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Амосова МВ, Полубояринова ИВ, Сальникова ПВ, Жеребчикова КЮ, Фадеев ВВ. [Hepatogenic diabetes: three cases report and literature review]. PROBLEMY ENDOKRINOLOGII 2025; 71:66-74. [PMID: 40411331 PMCID: PMC12117979 DOI: 10.14341/probl13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/07/2024] [Accepted: 05/15/2024] [Indexed: 05/26/2025]
Abstract
Hepatogenic diabetes (HepD) is a form of diabetes where the primary pathogenesis is a liver disease, usually cirrhosis, complicated by the development of portal hypertension with the formation of porto-caval shunts. In the development of HepD, in addition to traditional risk factors for carbohydrate metabolism disorders, the pathogenetic features of liver diseases play a significant role. However, the exact mechanism of HepD development remains unclear, and several questions are still open for discussion. Despite having distinct pathophysiological and clinical features, hepatogenic diabetes is currently not considered as an independent disease. This is likely due to the difficulties in differentiating between types of diabetes due to the bidirectional relationship between glucose metabolism disorders and chronic liver diseases. It is known that diabetes negatively affects the development and progression of chronic liver diseases of various etiologies, and their combination is associated with worse clinical outcomes in terms of mortality, the occurrence of liver decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and the selection of optimal therapeutic strategies for diabetes may be challenging due to the lack of established clinical guidelines and the presence of comorbidities in patients with HepD.
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Affiliation(s)
- М. В. Амосова
- Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский университет)
| | - И. В. Полубояринова
- Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский университет)
| | - П. В. Сальникова
- Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский университет)
| | - К. Ю. Жеребчикова
- Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский университет)
| | - В. В. Фадеев
- Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский университет)
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Garcês Soares S, Frazão T, Tuna C, Montes M, Rocha A, Rodrigues Santos L, Carrola P, Carvalho S, Pinho I, Nogueira L, Marques-Cruz M, Presa J. Disorder of Glucose Metabolism and Therapy: Implications on the Natural History of Advanced Chronic Liver Disease. GE - PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024:1-9. [DOI: 10.1159/000541211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Introduction: Hepatogenous diabetes (HD) is a disorder of glucose metabolism (DGM) that develops as a complication of advanced chronic liver disease (ACLD) with an estimated prevalence of 20–70%. It appears to be associated with a larger number of decompensations, but its impact on the natural history of the disease is unclear. The treatment of DGM is hampered by the fact that some therapeutic agents are associated with a risk of complications in ACLD. The aim of this work was to study DGM in a population of patients with ACLD: prevalence, liver disease decompensation episodes, mortality analysis and study of the impact of antidiabetic therapies in patients with ACLD who developed DGM. Materials and Methods: A cohort of consecutive patients with ACLD without previous DGM, who attended a Hepatology clinic in the period of January to June 2015 was selected. Follow-up was carried out for 5 years. Data on age, gender, date of diagnosis and etiology of ACLD, Child-Pugh and MELD-Na classifications at enrollment, development of DGM, and antidiabetic therapy were collected. Logistic regression models for hospitalizations due to decompensated ACLD, ascites, hepatic encephalopathy (HE), upper gastrointestinal bleeding (UGB), hepatocellular carcinoma (HCC), portal vein thrombosis (PVT), infectious complications, acute-on-chronic liver failure (ACLF), and death were built. A survival analysis for patients with and without DGM was also performed. Treatment effectiveness for patients with DGM was assessed. Results: Initially, 221 patients were included, 154 (69.7%) of whom developed DGM after the diagnosis of ACLD. DGM patients presented a significantly higher number of hospitalizations. Odds ratio (OR) for death was not significantly related with DGM. At 5 years of follow-up, 68.9% of patients with DGM were alive, against 81.8% without DGM (p = 0.087). From the 154 patients who were diagnosed with DGM, 42.9% were not receiving pharmacological treatment for DGM. Treated patients were prescribed with either biguanides (34.8%), a SGLT2 inhibitor (8.6%), or insulin (7.7%). Only 1 patient was treated with a GLP-1 analogue. A tendency of OR favoring treatment was observed for biguanides and SGLT2 inhibitors in all outcomes except ascites. In the univariable analysis, the use of biguanides was associated with lower risk of death (OR: 0.84 [95% CI: 0.73–0.96]) and HE (OR: 0.85 [95% CI: 0.73–0.98]). Conclusion: DGM occurs with high prevalence in patients with ACLD and it seems to be related to more hospitalizations, which highlights the importance of its early identification and appropriate therapeutic approach. In the absence of contraindications, biguanides should be considered for treatment of patients with ACLD and DGM as they appear to be associated with a tendency to better outcomes and may present some advantage in terms of survival.
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Yadav M, Verma S, Tiwari P, Mugale MN. Unraveling the mechanisms of hepatogenous diabetes and its therapeutic perspectives. Life Sci 2024; 353:122934. [PMID: 39089644 DOI: 10.1016/j.lfs.2024.122934] [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: 05/09/2024] [Revised: 06/26/2024] [Accepted: 07/25/2024] [Indexed: 08/04/2024]
Abstract
The review focused mainly on the pathogenesis of hepatogenous diabetes (HD) in liver cirrhosis (LC). This review reveals parallels between the mechanisms of metabolic dysfunction observed in LC and type II diabetes (T2DM), suggesting a shared pathway leading to HD. It underscores the role of insulin in HD pathogenesis, highlighting key factors such as insulin signaling, glucose metabolism, insulin resistance (IR), and the influence of adipocytes. Furthermore, the impact of adipose tissue accumulation, fatty acid metabolism, and pro-inflammatory cytokines like Tumor necrosis factor-α (TNF-α) on IR are discussed in the context of HD. Altered signaling pathways, disruptions in the endocrine system, liver inflammation, changes in muscle mass and composition, and modifications to the gut microbiota collectively contribute to the complex interplay linking cirrhosis and HD. This study highlights how important it is to identify and treat this complex condition in cirrhotic patients by thoroughly analyzing the link between cirrhosis, IR, and HD. It also emphasizes the vitality of targeted interventions. Cellular and molecular investigations into IR have revealed potential therapeutic targets for managing and preventing HD.
