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Wakiya T, Sakuma Y, Onishi Y, Sanada Y, Okada N, Hirata Y, Horiuchi T, Omameuda T, Takadera K, Sata N. Liver resection volume-dependent pancreatic strain following living donor hepatectomy. Sci Rep 2024; 14:6753. [PMID: 38514681 PMCID: PMC10957952 DOI: 10.1038/s41598-024-57431-1] [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: 11/14/2023] [Accepted: 03/18/2024] [Indexed: 03/23/2024] Open
Abstract
The liver and pancreas work together to recover homeostasis after hepatectomy. This study aimed to investigate the effect of liver resection volume on the pancreas. We collected clinical data from 336 living liver donors. They were categorized into left lateral sectionectomy (LLS), left lobectomy, and right lobectomy (RL) groups. Serum pancreatic enzymes were compared among the groups. Serum amylase values peaked on postoperative day (POD) 1. Though they quickly returned to preoperative levels on POD 3, 46% of cases showed abnormal values on POD 7 in the RL group. Serum lipase levels were highest at POD 7. Lipase values increased 5.7-fold on POD 7 in the RL group and 82% of cases showed abnormal values. The RL group's lipase was twice that of the LLS group. A negative correlation existed between the remnant liver volume and amylase (r = - 0.326)/lipase (r = - 0.367) on POD 7. Furthermore, a significant correlation was observed between POD 7 serum bilirubin and amylase (r = 0.379)/lipase (r = 0.381) levels, indicating cooccurrence with liver and pancreatic strain. Pancreatic strain due to hepatectomy occurs in a resection/remnant liver volume-dependent manner. It would be beneficial to closely monitor pancreatic function in patients undergoing a major hepatectomy.
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Affiliation(s)
- Taiichi Wakiya
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
| | - Yasunaru Sakuma
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Yasuharu Onishi
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Yukihiro Sanada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Noriki Okada
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Yuta Hirata
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Toshio Horiuchi
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Takahiko Omameuda
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Kiichiro Takadera
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Naohiro Sata
- Division of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
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Hu R, Zeng GF, Fang Y, Nie L, Liang HL, Wang ZG, Yang H. Intravoxel incoherent motion diffusion-weighted imaging for evaluating the pancreatic perfusion in cirrhotic patients. Abdom Radiol (NY) 2024; 49:492-500. [PMID: 38052890 DOI: 10.1007/s00261-023-04063-0] [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: 04/17/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 12/07/2023]
Abstract
PURPOSE To assess the characteristics of pancreatic perfusion in normal pancreas versus cirrhotic patients using intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI). METHODS A total of 67 cirrhotic patients and 33 healthy subjects underwent IVIM on a 3.0 T MRI scanner. Diffusion coefficient (ADCslow), pseudo-diffusion coefficient (ADCfast), and perfusion fraction (f) were calculated based on the bi-exponential model. The pancreatic IVIM-derived parameters were then compared. In the cirrhotic group, the relationship was analyzed between IVIM-derived pancreatic parameters and different classes of hepatic function as determined by the Child-Pugh classification. Also, the pancreatic IVIM-derived parameters were compared among different classes of cirrhosis as determined by the Child-Pugh classification. RESULTS The f value of the pancreas in cirrhotic patients was significantly lower than that in normal subjects (p = 0.01). In the cirrhotic group, the f value of the pancreas decreased with the increase of the Child-Pugh classification (R = - 0.49, p = 0.00). The f value of the pancreas was significantly higher in Child-Pugh class A patients than in class B and C patients (p = 0.02, 0.00, respectively), whereas there was no significant difference between class B and C patients (p = 0.16). CONCLUSION The IVIM-derived perfusion-related parameter (f value) could be helpful for the evaluation of pancreatic perfusion in liver cirrhosis. Our data also suggest that the blood perfusion decrease in the pancreas is present in liver cirrhosis, and the pancreatic perfusion tends to decrease with the increasing severity of hepatic function. TRIAL REGISTRATION Trial registration number is 2021-ky-68 and date of registration for prospectively registered trials is February 23, 2022.
