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Rocha GR, de Melo FF. Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes. World J Diabetes 2025; 16:99928. [PMID: 39959274 PMCID: PMC11718485 DOI: 10.4239/wjd.v16.i2.99928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 12/30/2024] Open
Abstract
This letter comments on a study by Jin et al, published recently in the World Journal of Diabetes. Hypoglycemia is a significant complication of diabetes, with primary defense mechanisms involving the stimulation of glucagon secretion in α-cells and the inhibition of insulin secretion in pancreatic β-cells, which are often compromised in type 1 diabetes mellitus (T1DM) and advanced type 2 diabetes mellitus. Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness, a condition underpinned by complex pathophysiological processes, encompassing central nervous system adaptations and several hormonal interactions, including a potential role for glucagon-like peptide-1 (GLP-1) in paracrine and endocrine vias. Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreatic δ-cells, which inhibits glucagon secretion from neighboring α-cells. However, current trials evaluating GLP-1 receptor agonists (GLP-1 RAs) in T1DM patients have shown promising benefits in reducing insulin requirements and body weight, without increasing the risk of hypoglycemia. Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex, and their impact on hypoglycemia unawareness in T1DM patients.
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Affiliation(s)
- Gabriel Reis Rocha
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45065-430, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45065-430, Bahia, Brazil
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2
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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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3
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Portincasa P, Bonfrate L, Wang DQH, Frühbeck G, Garruti G, Di Ciaula A. Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract. Eur J Clin Invest 2022; 52:e13846. [PMID: 35904418 DOI: 10.1111/eci.13846] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022]
Abstract
Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - David Q-H Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Gabriella Garruti
- Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
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Ghazanfar H, Allena N, Javed N, Ponnachan D, Narasimhadevara S, Komadur T, Ghazanfar A, Acherjee T, Patel H. Diagnostic Modalities Used in Diagnosing Gastroparesis: A Clinical Review. Cureus 2022; 14:e30540. [PMID: 36415382 PMCID: PMC9675943 DOI: 10.7759/cureus.30540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/21/2022] [Indexed: 01/25/2023] Open
Abstract
Gastroparesis is associated with abnormal gastric motility characterized by delayed gastric emptying without any obvious mechanical gastric outlet obstruction or blockage. Gastroparesis is associated with significant morbidity and mortality. It is pertinent to make a timely diagnosis of gastroparesis so that prompt treatment can be initiated. The purpose of this clinical review article is to help the internist and the primary care providers to get a better idea of various diagnostic modalities used in diagnosing gastroparesis. We have also discussed the advantages and disadvantages of various diagnostic modalities based on the latest evidence.
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Affiliation(s)
| | | | - Nismat Javed
- Internal Medicine, BronxCare Health System, Bronx, USA
| | | | | | | | - Ali Ghazanfar
- Internal Medicine, Federal Medical and Dental College, Islamabad, PAK
| | | | - Harish Patel
- Internal Medicine, BronxCare Health System, Bronx, USA
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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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Fischer-Tlustos A, Lopez A, Hare K, Wood K, Steele M. Effects of colostrum management on transfer of passive immunity and the potential role of colostral bioactive components on neonatal calf development and metabolism. CANADIAN JOURNAL OF ANIMAL SCIENCE 2021. [DOI: 10.1139/cjas-2020-0149] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Neonatal dairy and beef calves are required to ingest adequate volumes of high-quality colostrum during their first hours of life to acquire transfer of passive immunity (TPI). As such, immunoglobulin G (IgG) has largely been the focus of colostrum research over recent decades. Yet, little is known about the additional bioactive compounds in colostrum that potentially influence newborn calf development and metabolism. The purpose of this narrative review is to synthesize research regarding the effects of colostrum management practices on TPI, as well as to address the potential role of additional colostral bioactive molecules, including oligosaccharides, fatty acids, insulin, and insulin-like growth factor-I, in promoting calf development and metabolism. Due to the importance of IgG in ensuring calf immunity and health, we review past research describing the process of colostrogenesis and dam factors influencing the concentrations of IgG in an effort to maximize TPI. We also address the transfer of additional bioactive compounds in colostrum and prepartum management and dam factors that influence their concentrations. Finally, we highlight key areas of future research for the scientific community to pursue to ultimately improve the health and welfare of neonatal dairy calves.
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Affiliation(s)
- A.J. Fischer-Tlustos
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
| | - A. Lopez
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
| | - K.S. Hare
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
| | - K.M. Wood
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
| | - M.A. Steele
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON N1G 1Y2, Canada
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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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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: 4] [Impact Index Per Article: 1.0] [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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Aigner L, Becker B, Gerken S, Quast DR, Meier JJ, Nauck MA. Day-to-Day Variations in Fasting Plasma Glucose Do Not Influence Gastric Emptying in Subjects With Type 1 Diabetes. Diabetes Care 2021; 44:479-488. [PMID: 33288653 DOI: 10.2337/dc20-1660] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 09/17/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Acute experimental variations in glycemia decelerate (hyperglycemia) or accelerate (hypoglycemia) gastric emptying. Whether spontaneous variations in fasting plasma glucose (FPG) have a similar influence on gastric emptying is yet unclear. RESEARCH DESIGN AND METHODS Gastric emptying of a mixed meal was prospectively studied three times in 20 patients with type 1 diabetes and 10 healthy subjects with normal glucose tolerance using a 13C-CO2 octanoate breath test with Wagner-Nelson analysis. The velocity of gastric emptying was related to FPG measured before the test (grouped as low, intermediate, or high). In addition, gastric emptying data from 255 patients with type 1 diabetes studied for clinical indications were compared by tertiles of baseline FPG. RESULTS Despite marked variations in FPG (by 4.8 [95% CI 3.4; 6.2] mmol/L), gastric emptying did not differ among the three prospective examinations in patients with type 1 diabetes (Δ T1/2 between highest and lowest FPG: 1 [95% CI -35; 37] min; P = 0.90). The coefficient of variation for T1/2 determined three times was 21.0%. Similar results at much lower variations in FPG were found in healthy subjects. In the cross-sectional analysis, gastric emptying did not differ between the tertiles of FPG (Δ T1/2 between highest and lowest FPG: 7 [95% CI -10; 23] min; P = 0.66), when FPG varied by 7.2 (6.7; 7.8) mmol/L. However, higher HbA1c was significantly related to slower gastric emptying. CONCLUSIONS Day-to-day variations in FPG not induced by therapeutic measures do not influence gastric emptying significantly. These findings are in contrast with those obtained after rapidly clamping plasma glucose in the hyper- or hypoglycemic concentrations range and challenge the clinical importance of short-term glucose fluctuations for gastric emptying in patients with type 1 diabetes. Rather, chronic hyperglycemia is associated with slowed gastric emptying.
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Affiliation(s)
- Lea Aigner
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Björn Becker
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Sonja Gerken
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Daniel R Quast
- Division of Diabetology, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University, Bochum, Germany
| | - Juris J Meier
- Division of Diabetology, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University, Bochum, Germany
| | - Michael A Nauck
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany .,Division of Diabetology, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University, Bochum, Germany
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10
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Murthy TA, Grivell J, Hatzinikolas S, Chapple LAS, Chapman MJ, Stevens JE, Malbert CH, Rayner CK, Horowitz M, Jones KL, Marathe CS. Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia. J Clin Endocrinol Metab 2021; 106:364-371. [PMID: 33230553 DOI: 10.1210/clinem/dgaa854] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Indexed: 02/07/2023]
Abstract
CONTEXT Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe" hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked" hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild" hypoglycemia (3.0-3.9 mmol/L) is unknown. OBJECTIVE To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health. DESIGN, SETTING, AND SUBJECTS Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. RESULTS Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia. CONCLUSION In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.