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Affiliation(s)
- Manisha Yadav
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Smriti Verma
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Purnima Tiwari
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India
| | - Madhav Nilakanth Mugale
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Maji T, Mahto M, Kumar S, Anand U, Priyadarshi RN, Arya R, Kumar R. Hepatogenous Diabetes as Compared to Type-2 Diabetes Mellitus and Non-diabetes in Patients With Liver Cirrhosis: Magnitude, Characteristics, and Implications. J Clin Exp Hepatol 2024; 14:101411. [PMID: 38699514 PMCID: PMC11061214 DOI: 10.1016/j.jceh.2024.101411] [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: 12/28/2023] [Accepted: 04/07/2024] [Indexed: 05/05/2024] Open
Abstract
AIM Hepatogenous diabetes (HD) is frequently underestimated among cirrhosis patients. The current study assessed the magnitude, clinical characteristics, and implications of HD in cirrhosis patients as compared to the patients with type-2 diabetes mellitus (T2DM) and non-diabetes (ND) cirrhosis. METHODS In a prospective observational study, 338 consecutive eligible cirrhosis patients were screened for diabetes mellitus. A 2-hour oral glucose tolerance test (OGTT) was used to detect HD. The clinical characteristics, complications, and outcomes were ascertained and compared amongst HD, T2DM, and ND patients. RESULTS In the final study cohort of 316 patients, the proportion of HD, T2DM, and ND was 22.5% (n = 71), 26.3% (n = 83), and 51.3% (n = 162), respectively. HD was the predominant form of diabetes (68.9%) in Child-Pugh class-C cirrhosis. The majority (73%) of HD patients had abnormal OGTT without fasting hyperglycaemia. A lower cut-off of 98.5 mg/dl for fasting blood glucose had a modest sensitivity (72%) and specificity (75%) for predicting HD. In comparison to T2DM patients, HD patients were younger, leaner, and had more advanced cirrhosis. In comparison to ND patients, HD patients were leaner but had higher glycemic indices, serum cholesterol, and arterial ammonia levels. During a median follow-up period of 12 (03-21) months, the frequency of hepatic encephalopathy and variceal haemorrhage were higher in HD and T2DM patients compared to that in the ND group. CONCLUSIONS HD is prevalent in about one fifth of cirrhosis patients. It differs from T2DM and ND in a number of ways, and has association with complications of cirrhosis.
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Affiliation(s)
- Tanmoy Maji
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Mala Mahto
- Department of Biochemistry, All India Institute of Medical Sciences, Patna, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | | | - Rahul Arya
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, India
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Abdullah MA, Kadhum FJ, Issa SS. Assessment of Liver Involvement in Patients With Type 2 Diabetes Mellitus in Basrah City, Iraq, Using FibroScan and Correlation With Risk Factors. Cureus 2024; 16:e65089. [PMID: 39171003 PMCID: PMC11337731 DOI: 10.7759/cureus.65089] [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: 07/22/2024] [Indexed: 08/23/2024] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases caused by the accumulation of fat in the liver, which can progress to fibrosis, cirrhosis, and primary liver cancer. Insulin resistance is a causative factor in the development of NAFLD. FibroScan, or transient elastography, is a noninvasive imaging technique for evaluating liver disease. Aim To use FibroScan for evaluating liver involvement in type 2 diabetes mellitus (T2DM) patients with some associated risk factors. Materials and methods A cross-sectional prospective study was conducted from February to August 2023 in the outpatient clinic of Basrah Gastroenterology and Hepatology Hospital. Data collection included demographic data, past medical history, and biochemical tests including fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid profile (consisting of low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum triglycerides, and total cholesterol), then, patients underwent FibroScan examination. Results The study included 50 patients with T2DM, of whom 23 (46%) were male and 27 (54%) were female. The mean age of the studied population was 47.72 ± 8.31 years, with a range of 28-64 years. The mean BMI was 28.44 ± 4.24, with most patients being either overweight or obese. The fibrosis score was 4.74 ± 1.02 kPa (stage 0), while the mean steatosis score was 282.88 ± 44.99 (grade III). Diastolic blood pressure (BP), serum ALT, and serum HDL level were the variables that showed statistically significant differences when compared according to the stages of steatosis measured by FibroScan, with p-values of 0.016, 0.048, and 0.028, respectively. Conclusion Some risk factors associated with diabetes, such as dyslipidemia, liver enzymes, and BP, are highly associated with the development of steatosis rather than fibrosis.
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Affiliation(s)
- Muntadher A Abdullah
- College of Medicine, University of Basrah, Basrah Gastroenterology and Hepatology Hospital, Basrah, IRQ
| | | | - Sajjad S Issa
- Family Medicine, College of Nursing, University of Basra, Basrah, IRQ
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Quiroz-Aldave JE, Gamarra-Osorio ER, Durand-Vásquez MDC, Rafael-Robles LDP, Gonzáles-Yovera JG, Quispe-Flores MA, Concepción-Urteaga LA, Román-González A, Paz-Ibarra J, Concepción-Zavaleta MJ. From liver to hormones: The endocrine consequences of cirrhosis. World J Gastroenterol 2024; 30:1073-1095. [PMID: 38577191 PMCID: PMC10989500 DOI: 10.3748/wjg.v30.i9.1073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 01/02/2024] [Accepted: 02/06/2024] [Indexed: 03/06/2024] Open
Abstract
Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.
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Affiliation(s)
| | | | | | | | | | | | | | - Alejandro Román-González
- Department of Endocrinology, Hospital Universitario de San Vicente Fundación, Medellin 050010, Colombia
- Internal Medicine, Universidad de Antioquia, Medellín 050010, Colombia
| | - José Paz-Ibarra
- School of Medicine, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru
- Department of Endocrinology, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
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Pashayee-Khamene F, Hatami B, Cheraghpour M, Yari Z. Keeping an eye on the nutrition: The importance of nutrition management on cardiometabolic risk factors in cirrhotic patients. Clin Nutr ESPEN 2023; 58:186-192. [PMID: 38057004 DOI: 10.1016/j.clnesp.2023.09.927] [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: 05/24/2023] [Revised: 08/26/2023] [Accepted: 09/26/2023] [Indexed: 11/07/2023]
Abstract
Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients.
