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Dao GM, Kowalski GM, Bruce CR, O'Neal DN, Smart CE, Zaharieva DP, Hennessy DT, Zhao S, Morrison DJ. The Glycemic Impact of Protein Ingestion in People With Type 1 Diabetes. Diabetes Care 2025; 48:509-518. [PMID: 39951019 DOI: 10.2337/dci24-0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/07/2025] [Indexed: 03/23/2025]
Abstract
In individuals with type 1 diabetes, carbohydrate is commonly recognized as the primary macronutrient influencing postprandial glucose levels. Accumulating evidence indicates that protein ingestion also contributes to the increment in postprandial glucose levels, despite endocrine and metabolic responses different from those with carbohydrate ingestion. However, findings regarding protein ingestion's glycemic effect in people with type 1 diabetes are equivocal, with the magnitude of glycemic response seemingly dependent on the rate of absorption and composition of protein ingested. Therefore, the aim of this article is to outline the physiological mechanisms by which ingested protein influences blood glucose regulation in individuals with type 1 diabetes and provide clinical implications on use of dietary protein in the context of glycemic management. Specifically, protein ingestion raises plasma amino acid levels, which directly or indirectly (via gut hormones) stimulates glucagon secretion. Together with the increase in gluconeogenic precursors and an absent endogenous insulin response in individuals with type 1 diabetes, this provides a synergistic physiological environment for increased endogenous glucose production and subsequently increasing circulating glucose levels for several hours. While there is a dearth of well-controlled studies in this area, we provide clinical implications and directions for future research regarding the potential for using ingestion of fast-absorbing protein (such as whey protein) as a tool to prevent and mitigate overnight- and exercise-induced hypoglycemia in people with type 1 diabetes.
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Affiliation(s)
- Giang M Dao
- Institute for Physical Activity and Nutrition, School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Greg M Kowalski
- Institute for Physical Activity and Nutrition, School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Clinton R Bruce
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - David N O'Neal
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Carmel E Smart
- Department of Pediatrics Diabetes and Endocrinology, John Hunter Children's Hospital, Newcastle, New South Wales, Australia
| | - Dessi P Zaharieva
- Division of Pediatric Endocrinology, Department of Pediatrics, Stanford University, Stanford, CA
| | - Declan T Hennessy
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Sam Zhao
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Dale J Morrison
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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Barrientos-Ávalos JR, Morel-Cerda EC, Félix-Téllez FA, Vidrio-Huerta BE, Aceves-Ayala AR, Flores-Rendón ÁR, Velarde-Ruiz Velasco JA. Gastrointestinal adverse effects of old and new antidiabetics: How do we deal with them in real life? REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2024; 89:521-532. [PMID: 39455403 DOI: 10.1016/j.rgmxen.2024.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 07/15/2024] [Indexed: 10/28/2024]
Abstract
Diabetes is a public health problem with an estimated worldwide prevalence of 10% and a prevalence of 12% in Mexico. The costs resulting from this chronic-degenerative disease are significant. Treatment for diabetes involves different medication groups, some of which can cause significant gastrointestinal adverse effects, such as dyspepsia, nausea, vomiting, bloating, diarrhea, and constipation. The medications most frequently associated with said adverse effects are metformin, acarbose, and GLP-1 agonists. Gastrointestinal adverse effects negatively impact the quality of life and management of patients with diabetes. The factors of visceral neuropathy, acute dysglycemia, dysbiosis, and intestinal bacterial overgrowth contribute to the gastrointestinal symptoms in patients with diabetes, making it necessary to consider multiple etiologic factors in the presence of gastrointestinal symptoms, and not exclusively attribute them to the use of antidiabetics. Personalized treatment, considering gastrointestinal comorbidity and the type of drug utilized, is essential for mitigating the adverse effects and improving the quality of life in patients with diabetes. The aim of the present narrative review was to describe the gastrointestinal adverse effects of the antidiabetic drugs, their pathophysiologic mechanisms, and the corresponding therapeutic measures.
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Affiliation(s)
- J R Barrientos-Ávalos
- Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico; Servicio de Endocrinología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - E C Morel-Cerda
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - F A Félix-Téllez
- Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - B E Vidrio-Huerta
- Servicio de Endocrinología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - A R Aceves-Ayala
- Servicio de Endocrinología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico
| | - Á R Flores-Rendón
- Instituto de Seguridad y Servicios Sociales de los Trabajadores del Gobierno y Municipios del Estado de Baja California, Hospital Mexicali, Mexicali, Baja California, Mexico
| | - J A Velarde-Ruiz Velasco
- Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico; Servicio de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, Mexico.
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Barrientos-Ávalos J, Morel-Cerda E, Félix-Téllez F, Vidrio-Huerta B, Aceves-Ayala A, Flores-Rendón Á, Velarde-Ruiz Velasco J. Efectos adversos gastrointestinales de viejos y nuevos antidiabéticos: ¿cómo los enfrentamos en la vida real? REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2024; 89:521-532. [DOI: 10.1016/j.rgmx.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Stringer F, Ashkar C, Franco P, Moroney E, Denton M, Read M, Nathanson A, Ward GM, MacIsaac RJ. Ketoacidosis: 'A diagnosis that is difficult to stomach'. Diabet Med 2024; 41:e15341. [PMID: 38687833 DOI: 10.1111/dme.15341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 04/16/2024] [Accepted: 04/19/2024] [Indexed: 05/02/2024]
Affiliation(s)
| | - Claudia Ashkar
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Pamela Franco
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Emily Moroney
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Matthew Denton
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Matthew Read
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Surgery, University of Melbourne, Parkville, Victoria, Australia
| | | | - Glenn M Ward
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
| | - Richard J MacIsaac
- St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
- Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
- Australian Centre for Accelerating Diabetes Innovations, University of Melbourne, Parkville, Victoria, Australia
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Sun Y, Luo Y, Xiang C, Xie C, Huang W, Sun Z, Jones KL, Horowitz M, Rayner CK, Ma J, Wu T. Gastric emptying in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes and the impact of 4-week insulin pump therapy. Diabetes Obes Metab 2024; 26:3078-3087. [PMID: 38698647 DOI: 10.1111/dom.15626] [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: 03/06/2024] [Revised: 04/05/2024] [Accepted: 04/10/2024] [Indexed: 05/05/2024]
Abstract
AIM To evaluate gastric emptying (GE) and the glycaemic response to a 75-g oral glucose load in newly diagnosed, treatment-naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12-15 months after insulin pump therapy. MATERIALS AND METHODS Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75-g glucose drink containing 150 mg 13C-acetate, to determine the gastric half-emptying time, and underwent assessment of plasma glucose and serum insulin, C-peptide and glucagon-like peptide-1 (GLP-1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re-assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12-15 months, GE was re-measured in 14 of the T2D participants. RESULTS At baseline, participants with T2D exhibited substantially augmented fasting and post-glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP-1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP-1 secretion was attenuated, fasting and post-glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12-15 months of follow-up. CONCLUSIONS In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short-term insulin pump therapy. The effect on GE is maintained for at least 12 months.
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Affiliation(s)
- Yixuan Sun
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Yong Luo
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Chunjie Xiang
- Institute of Diabetes, Southeast University, Nanjing, China
| | - Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Zilin Sun
- Institute of Diabetes, Southeast University, Nanjing, China
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
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Yamamori I. Acute Gastric Dilatation. Intern Med 2024; 63:1665-1666. [PMID: 37813604 PMCID: PMC11189712 DOI: 10.2169/internalmedicine.2692-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 08/24/2023] [Indexed: 10/11/2023] Open
Affiliation(s)
- Ikuo Yamamori
- Department of Endocrinology and Diabetes, Toyohashi Municipal Hospital, Japan
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Xiang C, Sun Y, Luo Y, Xie C, Huang W, Sun Z, Jones KL, Horowitz M, Rayner CK, Ma J, Wu T. Gastric emptying of a glucose drink is predictive of the glycaemic response to oral glucose and mixed meals, but unrelated to antecedent glycaemic control, in type 2 diabetes. Nutr Diabetes 2024; 14:13. [PMID: 38589353 PMCID: PMC11001856 DOI: 10.1038/s41387-024-00264-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 02/06/2024] [Accepted: 02/08/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. METHODS Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. RESULTS Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. CONCLUSIONS In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.
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Affiliation(s)
- Chunjie Xiang
- School of Medicine, Southeast University, Nanjing, 210009, China
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Yixuan Sun
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Yong Luo
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210029, China
| | - Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Zilin Sun
- School of Medicine, Southeast University, Nanjing, 210009, China
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia
| | - Jianhua Ma
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210029, China.
| | - Tongzhi Wu
- School of Medicine, Southeast University, Nanjing, 210009, China.
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, 5000, Australia.
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Aydın BS, Güldoğan IK. Determinants of gastric residual volume before elective surgery in diabetic patients: An observational study. Saudi J Anaesth 2024; 18:167-172. [PMID: 38654864 PMCID: PMC11033908 DOI: 10.4103/sja.sja_339_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 05/15/2023] [Indexed: 04/26/2024] Open
Abstract
Background We investigated factors affecting the low- and high-risk groups for aspiration by measuring gastric volume with ultrasound in diabetic patients who fasted for elective surgery. Methods The study was conducted as an observational study. Sixty-five patients scheduled for elective surgery, aged 18-86 years, with American Society of Anesthesiologists (ASA) scores II-III, and who have diabetes were included after local ethics committee approval. Written informed consent was obtained from all participants. Demographic data of cases were recorded. Patients whose gastric residual volume (GRV) was calculated using the pupils equal, round, reactive to light, and accommodation (PERLA) formula following gastric antrum measurement in the right lateral decubitus and supine position by ultrasound were categorized as low or high risk for aspiration. Results Thirty-one patients were in the low-risk group, and 34 patients were in the high-risk group. Sex, weight, body mass index (BMI), hemoglobin A1c (HbA1c) values, and duration of diabetes were not statistically significant (p > 0.5). Age (p = 0.006) and fasting blood glucose (FBG) (p = 0.005) were statistically significant. The risk of aspiration decreases with age. Hyperglycemia is related to delayed gastric emptying and a high risk for aspiration. The duration of fasting, GRV, and cross-sectional area (CSA) were statistically significant (p = 0.017, p = 0.000, and p = 0.000, respectively). Conclusion Gastric emptying might be delayed in diabetic patients resulting in a high risk for aspiration pneumonia. The risk of aspiration increases in young diabetic patients, and preoperative FBG measurements can provide an idea about gastric emptying in diabetic patients. Gastric ultrasound (USG) may contribute to guidelines for determining more appropriate fasting times for other patient populations, such as obese, pregnant, or child patients.