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Affiliation(s)
- Ran Hu
- Department of Radiology, Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, People's Republic of China
| | - Guo-Fei Zeng
- Department of Radiology, Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, People's Republic of China
| | - Yu Fang
- Department of Radiology, Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, People's Republic of China
| | - Lisha Nie
- GE Healthcare, MR Research China, Beijing, People's Republic of China
| | - Hui-Lou Liang
- GE Healthcare, MR Research China, Beijing, People's Republic of China
| | - Zhi-Gang Wang
- Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Yuzhong Distinct, Chongqing, 400010, People's Republic of China.
| | - Hua Yang
- Department of Radiology, Chongqing Hospital of Traditional Chinese Medicine, No.6, Panxi 7th Road, Jiangbei District, Chongqing, 400021, People's Republic of China.
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Kumar R, García-Compeán D, Maji T. Hepatogenous diabetes: Knowledge, evidence, and skepticism. World J Hepatol 2022; 14:1291-1306. [PMID: 36158904 PMCID: PMC9376767 DOI: 10.4254/wjh.v14.i7.1291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 04/27/2022] [Accepted: 07/05/2022] [Indexed: 02/06/2023] Open
Abstract
The diabetogenic potential of liver cirrhosis (LC) has been known for a long time, and the name "hepatogenous diabetes" (HD) was coined in 1906 to define the condition. Diabetes mellitus (DM) that develops as a consequence of LC is referred to as HD. In patients with LC, the prevalence rates of HD have been reported to vary from 21% to 57%. The pathophysiological basis of HD seems to involve insulin resistance (IR) and pancreatic β-cell dysfunction. The neurohormonal changes, endotoxemia, and chronic inflammation of LC initially create IR; however, the toxic effects eventually lead to β-cell dysfunction, which marks the transition from impaired glucose tolerance to HD. In addition, a number of factors, including sarcopenia, sarcopenic obesity, gut dysbiosis, and hyperammonemia, have recently been linked to impaired glucose metabolism in LC. DM is associated with complications and poor outcomes in patients with LC, although the individual impact of each type 2 DM and HD is unknown due to a lack of categorization of diabetes in most published research. In fact, there is much skepticism within scientific organizations over the recognition of HD as a separate disease and a consequence of LC. Currently, T2DM and HD are being treated in a similar manner although no standardized guidelines are available. The different pathophysiological basis of HD may have an impact on treatment options. This review article discusses the existence of HD as a distinct entity with high prevalence rates, a strong pathophysiological basis, clinical and therapeutic implications, as well as widespread skepticism and knowledge gaps.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India.
| | - Diego García-Compeán
- Department of Gastroenterology, University Hospital, Universidad Autónoma de Nuevo León, México, Monterrey 64700, México
| | - Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Dams OC, Vijver MAT, van Veldhuisen CL, Verdonk RC, Besselink MG, van Veldhuisen DJ. Heart Failure and Pancreas Exocrine Insufficiency: Pathophysiological Mechanisms and Clinical Point of View. J Clin Med 2022; 11:4128. [PMID: 35887892 PMCID: PMC9324511 DOI: 10.3390/jcm11144128] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Revised: 06/28/2022] [Accepted: 07/14/2022] [Indexed: 01/27/2023] Open
Abstract
Heart failure is associated with decreased tissue perfusion and increased venous congestion that may result in organ dysfunction. This dysfunction has been investigated extensively for many organs, but data regarding pancreatic (exocrine) dysfunction are scarce. In the present review we will discuss the available data on the mechanisms of pancreatic damage, how heart failure can lead to exocrine dysfunction, and its clinical consequences. We will show that heart failure causes significant impairment of pancreatic exocrine function, particularly in the elderly, which may exacerbate the clinical syndrome of heart failure. In addition, pancreatic exocrine insufficiency may lead to further deterioration of cardiovascular disease and heart failure, thus constituting a true vicious circle. We aim to provide insight into the pathophysiological mechanisms that constitute this reciprocal relation. Finally, novel treatment options for pancreatic dysfunction in heart failure are discussed.