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Affiliation(s)
- Tejaswini Arunachala Murthy
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia
| | | | - Seva Hatzinikolas
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
| | - Lee-Anne S Chapple
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Marianne J Chapman
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia
| | | | | | - Christopher K Rayner
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Karen L Jones
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Chinmay S Marathe
- Adelaide Medical School, University of Adelaide, Adelaide, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
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11
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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] [Received: 05/12/2020] [Accepted: 10/04/2020] [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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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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Porter JA, MacKenzie KE, Darlow BA, Butler R, Day AS. Gastric emptying in children with type 1 diabetes mellitus: A pilot study. J Paediatr Child Health 2019; 55:416-420. [PMID: 30226023 DOI: 10.1111/jpc.14215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 07/11/2018] [Accepted: 08/09/2018] [Indexed: 01/28/2023]
Abstract
AIM Delayed gastric emptying (GE) has been demonstrated in adults with type 1 diabetes mellitus (T1DM). Little is known about GE in children with T1DM. Most methods to measure GE are invasive, that is, scintigraphy, or are only indirectly related to GE, that is, electrogastrography. Carbon-13 breath testing is a non-invasive, very low-risk procedure that accurately correlates with GE time. This was a pilot study to determine the feasibility of using carbon-13 breath testing to measure GE in children with T1DM and healthy controls. METHODS Cases were recruited from children aged 7-15 years presenting to the paediatric diabetic clinic at Christchurch Hospital. Controls were peers of the cases. Children with known gastrointestinal disease were excluded. After an overnight fast, each child ate a standardised pancake labelled with carbon-13 sodium octanoate. Samples of breath were collected over a 4-h period. Samples were analysed by mass spectrometry. GE half time (GET1/2 ) and GE coefficients (GEC) were calculated by linear regression to obtain a measure of GE. RESULTS A total of 19 cases and 15 age- and gender-matched controls underwent testing. The mean GEC in the cases was 3.19 (±0.38) and 2.90 (±0.29) in controls (P = 0.03), with an effect size = 0.86. Mean GET1/2 in the cases was 99 (52.1) min and 103 (27.5) in controls (P = 0.8), with an effect size = 0.1. CONCLUSION The study generated results suggesting that a larger study will be worthwhile to investigate the relationship between GE and T1DM.
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Affiliation(s)
- Jody A Porter
- Paediatric Department, University of Otago, Christchurch, New Zealand
| | - Karen E MacKenzie
- Paediatric Department, University of Otago, Christchurch, New Zealand
| | - Brian A Darlow
- Paediatric Department, University of Otago, Christchurch, New Zealand
| | - Ross Butler
- School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia, Australia
| | - Andrew S Day
- Paediatric Department, University of Otago, Christchurch, New Zealand
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Marathe CS, Marathe JA, Rayner CK, Kar P, Jones KL, Horowitz M. Hypoglycaemia and gastric emptying. Diabetes Obes Metab 2019; 21:491-498. [PMID: 30378748 DOI: 10.1111/dom.13570] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2018] [Revised: 10/15/2018] [Accepted: 10/26/2018] [Indexed: 02/06/2023]
Abstract
Hypoglycaemia is arguably the most important complication of insulin therapy in type 1 and type 2 diabetes. Counter-regulation of hypoglycaemia is dependent on autonomic function and frequent hypoglycaemia may lead to reductions in both autonomic warning signals and the catecholamine response, the so-called "impaired awareness of hypoglycaemia". It is now appreciated that gastric emptying is a major determinant of the glycaemic response to carbohydrate-containing meals in both health and diabetes, that disordered (especially delayed) gastric emptying occurs frequently in diabetes, and that acute hypoglycaemia accelerates gastric emptying substantially. However, the potential relevance of gastric emptying to the predisposition to, and counter-regulation of, hypoglycaemia has received little attention. In insulin-treated patients, the rate of gastric emptying influences the timing of the postprandial insulin requirement, and gastroparesis is likely to predispose to postprandial hypoglycaemia. Conversely, the marked acceleration of gastric emptying induced by hypoglycaemia probably represents an important counter-regulatory response to increase the rate of carbohydrate absorption. This review summarizes the current knowledge of the inter-relationships between hypoglycaemia and gastric emptying, with a focus on clinical implications.
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Affiliation(s)
- Chinmay S Marathe
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Jessica A Marathe
- Department of Cardiology, Central Adelaide Local Health Network, Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Palash Kar
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Michael Horowitz
- Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia
- NHMRC Centre of Clinical Research Excellence in Nutritional Physiology, Interventions and Outcomes, University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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15
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Shen S, Xu J, Lamm V, Vachaparambil CT, Chen H, Cai Q. Diabetic Gastroparesis and Nondiabetic Gastroparesis. Gastrointest Endosc Clin N Am 2019; 29:15-25. [PMID: 30396524 DOI: 10.1016/j.giec.2018.08.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Gastroparesis can be divided into diabetic and nondiabetic, and the 3 main causes of gastroparesis are diabetic, postsurgical, and idiopathic. Delayed gastric emptying is the main manifestation of motility disorders for gastroparesis. Symptoms of gastroparesis are nonspecific and severity can vary. Nausea and vomiting are more common in diabetic gastroparesis whereas abdominal pain and early satiety are more frequent in idiopathic gastroparesis. Medication is still the mainstay of treatment of gastroparesis; however, the development of gastric electric stimulation and gastric peroral endoscopic pyloromyotomy brings more options for the treatment of diabetic and nondiabetic gastroparesis.
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Affiliation(s)
- Shanshan Shen
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, China
| | - Jennifer Xu
- Division of Digestive Diseases, Emory University, 1365 Clifton Road, Atlanta, GA 30322, USA
| | - Vladimir Lamm
- Division of Digestive Diseases, Emory University, 1365 Clifton Road, Atlanta, GA 30322, USA
| | - Cicily T Vachaparambil
- Division of Digestive Diseases, Emory University, 1365 Clifton Road, Atlanta, GA 30322, USA
| | - Huimin Chen
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai 200127, China
| | - Qiang Cai
- Division of Digestive Diseases, Emory University, 1365 Clifton Road, Atlanta, GA 30322, USA.
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Leeds JS, Hadjivassiliou M, Tesfaye S, Sanders DS. Lower gastrointestinal symptoms are associated with worse glycemic control and quality of life in type 1 diabetes mellitus. BMJ Open Diabetes Res Care 2018; 6:e000514. [PMID: 29892338 PMCID: PMC5992466 DOI: 10.1136/bmjdrc-2018-000514] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 05/13/2018] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVES Lower gastrointestinal symptoms are not well characterized in people with type 1 diabetes, and the effects on quality of life and glycemic control are unknown. This study aimed to determine the prevalence of lower gastrointestinal symptoms and the effects on glycemic control and quality of life, and to investigate for underlying causes. RESEARCH DESIGN AND METHODS This is a prospective, cohort study in secondary care. Patients with type 1 diabetes completed a gastrointestinal symptom questionnaire and the Short Form 36 V.2 quality of life questionnaire and had their hemoglobin A1c measured. Patients with diarrhea were offered reassessment and investigation as per the national guidelines. Controls without diabetes were used to compare symptom prevalence and quality of life scores. RESULTS 706 with type 1 diabetes (mean age 41.9 years) and 604 controls (mean age 41.9 years) were enrolled. Gastrointestinal symptoms were significantly more frequent in type 1 diabetes compared with controls, in particular constipation (OR 2.4), diarrhea (OR 2.5), alternating bowel habit (OR 2.1), abdominal pain (OR 1.4), floating stools (OR 2.7), bloating (OR 1.4) and flatulence (OR 1.3) (all p<0.05). Previous pancreatitis was more frequent in type 1 diabetes (OR 4.6), but other gastrointestinal conditions were not. Gastrointestinal symptoms were associated with poorer glycemic control (p<0.01) and worse quality of life particularly in those with diarrhea. Investigation of those with diarrhea, including those with alternating bowel habit, (n=105), identified a cause in 72.3% with subsequent change in management. CONCLUSIONS Gastrointestinal symptoms are twice as common in type 1 diabetes and associated with poorer quality of life and glycemic control. Investigation of diarrhea in people with type 1 diabetes leads to a high yield of treatable conditions and a change in management in about three-quarters.