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Affiliation(s)
- Berrak Sebil Aydın
- Department of Anesthesiology and Reanimation, Tepecik Training and Research Hospital, Turkey
| | - Işıl Köse Güldoğan
- Department of Anesthesiology and Reanimation, Tepecik Training and Research Hospital, Turkey
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Tafti D, Farrell MB, Dearborn MC, Banks KP. Reexamining Compliance with Gastric Emptying Scintigraphy Guidelines: An Updated Analysis of the Intersocietal Accreditation Commission Database. J Nucl Med Technol 2024; 52:26-31. [PMID: 37316303 PMCID: PMC10924152 DOI: 10.2967/jnmt.123.265496] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 03/10/2023] [Indexed: 06/16/2023] Open
Abstract
Many variables can influence the results of gastric emptying scintigraphy (GES). A lack of standardization causes variability, limits comparisons, and decreases the credibility of the study. To increase standardization, in 2009 the Society of Nuclear Medicine and Molecular Imaging (SNMMI) published a guideline for a standardized, validated GES protocol for adults based on a 2008 consensus document. Laboratories must closely follow the consensus guideline to provide valid and standardized results as an incentive to achieve consistency in patient care. As part of the accreditation process, the Intersocietal Accreditation Commission (IAC) evaluates compliance with such guidelines. The rate of compliance with the SNMMI guideline was assessed in 2016 and showed a substantial degree of noncompliance. The aim of this study was to reassess compliance with the standardized protocol across the same cohort of laboratories, looking for changes and trends. Methods: The IAC nuclear/PET database was used to extract GES protocols from all laboratories applying for accreditation from 2018 to 2021, 5 y after the initial assessment. The number of labs was 118 (vs. 127 in the initial assessment). Each protocol was again evaluated for compliance with the methods described in the SNMMI guideline. The same 14 variables were assessed in a binary fashion: patient preparation (4 variables-types of medications withheld, withholding of these medication for 48 h, blood glucose ≤ 200 mg/dL, blood glucose recorded), meal (5 variables-use of consensus meal, nothing by mouth for 4 h or more, meal consumed within 10 min, documentation of percentage of meal consumed, meal labeled with 18.5-37 MBq [0.5-1.0 mCi]), acquisition (2 variables-anterior and posterior projections obtained, imaging each hour out to 4 h), and processing (3 variables-use of the geometric mean, decay correction of data, and measurement of percentage retention). Results: Protocols from the 118 labs demonstrated that compliance is improving in some key areas but remains suboptimal in others. Overall, labs were compliant with an average of 8 of the 14 variables, with a low of 1-variable compliance at 1 site, and only 4 sites compliant with all 14 variables. Nineteen sites met an 80% threshold for compliance (11+ variables). The variable with the highest compliance was the patient's taking nothing by mouth for 4 h or more before the exam (97%). The variable with the lowest compliance was the recording of blood glucose values (3%). Notable areas of improvement include the use of the consensus meal, now 62% versus previously only 30% of labs. Greater compliance was also noted with measurement of retention percentages (instead of emptying percentages or half-times), with compliance by 65% of sites versus only 35% 5 y prior. Conclusion: Almost 13 y after the publication of the SNMMI GES guidelines, there is improving but still suboptimal protocol adherence among laboratories applying for IAC accreditation. Persistent variation in the performance of GES protocols may significantly affect patient management, as results may be unreliable. Using the standardized GES protocol permits interpretation of results in a consistent manner that allows interlaboratory comparisons and fosters acceptance of the test validity by referring clinicians.
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Affiliation(s)
- Dawood Tafti
- Uniformed Services University of the Health Sciences, Bethesda, Maryland
- Department of Radiology, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas; and
| | | | - M Cory Dearborn
- Department of Radiology, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas; and
| | - Kevin P Banks
- Uniformed Services University of the Health Sciences, Bethesda, Maryland
- Department of Radiology, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas; and
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Maurer AH, Donahoe K. Gastric Emptying Scintigraphy 2024: Still A Need for Compliance with Published Guidelines. J Nucl Med Technol 2024; 52:24-25. [PMID: 37963778 DOI: 10.2967/jnmt.123.266799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 10/04/2023] [Indexed: 11/16/2023] Open
Affiliation(s)
- Alan H Maurer
- Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania; and
| | - Kevin Donahoe
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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Meling S, Tjora E, Eichele H, Nedergaard RB, Knop FK, Ejskjaer N, Carlsen S, Njølstad PR, Brock C, Søfteland E. Rectal sensitivity correlated with gastrointestinal-mediated glucose disposal, but not the incretin effect. Endocrinol Diabetes Metab 2024; 7:e463. [PMID: 38059537 PMCID: PMC10782140 DOI: 10.1002/edm2.463] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 11/08/2023] [Accepted: 11/19/2023] [Indexed: 12/08/2023] Open
Abstract
OBJECTIVE The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes. DESIGN AND METHODS For a cross-sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). RESULTS Sixty-five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p = .005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = -0.204, p = .106), but an association was found with GIGD (rho -0.341, p = .005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes. CONCLUSIONS Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes. PREVIOUSLY PUBLISHED Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658-P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658-P. https://doi.org/10.2337/db23-1658-P.
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Affiliation(s)
- Sondre Meling
- Department of MedicineStavanger University HospitalStavangerNorway
- Department of Clinical ScienceUniversity of BergenBergenNorway
| | - Erling Tjora
- Department of Clinical ScienceUniversity of BergenBergenNorway
- Children and Youth ClinicHaukeland University HospitalBergenNorway
| | - Heike Eichele
- Department of Biological and Medical Psychology, Faculty of PsychologyUniversity of BergenBergenNorway
- Regional resource Centre for Autism, ADHD and Tourette Syndrome Western Norway, Division of PsychiatryHaukeland University HospitalBergenNorway
| | - Rasmus B. Nedergaard
- Mech‐Sense, Department of Gastroenterology and HepatologyAalborg University HospitalAalborgDenmark
| | - Filip K. Knop
- Center for Clinical Metabolic ResearchCopenhagen University Hospital—Herlev and GentofteCopenhagenDenmark
- Department of Clinical Medicine, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Steno Diabetes Center CopenhagenGentofteDenmark
- Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of CopenhagenCopenhagenDenmark
| | - Niels Ejskjaer
- Department of Clinical Medicine, Faculty of MedicineAalborg University HospitalAalborgDenmark
- Steno Diabetes Center North DenmarkAalborg University HospitalAalborgDenmark
- Department of EndocrinologyAalborg University HospitalAalborgDenmark
| | - Siri Carlsen
- Department of MedicineStavanger University HospitalStavangerNorway
| | - Pål R. Njølstad
- Department of Clinical ScienceUniversity of BergenBergenNorway
- Children and Youth ClinicHaukeland University HospitalBergenNorway
- Mohn Center for Diabetes Precision Medicine, Department of Clinical ScienceUniversity of BergenBergenNorway
| | - Christina Brock
- Mech‐Sense, Department of Gastroenterology and HepatologyAalborg University HospitalAalborgDenmark
- Department of Clinical Medicine, Faculty of MedicineAalborg University HospitalAalborgDenmark
- Steno Diabetes Center North DenmarkAalborg University HospitalAalborgDenmark
| | - Eirik Søfteland
- Department of Clinical ScienceUniversity of BergenBergenNorway
- Department of MedicineHaukeland University HospitalBergenNorway
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Sugimori H, Masaki S, Honjo H, Kudo M, Watanabe T. Visualization of Gastrointestinal Bezoar Movement Causing and Releasing Small Bowel Obstruction on Computed Tomography in a Patient With Diabetes Mellitus. Cureus 2023; 15:e49133. [PMID: 38130514 PMCID: PMC10733117 DOI: 10.7759/cureus.49133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2023] [Indexed: 12/23/2023] Open
Abstract
Although delayed gastric emptying promotes gastrointestinal bezoar formation in patients with diabetes mellitus (DM), the association between movement of gastrointestinal bezoars and glycemic status remains unclear. We report a case of small bowel obstruction (SBO) caused by impaction of the migrated gastric bezoar into the small bowel in a patient with DM. Correction of hyperglycemia and lactic acidosis led to normalization of gastrointestinal motility, followed by expulsion of the impacted bezoar and resolution of SBO. This case suggests a link between hyperglycemia, metabolic acidosis, and gastrointestinal motility based on visualization of gastrointestinal bezoar movement in the gastrointestinal tract using computed tomography.
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Affiliation(s)
- Hironobu Sugimori
- Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JPN
| | - Sho Masaki
- Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JPN
| | - Hajime Honjo
- Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JPN
| | - Masatoshi Kudo
- Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JPN
| | - Tomohiro Watanabe
- Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, JPN
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13
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Salman UA, McMahan CA, Schwartz JG, Michalek JE, Phillips WT. Rapid gastric emptying during pregnancy in a rat model. Eur J Obstet Gynecol Reprod Biol 2023; 289:74-78. [PMID: 37639818 DOI: 10.1016/j.ejogrb.2023.08.370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 05/13/2023] [Accepted: 08/18/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND/AIMS The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy. We hypothesized that the rate of emptying of nutrients during pregnancy is not delayed, but is actually more rapid when compared to the non-pregnant state. The rate of gastric emptying is a major determinant of postprandial glucose elevations. MATERIALS AND METHODS 24 female and 4 male Spague-Dawley rats were used. Female rats were randomly divided into two groups: eight rats for the control group and sixteen rats for the pregnant group. Using physiologic, non-traumatic nuclear medicine scintigraphy imaging methodology, the authors studied gastric emptying of a liquid mixed meal in pregnant rats and non-pregnant controls. Body weights, daily food ingestion, and the rate of nutrient gastric emptying were recorded in both groups at pre-pregnancy, early pregnancy, and late pregnancy. RESULTS The authors found that pregnancy in this rat model is associated with a 37-43% increased rate of nutrient gastric emptying from the stomach in late pregnancy as compared to non-pregnant control rats and pre-pregnancy rats. CONCLUSION These findings contradict the current clinical assumption that gastric emptying is delayed in pregnancy. If further studies confirm a more rapid gastric emptying rate during human pregnancy, new therapies aimed at slowing the rate of nutrient absorption should be considered for the prevention and treatment of pregnancy-associated nausea, gestational diabetes, and other insulin-resistant pregnancy-associated states such as pre-eclampsia.