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Affiliation(s)
- Olivier C. Dams
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.A.T.V.); (D.J.v.V.)
| | - Marlene A. T. Vijver
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.A.T.V.); (D.J.v.V.)
| | - Charlotte L. van Veldhuisen
- Department of Surgery, Amsterdam UMC, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; (C.L.v.V.); (M.G.B.)
- Amsterdam Gastroenterology Endocrinology Metabolism, 1100 DD Amsterdam, The Netherlands
| | - Robert C. Verdonk
- Department of Gastroenterology and Hepatology, St. Antonius Hospital, 3435 CM Nieuwegein, The Netherlands;
| | - Marc G. Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; (C.L.v.V.); (M.G.B.)
- Amsterdam Gastroenterology Endocrinology Metabolism, 1100 DD Amsterdam, The Netherlands
| | - Dirk J. van Veldhuisen
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.A.T.V.); (D.J.v.V.)
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5
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Todo Y, Miyake T, Furukawa S, Matsuura B, Ishihara T, Miyazaki M, Shiomi A, Nakaguchi H, Kanzaki S, Yamamoto Y, Koizumi Y, Yoshida O, Tokumoto Y, Hirooka M, Takeshita E, Kumagi T, Ikeda Y, Abe M, Iwata T, Hiasa Y. Combined evaluation of Fibrosis-4 index and fatty liver for stratifying the risk for diabetes mellitus. J Diabetes Investig 2022; 13:1577-1584. [PMID: 35437902 PMCID: PMC9434594 DOI: 10.1111/jdi.13812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/29/2022] [Accepted: 04/13/2022] [Indexed: 11/29/2022] Open
Abstract
Aims/Introduction To investigate whether the Fibrosis‐4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease. Materials and Methods Based on fatty liver disease and Fibrosis‐4 index (cut‐off value 1.3), we retrospectively divided 9,449 individuals, who underwent at least two annual health checkups, into four groups stratified by sex: normal; high Fibrosis‐4 index without fatty liver disease; low Fibrosis‐4 index with fatty liver disease; and high Fibrosis‐4 index with fatty liver disease. Results Onset rates for diabetes mellitus in the normal, high Fibrosis‐4 index without fatty liver disease, low Fibrosis‐4 index with fatty liver disease and high Fibrosis‐4 index with fatty liver disease groups were 1.6%, 4.3%, 6.8% and 10.2%, respectively, in men, and 0.6%, 0.9%, 5.3% and 7.0%, respectively, in women. Compared with the normal group, the high Fibrosis‐4 index without fatty liver disease, low Fibrosis‐4 index with fatty liver disease and high Fibrosis‐4 index with fatty liver disease groups were at a significant risk for diabetes mellitus onset in both male and female participants. Furthermore, in both sexes, high Fibrosis‐4 index with fatty liver disease remained a significant risk factor on multivariate analysis (high fibrosis‐4 index with fatty liver disease group: adjusted hazard ratio 4.03, 95% confidence interval 2.19–7.42 [men] and adjusted hazard ratio 6.40, 95% confidence interval 1.77–23.14 [women]). Conclusions Individuals with fatty liver disease and high Fibrosis‐4 index had a higher risk of diabetes mellitus onset. Therefore, Fibrosis‐4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease and identify patients requiring intervention.