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Affiliation(s)
- Fereshteh Pashayee-Khamene
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Deng Y, Li K, Li A, Hu W, Hu W. Advances in the treatment of hepatogenous diabetes: A review. Medicine (Baltimore) 2023; 102:e36068. [PMID: 37986334 PMCID: PMC10659649 DOI: 10.1097/md.0000000000036068] [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: 07/06/2023] [Revised: 10/18/2023] [Accepted: 10/20/2023] [Indexed: 11/22/2023] Open
Abstract
Hepatogenous diabetes (HD) is a glycogen metabolism disorder that arises as a consequence of chronic liver disease. The condition is frequently detected in patients diagnosed with cirrhosis, which is a result of advanced liver disease. The prognosis for patients with HD is generally poor, and they are at a heightened risk for serious complications such as gastrointestinal bleeding, primary peritonitis, and hepatic encephalopathy. Hepatogenous diabetes progression is often associated with cirrhosis progression, which leads to the development of liver cancer and increased patient mortality. Despite the prevalence and severity of HD, no systematic treatment strategy for clinical management of the condition has been proposed by any research or institutions to date. This paper conducts an extensive review of recent advancements in HD treatment in the quest for an effective treatment approach that may improve the overall prognosis of HD.
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Affiliation(s)
- Yanru Deng
- Department of Clinical Nutrition, West China Hospital; Sichuan University, Chengdu, Sichuan Province, China
| | - Keyu Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital; Sichuan University, Chengdu, Sichuan Province, China
| | - Ang Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital; Sichuan University, Chengdu, Sichuan Province, China
| | - WeiMing Hu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital; Sichuan University, Chengdu, Sichuan Province, China
| | - Wen Hu
- Department of Clinical Nutrition, West China Hospital; Sichuan University, Chengdu, Sichuan Province, China
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Hassouna MM, Moustafa MS, Hamdy M, Abdelsameea E, Abbasy M, Naguib M. Study of transcription factor 7-like 2 (TCF7L2) gene polymorphism in cirrhotic patients with diabetes. EGYPTIAN LIVER JOURNAL 2023; 13:54. [DOI: 10.1186/s43066-023-00285-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 09/21/2023] [Indexed: 01/04/2025] Open
Abstract
AbstractPatients with chronic liver disease (CLD) as chronic hepatitis C (CHC) are at high risk of diabetes type 2 (T2D). Genetic factors are suggested to modulate diabetes development in cirrhotic patients. TCF7L2 gene has been reported to be associated with type 2 diabetes, but the association of TCF7L2 with cirrhotic patients with diabetes is unclear. We aimed to study the TCF7L2 gene polymorphisms (rs 290487) in cirrhotic patients with diabetes.Method The study was assessed on 25 cirrhotic patients with type 2 diabetes who were compared to 25 cirrhotic HCV patients (nondiabetic), 25 diabetic type 2 patients, and 25 age- and gender-matched healthy control groups. After the collection of relevant clinical data and basic laboratory tests, single-nucleotide polymorphism (SNP) in the TCF7L2 gene (rs290487) was performed by a real-time PCR technique.Results Cirrhotic patients with diabetes presented significantly poorer liver function, higher incidence of cirrhotic complications, and higher glucose levels compared with cirrhotic nondiabetic patients. The TCF7L2 rs290487 TT variant showed significantly increased diabetes risk in cirrhotic patients compared with CC and CT genotypes.Conclusions TCF7L2 rs290487 polymorphism could be associated with increased diabetic risk in cirrhotic patients.
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Kumar R, Kumar S, Prakash SS. Compensated liver cirrhosis: Natural course and disease-modifying strategies. World J Methodol 2023; 13:179-193. [PMID: 37771878 PMCID: PMC10523240 DOI: 10.5662/wjm.v13.i4.179] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 06/05/2023] [Accepted: 06/27/2023] [Indexed: 09/20/2023] Open
Abstract
Compensated liver cirrhosis (CLC) is defined as cirrhosis with one or more decompensating events, such as ascites, variceal haemorrhage, or hepatic encephalopathy. Patients with CLC are largely asymptomatic with preserved hepatic function. The transition from CLC to decompensated cirrhosis occurs as a result of a complex interaction between multiple predisposing and precipitating factors. The first decompensation event in CLC patients is considered a significant turning point in the progression of cirrhosis, as it signals a drastic decline in median survival rates from 10-12 years to only 1-2 years. Furthermore, early cirrhosis has the potential to regress as liver fibrosis is a dynamic condition. With the advent of effective non-invasive tools for detecting hepatic fibrosis, more and more patients with CLC are currently being recognised. This offers clinicians a unique opportunity to properly manage such patients in order to achieve cirrhosis regression or, at the very least, prevent its progression. There are numerous emerging approaches for preventing or delaying decompensation in CLC patients. A growing body of evidence indicates that treating the underlying cause can lead to cirrhosis regression, and the use of non-selective beta-blockers can prevent decompensation by lowering portal hypertension. Additionally, addressing various cofactors (such as obesity, diabetes, dyslipidaemia, and alcoholism) and precipitating factors (such as infection, viral hepatitis, and hepatotoxic drugs) that have a detrimental impact on the natural course of cirrhosis may benefit patients with CLC. However, high-quality data must be generated through well-designed and adequately powered randomised clinical trials to validate these disease-modifying techniques for CLC patients. This article discussed the natural history of CLC, risk factors for its progression, and therapeutic approaches that could alter the trajectory of CLC evolution and improve outcomes.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Sabbu Surya Prakash
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Manilla V, Santopaolo F, Gasbarrini A, Ponziani FR. Type 2 Diabetes Mellitus and Liver Disease: Across the Gut-Liver Axis from Fibrosis to Cancer. Nutrients 2023; 15:nu15112521. [PMID: 37299482 DOI: 10.3390/nu15112521] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/23/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Type 2 diabetes mellitus is a widespread disease worldwide, and is one of the cornerstones of metabolic syndrome. The existence of a strong relationship between diabetes and the progression of liver fibrosis has been demonstrated by several studies, using invasive and noninvasive techniques. Patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) show faster progression of fibrosis than patients without diabetes. Many confounding factors make it difficult to determine the exact mechanisms involved. What we know so far is that both liver fibrosis and T2DM are expressions of metabolic dysfunction, and we recognize similar risk factors. Interestingly, both are promoted by metabolic endotoxemia, a low-grade inflammatory condition caused by increased endotoxin levels and linked to intestinal dysbiosis and increased intestinal permeability. There is broad evidence on the role of the gut microbiota in the progression of liver disease, through both metabolic and inflammatory mechanisms. Therefore, dysbiosis that is associated with diabetes can act as a modifier of the natural evolution of NAFLD. In addition to diet, hypoglycemic drugs play an important role in this scenario, and their benefit is also the result of effects exerted in the gut. Here, we provide an overview of the mechanisms that explain why diabetic patients show a more rapid progression of liver disease up to hepatocellular carcinoma (HCC), focusing especially on those involving the gut-liver axis.
