USA.,Division of Interventional Oncology and Surgical Endoscopy (IOSE), Parkview Cancer Institute, Fort Wayne, IN, USA
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Tendulkar P, Kant R, Rana S, Yadav P, Mirza AA, Agarwal D. Efficacy of Pro-Kinetic Agents in Type 2 Diabetes Mellitus Patients With Gastroparesis Using Lactulose Hydrogen Breath Testing: A Randomized Trial. Cureus 2022; 14:e20990. [PMID: 35154966 PMCID: PMC8817741 DOI: 10.7759/cureus.20990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/06/2022] [Indexed: 11/08/2022] Open
Abstract
Aim The aim of the study was to determine the efficacy of prokinetic agents in diabetic gastroparesis patients. Method This was a randomized open-label trial conducted on 50 patients with type 2 diabetes experiencing diabetic gastroparesis, which was diagnosed with the lactulose hydrogen breath test. After randomization, all 50 patients were divided into four arms (cinitapride, metoclopramide, levosulpiride, and domperidone) of different prokinetics and followed up for four weeks; after which, repeat gastroparesis cardinal symptom index score and orocecal transit time were recorded in order to assess the response to the treatment. Result There was no statistically significant difference among the four groups in terms of all the baseline characteristics except for gender (p=0.032). The follow-up gastroparesis cardinal symptom index was collected for 50 patients but repeat orocecal transit time could be performed only in 37 patients. In all four groups, there was a statistically significant (p<0.05) improvement in terms of orocecal transit time and gastroparesis cardinal symptom index scores. But there was no statistically significant difference in relative efficacy amongst these study groups. Conclusion Our study showed statistically significant improvement with four prokinetics drugs in terms of gastroparesis cardinal symptom index score and orocecal transit time, but there was no statistically significant benefit of one prokinetic drug over the other. Our study showed promising results with regard to prokinetic use in diabetic gastroparesis.
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Abstract
Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
| | - Kenton M. Sanders
- Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV
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13
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Jalleh RJ, Marathe CS, Jones KL, Horowitz M, Rayner CK. Digesting the pathogenesis of diabetic gastroparesis. J Diabetes Complications 2021; 35:107992. [PMID: 34389236 DOI: 10.1016/j.jdiacomp.2021.107992] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 07/08/2021] [Indexed: 02/07/2023]
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14
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Viola MF, Boeckxstaens G. Niche-specific functional heterogeneity of intestinal resident macrophages. Gut 2021; 70:1383-1395. [PMID: 33384336 PMCID: PMC8223647 DOI: 10.1136/gutjnl-2020-323121] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 12/11/2020] [Accepted: 12/12/2020] [Indexed: 12/22/2022]
Abstract
Intestinal resident macrophages are at the front line of host defence at the mucosal barrier within the gastrointestinal tract and have long been known to play a crucial role in the response to food antigens and bacteria that are able to penetrate the mucosal barrier. However, recent advances in single-cell RNA sequencing technology have revealed that resident macrophages throughout the gut are functionally specialised to carry out specific roles in the niche they occupy, leading to an unprecedented understanding of the heterogeneity and potential biological functions of these cells. This review aims to integrate these novel findings with long-standing knowledge, to provide an updated overview on our understanding of macrophage function in the gastrointestinal tract and to speculate on the role of specialised subsets in the context of homoeostasis and disease.
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Affiliation(s)
- Maria Francesca Viola
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (Chrometa), KU Leuven, Leuven, Flanders, Belgium
| | - Guy Boeckxstaens
- Translational Research in Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing (Chrometa), KU Leuven, Leuven, Flanders, Belgium
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15
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Dahiya DS, Kichloo A, Shaka H, Singh J, Edigin E, Solanki D, Eseaton PO, Wani F. Gastroparesis with Cannabis Use: A Retrospective Study from the Nationwide Inpatient Sample. Postgrad Med 2021; 133:791-797. [PMID: 34096455 DOI: 10.1080/00325481.2021.1940219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Background: With increasing utilization of cannabis in the United States (US), clinicians may encounter more cases of Gastroparesis (GP) in coming years.Objective: The primary outcome was inpatient mortality for GP with cannabis use. Secondary outcomes included system-based complications and the burden of the disease on the US healthcare system.Methods: From the Nationwide Inpatient Sample (NIS), we identified adult hospitalizations with a primary discharge diagnosis of GP for 2016 and 2017. Individuals ≤18 years of age were excluded. The study population was subdivided based on a secondary diagnosis of cannabis use. The outcomes included biodemographic characteristics, mortality, complications, and burden of disease on the US healthcare system.Results: For 2016 and 2017, we identified 99,695 hospitalizations with GP. Of these hospitalizations, 8,870 had a secondary diagnosis of cannabis use while 90,825 served as controls. The prevalence of GP with cannabis use was 8.9%. For GP with cannabis use, the patients were younger (38.5 vs 48.1 years, p < 0.001) with a Black predominance (Table 1) and lower proportion of females (52.3 vs 68.3%, p < 0.001) compared to the non-cannabis use cohort. Additionally, the cannabis use cohort had higher percentage of patients with co-morbidities like hypertension, diabetes mellitus and a history of smoking. The inpatient mortality for GP with cannabis use was noted to be 0.27%. Furthermore, we noted shorter mean length of stay (LOS) (3.4 vs 4.4 days, aMD: -0.7, 95%CI: -0.9 - [-0.5], p < 0.001), lower mean total hospital charge (THC) ($30,400 vs $38,100, aMD: -5100, 95%CI: -6900 - [-3200], p < 0.001), and lower rates of sepsis (0.11 vs 0.60%, aOR: 0.22, 95% CI: 0.05-0.91, p = 0.036) for GP hospitalizations with cannabis use compared to the non-cannabis use cohort.Conclusion: Inpatient mortality for GP hospitalizations with cannabis use was 0.27%. Additionally, these patients had shorter LOS, lower THC, and lower sepsis rates.
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Affiliation(s)
- Dushyant Singh Dahiya
- Department of Internal Medicine, Central Michigan University, Saginaw, Michigan, USA
| | - Asim Kichloo
- Department of Internal Medicine, Central Michigan University, Saginaw, Michigan, USA.,Department of Internal Medicine, Samaritan Medical Center, Watertown, New York, USA
| | - Hafeez Shaka
- Department of Internal Medicine, John H Stroger Jr. Hospital Cook County, Chicago, Ilinois, USA
| | - Jagmeet Singh
- Department of Internal Medicine, Geisinger School of Medicine, Scranton, Pennsylvania, USA
| | - Ehizogie Edigin
- Department of Internal Medicine, John H Stroger Jr. Hospital Cook County, Chicago, Ilinois, USA
| | - Dhanshree Solanki
- Department of Internal Medicine, Rutgers University, New Brunswick, New Jersey, USA
| | | | - Farah Wani
- Department of Family Medicine, Samaritan Medical Center, Watertown, New York, USA
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Affiliation(s)
- Raj K Goyal
- From the Division of Gastroenterology, Department of Medicine, Veterans Affairs Boston Healthcare System, West Roxbury, and the Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston - both in Massachusetts
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Camilleri M. Relationship of motor mechanisms to gastroparesis symptoms: toward individualized treatment. Am J Physiol Gastrointest Liver Physiol 2021; 320:G558-G563. [PMID: 33566731 PMCID: PMC8238170 DOI: 10.1152/ajpgi.00006.2021] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Following a classical paper by Dr. Keith A. Kelly published in this journal, and over the past 40 years, there has been increased understanding of the functions of different regions of the stomach, specifically the fundus, antrum, and pylorus. Several of the important physiological principles were based on in vivo animal studies that led to the appreciation of regional function and control mechanisms. These include the roles of the extrinsic parasympathetic vagal innervation, the gastric enteric nervous system and electrical syncytium consisting of pacemaker cells and smooth muscle cells, and duodenogastric reflexes providing feedback regulation following the arrival of food and hydrogen ions stimulating the release of hormones and vagal afferent mechanisms that inhibit gastric motility and stimulate pyloric contractility. Further insights on the role of regional motor functions in gastric emptying were obtained from observations in patients following diverse gastric surgeries or bariatric procedures, including fundoplication, Billroth I and sleeve gastrectomy, and sleeve gastroplasty. Antropyloroduodenal manometry and measurements of pyloric diameter and distensibility index provided important assessments of the role of antral hypomotility and pylorospasm, and these constitute specific targets for individualized treatment of patients with gastroparesis. Moreover, in patients with upper gastrointestinal symptoms suggestive of gastroparesis, the availability of measurements of gastric accommodation and pharmacological agents to reduce gastric sensitivity or enhance gastric accommodation provide additional specific targets for individualized treatment. It is anticipated that, in the future, such physiological measurements will be applied in patients to optimize choice of therapy, possibly including identifying the best candidate for pyloric interventions.