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14
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De Fano M, Porcellati F, Fanelli CG, Corio S, Mazzieri A, Lucidi P, Bolli GB, Bassotti G. The role of gastric emptying in glucose homeostasis and defense against hypoglycemia: Innocent bystander or partner in crime? Diabetes Res Clin Pract 2023; 203:110828. [PMID: 37481116 DOI: 10.1016/j.diabres.2023.110828] [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] [Received: 04/09/2023] [Revised: 06/30/2023] [Accepted: 07/11/2023] [Indexed: 07/24/2023]
Abstract
Maintenance of plasma glucose (PG) homeostasis is due to a complex network system. Even a minor fall in PG activates multiple neuroendocrine actions promoting hormonal, metabolic and behavioral responses, which prevent and ultimately recover hypoglycemia, primarily neuroglycopenia. Among these responses, gastric emptying (GE) plays an important role by coordinated mechanisms which regulate transit and absorption of nutrients through the small intestine. A bidirectional relationship between GE and glycemia has been established: GE may explain the up to 30-40 % variance in glycemic response following a carbohydrate-rich meal. In addition, acute and chronic hyperglycemia induce deceleration of GE after meals. Hypoglycemia accelerates GE, but its role in counterregulation has been poorly investigated. The role of GE as a counterregulatory mechanism has been confirmed in pathophysiological conditions, such as gastroparesis or following recurrent hypoglycemia. Therefore, it could represent an "ancestral" mechanism, highly conservative and effective in all individuals, conditions and clinical contexts. Recent guidelines recommend GLP-1 receptor agonists (GLP-1RAs) either as the first injectable therapy for type 2 diabetes mellitus or in combination with insulin. Considering the potential impact on GE, it would be important to study subjects on GLP-1 RAs during hypoglycemia, to establish whether a possible deceleration of GE impairs glucose counterregulation.
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Affiliation(s)
- Michelantonio De Fano
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Francesca Porcellati
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
| | - Carmine G Fanelli
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Sofia Corio
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Alessio Mazzieri
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Paola Lucidi
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Geremia B Bolli
- Endocrine and Metabolic Sciences Section, Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Gabrio Bassotti
- Gastroenterology, Hepatology and Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
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15
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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: 3] [Impact Index Per Article: 1.5] [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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16
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Arunachala Murthy T, Chapman M, Jones KL, Horowitz M, Marathe CS. Inter-relationships between gastric emptying and glycaemia: Implications for clinical practice. World J Diabetes 2023; 14:447-459. [PMID: 37273253 PMCID: PMC10236995 DOI: 10.4239/wjd.v14.i5.447] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Revised: 12/09/2022] [Accepted: 04/07/2023] [Indexed: 05/15/2023] Open
Abstract
Gastric emptying (GE) exhibits a wide inter-individual variation and is a major determinant of postprandial glycaemia in health and diabetes; the rise in blood glucose following oral carbohydrate is greater when GE is relatively more rapid and more sustained when glucose tolerance is impaired. Conversely, GE is influenced by the acute glycaemic environment acute hyperglycaemia slows, while acute hypoglycaemia accelerates it. Delayed GE (gastroparesis) occurs frequently in diabetes and critical illness. In diabetes, this poses challenges for management, particularly in hospitalised individuals and/or those using insulin. In critical illness it compromises the delivery of nutrition and increases the risk of regurgitation and aspiration with consequent lung dysfunction and ventilator dependence. Substantial advances in knowledge relating to GE, which is now recognised as a major determinant of the magnitude of the rise in blood glucose after a meal in both health and diabetes and, the impact of acute glycaemic environment on the rate of GE have been made and the use of gut-based therapies such as glucagon-like peptide-1 receptor agonists, which may profoundly impact GE, in the management of type 2 diabetes, has become commonplace. This necessitates an increased understanding of the complex inter-relationships of GE with glycaemia, its implications in hospitalised patients and the relevance of dysglycaemia and its management, particularly in critical illness. Current approaches to management of gastroparesis to achieve more personalised diabetes care, relevant to clinical practice, is detailed. Further studies focusing on the interactions of medications affecting GE and the glycaemic environment in hospitalised patients, are required.
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Affiliation(s)
- Tejaswini Arunachala Murthy
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
| | - Marianne Chapman
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
| | - Karen L Jones
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide 5000, SA, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide 5000, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide 5000, SA, Australia
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17
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Dickerson RN, Corley CE, Holmes WL, Byerly S, Filiberto DM, Fischer PE. Gastric feeding intolerance in critically ill patients during sustained pharmacologic neuromuscular blockade. Nutr Clin Pract 2023; 38:350-359. [PMID: 36156827 DOI: 10.1002/ncp.10911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/23/2022] [Accepted: 08/28/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The purpose of this study was to assess gastric feeding intolerance for critically ill patients who received sustained neuromuscular blocker (NMB) pharmacotherapy. METHODS Adult patients (>17 years of age) admitted to the trauma intensive care unit who received continuous intravenous NMB pharmacotherapy (rocuronium, cisatracurium, vecuronium, or pancuronium) for ≥48 h during continuous intragastric enteral nutrition (EN) were retrospectively evaluated. Gastric feeding intolerance was defined by initiation of a prokinetic agent (metoclopramide, erythromycin, or both) for an elevated gastric residual volume (GRV) >300 ml and with distention of the abdomen by physical examination, observation of regurgitation or emesis, temporary discontinuation of EN with low intermittent gastric suctioning, or initiation of parenteral nutrition (PN). Patients were evaluated for gastric feeding intolerance for the first 3 days of combined EN and NMB pharmacotherapy. A P value < 0.05 was considered statistically significant. RESULTS Ten patients of the 47 patients (21%) were intolerant to EN during NMB pharmacotherapy. No statistically or clinically relevant differences in patient characteristics were found between patients who tolerated EN vs those who experienced gastric feeding intolerance, except for a higher median maximum GRV of 125 ml (28, 200) vs 300 (250, 400) ml, respectively (P < 0.001). Five patients responded to prokinetic therapy and five required PN. CONCLUSION Most patients tolerated intragastric EN during sustained NMB pharmacotherapy. Presence of NMB pharmacotherapy is not an absolute contraindication for EN.
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Affiliation(s)
- Roland N Dickerson
- Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | | | - Whitney L Holmes
- Department of Pharmacy, Regional One Health, Memphis, Tennessee, USA
| | - Saskya Byerly
- Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Dina M Filiberto
- Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Peter E Fischer
- Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA
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18
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Bertoli D, Steinkohl E, Mark EB, Brock C, Drewes AM, Frøkjaer JB. Quantification of gastric emptying with magnetic resonance imaging in healthy volunteers: A systematic review. Neurogastroenterol Motil 2022; 34:e14371. [PMID: 35340100 PMCID: PMC10078504 DOI: 10.1111/nmo.14371] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/17/2022] [Accepted: 03/14/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several magnetic resonance imaging (MRI) protocols have been used to assess gastric emptying (GE) with MRI. This systematic review summarizes the current literature on the topic. The aim was to provide an overview of the available imaging protocols and underline the items that appear most agreed upon and those that deserve further investigation. METHODS According to PRISMA guidelines, two independent reviewers conducted a systematic literature search with a pre-specified strategy in different databases. Peer-reviewed articles that utilized MRI techniques to assess GE in healthy volunteers (HVs) were included. The quality and the outcomes of the studies were reported and analyzed. KEY RESULTS The literature search yielded 30 studies (531 HVs, weighted mean age 27.4, weighted mean body mass index 23.0 kg/m2 ), T2-weighted sequences, balanced turbo field echo, and balanced gradient echo were evenly utilized, with volunteers in the supine position (74% of the studies). After overnight fasting, both liquid (56%) and mixed (44%) meals were equally utilized. Segmentation of the volumes was predominantly performed manually (63%) with a reported mean T50 ranging from 7 to 330 min. CONCLUSIONS & INFERENCES As observed in this systematic review, MRI is a flexible tool for assessing GE. Different protocols were analyzed, showing an equal capacity to assess the GE. However, many items in these protocols still require further investigation to obtain a common standard and increase this assessment quality.
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Affiliation(s)
- Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Emily Steinkohl
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Esben Bolvig Mark
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Jens Brøndum Frøkjaer
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.,Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
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19
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Portincasa P, Bonfrate L, Wang DQH, Frühbeck G, Garruti G, Di Ciaula A. Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract. Eur J Clin Invest 2022; 52:e13846. [PMID: 35904418 DOI: 10.1111/eci.13846] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022]
Abstract
Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - David Q-H Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, Pamplona, Spain.,Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Gabriella Garruti
- Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
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20
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Кузнецов КО, Михеева АЮ, Ишмухаметова АА, Толстых ТА, Галляметдинова АР, Ботирова ЗУ, Забирова АА, Шарипова АШ, Шайхлисламова АБ, Абрахманова ДР. [Diabetic gastroenteropathy: modern methods of diagnosis and treatment]. PROBLEMY ENDOKRINOLOGII 2022; 68:67-78. [PMID: 36337020 PMCID: PMC9762451 DOI: 10.14341/probl13082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 05/14/2022] [Accepted: 07/13/2022] [Indexed: 11/09/2022]
Abstract
Diabetes mellitus is a chronic disease with a growing prevalence worldwide, however, the prevalence of its complications, including gastroenteropathy, is also increasing. The pathophysiology of diabetic gastroenteropathy (DH) combines hyperglycemia, vagus nerve dysfunction, decreased expression of nitric oxide synthase in the myenteric plexus, changes in the interstitial Cajal cell network, as well as oxidative stress. Clinical signs of DH are gastroesophageal reflux, gastroparesis, constipation, abdominal pain and diarrhea. Among the diagnostic methods are manometry with pH measurement (assessment of esophageal motility), gastric emptying scintigraphy, respiratory test (to assess gastroparesis), aspiration and cultivation of the contents of the jejunum (to diagnose bacterial overgrowth syndrome). To date, there is no definitive treatment for DH - an interdisciplinary approach is aimed at slowing the progression of the disease, relieving symptoms and restoring gastrointestinal function. Patients are recommended a diet low in simple sugars and high in fiber; optimization of glycemic control with a target glycemia of less than 180 mg/dl. As for drug therapy, the use of prokinetics and antiemetics is justified, and in case of excessive bacterial growth syndrome, antibacterial therapy (rifaximin) is carried out. Modern approaches to the treatment of DH are also accumulating, including the use of botulinum toxin, pyloroplasty and electrical stimulation of the stomach in individual patients. Despite the constant development of new treatments, they are not yet able to completely cure DH in the near future, which makes it necessary to conduct further research in this area.