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Affiliation(s)
- John S Leeds
- Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK
| | | | - Solomon Tesfaye
- Department of Diabetes, Royal Hallamshire Hospital, Sheffield, UK
| | - David S Sanders
- Gastroenterology and Liver Unit, Royal Hallamshire Hospital, Sheffield, UK
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17
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Kar P, Jones KL, Plummer MP, Ali Abdelhamid Y, Giersch EJ, Summers MJ, Hatzinikolas S, Heller S, Horowitz M, Deane AM. Antecedent Hypoglycemia Does Not Attenuate the Acceleration of Gastric Emptying by Hypoglycemia. J Clin Endocrinol Metab 2017; 102:3953-3960. [PMID: 28973430 PMCID: PMC5673277 DOI: 10.1210/jc.2017-00051] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 07/21/2017] [Indexed: 02/07/2023]
Abstract
CONTEXT Acute hypoglycemia accelerates gastric emptying and increases cardiac contractility. However, antecedent hypoglycemia attenuates counterregulatory hormonal responses to subsequent hypoglycemia. OBJECTIVE To determine the effect of antecedent hypoglycemia on gastric and cardiac responses to subsequent hypoglycemia in health. DESIGN A prospective, single-blind, randomized, crossover study (performed at the Royal Adelaide Hospital, Adelaide, South Australia, Australia). PATIENTS Ten healthy young men 18 to 35 years of age were studied for 36 hours on two occasions. INTERVENTIONS Participants were randomly assigned to either antecedent hypoglycemia [three 45-minute periods of strict hypoglycemia (2.8 mmol/L] or control [three 45-minute periods of strict euglycemia (6 mmol/L)] during the initial 12-hour period. Participants were monitored overnight, and the following morning blood glucose was clamped at 2.8 mmol/L for 60 minutes and then at 6 mmol/L for 120 minutes. At least 6 weeks later participants returned for the alternative intervention. Gastric emptying and cardiac fractional shortening were measured with scintigraphy and two-dimensional echocardiography, respectively, on the morning of all 4 study days. RESULTS A single, acute episode of hypoglycemia accelerated gastric emptying (P = 0.01) and augmented fractional shortening (P < 0.01). Gastric emptying was unaffected by antecedent hypoglycemia (P = 0.74) whereas fractional shortening showed a trend to attenuation (P = 0.06). The adrenaline response was diminished (P < 0.05) by antecedent hypoglycemia. CONCLUSIONS In health, the acceleration of gastric emptying during hypoglycemia is unaffected by antecedent hypoglycemia, whereas the increase in cardiac contractility may be attenuated.
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Affiliation(s)
- Palash Kar
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia
| | - Karen L. Jones
- National Health and Medical Research Council Centre of Research Excellence in the Translation of Nutritional Science into Good Health, University of Adelaide, Adelaide, South Australia 5005, Australia
- Discipline of Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Mark P. Plummer
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia
| | - Yasmine Ali Abdelhamid
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia
| | - Emma J. Giersch
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia
| | - Matthew J. Summers
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia
| | - Seva Hatzinikolas
- National Health and Medical Research Council Centre of Research Excellence in the Translation of Nutritional Science into Good Health, University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Simon Heller
- Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield S10 2TN, United Kingdom
| | - Michael Horowitz
- National Health and Medical Research Council Centre of Research Excellence in the Translation of Nutritional Science into Good Health, University of Adelaide, Adelaide, South Australia 5005, Australia
- Discipline of Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia
| | - Adam M. Deane
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia
- Intensive Care Unit, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
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18
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Frandsen CS, Dejgaard TF, Andersen HU, Holst JJ, Hartmann B, Thorsteinsson B, Madsbad S. Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: A randomized, placebo-controlled, double-blind, parallel-group study. Diabetes Obes Metab 2017; 19:773-782. [PMID: 27868372 DOI: 10.1111/dom.12830] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 11/03/2016] [Accepted: 11/15/2016] [Indexed: 11/30/2022]
Abstract
AIM Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay the gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. MATERIALS AND METHODS In a 12-week, randomized, double-blind, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak). Secondary endpoints included changes in glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure and heart rate. RESULTS During the period June 2013 to October 2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates did not differ significantly between groups ( P = .96), with no significant changes from baseline, whether evaluated from AUCs or time to peak. The secondary endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic blood pressure and GLP-1 and PP responses, were also similar. Heart rate increased with liraglutide from 69 ± 4 to 80 ± 5 beats/min ( P = .02). CONCLUSIONS Liraglutide does not compromise glycaemic recovery, GE rate or counter-regulatory hormone responses in T1D patients during hypoglycaemia. No treatment-related safety issues were identified.
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Affiliation(s)
- Christian S Frandsen
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
- Department of Biomedical Sciences and The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Thomas F Dejgaard
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
- Steno Diabetes Center, Gentofte, Denmark
| | | | - Jens J Holst
- Department of Biomedical Sciences and The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Bolette Hartmann
- Department of Biomedical Sciences and The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Birger Thorsteinsson
- Department of Cardiology, Nephrology and Endocrinology, Nordsjaellands Hospital Hillerød, University of Copenhagen, Hillerød, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
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Pop-Busui R, Boulton AJM, Feldman EL, Bril V, Freeman R, Malik RA, Sosenko JM, Ziegler D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care 2017; 40:136-154. [PMID: 27999003 PMCID: PMC6977405 DOI: 10.2337/dc16-2042] [Citation(s) in RCA: 1407] [Impact Index Per Article: 175.9] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Rodica Pop-Busui
- Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | | | - Eva L Feldman
- Department of Neurology, University of Michigan, Ann Arbor, MI
| | - Vera Bril
- Department of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Roy Freeman
- Department of Neurology, Harvard Medical School, Boston, MA
| | - Rayaz A Malik
- Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and New York, NY
| | - Jay M Sosenko
- Division of Endocrinology, University of Miami Miller School of Medicine, Miami, FL
| | - Dan Ziegler
- German Diabetes Center Düsseldorf, Leibniz Center for Diabetes Research at Heinrich Heine University, and Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
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20
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Ouyang X, Li S, Foreman R, Farber J, Lin L, Yin J, Chen JDZ. Hyperglycemia-induced small intestinal dysrhythmias attributed to sympathovagal imbalance in normal and diabetic rats. Neurogastroenterol Motil 2015; 27:406-15. [PMID: 25630445 DOI: 10.1111/nmo.12506] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Accepted: 12/07/2014] [Indexed: 01/16/2023]
Abstract
BACKGROUND Hyperglycemia is known to induce dysrhythmias in the stomach; however, it is unknown whether they are also induced in the small intestine. Autonomic dysfunction is commonly noted in diabetes but the role it plays in hyperglycemia-induced dysrhythmias remains unknown. This study aimed to explore the effects of hyperglycemia on intestinal myoelectrical activity and the role of autonomic functions in hyperglycemia. METHODS Small intestinal myoelectrical activity (slow wave and spike activity) and autonomic functions (assessed by the spectral analysis of heart rate variability) were measured in Goto-Kakizaki diabetic rats and control rats treated with acute glucagon. Blood glucose was measured and its correlation with intestinal slow waves was determined. KEY RESULTS (1) The diabetic rats showed reduced regularity in intestinal slow waves in fasting and fed states (p < 0.001 for both), and increased sympathovagal balance (p < 0.05) in comparison with the control rats. The regularity in intestinal slow waves was negatively correlated with the HbA1c level in all rats (r = -0.663, p = 0.000). (2) Glucagon injection in the control rats induced transient hyperglycemia, intestinal slow wave dysrhythmias and impaired autonomic functions, similar to those observed in the diabetic rats. The increase in blood glucose was correlated with the decrease in the regularity of intestinal slow waves (r = -0.739, p = 0.015). CONCLUSIONS & INFERENCES Both spontaneous and glucagon-induced hyperglycemia results in slow wave dysrhythmias in the small intestine. Impairment in autonomic functions (increased sympathovagal balance) may play a role in hyperglycemia-induced dysrhythmias.