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Affiliation(s)
- Michael Camilleri
- Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota
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18
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Aigner L, Becker B, Gerken S, Quast DR, Meier JJ, Nauck MA. Day-to-Day Variations in Fasting Plasma Glucose Do Not Influence Gastric Emptying in Subjects With Type 1 Diabetes. Diabetes Care 2021; 44:479-488. [PMID: 33288653 DOI: 10.2337/dc20-1660] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 09/17/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Acute experimental variations in glycemia decelerate (hyperglycemia) or accelerate (hypoglycemia) gastric emptying. Whether spontaneous variations in fasting plasma glucose (FPG) have a similar influence on gastric emptying is yet unclear. RESEARCH DESIGN AND METHODS Gastric emptying of a mixed meal was prospectively studied three times in 20 patients with type 1 diabetes and 10 healthy subjects with normal glucose tolerance using a 13C-CO2 octanoate breath test with Wagner-Nelson analysis. The velocity of gastric emptying was related to FPG measured before the test (grouped as low, intermediate, or high). In addition, gastric emptying data from 255 patients with type 1 diabetes studied for clinical indications were compared by tertiles of baseline FPG. RESULTS Despite marked variations in FPG (by 4.8 [95% CI 3.4; 6.2] mmol/L), gastric emptying did not differ among the three prospective examinations in patients with type 1 diabetes (Δ T1/2 between highest and lowest FPG: 1 [95% CI -35; 37] min; P = 0.90). The coefficient of variation for T1/2 determined three times was 21.0%. Similar results at much lower variations in FPG were found in healthy subjects. In the cross-sectional analysis, gastric emptying did not differ between the tertiles of FPG (Δ T1/2 between highest and lowest FPG: 7 [95% CI -10; 23] min; P = 0.66), when FPG varied by 7.2 (6.7; 7.8) mmol/L. However, higher HbA1c was significantly related to slower gastric emptying. CONCLUSIONS Day-to-day variations in FPG not induced by therapeutic measures do not influence gastric emptying significantly. These findings are in contrast with those obtained after rapidly clamping plasma glucose in the hyper- or hypoglycemic concentrations range and challenge the clinical importance of short-term glucose fluctuations for gastric emptying in patients with type 1 diabetes. Rather, chronic hyperglycemia is associated with slowed gastric emptying.
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Affiliation(s)
- Lea Aigner
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Björn Becker
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Sonja Gerken
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Daniel R Quast
- Division of Diabetology, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University, Bochum, Germany
| | - Juris J Meier
- Division of Diabetology, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University, Bochum, Germany
| | - Michael A Nauck
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany .,Division of Diabetology, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University, Bochum, Germany
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19
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Marathe CS, Jones KL, Wu T, Rayner CK, Horowitz M. Gastrointestinal autonomic neuropathy in diabetes. Auton Neurosci 2020; 229:102718. [PMID: 32916479 DOI: 10.1016/j.autneu.2020.102718] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 04/22/2020] [Accepted: 07/22/2020] [Indexed: 02/07/2023]
Abstract
Gastrointestinal autonomic neuropathy represents an important and diverse, but poorly appreciated, manifestation of diabetic autonomic neuropathy that impacts negatively on quality of life. There is no test to assess gastrointestinal autonomic nerve damage directly in humans; cardiovascular autonomic reflex tests are often used as a surrogate, but are suboptimal. Gastrointestinal symptoms are common in diabetes, but usually correlate only weakly with disordered motility. Diabetic gastroparesis, or abnormally delayed gastric emptying, occurs frequently and is the best characterized manifestation of gastrointestinal autonomic neuropathy. There is a bi-directional relationship between postprandial glycaemia and the rate of gastric emptying. However, autonomic neuropathy can affect the function of any gut segment from the esophagus to the anus. Current management options for gastrointestinal autonomic neuropathy are, for the main part, empirical and sub-optimal.
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Affiliation(s)
- Chinmay S Marathe
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia.
| | - Karen L Jones
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia.
| | - Tongzhi Wu
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia.
| | - Christopher K Rayner
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Australia.
| | - Michael Horowitz
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia.
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20
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Wu T, Yue R, Li L, He M. Study on the Mechanisms of Banxia Xiexin Decoction in Treating Diabetic Gastroparesis Based on Network Pharmacology. Interdiscip Sci 2020; 12:487-498. [PMID: 32914205 DOI: 10.1007/s12539-020-00389-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 08/25/2020] [Accepted: 08/31/2020] [Indexed: 02/08/2023]
Abstract
In China, Banxia Xiexin decoction (BXD) is applied to treat diabetic gastroparesis (DGP), but its key active ingredients and mechanisms against DGP are unclear. This study is designated to reveal the molecular mechanisms of BXD in treating DGP by adopting a creative approach known as network pharmacology to explore the active ingredients and therapeutic targets of BXD. In our study, 730 differentially expressed genes of DGP were obtained, and 30 potential targets of BXD against DGP were screened out (including ADRB2, DRD1, FOS, MMP9, FOSL1, FOSL2, JUN, MAP2, DRD2, MYC, F3, CDKN1A, IL6, NFKBIA, ICAM1, CCL2, SELE, DUOX2, MGAM, THBD, SERPINE1, ALOX5, CXCL11, CXCL2, CXCL10, RUNX2, CD40LG, C1QB, MCL1, and ADCYAP1). Based on the findings, BXD contains 60 compounds with therapeutic effect on DGP, including the key active ingredients such as quercetin, wogonin, baicalein, beta-sitosterol, and kaempferol. Sixty-eight pathways including TNF signaling pathway, IL-17 signaling pathway, and AGE-RAGE signaling pathway were significantly enriched. In this study, the mechanisms of BXD in treating DGP are affirmed to be a complex network with multi-target and multi-pathway, which provides a reference for future experimental studies.
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Affiliation(s)
- Tingchao Wu
- Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, SiChuan, China
| | - Rensong Yue
- Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, SiChuan, China.
| | - Liang Li
- University of Electronic Science and Technology of China, Chengdu, SiChuan, China
| | - Mingmin He
- Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, SiChuan, China
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Chikkamenahalli LL, Pasricha PJ, Farrugia G, Grover M. Gastric Biopsies in Gastroparesis: Insights into Gastric Neuromuscular Disorders to Aid Treatment. Gastroenterol Clin North Am 2020; 49:557-570. [PMID: 32718570 PMCID: PMC7387746 DOI: 10.1016/j.gtc.2020.04.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The cellular and molecular understanding of human gastroparesis has markedly improved due to studies on full-thickness gastric biopsies. A decrease in the number of interstitial cells of Cajal (ICC) and functional changes in ICC constitutes the hallmark cellular feature of gastroparesis. More recently, in animal models, macrophages have also been identified to play a central role in development of delayed gastric emptying. Activation of macrophages leads to loss of ICC. In human gastroparesis, loss of anti-inflammatory macrophages in gastric muscle has been shown. Deeper molecular characterization using transcriptomics and proteomics has identified macrophage-based immune dysregulation in human gastroparesis.