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Affiliation(s)
- К. О. Кузнецов
- Российский национальный исследовательский медицинский университет им. Н.И. Пирогова
| | - А. Ю. Михеева
- Национальный медицинский исследовательский центр им. В.А. Алмазова
| | - А. А. Ишмухаметова
- Первый Московский государственный медицинский университет им. И.М. Сеченова
| | - Т. А. Толстых
- Первый Московский государственный медицинский университет им. И.М. Сеченова
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21
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Alecrim MDJ, Mattar R, Torloni MR. Pregnant women's experience of undergoing an oral glucose tolerance test: A cross-sectional study. Diabetes Res Clin Pract 2022; 189:109941. [PMID: 35690268 DOI: 10.1016/j.diabres.2022.109941] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/25/2022] [Accepted: 06/02/2022] [Indexed: 11/22/2022]
Abstract
AIMS The oral glucose tolerance test (OGTT) is routinely performed in most pregnancies; however, there are few studies which document the experience of taking this test. We assessed the experience of pregnant women during an OGTT. METHODS This cross-sectional study included 152 women (24-32 weeks' gestation) and assessed their knowledge, anxiety (Spielberg anxiety inventory test-STAI), and physical pain (0-10 visual analog scale) during the OGTT. The Friedman test was used to compare pain scores over time. RESULTS 61 (40%) participants did not know why they were doing the OGTT and 73 (48%) women had high state-anxiety levels (STAI ≥ 41 points, 20-80 scale). Participants had mild to moderate pain scores immediately after the first and second blood draws (3.9 ± 2.7 and 3.8 ± 2.3, respectively) that decreased significantly after the third blood draw (2.8 ± 2.4, P < 0.001). Nearly half (n = 71, 47%) of the participants were very or extremely bothered with having to drink the glucose solution. CONCLUSIONS The OGTT was associated with high levels of anxiety and mild to moderate physical pain. Ingestion of the glucose solution was perceived as the most difficult part of the test. Good strategies can help to mitigate some of these negative experiences while undergoing an OGTT.
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Affiliation(s)
- Maria de J Alecrim
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo, SP 04024-002, Brazil.
| | - Rosiane Mattar
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo, SP 04024-002, Brazil.
| | - Maria R Torloni
- Department of Obstetrics, São Paulo Federal University, Rua Napoleão de Barros, 875, São Paulo, SP 04024-002, Brazil; Evidence Based Health Care Post-Graduate Program, Department of Medicine, São Paulo Federal University, Rua Botucatu 740, 3° andar, São Paulo, SP 04023-900, Brazil.
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22
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De Melo EN, Clarke ABM, McDonald C, Saibil F, Lochnan HA, Punthakee Z, Assor E, Marcon MA, Mahmud FH. Gastrointestinal Symptoms in Type 1 Diabetes: Relationship With Autoimmune and Microvascular Complications. J Clin Endocrinol Metab 2022; 107:e2431-e2437. [PMID: 35176765 DOI: 10.1210/clinem/dgac093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Indexed: 02/13/2023]
Abstract
PURPOSE To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. METHODS The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. RESULTS Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P < 0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher hemoglobin A1c (HbA1c) levels (68 ± 14mmol/mol; 8.35 ± 1.37%) than those without symptoms (66 ± 15mmol/mol; 8.22 ± 1.40%; P = 0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95% CI: 1.26-2.60; P < 0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (odds ratio = 1.1; 95% CI: 0.86-1.42; P = 0.45). MAIN CONCLUSIONS These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.
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Affiliation(s)
- Emilia N De Melo
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Antoine B M Clarke
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Charlotte McDonald
- Division of Endocrinology and Metabolism, St. Joseph's Health Care, Western University, London, Canada
| | - Fred Saibil
- Division of Gastroenterology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada
| | | | - Zubin Punthakee
- Department of Endocrinology, McMaster University, Hamilton, Canada
| | - Esther Assor
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Margaret A Marcon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - Farid H Mahmud
- Division of Endocrinology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada
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Degisors S, Caiazzo R, Dokmak S, Truant S, Aussilhou B, Eveno C, Pattou F, El Amrani M, Piessen G, Sauvanet A. Delayed gastric emptying following distal pancreatectomy: incidence and predisposing factors. HPB (Oxford) 2022; 24:772-781. [PMID: 34753675 DOI: 10.1016/j.hpb.2021.09.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 07/06/2021] [Accepted: 09/30/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Delayed gastric emptying (DGE) following elective distal pancreatectomy (DP) is poorly known. This study aimed to report incidence of DGE following DP, to identify its predisposing factors, and to assess its impact on hospital stay. METHODS Patients who had elective DP without additional organ or vascular resection (2012-2017) in two academic hospitals were included. Factors predisposing to DGE, defined according to the International Study Group of Pancreatic Surgery, were identified by multivariate analysis. A systematic review was performed to evaluate DGE incidence following elective DP. RESULTS 311 elective DPs were performed. Three perioperative mortalities (1.0%) were unrelated to DGE. DGE occurred in 31 (10.0%) patients (grade A = 21, grade B = 7, grade C = 3) with a median hospital stay of 16 (13-22) days versus 10 (7-14) without DGE (p < 0.001). In multivariate analysis, predisposing factors of DGE were age>75 years (OR = 4.32 [1.53-12.19]; p = 0.006), open approach (OR = 2.97 [1.1-8]; p = 0.031) and POPF grade B-C (OR = 2.54 [1.05-6.1]; p = 0.038). The systematic review identified 7 series including 876 patients with an overall 8.1% DGE incidence. CONCLUSION DGE complicates around 10% of elective DP. Laparoscopic approach and prevention of POPF should be encouraged to reduce DGE incidence.
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Affiliation(s)
- Sébastien Degisors
- CHU Lille, Department of Digestive and Oncological Surgery, University of Lille, F-59000, Lille, France
| | - Robert Caiazzo
- CHU Lille, General and Endocrine Surgery, University of Lille, F-59000, Lille, France
| | - Safi Dokmak
- AP-HP, Department of HBP Surgery, Hôpital Beaujon, University of Paris, F-92110, Clichy, France
| | - Stéphanie Truant
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, F-59000, Lille, France
| | - Béatrice Aussilhou
- AP-HP, Department of HBP Surgery, Hôpital Beaujon, University of Paris, F-92110, Clichy, France
| | - Clarisse Eveno
- CHU Lille, Department of Digestive and Oncological Surgery, University of Lille, F-59000, Lille, France
| | - François Pattou
- CHU Lille, General and Endocrine Surgery, University of Lille, F-59000, Lille, France
| | - Mehdi El Amrani
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, F-59000, Lille, France
| | - Guillaume Piessen
- CHU Lille, Department of Digestive and Oncological Surgery, University of Lille, F-59000, Lille, France
| | - Alain Sauvanet
- AP-HP, Department of HBP Surgery, Hôpital Beaujon, University of Paris, F-92110, Clichy, France.
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Meling S, Bertoli D, Sangnes DA, Brock C, Drewes A, Ejskjaer N, Dimcevski G, Søfteland E. Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure? Curr Diabetes Rev 2022; 18:e220321192412. [PMID: 34225633 DOI: 10.2174/1573399817666210322154618] [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: 11/16/2020] [Revised: 01/19/2021] [Accepted: 02/13/2021] [Indexed: 11/22/2022]
Abstract
Autonomic neuropathy in patients with diabetes mellitus, and especially complications related to gastrointestinal neuropathy, are often overlooked in the clinic. Diabetic gastroenteropathy affects every segment of the gastrointestinal tract and generates symptoms that may include nausea, early satiety, vomiting, abdominal pain, constipation, and diarrhea. Severe cases can be complicated by weight loss, dehydration, and electrolyte disturbances. The pathophysiology is complex, the diagnostics and treatment options are multidisciplinary, and there is generally a lack of evidence for the treatment options. The aims for this review are first to summarize the pathophysiology and describe possible and expected symptoms and complications.Further, we will try to supply the clinician with a straightforward tool for diagnostics, and then, we shall summarize established treatment options, including diet recommendations, pharmacological and non-pharmacological options. Finally, we will explore the multiple possibilities of novel treatment, looking at medications related to the pathophysiology of neuropathy, other manifestations of autonomic neuropathies, and symptomatic treatment for other gastrointestinal disorders, also including new knowledge of endosurgical and neuromodulatory treatment. The overall goal is to increase awareness and knowledge on this frequent diabetic complication and to provide better tools for diagnosis and treatment. Ultimately, we hope to encourage further research in this field, as there are clear shortcomings in terms of biomarkers, pathophysiology, as well as treatment possibilities. In conclusion, diagnosis and management of diabetic gastroenteropathy are challenging and often require multidisciplinary teams and multimodal therapies. Treatment options are sparse, but new pharmacological, endoscopic, and neuromodulatory techniques have shown promising results in initial studies.
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Affiliation(s)
- Sondre Meling
- Department of Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Davide Bertoli
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Dag A Sangnes
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Christina Brock
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Asbjørn Drewes
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Niels Ejskjaer
- Steno Diabetes Center North Jutland, Aalborg, Denmark
- Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Eirik Søfteland
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
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25
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Sangnes DA, Lundervold K, Bekkelund M, von Volkmann HL, Berentsen B, Gilja OH, Dimcevski G, Søfteland E. Gastrointestinal transit and contractility in diabetic constipation: A wireless motility capsule study on diabetes patients and healthy controls. United European Gastroenterol J 2021; 9:1168-1177. [PMID: 34687494 PMCID: PMC8672085 DOI: 10.1002/ueg2.12169] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/29/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Diabetic constipation is traditionally attributed to slow colonic transit, despite limited evidence. More than half of patients find treatment unsatisfactory. To improve treatment, there is a need for better diagnostic understanding of the condition. OBJECTIVE In this wireless motility capsule study, we aimed to investigate gastrointestinal transit and contractility in diabetes patients with and without constipation, and in healthy controls. METHODS We prospectively included type 1 or type 2 diabetes patients with gastrointestinal symptoms. Based on the Gastrointestinal Symptom Rating Scale we distinguished into two groups: with constipation and without constipation. Non-diabetic controls were asymptomatic. All were examined with wireless motility capsule, determining transit times and contractility parameters. RESULTS 57 patients (42 women, 46 with type 1 diabetes) and 26 healthy controls (14 women) were included. We found no difference in transit times between diabetes patients with and without constipation. Compared to healthy controls (35:55, h:min), whole-gut transit was slower in both diabetes patients with constipation (66:15, p = 0.03) and without constipation (71:16, p < 0.001). Small bowel motility index correlated rs = -0.32 (p = 0.01) with constipation symptoms. CONCLUSIONS Diabetes patients with constipation had similar transit times as those without constipation. Both groups had slower whole-gut transit than healthy controls. Constipation was associated with reduced small bowel, but not colonic contractility. Our results imply that other mechanisms than slow colonic transit may be more important in the pathogenesis of diabetic constipation.
