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Deng Y, Moniruzzaman M, Rogers B, Hu L, Jagannathan R, Tamura K. Unveiling inequalities: Racial, ethnic, and socioeconomic disparities in diabetes: Findings from the 2007-2020 NHANES data among U.S. adults. Prev Med Rep 2025; 50:102957. [PMID: 40007950 PMCID: PMC11852695 DOI: 10.1016/j.pmedr.2024.102957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/20/2024] [Accepted: 12/20/2024] [Indexed: 02/27/2025] Open
Abstract
Objective Despite persistent disparities in diabetes prevalence among racial and ethnic minorities, there remains a significant lack of understanding regarding the intersectionality of racial and ethnic groups and socioeconomic status (SES) with diabetes. Methods The data came from the National Health and Nutrition Examination Survey (NHANES; N = 30,754, mean age = 47.4) using cross-sectional survey cycles from 2007 to 2008 through 2017-2020. Diabetes status was self-reported by physician diagnosis. Sociodemographic factors included racial and ethnic groups and SES. Weighted Poisson models were used to examine the association of racial and ethnic groups and SES with diabetes, stratified by age groups (20-44, 45-64, 65-79), sex, and racial and ethnic groups for SES, separately. Results Non-Hispanic Black, Hispanic, and other adults had a 47 %, 31 %, and 76 % higher prevalence of diabetes than non-Hispanic White adults, while adults from low and middle SES compared to high SES had a 37 % and 22 % higher prevalence of diabetes. Non-Hispanic Black, Hispanic, and other adults aged 45-64 years had a 45 %, 34 %, and 78 % higher prevalence of diabetes, and low and middle SES had a 57 % and 32 % higher prevalence of diabetes. Similar patterns were observed for adults aged 65-79. Males among non-Hispanic Black, Hispanic, and other adults and females from low and middle-SES families had a higher prevalence of diabetes. Conclusion Minority groups, middle and older-aged adults, males from minority groups, and females from low SES had a greater prevalence of diabetes. Effective interventions should prioritize tailoring efforts to specific minoritized and low SES groups to address diabetes disparities.
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Affiliation(s)
- Yangyang Deng
- Socio-Spatial Determinants of Health (SSDH) Laboratory, Population and Community Health Sciences Branch, Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA
| | - Mohammad Moniruzzaman
- Socio-Spatial Determinants of Health (SSDH) Laboratory, Population and Community Health Sciences Branch, Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA
| | - Breanna Rogers
- Socio-Spatial Determinants of Health (SSDH) Laboratory, Population and Community Health Sciences Branch, Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA
| | - Lu Hu
- Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA
| | - Ram Jagannathan
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Kosuke Tamura
- Socio-Spatial Determinants of Health (SSDH) Laboratory, Population and Community Health Sciences Branch, Division of Intramural Research, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA
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Kasa M, Rroji M, Spahia N, Gjana G, Elezi B. Clonidine to the Rescue: A Novel Approach to Refractory Diabetic Gastroparesis in the Postoperative Setting. Cureus 2025; 17:e79769. [PMID: 40161170 PMCID: PMC11954566 DOI: 10.7759/cureus.79769] [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: 02/27/2025] [Indexed: 04/02/2025] Open
Abstract
Gastroparesis is a recognized complication in patients with long-standing diabetes mellitus (DM), characterized by delayed gastric emptying without mechanical obstruction. Common symptoms include nausea, vomiting, bloating, and early satiety, all of which can significantly impair both quality of life and glycemic control. Standard therapies, such as prokinetic agents (e.g., metoclopramide and domperidone) and antiemetics (e.g., ondansetron), are commonly used but may fail in refractory cases, prompting an investigation into alternative treatments. Clonidine, an α2-adrenergic agonist traditionally prescribed for diabetic diarrhea, has demonstrated promise in managing autonomic dysfunction and thus may represent a novel option for gastroparesis management. This case report describes a 65-year-old man with type 2 DM and stage 3 chronic kidney disease (CKD), presumed secondary to diabetic nephropathy, retinopathy, and peripheral neuropathy. Following orthopedic surgery, he developed severe postoperative vomiting, leading to the discontinuation of his antihypertensive therapy. After two days without antihypertensive medications, a hypertensive crisis occurred (blood pressure, 210/120 mmHg), accompanied by an acute rise in serum creatinine to 5 mg/dL, oliguria, and generalized edema. The ongoing vomiting further contributed to dehydration and worsening acute renal dysfunction. Despite receiving continuous veno-venous hemodialysis (CVVHD) for 48 hours and antiemetic treatment with metoclopramide and ondansetron for one week, his nausea and vomiting persisted. Other etiologies were excluded, and a diagnosis of diabetic gastroparesis was established. Initiation of clonidine at a dose of 100 mcg twice daily produced marked symptom improvement within 48 hours, enabling the resumption of regular oral intake and stabilization of renal function. The patient was discharged in stable condition and remained asymptomatic at his six-month follow-up appointment. This case underscores the potential of clonidine as an adjunct treatment for patients with refractory diabetic gastroparesis, highlighting its impact on autonomic regulation and symptom alleviation. Further studies are warranted to substantiate its efficacy and safety in larger patient populations.
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Affiliation(s)
- Marsida Kasa
- Department of Internal Medicine, University Hospital of Trauma, Tirana, ALB
| | - Merita Rroji
- Department of Nephrology, University of Medicine, Tirana, ALB
| | - Nereida Spahia
- Department of Nephrology, University of Medicine, Tirana, ALB
| | - Grisilda Gjana
- Department of Internal Medicine, University Hospital of Trauma, Tirana, ALB
| | - Brunilda Elezi
- Faculty of Medical Technical Sciences, University Aleksander Xhuvani, Elbasan, ALB
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Sattaru K, Thipani Madhu M, Kumar Singh J, Kandi V, Gupta A, Ca J, Balaji O, Sridhar N, Talla V. A Comprehensive Review of the Effects of Diabetes Mellitus on the Gastrointestinal System. Cureus 2025; 17:e77845. [PMID: 39991373 PMCID: PMC11845257 DOI: 10.7759/cureus.77845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/22/2025] [Indexed: 02/25/2025] Open
Abstract
Diabetes mellitus (DM) is a worldwide epidemic, making it a major non-communicable disease of public health concern. DM is a chronic disease affecting various organs of the body, leading to increased morbidity and frequently causing patients to seek medical care. Patients with DM often suffer from gastrointestinal disturbances, indicating the involvement of the gastrointestinal system (GIS). Common effects on the gastrointestinal tract (GIT) include esophageal dysmotility, gastroesophageal reflux disease (GERD), non-alcoholic fatty liver disease (NAFLD), glycogenic hepatopathy, gastroparesis, and enteropathy. Despite the high rates of GIT complications associated with diabetes, they are often under-recognized by physicians, leading to suboptimal treatment and a poor quality of life for patients. This article reviews the GIT manifestations of DM from the esophagus to the anal canal, including their pathophysiology and current management strategies.
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Affiliation(s)
- Koushal Sattaru
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, IND
| | - Mansi Thipani Madhu
- Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, IND
| | - Janmejay Kumar Singh
- Medicine, Teerthanker Mahaveer Medical College and Research Centre, Moradabad, IND
| | - Venkataramana Kandi
- Clinical Microbiology, Prathima Institute of Medical Sciences, Karimnagar, IND
| | - Aastha Gupta
- Medicine, Maulana Azad Medical College, Delhi, IND
| | - Jayashankar Ca
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, IND
| | - Ojas Balaji
- Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, IND
| | - Nidhishri Sridhar
- Internal Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, IND
| | - Vennela Talla
- General Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, IND
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Esteves-Monteiro M, Ferreira-Duarte M, Vitorino-Oliveira C, Costa-Pires J, Oliveira S, Matafome P, Morato M, Dias-Pereira P, Costa VM, Duarte-Araújo M. Oxidative Stress and Histomorphometric Remodeling: Two Key Intestinal Features of Type 2 Diabetes in Goto-Kakizaki Rats. Int J Mol Sci 2024; 25:12115. [PMID: 39596183 PMCID: PMC11594829 DOI: 10.3390/ijms252212115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/30/2024] [Accepted: 11/01/2024] [Indexed: 11/28/2024] Open
Abstract
Gastrointestinal complications of diabetes are often overlooked, despite affecting up to 75% of patients. This study innovatively explores local glutathione levels and morphometric changes in the gut of Goto-Kakizaki (GK) rats, a type 2 diabetes animal model. Segments of the intestine, cecum, and colon were collected for histopathological analysis and glutathione quantification. A significant increase in the total thickness of the intestinal wall of GK rats was observed, particularly in the duodenum (1089.02 ± 39.19 vs. 864.19 ± 37.17 µm), ileum (726.29 ± 24.75 vs. 498.76 ± 16.86 µm), cecum (642.24 ± 34.15 vs. 500.97 ± 28.81 µm), and distal colon (1211.81 ± 51.32 vs. 831.71 ± 53.2 µm). Additionally, diabetic rats exhibited thickening of the muscular layers in all segments, except for the duodenum, which was also the only portion where the number of smooth muscle cells did not decrease. Moreover, myenteric neuronal density was lower in GK rats, suggesting neurological loss. Total glutathione levels were lower in all intestinal segments of diabetic rats (except duodenum), and the reduced/oxidized glutathione ratio (GSH/GSSG) was significantly decreased in GK rats, indicating increased oxidative stress. These findings strongly indicate that GK rats undergo significant intestinal remodeling, notable shifts in neuronal populations, and heightened oxidative stress-factors that likely contribute to the functional gastrointestinal alterations seen in diabetic patients.
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Affiliation(s)
- Marisa Esteves-Monteiro
- Associated Laboratory for Green Chemistry (LAQV) Network of Chemistry and Technology (REQUIMTE), University of Porto, 4050-313 Porto, Portugal (M.M.)
- Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Mariana Ferreira-Duarte
- Associated Laboratory for Green Chemistry (LAQV) Network of Chemistry and Technology (REQUIMTE), University of Porto, 4050-313 Porto, Portugal (M.M.)
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Cláudia Vitorino-Oliveira
- Institute for Health and Bioeconomy (i4HB), Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal (V.M.C.)
- Research Unit on Applied Molecular Biosciences (UCIBIO), FFUP, Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal
| | - José Costa-Pires
- Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
| | - Sara Oliveira
- Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra (UC), 3000-548 Coimbra, Portugal; (S.O.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), UC, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal
| | - Paulo Matafome
- Coimbra Institute for Clinical and Biomedical Research (iCBR) and Institute of Physiology, Faculty of Medicine, University of Coimbra (UC), 3000-548 Coimbra, Portugal; (S.O.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), UC, 3000-548 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal
- Coimbra Health School (ESTeSC), Polytechnic University of Coimbra, 3046-854 Coimbra, Portugal
| | - Manuela Morato
- Associated Laboratory for Green Chemistry (LAQV) Network of Chemistry and Technology (REQUIMTE), University of Porto, 4050-313 Porto, Portugal (M.M.)
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Patrícia Dias-Pereira
- Department of Pathology and Molecular Immunology, ICBAS-UP, 4050-313 Porto, Portugal;
| | - Vera Marisa Costa
- Institute for Health and Bioeconomy (i4HB), Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal (V.M.C.)
- Research Unit on Applied Molecular Biosciences (UCIBIO), FFUP, Laboratory of Toxicology, Department of Biological Sciences, FFUP, 4050-313 Porto, Portugal
| | - Margarida Duarte-Araújo
- Associated Laboratory for Green Chemistry (LAQV) Network of Chemistry and Technology (REQUIMTE), University of Porto, 4050-313 Porto, Portugal (M.M.)
- Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
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Karpuzcu HC, Turan Erdoğan B, Erdoğan Ç. The effect of adding pancreatin to standard otilinium bromide and simethicone treatment in type 2 diabetes mellitus patients with irritable bowel syndrome. Sci Rep 2024; 14:24661. [PMID: 39433866 PMCID: PMC11493971 DOI: 10.1038/s41598-024-74694-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 09/27/2024] [Indexed: 10/23/2024] Open
Abstract
This study aimed to assess the impact of adding pancreatin (a pancreatic enzyme derivative) to standard treatment on patients diagnosed with Irritable Bowel Syndrome (IBS) and Type 2 Diabetes Mellitus (T2DM). IBS and T2DM frequently coexist, leading to significant gastrointestinal symptoms and a decrease in quality of life. Gastrointestinal symptoms arising in T2DM patients present challenges in management for both clinicians and patients. Standard treatments may not fully address these symptoms. Recent studies suggest that pancreatic enzyme replacement therapy may offer additional benefits. This study investigates whether adding pancreatin to standard treatment can improve gastrointestinal outcomes in this patient population. Conducted as a prospective observational study, the research involved patients diagnosed with IBS according to Rome IV criteria and having concomitant T2DM. The patients were divided into two groups: one receiving standard dual treatment (otilinium bromide + simethicone) and the other receiving a triple therapy including a pancreatin derivative in addition to the standard treatment. Various clinical scores and measurements, including Visual Analog Scale (VAS), Bristol Stool Chart (BSC), Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS), and Irritable Bowel Syndrome Quality of Life Instrument (IBS-QOL), were assessed before and after treatment. The study comprised 121 patients, with a median age of 41 years (interquartile range [IQR] 38-48), of whom approximately 70.2% were female. Fifty-eight patients (47.9%) received dual therapy, while sixty-three patients (52.1%) received triple therapy. Before treatment, both groups exhibited similar pre-treatment Bristol stool scale results: normal (39.7% and 49.2%) and constipation (37.9% and 31.7%) in the dual and triple therapy subgroups, respectively (p > 0.05). Post-treatment, the triple therapy group showed a significantly higher proportion of normal cases on the Bristol stool scale (82.5%) compared to the dual therapy group (44.8%) (p < 0.001). After treatment, the triple therapy group demonstrated statistically significant improvements in VAS score (p < 0.001), IBS-SSS (p < 0.001), and IBS-QOL (p < 0.001) compared to the dual therapy group. There were no significant differences between groups in BMI, HbA1c levels, duration of diabetes, or diabetes treatment at baseline (p > 0.05 for all parameters). The findings suggest that adding pancreatin to standard therapies significantly enhanced the quality of life for patients with both IBS and T2DM, demonstrating improvements across various symptom measurements and indicating the potential benefits of this supplementary therapy in managing gastrointestinal symptoms in this population. Further studies are warranted to explore its broader clinical implications and mechanisms of action.
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Affiliation(s)
- Hulusi Can Karpuzcu
- Department of Gastroenterology, Ankara Etlik City Hospital, University of Health Sciences, Varlık Mahallesi, Halil Sezai Erkut Caddesi Yenimahalle, Ankara, Turkey.
| | - Beril Turan Erdoğan
- Department of Endocrinology and Metabolism, Ankara City Hospital, Ankara, Turkey
| | - Çağdaş Erdoğan
- Department of Gastroenterology, Ankara Etlik City Hospital, University of Health Sciences, Varlık Mahallesi, Halil Sezai Erkut Caddesi Yenimahalle, Ankara, Turkey
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Gimenes GM, Pereira JNB, Borges da Silva E, dos Santos AAC, Rodrigues TM, Santana GDO, Scervino MVM, Pithon-Curi TC, Hirabara SM, Gorjão R, Curi R. Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus. Cells 2024; 13:1626. [PMID: 39404390 PMCID: PMC11475219 DOI: 10.3390/cells13191626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 09/25/2024] [Accepted: 09/26/2024] [Indexed: 10/19/2024] Open
Abstract
Diabetes mellitus is associated with changes in intestinal morphology and the enteric nervous system. We previously reported constipation in Goto-Kakizaki (GK) rats, a non-obese model for type 2 diabetes mellitus. AIM The morpho-quantitative analysis of myenteric plexus neurons in the small and large intestines of 120-day-old male GK rats was investigated. METHODS The diabetes was confirmed by high fasting blood glucose levels. The myenteric plexus was evaluated through wholemount immunofluorescence. The morpho-quantitative analyses included evaluating neuronal density (neurons per ganglion) of the total neuronal population, the cholinergic and nitrergic subpopulations, and enteric glial cells per ganglion. The cell body area of 100 neurons per segment per animal was measured. RESULTS The total neurons and nitrergic subpopulation were unaltered in the GK rats' small and large intestines. The cholinergic subpopulation exhibited decreased density in the three segments of the small intestine and an increased number in the proximal colon of the GK rats. The number of enteric glial cells increased in the ileum of the GK rats, which could indicate enteric gliosis caused by the intestinal inflammatory state. The area of the cell body was increased in the total neuronal population of the jejunum and ileum of the GK rats. Frequency histograms of the cell body area distribution revealed the contribution of cholinergic neurons to larger areas in the jejunum and nitrergic neurons in the ileum. CONCLUSION The constipation previously reported in GK rats might be explained by the decrease in the density of cholinergic neurons in the small intestine of this animal model.
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Affiliation(s)
- Gabriela Mandú Gimenes
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | | | - Eliane Borges da Silva
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Alef Aragão Carneiro dos Santos
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Thais Martins Rodrigues
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Giovanna de Oliveira Santana
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Maria Vitoria Martins Scervino
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Tania Cristina Pithon-Curi
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Sandro Massao Hirabara
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Renata Gorjão
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
| | - Rui Curi
- Interdisciplinary Post-Graduate Program in Health Science, Institute of Physical Activity and Sports Sciences, Cruzeiro do Sul University, Rua Galvão Bueno, 868, Liberdade, São Paulo 01506-000, Brazil
- Butantan Institute, São Paulo 05585-000, Brazil
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Alshaikh AA, Alshehri AAA, Alshehri AZA, Alobaid AS, Mohammed AA, Saeed F Alshahrani T, Albarqi AZM, Sultan HSH, Alhussen M, Shehri ADA, Ghazy RM. Prevalence of gastrointestinal manifestations among diabetic patients in the Aseer region: A cross-sectional study. Medicine (Baltimore) 2024; 103:e39895. [PMID: 39331911 PMCID: PMC11441854 DOI: 10.1097/md.0000000000039895] [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: 08/10/2024] [Accepted: 09/11/2024] [Indexed: 09/29/2024] Open
Abstract
Diabetes mellitus (DM) has a systemic consequence, influencing many systems of the body, including metabolic functions. This study aimed to determine the prevalence of gastrointestinal complications among patients with type 2 DM in the Asser region of Saudi Arabia, identify sources of information, and investigate the association of these symptoms with disease duration and glycated hemoglobin. This cross-sectional study was conducted between November 13 and December 27, 2023. The questionnaire collected demographic data including age, sex, education, employment, income, and nationality, and 16 questions (5 points for each symptom) about the frequency of gastrointestinal symptoms in the past 3 months. The total score was 80, participants were categorized based on their total scores into 2 groups: those scoring 40 or below, and those scoring above 40. A total of 230 patients were included in this study, their median age was 32.0 (24.00) years, 60% were men, 63.9% were married, 38.7% earned between 5000 and 10,000 Saudi Riyal/month, 85.2% did not work in the medical field, 39.1% held university degrees, 54.8% did not have health insurance, 70.4% did not smoke, 35.7% worked in government jobs, 63% lived in urban areas, 95.2% were Saudi and 53.5% had only DM. More than half of the respondents, 57.4%, relied on doctors for information about DM. Dysmotility symptoms were common: dyspepsia affected 26.5% often and 5.7% always; early satiety impacted 24.3% often and 5.2% always; and bloating affected 28.3% often and 10.9% always. Constipation/diarrhea were a common complaint, with 23.5% of patients experiencing them often and an additional 4.8% reporting it always. Stool consistency also varied widely, with 21.7% experiencing lumpy or hardened stool. Health insurance status and having chronic diseases showed significant association with the severity of symptoms. Duration of diabetes and glycated hemoglobin were associated with the frequency of the symptoms. Gastrointestinal symptoms are common among diabetic patients in Aseer. The frequency of symptoms is associated with glycemic control, duration of diabetes, and health insurance status. These findings highlight the need for improved management and support for better gastrointestinal health in diabetes.
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Affiliation(s)
- Ayoub Ali Alshaikh
- Family & Community Medicine Department, College of Medicine, King Khalid University, Abha, Saudia Arabia
| | | | | | | | | | | | | | | | - Mohammed Alhussen
- Medical Colleague, College of Medicine, King Khalid University, Abha, Saudia Arabia
| | | | - Ramy Mohamed Ghazy
- Family & Community Medicine Department, College of Medicine, King Khalid University, Abha, Saudia Arabia
- Tropical Health Department, High Institute of Public Health, Alexandria University, Alexandria, Egypt
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8
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Nag S, Kar S, Mishra S, Stany B, Seelan A, Mohanto S, Haryini S S, Kamaraj C, Subramaniyan V. Unveiling Green Synthesis and Biomedical Theranostic paradigms of Selenium Nanoparticles (SeNPs) - A state-of-the-art comprehensive update. Int J Pharm 2024; 662:124535. [PMID: 39094922 DOI: 10.1016/j.ijpharm.2024.124535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 07/15/2024] [Accepted: 07/26/2024] [Indexed: 08/04/2024]
Abstract
The advancements in nanotechnology, pharmaceutical sciences, and healthcare are propelling the field of theranostics, which combines therapy and diagnostics, to new heights; emphasizing the emergence of selenium nanoparticles (SeNPs) as versatile theranostic agents. This comprehensive update offers a holistic perspective on recent developments in the synthesis and theranostic applications of SeNPs, underscoring their growing importance in nanotechnology and healthcare. SeNPs have shown significant potential in multiple domains, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antidiabetic, wound healing, and cytoprotective therapies. The review highlights the adaptability and biocompatibility of SeNPs, which are crucial for advanced disease detection, monitoring, and personalized treatment. Special emphasis is placed on advancements in green synthesis techniques, underscoring their eco-friendly and cost-effective benefits in biosensing, diagnostics, imaging and therapeutic applications. Additionally, the appraisal scrutinizes the progressive trends in smart stimuli-responsive SeNPs, conferring their role in innovative solutions for disease management and diagnostics. Despite their promising therapeutic and prophylactic potential, SeNPs also present several challenges, particularly regarding toxicity concerns. These challenges and their implications for clinical translation are thoroughly explored, providing a balanced view of the current state and prospects of SeNPs in theranostic applications.
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Affiliation(s)
- Sagnik Nag
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia.
| | - Shinjini Kar
- Department of Life Science and Biotechnology, Jadavpur University (JU), 188 Raja S.C. Mallick Road, Kolkata 700032, India; Department of Biotechnology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Shatakshi Mishra
- Department of Bio-Sciences, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; Department of Applied Microbiology, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - B Stany
- Department of Bio-Sciences, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; Department of Applied Microbiology, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Anmol Seelan
- Department of Biological Sciences, Sunandan Divatia School of Science, Narsee Monjee Institute of Management Studies (NMIMS), Pherozeshah Mehta Rd., Mumbai 400056, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka 575018, India
| | - Sree Haryini S
- Department of Bio-Sciences, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India; Department of Applied Microbiology, School of Bio-Sciences & Technology (SBST), Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Chinnaperumal Kamaraj
- Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology (SRMIST), Chennai, India; Interdisciplinary Institute of Indian System of Medicine, Directorate of Research, SRM Institute of Science and Technology, Chennai, India.
| | - Vetriselvan Subramaniyan
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500 Selangor, Darul Ehsan, Malaysia
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9
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Ju M, Deng T, Jia X, Gong M, Li Y, Liu F, Yin Y. The causal relationship between anti-diabetic drugs and gastrointestinal disorders: a drug-targeted mendelian randomization study. Diabetol Metab Syndr 2024; 16:141. [PMID: 38918852 PMCID: PMC11201305 DOI: 10.1186/s13098-024-01359-z] [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: 04/08/2024] [Accepted: 05/24/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND The incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs. METHODS We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn's disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control. RESULTS Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10- 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10- 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10- 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10- 2). CONCLUSIONS The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases.