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Affiliation(s)
- Lakshmikanth L. Chikkamenahalli
- Enteric NeuroScience Program, Mayo clinic, Division of Gastroenterology & Hepatology, Physiology & Biomedical Engineering Mayo Clinic, 200 1 Street SW, Rochester, MN 55905, Tel: +1 507-538-0337
| | - Pankaj J. Pasricha
- Center for Neurogastroenterology, Division of Gastroenterology & Hepatology Johns Hopkins School of Medicine, Ross 958, 720 Rutland Avenue, Baltimore, MD 21205, Tel: +1 443-613-8152
| | - Gianrico Farrugia
- Enteric NeuroScience Program, Division of Gastroenterology & Hepatology, Physiology & Biomedical Engineering Mayo Clinic, 200 1 Street SW, Rochester, MN 55905, Tel: +1 507-284-4695
| | - Madhusudan Grover
- Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA; Division of Physiology and Biomedical Engineering, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
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22
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Usai-Satta P, Bellini M, Morelli O, Geri F, Lai M, Bassotti G. Gastroparesis: New insights into an old disease. World J Gastroenterol 2020. [DOI: 10.3748/wjg.v26.i19.2332] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/24/2023] Open
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Usai-Satta P, Bellini M, Morelli O, Geri F, Lai M, Bassotti G. Gastroparesis: New insights into an old disease. World J Gastroenterol 2020; 26:2333-2348. [PMID: 32476797 PMCID: PMC7243643 DOI: 10.3748/wjg.v26.i19.2333] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 03/08/2020] [Accepted: 05/01/2020] [Indexed: 02/06/2023] Open
Abstract
Gastroparesis (Gp) is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction. Although this condition has been reported in the literature since the mid-1900s, only recently has there been renewed clinical and scientific interest in this disease, which has a potentially great impact on the quality of life. The aim of this review is to explore the pathophysiological, diagnostic and therapeutical aspects of Gp according to the most recent evidence. A comprehensive online search for Gp was carried out using MEDLINE and EMBASE. Gp is the result of neuromuscular abnormalities of the gastric motor function. There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes. As regards diagnostic approach, 99-Technetium scintigraphy is currently considered to be the gold standard for Gp. Its limits are a lack of standardization and a mild risk of radiation exposure. The C13 breath testing is a valid and safe alternative method. 13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits. The wireless motility capsule is a promising technique, but its use is limited by costs and scarce availability in many countries. Finally, therapeutic strategies are related to the clinical severity of Gp. In mild and moderate Gp, dietary modification and prokinetic agents are generally sufficient. Metoclopramide is the only drug approved by the Food and Drug Administration for Gp. However, other older and new prokinetics and antiemetics can be considered. As a second-line therapy, tricyclic antidepressants and cannabinoids have been proposed. In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed. In drug-unresponsive Gp patients some alternative strategies (endoscopic, electric stimulation or surgery) are available.
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Affiliation(s)
- Paolo Usai-Satta
- Department of Internal Medicine, Division of Gastroenterology, Brotzu Hospital, Cagliari 09124, Italy
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Olivia Morelli
- Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia Medical School, Perugia 06123, Italy
| | - Francesca Geri
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Mariantonia Lai
- Gastroenterology Unit, University of Cagliari, Monserrato 09042, Italy
| | - Gabrio Bassotti
- Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia Medical School, Perugia 06123, Italy
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Grybäck P, Jacobsson H, Neuger L, Hellström PM. Gastroparesis versus dyspepsia by intragastric meal distribution: new diagnostics and definitions ahead. Scand J Gastroenterol 2020; 55:251-255. [PMID: 31928242 DOI: 10.1080/00365521.2019.1710244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Gastroparesis often presents a challenge to the practicing gastroenterologist. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also significant disruption of social activities that often center around food. The treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic and idiosyncratic nature of the illness, often with some common psychiatric co-morbidity, parallels other functional disorders of the gastrointestinal tract. These parallels have provided the rationale for studies investigating alternative diagnostic features of the gastric emptying test as employed in the clinical setting. Hence, not only the regular cut-offs of 60% or 10% gastric retention of a meal at 2 and 4 h, but also a new concept, the intragastric meal distribution at time 0 (IMD0) is now introduced as a plausible diagnostic feature that should be more aligned with the patients' symptoms as they appear in close connection with the meal. Impaired gastric accommodation with absence of fundic relaxation followed by dumping of the meal into antrum is suggested to be diagnostic for functional dyspepsia and gastroparesis. The diagnostic cut-off is considered when more than 57% of the meal is distributed to the distal part of the stomach immediately on food intake. This new diagnostic feature of the gastric emptying profile lend support to better understanding of the patients' symptoms and provides a new basis for pharmacological treatment options in gastroparesis that may provide an improved quality of life in affected individuals.
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Affiliation(s)
- Per Grybäck
- Department of Hospital Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Hans Jacobsson
- Department of Hospital Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Lucyna Neuger
- Department of Nuclear Medicine, Uppsala University, Uppsala, Sweden
| | - Per M Hellström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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25
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Rahmani B, Gandhi J, Joshi G, Smith NL, Reid I, Khan SA. The Role of Diabetes Mellitus in Diseases of the Gallbladder and Biliary Tract. Curr Diabetes Rev 2020; 16:931-948. [PMID: 32133965 DOI: 10.2174/1573399816666200305094727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 02/18/2020] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increasing prevalence of diabetes mellitus worldwide continues to pose a heavy burden. Though its gastrointestinal impact is appropriately recognized, the lesser known associations may be overlooked. OBJECTIVE We aim to review the negative implications of diabetes on the gallbladder and the biliary tract. METHODS A MEDLINE® database search of literature was conducted with emphasis on the previous five years, combining keywords such as "diabetes," "gallbladder," and "biliary". RESULTS The association of diabetes to the formation of gallstones, gallbladder cancer, and cancer of the biliary tract are discussed along with diagnosis and treatment. CONCLUSION Though we uncover the role of diabetic neuropathy in gallbladder and biliary complications, the specific individual diabetic risk factors behind these developments is unclear. Also, in addition to diabetes control and surgical gallbladder management, the treatment approach also requires further focus.
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Affiliation(s)
- Benjamin Rahmani
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Jason Gandhi
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Medical Student Research Institute, St. George’s University School of Medicine, Grenada, West Indies
| | - Gunjan Joshi
- Department of Internal Medicine, Stony Brook Southampton Hospital, Southampton, NY, USA
| | | | - Inefta Reid
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Sardar Ali Khan
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Department of Urology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
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26
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Asha MZ, Khalil SFH. Pharmacological Approaches to Diabetic Gastroparesis: A systematic review of randomised clinical trials. Sultan Qaboos Univ Med J 2019; 19:e291-e304. [PMID: 31897312 PMCID: PMC6930032 DOI: 10.18295/squmj.2019.19.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 07/10/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023] Open
Abstract
Pharmacological interventions of diabetic gastroparesis (DG) constitute an essential element of a patient’s management. This article aimed to systematically review the available pharmacological approaches of DG, including their efficacy and safety. A total of 24 randomised clinical trials (RCTs) that investigated the efficacy and/or safety of medications targeting DG symptoms were identified using several online databases. Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. However, this medication may have several adverse effects on the cardiovascular and nervous systems, which might be resolved with a new intranasal preparation. Acceptable alternatives are oral domperidone for patients without cardiovascular risk factors or intravenous erythromycin for hospitalised patients. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes.