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Affiliation(s)
- Dag A. Sangnes
- Department of MedicineHaukeland University HospitalBergenNorway
- Department of Clinical MedicineUniversity of BergenBergenNorway
| | - Katarina Lundervold
- The National Centre for Functional Gastrointestinal DisordersHaukeland University HospitalBergenNorway
- National Centre for Ultrasound in GastroenterologyHaukeland University HospitalBergenNorway
- Department of NeurologyHaukeland University HospitalBergenNorway
| | - Mattis Bekkelund
- The National Centre for Functional Gastrointestinal DisordersHaukeland University HospitalBergenNorway
- Department of Clinical MedicineUniversity of OsloOsloNorway
| | | | - Birgitte Berentsen
- Department of MedicineHaukeland University HospitalBergenNorway
- The National Centre for Functional Gastrointestinal DisordersHaukeland University HospitalBergenNorway
| | - Odd Helge Gilja
- Department of MedicineHaukeland University HospitalBergenNorway
- Department of Clinical MedicineUniversity of BergenBergenNorway
- National Centre for Ultrasound in GastroenterologyHaukeland University HospitalBergenNorway
| | - Georg Dimcevski
- Department of Clinical MedicineUniversity of BergenBergenNorway
- National Centre for Ultrasound in GastroenterologyHaukeland University HospitalBergenNorway
| | - Eirik Søfteland
- Department of MedicineHaukeland University HospitalBergenNorway
- Department of Clinical ScienceUniversity of BergenBergenNorway
- Hormone LaboratoryHaukeland University HospitalBergenNorway
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26
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Martins-Oliveira M, Tavares I, Goadsby PJ. Was it something I ate? Understanding the bidirectional interaction of migraine and appetite neural circuits. Brain Res 2021; 1770:147629. [PMID: 34428465 DOI: 10.1016/j.brainres.2021.147629] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 08/16/2021] [Accepted: 08/17/2021] [Indexed: 12/18/2022]
Abstract
Migraine attacks can involve changes of appetite: while fasting or skipping meals are often reported triggers in susceptible individuals, hunger or food craving are reported in the premonitory phase. Over the last decade, there has been a growing interest and recognition of the importance of studying these overlapping fields of neuroscience, which has led to novel findings. The data suggest additional studies are needed to unravel key neurobiological mechanisms underlying the bidirectional interaction between migraine and appetite. Herein, we review information about the metabolic migraine phenotype and explore migraine therapeutic targets that have a strong input on appetite neuronal circuits, including the calcitonin gene-related peptide (CGRP), the pituitary adenylate cyclase-activating polypeptide (PACAP) and the orexins. Furthermore, we focus on potential therapeutic peptide targets that are involved in regulation of feeding and play a role in migraine pathophysiology, such as neuropeptide Y, insulin, glucagon and leptin. We then examine the orexigenic - anorexigenic circuit feedback loop and explore glucose metabolism disturbances. Additionally, it is proposed a different perspective on the most reported feeding-related trigger - skipping meals - as well as a link between contrasting feeding behaviors (skipping meals vs food craving). Our review aims to increase awareness of migraine through the lens of appetite neurobiology in order to improve our understanding of the earlier phase of migraine, encourage better studies and cross-disciplinary collaborations, and provide novel migraine-specific therapeutic opportunities.
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Affiliation(s)
- Margarida Martins-Oliveira
- Headache Group, Wolfson Centre for Age-Related Disease, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Nutrition and Metabolism Department, NOVA Medical School, Faculdade de Ciências Médicas de Lisboa, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisbon, Portugal.
| | - Isaura Tavares
- Department of Biomedicine, Unit of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Institute of Investigation and Innovation in Health (i3S), University of Porto, Portugal.
| | - Peter J Goadsby
- Headache Group, Wolfson Centre for Age-Related Disease, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK; Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
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27
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Robinson KN, Cassady BA, Hegazi RA, Wischmeyer PE. Preoperative carbohydrate loading in surgical patients with type 2 diabetes: Are concerns supported by data? Clin Nutr ESPEN 2021; 45:1-8. [PMID: 34620304 DOI: 10.1016/j.clnesp.2021.08.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/24/2021] [Accepted: 08/24/2021] [Indexed: 12/17/2022]
Abstract
Currently, there is a lack of consensus on the provision of preoperative carbohydrate loading in patients with type 2 diabetes mellitus (T2DM) due to theoretical concerns including the possibility of delayed gastric emptying, perioperative hyperglycemia, and poor surgical outcomes. This narrative review summarizes the accumulating evidence on preoperative carbohydrate loading in this population and whether these concerns are supported by preliminary evidence. In general, the available research suggests that carbohydrate loading may be implemented in those with T2DM without increased risk for intra- and postoperative hyperglycemia or surgical complications. However, there is strong justification for future research to definitively study this highly debated and timely topic. Ultimately, the inclusion of preoperative carbohydrate loading for surgical patients with DM should be guided by the surgical team's clinical judgment and individualized based on patient needs and characteristics.
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Affiliation(s)
- Katie N Robinson
- Scientific and Medical Affairs, Abbott Nutrition, 2900 Easton Square Place, Columbus, OH, 43219 USA.
| | - Bridget A Cassady
- Scientific and Medical Affairs, Abbott Nutrition, 2900 Easton Square Place, Columbus, OH, 43219 USA.
| | - Refaat A Hegazi
- Scientific and Medical Affairs, Abbott Nutrition, 2900 Easton Square Place, Columbus, OH, 43219 USA.
| | - Paul E Wischmeyer
- Duke University School of Medicine, Department of Anesthesiology and Surgery, Center for Perioperative Organ Protection (CPOP), DUMC, Box 3094 Mail # 41, 2301 Erwin Road, 5692 HAFS, Durham, NC, 27710 USA.
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28
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Wise JL, Vazquez-Roque MI, McKinney CJ, Zickella MA, Crowell MD, Lacy BE. Gastric Emptying Scans: Poor Adherence to National Guidelines. Dig Dis Sci 2021; 66:2897-2906. [PMID: 32418002 DOI: 10.1007/s10620-020-06314-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 05/02/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Accurately diagnosing gastroparesis relies upon gastric emptying scintigraphy (GES) being performed correctly. Jointly published protocol guidelines have long been available; however, the extent to which practitioners adhere to these guidelines is unknown. AIMS This study aimed to assess national compliance with established GES protocol guidelines. METHODS We developed a questionnaire addressing the key protocol measures outlined in the Consensus Recommendations for Gastric Emptying Scintigraphy. Survey questions addressed patient information collection (15), patient preparation and procedure protocol (16), meal content and preparation (7), imaging (3), interpretation (4), reporting (7), and institutional demographic data (7). The anonymous questionnaire was distributed electronically to members of the Society of Nuclear Medicine and Medical Imaging (SNMMI) and non-member recipients of the SNMMI daily email newsletter. One response per medical institution was permitted. RESULTS A total of 121 out of 872 potential medical institutions (MI) responded (13.9%); 49 (40.4%) were academic/teaching medical centers. The annual number (mean) of GES procedures was 199.9 (range 5-2000 GES/year). On average, MI performed 33.5/52 (64%) of protocol measures according to guidelines while academic medical centers performed 31.5/52 (61%) of protocol measures according to guidelines. Only 4 out of 88 MI (4.5%) performed GES while adhering to three critical measures: validated study duration; controlled blood glucose levels; and proper restriction of medications. CONCLUSIONS Low compliance with GES protocol guidelines, even among academic medical centers, raises the likely possibility of misdiagnosis and improper management of upper gastrointestinal symptoms. These results highlight a need for increased awareness of protocol guidelines for gastric scintigraphy.
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Affiliation(s)
- Journey L Wise
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Maria I Vazquez-Roque
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Caleb J McKinney
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Michael A Zickella
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
| | - Michael D Crowell
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA
| | - Brian E Lacy
- Division of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
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Desprez C, Chambaz M, Melchior C, Basile P, Prevost G, Jacques J, Leroi AM, Gourcerol G. Assessment of pyloric sphincter distensibility and pressure in patients with diabetic gastroparesis. Neurogastroenterol Motil 2021; 33:e14064. [PMID: 33314491 DOI: 10.1111/nmo.14064] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 10/16/2020] [Accepted: 11/25/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Recent studies have shown that pyloric distensibility is altered in 30-50% of gastroparetic patients but the number of diabetic patients included in prior reports has been small. The aim of the present study was to assess pyloric sphincter measurements in diabetic patients with gastroparesis and to determine whether diabetes characteristics were correlated to pyloric disfunction. METHODS Pyloric distensibility and pressure were measured using EndoFLIP® system in 46 patients with diabetic gastroparesis (DGP) and compared with 21 healthy volunteers (HV), and 33 patients with idiopathic gastroparesis (IGP). Altered pyloric distensibility was defined as the measurement below 10 mm2 /mmHg at 40 ml of inflation. In diabetic patients, blood glucose, glycated hemoglobin, duration, complications, and treatments were collected. KEY RESULTS Mean pyloric distensibility at 40 ml of inflation was lower in DGP and IGP groups with, respectively, 10.8 ± 0.9 mm2 /mmHg and 14.8 ± 2.2 mm2 /mmHg in comparison with the HV group (25.2 ± 2.3 mm2 /mmHg; p < 0.005). 56.5% of patients had a decreased pyloric distensibility in the DGP group, 51.5% of patients in the IGP group, and 10% of patients in the HV group. No correlation was found between pyloric sphincter measurements and diabetes characteristics, including blood glucose, glycated hemoglobin, diabetes mellitus type, neuropathy, or GLP1 agonists intake. CONCLUSION AND INTERFERENCES Pyloric sphincter distensibility and pressure were altered both in diabetic and idiopathic gastroparesis. Pyloric sphincter distensibility was not correlated to diabetes parameters.