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Affiliation(s)
- Yasuhiko Todo
- Department of Diabetes and Endocrinology, Uwajima City Hospital, Gotenmachi, Uwajima, Ehime, Japan
| | - Teruki Miyake
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Shinya Furukawa
- Health Services Center, Ehime University, Bunkyo, Matsuyama, Ehime, Japan
| | - Bunzo Matsuura
- Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Toru Ishihara
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.,Ehime General Health Care Association, Misake, Matsuyama, Ehime, Japan
| | - Masumi Miyazaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Akihito Shiomi
- Department of Diabetes and Endocrinology, Uwajima City Hospital, Gotenmachi, Uwajima, Ehime, Japan
| | - Hironobu Nakaguchi
- Health Services Center, Ehime University, Bunkyo, Matsuyama, Ehime, Japan
| | - Sayaka Kanzaki
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yasunori Yamamoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yohei Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Yoshio Tokumoto
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Eiji Takeshita
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Teru Kumagi
- Postgraduate Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan
| | - Yoshio Ikeda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Masanori Abe
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
| | - Takeru Iwata
- Ehime General Health Care Association, Misake, Matsuyama, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
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Disorders in blood circulation as a probable cause of death in dogs infected with Babesia canis. J Vet Res 2021; 65:277-285. [PMID: 34917839 PMCID: PMC8643085 DOI: 10.2478/jvetres-2021-0036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/16/2021] [Indexed: 11/21/2022] Open
Abstract
Introduction The purpose of the study was to investigate post-mortem changes in dogs infected with Babesia canis and to establish the probable cause of death of the affected animals. Material and Methods Cadavers of six dogs that did not survive babesiosis were collected. Necropsies were performed and samples of various organs were collected for histological examination. Results Necropsies and histological examinations revealed congestion and oedemata in various organs. Most of the dogs had ascites, hydrothorax or hydropericardium, pulmonary oedema, pulmonary, renal, hepatic, and cerebral congestion, and necrosis of cardiomyocytes. Conclusion These results suggested disorders in blood circulation as the most probable cause of death. However, the pulmonary inflammatory response and cerebral babesiosis observed in some of these dogs could also be considered possible causes of death. This study also showed a possible role for renal congestion in the development of renal hypoxia and azotaemia in canine babesiosis.
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Imamura Y, Kumagi T, Kuroda T, Koizumi M, Yoshida O, Kanemitsu K, Tada F, Tanaka Y, Hirooka M, Hiasa Y. Pancreas stiffness in liver cirrhosis is an indicator of insulin secretion caused by portal hypertension and pancreatic congestion. Hepatol Res 2021; 51:775-785. [PMID: 34018285 DOI: 10.1111/hepr.13672] [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: 03/03/2021] [Revised: 05/03/2021] [Accepted: 05/10/2021] [Indexed: 12/21/2022]
Abstract
AIM Portal hypertension induces pancreatic congestion and impaired insulin secretion in patients with liver cirrhosis (LC). However, its mechanism is unclear, with no established noninvasive imaging method for the evaluation of its pathogeneses. The present study focused on pancreas stiffness, as assessed by shear wave elastography (SWE), and examined its association with portal hypertension and insulin secretion. METHODS Shear wave elastography and contrast-enhanced ultrasonography were utilized to evaluate pancreas stiffness and congestion, respectively. A glucagon challenge test was used for insulin secretion assessment. Furthermore, rat models of carbon tetrachloride (CCl4 )-induced LC and portal hypertension were used to identify the direct effects of pancreatic congestion. Immunohistochemistry staining of the pancreas was carried out on human autopsy samples. RESULTS Pancreas stiffness measured by SWE was higher in patients with LC than in controls and showed significant correlation with pancreatic congestion. The glucagon challenge test indicated a lower value for the change in C-peptide immunoreactivity in the LC group, which was inversely correlated with pancreas stiffness and congestion. Additionally, portal hypertension and insulin secretion dysfunction were confirmed in CCl4 rat models. Autopsy of human samples revealed congestive and fibrotic changes in the pancreas and the relationship between insulin secretion and their factors in patients with LC. CONCLUSIONS In patients with LC, pancreas stiffness measured by SWE could be a potential noninvasive test for evaluating pancreatic congestion and fibrosis due to portal hypertension. Moreover, it was associated with impaired insulin secretion, and could aid in guiding the treatment for hepatogenous diabetes.