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Affiliation(s)
- Mohammad Z Asha
- Department of Internal Medicine, Dr Mohamad Amine Zbeib Polyclinic, Doha, Qatar
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27
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Goyal RK, Cristofaro V, Sullivan MP. Rapid gastric emptying in diabetes mellitus: Pathophysiology and clinical importance. J Diabetes Complications 2019; 33:107414. [PMID: 31439470 PMCID: PMC7707148 DOI: 10.1016/j.jdiacomp.2019.107414] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Revised: 07/20/2019] [Accepted: 08/07/2019] [Indexed: 12/23/2022]
Abstract
Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid gastric emptying also is a frequent and important diabetic complication. In contrast, acute hyperglycemia causes slow gastric emptying, and acute hypoglycemia causes rapid gastric emptying. Rapid gastric emptying is frequent in T2DM; however, it may also occur in T1DM, particularly in the early stages of the disease, but may persist even into late stages. Recent studies suggest that usually, the stomach restricts the emptying of nutrients to 1-4 kcals/min. This restriction is due to the action of the gastric 'braking' hormones such as GLP-1, leptin, and amylin acting via the gastric inhibitory vagal motor circuit (GIVMC). Disruption of this braking system leads to rapid gastric emptying. Acute hyperglycemia also slows gastric emptying by stimulating the GIVMC, while acute hypoglycemia causes rapid gastric emptying by stimulating the gastric excitatory vagal motor circuit (GEVMC). In contrast, chronic hyperglycemia causes rapid gastric emptying by inducing oxidative stress in the stomach wall that disrupts inhibitory neuromuscular transmission and increases the contractility of the smooth muscle, while chronic hyperglycemia may also cause slow gastric emptying via severe inflammatory stress caused by proinflammatory macrophages and reduce contractility of the smooth muscle. There is a bidirectional relationship between blood glucose and gastric emptying. Thus, rapid gastric emptying may lead to a sizeable postprandial spike, and slow gastric emptying may blunt it. Postprandial hyperglycemia is involved in the development, progression, and complications of DM. Correction of fast gastric emptying involves agents that activate GIVMC and the use of gastric 'braking' hormones or their analogs. Recognition and treatment of rapid gastric emptying may contribute to better management of postprandial hyperglycemia and prevention of some diabetic complications.
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Affiliation(s)
- Raj K Goyal
- Departments of Medicine and Surgery, VA Boston Healthcare System and Harvard Medical School, Boston, MA, United States of America.
| | - Vivian Cristofaro
- Departments of Medicine and Surgery, VA Boston Healthcare System and Harvard Medical School, Boston, MA, United States of America
| | - Maryrose P Sullivan
- Departments of Medicine and Surgery, VA Boston Healthcare System and Harvard Medical School, Boston, MA, United States of America
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Abstract
This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.
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Affiliation(s)
- Adil E Bharucha
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Yogish C Kudva
- Division of Endocrinology. Mayo Clinic, Rochester, Minnesota
| | - David O Prichard
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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29
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Loganathan P, Gajendran M, McCallum RW. Clinical Manifestation and Natural History of Gastroparesis. Gastrointest Endosc Clin N Am 2019; 29:27-38. [PMID: 30396526 DOI: 10.1016/j.giec.2018.08.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Although gastroparesis was described more than 60 years ago, the natural history and the long-term outcome are still being clarified. The patients with more severe gastroparesis often seek health care treatment in university medical centers specializing in gastrointestinal motility disorders and hence reports in the literature tend to be based on this population and may not be representative of the entire spectrum. The clinical manifestations of gastroparesis are heterogeneous but a significant proportion of patients end up with substantially poorer quality of life. In this article, the focus is on the clinical presentation and natural history of gastroparesis.
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Affiliation(s)
- Priyadarshini Loganathan
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905, USA
| | - Mahesh Gajendran
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905, USA
| | - Richard W McCallum
- Division of Gastroenterology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905, USA.
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30
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Chedid V, Brandler J, Vijayvargiya P, Park SY, Szarka LA, Camilleri M. Characterization of Upper Gastrointestinal Symptoms, Gastric Motor Functions, and Associations in Patients with Diabetes at a Referral Center. Am J Gastroenterol 2019; 114:143-154. [PMID: 30166634 DOI: 10.1038/s41395-018-0234-1] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Our aim was to characterize upper gastrointestinal (UGI) symptoms and associations in individuals with diabetes mellitus (DM) who had undergone evaluation of gastric emptying (GE) and accommodation (GA) at a referral center. METHODS From the Mayo Clinic Rochester electronic medical records of adults with diabetes types 1 and 2 (DM1 and DM2) evaluated between January 1997 and December 2015, we extracted demographics, UGI symptoms, current medications, treatments for diabetes, GE solids by scintigraphy, GA by single photon emission computed tomography (SPECT), and diabetes complications. We compared subgroups with delayed (GE at 2 h <25% or GE at 4 h <75%), rapid (GE at 1 h > 35%), and normal GE, as well as reduced (<428 mL) and normal GA. RESULTS We reviewed 108 patients (60.2% females, median age 49.0 years). Overall, 71.3% had DM2; one-third of these were insulin dependent and had fairly well-controlled diabetes (median HbA1c 6.7% (IQR 6.2; 7.9)). Manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, and retinopathy) were uncommon at presentation with UGI symptoms. Nausea was the most common symptom (80.6%). There were single or combined GE (total 56%: rapid in 37%, slow in 19%) and GA (total 39%) abnormalities; there was normal GA and GE in 28%; 40.3% of the DM2 patients had accelerated GE at 1 h. GE at 1 h is associated with nausea/vomiting, and fasting gastric volume is associated with bloating. CONCLUSIONS Among referred diabetic patients with UGI symptoms, GE and GA testing identifies potential targets for individualizing treatment and avoidance of empirical trials for the 28% with no disturbance of GE and GA.
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Affiliation(s)
- Victor Chedid
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA
| | - Justin Brandler
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA
| | - Priya Vijayvargiya
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA
| | - Seon-Young Park
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA.,Present address: Department of Internal Medicine, Chonnam National University Hospital, Gwangju, South Korea
| | - Lawrence A Szarka
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN, USA
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31
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Mihai BM, Mihai C, Cijevschi-Prelipcean C, Grigorescu ED, Dranga M, Drug V, Sporea I, Lăcătușu CM. Bidirectional Relationship between Gastric Emptying and Plasma Glucose Control in Normoglycemic Individuals and Diabetic Patients. J Diabetes Res 2018; 2018:1736959. [PMID: 30402500 PMCID: PMC6192082 DOI: 10.1155/2018/1736959] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 05/14/2018] [Accepted: 09/12/2018] [Indexed: 12/21/2022] Open
Abstract
Gastric emptying and glycemic control pathways are closely interrelated processes. Gastric chyme is transferred into the duodenum with velocities depending on its solid or liquid state, as well as on its caloric and nutritional composition. Once nutrients enter the intestine, the secretion of incretins (hormonal products of intestinal cells) is stimulated. Among incretins, glucagon-like peptide-1 (GLP-1) has multiple glycemic-regulatory effects that include delayed gastric emptying, thus triggering a feedback loop lowering postprandial serum glucose levels. Glycemic values also influence gastric emptying; hyperglycemia slows it down, and hypoglycemia accelerates it, both limiting glycemic fluctuations. Disordered gastric emptying in diabetes mellitus is understood today as a complex pathophysiological condition, with both irreversible and reversible components and high intra- and interindividual variability of time span and clinical features. While limited delays may be useful for reducing postprandial hyperglycemias, severely hindered gastric emptying may be associated with higher glycemic variability and worsened long-term glycemic control. Therapeutic approaches for both gastric emptying and glycemic control include dietary modifications of meal structure or content and drugs acting as GLP-1 receptor agonists. In the foreseeable future, we will probably witness a wider range of dietary interventions and more incretin-based medications used for restoring both gastric emptying and glycemic levels to nearly physiological levels.