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Affiliation(s)
- X Ouyang
- Nanjing Medical University, Nanjing, Jiangsu, China; Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA; Diabetes Care & Research Center, Jiangsu Province Institute of Geriatrics, Nanjing, Jiangsu, China; Department of Physiology, University of Oklahoma, Oklahoma City, OK, USA
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21
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Pozzilli P, Raz I, Peled D, Elias D, Avron A, Tamir M, Eren R, Dagan S, Cohen IR. Evaluation of long-term treatment effect in a type 1 diabetes intervention trial: differences after stimulation with glucagon or a mixed meal. Diabetes Care 2014; 37:1384-91. [PMID: 24408401 DOI: 10.2337/dc13-1392] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Endogenous insulin secretion, measured by C-peptide area under the curve (AUC), can be tested using both the glucagon stimulation test (GST) and the mixed-meal tolerance test (MMTT). This study compares these two stimulation methods using long-term data from patients newly diagnosed with type 1 diabetes or with latent autoimmune diabetes. RESEARCH DESIGN AND METHODS A recently completed phase 3 intervention study with DiaPep277 demonstrated improved glycemic control and a significant treatment effect of glucagon-stimulated C-peptide secretion. Unexpectedly, MMTT failed to detect differences between the treated and control groups. Data from 343 patients in two balanced-randomized, double-blind, placebo-controlled, parallel-group trials of DiaPep277 were used to compare and correlate between GST- and MMTT-derived C-peptide AUC. Pearson's correlations were calculated for absolute C-peptide AUC at baseline and 12 and 24 months and for long-term changes in AUC (AUC). RESULTS The absolute AUC values obtained at any single time point by the two tests were well correlated in both data sets (r = 0.74-0.9). However, the correlations between the AUC were much weaker (r = 0.39-0.58). GST-stimulated C-peptide secretion was stable over the fasting glucose range permitted for the test (4-11.1 mmol/L), but MMTT-stimulated C-peptide secretion decreased over the same range, implying differences in sensitivity to glucose. CONCLUSIONS Measurement of long-term changes in stimulated C-peptide, reflecting endogenous insulin secretion, during the course of intervention trials may be affected by the method of stimulation, possibly reflecting different sensitivities to the physiological status of the tested subject.
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Shalaby MAF, Latif HAAE, Sayed MEE. Interaction of insulin with prokinetic drugs in STZ-induced diabetic mice. World J Gastrointest Pharmacol Ther 2013; 4:28-38. [PMID: 23667771 PMCID: PMC3644615 DOI: 10.4292/wjgpt.v4.i2.28] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2012] [Revised: 10/29/2012] [Accepted: 01/21/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the possible interactions of metoclopramide, domperidone and erythromycin in streptozotocin-induced diabetic mice treated with insulin by various parameters.
METHODS: Effects of the individual as well as combined drugs were studied in diabetic mice via estimation of the blood glucose and serum insulin levels, small intestinal transit (SIT), gastric emptying (GE), xylose absorption and glucose tolerance tests. Groups were given insulin 2 IU/kg s.c., metoclopramide 20 mg/kg p.o., domperidone 20 mg/kg p.o. and erythromycin 6 mg/kg p.o. individually and in combination. There were also normal and diabetic control groups. The first set of experiments was carried out to investigate the subchronic effect on blood glucose and serum insulin levels in diabetic mice of one week of daily dose administration of the tested drugs individually as well as the combination of insulin with each prokinetic drug. The other five sets of experiments were carried out to investigate the acute effect of a single dose of each drug individually and in combination on blood glucose and serum insulin levels, SIT, GE, oral xylose absorption and glucose tolerance tests.
RESULTS: The study included the prokinetic drugs metoclopramide (20 mg/kg), domperidone (20 mg/kg) and erythromycin (6 mg/kg), as well as insulin (2 IU/kg), which was individually effective in decreasing SIT, enhancing GE and increasing xylose absorption significantly in diabetic mice. Erythromycin tended to decrease blood glucose level and increase serum insulin level after 1 wk of daily administration in diabetic mice. Erythromycin potentiated the effect of insulin on blood glucose level and serum insulin level whereas other prokinetic agents failed to do so after repeated dose administration in diabetic mice. Metoclopramide or erythromycin in combination with insulin significantly decreased SIT, in diabetic mice, to lower levels than with insulin alone. Administration of prokinetic drugs along with insulin antagonized the action of insulin on xylose absorption. These combinations also increased the rate of glucose absorption from the gut.
CONCLUSION: The present study suggests that prokinetic drugs could potentially improve glycemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients, matched to the action of exogenous insulin. The use of prokinetics, such as erythromycin, may be interesting in the clinic in decreasing the need for insulin in diabetic patients. The dose of insulin may be safely decreased with erythromycin in chronic treatments.
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Abstract
Maintenance of normal blood glucose levels is important for avoiding chronic diseases such as type 2 diabetes, cardiovascular problems, and obesity. Type 2 diabetes is one of the major health problems affecting the world population and this condition can be exacerbated by poor diet, low physical activity, and genetic abnormalities. Food plays an important role in the management of blood glucose and associated complications in diabetes. This is attributed to the ability of food-based ingredients to modulate blood glucose without causing any adverse health consequences. This chapter focuses on four important food groups such as cereals, legumes, fruits, and spices that have active ingredients such as soluble dietary fiber, polyphenols, and antinutrients with the ability to reduce glycemic and insulin response in humans. Other food ingredients such as simple sugars, sugar alcohols, and some proteins are also discussed in moderation.
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Abstract
BACKGROUND Diabetic gastroparesis (DGP) is a gastric complication of diabetes mellitus that causes nausea, vomiting, early satiety, bloating and abdominal pain, in addition to significant morbidity. SOURCES OF DATA Original and review articles were reviewed through PubMed, including relevant guidelines from the European and American Neurogastroenterology Societies. AREAS OF AGREEMENT Diagnosis of DGP requires endoscopy and measurement of gastric emptying. Management requires prokinetic therapy, usually in addition to antinausea or other medications. AREAS OF CONTROVERSY The pathogenesis of DGP is poorly understood. Management strategies are highly variable. Growing points Prokinetic and neuromodulatory medications are in human clinical trials specifically for gastroparesis. AREAS TIMELY FOR DEVELOPING RESEARCH Further understanding of the molecular pathology leading to DGP is required to potentially arrest the development of this serious diabetic complication. Evaluation of novel agents for use in DGP is sorely needed.
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Brainstem sensing of meal-related signals in energy homeostasis. Neuropharmacology 2012; 63:31-45. [DOI: 10.1016/j.neuropharm.2012.03.019] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 03/12/2012] [Accepted: 03/23/2012] [Indexed: 11/15/2022]
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Younk LM, Mikeladze M, Davis SN. Pramlintide and the treatment of diabetes: a review of the data since its introduction. Expert Opin Pharmacother 2011; 12:1439-51. [PMID: 21564002 DOI: 10.1517/14656566.2011.581663] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Postprandial glucose excursions negatively affect glycemic control and markers of cardiovascular health. Pramlintide, an amylinomimetic, is approved for treatment of elevated postprandial glucose levels in type 1 and type 2 diabetes mellitus. AREAS COVERED A literature search of PubMed was conducted to locate articles (up to January 2011) pertaining to original preclinical and clinical research and reviews of amylin and pramlintide. Additional sources were selected from reference lists within articles obtained through the original literature search and from the internet. This article describes the known effects of endogenous amylin and the pharmacodynamics, pharmacokinetics and clinical efficacy of pramlintide. Drug-drug interactions and safety and tolerability are also reviewed. EXPERT OPINION Pramlintide significantly reduces hemoglobin A(1c) and body weight in patients with type 1 and type 2 diabetes mellitus. Newer research is focusing on weight loss effects of pramlintide and pramlintide plus metreleptin in nondiabetic obese individuals. Preliminary results of these studies are discussed.
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Affiliation(s)
- Lisa M Younk
- University of Maryland School of Medicine, Department of Medicine, Baltimore, MD 21201 USA
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Kielgast U, Holst JJ, Madsbad S. Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual β-cell function. Diabetes 2011; 60:1599-607. [PMID: 21441444 PMCID: PMC3292336 DOI: 10.2337/db10-1790] [Citation(s) in RCA: 118] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To investigate the effect of exogenous as well as endogenous glucagon-like peptide 1 (GLP-1) on postprandial glucose excursions and to characterize the secretion of incretin hormones in type 1 diabetic patients with and without residual β-cell function. RESEARCH DESIGN AND METHODS Eight type 1 diabetic patients with (T1D+), eight without (T1D-) residual β-cell function, and eight healthy matched control subjects were studied during a mixed meal with concomitant infusion of GLP-1 (1.2 pmol/kg/min), saline, or exendin 9-39 (300 pmol/kg/min). Before the meal, half dose of usual fast-acting insulin was injected. Plasma glucose (PG), glucagon, C-peptide, total GLP-1, intact glucose-dependent insulinotropic polypeptide (GIP), free fatty acids, triglycerides, and gastric emptying rate (GE) by plasma acetaminophen were measured. RESULTS Incretin responses did not differ between patients and control subjects. Infusion of GLP-1 decreased peak PG by 45% in both groups of type 1 diabetic patients. In T1D+ patients, postprandial PG decreased below fasting levels and was indistinguishable from control subjects infused with saline. In T1D- patients, postprandial PG remained at fasting levels. GLP-1 infusion reduced GE and glucagon levels in all groups and increased fasting C-peptide in T1D+ patients and control subjects. Blocking endogenous GLP-1 receptor action increased endogenous GLP-1 secretion in all groups and increased postprandial glucose, glucagon, and GE in T1D+ and T1D- patients. The insulinogenic index (the ratio of insulin to glucose) decreased in T1D+ patients during blockade of endogenous GLP-1 receptor action. CONCLUSIONS Type 1 diabetic patients have normal incretin responses to meals. In type 1 diabetic patients, exogenous GLP-1 decreases peak postprandial glucose by 45% regardless of residual β-cell function. Endogenous GLP-1 regulates postprandial glucose excursions by modulating glucagon levels, GE, and β-cell responsiveness to glucose. Long-term effects of GLP-1 in type 1 diabetic patients should be investigated in future clinical trials.
