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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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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: 07/06/2022] [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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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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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: 6] [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: 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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Management of diabetes mellitus in patients with cirrhosis: An overview and joint statement. DIABETES & METABOLISM 2021; 47:101272. [PMID: 34363981 DOI: 10.1016/j.diabet.2021.101272] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/25/2021] [Accepted: 07/12/2021] [Indexed: 12/18/2022]
Abstract
Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.
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Bai XP, Fan YM, Zhang L, Yang GH, Li X. Influence of Liver Cirrhosis on Blood Glucose, Insulin Sensitivity and Islet Function in Mice. Am J Med Sci 2021; 362:403-417. [PMID: 34274322 DOI: 10.1016/j.amjms.2021.07.005] [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: 05/26/2020] [Revised: 02/27/2021] [Accepted: 07/09/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The relationship between cirrhosis and diabetes is controversial. We studied the influence of cirrhosis on glucose levels and islet function and explored its possible mechanisms. MATERIALS AND METHODS Cirrhosis was induced in male C57BL/6 mice by bile duct ligation (BDL). Serum biochemical parameters were determined, and oral glucose tolerance tests (OGTT) were performed at 4 and 8 weeks after BDL. Histopathology and phospho-NF-κB-p65/I-kappa B α immunohistochemical staining of the liver and islet were observed. The protein levels of the insulin signaling system and the gene expression of insulin-degrading enzyme (IDE) in the liver and muscle were determined. The activity of glucokinase (GCK) and glucose 6-phosphatase (G6P) and glycogen levels in liver homogenates were measured. RESULTS After BDL, the mice developed cirrhosis, and fasting glucose decreased significantly, but 2 h postprandial glucose increased, and the insulin areas under the curves increased. At 4 weeks of BDL, the ratios of phospho-NF-κB-p65/I-kappa B α accumulation in the liver and islet increased, the activity of G6P and the glycogen content in liver homogenates decreased, the insulin signaling system and the gene expression of IDE in the liver was downregulated, and the islet areas were decreased. After 8 weeks, these changes were more severe. CONCLUSIONS In different periods of cirrhosis, the levels of fasting glucose and 2 h postprandial glucose changed in different amplitudes. Glycogen concentrations and the activity of G6P in the liver were decreased. The mice developed insulin resistance and the islet areas were decreased. The NF-κB pathway may play a role in the process.
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Affiliation(s)
- Xiu-Ping Bai
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China.
| | - Yong-Mei Fan
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Lei Zhang
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Guo-Hua Yang
- Central Laboratory, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
| | - Xing Li
- Endocrinology Division, The Second Hospital of ShanXi Medical University, TaiYuan 030001, ShanXi, China
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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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9
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Chung W, Promrat K, Wands J. Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases. World J Hepatol 2020; 12:533-557. [PMID: 33033564 PMCID: PMC7522556 DOI: 10.4254/wjh.v12.i9.533] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/15/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
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Affiliation(s)
- Waihong Chung
- Division of Gastroenterology, Department of Medicine, Rhode Island Hospital, Providence, RI 02905, United States.
| | - Kittichai Promrat
- Division of Gastroenterology and Hepatology, Providence VA Medical Center, Providence, RI 02908, United States
| | - Jack Wands
- Liver Research Center, The Warren Alpert Medical School of Brown University, Providence, RI 02903, United States
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Philips CA, Ahamed R, Rajesh S, George T, Mohanan M, Augustine P. Update on diagnosis and management of sepsis in cirrhosis: Current advances. World J Hepatol 2020; 12:451-474. [PMID: 32952873 PMCID: PMC7475781 DOI: 10.4254/wjh.v12.i8.451] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 05/28/2020] [Accepted: 06/27/2020] [Indexed: 02/06/2023] Open
Abstract
Sepsis and septic shock are catastrophic disease entities that portend high mortality in patients with cirrhosis. In cirrhosis, hemodynamic perturbations, immune dysregulation, and persistent systemic inflammation with altered gut microbiota in the background of portal hypertension enhance the risk of infections and resistance to antimicrobials. Patients with cirrhosis develop recurrent life-threatening infections that progress to multiple organ failure. The definition, pathophysiology, and treatment options for sepsis have been ever evolving. In this exhaustive review, we discuss novel advances in the understanding of sepsis, describe current and future biomarkers and scoring systems for sepsis, and delineate newer modalities and adjuvant therapies for the treatment of sepsis from existing literature to extrapolate the same concerning the management of sepsis in cirrhosis. We also provide insights into the role of gut microbiota in initiation and progression of sepsis and finally, propose a treatment algorithm for management of sepsis in patients with cirrhosis.