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Affiliation(s)
- Charlotte Desprez
- Digestive Physiology Department, Rouen University Hospital, Rouen, France.,Nutrition, Brain and Gut Laboratory UMR 1073, Rouen University, Rouen, France
| | - Marion Chambaz
- Gastroenterology Department, Rennes University Hospital, Rennes, France
| | - Chloé Melchior
- Nutrition, Brain and Gut Laboratory UMR 1073, Rouen University, Rouen, France.,Gastroenterology Department, Rouen University Hospital, Rouen, France
| | - Paul Basile
- Gastroenterology Department, Rouen University Hospital, Rouen, France
| | - Gaetan Prevost
- Endocrinology Department, Rouen University Hospital, Rouen, France
| | - Jérémie Jacques
- Gastroenterology Department, Limoges University Hospital, Limoges, France
| | - Anne-Marie Leroi
- Digestive Physiology Department, Rouen University Hospital, Rouen, France.,Nutrition, Brain and Gut Laboratory UMR 1073, Rouen University, Rouen, France.,INSERM CIC-CRB 1404, Rouen University Hospital, Rouen, France
| | - Guillaume Gourcerol
- Digestive Physiology Department, Rouen University Hospital, Rouen, France.,Nutrition, Brain and Gut Laboratory UMR 1073, Rouen University, Rouen, France.,INSERM CIC-CRB 1404, Rouen University Hospital, Rouen, France
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30
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Borg DJ, Faridi P, Giam KL, Reeves P, Fotheringham AK, McCarthy DA, Leung S, Ward MS, Harcourt BE, Ayala R, Scheijen JL, Briskey D, Dudek NL, Schalkwijk CG, Steptoe R, Purcell AW, Forbes JM. Short Duration Alagebrium Chloride Therapy Prediabetes Does Not Inhibit Progression to Autoimmune Diabetes in an Experimental Model. Metabolites 2021; 11:426. [PMID: 34203471 PMCID: PMC8305727 DOI: 10.3390/metabo11070426] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 12/17/2022] Open
Abstract
Mechanisms by which advanced glycation end products (AGEs) contribute to type 1 diabetes (T1D) pathogenesis are poorly understood. Since life-long pharmacotherapy with alagebrium chloride (ALT) slows progression to experimental T1D, we hypothesized that acute ALT therapy delivered prediabetes, may be effective. However, in female, non-obese diabetic (NODShiLt) mice, ALT administered prediabetes (day 50-100) did not protect against experimental T1D. ALT did not decrease circulating AGEs or their precursors. Despite this, pancreatic β-cell function was improved, and insulitis and pancreatic CD45.1+ cell infiltration was reduced. Lymphoid tissues were unaffected. ALT pre-treatment, prior to transfer of primed GC98 CD8+ T cell receptor transgenic T cells, reduced blood glucose concentrations and delayed diabetes, suggesting islet effects rather than immune modulation by ALT. Indeed, ALT did not reduce interferon-γ production by leukocytes from ovalbumin-pre-immunised NODShiLt mice and NODscid recipients given diabetogenic ALT treated NOD splenocytes were not protected against T1D. To elucidate β-cell effects, NOD-derived MIN6N8 β-cell major histocompatibility complex (MHC) Class Ia surface antigens were examined using immunopeptidomics. Overall, no major changes in the immunopeptidome were observed during the various treatments with all peptides exhibiting allele specific consensus binding motifs. As expected, longer MHC Class Ia peptides were captured bound to H-2Db than H-2Kb under all conditions. Moreover, more 10-12 mer peptides were isolated from H-2Db after AGE modified bovine serum albumin (AGE-BSA) treatment, compared with bovine serum albumin (BSA) or AGE-BSA+ALT treatment. Proteomics of MIN6N8 cells showed enrichment of processes associated with catabolism, the immune system, cell cycling and presynaptic endocytosis with AGE-BSA compared with BSA treatments. These data show that short-term ALT intervention, given prediabetes, does not arrest experimental T1D but transiently impacts β-cell function.
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Affiliation(s)
- Danielle J. Borg
- Glycation and Diabetes Complications, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia; (D.J.B.); (A.K.F.); (D.A.M.); (S.L.); (M.S.W.); (B.E.H.)
- Pregnancy and Development, Mater Research Institute, The University of Queensland, South Brisbane, QLD 4101, Australia
| | - Pouya Faridi
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; (P.F.); (K.L.G.); (R.A.); (N.L.D.); (A.W.P.)
| | - Kai Lin Giam
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; (P.F.); (K.L.G.); (R.A.); (N.L.D.); (A.W.P.)
| | - Peta Reeves
- Tolerance and Autoimmunity Group, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD 4102, Australia; (P.R.); (R.S.)
| | - Amelia K. Fotheringham
- Glycation and Diabetes Complications, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia; (D.J.B.); (A.K.F.); (D.A.M.); (S.L.); (M.S.W.); (B.E.H.)
| | - Domenica A. McCarthy
- Glycation and Diabetes Complications, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia; (D.J.B.); (A.K.F.); (D.A.M.); (S.L.); (M.S.W.); (B.E.H.)
| | - Sherman Leung
- Glycation and Diabetes Complications, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia; (D.J.B.); (A.K.F.); (D.A.M.); (S.L.); (M.S.W.); (B.E.H.)
| | - Micheal S. Ward
- Glycation and Diabetes Complications, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia; (D.J.B.); (A.K.F.); (D.A.M.); (S.L.); (M.S.W.); (B.E.H.)
| | - Brooke E. Harcourt
- Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, Australia
| | - Rochelle Ayala
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; (P.F.); (K.L.G.); (R.A.); (N.L.D.); (A.W.P.)
| | - Jean L. Scheijen
- Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University, 6211 Maastricht, The Netherlands; (J.L.S.); (C.G.S.)
- Cardiovascular Research Institute Maastricht, 6211 Maastricht, The Netherlands
| | - David Briskey
- School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, QLD 4067, Australia;
| | - Nadine L. Dudek
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; (P.F.); (K.L.G.); (R.A.); (N.L.D.); (A.W.P.)
| | - Casper G. Schalkwijk
- Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine, Maastricht University, 6211 Maastricht, The Netherlands; (J.L.S.); (C.G.S.)
- Cardiovascular Research Institute Maastricht, 6211 Maastricht, The Netherlands
| | - Raymond Steptoe
- Tolerance and Autoimmunity Group, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD 4102, Australia; (P.R.); (R.S.)
| | - Anthony W. Purcell
- Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; (P.F.); (K.L.G.); (R.A.); (N.L.D.); (A.W.P.)
| | - Josephine M. Forbes
- Glycation and Diabetes Complications, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia; (D.J.B.); (A.K.F.); (D.A.M.); (S.L.); (M.S.W.); (B.E.H.)
- Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, Australia
- Mater Clinical School, The University of Queensland, Brisbane, QLD 4101, Australia
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Concepción Zavaleta MJ, Gonzáles Yovera JG, Moreno Marreros DM, Rafael Robles LDP, Palomino Taype KR, Soto Gálvez KN, Arriola Torres LF, Coronado Arroyo JC, Concepción Urteaga LA. Diabetic gastroenteropathy: An underdiagnosed complication. World J Diabetes 2021; 12:794-809. [PMID: 34168729 PMCID: PMC8192258 DOI: 10.4239/wjd.v12.i6.794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/28/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
This article is an extensive review that provides an update on the pathophysiology, symptoms, diagnosis, and treatment of diabetic gastroenteropathy. There is no reported prevalence, but it has been described that patients with type 1 diabetes have a cumulative incidence at 10 years of 5.2%, and type 2 patients, 1%. Also, in the group of type 1 diabetes, it has been observed that women are more likely to present this condition (5.8% vs 3.5%). Many factors are associate with its development (e.g., hyperglycemia, vagal dysfunction, loss of expression of neural nitric oxide synthase in the myenteric plexus, alterations in the Cajal interstitial cell network, and oxidative stress). Gastrointestinal discomfort could be perceived 70% higher in diabetic patients, describing that 25% of diabetic patients experience gastrointestinal symptoms. Diabetic enteropathy could affect any portion of the gastrointestinal tract, but esophageal alterations were described in more than 60% of diabetic patients, also 60% of them present constipation, and 20%, diarrhea. Gastric emptying scintigraphy is useful to evaluate gastroparesis, therefore, gastric retention of more than 60% at 2 h has a sensitivity of 100% and specificity of 20% for diagnosis; however, other studies such as breath tests, with a sensitivity of 89% and a specificity of 80%, or the endoscopic capsule contribute to the diagnosis. There is no cure; however, management must be multidisciplinary, focused on slowing the progression of diabetic gastroenteropathy, reducing symptoms, and restoring function; that includes nutritional recommendation, maintain glucose levels kept below 180 mg/dL, use of prokinetics, anti-emetics; nowadays, it has been special interest in surgical treatment, such as pyloroplasty, also gastric electrical stimulation appears to be another alternative.
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32
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Shaikh DH, Jyala A, Mehershahi S, Sinha C, Chilimuri S. Acute Gastric Dilatation: A Cause for Concern. Case Rep Gastroenterol 2021; 15:171-177. [PMID: 33708066 PMCID: PMC7923726 DOI: 10.1159/000512401] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/16/2020] [Indexed: 12/27/2022] Open
Abstract
Acute gastric dilatation is the radiological finding of a massively enlarged stomach as seen on plain film X-ray or a computerized tomography scan of the abdomen. It is a rare entity with high mortality if not treated promptly and is often not reported due to a lack of physician awareness. It can occur due to both mechanical obstruction of the gastric outflow tract, or due to nonmechanical causes, such as eating disorders and gastroparesis. Acute hyperglycemia without diagnosed gastroparesis, such as in patients with diabetic ketoacidosis, may also predispose to acute gastric dilatation. Prompt placement of a nasogastric tube can help deter its serious complications of gastric emphysema, ischemia, and/or perforation. We present our experience of 2 patients who presented with severe hyperglycemia and were found to have acute gastric dilation on imaging. Only one of the patients was treated with nasogastric tube placement for decompression and eventually made a full recovery.
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Affiliation(s)
- Danial Haris Shaikh
- Division of Gastroenterology, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA.,Department of Medicine, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA
| | - Abhilasha Jyala
- Department of Medicine, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA
| | - Shehriyar Mehershahi
- Division of Gastroenterology, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA.,Department of Medicine, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA
| | - Chandni Sinha
- Department of Medicine, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA
| | - Sridhar Chilimuri
- Division of Gastroenterology, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA.,Department of Medicine, BronxCare Health System, Icahn School of Medicine, Bronx, New York, USA
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33
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How JA, Siedel JH, Shafer A. Post-operative gastroparesis following carbohydrate loading in a diabetic patient. Gynecol Oncol Rep 2021; 36:100714. [PMID: 33644283 PMCID: PMC7887383 DOI: 10.1016/j.gore.2021.100714] [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: 12/14/2020] [Revised: 01/19/2021] [Accepted: 01/24/2021] [Indexed: 12/21/2022] Open
Abstract
Gastroparesis may present with post-operative nausea/vomiting in diabetics. Pre-operative carbohydrate loading should be used with caution in diabetics. In enhanced recovery pathways, the role of carbohydrate loading should be clarified in diabetics. Gastroparesis is a syndrome of delayed gastric emptying associated with nausea, vomiting, and postprandial fullness. Despite multiple etiologies, diabetes is one of the principal causes of gastroparesis. This case report examines a 57 year-old woman with poorly controlled diabetes type II (HbA1c 8.3%) complicated by diabetic nephropathy who was readmitted for gastroparesis after two days following uncomplicated robotic surgical staging for endometrial cancer. Prior to the procedure, the patient had received carbohydrate loading in accordance with our center’s enhanced recovery pathway; this resulted in severe acute hyperglycemia, a recognized cause of gastroparesis in women with diabetes. During her readmission, she improved with bowel rest and optimization of glycemic control. This case suggests that routine pre-operative carbohydrate loading should be used with caution in poorly controlled diabetic patients.