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Affiliation(s)
- Urd Kielgast
- Department of Endocrinology, Hvidovre University Hospital, Copenhagen, Denmark.
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Abstract
Diabetic gastroparesis was once thought to be rare, associated with a poor prognosis, and to affect only patients with type 1 diabetes and irreversible autonomic neuropathy. A landmark study conducted by Horowitz et al. and published in JGH in 1986 paved the way for further studies to examine the pathophysiology, natural history and prognosis of diabetic gastroparesis, as well as its optimal management. This review summarizes the developments in knowledge gained over the last ∼25 years that have led to understanding about normal and disordered gastric emptying in diabetes, with a particular emphasis on the inter-relationship between the rate of gastric emptying and the regulation of blood glucose.
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Affiliation(s)
- Jessica Chang
- University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, South Australia, Australia
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Abstract
Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient's quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG.
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Affiliation(s)
- Uazman Alam
- Department of Cardiovascular Sciences, University of Manchester, Core Technology Facility (3rd Floor), Grafton Street, Manchester, M13 9NT UK
| | - Omar Asghar
- Department of Cardiovascular Sciences, University of Manchester, Core Technology Facility (3rd Floor), Grafton Street, Manchester, M13 9NT UK
| | - Rayaz Ahmed Malik
- Department of Cardiovascular Sciences, University of Manchester, Core Technology Facility (3rd Floor), Grafton Street, Manchester, M13 9NT UK
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Abstract
Insulin replacement therapy in type 1 diabetes mellitus (T1DM) is nonphysiologic. Hyperinsulinemia is generated in the periphery to achieve normal insulin concentrations in the liver. This mismatch results in increased hypoglycemia, increased food intake with weight gain, and insufficient regulation of postprandial glucose excursions. Islet amyloid polypeptide is a hormone synthesized in pancreatic beta cells and cosecreted with insulin. Circulating islet amyloid polypeptide binds to receptors located in the hindbrain and increases satiety, delays gastric emptying and suppresses glucagon secretion. Thus, islet amyloid polypeptide complements the effects of insulin. T1DM is a state of both islet amyloid polypeptide and insulin deficiency. Pramlintide, a synthetic analog of islet amyloid polypeptide, can replace this hormone in patients with T1DM. When administered as adjunctive therapy to such patients treated with insulin, pramlintide decreases food intake and causes weight loss. Pramlintide therapy is also associated with suppression of glucagon secretion and delayed gastric emptying, both of which decrease postprandial plasma glucose excursions. Pramlintide therapy improves glycemic control and lessens weight gain. Agents that decrease intestinal carbohydrate digestion (alpha-glucosidase inhibitors) or decrease insulin resistance (metformin) might be alternative adjunctive therapies in T1DM, though its benefits are marginally supported by clinical data.
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Affiliation(s)
- Harold E Lebovitz
- Department of Medicine, Division of Endocrinology, State University of New York Health Science Center at Brooklyn, 450 Clarkson Avenue, New York, NY 11203, USA.
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Husband AC, Crawford S, McCoy LA, Pacaud D. The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes. Pediatr Diabetes 2010; 11:154-8. [PMID: 19663922 DOI: 10.1111/j.1399-5448.2009.00558.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE There is a lack of evidence regarding the most effective treatment option for managing naturally occurring hypoglycemia in children with type 1 diabetes. The objectives of this study were (i) to determine if sucrose and fructose are equally effective as glucose in the treatment of spontaneous hypoglycemia in children with type 1 diabetes; and (ii) to determine prestudy and poststudy hypoglycemia treatment preferences. METHODS Thirty-three subjects [aged 5.4-15.5 yr and average duration of type 1 diabetes of 3.1 yr (SD = 2.3)] participated in a randomized, crossover design. The main outcome was the effectiveness of treatment as defined by a blood glucose meter reading that was > or = 4.0 mmol/L 15 min after treatment. Each subject treated five hypoglycemic events with each treatment type: glucose (BD Glucose Tablets), sucrose (Skittles), and fructose (Fruit to Go). RESULTS There was a significant difference between the effectiveness of the three treatments [Wilk's Lambda F(2,28) = 8.64, p = 0.001]. No significant difference between treatment with glucose and treatment with sucrose was noted, but the treatment effectiveness for fructose was significantly lower than sucrose [F (1,29) = 16.09, p < 0.001] and glucose [F (1,29) = 15.64, p < 0.001]. The preferred treatment choices before the study were as follows: 36% glucose, 18% sucrose, and 33% fructose sources. Poststudy, 52% of children preferred the same treatment, which was effective (glucose or sucrose), followed by 35% who changed their preference to an effective treatment. CONCLUSION Skittles are as effective in treating hypoglycemia as more expensive BD Glucose Tablets in children with type 1 diabetes.
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Affiliation(s)
- Allison C Husband
- Diabetes Clinic, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.
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32
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Souza MAN, Souza MHLP, Palheta RC, Cruz PRM, Medeiros BA, Rola FH, Magalhães PJC, Troncon LEA, Santos AA. Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students. ADVANCES IN PHYSIOLOGY EDUCATION 2009; 33:343-348. [PMID: 19948686 DOI: 10.1152/advan.90176.2008] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols. Insulin and control rats were gavage fed with 5% glucose solution, whereas hypertonic-fed rats were gavage fed with 50% glucose solution. Insulin treatment was performed 30 min before a meal. All meals (1.5 ml) contained an equal mass of phenol red dye. After 10, 15, or 20 min of meal gavage, rats were euthanized. Each subset consisted of six to eight rats. Dye recovery in the stomach and proximal, middle, and distal small intestine was measured by spectrophotometry, a safe and reliable method that can be performed by minimally trained students. In a separate group of rats, we used the same protocols except that the test meal contained (99m)Tc as a marker. Compared with control, the hypertonic meal delayed gastric emptying and gastrointestinal transit, whereas insulinic hypoglycemia accelerated them. The session helped engage our undergraduate students in observing and analyzing gut motor behavior. In conclusion, the fractional dye retention test can be used as a teaching tool to strengthen the understanding of basic physiopathological features of gastrointestinal motility.
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Affiliation(s)
- M A N Souza
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, São Paulo, Brazil
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Hlebowicz J. Postprandial blood glucose response in relation to gastric emptying and satiety in healthy subjects. Appetite 2009; 53:249-52. [DOI: 10.1016/j.appet.2009.06.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2008] [Revised: 04/21/2009] [Accepted: 06/08/2009] [Indexed: 11/25/2022]
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Samsom M, Bharucha A, Gerich JE, Herrmann K, Limmer J, Linke R, Maggs D, Schirra J, Vella A, Wörle HJ, Göke B. Diabetes mellitus and gastric emptying: questions and issues in clinical practice. Diabetes Metab Res Rev 2009; 25:502-14. [PMID: 19610128 DOI: 10.1002/dmrr.974] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
It is long known that both type 1 and type 2 diabetes can be associated with changes in gastric emptying; a number of publications have linked diabetes to delayed gastric emptying of variable severity and often with poor relationship to gastrointestinal symptomatology. In contrast, more recent studies have reported accelerated gastric emptying when adjusted for glucose concentration in patients with diabetes, indicating a reciprocal relationship between gastric emptying and ambient glucose concentrations. This review proposes that gastroparesis or gastroparesis diabeticorum, a severe condition characterized by a significant impairment of gastric emptying accompanied by severe nausea, vomiting, and malnutrition, is often overdiagnosed and not well contrasted with delays in gastric emptying. The article offers a clinically relevant definition of gastroparesis that should help differentiate this rare condition from (often asymptomatic) delays in gastric emptying. The fact that delayed gastric emptying can also be observed in non-diabetic individuals under experimental conditions in which hyperglycaemia is artificially induced suggests that a delay in gastric emptying rate when blood glucose concentrations are high is actually an appropriate physiological response to hyperglycaemia, slowing further increases in blood glucose. The article discusses the strengths and weaknesses of various methodologies for assessing gastric emptying, especially with respect to the diabetes population, and reviews newer diabetes therapies that decelerate the rate of gastric emptying. These therapies may be a beneficial tool in managing postprandial hyperglycaemia because they attenuate rapid surges in glucose concentrations by slowing the delivery of meal-derived glucose.