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Affiliation(s)
- Bogdan Mircea Mihai
- “Grigore T. Popa” University of Medicine and Pharmacy, Clinical Centre of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” Clinical Hospital, Iași, Romania
| | - Cătălina Mihai
- “Grigore T. Popa” University of Medicine and Pharmacy, Institute of Gastroenterology and Hepatology, “Sf. Spiridon” Clinical Hospital, Iași, Romania
| | - Cristina Cijevschi-Prelipcean
- “Grigore T. Popa” University of Medicine and Pharmacy, Institute of Gastroenterology and Hepatology, “Sf. Spiridon” Clinical Hospital, Iași, Romania
| | - Elena-Daniela Grigorescu
- “Grigore T. Popa” University of Medicine and Pharmacy, Clinical Centre of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” Clinical Hospital, Iași, Romania
| | - Mihaela Dranga
- “Grigore T. Popa” University of Medicine and Pharmacy, Institute of Gastroenterology and Hepatology, “Sf. Spiridon” Clinical Hospital, Iași, Romania
| | - Vasile Drug
- “Grigore T. Popa” University of Medicine and Pharmacy, Institute of Gastroenterology and Hepatology, “Sf. Spiridon” Clinical Hospital, Iași, Romania
| | - Ioan Sporea
- Gastroenterology, “Victor Babes” University of Medicine and Pharmacy Timișoara, Romania
| | - Cristina Mihaela Lăcătușu
- “Grigore T. Popa” University of Medicine and Pharmacy, Clinical Centre of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” Clinical Hospital, Iași, Romania
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32
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Marathe CS, Rayner CK, Wu T, Jones KL, Horowitz M. Gastric Emptying and the Personalized Management of Type 1 Diabetes. J Clin Endocrinol Metab 2018; 103:3503-3506. [PMID: 29788123 DOI: 10.1210/jc.2018-00849] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 05/11/2018] [Indexed: 02/07/2023]
Affiliation(s)
- Chinmay S Marathe
- Faculty of Health and Medical Sciences, Adelaide Medical School, 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
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Faculty of Health and Medical Sciences, Adelaide Medical School, 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
| | - Tongzhi Wu
- Faculty of Health and Medical Sciences, Adelaide Medical School, 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
| | - Karen L Jones
- Faculty of Health and Medical Sciences, Adelaide Medical School, 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
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Michael Horowitz
- Faculty of Health and Medical Sciences, Adelaide Medical School, 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
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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33
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Huang J. Analysis of the Relationship between Helicobacter pylori Infection and Diabetic Gastroparesis. Chin Med J (Engl) 2018; 130:2680-2685. [PMID: 29133755 PMCID: PMC5695052 DOI: 10.4103/0366-6999.218012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Background: Whether Helicobacter pylori infection is associated with diabetic gastroparesis (DGP) is unclear. This study aimed to investigate the potential correlation between H. pylori infection and DGP. Methods: In this study, 163 patients with type 2 diabetes mellitus and 175 nondiabetic patients who were treated in our department were divided into DGP, simple diabetes, non-DGP (NDG), and normal groups based on their conditions. The H. pylori infection rate in each group was calculated. H. pylori eradication therapy was performed for patients with H. pylori infection in each group. The eradication rates were compared between the groups, and the improvements in gastroparesis-associated symptoms were compared before and after treatment in patients with DGP. Results: The H. pylori infection rate was 74.6% in the DGP group, which was significantly higher than that in the simple diabetes (51.1%, P < 0.01), NDG (57.7%, P < 0.05), and normal groups (48.0%, P < 0.01). With increased disease course, the incidence of DGP and the H. pylori infection rate gradually increased (P < 0.05). In the DGP group, the incidences of upper abdominal pain and distention, early satiety, and anorexia were 75.5%, 66.0%, and 67.9%, respectively, before eradication treatment; and 43.4%, 35.8%, and 39.6%, respectively, after eradication treatment, and the difference was statistically significant (P < 0.01). In patients with DGP with successful H. pylori eradication, the number of barium strips discharged after eradication was 5.9 ± 1.0, which was significantly larger than that before treatment (4.1 ± 0.7, P < 0.01). In addition, the number of barium strips discharged was significantly larger in patients with DGP with successful H. pylori eradication than those with failed H. pylori eradication (P < 0.01). Conclusions: DGP development might be associated with H. pylori infection. H. pylori eradication can effectively improve dyspepsia-associated symptoms and delayed gastric emptying in patients with DGP.
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Affiliation(s)
- Ju Huang
- Department of Clinical Medicine, Queen Mary School of Nanchang University, Nanchang, Jiangxi 330031, China
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34
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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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35
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Abstract
Gastroparesis is defined as a combination of chronic dyspeptic symptoms and delayed emptying of a solid test meal. It remains a difficult-to-treat disorder with a significant impact on quality of life. Although gastroparesis is defined by delayed emptying, several important studies did not find a correlation between this biomarker and symptom severity or treatment success. Thus, some of the more recent trials explored strategies that ranged from antiemetics to antidepressants. Although dietary management showed benefit, most of the other interventions were barely superior to placebo or were not superior at all. Placebo responses were often quite high and this complicates the assessment of active agents. While it complicates the design and interpretation of clinical trials, high response rates for active and sham interventions indicate that we can achieve symptom relief in many patients and thus give them some reassurance. If indeed most therapies are only marginally better than placebo, the differences in adverse effects should be weighed more strongly, a point that is especially important in view of the controversy surrounding metoclopramide. Mechanistic studies introduced the network of macrophages as another potentially important player in the development of gastroparesis. Results are too preliminary and are largely based on preclinical data but show up- and downregulation of cellular elements controlling gastric function. Thus, future developments may teach us how they interfere with some of these mechanisms in clinical settings, potentially making gastroparesis a reversible process.
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Affiliation(s)
| | - Klaus Bielefeldt
- Division of Gastroenterology, University of Utah, UT, USA.,Gastroenterology Section, George E. Wahlen Department of Veterans Affairs Medical Center, 500 Foothill Drive, Salt Lake City, UT 84103, USA
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36
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Min YW, Ko EJ, Lee JY, Rhee PL. Impaired neural pathway in gastric muscles of patients with diabetes. Sci Rep 2018; 8:7101. [PMID: 29739973 PMCID: PMC5940896 DOI: 10.1038/s41598-018-24147-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 03/22/2018] [Indexed: 12/22/2022] Open
Abstract
To explore the pathogenic mechanism of diabetic gastropathy, we investigated differences in response to electrical field stimulation (EFS) of gastric muscles from diabetic and non-diabetic (control) patients. Gastric specimens were obtained from 34 patients and 45 controls who underwent gastrectomy for early gastric cancer. Using organ bath techniques, we examined peak and nadir values of contraction under EFS. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine, MRS2500, and N-nitro-L-arginine (L-NNA) were added sequentially to the organ bath. Tetrodotoxin (TTX) was used to confirm that the responses to EFS were mediated via neural stimulation. In the absence of pharmacological agents, peak contraction amplitude was greater in non-diabetic controls compared to diabetics only in the distal longitudinal gastric muscles. However, the nadir was greater in controls than in patients in both proximal and distal gastric circular muscles. Addition of MRS2500 could not decrease the nadir in both controls and patients, both in the proximal and distal stomach. However, L-NNA completely reversed the relaxation. TTX had no further effect on nadir. In conclusion, impaired inhibitory nitrergic neural pathway in both proximal and distal stomach and impaired excitatory cholinergic neural pathway in the distal stomach may contribute to the pathogenic mechanism underlying diabetic gastropathy.