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Affiliation(s)
- Cyriac Abby Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Rizwan Ahamed
- Gastroenterology and Advanced G.I Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Sasidharan Rajesh
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Tom George
- Division of Hepatobiliary Interventional Radiology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Meera Mohanan
- Anaesthesia and Critical Care, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
| | - Philip Augustine
- Gastroenterology and Advanced G.I Endoscopy, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi 682028, Kerala, India
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Cigrovski Berkovic M, Virovic-Jukic L, Bilic-Curcic I, Mrzljak A. Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management. World J Gastroenterol 2020; 26:2740-2757. [PMID: 32550751 PMCID: PMC7284186 DOI: 10.3748/wjg.v26.i21.2740] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/24/2020] [Accepted: 05/13/2020] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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Affiliation(s)
- Maja Cigrovski Berkovic
- Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Dubrava, Zagreb 10000, Croatia
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
| | - Lucija Virovic-Jukic
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
| | - Ines Bilic-Curcic
- Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Clinical Hospital Center Osijek, Osijek 31000, Croatia
| | - Anna Mrzljak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
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12
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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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13
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Amjo OO, Soyoye DO, Amjo I, Yusuff OT, Kolawole BA, Ikem RT, Adekanle O, Ndububa DA. Insulin resistance and plasma glucose tolerance abnormalities in Nigerians with chronic liver disease. Diabetes Metab Syndr 2019; 13:2208-2213. [PMID: 31235158 DOI: 10.1016/j.dsx.2019.05.014] [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: 05/15/2019] [Accepted: 05/21/2019] [Indexed: 02/07/2023]
Abstract
AIMS Glucose tolerance abnormalities are frequently observed in patients with chronic liver disease (CLD). Insulin resistance (IR) has been suggested to be a major factor responsible for these abnormalities in CLD. However studies relating IR with severity of CLD are scarce in Nigeria. This study assessed insulin resistance and glucose tolerance abnormalities in CLD and their relationship with the severity of CLD in a tertiary hospital in South-West, Nigeria. METHODS This cross sectional study involved 100 subjects with CLD. Ethical clearance was obtained and informed consent was granted by participants. Participants were interviewed using a structured proforma; physical examination and relevant investigations were performed. Insulin resistance was measured using the homeostasis model assessment (HOMA-IR) Data was analysed using Statistical Package for Social Sciences version 20.0 and p value of <0.05 was considered significant. RESULTS Mean age of the study participants was 51.9 ± 11.9 years, and mean duration of CLD was 15.9 ± 5.8 months. Glucose tolerance abnormalities were present in 66 subjects (66%) and increased from 16.1% in Child Pugh's class A to 90.0% in class C. HOMA-IR positively correlated with age, body mass index, serum blood glucose, duration and severity of CLD. Increasing age, presence of hepatocellular carcinoma, Child Pugh's class B and class C were associated with glucose tolerance abnormalities. CONCLUSION Glucose tolerance abnormalities and insulin resistance were highly prevalent among chronic liver disease subjects studied and seemed to parallel the severity of CLD, determined by the Child Pugh's score.