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Affiliation(s)
- Mingyan Ju
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Tingting Deng
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xuemin Jia
- Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Menglin Gong
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yuying Li
- College of Acupuncture and moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Fanjie Liu
- Bone Biomechanics Engineering Laboratory of Shandong Province, Shandong Medicinal Biotechnology Center (School of Biomedical Sciences), Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
| | - Ying Yin
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
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10
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Abdalla MMI. Enteric neuropathy in diabetes: Implications for gastrointestinal function. World J Gastroenterol 2024; 30:2852-2865. [PMID: 38947292 PMCID: PMC11212710 DOI: 10.3748/wjg.v30.i22.2852] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 05/04/2024] [Accepted: 05/21/2024] [Indexed: 06/05/2024] Open
Abstract
Diabetes, commonly known for its metabolic effects, also critically affects the enteric nervous system (ENS), which is essential in regulating gastrointestinal (GI) motility, secretion, and absorption. The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions, such as gastroparesis and irregular bowel habits, primarily due to disruptions in the function of neuronal and glial cells within the ENS, as well as oxidative stress and inflammation. This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients. Additionally, it discusses the latest advances in diagnostic approaches, emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals. The editorial also reviews current and emerging therapeutic strategies, focusing on pharmacological treatments, dietary management, and potential neuromodulatory interventions. Ultimately, this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes, aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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11
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Bharadiya V, Rong Y, Zhang Z, Lin R, Guerrerio AL, Tse CM, Donowitz M, Singh V. Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment. Sci Rep 2024; 14:11911. [PMID: 38789719 PMCID: PMC11126659 DOI: 10.1038/s41598-024-62282-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 05/15/2024] [Indexed: 05/26/2024] Open
Abstract
Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.
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Affiliation(s)
- Vishwesh Bharadiya
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Yan Rong
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Zixin Zhang
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Ruxian Lin
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | | | - C Ming Tse
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Mark Donowitz
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
- Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Varsha Singh
- Divisions of Gastroenterology and Hepatology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
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12
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Hixon JC, Rivas Zarete JI, White J, Hilaire M, Muhammad A, Yusuf AP, Adu-Addai B, Yates CC, Mahavadi S. Epigenetic Modulation of GPER Expression in Gastric and Colonic Smooth Muscle of Male and Female Non-Obese Diabetic (NOD) Mice: Insights into H3K4me3 and H3K27ac Modifications. Int J Mol Sci 2024; 25:5260. [PMID: 38791299 PMCID: PMC11121689 DOI: 10.3390/ijms25105260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/04/2024] [Accepted: 05/10/2024] [Indexed: 05/26/2024] Open
Abstract
Type 1 diabetes (T1D) affects gastrointestinal (GI) motility, favoring gastroparesis, constipation, and fecal incontinence, which are more prevalent in women. The mechanisms are unknown. Given the G-protein-coupled estrogen receptor's (GPER) role in GI motility, we investigated sex-related diabetes-induced epigenetic changes in GPER. We assessed GPER mRNA and protein expression levels using qPCR and Western blot analyses, and quantified the changes in nuclear DNA methyltransferases and histone modifications (H3K4me3, H3Ac, and H3K27Ac) by ELISA kits. Targeted bisulfite and chromatin immunoprecipitation assays were used to evaluate DNA methylation and histone modifications around the GPER promoter by chromatin immunoprecipitation assays in gastric and colonic smooth muscle tissues of male and female control (CTR) and non-obese diabetic (NOD) mice. GPER expression was downregulated in NOD, with sex-dependent variations. In the gastric smooth muscle, not in colonic smooth muscle, downregulation coincided with differences in methylation ratios between regions 1 and 2 of the GPER promoter of NOD. DNA methylation was higher in NOD male colonic smooth muscle than in NOD females. H3K4me3 and H3ac enrichment decreased in NOD gastric smooth muscle. H3K4me3 levels diminished in the colonic smooth muscle of NOD. H3K27ac levels were unaffected, but enrichment decreased in NOD male gastric smooth muscle; however, it increased in the NOD male colonic smooth muscle and decreased in the female NOD colonic smooth muscle. Male NOD colonic smooth muscle exhibited decreased H3K27ac levels, not female, whereas female NOD colonic smooth muscle demonstrated diminished enrichment of H3ac at the GPER promoter, contrary to male NOD. Sex-specific epigenetic mechanisms contribute to T1D-mediated suppression of GPER expression in the GI tract. These insights advance our understanding of T1D complications and suggest promising avenues for targeted therapeutic interventions.
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MESH Headings
- Animals
- Female
- Male
- Mice
- Colon/metabolism
- Colon/pathology
- Diabetes Mellitus, Type 1/metabolism
- Diabetes Mellitus, Type 1/genetics
- DNA Methylation
- Epigenesis, Genetic
- Histones/metabolism
- Mice, Inbred NOD
- Muscle, Smooth/metabolism
- Promoter Regions, Genetic
- Receptors, Estrogen/metabolism
- Receptors, Estrogen/genetics
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism
- Stomach/pathology
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Affiliation(s)
- Juanita C. Hixon
- Center for Cancer Research, Department of Biology, Tuskegee University, Tuskegee, AL 36088, USA; (J.C.H.); (J.W.); (A.M.)
| | - Jatna I. Rivas Zarete
- Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, USA; (J.I.R.Z.); (B.A.-A.)
| | - Jason White
- Center for Cancer Research, Department of Biology, Tuskegee University, Tuskegee, AL 36088, USA; (J.C.H.); (J.W.); (A.M.)
| | - Mariline Hilaire
- Department of Environment & Nutrition Sciences, College of Agriculture, Tuskegee University, Tuskegee, AL 36088, USA;
| | - Aliyu Muhammad
- Center for Cancer Research, Department of Biology, Tuskegee University, Tuskegee, AL 36088, USA; (J.C.H.); (J.W.); (A.M.)
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, P.M.B. 1044, Zaria 810211, Kaduna State, Nigeria
| | - Abdurrahman Pharmacy Yusuf
- Department of Biochemistry, Federal University of Technology, P.M.B. 65, Minna 920101, Niger State, Nigeria;
| | - Benjamin Adu-Addai
- Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, USA; (J.I.R.Z.); (B.A.-A.)
| | - Clayton C. Yates
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21218, USA;
| | - Sunila Mahavadi
- Center for Cancer Research, Department of Biology, Tuskegee University, Tuskegee, AL 36088, USA; (J.C.H.); (J.W.); (A.M.)
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13
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Shehata M, Al Hosani I, Singh Y, Alali A, Khan S, Al Zaabi M, Khadam O, Alahmad M, Syed R, Al Tiniji K, Aljanahi A, Al Akrad E. Factors Associated With Delayed Gastric Emptying in Symptomatic Diabetic and Non-diabetic Patients: A Retrospective Observational Study. Cureus 2024; 16:e58038. [PMID: 38606023 PMCID: PMC11008549 DOI: 10.7759/cureus.58038] [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: 04/11/2024] [Indexed: 04/13/2024] Open
Abstract
Background Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a significant complication, especially in diabetic individuals. It manifests through symptoms such as abdominal bloating, feelings of fullness, and pain. This study investigates the prevalence of gastroparesis among non-diabetic and diabetic patients, exploring associations with demographic data, hemoglobin A1C (HbA1C) levels, and symptoms. Methodology This retrospective, observational, cohort study included patients with gastroparesis symptoms who underwent a nuclear gastric emptying study from January 2021 to April 2023. The study analyzed demographic data, symptoms, and HbA1c levels to identify correlations with delayed gastric emptying. Results Of 157 patients, 34.4% exhibited delayed gastric emptying. Diabetic patients comprised 29.3% of the sample, with a notable disease duration of over 10 years in 77.3% of cases. Symptoms such as nausea, vomiting, epigastric pain, and early satiety were prevalent, with significant associations between delayed emptying and female gender, higher HbA1c, and vomiting. Conclusions Delayed gastric emptying is significantly associated with female gender, elevated HbA1c levels, and when vomiting is the presenting symptom. Highlighting the importance of awareness among healthcare providers and the community, the findings encourage collaborative efforts for further gastroparesis research to better understand the predictive factors and mechanisms.
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Affiliation(s)
- Mostafa Shehata
- Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | | | - Yashbir Singh
- Department of Radiology, Mayo Clinic, Rochester, USA
| | - Ameirah Alali
- Gastroenterology and Hepatology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | - Shaima Khan
- Gastroenterology and Hepatology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | - Mohamed Al Zaabi
- Gastroenterology and Hepatology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | - Omar Khadam
- Internal Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | - Maryam Alahmad
- Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | - Rizwan Syed
- Radiology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | | | - Abdulla Aljanahi
- Internal Medicine, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
| | - Eyad Al Akrad
- Gastroenterology, Sheikh Shakhbout Medical City, Abu Dhabi, ARE
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14
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Muhammad A, Hixon JC, Pharmacy Yusuf A, Rivas Zarete JI, Johnson I, Miller J, Adu-Addai B, Yates C, Mahavadi S. Sex-specific epigenetics drive low GPER expression in gastrointestinal smooth muscles in type 2 diabetic mice. Sci Rep 2024; 14:5633. [PMID: 38453938 PMCID: PMC10920797 DOI: 10.1038/s41598-024-54213-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Accepted: 02/09/2024] [Indexed: 03/09/2024] Open
Abstract
Type 2 diabetes mellitus (T2D) causes gastroparesis, delayed intestinal transit, and constipation, for unknown reasons. Complications are predominant in women than men (particularly pregnant and postmenopausal women), suggesting a female hormone-mediated mechanism. Low G-protein coupled estrogen receptor (GPER) expression from epigenetic modifications may explain it. We explored sexually differentiated GPER expression and gastrointestinal symptoms related to GPER alterations in wild-type (WT) and T2D mice (db/db). We also created smooth muscle-specific GPER knockout (GPER KO) mice to phenotypically explore the effect of GPER deficiency on gastrointestinal motility. GPER mRNA and protein expression, DNA methylation and histone modifications were measured from stomach and colon samples of db/db and WT mice. Changes in gut motility were also evaluated as daily fecal pellet production patterns. We found that WT female tissues have the highest GPER mRNA and protein expressions. The expression is lowest in all db/db. GPER downregulation is associated with promoter hypermethylation and reduced enrichment of H3K4me3 and H3K27ac marks around the GPER promoter. We also observed sex-specific disparities in fecal pellet production patterns of the GPER KO mice compared to WT. We thus, conclude that T2D impairs gut GPER expression, and epigenetic sex-specific mechanisms matter in the downregulation.
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Affiliation(s)
- Aliyu Muhammad
- Department of Biology, Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA
- Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, P.M.B. 1044, Zaria, Kaduna State, Nigeria
| | - Juanita C Hixon
- Department of Biology, Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA
| | | | - Jatna I Rivas Zarete
- Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, 36088, USA
| | - India Johnson
- Department of Biology, Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA
| | - Jamial Miller
- Department of Biology, Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA
| | - Benjamin Adu-Addai
- Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL, 36088, USA
| | - Clayton Yates
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sunila Mahavadi
- Department of Biology, Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA.
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15
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Madyarov V, Kuzikeev M, Malgazhdarov M, Abzalbek Y, Ashimov G. A forecasting method of postoperative intestinal paralysis and its timely resolution. PRZEGLAD GASTROENTEROLOGICZNY 2023; 18:393-401. [PMID: 38572460 PMCID: PMC10985748 DOI: 10.5114/pg.2023.133063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 08/17/2022] [Indexed: 04/05/2024]
Abstract
Introduction The development of intestinal paresis after surgery in patients with acute surgical conditions complicated by peritonitis is an urgent problem of abdominal surgery. Aim To study the effectiveness of the developed methods, as well as to predict the risk of intestinal paresis, and establish the possibilities of correcting this condition in patients with acute surgical pathology complicated by peritonitis. Material and methods Twenty patients were examined, in whom the temperature parameters of the mucous membrane and skin of the cheek were measured, based on which the probability of developing paresis was predicted. Results The proposed method of thermometry of the mucous membrane and cheek skin made it possible to predict a high risk of intestinal paresis in 75% of patients and low risk in 25% of patients. It was shown that 80% of patients had a complete restoration of intestinal motility on the first day after the start of treatment. In 20% of cases, a partial improvement in the motor evacuation function of the intestine was observed on the first day, and full recovery was noted on the second day after the start of therapy. Conclusions The developed methods are highly effective and suitable for predicting and correcting intestinal paresis in patients with acute surgical conditions in the postoperative period.