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Affiliation(s)
- Yoshiki Imamura
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Teru Kumagi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.,Postgraduate Medical Education Center, Ehime University Hospital, Ehime, Japan
| | - Taira Kuroda
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Mitsuhito Koizumi
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Osamu Yoshida
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Kozue Kanemitsu
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Fujimasa Tada
- Department of Internal Medicine, Saiseikai Matsuyama Hospital, Ehime, Japan
| | - Yoshinori Tanaka
- Department of Gastroenterology, Matsuyama Shimin Hospital, Ehime, Japan
| | - Masashi Hirooka
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
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8
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The extracellular volume fraction of the pancreas measured by dual-energy computed tomography: The association with impaired glucose tolerance. Eur J Radiol 2021; 141:109775. [PMID: 34020172 DOI: 10.1016/j.ejrad.2021.109775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 04/29/2021] [Accepted: 05/07/2021] [Indexed: 11/21/2022]
Abstract
PURPOSE To investigate the clinical value of measuring the ECV fraction of the pancreas by DECT in association with an impaired glucose tolerance (IGT) estimated by the hemoglobin A1C (HbA1C) value in patients with or without cirrhosis. MATERIALS AND METHODS This retrospective study included patients who underwent contrast-enhanced dynamic CT with dual-energy mode between March 2018 and February 2019. The ECV fraction of the pancreas was calculated from iodine map images created from equilibrium-phase contrast-enhanced DECT images. The cross-sectional areas of the pancreas were also measured. RESULTS In total, 51 patients were analyzed (median age, 69 years old; 22 women). The ECV fraction of the pancreas showed a significant negative correlation with the HbA1c value in the cirrhotic group (ρ=-0.346, p = 0.048), while there was no significant correlation in the non-cirrhotic group (ρ=-0.086, p = 0.734). In the elevated HbA1C group, the ECV fraction of the pancreas in the cirrhotic patients (median, 0.247; interquartile range [IQR], 0.098) was significantly lower than that in the non-cirrhotic patients (0.332, IQR 0.113) (p = 0.024). In the elevated HbA1C group, the cross-sectional area of the pancreas was significantly larger in the cirrhotic patients than that in the non-cirrhotic patients (median [IQR]; 2945 [904] vs. 1885 [909] mm2, p = 0.019). CONCLUSION A reduction in the ECV fraction of the pancreas measured by DECT as well as the enlargement of the pancreatic parenchyma was observed in cirrhotic patients with IGT. These findings suggest that the measurement of the pancreatic ECV fraction by DECT may help clarify the pathophysiology of IGT in patients with cirrhosis.
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9
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Cirrhosis and insulin resistance: current knowledge, pathophysiological mechanisms, complications and potential treatments. Clin Sci (Lond) 2020; 134:2117-2135. [PMID: 32820802 DOI: 10.1042/cs20200022] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 07/17/2020] [Accepted: 07/31/2020] [Indexed: 12/12/2022]
Abstract
End-stage chronic liver diseases are often associated with insulin resistance (IR) and diabetes mellitus (DM). Indeed, to quantify insulin sensitivity the euglycemic clamp technique was utilized, allowing the following to be stated: in small groups of patients, an IR in almost all cirrhotic patients can be observed, compared with a control group. Additionally, it has been demonstrated that IR in cirrhosis is linked to a decreased peripheral (muscle) glucose uptake rather than an increased liver glucose production. The homoeostasis model of IR (HOMA-IR) technique, devised only later, was then exploited to assess this same phenomenon in a larger sample population. The research established that even in patients with preserved liver function, cirrhosis is associated with significant alterations in glucose homoeostasis levels. The purpose of the present paper is to present the current research around the affiliation of cirrhosis and IR, discuss potential mechanisms explaining the association between cirrhosis and IR (i.e. endocrine perturbation, liver inflammation, altered muscle mass and composition, altered gut microbiota and permeability), complications that can arise as well as treatment options, through a critical review of the literature surrounding this subject. This research will also be investigating the beneficial impact, if there is any, of identifying and curing IR in patients with cirrhosis.