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Affiliation(s)
- Oluwadamilola O Amjo
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - David O Soyoye
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria.
| | - Ifeoluwa Amjo
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Olaoluwatomi T Yusuff
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria
| | - Babatope A Kolawole
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Rosemary T Ikem
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Olusegun Adekanle
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
| | - Dennis A Ndububa
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria; Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria
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Abstract
The prevalence of diabetes mellitus in cirrhotic patients is much higher than that in the general population. Two types of diabetes are usually seen in patients with cirrhosis: type 2 diabetes mellitus and hepatogenous diabetes (HD). The HD is an acquired condition which is believed to be caused by impaired insulin clearance and pancreatic β-cell dysfunction in cirrhotic patients. Increased levels of advanced glycation end products and hypoxia-inducible factors have been implicated in the pathogenesis of HD. Patients with HD typically present with normal fasting glucose, but abnormal response to an oral glucose tolerance test, which is required for the diagnosis. Because the level of glycated hemoglobin is often falsely low in patients with cirrhosis, it does not help in the early diagnosis of HD. HD is associated with an increased rate of complications of cirrhosis, decreased 5-year survival rate, and increased risk of hepatocellular carcinoma. The major complications of cirrhosis associated with HD include hepatic encephalopathy (HE), spontaneous bacterial peritonitis, sepsis, variceal hemorrhage, and renal dysfunction. Treatment of HD may be difficult as many antihyperglycemic therapies are associated with increased risk of complications in cirrhosis, particularly hypoglycemia. Biguanides, alpha-glucosidase inhibitors, and new medications such as dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter 2 inhibitors appear to be safe in patients with cirrhosis. Though insulin therapy is currently advocated, requirement of insulin is variable and is difficult to predict. The liver transplantation usually results in reversal of HD. This review article provides an overview of magnitude, patients' characteristics, clinical implications, pathophysiological mechanisms, diagnosis, and management of HD.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India
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15
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Orsi E, Grancini V, Menini S, Aghemo A, Pugliese G. Hepatogenous diabetes: Is it time to separate it from type 2 diabetes? Liver Int 2017; 37:950-962. [PMID: 27943508 DOI: 10.1111/liv.13337] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Accepted: 11/29/2016] [Indexed: 12/12/2022]
Abstract
By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.
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Affiliation(s)
- Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.,Department of Medical Sciences, University of Milan, Milan, Italy
| | - Stefano Menini
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
| | - Alessio Aghemo
- Division of Gastroenterology and Hepatology, A.M. and A. Migliavacca Center for Liver Disease, IRCCS "Cà Granda-Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Rome, Italy.,Diabetes Unit, Sant'Andrea Hospital, Rome, Italy
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16
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Nishida T. Diagnosis and Clinical Implications of Diabetes in Liver Cirrhosis: A Focus on the Oral Glucose Tolerance Test. J Endocr Soc 2017; 1:886-896. [PMID: 29264539 PMCID: PMC5686620 DOI: 10.1210/js.2017-00183] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 05/18/2017] [Indexed: 02/08/2023] Open
Abstract
The liver and skeletal muscles are responsible for maintaining glucose metabolism. As chronic liver disease progresses to cirrhosis, the loss of liver function is exacerbated and leads to the deterioration of skeletal muscle. Consequently, impaired glucose tolerance (IGT) and insulin resistance are often observed in patients with liver cirrhosis. Early stage cirrhosis with hepatogenous diabetes is characterized by marked postprandial hyperglycemia and hyperinsulinemia. Generally, it is possible to underestimate IGT when using either the conventional fasting plasma glucose (FPG) criterion or hemoglobin A1c (HbA1c) levels despite their status as the gold standard for diagnosing diabetes. The number of cirrhotic patients with diabetes tends to be underestimated because many of these patients show lower FPG levels or HbA1c, which masks their IGT. In such cases, the oral glucose tolerance test is recommended to evaluate patients with suspected postprandial hyperglycemia who present with a normal FPG. Moreover, in addition to the Child-Pugh score, the early detection of diabetes may be a useful prognostic marker for patients with liver cirrhosis.