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Affiliation(s)
- Melvin Samsom
- University Medical Center St Radboud, Gastroenterology, Nijmegen, The Netherlands.
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Abstract
Gastric emptying is frequently abnormal in patients with long-standing type 1 and type 2 diabetes mellitus. Symptoms commonly associated with disordered gastric emptying include nausea, vomiting, bloating and epigastric pain, while patients are also at risk of malnutrition, weight loss, impaired drug absorption, disordered glycaemic control and poor quality of life. Although often attributed to the presence of irreversible autonomic neuropathy, acute hyperglycaemia represents a potentially reversible cause of gastric dysfunction in diabetes. Scintigraphy represents the gold standard for measuring gastric emptying. The management of diabetic gastroparesis is less than optimal, partly because the pathogenesis has not been clearly defined. Treatment approaches include dietary modification and optimization of glycaemia, and the use of prokinetic drugs, while novel therapies such as gastric electrical stimulation are the subject of ongoing investigation.
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Affiliation(s)
- Jing Ma
- University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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36
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Wang CP, Kao CH, Chen WK, Lo WY, Hsieh CL. A single-blinded, randomized pilot study evaluating effects of electroacupuncture in diabetic patients with symptoms suggestive of gastroparesis. J Altern Complement Med 2009; 14:833-9. [PMID: 18721079 DOI: 10.1089/acm.2008.0107] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND OBJECTIVES The current pharmacological management of diabetic gastroparesis remains difficult. Acupuncture has been widely used for gastrointestinal symptoms. The aim of this study was to investigate the effects of electroacupuncture (EA) on solid gastric emptying time, serum gastrin, motilin, pancreatic polypeptide (PP), fasting and postprandial blood glucose, and symptoms in patients with diabetic gastroparesis. INTERVENTIONS EA at the Zusanli (ST 36) and Hegu (LI 4) points and sham EA as control were administered by an experienced and licensed acupuncturist. DESIGN This was a pilot study with a randomized, single-blinded design. SUBJECTS AND SETTING Nineteen (19) patients with type 2 diabetes who had had symptoms of gastroparesis for more than 3 months were included in the trial and randomized into two groups. Each group received EA (n = 9) or sham EA (n = 10) consisting of 4 sessions over 2 weeks. OUTCOME MEASURES Symptom severity was evaluated using the Gastroparesis Cardinal Symptom Index (GCSI) at baseline, at the end of treatment, and 2 weeks after the end of the trial; solid-phase gastric half-emptying time was measured by scintigraphy; in addition, serum gastrin, motilin, PP, fasting, and postprandial blood glucose levels were also measured. RESULTS Gastric half-emptying time in 9 patients with diabetic gastroparesis was significantly shortened by EA treatment (143.8 +/- 55.9 minutes versus 98.8 +/- 28.6 minutes, p < 0.03). Half-emptying time did not change (98.9 +/- 26.4 minutes versus 90.9 +/- 24.8 minutes, p > 0.05) in the sham EA group. Symptom severity, as measured by GCSI total score, improved significantly both at the end of treatment (2.38 +/- 0.56 versus 1.48 +/- 0.19, p < 0.001) and 2 weeks after the end of the trial (2.38 +/- 0.56 versus 1.65 +/- 0.44, p < 0.01) when compared with the baseline in the EA group, but did not change from baseline with sham EA treatment. There were no significant changes in fasting and postprandial blood glucose, serum gastrin, motilin, and PP in both groups. No significant adverse events occurred. CONCLUSIONS This study demonstrates that short-term EA at the Zusanli and Hegu points effectively reduces the dyspeptic symptoms of diabetic gastroparesis and accelerates solid gastric emptying. Sustained improvement in dyspeptic symptoms was observed at 2 weeks after the end of the trial. Its potential for treating gastroparesis may be explored, and a larger trial is required to draw definitive conclusions.
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Affiliation(s)
- Chung-Pang Wang
- Department of Emergency Medicine, China Medical University Hospital, Taichung City, Taiwan, Republic of China
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37
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Lodefalk M, Aman J, Bang P. Effects of fat supplementation on glycaemic response and gastric emptying in adolescents with Type 1 diabetes. Diabet Med 2008; 25:1030-5. [PMID: 19183308 DOI: 10.1111/j.1464-5491.2008.02530.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
AIMS To compare the glycaemic response to meals with different fat content in adolescents with Type 1 diabetes mellitus (T1DM) and to investigate associations with gastric emptying. METHODS In this randomized, cross-over study, paired results were obtained from seven adolescents with T1DM who ingested on different days two meals with the same carbohydrate and protein content, but different fat and energy content (2 and 38 g fat, 320 and 640 kcal, respectively). Paracetamol was mixed into the meals and gastric emptying was estimated by the paracetamol absorption method. All subjects were normoglycaemic and given 7 IU insulin aspart at commencement of ingestion. Postprandial blood samples were taken during 4 h. RESULTS The areas under the curves for plasma glucose and serum paracetamol concentrations were larger after the low-fat than after the high-fat meal during the first 2 h (P = 0.047 and P = 0.041, respectively). The difference between meals in time-to-peak in glucose and paracetamol concentrations did not reach statistical significance (high-fat vs. low-fat meal: 210 min (120-240) vs. 120 min (50-240), P = 0.080 and 120 min (75-180) vs. 60 min (60-120), P = 0.051, respectively). Changes in glucose concentrations correlated with simultaneous changes in paracetamol concentrations (P < 0.001). CONCLUSIONS For the first time, we have shown that the initial glycaemic response is reduced after a meal with higher compared with a meal with lower fat content in adolescents with T1DM given a rapid-acting insulin analogue preprandially. The type and dose of preprandial insulin may need adjustment to the fat content of the meal to reach postprandial normoglycaemia.
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Affiliation(s)
- M Lodefalk
- Paediatric Endocrinology and Diabetes Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
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Quan C, Talley NJ, Jones MP, Howell S, Horowitz M. Gastrointestinal symptoms and glycemic control in diabetes mellitus: a longitudinal population study. Eur J Gastroenterol Hepatol 2008; 20:888-897. [PMID: 18794603 DOI: 10.1097/meg.0b013e3282f5f734] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prevalence of gastrointestinal (GI) symptoms is increased in diabetes, but their natural history is understood poorly and any impact of glycemic control is controversial. We aimed to quantify changes in GI symptom status and glycemic control among a population sample of patients with diabetes. METHODS Data on 10 chronic GI symptom complexes were obtained from a validated questionnaire at baseline and after 12 months. Changes in acute and chronic glycemic control were classified as always adequate, variable (deteriorated or improved), or always inadequate; acute glycemic control was assessed by fasting plasma glucose and chronic glycemic control by a validated self-report 5-point graded scale. RESULTS Baseline and follow-up data were available in 136 individuals with diabetes (mean age 59 years; 66% males; 95% type 2). The most prevalent GI symptom complexes were abdominal bloating/distension (35%), ulcer-like dyspepsia (35%), and irritable bowel syndrome (27%). Overall, between 7 and 24% reported a change in GI symptoms with the largest change in irritable bowel syndrome (24%), bloating/distension (22%), and ulcer-like dyspepsia (21%). Those who had a change in abdominal bloating (either loss or gain) over 12 months were more likely to have increased their mean fasting plasma glucose (P<0.05). Contrary to expectations, consistently poor self-reported glycemic control was only weakly associated with less persistent abdominal pain (r=-0.2, P=0.03), diarrhea (r=-0.22, P=0.01), and abdominal bloating (r=-0.2, P=0.03). Acute glycemic control was not significantly related to any GI symptoms. CONCLUSION We were unable to demonstrate any association between worsening GI symptoms and glycemic control.