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Affiliation(s)
- Vittoria Manilla
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Santopaolo
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Digestive Disease Center-CEMAD, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Cook TW, Wilstermann AM, Mitchell JT, Arnold NE, Rajasekaran S, Bupp CP, Prokop JW. Understanding Insulin in the Age of Precision Medicine and Big Data: Under-Explored Nature of Genomics. Biomolecules 2023; 13:257. [PMID: 36830626 PMCID: PMC9953665 DOI: 10.3390/biom13020257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/20/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023] Open
Abstract
Insulin is amongst the human genome's most well-studied genes/proteins due to its connection to metabolic health. Within this article, we review literature and data to build a knowledge base of Insulin (INS) genetics that influence transcription, transcript processing, translation, hormone maturation, secretion, receptor binding, and metabolism while highlighting the future needs of insulin research. The INS gene region has 2076 unique variants from population genetics. Several variants are found near the transcriptional start site, enhancers, and following the INS transcripts that might influence the readthrough fusion transcript INS-IGF2. This INS-IGF2 transcript splice site was confirmed within hundreds of pancreatic RNAseq samples, lacks drift based on human genome sequencing, and has possible elevated expression due to viral regulation within the liver. Moreover, a rare, poorly characterized African population-enriched variant of INS-IGF2 results in a loss of the stop codon. INS transcript UTR variants rs689 and rs3842753, associated with type 1 diabetes, are found in many pancreatic RNAseq datasets with an elevation of the 3'UTR alternatively spliced INS transcript. Finally, by combining literature, evolutionary profiling, and structural biology, we map rare missense variants that influence preproinsulin translation, proinsulin processing, dimer/hexamer secretory storage, receptor activation, and C-peptide detection for quasi-insulin blood measurements.
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Affiliation(s)
- Taylor W. Cook
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
| | | | - Jackson T. Mitchell
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
| | - Nicholas E. Arnold
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
| | - Surender Rajasekaran
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
- Office of Research, Corewell Health, Grand Rapids, MI 49503, USA
| | - Caleb P. Bupp
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
- Division of Medical Genetics, Corewell Health, Grand Rapids, MI 49503, USA
| | - Jeremy W. Prokop
- Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA
- Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
- Office of Research, Corewell Health, Grand Rapids, MI 49503, USA
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13
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Sharma S, Stine JG, Verbeek T, Bezinover D. Management of Patients With Non-alcoholic Steatohepatitis Undergoing Liver Transplantation: Considerations for the Anesthesiologist. J Cardiothorac Vasc Anesth 2022; 36:2616-2627. [PMID: 34391652 DOI: 10.1053/j.jvca.2021.07.020] [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: 04/21/2021] [Revised: 06/24/2021] [Accepted: 07/09/2021] [Indexed: 11/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.
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Affiliation(s)
- Sonal Sharma
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA.
| | - Jonathan G Stine
- Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA; Department of Medicine and Public Health Sciences, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Division of Gastroenterology and Hepatology, Department of Medicine, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA; Cancer Institute, Pennsylvania State University, Penn State Milton S Hershey Medical Center, Hershey, PA
| | - Thomas Verbeek
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA; Liver Center, Pennsylvania State University, Penn State Health Milton S Hershey Medical Center, Hershey, PA
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14
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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: 13] [Impact Index Per Article: 4.3] [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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15
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Gundling F. Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie. JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2022; 15:42-52. [DOI: 10.1007/s41969-022-00158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/23/2022] [Indexed: 01/04/2025]
Abstract
Zusammenfassung
Hintergrund
Patienten mit Leberzirrhose entwickeln häufig Störungen des Glukosemetabolismus wie Glukoseintoleranz oder einen hepatogenen Diabetes, welche neben der hepatozellulären Funktionseinschränkung durch die ausgeprägte Insulinresistenz als Folge der chronischen Lebererkrankung verursacht sind.
Diskussion
Empfehlungen mit Leitliniencharakter zur Diagnostik und Therapie des hepatogenen Diabetes fehlen bislang. Im Hinblick auf basistherapeutische Maßnahmen sollte eine ausreichende Deckung des Energie- und Proteinstoffwechsels gewährleistet sein, da ein Großteil der Zirrhosepatienten mangelernährt ist. Bei der medikamentösen Behandlung des hepatogenen Diabetes muss auf die erhöhte Hypoglykämiegefährdung geachtet werden. Aufgrund der Nebenwirkungen sind Biguanide sowie PPAR-gamma-Liganden bei Leberzirrhose kontraindiziert. Geeignete orale Antidiabetika sind insbesondere Sulfonylharnstoffanaloga und kurz wirksame Sulfonylharnstoffe. Wenn eine suffiziente Diabeteseinstellung mit oralen Antidiabetika nicht gelingt, sollte eine prandiale Insulintherapie mit Insulinen von kurzer Wirkdauer oder kurz wirksamen Insulinanaloga eingesetzt werden.
Schlussfolgerung
Die Optimierung einer diabetischen Stoffwechsellage hat neben der Vermeidung typischer diabetischer Spätkomplikationen eine wichtige Bedeutung für die Vermeidung und Reduzierung von Zirrhose-assoziierten Komplikationen wie z. B. gastrointestinalen Blutungsereignissen, hepatischer Enzephalopathie oder dem Auftreten eines hepatozellulären Karzinoms.