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Affiliation(s)
- Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565 Japan
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17
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De Vincentis A, Pennazza G, Santonico M, Vespasiani-Gentilucci U, Galati G, Gallo P, Zompanti A, Pedone C, Antonelli Incalzi R, Picardi A. Breath-print analysis by e-nose may refine risk stratification for adverse outcomes in cirrhotic patients. Liver Int 2017; 37:242-250. [PMID: 27496750 DOI: 10.1111/liv.13214] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Accepted: 08/02/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS The spectrum of volatile organic compounds in the exhaled breath (breath-print, BP) has been shown to characterize patients with cirrhosis and with worse hepatic function. However, the association of different BPs with clinically relevant outcomes has not been described yet. Hence, we aimed to evaluate the association between BPs, mortality and hospitalization in cirrhotic patients and to compare it with that of the "classical" prognostic indices (Child-Pugh Classification [CPC] and MELD). METHODS Eighty-nine cirrhotic patients (M/F 59/30, mean age 64.8 ± 11.3, CPC A/B/C 37/33/19) were recruited and followed up for a median time of 23 months. Clinical and biochemical data were collected. Breath collection and analysis were obtained through Pneumopipe® and BIONOTE e-nose respectively. RESULTS Four different BP clusters (A, B, C, D) were identified. BP clusters A and D were associated with a significantly increased risk of mortality (HR 2.9, 95% confidence intervals [CI] 1.5-5.6) and hospitalization (HR 2.6, 95% CI 1.4-4.6), even in multiple adjusted models including CPC and MELD score (adjusted [a]HR 2.8, 95% CI 1.1-7.0 for mortality and aHR 2.2, 95% CI 1.1-4.2 for hospitalization). CPC C maintained the strongest association with both mortality (aHR 17.6, 95% CI 1.8-174.0) and hospitalization (aHR 12.4, 95% CI 2.0-75.8). CONCLUSIONS This pilot study demonstrates that BP clusters are associated with significant clinical endpoints (mortality and hospitalization) even independently from "classical" prognostic indices. Even though further studies are warranted on this topic, our findings suggest that the e-nose may become an adjunctive aid to stratify the risk of adverse outcomes in cirrhotic patients.
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Affiliation(s)
- Antonio De Vincentis
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Giorgio Pennazza
- Center for Integrated Research - CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy
| | - Marco Santonico
- Center for Integrated Research - CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy
| | | | - Giovanni Galati
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Paolo Gallo
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
| | - Alessandro Zompanti
- Center for Integrated Research - CIR, Unit of Electronics for Sensor Systems, Campus Bio-Medico University, Rome, Italy
| | - Claudio Pedone
- Chair of Geriatrics, Unit of Respiratory Pathophysiology, Campus Bio-Medico University, Rome, Italy
| | - Raffaele Antonelli Incalzi
- Chair of Geriatrics, Unit of Respiratory Pathophysiology, Campus Bio-Medico University, Rome, Italy.,San Raffaele- Cittadella della Carità Foundation, Taranto, Italy
| | - Antonio Picardi
- Clinical Medicine and Hepatology Department, Campus Bio-Medico University, Rome, Italy
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18
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Lin M, Pappas SC. Diabetes, Cirrhosis, and Liver Transplantation. MANAGING GASTROINTESTINAL COMPLICATIONS OF DIABETES 2017:107-115. [DOI: 10.1007/978-3-319-48662-8_8] [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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19
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Lin M, Pappas SC. Diabetes, Specific Hepatobiliary Diseases, and Treatment. MANAGING GASTROINTESTINAL COMPLICATIONS OF DIABETES 2017:93-105. [DOI: 10.1007/978-3-319-48662-8_7] [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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20
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Saeed MJ, Olsen MA, Powderly WG, Presti RM. Diabetes Mellitus is Associated With Higher Risk of Developing Decompensated Cirrhosis in Chronic Hepatitis C Patients. J Clin Gastroenterol 2017; 51:70-76. [PMID: 27306942 PMCID: PMC5154898 DOI: 10.1097/mcg.0000000000000566] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
GOALS To investigate the association of diabetes with risk of decompensated cirrhosis in patients with chronic hepatitis C (CHC). BACKGROUND Direct-acting antivirals are highly effective in treating CHC but very expensive. CHC patients at high risk of progression to symptomatic liver disease may benefit most from early treatment. STUDY We conducted a retrospective cohort study using the 2006 to 2013 Truven Health Analytics MarketScan Commercial Claims and Encounters database including inpatient, outpatient, and pharmacy claims from private insurers. CHC and cirrhosis were identified using ICD-9-CM diagnosis codes; baseline diabetes was identified by diagnosis codes or antidiabetic medications. CHC patients were followed to identify decompensated cirrhosis. Multivariable Cox proportional hazards regression was used to model the risk of decompensated cirrhosis by baseline cirrhosis. RESULTS There were 75,805 CHC patients with median 1.9 years follow-up. A total of 10,317 (13.6%) of the CHC population had diabetes. The rates of decompensated cirrhosis per 1000 person-years were: 185.5 for persons with baseline cirrhosis and diabetes, 119.8 for persons with cirrhosis and no diabetes, 35.3 for persons with no cirrhosis and diabetes, and 17.1 for persons with no cirrhosis and no diabetes. Diabetes was associated with increased risk of decompensated cirrhosis in persons with baseline cirrhosis (adjusted hazard ratio=1.4; 95% confidence interval, 1.3-1.6) and in persons without baseline cirrhosis (adjusted hazard ratio=1.9; 95% confidence interval, 1.7-2.1). CONCLUSIONS In a privately insured US population with CHC, the adjusted risk of decompensated cirrhosis was higher in diabetic compared with nondiabetic patients. Diabetes status should be included in prioritization of antiviral treatment.
