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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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Tay PWL, Xiao J, Tan DJH, Ng C, Lye YN, Lim WH, Teo VXY, Heng RRY, Yeow MWX, Lum LHW, Tan EXX, Kew GS, Lee GH, Muthiah MD. An Epidemiological Meta-Analysis on the Worldwide Prevalence, Resistance, and Outcomes of Spontaneous Bacterial Peritonitis in Cirrhosis. Front Med (Lausanne) 2021; 8:693652. [PMID: 34422858 PMCID: PMC8375592 DOI: 10.3389/fmed.2021.693652] [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: 04/11/2021] [Accepted: 07/12/2021] [Indexed: 01/30/2023] Open
Abstract
Background and Aims: Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP. Methods: A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals. Results: Ninety-Nine articles, comprising a total of 5,861,142 individuals with cirrhosis were included. Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63-21.30%), highest in Africa (68.20%; CI: 12.17-97.08%), and lowest in North America (10.81%; CI: 5.32-20.73%). Prevalence of community-acquired SBP was 6.05% (CI: 4.32-8.40%), and 11.11% (CI: 5.84-20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.77% (CI: 7.63-17.73%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83-9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32-11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41-8.46%). Subgroup analysis comparing prevalence, antibiotic resistance, and outcomes between income groups was conducted to explore a link between socioeconomic status and SBP, which revealed decreased risk of SBP and negative outcomes in high-income countries. Conclusion: SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.
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Affiliation(s)
- Phoebe Wen Lin Tay
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Jieling Xiao
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Cheng Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Yan Nerng Lye
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Vanessa Xin Yi Teo
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Ryan Rui Yang Heng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Marcus Wei Xuan Yeow
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Lionel Hon Wai Lum
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Infectious Diseases, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Guan Sen Kew
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Guan Huei Lee
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
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Liu ZJ, Yan YJ, Weng HL, Ding HG. Type 2 diabetes mellitus increases liver transplant-free mortality in patients with cirrhosis: A systematic review and meta-analysis. World J Clin Cases 2021; 9:5514-5525. [PMID: 34307604 PMCID: PMC8281398 DOI: 10.12998/wjcc.v9.i20.5514] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/27/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The impact of type 2 diabetes mellitus (T2DM) on the prognosis and complications of liver cirrhosis is not fully clarified. AIM To clarify the mortality and related risk factors as well as complications in cirrhotic patients with T2DM. METHODS We searched PubMed, EMBASE, and the Cochrane Library from their inception to December 1, 2020 for cohort studies comparing liver transplant-free mortality, hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy (HE) in cirrhotic patients with vs without T2DM. Odds ratios (ORs) were combined by using fixed-effects or random-effects models with RevMan software. RESULTS The database search generated a total of 17 cohort studies that met the inclusion criteria. Among these studies, eight reported the risk of mortality, and eight reported the risk of HCC. Three studies provided SBP rates, and two documented ascites rates. Four articles focused on HE rates, and three focused on variceal bleeding rates. Meta-analysis indicated that T2DM was significantly associated with an increased risk of liver transplant-free mortality [OR: 1.28, 95% confidence intervals (CI): 1.16-1.41, P < 0.0001] and HCC incidence (OR: 1.82, 95%CI: 1.32-2.51, P = 0.003). The risk of SBP was not significantly increased (OR: 1.16 95%CI: 0.86-1.57, P = 0.34). Additionally, T2DM did not significantly increase HE (OR: 1.31 95%CI: 0.97-1.77, P = 0.08), ascites (OR: 1.11 95%CI: 0.84-1.46, P = 0.46), and variceal bleeding (OR: 1.34, 95%CI: 0.99-1.82, P = 0.06). CONCLUSION The findings suggest that cirrhotic patients with T2DM have a poor prognosis and high risk of HCC. T2DM may not be associated with an increased risk of SBP, variceal bleeding, ascites, or HE in cirrhotic patients with T2DM.