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Affiliation(s)
- Carolyn Quan
- Department of Medicine, Nepean Hospital, University of Sydney, Australia
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Olausson EA, Alpsten M, Larsson A, Mattsson H, Andersson H, Attvall S. Small particle size of a solid meal increases gastric emptying and late postprandial glycaemic response in diabetic subjects with gastroparesis. Diabetes Res Clin Pract 2008; 80:231-7. [PMID: 18237818 DOI: 10.1016/j.diabres.2007.12.006] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2007] [Accepted: 12/08/2007] [Indexed: 01/15/2023]
Abstract
Our goal was to investigate if food of small particle size increases the gastric emptying rate and lessens the fall in postprandial blood glucose in seven subjects with Type 1 diabetes and gastroparesis. Two solid meals of identical composition but of different particle size, with 5MBq (99m)Tc added to the meals, were ingested in randomized order in seven subjects with Type 1 Diabetes Mellitus and gastroparesis and seven healthy subjects. During 180min blood glucose and insulin concentrations were measured and gastric emptying of the ingested meals was registered by a gamma camera. The lag phase in the stomach was significantly shorter, the radioactivity remaining in the stomach after 120min (T(120)) was significant less and the postprandial blood glucose dip was less and of shorter duration after a small particle (SP) meal, compared to a large particle (LP) meal in diabetic subjects. Gastric emptying did not differ significantly between groups after an SP meal. Food of small particle size increases the gastric emptying rate and reduces the postprandial blood glucose dip in both magnitude and duration in Type 1 diabetic subjects with gastroparesis, which is likely to be of importance in achieving good metabolic control.
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Affiliation(s)
- Eva A Olausson
- Diabetic Centre, Institute of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden
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40
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Punkkinen J, Färkkilä M, Mätzke S, Korppi-Tommola T, Sane T, Piirilä P, Koskenpato J. Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy. Diabet Med 2008; 25:570-7. [PMID: 18445170 DOI: 10.1111/j.1464-5491.2008.02428.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIMS Diabetic gastroparesis is a common condition occurring in some 30-50% of patients with long-term diabetes. Some studies have found a relationship between autonomic neuropathy and diabetic gastroparesis. In addition to autonomic neuropathy, acute changes in plasma glucose concentration can also affect gastric emptying. The objective was to examine the relationship between autonomic nerve function, glucose concentration, gastric emptying, and upper abdominal symptoms in Type 1 diabetic patients. METHODS Gastric emptying of solids and liquids was measured with scintigraphy in 27 patients with longstanding Type 1 diabetes with upper abdominal symptoms. Autonomic nerve function was examined by standardized cardiovascular tests, and plasma glucose concentrations were measured during scintigraphy. Severity of abdominal symptoms and quality of life were explored by validated questionnaires. RESULTS Seven patients (26%) had delayed gastric emptying of solids and three (11%) of liquids. Mean gastric half-emptying time of solids was 128 +/- 116 min and of liquids 42 +/- 30 min. Of the 26 patients undergoing tests, 16 (62%) had autonomic nerve dysfunction. Autonomic neuropathy score (1.6 +/- 1.7) correlated positively with the gastric emptying rate of solids (P = 0.006), a rate unrelated to symptom scores or plasma glucose concentrations during scintigraphy. Quality of life in patients with abdominal symptoms was lower than in the normal Finnish population. CONCLUSIONS Impaired gastric emptying of solids in patients with Type 1 diabetes is related to autonomic neuropathy, but not to actual glycaemic control. The upper abdominal symptoms observed in these patients cannot be explained, however, by impaired gastric emptying.
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Affiliation(s)
- J Punkkinen
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.
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Kojecky V, Bernatek J, Horowitz M, Zemek S, Bakala J, Hep A. Prevalence and determinants of delayed gastric emptying in hospitalised Type 2 diabetic patients. World J Gastroenterol 2008; 14:1564-1569. [PMID: 18330949 PMCID: PMC2693753 DOI: 10.3748/wjg.14.1564] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2006] [Revised: 02/05/2008] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the prevalence of delayed gastric emptying (GE) in older patients with Type 2 diabetes mellitus. METHODS One hundred and forty seven patients with Type 2 diabetes, of whom 140 had been hospitalised, mean age 62.3 +/- 8.0 years, HbA1c 9.1% +/- 1.9%, treated with either oral hypoglycemic drugs or insulin were studied. GE of a solid meal (scintigraphy), autonomic nerve function, upper gastrointestinal symptoms, acute and chronic glycemic control were evaluated. Gastric emptying results were compared to a control range of hospitalised patients who did not have diabetes. RESULTS Gastric emptying was delayed (T50 > 85 min) in 17.7% patients. Mean gastric emptying was slower in females (T50 72.1 +/- 72.1 min vs 56.9 +/- 68.1 min, P = 0.02) and in those reporting nausea (112.3 +/- 67.3 vs 62.7 +/- 70.0 min, P < 0.01) and early satiety (114.0 +/- 135.2 vs 61.1 +/- 62.6 min, P = 0.02). There was no correlation between GE with age, body weight, duration of diabetes, neuropathy, current glycemia or the total score for upper gastrointestinal symptoms. CONCLUSION Prolonged GE occurs in about 20% of hospitalised elderly patients with Type 2 diabetes when compared to hospitalised patients who do not have diabetes. Female gender, nausea and early satiety are associated with higher probability of delayed GE.
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Maggs D, MacDonald I, Nauck MA. Glucose homeostasis and the gastrointestinal tract: insights into the treatment of diabetes. Diabetes Obes Metab 2008; 10:18-33. [PMID: 17490426 DOI: 10.1111/j.1463-1326.2007.00737.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The gastrointestinal tract is increasingly viewed as a critical organ in glucose metabolism because of its role in delivering glucose to the circulation and in secreting multiple glucoregulatory hormones that, in concert with insulin and glucagon, regulate glucose homeostasis. Under normal conditions, a complex interplay of these hormones acts to maintain plasma glucose within a narrow range despite large variations in the availability of glucose, particularly during transition from the fasting to fed state. In the fed state, the rate at which nutrients are passed from the stomach to the duodenum, termed gastric emptying rate, is a key determinant of postprandial glucose flux. In patients with diabetes, the regulation of glucose metabolism is disrupted resulting in fasting and postprandial hyperglycaemia. Elucidation of the role of the gastrointestinal tract, gut-derived glucoregulatory peptides and gastric emptying rate offers a new perspective on glucose homeostasis and the respective importance of these factors in the diabetes state. This review will highlight the importance of the gastrointestinal tract in playing a key role in glucose homeostasis, particularly in the postprandial period, and the role of established or new therapies that either leverage or modify gastrointestinal function to improve glycaemic state.
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Affiliation(s)
- D Maggs
- Medical Affairs, Amylin Pharmaceuticals, Inc., San Diego, CA 92121, USA.
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Hlebowicz J, Darwiche G, Björgell O, Almér LO. Effect of apple cider vinegar on delayed gastric emptying in patients with type 1 diabetes mellitus: a pilot study. BMC Gastroenterol 2007; 7:46. [PMID: 18093343 PMCID: PMC2245945 DOI: 10.1186/1471-230x-7-46] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2007] [Accepted: 12/20/2007] [Indexed: 11/16/2022] Open
Abstract
Background Previous studies on healthy people show that vinegar delays gastric emptying and lowers postprandial blood glucose and insulin levels. The aim of this study was to investigate the effect of apple cider vinegar on delayed gastric emptying rate on diabetes mellitus patients. Methods Ten patients with type 1 diabetes and diabetic gastroparesis, including one patient who had undergone vagotomy, were included and completed the investigator blinded crossover trial. The gastric emptying rate (GER) was measured using standardized real-time ultrasonography. The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of 300 g rice pudding and 200 ml water (GER1), or 300 g rice pudding and 200 ml water with 30 ml apple cider vinegar (GER2). The subjects drank 200 ml water daily before breakfast one week before the measurement of GER1. The same subjects drank 200 ml water with 30 ml vinegar daily before breakfast for two weeks before the measurement of GER2. Results The median values of GER1 and GER2 were 27% and 17%, respectively. The effect of vinegar on the rate of gastric emptying was statistically significant (p < 0.05). Conclusion This study shows that vinegar affects insulin-dependent diabetes mellitus patients with diabetic gastroparesis by reducing the gastric emptying rate even further, and this might be a disadvantage regarding to their glycaemic control. Trial registration number ISRCTN33841495.