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Affiliation(s)
- Valentin Madyarov
- Department of Surgeons with Anaesthesiology and Intensive Care, Kazakh-Russian Medical University, Almaty, Republic of Kazakhstan
| | - Marat Kuzikeev
- Department of Surgeons with Anaesthesiology and Intensive Care, Kazakh-Russian Medical University, Almaty, Republic of Kazakhstan
| | - Maulen Malgazhdarov
- Department of Surgeons with Anaesthesiology and Intensive Care, Kazakh-Russian Medical University, Almaty, Republic of Kazakhstan
| | - Yestay Abzalbek
- Department of Oncology, Central Clinical Hospital, Almaty, Republic of Kazakhstan
| | - Gulmamed Ashimov
- Surgical Department, Medical Centre Rahat, Almaty, Republic of Kazakhstan
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16
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Abdu Seid M, Diress M, Mohammed A, Sinamaw D. Chronic constipation and its associated factors in patients with type-2 diabetes: A multicenter cross-sectional study. Diabetes Res Clin Pract 2023; 204:110905. [PMID: 37757985 DOI: 10.1016/j.diabres.2023.110905] [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: 07/07/2023] [Revised: 09/04/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023]
Abstract
INTRODUCTION Diabetes is one of the global public health concern and constipation is frequently seen among gastrointestinal symptoms in diabetes. Despite the fact that constipation is common, doctors and/or patients disregard it. This study aimed to determine the prevalence and contributing factors of constipation in patients with diabetes. METHODS Multi-center cross-sectional study was carried out and the data was analyzed using STATA 14. Binary and multilevel logistic regressions were also carried out to identify associated to factors. Factors having a p-value of less than 0.05 were deemed statistically significant in the final model. RESULTS 206 diabetics participated in the survey. The mean age of the participants was 52.7 years (SD ± 11.9). The prevalence of constipation was 16% (95% CI: 10.97-21.07). Age (AOR = 13.56; 95% CI: 1.71, 107.21), females (AOR = 4.58; 95% CI: 1.76, 11.87), the duration of the diabetes (AOR = 3.16; 95% CI: 1.21, 8.24), and psychological distress (AOR = 12.49, 95% CI: 1.53, 101.8) were significant factors. CONCLUSION The magnitude of constipation was considerable, and it was linked to psychological distress, longer-lasting diabetes, being a woman, and ageing. Patients with type-2 diabetes need to receive careful treatment in order to reduce the severity of the condition and its additional complications.
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Affiliation(s)
- Mohammed Abdu Seid
- Department of Biomedical Sciences, College of Health Sciences, Debre Tabor University, Ethiopia.
| | | | | | - Deresse Sinamaw
- Department of Biomedical Science, Debre Markos University, Ethiopia.
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17
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Wei L, Ji L, Miao Y, Han X, Li Y, Wang Z, Fu J, Guo L, Su Y, Zhang Y. Constipation in DM are associated with both poor glycemic control and diabetic complications: Current status and future directions. Biomed Pharmacother 2023; 165:115202. [PMID: 37506579 DOI: 10.1016/j.biopha.2023.115202] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/15/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Constipation is a major complications of diabetes mellitus. With the accelerating prevalence of diabetes worldwide and an aging population, there is considerable research interest regarding the altered function and structure of the gastrointestinal tract in diabetic patients. Despite current advances in hyperglycemic treatment strategies, the specific pathogenesis of diabetic constipation remains unknown. Patients with constipation, may be reluctant to eat regularly, which may worsen glycemic control and thus worsen symptoms associated with underlying diabetic bowel disease. This paper presents a review of the complex relationship between diabetes and constipation, exploring the morphological alterations and biomechanical remodeling associated with intestinal motility dysfunction, as well as alterations in intestinal neurons, cellular signaling pathways, and oxidative stress. Further studies focusing on new targets that may play a role in the pathogenesis of diabetic constipation may, provide new ideas for the development of novel therapies to treat or even prevent diabetic constipation.
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Affiliation(s)
- Luge Wei
- Tianjin University of Traditional Chinese Medicine, China.
| | - Lanqi Ji
- Tianjin University of Traditional Chinese Medicine, China
| | - Yulu Miao
- Tianjin University of Traditional Chinese Medicine, China
| | - Xu Han
- Tianjin University of Traditional Chinese Medicine, China
| | - Ying Li
- Tianjin University of Traditional Chinese Medicine, China
| | - Zhe Wang
- Tianjin University of Traditional Chinese Medicine, China
| | - Jiafeng Fu
- Tianjin University of Traditional Chinese Medicine, China
| | - Liuli Guo
- Tianjin University of Traditional Chinese Medicine, China
| | - Yuanyuan Su
- Tianjin University of Traditional Chinese Medicine, China
| | - Yanjun Zhang
- Tianjin University of Traditional Chinese Medicine, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, China
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18
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Koyama K, Anno T, Takenouchi H, Kimura T, Kaku K, Kaneto H. Case Report: Repeated esophageal obstruction in a patient with type 3C diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1225385. [PMID: 37576980 PMCID: PMC10420082 DOI: 10.3389/fendo.2023.1225385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 07/10/2023] [Indexed: 08/15/2023] Open
Abstract
Although diabetic neuropathy is a well-known cause of gastrointestinal motility disorders, it is rare that diabetic neuropathy brings about esophageal obstruction. Here, we report a case with Type 3C diabetes mellitus (DM) lasting over 15 years and repeated esophageal obstruction resulting in chicken-meat-induced esophageal obstruction and candidiasis. This case highlights the importance of management of DM to prevent the development of complications such as diabetic neuropathy and associated symptoms.
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Affiliation(s)
- Katsumasa Koyama
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan
| | - Takatoshi Anno
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan
- Department of Diabetic Medicine, Kurashiki Central Hospital, Kurashiki, Japan
| | - Haruka Takenouchi
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan
| | - Tomohiko Kimura
- Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan
| | - Kohei Kaku
- Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan
| | - Hideaki Kaneto
- Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan
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19
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Amdanee N, Shao M, Hu X, Fang X, Zhou C, Chen J, Ridwan Chattun M, Wen L, Pan X, Zhang X, Xu Y. Serum Metabolic Profile in Schizophrenia Patients With Antipsychotic-Induced Constipation and Its relationship With Gut Microbiome. Schizophr Bull 2023; 49:646-658. [PMID: 36723169 PMCID: PMC10154739 DOI: 10.1093/schbul/sbac202] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND AND HYPOTHESIS Antipsychotics (APs), the cornerstone of schizophrenia treatment, confer a relatively high risk of constipation. However, the mechanisms underpinning AP-induced constipation are poorly understood. Thus, we hypothesized that (1) schizophrenia patients with AP-induced constipation have distinct metabolic patterns; (2) there is more than one mechanism at play in producing this adverse drug effect; and (3) AP-associated changes in the gut microbiome are related to the altered metabolic profiles. STUDY DESIGN Eighty-eight schizophrenia patients, including 44 with constipation (C) and 44 matched patients without constipation (NC), were enrolled in this study. Constipation was diagnosed by Rome IV criteria for constipation and colonic transit time using radiopaque markers (ROMs) while severity was evaluated with the Bristol Stool Form Scale (BSS) and Constipation Assessment Scale (CAS). Fasting blood samples were drawn from all participants and were subjected to non-targeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. STUDY RESULTS Eleven metabolites were significantly altered in AP-induced constipation which primarily disturbed sphingolipid metabolism, choline metabolism, and sphingolipid signaling pathway (P value < .05, FDR < 0.05). In the C group, changes in the gut bacteria showed a certain degree of correlation with 2 of the significantly altered serum metabolites and were associated with alterations in choline metabolism. CONCLUSIONS Our findings indicated that there were disturbances in distinct metabolic pathways that were associated with AP-induced constipation. In addition, this study presents evidence of a link between alterations in the gut microbiome and host metabolism which provides additional mechanistic insights on AP-induced constipation.
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Affiliation(s)
- Nousayhah Amdanee
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Miaomiao Shao
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xiuxiu Hu
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xinyu Fang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Zhou
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Jiu Chen
- Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Mohammad Ridwan Chattun
- Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Lu Wen
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xinming Pan
- Department of Psychiatry, The Second People’s Hospital of Jiangning District, Nanjing, Jiangsu, China
| | - Xiangrong Zhang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yue Xu
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
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Remenchik E, Mayo PR, Hobbs TM, Greytok JA, Foster EP, Zhao C, Ure D, Trepanier DJ, Foster RT. Effect of a High-Fat Meal on Single-Dose Rencofilstat (CRV431) Oral Bioavailability in Healthy Human Subjects. Clin Pharmacol Drug Dev 2023; 12:287-293. [PMID: 36251165 DOI: 10.1002/cpdd.1179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 09/12/2022] [Indexed: 11/08/2022]
Abstract
Rencofilstat (RCF) is a novel cyclophilin inhibitor under development for the treatment of nonalcoholic steatohepatitis and hepatocellular carcinoma. This phase 1, randomized, open-label study in healthy participants assessed the relative bioavailability of a single dose of RCF 225-mg soft gelatin capsules in both fasted and high-fat conditions. Forty-four participants were enrolled to either the fasted (n = 24) or the high-fat fed (n = 20) arm. Noncompartmental pharmacokinetics were evaluated following a single 225-mg oral dose. Administration of RCF with a high-fat meal led to increases in maximum concentration, area under the concentration-time curve (AUC) from time 0 to 24 hours, and AUC from time 0 to infinity fed-to-fasted geometric mean ratios of 102.2%, 114.5%, and 132.9%, respectively. All AUC geometric mean ratios were outside of the 80% to 125% range, suggesting that a high-fat meal can increase the extent of RCF exposure. Time to maximum concentration increased from 1.5 to 1.8 hours in the fasted and high-fat groups, respectively, suggesting slightly delayed absorption. High fat intake may delay gastric emptying while increasing the absorption and bioavailability of RCF. No treatment-emergent adverse events were observed in the fasted group, and 1 treatment-emergent adverse event occurred in the high-fat meal group. The differences in observed whole-blood concentrations are unlikely to have clinically relevant effects given the wide therapeutic index of RCF demonstrated in previous phase 1 studies.
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Affiliation(s)
| | | | | | | | | | | | - Daren Ure
- Hepion Pharmaceuticals, Edison, New Jersey, USA
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21
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Veličkov AI, Djordjević B, Lazarević M, Veličkov AV, Petrović V, Jović M, Denčić T, Radenković G. Distributions of Platelet-Derived Growth Factor Receptor-α Positive Cells and Interstitial Cells of Cajal in the Colon of Rats with Diabetes Mellitus Type 2. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020308. [PMID: 36837509 PMCID: PMC9964132 DOI: 10.3390/medicina59020308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/23/2023] [Accepted: 02/02/2023] [Indexed: 02/10/2023]
Abstract
Background and Objectives: Diabetic gastroenteropathy (DG) is a common complication of diabetes mellitus type 2. Interstitial cells are non-neural cells of mesenchymal origin inserted between nerve elements and smooth muscle cells, necessary for normal function and peristaltic contractions in the gastrointestinal (GI) tract. There are at least two types of interstitial cells within the GI muscle layer-interstitial cells of Cajal (ICC) and interstitial platelet-derived growth factor receptor α-positive cells (IPC). The mechanism of diabetic gastroenteropathy is unclear, and interstitial cells disorders caused by metabolic changes in diabetes mellitus (DM) could explain the symptoms of DG (slow intestinal transit, constipation, fecal incontinence). The aim of this study was to identify PDGFRα and c-kit immunoreactive cells in the colon of rats with streptozotocin-nicotinamide-induced diabetes mellitus type 2, as well as to determine their distribution in relation to smooth muscle cells and enteric nerve structures. Materials and Methods: Male Wistar rats were used, and diabetes type 2 was induced by an intraperitoneal injection of streptozotocin, immediately after intraperitoneal application of nicotinamide. The colon specimens were exposed to PDGFRα and anti-c-kit antibodies to investigate interstitial cells; enteric neurons and smooth muscle cells were immunohistochemically labeled with NF-M and desmin antibodies. Results: Significant loss of the intramuscular ICC, myenteric ICC, and loss of their connection in intramuscular linear arrays and around the ganglion of the myenteric plexus were observed with no changes in nerve fiber distribution in the colon of rats with diabetes mellitus type 2. IPC were rarely present within the colon muscle layer with densely distributed PDGFRα+ cells in the colon mucosa and submucosa of both experimental groups. In summary, a decrease in intramuscular ICC, discontinuities and breakdown of contacts between myenteric ICC without changes in IPC and nerve fibers distribution were observed in the colon of streptozotocin/nicotinamide-induced diabetes type 2 rats.