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Affiliation(s)
- Yang Won Min
- Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eun-Ju Ko
- Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji-Yeon Lee
- Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Poong-Lyul Rhee
- Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
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37
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The Investigation and Treatment of Diabetic Gastroparesis. Clin Ther 2018; 40:850-861. [PMID: 29748143 DOI: 10.1016/j.clinthera.2018.04.012] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 04/05/2018] [Accepted: 04/17/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE This review provides an update on the investigations and treatment options for gastroparesis. METHODS A comprehensive literature search of Medline, PubMed, Embase and OVID was conducted which included all systematic reviews and research articles that focused on the diagnosis, investigations and management diabetic gastroparesis. FINDINGS Dietary modifications and pharmacologic treatment with prokinetics to increase gastric motility form the mainstay of treatment. However, the use of prokinetics is limited by adverse effects and serious adverse effects, leaving metoclopramide as the only drug approved by the US Food and Drug Administration for the treatment of gastroparesis. Newer therapies, including motilin receptor agonists, ghrelin receptor agonists, and neurokinin receptor antagonists, are currently being investigated. Transpyloric stenting, gastric electrical stimulation, and gastric per-oral endoscopic myotomy provide mechanical options for intervention, and surgical interventions in severe intractable gastroparesis include laparoscopic pyloroplasty or gastrectomy. IMPLICATIONS Advances to better understand the pathophysiology and management of diabetic gastroparesis have been limited, especially with discordance between symptoms and severity of delay in gastric emptying. Established treatment options are limited; however, recent pharmacologic and surgical interventions show promise.
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Halawi H, Camilleri M, Acosta A, Vazquez-Roque M, Oduyebo I, Burton D, Busciglio I, Zinsmeister AR. Relationship of gastric emptying or accommodation with satiation, satiety, and postprandial symptoms in health. Am J Physiol Gastrointest Liver Physiol 2017; 313:G442-G447. [PMID: 28774870 PMCID: PMC5792209 DOI: 10.1152/ajpgi.00190.2017] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 07/19/2017] [Accepted: 07/24/2017] [Indexed: 01/31/2023]
Abstract
The contributions of gastric emptying (GE) and gastric accommodation (GA) to satiation, satiety, and postprandial symptoms remain unclear. We aimed to evaluate the relationships between GA or GE with satiation, satiety, and postprandial symptoms in healthy overweight or obese volunteers (total n = 285, 73% women, mean BMI 33.5 kg/m2): 26 prospectively studied obese, otherwise healthy participants and 259 healthy subjects with previous similar GI testing. We assessed GE of solids, gastric volumes, calorie intake at buffet meal, and satiation by measuring volume to comfortable fullness (VTF) and maximum tolerated volume (MTV) by using Ensure nutrient drink test (30 ml/min) and symptoms 30 min after MTV. Relationships between GE or GA with satiety, satiation, and symptoms were analyzed using Spearman rank (rs ) and Pearson (R) linear correlation coefficients. We found a higher VTF during satiation test correlated with a higher calorie intake at ad libitum buffet meal (rs = 0.535, P < 0.001). There was a significant inverse correlation between gastric half-emptying time (GE T1/2) and VTF (rs = -0.317, P < 0.001) and the calorie intake at buffet meal (rs = -0.329, P < 0.001), and an inverse correlation between GE Tlag and GE25% emptied with VTF (rs = -0.273, P < 0.001 and rs = -0.248, P < 0.001, respectively). GE T1/2 was significantly associated with satiation (MTV, R = -0.234, P < 0.0001), nausea (R = 0.145, P = 0.023), pain (R = 0.149, P = 0.012), and higher aggregate symptom score (R = 0.132, P = 0.026). There was no significant correlation between GA and satiation, satiety, postprandial symptoms, or GE. We concluded that GE of solids, rather than GA, is associated with postprandial symptoms, satiation, and satiety in healthy participants.NEW & NOTEWORTHY A higher volume to comfortable fullness postprandially correlated with a higher calorie intake at ad libitum buffet meal. Gastric emptying of solids is correlated to satiation (volume to fullness and maximum tolerated volume) and satiety (the calorie intake at buffet meal) and symptoms of nausea, pain, and aggregate symptom score after a fully satiating meal. There was no significant correlation between gastric accommodation and either satiation or satiety indices, postprandial symptoms, or gastric emptying.
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Affiliation(s)
- Houssam Halawi
- 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Andres Acosta
- 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Maria Vazquez-Roque
- 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Ibironke Oduyebo
- 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Duane Burton
- 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Irene Busciglio
- 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota; and
| | - Alan R. Zinsmeister
- 2Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
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Abstract
OPINION STATEMENT Longstanding diabetes mellitus (both type 1 and type 2) can impair gastric motor function and cause significant upper gastrointestinal symptoms which significantly degrade quality of life, cause nutritional deficits, and degrade healthcare resource use. The most commonly considered gut complication of diabetes, diabetic gastroparesis, is a syndrome of delayed gastric emptying in the absence of mechanical obstruction which leads to symptoms of nausea, vomiting, postprandial fullness, early satiation, bloating, and upper abdominal pain. Gastroparesis also can lead to loss of glycemic control. A diagnosis of gastroparesis is made by documenting delayed gastric emptying and excluding mechanical obstruction. Gastric emptying scintigraphy is the most commonly utilized test for the diagnosis of gastroparesis but novel tests of gastric function have recently been introduced including the gastric emptying breath test and wireless motility capsule. Management most often is aimed at controlling symptoms, which includes dietary modification, optimization of glycemic control, and medication therapy with prokinetics, antiemetics, and neuromodulatory agents. Endoscopic and/or surgical therapies may be considered for refractory cases of gastroparesis. Recent research has provided new insights into the pathophysiology of this disease and is characterizing potential benefits of novel therapeutic agents which show promise in the treatment of this condition. This article will review the pathophysiology, new insights into disease mechanism, and treatment options for diabetic gastroparesis.
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Affiliation(s)
- Allen A Lee
- Division of Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA
| | - William L Hasler
- Division of Gastroenterology, University of Michigan Health System, 3912 Taubman Center, SPC 5362, Ann Arbor, MI, 48109, USA.
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Rouphael C, Arora Z, Thota PN, Lopez R, Santisi J, Funk C, Cline M. Role of wireless motility capsule in the assessment and management of gastrointestinal dysmotility in patients with diabetes mellitus. Neurogastroenterol Motil 2017; 29. [PMID: 28444862 DOI: 10.1111/nmo.13087] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 03/13/2017] [Indexed: 12/23/2022]
Abstract
BACKGROUND Gastrointestinal (GI) dysmotility is common in diabetic patients. Wireless Motility Capsule (WMC) provides the transit profile of the entire GI tract in a single study. Factors affecting GI dysmotility and utility of WMC study are not clearly established in diabetic patients. Our aims were to study the pattern of GI dysmotility using WMC and evaluate the effect of glycemic control and presence of diabetic microvascular complications on motility impairment in diabetic patients. We also assessed the impact of WMC findings on clinical management. METHODS Retrospective chart review of all diabetic patients who underwent WMC testing at our institution from 2010 to 2015 was performed. Demographics, hemoglobinA1c levels, microvascular complications, and WMC findings were obtained. Impact of WMC on clinical management was assessed. KEY RESULTS A total of 100 patients were included. Mean age was 45±19 years and 76% were female. Seventy-two percentage had abnormal WMC testing, of which 29 (40%) had multiregional dysmotility. There were no significant differences in demographics, diabetic microvascular complications or hemoglobinA1c levels among patients with normal and abnormal WMC testing or among patients with isolated vs multiregional dysmotility. Information about subsequent clinical management was available for 47 patients. WMC testing was abnormal in 33 (70%) patients and treatment changes based on WMC results were made in 24 patients (73%). CONCLUSIONS & INFERENCES There was no association between hemoglobinA1c levels, microvascular complications and pattern of GI dysmotility in diabetic patients undergoing WMC. WMC testing lead to management changes in approximately 75% of diabetic patients with GI dysmotility.