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16
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Mansour MM, Obeidat AE, Darweesh M, Mahfouz R, Kuwada S, Pyrsopoulos NT. The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study. Cureus 2022; 14:e25870. [PMID: 35836436 PMCID: PMC9275525 DOI: 10.7759/cureus.25870] [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] [Accepted: 06/12/2022] [Indexed: 11/06/2022] Open
Abstract
Introduction Diabetic ketoacidosis (DKA) is the most common acute hyperglycemic emergency in people with diabetes mellitus (DM). Cirrhosis is a consequence of chronic inflammation that is followed by hepatic fibrosis. It has been noted that cirrhosis is associated with an increased risk of developing type II DM due to altered glucose homeostasis. The prognostic value of DM in cirrhotic patients has been studied before and was found to be associated with lower survival. However, the risk of mortality and adverse events in cirrhotic patients admitted with DKA needs further evaluation. The aim of this study is to compare outcomes in patients with cirrhosis admitted to the hospital with DKA compared to non-cirrhotic patients. Methods The data for this study were extracted from the National Inpatient Sample (NIS) 2016-2019. The NIS was queried for all patients who had a discharge diagnosis of DKA. Patients with cirrhosis were identified and subclassified into compensated and decompensated cirrhosis using the International Classification of Diseases 10th revision, Clinical Modification (ICD-10-CM) codes. Patients without cirrhosis were the control group. ICD-10-CM codes that have been validated for cirrhosis were utilized. The primary outcome was in-hospital mortality. Secondary outcomes were hospital charges, length of stay (LOS), and in-hospital complications, including shock, mechanical ventilation, and acute kidney injury (AKI) requiring dialysis. Results We included 1,098,875 hospitalizations with a discharge diagnosis of DKA. Overall, 9,190 patients had compensated cirrhosis and 4,355 had decompensated cirrhosis. Cirrhotic patients had overall worse outcomes compared to non-cirrhotics. Decompensated cirrhotics had the highest mortality (11.26%; 95% confidence interval [CI]: 9.36% to 13.49%) compared to compensated cirrhotics (3.54%; 95% CI: 2.79% to 4.48%) and non-cirrhotics (2.15%; 95% CI: 1.89% to 2.43%). Similarly, decompensated cirrhotics also had the highest LOS, total charges, and in-hospital complications among the groups. On multivariate analysis, decompensated cirrhosis, rather than compensated cirrhosis, was an independent predictor of higher mortality (adjusted odds ratio [AOR]: 2.30; 95% CI: 1.81 to 2.92), LOS (regression coefficient: +1.82 days; 95% CI: +1.19 to +2.44 days), hospital charges (regression coefficient: +$28,497; 95% CI: +$18,107 to +$38,887), shock (AOR: 2.31; 95% CI: 1.68 to 3.18), mechanical ventilation (AOR: 1.91; 95% CI: 1.58 to 2.29), and AKI requiring dialysis (AOR: 2.31; 95% CI: 1.68 to 3.18). Conclusion This study showed that patients with decompensated liver cirrhosis who were admitted with DKA had the worst in-hospital outcomes. Additionally, only decompensated cirrhosis was an independent predictor of worse outcomes. Decompensated cirrhotics who develop DKA should be approached with more caution with a probable lower threshold for intensive care unit admission for a higher level management.
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Affiliation(s)
- Mahmoud M Mansour
- Internal Medicine, University of Missouri School of Medicine, Columbia, USA
| | | | - Mohammad Darweesh
- Internal Medicine, East Tennessee State University, Johnson City, USA
| | - Ratib Mahfouz
- Internal Medicine, Kent Hospital, Brown University, Warwick, USA
| | - Scott Kuwada
- Gastroenterology and Hepatology, University of Hawaii, Honolulu, USA
| | - Nikolaos T Pyrsopoulos
- Gastroenterology and Hepatology, Rutgers University New Jersey Medical School, New Jersey, USA
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17
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Puri P, Kotwal N. An Approach to the Management of Diabetes Mellitus in Cirrhosis: A Primer for the Hepatologist. J Clin Exp Hepatol 2022; 12:560-574. [PMID: 35535116 PMCID: PMC9077234 DOI: 10.1016/j.jceh.2021.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/07/2021] [Indexed: 12/12/2022] Open
Abstract
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
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Key Words
- ADA, American Diabetes Association
- AGI, Alfa Glucosidase inhibitors
- BMI, Body mass index
- CLD, Chronic liver disease
- CYP-450, Cytochrome P-450
- Dipeptidyl-peptidase 4, DPP-4
- GLP-1, Glucagon-like peptide-1
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus
- HbA1c, Hemoglobin A1c
- IGF, Insulin-like growth factor
- MALA, Metformin-associated lactic acidosis
- NASH, Nonalcoholic steatohepatitis
- NPL, Neutral protamine lispro
- OGTT, Oral glucose tolerance test
- SMBG, Self-monitoring of blood glucose
- Sodium-glucose cotransporter 2, SGLT2
- VEGF, Vascular endothelial growth factor
- antidiabetic agents
- antihyperglycemic drugs
- chronic liver disease
- cirrhosis
- diabetes mellitus
- eGFR, estimated glomerular filtration rates
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, New Delhi, 110025, India
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18
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García-Compeán D, Orsi E, Kumar R, Gundling F, Nishida T, Villarreal-Pérez JZ, Del Cueto-Aguilera ÁN, González-González JA, Pugliese G. Clinical implications of diabetes in chronic liver disease: Diagnosis, outcomes and management, current and future perspectives. World J Gastroenterol 2022; 28:775-793. [PMID: 35317103 PMCID: PMC8900578 DOI: 10.3748/wjg.v28.i8.775] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 11/19/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is common in liver cirrhosis (LC). The pathophysiological association is bidirectional. DM is a risk factor of LC and LC is a diabetogenic condition. In the recent years, research on different aspects of the association DM and LC has been intensified. Nevertheless, it has been insufficient and still exist many gaps. The aims of this review are: (1) To discuss the latest understandings of the association of DM and LC in order to identify the strategies of early diagnosis; (2) To evaluate the impact of DM on outcomes of LC patients; and (3) To select the most adequate management benefiting the two conditions. Literature searches were conducted using PubMed, Ovid and Scopus engines for DM and LC, diagnosis, outcomes and management. The authors also provided insight from their own published experience. Based on the published studies, two types of DM associated with LC have emerged: Type 2 DM (T2DM) and hepatogenous diabetes (HD). High-quality evidences have determined that T2DM or HD significantly increase complications and death pre and post-liver transplantation. HD has been poorly studied and has not been recognized as a complication of LC. The management of DM in LC patients continues to be difficult and should be based on drug pharmacokinetics and the degree of liver failure. In conclusion, the clinical impact of DM in outcomes of LC patients has been the most studied item recently. Nevertheless many gaps still exist particularly in the management. These most important gaps were highlighted in order to propose future lines for research.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service and Department of Internal Medicine, Faculty of Medicine, University Hospital “Dr. José E. González”, Universidad Autónoma de Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, Fdn IRCCS Ca Granda, Endocrine Unit, Padigl Granelli, Milan 20121, Italy
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Felix Gundling
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Diabetics, Metabolism and Infectious Diseases, Sozialstiftung Bamberg, Bamberg 96049, Germany
| | - Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka 560-8565, Japan
| | | | - Ángel N Del Cueto-Aguilera
- Department of Gastroenterology and Internal Medicine, Faculty of Medicine, University Hospital, Autonomous University of Nuevo León, Monterrey 64700, Nuevo León, Mexico