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10
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Wang N, Wang Y, Zhang W, Chen Y, Chen X, Wang C, Li Q, Chen C, Jiang B, Lu Y. C-peptide is associated with NAFLD inflammatory and fibrotic progression in type 2 diabetes. Diabetes Metab Res Rev 2020; 36:e3210. [PMID: 31351021 DOI: 10.1002/dmrr.3210] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 07/22/2019] [Accepted: 07/23/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND A higher prevalence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis was observed in type 2 diabetes. We aim to investigate whether C-peptide is associated with nonalcoholic fatty liver disease (NAFLD) progression in type 2 diabetic adults. METHODS A total of 4937 diabetic participants were enrolled from China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable NASH by the concurrent presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. RESULTS Individuals with a longer history of type 2 diabetes had a lower C-peptide level and a lower prevalence of probable NASH but a higher prevalence of advanced fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with odds ratios (ORs) of 4.55 [95% confidence interval (CI) 3.16, 6.55] and 5.28 (95% CI 3.94, 7.09), respectively, comparing quartile 4 with quartile 1 (both p for trend <0.001). However, C-peptide quartiles were negatively associated with the probable presence of advanced fibrosis (Q4 vs. Q1, OR 0.59, 95% CI 0.36, 0.97, p for trend <0.05). A 1-SD increment of ln(C-peptide) was also significantly associated with inflammatory and fibrotic progression (OR 1.34, 95% CI 1.27, 1.41; OR 0.88, 95% CI 0.79, 0.98, respectively). CONCLUSIONS Significant but opposite associations between C-peptide and inflammatory and fibrotic progression of NAFLD were observed. Understanding islet hormone changes during type 2 diabetes and differentiating the stage of NAFLD may help to personalize treatment strategies for NAFLD patients with type 2 diabetes.
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Affiliation(s)
- Ningjian Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuying Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen Zhang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoman Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chiyu Wang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Li
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chi Chen
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Boren Jiang
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yingli Lu
- Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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11
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Bianucci R, Abenavoli L, Charlier P, Lippi D, Appenzeller O, Perciaccante A. A great legal scholar of the 18th century with liver cirrhosis and septicemia. Med Hypotheses 2019; 127:88-89. [PMID: 31088655 DOI: 10.1016/j.mehy.2019.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 03/28/2019] [Accepted: 04/08/2019] [Indexed: 11/30/2022]
Affiliation(s)
- R Bianucci
- Legal Medicine Section, Department of Public Health and Paediatric Sciences, University of Turin, Italy; Warwick Medical School, Microbiology and Infection Division, University of Warwick, United Kingdom; UMR 7268, Laboratoire d'Anthropologie bio-culturelle, Droit, Etique & Santé (Adés), Faculté de Médecine de Marseille, France.
| | - L Abenavoli
- Department of Health Sciences, University Magna Graecia of Catanzaro, Italy
| | - P Charlier
- Section of Medical and Forensic Anthropology (UVSQ DANTE Laboratory EA 4498), Montigny-Le-Bretonneux, France; Direction Département de la Recherche et de l'Enseignement Musée du Quai Branly - Jacques Chirac, Paris, France
| | - D Lippi
- Department of Experimental and Clinical Medicine, University of Florence, Italy
| | - O Appenzeller
- New Mexico Health Enhancement and Marathon Clinics Research Foundation, 361 Big Horn Ridge Dr. NE, Albuquerque, NM, USA; New Mexico Museum of Natural History and Science, 1801 Mountain Road NW. Albuquerque, NM, USA
| | - A Perciaccante
- Department of Medicine, San Giovanni di Dio Hospital, Gorizia, Italy
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12
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Jansson L, Carlsson PO. Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans. Compr Physiol 2019; 9:799-837. [PMID: 30892693 DOI: 10.1002/cphy.c160050] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5- to 10-fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo-acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799-837, 2019.
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Affiliation(s)
- Leif Jansson
- Uppsala University, Department of Medical Cell Biology, Uppsala, Sweden
| | - Per-Ola Carlsson
- Uppsala University, Department of Medical Cell Biology, Uppsala, Sweden.,Uppsala University, Department of Medical Sciences, Uppsala, Sweden
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13
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Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats. Chin J Integr Med 2017; 24:661-669. [PMID: 29209957 DOI: 10.1007/s11655-017-2773-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/11/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the preventive effect of salvianolate (Sal B) on glucose metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats. METHODS Fifty-five Wistar rats were randomly divided into a control group (n=10) and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups (n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B (50 mg/kg), metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline (HYP) and liver function were detected at the end of the treatment. Area under the curve (AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining (HE), Sirius Red staining and Masson's trichrome staining, respectively. Hepatic expression of α-smooth muscle actin (α-SMA) and collagen (Col I) were evaluated by immunohistochemical staining. RESULTS Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently than Sal B (P<0.05). CONCLUSIONS Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.