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Affiliation(s)
- C Rouphael
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Z Arora
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - P N Thota
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - R Lopez
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - J Santisi
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - C Funk
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - M Cline
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
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Alghamry A, Ponnuswamy SK, Agarwal A, Moattar H, Yerkovich ST, Vandeleur AE, Thomas J, Croese J, Rahman T, Hodgson R. Split-dose bowel preparation with polyethylene glycol for colonoscopy performed under propofol sedation. Is there an optimal timing? J Dig Dis 2017; 18:160-168. [PMID: 28188978 DOI: 10.1111/1751-2980.12458] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Revised: 01/29/2017] [Accepted: 02/07/2017] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Aspiration risk, especially with propofol sedation, remains a concern after split-dose bowel preparation of up to 1 L polyethylene glycol for the procedure. We aimed to identify the ideal timing of bowel preparation to achieve optimal colon cleansing with no increased risk of aspiration. METHODS A total of 892 consecutive patients undergoing simultaneous esophagogastroduodenoscopy (EGD) and colonoscopy were prospectively recruited. Residual gastric volume (RGV) and pH of gastric contents were measured at EGD, and patients' characteristics, runway time (duration between completion of the final liter of bowel preparation and colonoscopy commencement), and cleansing quality were recorded. RESULTS A shorter runway time resulted in better colon cleansing (r = -0.124, P < 0.001). No correlation between runway time and RGV or pH was found (r = -0.017, P = 0.62 and r = -0.030, P = 0.47, respectively). RGV and pH did not differ significantly with runway time of 4 or 5 h. RGV with runway time ≤3 h was 35.9 ± 11.8 mL and 17.4 ± 0.6 mL after runway time >3 h (P < 0.001). No aspiration pneumonia occurred. The only factors independently related to higher RGV were younger age and male sex. CONCLUSIONS The consumption of bowel preparation agent within 3-4 h before propofol sedation resulted in a similar RGV and pH as those achieved by more prolonged fasting, with no increased risk of aspiration even in patients perceived to be at high risk.
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Affiliation(s)
- Alaa Alghamry
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia.,School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Sureshkumar K Ponnuswamy
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia
| | - Aditya Agarwal
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia
| | - Hadi Moattar
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia
| | - Stephanie T Yerkovich
- School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.,QLD Lung Transplant Service, The Prince Charles Hospital, Chermside, Queensland, Australia
| | - Ann E Vandeleur
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia
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- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia
| | - James Thomas
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia.,School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - John Croese
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia.,Division of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
| | - Tony Rahman
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia.,Division of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia
| | - Ruth Hodgson
- Department of Gastroenterology and Hepatology, Centre for Service and Quality Improvement, The Prince Charles Hospital, Chermside, Queensland, Australia.,School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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Gastroparesis post-laparoscopic cholecystectomy in diabetic patients. Updates Surg 2017; 69:89-93. [PMID: 28188572 DOI: 10.1007/s13304-017-0417-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Accepted: 01/09/2017] [Indexed: 10/20/2022]
Abstract
Impairment of gastric emptying is well recognized in patients with diabetes mellitus. The aim of this study was to investigate the influencing factors for gastroparesis syndrome development after laparoscopic cholecystectomy in diabetic patients. This is a case-control study. Clinical data were collected retrospectively for 462 diabetic patients who underwent laparoscopic cholecystectomy from 2008 to 2013. We retrospectively analyzed the incidence of gastroparesis syndrome, clinical features, course of disease, and risk factors. The result showed strong positive relation between the diabetes duration, dose of insulin, patient age, other diabetes complications, and the incidence of gastroparesis. Gastroparesis is not uncommon post-laparoscopic cholecystectomy in diabetic patients.
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Abstract
Diabetes mellitus is the commonest cause of an autonomic neuropathy in the developed world. Diabetic autonomic neuropathy causes a constellation of symptoms and signs affecting cardiovascular, urogenital, gastrointestinal, pupillomotor, thermoregulatory, and sudomotor systems. Several discrete syndromes associated with diabetes cause autonomic dysfunction. The most prevalent of these are: generalized diabetic autonomic neuropathy, autonomic neuropathy associated with the prediabetic state, treatment-induced painful and autonomic neuropathy, and transient hypoglycemia-associated autonomic neuropathy. These autonomic manifestations of diabetes are responsible for the most troublesome and disabling features of diabetic peripheral neuropathy and result in a significant proportion of the mortality and morbidity associated with the disease.
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Affiliation(s)
- Roy Freeman
- Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
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Marathe CS, Rayner CK, Jones KL, Horowitz M. Novel insights into the effects of diabetes on gastric motility. Expert Rev Gastroenterol Hepatol 2016; 10:581-593. [PMID: 26647088 DOI: 10.1586/17474124.2016.1129898] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Recent data from the Diabetes Control and Complications Trial/Epidemiology of Diabetic Interventions and Complications cohort indicate that the disease burden of gastroparesis in diabetes remains high, consistent with the outcome of cross-sectional studies in type 1 and 2 diabetes. An improved understanding of the pathogenesis of diabetic gastroparesis at the cellular level has emerged in the last decade, particularly as a result of initiatives such as the National Institute of Health funded Gastroparesis Clinical Research Consortium in the US. Management of diabetic gastroparesis involves dietary and psychological support, attention to glycaemic control, and the use of prokinetic agents. Given that the relationship between upper gastrointestinal symptoms and the rate of gastric emptying is weak, therapies targeted specifically at symptoms, such as nausea or pain, are important. The relationship between gastric emptying and postprandial glycaemia is complex and inter-dependent. Short-acting glucagon-like peptide-1 agonists, that slow gastric emptying, can be used to reduce postprandial glycaemic excursions and, in combination with basal insulin, result in substantial reductions in glycated haemoglobin in type 2 patients.
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Affiliation(s)
- Chinmay S Marathe
- a Discipline of Medicine , The University of Adelaide, Royal Adelaide Hospital , Adelaide , Australia
- b Centre of Research Excellence in Translating Nutritional Science to Good Health , The University of Adelaide , Adelaide , Australia
| | - Christopher K Rayner
- a Discipline of Medicine , The University of Adelaide, Royal Adelaide Hospital , Adelaide , Australia
- b Centre of Research Excellence in Translating Nutritional Science to Good Health , The University of Adelaide , Adelaide , Australia
| | - Karen L Jones
- a Discipline of Medicine , The University of Adelaide, Royal Adelaide Hospital , Adelaide , Australia
- b Centre of Research Excellence in Translating Nutritional Science to Good Health , The University of Adelaide , Adelaide , Australia
| | - Michael Horowitz
- a Discipline of Medicine , The University of Adelaide, Royal Adelaide Hospital , Adelaide , Australia
- b Centre of Research Excellence in Translating Nutritional Science to Good Health , The University of Adelaide , Adelaide , Australia
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Neiberg RH, Rejeski JJ, Applegate WB, Clark JM, Knowler WC, Bray GA, Espeland MA, Cheskin LJ. Self-Reported Gastrointestinal Symptoms in Type 2 Diabetes Improve With an Intensive Lifestyle Intervention: Results From the Action for Health in Diabetes (Look AHEAD) Clinical Trial. Clin Diabetes 2015; 33:181-8. [PMID: 26487792 PMCID: PMC4608270 DOI: 10.2337/diaclin.33.4.181] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
In Brief This article reports on an investigation of whether an intensive lifestyle intervention (ILI) would reduce gastrointestinal symptoms over 4 years of follow-up for participants in the Action for Health in Diabetes (Look AHEAD) trial compared to a diabetes support and education (DSE) group. Look AHEAD is a randomized, multicenter trial comparing overweight and obese adults with type 2 diabetes treated with ILI versus DSE. ILI, and weight loss in general, had beneficial effects on gastrointestinal (GI) symptoms, with some variability in the strength of the effect depending on the specific symptom and time course. Potential modifiers were analyzed, yet ILI retained an association with improvement in GI symptoms.