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Affiliation(s)
- Aleksandra Ivana Veličkov
- Department of Histology and Embryology, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
- Correspondence:
| | - Branka Djordjević
- Department of Biochemistry, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
| | - Milica Lazarević
- Department of Histology and Embryology, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
| | - Asen Veselin Veličkov
- Clinic for Orthopedic Surgery and Traumatology, University Clinical Centre Niš, 18000 Niš, Serbia
| | - Vladimir Petrović
- Department of Histology and Embryology, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
| | - Marko Jović
- Department of Histology and Embryology, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
| | - Tijana Denčić
- Department of Pathology, Faculty of Medicine, Clinical Centre Niš, University of Niš, 18000 Niš, Serbia
| | - Goran Radenković
- Department of Histology and Embryology, Faculty of Medicine, University of Niš, 18000 Niš, Serbia
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22
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Yuan S, Chen J, Ruan X, Sun Y, Zhang K, Wang X, Li X, Gill D, Burgess S, Giovannucci E, Larsson SC. Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis. eLife 2023; 12:e84051. [PMID: 36727839 PMCID: PMC10017103 DOI: 10.7554/elife.84051] [Citation(s) in RCA: 90] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 02/01/2023] [Indexed: 02/03/2023] Open
Abstract
Background Whether the positive associations of smoking and alcohol consumption with gastrointestinal diseases are causal is uncertain. We conducted this Mendelian randomization (MR) to comprehensively examine associations of smoking and alcohol consumption with common gastrointestinal diseases. Methods Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption. Results Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis, and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease, and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, and acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 20 associations persisted after adjusting for genetically predicted alcohol consumption. Genetically predicted higher alcohol consumption was associated with increased risk of duodenal ulcer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain statistically significant after adjustment for genetic predisposition to smoking initiation. Conclusions This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases. Funding The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.
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Affiliation(s)
- Shuai Yuan
- School of Public Health and The Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangChina
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska InstitutetStockholmSweden
| | - Jie Chen
- School of Public Health and The Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangChina
- Department of Gastroenterology, The Third Xiangya Hospital, Central South UniversityChangshaChina
| | - Xixian Ruan
- Department of Gastroenterology, The Third Xiangya Hospital, Central South UniversityChangshaChina
| | - Yuhao Sun
- School of Public Health and The Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangChina
| | - Ke Zhang
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake UniversityHangzhouChina
- Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and BiomedicineHangzhouChina
| | - Xiaoyan Wang
- Department of Gastroenterology, The Third Xiangya Hospital, Central South UniversityChangshaChina
| | - Xue Li
- School of Public Health and The Second Affiliated Hospital, Zhejiang University School of MedicineZhejiangChina
- Centre for Global Health Research, Usher Institute, University of EdinburghEdinburghUnited Kingdom
| | - Dipender Gill
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonLondonUnited Kingdom
| | - Stephen Burgess
- MRC Biostatistics Unit, University of CambridgeCambridgeUnited Kingdom
- Department of Public Health and Primary Care, University of CambridgeCambridgeUnited Kingdom
| | - Edward Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public HealthBostonUnited States
- Department of Nutrition, Harvard T.H. Chan School of Public HealthBostonUnited States
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska InstitutetStockholmSweden
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala UniversityUppsalaSweden
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Muacevic A, Adler JR. Acute Colonic Pseudo-Obstruction Secondary to Renal Calculus: A Case Report and Review of Pathophysiology. Cureus 2023; 15:e34756. [PMID: 36777972 PMCID: PMC9905947 DOI: 10.7759/cureus.34756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2023] [Indexed: 02/11/2023] Open
Abstract
Acute colonic pseudo-obstruction (ACPO) is obstruction of the large bowel without a mechanical cause. The exact mechanism remains incompletely understood but is thought to result from disruption to the autonomic regulation of the colon, typically in the context of hospitalized patients with medical illness, precipitating medications, or recent surgical intervention. This paper presents an unusual case of ACPO in an ambulatory patient with a recently passed renal calculus, explores the anatomy and physiology underlying the autonomic dysfunction theory of ACPO pathogenesis in the context of the case, and provides a 3D reconstruction of the patient's CT to illustrate the abrupt caliber change at the splenic flexure characteristic of ACPO.
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24
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Drewes AM, Brock C, Drewes AM. Autonomic Visceral Neuropathy and Gastrointestinal Disorders. THE DIABETES TEXTBOOK 2023:967-978. [DOI: 10.1007/978-3-031-25519-9_58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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25
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Neag MA, Craciun AE, Inceu AI, Burlacu DE, Craciun CI, Buzoianu AD. Short-Chain Fatty Acids as Bacterial Enterocytes and Therapeutic Target in Diabetes Mellitus Type 2. Biomedicines 2022; 11:72. [PMID: 36672580 PMCID: PMC9855839 DOI: 10.3390/biomedicines11010072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 12/10/2022] [Accepted: 12/23/2022] [Indexed: 12/29/2022] Open
Abstract
Diabetes mellitus is a disease with multiple gastrointestinal symptoms (diarrhea or constipation, abdominal pain, bloating) whose pathogenesis is multifactorial. The most important of these factors is the enteric nervous system, also known as the "second brain"; a part of the peripheral nervous system capable of functioning independently of the central nervous system. Modulation of the enteric nervous system can be done by short-chain fatty acids, which are bacterial metabolites of the intestinal microbiota. In addition, these acids provide multiple benefits in diabetes, particularly by stimulating glucagon-like peptide 1 and insulin secretion. However, it is not clear what type of nutraceuticals (probiotics, prebiotics, and alimentary supplements) can be used to increase the amount of short-chain fatty acids and achieve the beneficial effects in diabetes. Thus, even if several studies demonstrate that the gut microbiota modulates the activity of the ENS, and thus, may have a positive effect in diabetes, further studies are needed to underline this effect. This review outlines the most recent data regarding the involvement of SCFAs as a disease modifying agent in diabetes mellitus type 2. For an in-depth understanding of the modulation of gut dysbiosis with SCFAs in diabetes, we provide an overview of the interplay between gut microbiota and ENS.
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Affiliation(s)
- Maria-Adriana Neag
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Anca-Elena Craciun
- Department of Diabetes and Nutrition Diseases, Iuliu Hatieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Andreea-Ioana Inceu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Diana-Elena Burlacu
- Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - Cristian-Ioan Craciun
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
| | - Anca-Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
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Triglyceride-glucose index is associated with gastroesophageal reflux disease and erosive reflux disease: a health checkup cohort study. Sci Rep 2022; 12:20959. [PMID: 36470993 PMCID: PMC9722682 DOI: 10.1038/s41598-022-25536-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
The triglyceride-glucose (TyG) index was proposed as a useful marker of metabolic syndrome. Insulin resistance, the main mechanism underlying metabolic syndrome, is related to gastroesophageal reflux disease (GERD). This study aimed to elucidate the association between the TyG index and GERD/erosive reflux disease (ERD). We retrospectively reviewed the electronic medical records of patients who underwent gastroduodenoscopy at a checkup center. The calculation of TyG index used following formula: ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). We divided the patients into four groups according to the TyG index quartile (Q). We evaluated the relationship between the alteration of the TyG index and GERD in patients who received health checkups two times. Among the 52,605 enrolled patients, 3073 (5.8%) and 434 (0.8%) were diagnosed with GERD and ERD, respectively. The odds ratios (ORs) for GERD in the TyG index progressively increased across quartiles (P < 0.001): Q2 (OR = 2.477), Q3 (OR = 3.013), and Q4 (OR = 4.027) compared with Q1, which was used as a reference, respectively. Those for ERD also progressively increased across quartiles (P < 0.001): Q2 (OR = 4.264), Q3 (OR = 4.841), and Q4 (OR = 7.390) compared with Q1, respectively. Moreover, the degree of TyG index increase during the first and second tests in the GERD group was more prominent than in the control group (P = 0.001). In conclusion, the higher TyG index was significantly associated with GERD. The TyG index may be a novel predictive biomarker of GERD and ERD.
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H19 and TUG1 lncRNAs as Novel Biomarkers for Irritable Bowel Syndrome in Diabetic Patients. Biomedicines 2022; 10:biomedicines10112978. [PMID: 36428545 PMCID: PMC9687602 DOI: 10.3390/biomedicines10112978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 11/10/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction: Irritable bowel syndrome (IBS) is a gastrointestinal disorder due to enteric nervous system impairment that produces different patterns of digestion. IBS is a common finding in diabetic patients. The functions of lncRNAs in IBS are still not clear and need to be further investigated. The aim of this study was to assess the diagnostic roles of lncRNA H19 and TUG1 for IBS associated with diabetes and to evaluate their association with clinical and laboratory findings. Subjects and Methods: Samples from 42 diabetic patients, 42 diabetic patients with IBS, and 42 healthy controls were obtained. The LncRNA H19 and TUG1 expressions were measured by quantitative real-time PCR. Results: The patients with IBS had significantly lower levels of lncRNA H19 and TUG1 expression than the healthy controls and diabetic-only patients (p < 0.001). LncRNA H19 and TUG1 can discriminate between diabetic-only patients and those with IBS (areas under the ROC curves of 0.95 and 0.722, respectively). The TUG1 expression levels were significantly different among types of IBS (IBS-D lower than IBS-M and IBS-C lower than IBS-M; p = 0.0165 and p = 0.043, respectively). H19 and TUG1 were downregulated in patients with poor glycemic control. lncRNA H19 and TUG1 expression in diabetic patients with IBS significantly negatively correlated with the IBS severity scoring system. Both lncRNAs’ expression significantly predicted the disease severity. LncRNA H19 expression can be an independent predictor for disease severity (adjusted odds ratio = 0.00001, 95% CI = 0−0.5, p = 0.045). Conclusions: Diabetic patients with IBS had significantly lower levels of lncRNA H19 and TUG1 expression than healthy controls and diabetic-only patients. LncRNA H19 had better diagnostic performance criteria for IBS. LncRNA H19 expression can be an independent predictor for IBS severity.
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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] [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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29
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Esteves-Monteiro M, Menezes-Pinto D, Ferreira-Duarte M, Dias-Pereira P, Morato M, Duarte-Araújo M. Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats. Int J Mol Sci 2022; 23:13233. [PMID: 36362021 PMCID: PMC9656372 DOI: 10.3390/ijms232113233] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/19/2022] [Accepted: 10/27/2022] [Indexed: 10/15/2023] Open
Abstract
Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.
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Affiliation(s)
- Marisa Esteves-Monteiro
- LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
- Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Daniela Menezes-Pinto
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Mariana Ferreira-Duarte
- LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Patrícia Dias-Pereira
- Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
| | - Manuela Morato
- LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
- Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto (FFUP), 4050-313 Porto, Portugal
| | - Margarida Duarte-Araújo
- LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
- Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal
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Thakur V, Bashashati M, Enriquez J, Chattopadhyay M. Inhibiting Fatty Acid Amide Hydrolase Ameliorates Enteropathy in Diabetic Mice: A Cannabinoid 1 Receptor Mediated Mechanism. Vet Sci 2022; 9:vetsci9070364. [PMID: 35878381 PMCID: PMC9319435 DOI: 10.3390/vetsci9070364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 07/09/2022] [Accepted: 07/13/2022] [Indexed: 11/16/2022] Open
Abstract
Gastrointestinal (GI) dysmotility in diabetics exhibits fecal incontinence or constipation which affects patients’ quality of life. In this study, we aimed to understand the pattern of GI transit in type 1 diabetic (T1D) mice and whether inhibiting endocannabinoid degradation would exhibit therapeutic effect. Whole gut-transit time and fecal-pellet output were measured at 16 week post-diabetes. T1D mice treated with fatty acid amide hydrolase (FAAH) inhibitor URB597 showed reduced fecal output as well as improved gut transit time. Cannabinoid 1 receptor antagonist, AM251 blocked the effects of URB597, which may demonstrate that FAAH inhibitor is a potential remedial strategy for GI dysmotility.