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Maruyama H, Kobayashi K, Kiyono S, Yokosuka O. Interrelationship between insulin resistance and portal haemodynamic abnormality in cirrhosis. Int J Med Sci 2017; 14:240-245. [PMID: 28367084 PMCID: PMC5370286 DOI: 10.7150/ijms.17738] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 12/28/2016] [Indexed: 01/16/2023] Open
Abstract
Background: There are only limited data regarding the effect of impaired portal circulation on the glucose metabolism. The study prospectively examined the interrelationship between insulin resistance (IR) and portal haemodynamic abnormality in cirrhosis. Methods: There were 53 cirrhosis patients (61.6 ± 13.0 years) all presenting gastroesophageal varices. Portal haemodynamics by both hepatic venous catheterisation and Doppler ultrasound were examined with respect to the homeostasis model assessment (HOMA)-IR and HOMA2-IR. The IR was defined by HOMA-IR > 3.0 or HOMA2-IR > 2.0. Results: Forty-two patients (79.2%) had collateral vessels, 38 with left gastric vein, 12 with short/posterior gastric vein, 9 with splenorenal shunt, and 3 with inferior mesenteric vein. Multivariate analysis provided significant factors; wedged hepatic venous pressure (HR1.183, 95% CI 1.012-1.383, p=0.035) for HOMA-IR > 3.0, body mass index for HOMA2-IR > 2.0 (HR1.490, 95% CI 1.176-1.888, p=0.001), and collateral flow volume for both HOMA-IR > 3.0 (HR1.007, 95% CI 1.001-1.014, p=0.015) and HOMA2-IR > 2.0 (HR 1.007, 95% CI 1.002-1.013, p=0.009). The best cut-off value of collateral flow volume was 165 ml/min for detecting the HOMA-IR > 3.0 showing area under the receiver operating characteristic curve (AUROC) 0.688 (Odds ratio, 5.33) with sensitivity 70% and specificity 69.6%, and was 165 ml/min for detecting median value of HOMA2-IR > 2.0 showing AUROC 0.698 (odds ratio, 5.7) with sensitivity 75% and specificity 65.5%. Conclusion: There is a close linkage between the IR and impaired portal haemodynamics presented by the collateral development, suggesting the underlying pathogenesis of portal hypertension in cirrhosis patients.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Kazufumi Kobayashi
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Soichiro Kiyono
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
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Maruyama H, Shiha G, Yokosuka O, Kumar A, Sharma BC, Ibrahim A, Saraswat V, Lesmana CRA, Omata M. Non-invasive assessment of portal hypertension and liver fibrosis using contrast-enhanced ultrasonography. Hepatol Int 2016; 10:267-276. [PMID: 26696585 DOI: 10.1007/s12072-015-9670-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 09/10/2015] [Indexed: 12/11/2022]
Abstract
Portal hypertension and hepatic fibrosis are key pathophysiologies with major manifestations in cirrhosis. Although the degree of portal pressure and hepatic fibrosis are pivotal parameters, both are determined using invasive procedures. Ultrasound (US) is a simple and non-invasive technique that is available for use worldwide in the abdominal field. Because of its safety and easy of use, contrast-enhanced US is one of the most frequently used tools in the management of liver tumors for the detection and characterization of lesions, assessment of malignancy grade, and evaluation of therapeutic effects. This wide range of applications drives the practical use of contrast-enhanced US for evaluation of the severity of portal hypertension and hepatic fibrosis. The present article reviews the recent progress in contrast-enhanced US for the assessment of portal hypertension and hepatic fibrosis.
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Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan.
| | - Gamal Shiha
- Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670, Japan
| | - Ashish Kumar
- Department of Gastroenterology & Hepatology, Ganga Ram Institute for Postgraduate Medical Education & Research (GRIPMER), Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | | | - Alaa Ibrahim
- GI/Liver division, GIT Endoscopy Unit, University of Benha, Banha, Egypt
| | - Vivek Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, 226014, India
| | - Cosmas Rinaldi A Lesmana
- Department of Internal Medicine, Hepatobiliary Division, Cipto Mangunkusumo Hospital, University of Indonesia, Jawa Barat, Indonesia
| | - Masao Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
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