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Affiliation(s)
- Mohammed J Saeed
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Margaret A Olsen
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - William G Powderly
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Rachel M Presti
- Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
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21
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Jones AL. Complications of Chronic Alcoholism That Affect Critical Illness. CRITICAL CARE TOXICOLOGY 2017:249-266. [DOI: 10.1007/978-3-319-17900-1_125] [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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22
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García-Compeán D, González-González JA, Lavalle-González FJ, González-Moreno EI, Villarreal-Pérez JZ, Maldonado-Garza HJ. Hepatogenous diabetes: Is it a neglected condition in chronic liver disease? World J Gastroenterol 2016; 22:2869-2874. [PMID: 26973383 PMCID: PMC4779910 DOI: 10.3748/wjg.v22.i10.2869] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 01/20/2016] [Accepted: 02/22/2016] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) that occurs because of chronic liver disease (CLD) is known as hepatogenous diabetes (HD). Although the association of diabetes and liver cirrhosis was described forty years ago, it was scarcely studied for long time. Patients suffering from this condition have low frequency of risk factors of type 2 DM. Its incidence is higher in CLD of viral, alcoholic and cryptogenic etiology. Its pathophysiology relates to liver damage, pancreatic dysfunction, interactions between hepatitis C virus (HCV) and glucose metabolism mechanisms and genetic susceptibility. It associates with increased rate of liver complications and hepatocellular carcinoma, and decreased 5-year survival rate. It reduces sustained virological response in HCV infected patients. In spite of these evidences, the American Diabetes Association does not recognize HD. In addition, the impact of glucose control on clinical outcomes of patients has not been evaluated. Treatment of diabetes may be difficult due to liver insufficiency and hepatotoxicity of antidiabetic drugs. Notwithstanding, no therapeutic guidelines have been implemented up to date. In this editorial, authors discuss the reasons why they think that HD may be a neglected pathological condition and call attention to the necessity for more clinical research on different fields of this disease.
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García-Compeán D, González-González JA, Lavalle-González FJ, González-Moreno EI, Villarreal-Pérez JZ, Maldonado-Garza HJ. Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy. Dig Dis Sci 2016; 61:371-80. [PMID: 26462490 DOI: 10.1007/s10620-015-3907-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/27/2015] [Indexed: 02/07/2023]
Abstract
Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.
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24
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García-Compeán D, González-González JA, Lavalle-González FJ, González-Moreno EI, Maldonado-Garza HJ, Villarreal-Pérez JZ. The treatment of diabetes mellitus of patients with chronic liver disease. Ann Hepatol 2015; 14:780-8. [PMID: 26436350 DOI: 10.5604/16652681.1171746] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.
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Affiliation(s)
- Diego García-Compeán
- Gastroenterology Service, University Hospital Dr. José E. González and Medical School
| | | | - Fernando J Lavalle-González
- Endocrinology Service and Department of Internal Medicine, University Hospital Dr. José E. González and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | | | | | - Jesús Zacarías Villarreal-Pérez
- Endocrinology Service and Department of Internal Medicine, University Hospital Dr. José E. González and Medical School. Universidad Autónoma de Nuevo León, Monterrey, Mexico
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