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Affiliation(s)
- Jeffrey A How
- Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.,The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA
| | - Jean Hansen Siedel
- Department of Gynecologic Oncology, University of Michigan, Ann Harbor, MI 48109, USA
| | - Aaron Shafer
- Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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34
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Horowitz M, Wu T, Rayner CK, Marathe CS, Jones KL. Spontaneous or Deliberate: Effects of Acute Variations in Glycemia on Gastric Emptying in Type 1 Diabetes. Diabetes Care 2021; 44:316-318. [PMID: 33472966 DOI: 10.2337/dci20-0067] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Tongzhi Wu
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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35
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Petri M, Singh I, Baker C, Underkofler C, Rasouli N. Diabetic gastroparesis: An overview of pathogenesis, clinical presentation and novel therapies, with a focus on ghrelin receptor agonists. J Diabetes Complications 2021; 35:107733. [PMID: 32948398 DOI: 10.1016/j.jdiacomp.2020.107733] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 08/29/2020] [Accepted: 08/29/2020] [Indexed: 12/19/2022]
Abstract
Diabetic gastroparesis is defined as delayed gastric emptying without mechanical obstruction in the setting of diabetes. Symptoms range from mild bloating to severe vomiting episodes and can result in frequent hospitalizations and poor quality of life. It is suspected that diabetic gastroparesis is underdiagnosed due to its similar presentation to other conditions such as gastroesophageal reflux disease. The pathogenesis of diabetic gastroparesis remains unclear, but proposed mechanisms include vagal dysfunction, hyperglycemia, interstitial cells of Cajal network disturbances, loss of neural nitric oxide synthase expression in the myenteric plexus, and oxidative stress. Current management for diabetic gastroparesis focuses on dietary and lifestyle changes as well as improved glycemic control. Limited options for medical therapies are available that include prokinetic and antiemetic medications. Metoclopramide is the only FDA-approved medication for the treatment of gastroparesis. Metoclopramide improves symptoms of gastroparesis although extended treatment presents challenges such as decreased efficacy over time and increased risks for adverse events. We summarize the current knowledge of the pathophysiology of diabetic gastroparesis and review current and investigational treatments for diabetes gastroparesis.
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Affiliation(s)
- Madison Petri
- Department of Medicine, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Aurora, CO, USA
| | - Inderpreet Singh
- Department of Medicine, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Aurora, CO, USA
| | - Chelsea Baker
- Department of Medicine, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Aurora, CO, USA
| | - Chantal Underkofler
- Department of Medicine, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Aurora, CO, USA
| | - Neda Rasouli
- Department of Medicine, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Aurora, CO, USA.
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36
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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: 6] [Impact Index Per Article: 1.5] [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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37
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Dimitriadis GD, Maratou E, Kountouri A, Board M, Lambadiari V. Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach. Nutrients 2021; 13:E159. [PMID: 33419065 PMCID: PMC7825450 DOI: 10.3390/nu13010159] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/18/2020] [Accepted: 12/24/2020] [Indexed: 12/18/2022] Open
Abstract
Glucose levels in blood must be constantly maintained within a tight physiological range to sustain anabolism. Insulin regulates glucose homeostasis via its effects on glucose production from the liver and kidneys and glucose disposal in peripheral tissues (mainly skeletal muscle). Blood levels of glucose are regulated simultaneously by insulin-mediated rates of glucose production from the liver (and kidneys) and removal from muscle; adipose tissue is a key partner in this scenario, providing nonesterified fatty acids (NEFA) as an alternative fuel for skeletal muscle and liver when blood glucose levels are depleted. During sleep at night, the gradual development of insulin resistance, due to growth hormone and cortisol surges, ensures that blood glucose levels will be maintained within normal levels by: (a) switching from glucose to NEFA oxidation in muscle; (b) modulating glucose production from the liver/kidneys. After meals, several mechanisms (sequence/composition of meals, gastric emptying/intestinal glucose absorption, gastrointestinal hormones, hyperglycemia mass action effects, insulin/glucagon secretion/action, de novo lipogenesis and glucose disposal) operate in concert for optimal regulation of postprandial glucose fluctuations. The contribution of the liver in postprandial glucose homeostasis is critical. The liver is preferentially used to dispose over 50% of the ingested glucose and restrict the acute increases of glucose and insulin in the bloodstream after meals, thus protecting the circulation and tissues from the adverse effects of marked hyperglycemia and hyperinsulinemia.
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Affiliation(s)
- George D. Dimitriadis
- Sector of Medicine, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece
| | - Eirini Maratou
- Department of Clinical Biochemistry, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece;
- Department of Clinical Biochemistry, Medical School, “Attikon” University Hospital, Rimini 1, 12462 Chaidari, Greece
| | - Aikaterini Kountouri
- Research Institute and Diabetes Center, 2nd Department of Internal Medicine, “Attikon” University Hospital, 1 Rimini Street, 12542 Haidari, Greece; (A.K.); (V.L.)
| | - Mary Board
- St. Hilda’s College, University of Oxford, Cowley, Oxford OX4 1DY, UK;
| | - Vaia Lambadiari
- Research Institute and Diabetes Center, 2nd Department of Internal Medicine, “Attikon” University Hospital, 1 Rimini Street, 12542 Haidari, Greece; (A.K.); (V.L.)
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38
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Xie C, Huang W, Wang X, Trahair LG, Pham HT, Marathe CS, Young RL, Jones KL, Horowitz M, Rayner CK, Wu T. Gastric emptying in health and type 2 diabetes: An evaluation using a 75 g oral glucose drink. Diabetes Res Clin Pract 2021; 171:108610. [PMID: 33301790 DOI: 10.1016/j.diabres.2020.108610] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 10/14/2020] [Accepted: 12/03/2020] [Indexed: 02/07/2023]
Abstract
AIM Gastric emptying is a major determinant of the glycaemic response to carbohydrate and is frequently abnormal in type 2 diabetes (T2DM). There is little information about how chronic glycaemic control affects gastric emptying in T2DM. We evaluated gastric emptying of a 75 g glucose drink in community-based patients with T2DM of short duration with good or poor glycaemic control, and compared this to young and older controls. METHODS T2DM patients managed by diet and/or metformin, either well-controlled or poorly-controlled, together with young and age-matched older controls without diabetes, consumed a 75 g oral glucose drink containing 150 mg 13C-acetate for evaluation of gastric emptying (breath test) and blood glucose over 180 min. RESULTS The gastric half-emptying time (T50) was longer in the older than the young non-diabetic subjects (P = 0.041), but shorter in well-controlled T2DM patients than age-matched older controls (P = 0.043). The T50 in poorly-controlled T2DM patients was shorter than in older controls (P = 0.006), but similar to young non-diabetic subjects. CONCLUSIONS Gastric emptying of a glucose drink is delayed with ageing, but more rapid in patients with T2DM of relatively short duration, regardless of their glycaemic status. These observations support interventions that slow gastric emptying to improve postprandial glycaemia in these patients with T2DM.
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Affiliation(s)
- Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Xuyi Wang
- Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China
| | - Laurence G Trahair
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Hung T Pham
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Chinmay S Marathe
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide, Australia
| | - Richard L Young
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide, Australia
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
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39
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Haller E, Bonkowski L, Schuchmann C, Doerfler B. Nutrition Therapy for Dysphagia, EoE, Gastroparesis, GERD, and Liver Disease. GERIATRIC GASTROENTEROLOGY 2021:819-835. [DOI: 10.1007/978-3-030-30192-7_107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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40
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Rangan V, Ukleja A. Gastroparesis in the Hospital Setting. Nutr Clin Pract 2020; 36:50-66. [PMID: 33336872 DOI: 10.1002/ncp.10611] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 11/04/2020] [Indexed: 12/15/2022] Open
Abstract
Gastroparesis (GP) is commonly seen in hospitalized patients. Refractory vomiting and related dehydration, electrolyte abnormalities, and malnutrition are indications for hospital admission. In addition, tube feeding intolerance is a common sign of gastric dysmotility in critically ill patients. The diagnosis and management of GP in the hospital setting can be quite challenging. Diagnostic tests are often deferred because of patient intolerance of the oral meal for standard scintigraphy or severity of the primary disease. The diagnosis of GP is often established on the basis of clinical scenario and risk factors for gastric motor dysfunction. Medical therapy in GP is directed toward controlling nausea and vomiting by prokinetic and antinausea medications and correcting nutrition risks or treating malnutrition with nutrition therapy. Enteral nutrition is the preferred nutrition intervention for patients with GP. Delayed gastric emptying in critically ill patients has a negative impact on the timely delivery of enteral feeding and meeting the energy and protein goals. Measures to improve gastric tolerance or provide feeding beyond the stomach are often needed, since early enteral nutrition has been an important target of therapy for critically ill patients. This review will address the current understanding of the mechanisms of GP and feeding intolerance in critical illness, diagnostic workup, drug therapies, and interventions to improve the provision of enteral nutrition in hospital settings when gastric dysmotility is present or suspected.
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Affiliation(s)
- Vikram Rangan
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Ukleja
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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41
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Abstract
PURPOSE OF REVIEW This article provides a summary of the autonomic neuropathies, including neuropathies associated with diabetes mellitus, neuropathies due to amyloid deposition, immune-mediated autonomic neuropathies (including those associated with a paraneoplastic syndrome), inherited autonomic neuropathies, and toxic autonomic neuropathies. The presenting features, diagnostic investigations, and natural history of these neuropathies are discussed. RECENT FINDINGS Recent findings in autonomic peripheral neuropathy include data on the epidemiology and atypical presentations of diabetic autonomic neuropathy, treatment-induced neuropathy of diabetes mellitus, the presentation of immune-mediated neuropathies, and advances in hereditary neuropathy associated with amyloidosis and other hereditary neuropathies. SUMMARY Knowledge and recognition of the clinical features of the autonomic neuropathies, combined with appropriate laboratory and electrophysiologic testing, will facilitate accurate diagnosis and management.