| | - José A González-González
- Gastroenterology Service and Department of Internal Medicine, University Hospital Dr. José E González and Medical School, Monterrey 64460, Nuevo León, Mexico
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, La Sapienza University, Roma 00161, Italy
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19
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Liu B, Cheng M, Lang L, Li L, Si Y, Wang G. Autologous Bone Marrow Cell Infusion for the Treatment of Decompensated Liver Cirrhosis Patients With Type 2 Diabetes Mellitus. Front Physiol 2021; 12:730797. [PMID: 35035357 PMCID: PMC8753408 DOI: 10.3389/fphys.2021.730797] [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: 07/14/2021] [Accepted: 10/26/2021] [Indexed: 11/13/2022] Open
Abstract
This study aimed to indicate whether autologous bone marrow cell infusion (ABMI) via the right omental vein (ROV) could have a regulatory effect on decompensated liver cirrhosis (DLC) patients with type 2 diabetes mellitus (T2DM). For this purpose, 24 DLC patients with T2DM were divided into observation group (n=14) and control group (n=10). Patients in the observation group were given ABMI through the ROV and right omental artery (ROA), and cases in the control group received ABMI through the ROV. At 1, 3, 6, and 12months after ABMI, it was revealed that the prothrombin time, the total bilirubin levels, and the amount of ascites were significantly lower, while the serum albumin levels in the two groups were markedly higher compared with those before ABMI (p<0.01), and there was no significant difference between the two groups at each time point (p>0.05). The fasting blood glucose and glycosylated hemoglobin levels at 6 and 12months after ABMI in the two groups significantly decreased compared with those before ABMI (p<0.05 or p<0.01), while the decreased levels in the observation group were more obvious than those in the control group at each time point (p<0.01). The amount of insulin in the observation group at 3, 6, and 12months after ABMI was significantly less than that before ABMI in the control group (p<0.01). In summary, ABMI showed a significant therapeutic efficacy for DLC patients with T2DM through ROV and ROA.
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Affiliation(s)
- Baochi Liu
- Department of Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
- *Correspondence: Baochi Liu,
| | - Mingrong Cheng
- Department of Anorectal Surgery, Panzhou People’s Hospital, Guizhou, China
- Shanghai New Hongqiao International Medical Center, Shanghai, China
| | - Lin Lang
- Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lei Li
- Department of Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yanhui Si
- Department of Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Guangmian Wang
- Shanghai New Hongqiao International Medical Center, Shanghai, China
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20
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Tsai LW, Lu YH, Dubey R, Chiou JF. Reenvisioning Traditional to Regenerative Therapeutic Advances in Managing Nonalcoholic Fatty Liver Disease in Diabetes Mellitus. J Diabetes Res 2021; 2021:7692447. [PMID: 34805412 PMCID: PMC8601846 DOI: 10.1155/2021/7692447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 10/23/2021] [Indexed: 12/07/2022] Open
Abstract
Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.
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Affiliation(s)
- Lung-Wen Tsai
- Department of Medicine Research, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Department of Information Technology Office, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei 11031, Taiwan
| | - Yi-Hsiang Lu
- Department of Otolaryngology, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Rajni Dubey
- Department of Medicine Research, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Jeng-Fong Chiou
- Department of Radiation Oncology, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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21
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Siddiqui ATS, Parkash O, Hashmi SA. Malnutrition and liver disease in a developing country. World J Gastroenterol 2021; 27:4985-4998. [PMID: 34497430 PMCID: PMC8384735 DOI: 10.3748/wjg.v27.i30.4985] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/19/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Malnutrition is a highly prevalent and under recognized condition in developing countries of South Asia. The presence of malnutrition causes a severe impact on patients with liver cirrhosis. The etiology of cirrhosis differs in the South Asian region compared to the West, with hepatitis B and C still being the leading causes and the prevalence of nonalcoholic fatty liver disease increasing over time. Comorbid malnutrition worsens outcomes for cirrhosis patients. Urgent attention to address malnutrition is needed to improve patient outcomes. The etiology and pathophysiology of malnutrition in liver diseases is multifactorial, as reduction in liver function affects both macronutrients and micronutrients. A need for nutritional status assessment for liver disease patients exists in all parts of the world. There are many widely studied tools in use to perform a thorough nutritional assessment, of which some tools are low cost and do not require extensive training. These tools can be studied and evaluated for use in the resource limited setting of a country like Pakistan. Treatment guidelines for proper nutrition maintenance in chronic liver disease exist for all parts of the world, but the knowledge and practice of nutritional counseling in Pakistan is poor, both amongst patients and physicians. Emphasis on assessment for nutritional status at the initial visit with recording of vital signs is needed. Simultaneously, treating physicians need to be made aware of the misconceptions surrounding nutritional restrictions in cirrhosis so that patient education is done correctly based on proper scientific evidence.
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Affiliation(s)
| | - Om Parkash
- Department of Medicine, Division of Gastroenterology, The Aga Khan University, Karachi 74800, Pakistan
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22
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Hung TH, Tseng CW, Tsai CC, Lee HF. Prognosis of hypoglycemia episode in cirrhotic patients during hospitalization. BMC Gastroenterol 2021; 21:319. [PMID: 34372791 PMCID: PMC8351368 DOI: 10.1186/s12876-021-01895-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 08/03/2021] [Indexed: 12/22/2022] Open
Abstract
Background Studies have shown that hyperglycemia in cirrhotic patients increases mortality. However, no population-based study has evaluated the influence of hypoglycemia upon hospital admission on death in these patients. The aim of this study was to assess the effect of hypoglycemia at admission on the mortality of patients with liver cirrhosis. Methods The Taiwan National Health Insurance Database was searched, and 636 cirrhotic patients without baseline diabetes mellitus who presented with hypoglycemia upon hospitalized from 2010 to 2013 were included in the study. A one-to-four propensity score matching was performed to select a comparison group based on age, sex and comorbidities. Results The overall 30-day mortality rate was 30.2% in the hypoglycemia group and 7.4% in the non-hypoglycemia group (P < 0.001). After Cox regression modeling adjusting for age, sex and comorbid disorders, cirrhotic patients with hypoglycemia had a hazard ratio (HR) of 30-day mortality of 4.96 (95% confidence interval [CI] 4.05–6.08, P < 0.001) as compared to the non-hypoglycemia group. In subgroup analysis, the cirrhotic patients with hypoglycemia and hepatocellular carcinoma (HCC) had a 30-day mortality HR of 6.11 (95% confidence interval [CI] 4.40–8.49, P < 0.001) compared to those with neither hypoglycemia nor HCC. Conclusions Hypoglycemia is a very important prognostic factor in the 30-day mortality of cirrhotic patients, especially in those with underlying HCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-021-01895-2.