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Affiliation(s)
- Vikram Thakur
- Center of Emphasis in Diabetes and Metabolism, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
| | - Mohammad Bashashati
- Division of Gastroenterology, Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
| | - Josue Enriquez
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
| | - Munmun Chattopadhyay
- Center of Emphasis in Diabetes and Metabolism, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
- Correspondence:
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31
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Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF Axis. Acta Biochim Biophys Sin (Shanghai) 2022; 54:999-1007. [PMID: 35880571 PMCID: PMC9828216 DOI: 10.3724/abbs.2022073] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Gastrointestinal (GI) complications of diabetes mellitus (DM) significantly impact on patients' quality of life. Enteric glial cells (EGC) are the key cell type of enteric nervous system (ENS), which contributes to the destruction of gut homeostasis in DM. Circular RNAs (circRNAs) are a novel type of RNAs abundant in the eukaryotic transcriptome, which form covalently closed continuous loops. In this study, the contribution of circRNAs to EGC damage in DM is investigated. Transcriptome sequencing analysis and functional study show that circVPS13A is significantly down-regulated in hyperglycemia-treated EGC, and circVPS13A overexpression attenuates EGC damage in both in vitro and in vivo DM models. In vitro mechanistic study using dual-luciferase reporter assay, affinity-isolation assay, fluorescence in situ hybridization (FISH) and immunostaining analysis identify that circVPS13A exerts its protective effect by sponging miR-182 and then up-regulates glial cell line-derived neurotrophic factor (GDNF) expression. In addition, in vivo study confirms that the circVPS13A-miR-182-GDNF network regulation can attenuate hyperglycemia-induced EGC damage of duodenum in streptozotocine (STZ)-induced DM mice. The findings of this study may provide novel insights into the protective role of circVPS13A in DM-associated EGC damage and clues for the development of new therapeutic approaches for the prevention of GI complications of DM.
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Wang Y, Xu X, Lin L. Prucalopride might improve intestinal motility by promoting the regeneration of the enteric nervous system in diabetic rats. Int J Mol Med 2022; 50:87. [PMID: 35543167 PMCID: PMC9162040 DOI: 10.3892/ijmm.2022.5143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 05/07/2021] [Indexed: 11/14/2022] Open
Abstract
The present study aimed to investigate whether prucalopride, as a 5-hydroxytryptamine 4 (5-HT4) receptor agonist, improved intestinal motility by promoting the regeneration of the enteric nervous system (ENS) in rats with diabetes mellitus (DM). A rat model of DM was established using an intraperitoneal injection of streptozotocin. The rats were randomly divided into four groups of 6 rats/group: Control, DM (DM model), DM + A (5 µg/kg prucalopride) and DM + B (10 µg/kg prucalopride). The rats in the Control group were given an equal volume of citric acid solvent. After successful model establishment, high blood glucose levels were maintained for 2 weeks before administration of prucalopride. The colonic transit time was measured using the glass bead discharge method. It was revealed that the colonic transit time of diabetic rats was the longest, and this was significantly shortened in the DM + B group. Subsequently, the colons were collected. The expression levels of Nestin, glial fibrillary acidic protein (GFAP), SOX10, RNA-binding protein human antigen D (HuD) and ubiquitin thiolesterase (PGP9.5) were determined via immunohistochemical analysis. Immunofluorescence double staining of 5-HT4 + Nestin and Ki67 + Nestin was performed. The 5-HT level was measured using ELISA. Compared with that in the control group, Nestin expression was significantly increased in the DM and DM + A groups, and it was concentrated in columnar epithelial cells and the mesenchyme. Furthermore, the expression levels of Nestin in the DM + A group were higher than those in the DM group. No difference was observed in the expression levels of Nestin between the DM + B group and the Control group. The expression levels of 5-HT protein were highest in the Control group; however, the expression levels of 5-HT protein in the DM group, DM + A group and DM + B group exhibited an increasing trend. Similar trends in the expression of 5-HT4 and Nestin were not observed; however, similar trends in the expression of Nestin and Ki67 were observed. The expression levels of GFAP, SOX10, PGP9.5 and Ki67 in the DM + A and DM + B groups were higher compared with those in the DM group. In the DM + A group, HuD expression was decreased compared with that in the Control group but it was markedly higher compared with that in the DM group. In conclusion, prucalopride may improve intestinal motility by promoting ENS regeneration in rats with DM.
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Affiliation(s)
- Yun Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Xinyu Xu
- Department of Spleen and Stomach Disease, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, Jiangsu 210014, P.R. China
| | - Lin Lin
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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33
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Syrine G, Mariem MK, Hend K, Imed L. Relationship Between Esophageal Motility Disorders and Autonomic Nervous System in Diabetic Patients: Pilot North African Study. Am J Mens Health 2022; 16:15579883221098588. [PMID: 35562861 PMCID: PMC9112418 DOI: 10.1177/15579883221098588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Little attention has been given to esophageal disorders in diabetes mellitus. Pathophysiology of esophageal motility disorders (EMD) in patients with diabetes mellitus is multifactorial. The aims of the present study were: (a) to evaluate the prevalence of EMD in patients with Type 2 diabetes mellitus and (b) to determine the relationship between EMD and autonomic neuropathy as assessed by heart rate variability (HRV). All the patients completed a questionnaire about diabetes characteristics and gastrointestinal symptoms. Conventional esophageal manometry was performed in all patients. HRV was measured in three different situations (Lying Position 1, standing position, and Lying Position 2). The temporal and frequency domain parameters were considered for analysis. The prevalence of EMD in our patients was 60.5% (n = 23). Low score physical activity was significantly more frequent in patients with EMD (p = .03). There was an increase in sympathetic activity represented by the low frequency (LF) parameter (p = .027) in the presence of EMD. Whereas parasympathetic modulation of heart rate represented by the high frequency (HF) parameter (p = .027) was declined in patients with EMD compared to those without. The LF/HF ratio was significantly higher (p = .002) in patients with EMD. EMD were prevalent in diabetes mellitus and were associated to autonomic nervous system dysfunction predominantly at the parasympathetic component.
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Affiliation(s)
- Gallas Syrine
- Research Laboratory, "Technologies et Imagerie Médicale" (LR12ES06), Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.,Department of Nervous System Exploration, Sahloul Hospital, Sousse, Tunisia
| | | | - Knaz Hend
- Research Laboratory, "Technologies et Imagerie Médicale" (LR12ES06), Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.,Department of Nervous System Exploration, Sahloul Hospital, Sousse, Tunisia
| | - Latiri Imed
- Laboratory of Physiology, Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia.,Research Laboratory, "Heart Failure" (LR12SP09), Farhat Hached University Hospital, Sousse, Tunisia
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34
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Rosenstock JL, Joab TMJ, DeVita MV, Yang Y, Sharma PD, Bijol V. Oxalate nephropathy: a review. Clin Kidney J 2022; 15:194-204. [PMID: 35145635 PMCID: PMC8825217 DOI: 10.1093/ckj/sfab145] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 07/21/2021] [Indexed: 01/13/2023] Open
Abstract
This review describes the clinical and pathological features of oxalate nephropathy (ON), defined as a syndrome of decreased renal function associated with deposition of calcium oxalate crystals in kidney tubules. We review the different causes of hyperoxaluria, including primary hyperoxaluria, enteric hyperoxaluria and ingestion-related hyperoxaluria. Recent case series of biopsy-proven ON are reviewed in detail, as well as the implications of these series. The possibility of antibiotic use predisposing to ON is discussed. Therapies for hyperoxaluria and ON are reviewed with an emphasis on newer treatments available and in development. Promising research avenues to explore in this area are discussed.
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Affiliation(s)
- Jordan L Rosenstock
- Division of Nephrology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA
| | - Tatyana M J Joab
- Division of Nephrology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA
| | - Maria V DeVita
- Division of Nephrology, Lenox Hill Hospital, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA
| | - Yihe Yang
- Department of Pathology, North Shore University Hospital and Long Island Jewish Medical Center, Donald and Barbara Zucker School of Medicine at Hostra/Northwell, New York, USA
| | - Purva D Sharma
- Division of Kidney Diseases and Hypertension, North Shore University Hospital and Long Island Jewish Medical Center, Donald and Barbara Zucker School of Medicine at Hostra/Northwell, New York, NY, USA
| | - Vanesa Bijol
- Department of Pathology, North Shore University Hospital and Long Island Jewish Medical Center, Donald and Barbara Zucker School of Medicine at Hostra/Northwell, New York, USA
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35
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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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36
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Chen Y, Zhang S, Li Y, Yan H, Ba Y, Wang X, Shi N, Liu C. Gastric Electrical Stimulation Increases the Proliferation of Interstitial Cells of Cajal and Alters the Enteric Nervous System in Diabetic Rats. Neuromodulation 2022; 25:1106-1114. [DOI: 10.1016/j.neurom.2021.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 09/14/2021] [Accepted: 09/20/2021] [Indexed: 11/26/2022]
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37
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Ambulkar R, Manampadi U, Bhosale S, Rana M, Agarwal V, Solanki SL. Pre-induction Ultrasonographic Evaluation of Gastric Residual Volume in Elective Gastrointestinal Cancer Surgeries. Indian J Surg Oncol 2021; 12:841-846. [PMID: 35110912 PMCID: PMC8764019 DOI: 10.1007/s13193-021-01456-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 09/28/2021] [Indexed: 02/07/2023] Open
Abstract
Pulmonary aspiration of gastric contents during elective surgery remains a major cause of airway-related mortality and morbidity. The preoperative fasting times for solids and liquids have been standardized across various anesthesia society guidelines. Enhanced Recovery After Surgery (ERAS) guidelines now advocate liberal clear fluid intake with carbohydrate loading up to 2 h preoperatively. The aim of the study was to assess whether practicing both ASA fasting guidelines and ERAS protocol makes the patients prone to a full stomach. The supine position standard curvilinear ultrasound probe (2-5 MHz) with Sonosite M-Turbo ©system was used to obtain the images. Gastric residual volume (GRV) was derived from the cross-sectional area (CSA) using the Perlas and colleagues model. A total of 102 patients were recruited and analyzed. The mean age and BMI were 50.65 years ± 13.35 years and 22.23 kg/m2 ± 3.7 kg/m2, respectively. A total of four patients (3.92%) had gastric volume > 1.5 ml/kg; out of these four patients, three were female and one was male. We did not observe any case of pulmonary aspiration in any of our patients. In conclusion, even though for elective surgeries, the current fasting guidelines are adequate, these findings cannot be extrapolated to patients with risk factors for high gastric residual volume where further studies need to be performed.
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Affiliation(s)
- Reshma Ambulkar
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, 2nd Floor Main Building, Dr E Borges Marg, Parel, Mumbai, India
| | - Unnathi Manampadi
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, 2nd Floor Main Building, Dr E Borges Marg, Parel, Mumbai, India
| | - Shilpushp Bhosale
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, 2nd Floor Main Building, Dr E Borges Marg, Parel, Mumbai, India
| | - Meenal Rana
- Department of Anesthesiology & Critical Care, Glenfield Hospital, Leicester, UK
| | - Vandana Agarwal
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, 2nd Floor Main Building, Dr E Borges Marg, Parel, Mumbai, India
| | - Sohan Lal Solanki
- Department of Anesthesiology, Critical Care and Pain, Tata Memorial Hospital, Homi Bhabha National Institute, 2nd Floor Main Building, Dr E Borges Marg, Parel, Mumbai, India
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Piccolo BD, Graham JL, Kang P, Randolph CE, Shankar K, Yeruva L, Fox R, Robeson MS, Moody B, LeRoith T, Stanhope KL, Adams SH, Havel PJ. Progression of diabetes is associated with changes in the ileal transcriptome and ileal-colon morphology in the UC Davis Type 2 Diabetes Mellitus rat. Physiol Rep 2021; 9:e15102. [PMID: 34806320 PMCID: PMC8606862 DOI: 10.14814/phy2.15102] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/15/2021] [Accepted: 10/18/2021] [Indexed: 12/12/2022] Open
Abstract
Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model. Male UCD-T2DM rats (age ~170 days) were included if <1-month (n = 6, D1M) or 3-month (n = 6, D3M) post-onset of diabetes. Younger nondiabetic UCD-T2DM rats were included as a nondiabetic comparison (n = 6, ND, age ~70 days). Ileum villi height/crypt depths and colon crypt depths were assessed by histology. Microbial abundance of colon content was measured with 16S rRNA sequencing. Ileum and colon transcriptional abundances were analyzed using RNA sequencing. Ileum villi height and crypt depth were greater in D3M rats compared to ND. Colon crypt depth was greatest in D3M rats compared to both ND and D1M rats. Colon abundances of Akkermansia and Muribaculaceae were lower in D3M rats relative to D1M, while Oscillospirales, Phascolarctobacterium, and an unidentified genus of Lachnospiraceae were higher. Only two transcripts were altered by diabetes advancement within the colon; however, 2039 ileal transcripts were altered. Only colonic abundances of Sptlc3, Enpp7, Slc7a15, and Kctd14 had more than twofold changes between D1M and D3M rats. The advancement of diabetes in the UCD-T2DM rat results in a trophic effect on the mucosal epithelia and was associated with regulation of gastrointestinal tract RNA expression, which appears more pronounced in the ileum relative to the colon.