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Affiliation(s)
- Joanna Hlebowicz
- Department of Medicine, University of Lund, Malmö University Hospital, Malmö, Sweden.
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Sanaka M, Yamamoto T, Anjiki H, Nagasawa K, Kuyama Y. Effects of agar and pectin on gastric emptying and post-prandial glycaemic profiles in healthy human volunteers. Clin Exp Pharmacol Physiol 2007; 34:1151-5. [PMID: 17880369 DOI: 10.1111/j.1440-1681.2007.04706.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
1. Dietary fibre, such as pectin, delays gastric emptying and may enhance post-prandial glucose tolerance. Agar, which is high in fibre content, is widely used in the traditional Japanese diet. Although long-term diet therapy with agar decreases fasting plasma glucose levels in diabetes, knowledge is lacking about the acute effects of agar on gastric emptying and the post-prandial glycaemic profiles. The present study was designed to investigate the acute effects of agar. 2. Ten healthy male volunteers were studied on three occasions with three different test meals (450 kcal/500 mL): (i) a fibre-free meal; (ii) a meal with 2.0 g agar; or (iii) a meal with 5.2 g pectin. On each occasion, participants underwent a [(13)C]-acetate breath test along with serial blood sampling. To quantify gastric emptying, the half [(13)CO(2)] excretion time (t((1/2)b)) and the time for maximal [(13)CO(2)] excretion rate (t(lag)) were determined. The post-prandial glycaemic response was expressed as an incremental change from the fasting value at each sampling time. Data were analysed using repeated-measures analysis of variance (anova), followed by a post hoc paired Student's t-test with Bonferroni adjustment. 3. The time-course for respiratory [(13)CO(2)] excretion differed significantly among the three test meals (P = 0.0004, anova). Compared with the control meal, [(13)CO(2)] excretion was significantly lower following consumption of the agar meal (between 40 and 105 min post-prandially; P < 0.025, Student's t-test) and the pectin meal (between 40 and 180 min post-prandially; P < 0.025, Student's t-test). Among the three meals, significant differences were found in t((1/2)b) (P = 0.002, anova) and t(lag) (P = 0.011, anova). Compared with the control meal, the agar and pectin meals exhibited a significantly prolonged t((1/2)b) (P = 0.007 and P < 0.0001, respectively, Student's t-test) and t(lag) (P = 0.006 and P = 0.002, respectively, Student's t-test). Neither the agar nor pectin meal affected the post-prandial glucose profile. 4. In healthy adults, agar and pectin delay gastric emptying but have no impact on the post-prandial glucose response.
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Affiliation(s)
- Masaki Sanaka
- Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. sanaka.koma.@cick.jp
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Choi KM, Zhu J, Stoltz GJ, Vernino S, Camilleri M, Szurszewski JH, Gibbons SJ, Farrugia G. Determination of gastric emptying in nonobese diabetic mice. Am J Physiol Gastrointest Liver Physiol 2007; 293:G1039-45. [PMID: 17884976 DOI: 10.1152/ajpgi.00317.2007] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Animal studies on diabetic gastroparesis are limited by inability to follow gastric emptying changes in the same mouse. The study aim was to validate a nonlethal gastric emptying method in nonobese diabetic (NOD) LtJ mice, a model of type 1 diabetes, and study sequential changes with age and early diabetic status. The reliability and responsiveness of a [(13)C]octanoic acid breath test in NOD LtJ mice was tested, and the test was used to measure solid gastric emptying in NOD LtJ mice and nonobese diabetes resistant (NOR) LtJ mice. The (13)C breath test produced results similar to postmortem recovery of a meal. Bethanechol accelerated gastric emptying [control: 92 +/- 9 min; bethanechol: 53 +/- 3 min, mean half emptying time (T(1/2)) +/- SE], and atropine slowed gastric emptying (control: 92 +/- 9 min; atropine: 184 +/- 31 min, mean T(1/2) +/- SE). Normal gastric emptying (T(1/2)) in nondiabetic NOD LtJ mice (8-12 wk) was 91 +/- 2 min. Aging had differing effects on gastric emptying in NOD LtJ and NOR LtJ mice. Onset of diabetes was accompanied by accelerated gastric emptying during weeks 1-2 of diabetes. Gastric emptying returned to normal by weeks 3-5 with no delay. The [(13)C]octanoic acid breath test accurately measures gastric emptying in NOD LtJ mice, is useful to study the time course of changes in gastric emptying in diabetic NOD LtJ mice, and is able to detect acceleration in gastric emptying early in diabetes. Opposing changes in gastric emptying between NOD LtJ and NOR LtJ mice suggest that NOR LtJ mice are not good controls for the study of gastric emptying in NOD LtJ mice.
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Affiliation(s)
- Kyoung Moo Choi
- Enteric NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905, USA
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Abstract
Gastroparesis presents with gastrointestinal symptoms and nongastrointestinal manifestations in association with objective delays in gastric emptying. The condition may complicate several systemic disorders or may be idiopathic in nature. The diagnosis is made by directed evaluation to exclude organic diseases, which can mimic the clinical presentation of gastroparesis coupled with quantification of gastric emptying. Current therapies rely on dietary modifications, medications to stimulate gastric evacuation, and agents to reduce vomiting. Endoscopic and surgical options are increasingly used for cases refractory to medication treatment.
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Affiliation(s)
- William L Hasler
- Division of Gastroenterology, University of Michigan Health System, University of Michigan Hospital, 3912 Taubman Center, Box 0362, Ann Arbor, MI 48109, USA.
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Hinninghofen H, Frieling T, Enck P. Diabetische Gastroparese. DER DIABETOLOGE 2006; 2:132-138. [DOI: 10.1007/s11428-006-0039-5] [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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Stevens JE, Russo A, Delaney CA, Collins PJ, Horowitz M, Jones KL. Acute effects of C-peptide on gastric emptying in longstanding type 1 diabetes. Clin Auton Res 2006; 16:55-57. [PMID: 16477496 DOI: 10.1007/s10286-006-0308-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2005] [Accepted: 07/22/2005] [Indexed: 02/07/2023]
Abstract
Gastric emptying (GE) of a solid (100 g beef) and liquid (150 ml 10 % dextrose) meal was measured in eight patients with type 1 diabetes during intravenous infusion of C-peptide (6 pmol/kg/ min) or isotonic saline. C-peptide had no effect on either solid or liquid GE.
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Affiliation(s)
- Julie E Stevens
- Dept. of Medicine, University of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia
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Phillips WT. Opposing glucose set points hypothesis of essential hypertension. Med Hypotheses 2006; 66:22-37. [PMID: 16181745 DOI: 10.1016/j.mehy.2005.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2005] [Accepted: 08/04/2005] [Indexed: 11/16/2022]
Abstract
Understanding of the mechanisms involved in the development of essential hypertension is incomplete. Many studies have demonstrated that sympathetic overactivity is involved in the development of essential hypertension. In addition, hypertensive patients, as a group, are insulin resistant. The relationship of increased sympathetic activity to insulin resistance in essential hypertension has not been adequately explained. Hypertensive subjects have been reported to have rapid gastric emptying compared to control subjects. They also have increased postprandial hypotensive responses to high carbohydrate meals compared with non-hypertensive control subjects. The author hypothesizes that essential hypertension is the result of a metabolic disregulation in which the body's glucose regulatory system splits into two separate glucose control systems with two different homeostatic set points for fasting and postprandial glucose levels. It is proposed that insulin is the principle regulator of the lower glucose set point while counter-regulatory hormones, predominantly catecholamines, as well as the rate of gastric emptying, are regulators of the upper glucose set point. The tension between these two opposing control systems results in increased sympathetic activity, increased fasting and postprandial glucose and insulin levels and an increased rate of gastric emptying in hypertension. It is hypothesized that increased sympathetic activity from these opposing regulatory systems initiates a vicious cycle that eventually leads to the development of essential hypertension. This hypothesis explains the beneficial effects of agents that either slow carbohydrate absorption or delay gastric emptying on essential hypertension and postprandial hypotension. New therapeutic strategies for treatment of hypertension are suggested by this hypothesis.
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Affiliation(s)
- William T Phillips
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
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