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Affiliation(s)
- Tsung-Hsing Hung
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Rd., Dalin Township, Chiayi County, 62247, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Wei Tseng
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Rd., Dalin Township, Chiayi County, 62247, Taiwan.,School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Chun Tsai
- Department of Mathematics, Tamkang University, Tamsui, Taiwan
| | - Hsing-Feng Lee
- Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Rd., Dalin Township, Chiayi County, 62247, Taiwan. .,School of Medicine, Tzu Chi University, Hualien, Taiwan.
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23
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Kalra S, Bhattacharya S, Rawal P. Hepatocrinology. Med Sci (Basel) 2021; 9:39. [PMID: 34205986 PMCID: PMC8293374 DOI: 10.3390/medsci9020039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/10/2021] [Accepted: 05/24/2021] [Indexed: 11/17/2022] Open
Abstract
Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field.
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Affiliation(s)
- Sanjay Kalra
- Department of Endocrinology, Bharti Hospital, Karnal 132001, India
| | | | - Pawan Rawal
- Department of Gastroenterology, Artemis Hospital, Gurgaon 122002, India;
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24
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Kumar R, Priyadarshi RN, Anand U. Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol 2021; 27:990-1005. [PMID: 33776368 PMCID: PMC7985728 DOI: 10.3748/wjg.v27.i11.990] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 01/17/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) in patients with liver cirrhosis has become a new frontier in hepatology. In recent years, a sharp increase in the diagnosis of CKD has been observed among patients with cirrhosis. The rising prevalence of risk factors, such as diabetes, hypertension and nonalcoholic fatty liver disease, appears to have contributed significantly to the high prevalence of CKD. Moreover, the diagnosis of CKD in cirrhosis is now based on a reduction in the estimated glomerular filtration rate of < 60 mL/min over more than 3 mo. This definition has resulted in a better differentiation of CKD from acute kidney injury (AKI), leading to its greater recognition. It has also been noted that a significant proportion of AKI transforms into CKD in patients with decompensated cirrhosis. CKD in cirrhosis can be structural CKD due to kidney injury or functional CKD secondary to circulatory and neurohormonal imbalances. The available literature on combined cirrhosis-CKD is extremely limited, as most attempts to assess renal dysfunction in cirrhosis have so far concentrated on AKI. Due to problems related to glomerular filtration rate estimation in cirrhosis, the absence of reliable biomarkers of CKD and technical difficulties in performing renal biopsy in advanced cirrhosis, CKD in cirrhosis can present many challenges for clinicians. With combined hepatorenal dysfunctions, fluid mobilization becomes problematic, and there may be difficulties with drug tolerance, hemodialysis and decision-making regarding the need for liver vs simultaneous liver and kidney transplantation. This paper offers a thorough overview of the increasingly known CKD in patients with cirrhosis, with clinical consequences and difficulties occurring in the diagnosis and treatment of such patients.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Rajeev Nayan Priyadarshi
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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25
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Scurt FG, Bose K, Canbay A, Mertens PR, Chatzikyrkou C. [Chronic kidney injury in patients with liver diseases - Reappraising pathophysiology and treatment options]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:560-579. [PMID: 33728618 DOI: 10.1055/a-1402-1502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.
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Affiliation(s)
- Florian Gunnar Scurt
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Katrin Bose
- Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany.,Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland
| | - Ali Canbay
- Ruhr-Universität Bochum, Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland
| | - Peter R Mertens
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Christos Chatzikyrkou
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
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26
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Zhong S, Deng Z, Jiang L, Zeng J, Yu T. Wilson’s Disease with Hepatogenous Diabetes: A Case Report. IRANIAN JOURNAL OF PEDIATRICS 2021; 31. [DOI: 10.5812/ijp.105261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Introduction: Wilson’s disease (WD) is a hereditary autosomal recessive disorder caused by pathogenic variants within the ATP7B gene. Early diagnosis of WD is important but it can be difficult in pediatric clinical practice because of varied presentations. Fortunately, with the development of genetic testing, molecular analysis of the ATP7B gene is helpful in the early diagnosis of WD. Hepatogenous diabetes (HD) is defined as a state of impaired glucose regulation caused by chronic liver disease. Here we report a child with WD with HD. Case Presentation: A 4-year-old girl was admitted to our hospital with diarrhea for two months. On admission, urine glucose was 4+, fasting glucose was 2.6 mmol/L, and postprandial blood glucose was 7.2 mmol/L. Further clinical manifestations and laboratory tests showed coagulation dysfunction, hemolytic anemia, and cirrhosis. After admission, she developed hepatic encephalopathy. Significant abnormal glucose metabolism was later detected, but by then, hypoglycemic convulsions had taken place. The final diagnosis of WD was confirmed by detection of mutations in the ATP7B gene. Genetic sequencing revealed compound heterozygous mutations in ATP7B, including c.2975C>T, p.Pro992Leu and c.3809A>G, p.Asn1270Ser. On day 40 of admission, the patient underwent successful orthotopic liver transplantation. Her liver function, blood glucose levels, and coagulation test results returned to normal one month after the liver transplantation. The symptom of diarrhea was also relieved after surgery. Her abnormal glucose level in hospital was considered to be HD. Conclusions: Blood glucose levels must be carefully monitored in Wilson’s disease. Moreover, genetic sequencing provides an accurate and minimally invasive diagnostic tool for WD.