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Affiliation(s)
- Brian D. Piccolo
- USDA‐ARS Arkansas Children's Nutrition CenterLittle RockArkansasUSA
- Department of PediatricsUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
| | - James L. Graham
- Department of Molecular BiosciencesSchool of Veterinary MedicineUniversity of California DavisDavisCaliforniaUSA
- Department of NutritionUniversity of California DavisDavisCaliforniaUSA
| | - Ping Kang
- USDA‐ARS Arkansas Children's Nutrition CenterLittle RockArkansasUSA
| | - Christopher E. Randolph
- Center for Translational Pediatric ResearchArkansas Children's Research InstituteLittle RockArkansasUSA
| | - Kartik Shankar
- Department of PediatricsSection of NutritionUniversity of Colorado School of MedicineAnschutz Medical CampusAuroraColoradoUSA
| | - Laxmi Yeruva
- USDA‐ARS Arkansas Children's Nutrition CenterLittle RockArkansasUSA
- Department of PediatricsUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
- Arkansas Children's Research InstituteLittle RockArkansasUSA
| | - Renee Fox
- USDA‐ARS Arkansas Children's Nutrition CenterLittle RockArkansasUSA
| | - Michael S. Robeson
- Department of Biomedical InformaticsUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
| | - Becky Moody
- USDA‐ARS Arkansas Children's Nutrition CenterLittle RockArkansasUSA
| | - Tanya LeRoith
- Department of Biomedical Science and PathobiologyVirginia Polytechnic Institute and State UniversityBlacksburgVirginiaUSA
| | - Kimber L. Stanhope
- Department of Molecular BiosciencesSchool of Veterinary MedicineUniversity of California DavisDavisCaliforniaUSA
- Department of NutritionUniversity of California DavisDavisCaliforniaUSA
| | - Sean H. Adams
- Department of SurgeryUniversity of California Davis School of MedicineSacramentoCaliforniaUSA
- Center for Alimentary and Metabolic ScienceUniversity of California Davis School of MedicineSacramentoCaliforniaUSA
| | - Peter J. Havel
- Department of Molecular BiosciencesSchool of Veterinary MedicineUniversity of California DavisDavisCaliforniaUSA
- Department of NutritionUniversity of California DavisDavisCaliforniaUSA
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Jiang Y, Rodgers B, Damiris K, Choi C, Ahlawat S. The effects of diabetes mellitus on clinical outcomes of hospitalized patients with acute diverticulitis. Eur J Gastroenterol Hepatol 2021; 33:1354-1360. [PMID: 32796358 DOI: 10.1097/meg.0000000000001895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Acute diverticulitis is a common gastrointestinal illness due to diverticular inflammation and focal necrosis. Diabetes mellitus has been reported to influence the outcomes of patients with diverticular disease. Our study aimed to examine the inpatient outcomes and complications of patients with acute diverticulitis and coexisting diabetes mellitus. METHODS The Nationwide Inpatient Sample was used to identify adult patients in 2014 admitted for acute diverticulitis. Primary outcomes were mortality, length of stay (LOS), and total hospitalization charges. Secondary outcomes were complications of acute diverticulitis and interventions. RESULTS In total, 44 330 of patients with acute diverticulitis and diabetes mellitus were included in the analysis. Acute diverticulitis patients with diabetes mellitus had a higher rate of diverticular bleeding (P < 0.0001), but lower rates of abscess (P < 0.0001), obstruction (P < 0.0001) and colectomy (P < 0.0001) when compared to acute diverticulitis patients without diabetes mellitus. Complicated diabetes mellitus was associated with a longer LOS (P = 0.00003) and greater total hospitalization charges (P = 0.0021) compared to uncomplicated diabetes mellitus when coexisting with acute diverticulitis. CONCLUSIONS Acute diverticulitis with diabetes mellitus is associated with a higher rate of diverticular bleeding, lower rates of abscess, obstruction, and colectomy compared to acute diverticulitis without diabetes mellitus. When coexisting with acute diverticulitis, complicated diabetes mellitus is not associated with higher rates of mortality or diverticulitis-related complications compared to uncomplicated diabetes mellitus.
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Affiliation(s)
| | | | | | | | - Sushil Ahlawat
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, New Jersey, USA
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40
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Çakmak G, Ganidağlı S, Efendioğlu EM, Öztürk E, Öztürk ZA. Do Long-Term Complications of Type 2 Diabetes Increase Susceptibility to Geriatric Syndromes in Older Adults? ACTA ACUST UNITED AC 2021; 57:medicina57090968. [PMID: 34577891 PMCID: PMC8466777 DOI: 10.3390/medicina57090968] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 08/30/2021] [Accepted: 09/13/2021] [Indexed: 11/16/2022]
Abstract
Background and Objectives: Type 2 diabetes is one of the common chronic diseases in the elderly. It is thought that long-term complications of type 2 diabetes will negatively affect the quality of life in elderly individuals. It is possible that geriatric syndromes, especially frailty syndrome, are associated with diabetic complications, too. In this study, we aimed to evaluate the effect of macrovascular and microvascular complications of type 2 diabetes on frailty and other geriatric syndromes. In addition, the effect of these complications on quality of life was also reviewed. Materials and Methods: We conducted a cross-sectional study for four months. Comprehensive geriatric assessment tests were done on all patients. The Fried frailty index (FFI) was used for the evaluation of frailty syndrome. We assessed malnutrition by mini nutritional assessment short-form (MNA-SF), and Global Leadership Initiative on Malnutrition criteria (GLIM). The EWGSOP 2 criteria were used for the diagnosis of sarcopenia. Quality of life (QoL) was evaluated using the short form-36 (SF-36) questionnaire. Data analysis was done by SPSS version 22. Results: 237 females and 142 males with a mean age of 71.7 ± 6.1 years were included in the study. The frequency of macrovascular and microvascular complications was 41.4% and 68.1%, respectively. Frailty was found to be associated with macrovascular complications (p = 0.003). Handgrip strength, skeletal muscle mass index, and gait speed were decreased in the presence of macrovascular complications (p = 0.043, p < 0.001, p < 0.001). QoL was also decreased in patients with macrovascular complications (p = 0.003). Nutritional status and handgrip strength were negatively affected in patients with diabetic neuropathy (p = 0.019, p = 0.014). Polypharmacy was also found to be associated with macrovascular complications (p < 0.001, p < 0.001). Macrovascular complications were 2.5 times more common in malnourished patients according to GLIM and 3.2 times more common in patients with decreased gait speed. Conclusion: In this study, we observed that both macrovascular and microvascular complications of diabetes increase susceptibility to geriatric syndromes in elderly individuals. It could be useful to conduct prospective studies in which we can compare the effectiveness of treatment methods on this subject.
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41
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Reed J, Bain S, Kanamarlapudi V. A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives. Diabetes Metab Syndr Obes 2021; 14:3567-3602. [PMID: 34413662 PMCID: PMC8369920 DOI: 10.2147/dmso.s319895] [Citation(s) in RCA: 164] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 07/09/2021] [Indexed: 12/13/2022] Open
Abstract
Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.
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Affiliation(s)
- Josh Reed
- Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UK
| | - Stephen Bain
- Institute of Life Science 1, Medical School, Swansea University, Swansea, SA2 8PP, UK
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Haffar S, Izzy M, Habib H, Sugihara T, Li DK, Sharma A, Wang Z, Murad MH, Watt KD, Bazerbachi F. Liver chemistries in glycogenic hepatopathy associated with type 1 diabetes mellitus: A systematic review and pooled analysis. Liver Int 2021; 41:1545-1555. [PMID: 33595181 DOI: 10.1111/liv.14827] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/07/2021] [Accepted: 02/08/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Glycogenic hepatopathy (GH) in type 1 diabetes-mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy-proven GH reports in T1DM patients to identify LC patterns. METHODS A systematic review identified reports of biopsy-proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST-to-ALT ratio, R-ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed. RESULTS A total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2 , median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate-to-severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis. CONCLUSION GH tends to have AST-predominant elevation with a median of 13 times the upper normal limit and R-ratio >2, which may distinguish it from other etiologies of AST-predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.
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Affiliation(s)
- Samir Haffar
- Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic
| | - Manhal Izzy
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University, Nashville, TN, USA
| | - Hany Habib
- Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic
| | - Takaaki Sugihara
- Division of Medicine and Clinical Science, Department of Gastroenterology and Nephrology, Tottori University, Tottori, Japan
| | - Darrick K Li
- Section of Digestive Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Ayush Sharma
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Zhen Wang
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA
| | - M Hassan Murad
- Evidence-Based Practice Center, Mayo Clinic, Rochester, MN, USA
| | - Kymberly D Watt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Fateh Bazerbachi
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Verma AK, Goyal Y, Bhatt D, Dev K, Alsahli MA, Rahmani AH, Almatroudi A. A Compendium of Perspectives on Diabetes: A Challenge for Sustainable Health in the Modern Era. Diabetes Metab Syndr Obes 2021; 14:2775-2787. [PMID: 34168477 PMCID: PMC8216699 DOI: 10.2147/dmso.s304751] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 03/23/2021] [Indexed: 12/13/2022] Open
Abstract
Diabetes is a chronic illness. Hyperglycemia is the characteristic of this disorder. Diabetes is a global crisis which affects the economy and health of all nations. Over the last decades, the number of individuals living with diabetes has significantly increased worldwide. Asia is a key epicenter of the emerging diabetes epidemic, with China and India the two nations having the highest number of diabetic people. Economic development, modernization, unhealthy diet, population aging, and sedentary lifestyles are the major factors responsible for the increasing diabetes epidemic. Diabetes is associated with several complications, and cardiovascular disease is the most important cause of morbidity and mortality among people with diabetes. These life-threatening problems can be prevented or delayed by proper management of diabetes. Lifestyle modification is an important factor to decrease the diabetes risk. The frequency of diabetic complications will rise if there is a lack of cost-effective and sustainable interventions. Hence, prevention of diabetes and its complications such as diabetic retinopathy and cardiovascular disease should be a crucial part of all future health-related public policies among all nations. This review summarizes current epidemiological aspects of diabetes in the world along with its complications, preventive measures, and treatment.