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42
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Porter JA, MacKenzie KE, Darlow BA, Pearson JF, Day AS. A questionnaire-based assessment of gastrointestinal symptoms in children with type 1 diabetes mellitus. Transl Pediatr 2020; 9:743-749. [PMID: 33457295 PMCID: PMC7804482 DOI: 10.21037/tp-20-139] [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: 11/30/2022] Open
Abstract
BACKGROUND Children commonly report gastrointestinal symptoms. Limited evidence suggests that children with type 1 diabetes mellitus (T1DM) report more gastrointestinal symptoms than healthy children without diabetes. The aim of this study was to ascertain the pattern and severity gastrointestinal symptoms reported by children with diabetes and healthy children without diabetes. METHODS After recruitment, children (less than 16 years of age) with type 1 diabetes and healthy control children reported their recent gastrointestinal symptoms using a short questionnaire. A five-point Likert scale was utilised to grade the severity of each symptom and an overall symptom score for each child was derived. RESULTS One hundred and fifty cases (88% of eligible population) and 94 controls completed the questionnaire. Both groups had similarly high rates of any gastrointestinal symptom [80% of controls vs. 85% cases, OR 1.5 (95% CI: 0.7-3.1)]. Children with diabetes had higher mean scores for abdominal pain (1.3 vs. 1.0, P=0.02) and reflux (0.4 vs. 0.20, P=0.02). Cases also had a higher overall mean score than controls (4.9 vs. 3.4, P=0.02). CONCLUSIONS Overall, gastrointestinal symptoms were reported at the same frequency by both groups of children. However, the children with diabetes had more severe symptoms, especially those of reflux and abdominal pain. The reasons for these differences remain to be elucidated.
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Affiliation(s)
- Jody A Porter
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand.,Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
| | - Karen E MacKenzie
- Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
| | - Brian A Darlow
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - John F Pearson
- Department of Population Health, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand.,Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
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43
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Affiliation(s)
- Clipper F. Young
- Primary Care Department, Touro University California College of Osteopathic Medicine, Vallejo, CA
| | - Marianne Moussa
- Graduate, Touro University California College of Pharmacy, Vallejo, CA
| | - Jay H. Shubrook
- Primary Care Department, Touro University California College of Osteopathic Medicine, Vallejo, CA
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44
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Abstract
Gastroparesis is characterized by delayed gastric emptying, with symptoms such as nausea, vomiting and abdominal pain, in the absence of mechanical obstruction. In most cases, it is idiopathic although diabetes mellitus is another leading cause. The physiology of gastric emptying is a complex process which is influenced by various inputs including the central nervous system, enteric nervous system and gut hormones. Developments in our understanding of gastroparesis have now demonstrated dysfunction in these systems, thus disrupting normal gastric emptying. Once mechanical obstruction is excluded, gastric scintigraphy remains the gold standard for diagnosis although wireless motility capsule and breath testing are alternative methods for diagnosis. Treatment for gastroparesis is challenging, and widely available therapies are often limited either by their poor evidence for efficacy or concerns over their long-term safety profile. Novel prokinetic agents have shown initial promise in clinical trials, and new endoscopic techniques such as gastric per-oral endoscopic myotomy are emerging. These new treatment modalities may provide an option in refractory gastroparesis with the adage of reduced morbidity compared to surgical treatments.
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Affiliation(s)
- A Sullivan
- Homerton University Hospital, London, UK
| | | | - A Ruban
- Department of Surgery and Cancer, Imperial College, London, UK.
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45
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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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46
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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: 37] [Impact Index Per Article: 7.4] [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: 04/30/2020] [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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Jones KL, Huynh LQ, Hatzinikolas S, Rigda RS, Phillips LK, Pham HT, Marathe CS, Wu T, Malbert CH, Stevens JE, Lange K, Rayner CK, Horowitz M. Exenatide once weekly slows gastric emptying of solids and liquids in healthy, overweight people at steady-state concentrations. Diabetes Obes Metab 2020; 22:788-797. [PMID: 31903712 DOI: 10.1111/dom.13956] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/10/2019] [Accepted: 12/18/2019] [Indexed: 02/05/2023]
Abstract
AIMS To evaluate the effects of 8 weeks' administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the "gold standard" technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people. MATERIAL AND METHODS A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m2 ) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m2 ) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99m Tc-sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67 Ga-EDTA), and containing 5 g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment. RESULTS The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC]0-120min : P < 0.05) and liquids (AUC0-120min : P = 0.01) substantially, and attenuated glucose absorption (3-OMG incremental AUC [iAUC]0-30min : P = 0.001) and the postprandial rise in plasma glucose (iAUC0-30min : P = 0.008). Plasma glucagon at 2 h was reduced by EXE once weekly (P = 0.001). The magnitude of the reduction in plasma glucose at t = 30 min from baseline to 8 weeks with EXE once weekly was related inversely to the 50% emptying time of the glucose drink (r = -0.55, P = 0.03). CONCLUSIONS In healthy participants, 8 weeks' administration of the "long-acting" glucagon-like peptide-1 receptor agonist EXE, slowed gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia.
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Affiliation(s)
- Karen L Jones
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Lian Q Huynh
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
| | - Seva Hatzinikolas
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
| | - Rachael S Rigda
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
| | - Liza K Phillips
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Hung T Pham
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
| | - Tongzhi Wu
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Charles H Malbert
- Ani-Scan, Institut National de la Rechercher Agronomique, Saint-Gilles, France
| | - Julie E Stevens
- School of Health and Biomedical Sciences, RMIT University, Victoria, Melbourne, Australia
| | - Kylie Lange
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, South Australia, Australia
- Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Haidar A, Tsoukas MA, Bernier-Twardy S, Yale JF, Rutkowski J, Bossy A, Pytka E, El Fathi A, Strauss N, Legault L. A Novel Dual-Hormone Insulin-and-Pramlintide Artificial Pancreas for Type 1 Diabetes: A Randomized Controlled Crossover Trial. Diabetes Care 2020; 43:597-606. [PMID: 31974099 DOI: 10.2337/dc19-1922] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 11/22/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The rapid insulin-alone artificial pancreas improves glycemia in type 1 diabetes but daytime control remains suboptimal. We propose two novel dual-hormone artificial pancreas systems. RESEARCH DESIGN AND METHODS We conducted a randomized crossover trial comparing a rapid insulin-alone artificial pancreas with rapid insulin-and-pramlintide and with regular insulin-and-pramlintide artificial pancreas systems in adults with type 1 diabetes. Participants were assigned to the interventions in random order during three 24-h inpatient visits. Each visit was preceded by an outpatient hormonal open-loop run-in period of 10-14 days. The dual-hormone artificial pancreas delivered pramlintide in a basal-bolus manner, using a novel dosing algorithm, with a fixed ratio relative to insulin. The primary outcome was time in the range 3.9-10.0 mmol/L. RESULTS Compared with the rapid insulin-alone artificial pancreas system, the rapid insulin-and-pramlintide system increased the time in range from 74% (SD 18%) to 84% (13%) (P = 0.0014), whereas the regular insulin-and-pramlintide system did not change the time in range (69% [19%]; P = 0.22). The increased time in range with the rapid insulin-and-pramlintide system was due to improved daytime control (daytime time in range increased from 63% [23%] to 78% [16%], P = 0.0004). There were 11 (1 per 2.5 days) hypoglycemic events (<3.3 mmol/L with symptoms or <3.0 mmol/L irrespective of symptoms) with the rapid insulin-alone system, compared with 12 (1 per 2.3 days) and 18 (1 per 1.4 days) with the rapid and regular insulin-and-pramlintide systems, respectively. Gastrointestinal symptoms were reported after 0% (0 of 112) of meals with the rapid insulin-alone system, compared with 6% (6 of 108) and 11% (11 of 104) with the rapid and regular insulin-and-pramlintide systems, respectively; none of the symptoms were severe. CONCLUSIONS A novel rapid insulin-and-pramlintide artificial pancreas improves glucose control compared with a rapid insulin-alone artificial pancreas (ClinicalTrials.gov number NCT02814123).
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Affiliation(s)
- Ahmad Haidar
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada .,The Research Institute of McGill University Health Centre, Montréal, Québec, Canada
| | - Michael A Tsoukas
- The Research Institute of McGill University Health Centre, Montréal, Québec, Canada.,Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada
| | - Sarah Bernier-Twardy
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada
| | - Jean-Francois Yale
- The Research Institute of McGill University Health Centre, Montréal, Québec, Canada.,Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada
| | - Joanna Rutkowski
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada
| | - Anne Bossy
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada
| | - Evelyne Pytka
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada
| | - Anas El Fathi
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada
| | - Natalia Strauss
- Department of Biomedical Engineering, McGill University, Montréal, Québec, Canada
| | - Laurent Legault
- Montreal Children's Hospital, McGill University Health Centre, Montréal, Québec, Canada
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Abstract
PURPOSE OF REVIEW Gastroparesis is an important complication of diabetes that may have a major impact on the quality of life as a result of upper gastrointestinal symptoms and impaired glycaemic control. Current management strategies include optimising blood glucose control, dietary modifications and supportive nutrition. Pharmacologic approaches with drugs that have prokinetic and/or antiemetic effects are also used widely; however, current available treatments have major limitations. There is increasing recognition that the rate of gastric emptying (GE) is a key determinant of the glycaemic response to a meal. RECENT FINDINGS There is ongoing uncertainty regarding the impact of longstanding hyperglycaemia on GE, which requires clarification. New diagnostic techniques have been developed to better characterise the mechanisms underlying gastroparesis in individual patients, and these have the potential to lead to more personalised therapy. Management of gastroparesis is complex and suboptimal; novel approaches are desirable. This review summarises recent advances in the understanding of diabetic gastroparesis, with an emphasis on the current therapies that influence GE, and the bidirectional relationship between glycaemic control and GE.
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Affiliation(s)
- Ryan Jalleh
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
| | - Chinmay S Marathe
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Michael Horowitz
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
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Gharibans AA, Coleman TP, Mousa H, Kunkel DC. Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis. Clin Gastroenterol Hepatol 2019; 17:2668-2677. [PMID: 31009794 DOI: 10.1016/j.cgh.2019.04.039] [Citation(s) in RCA: 81] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 04/08/2019] [Accepted: 04/13/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Invasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying. METHODS We performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array. RESULTS Spatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56; P < .001) and more severe abdominal pain (r = 0.46; P = .009). We found no correlation between symptoms and traditional EGG parameters. CONCLUSIONS In case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis.
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Affiliation(s)
- Armen A Gharibans
- GI Innovation Group, University of California-San Diego, La Jolla, California; Department of Bioengineering, University of California-San Diego, La Jolla, California; Department of Pediatrics, University of California-San Diego, La Jolla, California
| | - Todd P Coleman
- GI Innovation Group, University of California-San Diego, La Jolla, California; Department of Bioengineering, University of California-San Diego, La Jolla, California
| | - Hayat Mousa
- GI Innovation Group, University of California-San Diego, La Jolla, California; Department of Pediatrics, University of California-San Diego, La Jolla, California; Neurogastroenterology and Motility Center, Rady Children's Hospital, San Diego, California
| | - David C Kunkel
- GI Innovation Group, University of California-San Diego, La Jolla, California; GI Motility & Physiology Program, University of California-San Diego, La Jolla, California.
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