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Affiliation(s)
- Rebecca H. Neiberg
- Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Jared J. Rejeski
- Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - William B. Applegate
- Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Jeanne M. Clark
- Departments of Medicine and Epidemiology, Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD
| | - William C. Knowler
- Diabetes Epidemiology and Clinical Research Section, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ
| | - George A. Bray
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Mark A. Espeland
- Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC
| | - Lawrence J. Cheskin
- Departments of Medicine and Epidemiology, Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD
- Department of Health, Behavior & Society, Johns Hopkins Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD
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Bharucha AE, Batey-Schaefer B, Cleary PA, Murray JA, Cowie C, Lorenzi G, Driscoll M, Harth J, Larkin M, Christofi M, Bayless M, Wimmergren N, Herman W, Whitehouse F, Jones K, Kruger D, Martin C, Ziegler G, Zinsmeister AR, Nathan DM. Delayed Gastric Emptying Is Associated With Early and Long-term Hyperglycemia in Type 1 Diabetes Mellitus. Gastroenterology 2015; 149:330-9. [PMID: 25980755 PMCID: PMC4516593 DOI: 10.1053/j.gastro.2015.05.007] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS After the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study continued to show persistent benefit of prior intensive therapy on neuropathy, retinopathy, and nephropathy in type 1 diabetes mellitus (DM). The relationship between control of glycemia and gastric emptying (GE) is unclear. METHODS We assessed GE with a (13)C-spirulina breath test and symptoms in 78 participants with type 1 diabetes at year 20 of EDIC. The relationship between delayed GE and glycated hemoglobin (HbA1c), complications of DM, and gastrointestinal symptoms were evaluated. RESULTS GE was normal (37 participants; 50%), delayed (35 participants; 47%), or rapid (2 participants; 3%). The latest mean HbA1c was 7.7%. In univariate analyses, delayed GE was associated with greater DCCT baseline HbA1c and duration of DM before DCCT (P ≤ .04), greater mean HbA1c over an average of 27 years of follow-up evaluation (during DCCT-EDIC, P = .01), lower R-R variability during deep breathing (P = .03) and severe nephropathy (P = .05), and a greater composite upper gastrointestinal symptom score (P < .05). In multivariate models, retinopathy was the only complication of DM associated with delayed GE. Separately, DCCT baseline HbA1c (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.3) and duration of DM (OR, 1.2; 95% CI, 1.01-1.3) before DCCT entry and mean HbA1c during DCCT-EDIC (OR, 2.2; 95% CI, 1.04-4.5) were associated independently with delayed GE. CONCLUSIONS In the DCCT/EDIC study, delayed GE was remarkably common and associated with gastrointestinal symptoms and with measures of early and long-term hyperglycemia. ClinicalTrials.gov numbers NCT00360815 and NCT00360893.
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Gastric Electrical Stimulation with the Enterra System: A Systematic Review. Gastroenterol Res Pract 2015; 2015:762972. [PMID: 26246804 PMCID: PMC4515290 DOI: 10.1155/2015/762972] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 06/07/2015] [Accepted: 06/15/2015] [Indexed: 12/23/2022] Open
Abstract
Background. Gastric electrical stimulation (GES) is a surgically implanted treatment option for refractory gastroparesis. Aim. To systematically appraise the current evidence for the use of gastric electrical stimulation and suggest a method of standardisation of assessment and follow-up in these patients. Methods. A systematic review of PubMed, Web of Science, DISCOVER, and Cochrane Library was conducted using the keywords including gastric electrical stimulation, gastroparesis, nausea, and vomiting and neuromodulation, stomach, central nervous system, gastric pacing, electrical stimulation, and gastrointestinal. Results. 1139 potentially relevant articles were identified, of which 21 met the inclusion criteria and were included. The quality of studies was variable. There was a variation in outcome measures and follow-up methodology. Included studies suggested significant reductions in symptom severity reporting over the study period, but improvements in gastric emptying time were variable and rarely correlated with symptom improvement. Conclusion. The evidence in support of gastric electrical stimulation is limited and heterogeneous in quality. While current evidence has shown a degree of efficacy in these patients, high-quality, large clinical trials are needed to establish the efficacy of this therapy and to identify the patients for whom this therapy is inappropriate. A consensus view on essential preoperative assessment and postoperative measurement is needed.
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Tian JX, Li M, Zhen Z, Li JL, Cao Y, Yan SH, Tong XL. Establishment and evaluation of animal models of diabetic gastroparesis. Shijie Huaren Xiaohua Zazhi 2015; 23:2091-2097. [DOI: 10.11569/wcjd.v23.i13.2091] [Citation(s) in RCA: 0] [Impact Index Per Article: 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
The incidence of diabetic gastrointestinal disease, one of the most common complication of diabetes, is growing in recent years. Establishing an adequate animal model of diabetic gastrointestinal disease could effectively lay a solid foundation for the exploration of its mechanism and treatment. The rate of gastric emptying in diabetic gastrointestinal disease varies from acceleration to deceleration in different stages, and there is a lack of objective indicators to evaluate it. The establishment and evaluation of animals with diabetic gastrointestinal disease is still in the exploration stage. In this paper we summarize the establishment and evaluation of animal models of diabetic gastrointestinal disease. We compare the advantages and disadvantages of these animal models, in order to provide a reference for further study and treatment of this disease.
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Bharucha AE, Kudva Y, Basu A, Camilleri M, Low PA, Vella A, Zinsmeister AR. Relationship between glycemic control and gastric emptying in poorly controlled type 2 diabetes. Clin Gastroenterol Hepatol 2015; 13:466-476.e1. [PMID: 25041866 PMCID: PMC4297596 DOI: 10.1016/j.cgh.2014.06.034] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Revised: 03/19/2014] [Accepted: 06/28/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Acute hyperglycemia delays gastric emptying in patients with diabetes. However, it is not clear whether improved control of glycemia affects gastric emptying in these patients. We investigated whether overnight and short-term (6 mo) improvements in control of glycemia affect gastric emptying. METHODS We studied 30 patients with poorly controlled type 2 diabetes (level of glycosylated hemoglobin, >9%). We measured gastric emptying using the [(13)C]-Spirulina platensis breath test on the patients' first visit (visit 1), after overnight administration of insulin or saline, 1 week later (visit 2), and 6 months after intensive therapy for diabetes. We also measured fasting and postprandial plasma levels of C-peptide, glucagon-like peptide 1, and amylin, as well as autonomic functions. RESULTS At visit 1, gastric emptying was normal in 10 patients, delayed in 14, and accelerated in 6; 6 patients had gastrointestinal symptoms; vagal dysfunction was associated with delayed gastric emptying (P < .05). Higher fasting blood levels of glucose were associated with shorter half-times of gastric emptying (thalf) at visits 1 (r = -0.46; P = .01) and 2 (r = -0.43; P = .02). Although blood levels of glucose were lower after administration of insulin (132 ± 7 mg/dL) than saline (211 ± 15 mg/dL; P = .0002), gastric emptying thalf was not lower after administration of insulin, compared with saline. After 6 months of intensive therapy, levels of glycosylated hemoglobin decreased from 10.6% ± 0.3% to 9% ± 0.4% (P = .0003), but gastric emptying thalf did not change (92 ± 8 min before, 92 ± 7 min after). Gastric emptying did not correlate with plasma levels of glucagon-like peptide 1 and amylin. CONCLUSIONS Two-thirds of patients with poorly controlled type 2 diabetes have mostly asymptomatic yet abnormal gastric emptying. Higher fasting blood levels of glucose are associated with faster gastric emptying. Overnight and sustained (6 mo) improvements in glycemic control do not affect gastric emptying.
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Affiliation(s)
- Adil E Bharucha
- Clinical and Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota.
| | - Yogish Kudva
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
| | - Ananda Basu
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
| | - Michael Camilleri
- Clinical and Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota
| | - Phillip A Low
- Department of Neurology, Mayo Clinic, Rochester, Minnesota
| | - Adrian Vella
- Division of Endocrinology, Mayo Clinic, Rochester, Minnesota
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