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Affiliation(s)
- Amit K Verma
- Department of Biotechnology, Jamia Millia Islamia, New Delhi, India
| | - Yamini Goyal
- Department of Biotechnology, Jamia Millia Islamia, New Delhi, India
| | - Deepti Bhatt
- Department of Biotechnology, Jamia Millia Islamia, New Delhi, India
| | - Kapil Dev
- Department of Biotechnology, Jamia Millia Islamia, New Delhi, India
| | - Mohammed A Alsahli
- Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Buraidah, 52571, Saudi Arabia
| | - Arshad Husain Rahmani
- Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Buraidah, 52571, Saudi Arabia
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Science, Qassim University, Buraidah, 52571, Saudi Arabia
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Kim Y, Kesar V, LeBel D. Unusual cause of colonic mucosal ulceration and gastrointestinal bleeding. Frontline Gastroenterol 2021; 13:269-270. [PMID: 35493629 PMCID: PMC8996096 DOI: 10.1136/flgastro-2021-101844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/09/2021] [Indexed: 02/04/2023] Open
Affiliation(s)
- Youseung Kim
- Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - Varun Kesar
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
| | - David LeBel
- Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA,Dominion Pathology Associates, Roanoke, Virginia, USA
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Erosive Esophagitis and Symptoms of Gastroesophageal Reflux Disease in Patients with Morbid Obesity with and without Type 2 Diabetes: a Cross-sectional Study. Obes Surg 2021; 30:2667-2675. [PMID: 32193740 DOI: 10.1007/s11695-020-04545-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Type 2 diabetes (T2DM) is associated with gastroesophageal reflux disease (GERD) in the general population, but the relationship between these conditions in candidates for bariatric surgery is uncertain. We compared the prevalence of GERD and the association between GERD symptoms and esophagitis among bariatric candidates with and without T2DM. METHODS Cross-sectional study of baseline data from the Oseberg study in Norway. Both groups underwent gastroduodenoscopy and completed validated questionnaires: Gastrointestinal Symptom Rating Scale and Gastroesophageal Reflux Disease Questionnaire. Participants with T2DM underwent 24-h pH-metry. RESULTS A total of 124 patients with T2DM, 81 women, mean (SD) age 48.6 (9.4) years and BMI 42.3 (5.5) kg/m2, and 64 patients without T2DM, 46 women, age 43.0 (11.0) years and BMI 43.0 (5.0) kg/m2, were included. The proportions of patients reporting GERD-symptoms were low (< 29%) and did not differ significantly between groups, while the proportions of patients with esophagitis were high both in the T2DM and non-T2DM group, 58% versus 47%, p = 0.16. The majority of patients with esophagitis did not have GERD-symptoms (68-80%). Further, 55% of the patients with T2DM had pathologic acid reflux. Among these, 71% also had erosive esophagitis, whereof 67% were asymptomatic. CONCLUSIONS The prevalence of GERD was similar in bariatric patients with or without T2DM, and the proportion of patients with asymptomatic GERD was high independent of the presence or absence of T2DM. Accordingly, GERD may be underdiagnosed in patients not undergoing a preoperative endoscopy or acid reflux assessment. TRIAL REGISTRATION Clinical Trials.gov number NCT01778738.
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Abstract
Diabetes is a complex disorder responsible for the mortality and morbidity of millions of individuals worldwide. Although many approaches have been used to understand and treat diabetes, the role of proteoglycans, in particular heparan sulfate proteoglycans (HSPGs), has only recently received attention. The HSPGs are heterogeneous, highly negatively charged, and are found in all cells primarily attached to the plasma membrane or present in the extracellular matrix (ECM). HSPGs are involved in development, cell migration, signal transduction, hemostasis, inflammation, and antiviral activity, and regulate cytokines, chemokines, growth factors, and enzymes. Hyperglycemia, accompanying diabetes, increases reactive oxygen species and upregulates the enzyme heparanase that degrades HSPGs or affects the synthesis of the HSPGs altering their structure. The modified HSPGs in the endothelium and ECM in the blood vessel wall contribute to the nephropathy, cardiovascular disease, and retinopathy seen in diabetes. Besides the blood vessel, other cells and tissues in the heart, kidney, and eye are affected by diabetes. Although not well understood, the adipose tissue, intestine, and brain also reveal HSPG changes associated with diabetes. Further, HSPGs are significantly involved in protecting the β cells of the pancreas from autoimmune destruction and could be a focus of prevention of type I diabetes. In some circumstances, HSPGs may contribute to the pathology of the disease. Understanding the role of HSPGs and how they are modified by diabetes may lead to new treatments as well as preventative measures to reduce the morbidity and mortality associated with this complex condition.
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Affiliation(s)
- Linda M Hiebert
- Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada
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Castro VMDD, Medeiros KCDP, Lemos LICD, Pedrosa LDFC, Ladd FVL, Carvalho TGD, Araújo Júnior RFD, Abreu BJ, Farias NBDS. S-methyl cysteine sulfoxide ameliorates duodenal morphological alterations in streptozotocin-induced diabetic rats. Tissue Cell 2021; 69:101483. [PMID: 33444959 DOI: 10.1016/j.tice.2020.101483] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 12/08/2020] [Accepted: 12/22/2020] [Indexed: 12/14/2022]
Abstract
Diabetes mellitus (DM) is a metabolic disease associated with several intestinal disorders. S-methyl cysteine sulfoxide (SMCS) is an amino acid present in Allium cepa L with hypoglycemic effects. However, the effects of SMCS on diabetic intestinal changes are unknown. Thus, we aimed to investigate the effects of SMCS on duodenal morphology and immunomodulatory markers in diabetic rats. Twenty-six rats were divided into three groups: control (C), diabetic (D) and diabetic +200 mg/kg SMCS (DSM). DM was induced by intraperitoneal injection of streptozotocin (50 mg/kg). After 30 days, duodenum samples were processed to assess histopathological and stereological alterations in volume, villus length, and immunohistochemical expression of NF-kB, IL-10, BCL-2, and caspase-3. SMCS reduced hyperglycemia and mitigated the increase in total reference volume of the duodenum, the absolute volume of the mucosa, and the length of the intestinal crypts in the DMS group when compared to D. IL-10 immunostaining was reduced in D when compared to C, while NF-kB was increased in D in comparison to the other groups. SMCS supplementation could decrease the NF-kB immunostaining observed in D. Positive staining for BCL-2 and caspase-3 were not statistically different between groups. In summary, SMCS decreased hyperglycemia and mitigated the morphological changes of the duodenum in diabetic animals, and these beneficial effects can be partially explained by NF-kB modulation.
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Affiliation(s)
| | | | | | | | | | | | | | - Bento João Abreu
- Department of Morphology, Federal University of Rio Grande do Norte, Natal, Brazil.
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The Prevalence of Enteropathy Symptoms from the Lower Gastrointestinal Tract and the Evaluation of Anorectal Function in Diabetes Mellitus Patients. J Clin Med 2021; 10:jcm10030415. [PMID: 33499216 PMCID: PMC7866006 DOI: 10.3390/jcm10030415] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/16/2021] [Accepted: 01/19/2021] [Indexed: 02/07/2023] Open
Abstract
Complications affecting the gastrointestinal tract often occur in the course of diabetes mellitus (DM). The aim of this study was to evaluate enteropathy symptoms and anorectal function using high-resolution anorectal manometry (HRAM). Fifty DM patients and 20 non-DM controls were enrolled into the study. Clinical data and laboratory tests were collected, physical examination and HRAM were performed. Symptoms in the lower gastrointestinal tract were reported by 72% of patients. DM patients with a long disease duration reported anal region discomfort (p = 0.028) and a sensation of incomplete evacuation (p = 0.036) more often than patients with shorter diabetes duration. Overall, DM patients had a lower maximal squeeze pressure (MSP) (p = 0.001) and a higher mean threshold of minimal rectal sensation (p < 0.01) than control subjects. They presented with enhanced features of dyssynergic defection than the control group. MSP and maximal resting pressure (MRP) were significantly lower in the group of long-term diabetes (p = 0.024; p = 0.026 respectively) than in patients with a short-term diabetes. The same observation was noted for patients with enteropathy symptoms that control for MSP (p < 0.01; p < 0.01; p = 0.03) and MRP (p < 0.001; p = 0.0036; p = 0.0046), respectively, for incontinence, constipation, and diarrhea. Symptoms in the lower gastrointestinal tract are often reported by DM patients. All DM patients have impaired function of the external anal sphincter and present enhanced features of dyssynergic defecation and also impaired visceral sensation. Patients with long-standing DM and patients with enteropathy symptoms have severely impaired function of both anal sphincters.
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The influence of diabetes on postoperative complications following colorectal surgery. Tech Coloproctol 2021; 25:267-278. [PMID: 33386511 PMCID: PMC7775741 DOI: 10.1007/s10151-020-02373-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 10/29/2020] [Indexed: 01/04/2023]
Abstract
Background Diabetes mellitus has been commonly associated with poor surgical outcomes. The aim of this meta-analysis was to assess the impact of diabetes on postoperative complications following colorectal surgery. Methods Medline, Embase and China National Knowledge Infrastructure electronic databases were reviewed from inception until May 9th 2020. Meta-analysis of proportions and comparative meta-analysis were conducted. Studies that involved patients with diabetes mellitus having colorectal surgery, with the inclusion of patients without a history of diabetes as a control, were selected. The outcomes measured were postoperative complications. Results Fifty-five studies with a total of 666,886 patients comprising 93,173 patients with diabetes and 573,713 patients without diabetes were included. Anastomotic leak (OR 2.407; 95% CI 1.837–3.155; p < 0.001), surgical site infections (OR 1.979; 95% CI 1.636–2.394; p < 0.001), urinary complications (OR 1.687; 95% CI 1.210–2.353; p = 0.002), and hospital readmissions (OR 1.406; 95% CI 1.349–1.466; p < 0.001) were found to be significantly higher amongst patients with diabetes following colorectal surgery. The incidence of septicemia, intra-abdominal infections, mechanical failure of wound healing comprising wound dehiscence and disruption, pulmonary complications, reoperation, and 30-day mortality were not significantly increased. Conclusions This meta-analysis and systematic review found a higher incidence of postoperative complications including anastomotic leaks and a higher re-admission rate. Risk profiling for diabetes prior to surgery and perioperative optimization for patients with diabetes is critical to improve surgical outcomes. Electronic supplementary material The online version of this article (10.1007/s10151-020-02373-9) contains supplementary material, which is available to authorized users.
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Nyavor Y, Brands CR, Nicholson J, Kuther S, Cox KK, May G, Miller C, Yasuda A, Potter F, Cady J, Heyman HM, Metz TO, Stark TD, Hofmann T, Balemba OB. Supernatants of intestinal luminal contents from mice fed high-fat diet impair intestinal motility by injuring enteric neurons and smooth muscle cells. Neurogastroenterol Motil 2021; 33:e13990. [PMID: 32969549 DOI: 10.1111/nmo.13990] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 08/12/2020] [Accepted: 08/25/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Damage to enteric neurons and impaired gastrointestinal muscle contractions cause motility disorders in 70% of diabetic patients. It is thought that enteric neuropathy and dysmotility occur before overt diabetes, but triggers of these abnormalities are not fully known. We tested the hypothesis that intestinal contents of mice with and without high-fat diet- (HFD-) induced diabetic conditions contain molecules that impair gastrointestinal movements by damaging neurons and disrupting muscle contractions. METHODS Small and large intestinal segments were collected from healthy, standard chow diet (SCD) fed mice. Filtrates of ileocecal contents (ileocecal supernatants; ICS) from HFD or SCD mice were perfused through them. Cultured intact intestinal muscularis externa preparations were used to determine whether ICS and their fractions obtained by solid-phase extraction (SPE) and SPE subfractions collected by high-performance liquid chromatography (HPLC) disrupt muscle contractions by injuring neurons and smooth muscle cells. KEY RESULTS ICS from HFD mice reduced intestinal motility, but those from SCD mice had no effect. ICS, aqueous SPE fractions and two out of twenty HPLC subfractions of aqueous SPE fractions from HFD mice blocked muscle contractions, caused a loss of nitrergic myenteric neurons through inflammation, and reduced smooth muscle excitability. Lipopolysaccharide and palmitate caused a loss of nitrergic myenteric neurons but did not affect muscle contractions. CONCLUSIONS & INFERENCES Unknown molecules in intestinal contents of HFD mice trigger enteric neuropathy and dysmotility. Further studies are required to identify the toxic molecules and their mechanisms of action.
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Affiliation(s)
- Yvonne Nyavor
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | | | - Jessica Nicholson
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Sydney Kuther
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Kortni K Cox
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - George May
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | | | - Allysha Yasuda
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Forrest Potter
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Joshua Cady
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Heino M Heyman
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Thomas O Metz
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Timo D Stark
- Lehrstuhl für Lebensmittelchemie und Molekulare Sensorik, Technische Universität München, Freising, Germany
| | - Thomas Hofmann
- Lehrstuhl für Lebensmittelchemie und Molekulare Sensorik, Technische Universität München, Freising, Germany
| | - Onesmo B Balemba
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
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