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27
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Association between Liver Cirrhosis and Diabetes Mellitus: A Review on Hepatic Outcomes. J Clin Med 2021; 10:jcm10020262. [PMID: 33445629 PMCID: PMC7827383 DOI: 10.3390/jcm10020262] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 01/07/2021] [Accepted: 01/11/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Liver cirrhosis (LC) is largely associated with diabetes mellitus (DM). More than 80% of patients with LC manifest glucose intolerance and about 30% have type 2 DM. A particular and yet unrecognized entity is hepatogenous diabetes (HD), defined as impaired glucose regulation caused by altered liver function following LC. Numerous studies have shown that DM could negatively influence liver-related outcomes. AIM We aimed to investigate whether patients with LC and DM are at higher risk for hepatic encephalopathy (HE), variceal hemorrhage (VH), infections and hepatocellular carcinoma (HCC). The impact of DM on liver transplant (LT) outcomes was also addressed. METHODS Literature search was performed in PubMed, Ovid, and Elsevier databases. Population-based observational studies reporting liver outcomes in patients with LC were included. RESULTS Diabetics are at higher risk for HE, including post-transjugular intrahepatic portosystemic shunt HE. DM also increases the risk of VH and contributes to elevated portal pressure and variceal re-bleeding, while uncontrolled DM is associated with increased risk of bacterial infections. DM also increases the risk of HCC and contributes to adverse LT outcomes. CONCLUSIONS Patients with DM and LC may benefit from close follow-up in order to reduce readmissions and mortality. Due to the heterogeneity of available research, prospective multicenter clinical trials are needed to further validate these findings.
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28
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AGE PECULIARITIES OF MORPHOFUNCTIONAL CHANGES OF THE LIVER AT EARLY STAGES OF DIABETES MELLITUS DEVELOPMENT WITH THE USE OF CLUSTER ANALYSIS. WORLD OF MEDICINE AND BIOLOGY 2021. [DOI: 10.26724/2079-8334-2021-2-76-217-222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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29
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Gao H, Tayebee R, Abdizadeh MF, Mansouri E, Latifnia M, Pourmojahed Z. The efficient biogeneration of Ag and NiO nanoparticles from VPLE and a study of the anti-diabetic properties of the extract. RSC Adv 2020; 10:3005-3012. [PMID: 35496124 PMCID: PMC9048759 DOI: 10.1039/c9ra08668d] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 12/06/2019] [Indexed: 12/20/2022] Open
Abstract
Vitex pseudo-negundo leaf extract (VPLE) is used to mediate the green biosynthesis of Ag and NiO nanoparticles in aqueous solutions under mild conditions. The synthesized nanoparticles, with a narrow size range and good distribution, are characterized by means of powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) techniques. SEM and TEM micrographs proved formation of mostly spherical or ellipsoidal nanoparticles with little agglomeration, and the average particle size was less than 20–35 nm for both types of nanoparticle. Then, the protective role of VPLE toward the liver is assessed in streptozotocin-induced diabetic rats. For this purpose, diabetes is induced in rats through the intraperitoneal injection of streptozotocin, and VPLE is administered via oral gavage for 6 weeks. This study suggests that VPLE can ameliorate biochemical and structural changes in the livers of diabetic rats, showing that VPLE can improve the condition of rats with diabetic hepatopathy via a decrease in oxidative stress and an enhancement in the activity of antioxidant enzymes in the liver. Vitex pseudo-negundo leaf extract (VPLE) is a mediator for the green biosynthesis of Ag and NiO nanoparticles, and its protective effects are assessed in the livers of streptozotocin-induced diabetic rats.![]()
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Affiliation(s)
- Hongying Gao
- Department of Chinese Medicine
- Binzhou City Central Hospital
- Binzhou
- China
| | - Reza Tayebee
- Department of Chemistry
- School of Sciences
- Hakim Sabzevari University
- Sabzevar
- Iran
| | - Mojtaba Fattahi Abdizadeh
- Department of Lab Sciences
- Faculty of Paramedicine
- Sabzevar University of Medical Sciences
- Sabzevar
- Iran
| | - Esrafil Mansouri
- Department of Anatomical Sciences
- Cellular and Molecular Research Center
- Faculty of Medicine
- Ahvaz Jundishapur University of Medical Sciences
- Ahvaz
| | - Maryam Latifnia
- Department of Gasterointestinal and Liver Disease
- Faculty of Medicine
- Sabzevar University of Medical Sciences
- Sabzevar
- Iran
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30
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Infante M, Padilla N, Madiraju S, Alvarez A, Baidal D, Ricordi C, Alejandro R. Combined liver and islet transplantation in hepatogenous diabetes, cluster exenteration, and cirrhosis with type 1 diabetes. TRANSPLANTATION, BIOENGINEERING, AND REGENERATION OF THE ENDOCRINE PANCREAS 2020:439-453. [DOI: 10.1016/b978-0-12-814833-4.00037-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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31
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Yuan XX, Zhu HJ, Pan H, Chen S, Liu ZY, Li Y, Wang LJ, Lu L, Yang HB, Gong FY. Clinical characteristics of non-alcoholic fatty liver disease in Chinese adult hypopituitary patients. World J Gastroenterol 2019; 25:1741-1752. [PMID: 31011258 PMCID: PMC6465940 DOI: 10.3748/wjg.v25.i14.1741] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 03/13/2019] [Accepted: 03/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Patients with hypothalamic-pituitary disease have the feature of central obesity, insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease (NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.
AIM To analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.
METHODS Adult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospital between August 2012 and April 2018. According to abdominal ultrasonography, these patients were divided into an NAFLD (-) group and an NAFLD (+) group, and the latter was further divided into an NAFLD group and a cirrhotic group. The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.
RESULTS A total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43 (87.0%) of these patients exhibited growth hormone (GH) deficiency, and 39 (78.3%) had diabetes insipidus. A total of 27 (54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2O and 151.0 mmol/L, respectively, which were significantly higher than those of the NAFLD patients (P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index (BMI) and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD (P = 0.011 and 0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI (r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.
CONCLUSION NAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.
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Affiliation(s)
- Xian-Xian Yuan
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hui-Juan Zhu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hui Pan
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Shi Chen
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ze-Yu Liu
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lin-Jie Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lin Lu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hong-Bo Yang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Feng-Ying Gong
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission of the People's Republic of China, The Translational Medicine Center of Peking Union Medical College Hospital, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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