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Affiliation(s)
- Zi-Jin Liu
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing 100069, China
| | - Yi-Jie Yan
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing 100069, China
| | - Hong-Lei Weng
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Mannheim 68167, Germany
| | - Hui-Guo Ding
- Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated to Capital Medical University, Beijing 100069, China
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Lai RM, Chen TB, Hu YH, Wu G, Zheng Q. Effect of type 2 diabetic mellitus in the prognosis of acute-on-chronic liver failure patients in China. World J Gastroenterol 2021; 27:3372-3385. [PMID: 34163118 PMCID: PMC8218358 DOI: 10.3748/wjg.v27.i23.3372] [Citation(s) in RCA: 7] [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: 01/28/2021] [Revised: 04/14/2021] [Accepted: 05/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) patients have a high short-term mortality rate, and the severity evaluation of ACLF is necessary for prognostication. Therefore, it was meaningful to evaluate the association between type 2 diabetic mellitus (DM) and ACLF and further explore the feasibility of using DM as a prognostic indicator in ACLF patients. The association between type 2 DM and the prognosis of patients with severe liver disease remains unclear.
AIM To examine the effect of type 2 DM on the prognosis of patients with ACLF.
METHODS Clinical data from 222 ACLF patients were collected and analyzed. The patients were categorized into two groups depending on whether they had DM or not, and the clinical data of ACLF patients were measured within 48 h after admission. Complications of ACLF were documented during treatment, such as hepatic encephalopathy, hepatorenal syndrome, acute upper gastrointestinal hemorrhage, and spontaneous peritonitis (SBP). Values of laboratory parameters, complication rates, and hospital mortality rates were compared between two groups.
RESULTS Among 222 ACLF patients, 38 cases were categorized into DM groups, the mean age was 56.32 years and 73.68% were male. The prognosis of ACLF patients was significantly correlated with DM in univariate [hazard ratio (HR) = 2.4, 95% confidence interval (CI) =1.5-3.7, P < 0.001] and multivariable analysis (HR = 3.17, 95%CI =1.82-5.523, P < 0.001). The incident of SBP (34.21% vs 13.59%, P = 0.038) and other infections like lung, urinary, blood, and cholecyst (44.74% vs 28.26%, P = 0.046) were higher in DM patients than non-DM counterparts. In addition, the ACLF patients with DM tended to have a high mortality rate (P < 0.001). Cumulative survival time was also significantly shorter in the ACLF patients with DM than non-DM.
CONCLUSION A significant association between DM and the prognosis of ACLF patients was found in China. The ACLF patients with DM had higher incidence of hospital mortality and infection than those without DM.
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Affiliation(s)
- Rui-Min Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Tian-Bin Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yu-Hai Hu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Gui Wu
- Department of Orthopedics, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Ahn SB, Powell EE, Russell A, Hartel G, Irvine KM, Moser C, Valery PC. Type 2 Diabetes: A Risk Factor for Hospital Readmissions and Mortality in Australian Patients With Cirrhosis. Hepatol Commun 2020; 4:1279-1292. [PMID: 32923832 PMCID: PMC7471423 DOI: 10.1002/hep4.1536] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 03/05/2020] [Accepted: 04/15/2020] [Indexed: 12/23/2022] Open
Abstract
Although there is evidence that type 2 diabetes mellitus (T2D) impacts adversely on liver-related mortality, its influence on hospital readmissions and development of complications in patients with cirrhosis, particularly in alcohol-related cirrhosis (the most common etiological factor among Australian hospital admissions for cirrhosis) has not been well studied. This study aimed to investigate the association between T2D and liver cirrhosis in a population-based cohort of patients admitted for cirrhosis in the state of Queensland, Australia. A retrospective cohort analysis was conducted using data from the Queensland Hospital Admitted Patient Data Collection, which contains information on all hospital episodes of care for patients with liver cirrhosis, and the Death Registry during 2008-2017. We used demographic, clinical data, and socioeconomic characteristics. A total of 8,631 patients were analyzed. A higher proportion of patients with T2D had cryptogenic cirrhosis (42.4% vs. 27.3%, respectively; P < 0.001) or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (13.8% vs. 3.4%, respectively; P < 0.001) and an admission for hepatocellular carcinoma (18.0% vs. 12.2%, respectively; P < 0.001) compared to patients without T2D. Patients with liver cirrhosis with T2D compared to those without T2D had a significantly increased median length of hospital stay (6 [range, 1-11] vs. 5 [range, 1-11] days, respectively; P < 0.001), double the rate of noncirrhosis-related admissions (incidence rate ratios [IRR], 2.03; 95% confidence interval [CI], 1.98-2.07), a 1.35-fold increased rate of cirrhosis-related admissions (IRR, 1.35; 95% CI, 1.30-1.41), and significantly lower survival (P < 0.001). Conclusion: Among hospitalized patients with cirrhosis, the cohort with T2D is at higher risk and may benefit from attention to comorbidities and additional support to reduce readmissions.
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Affiliation(s)
- Sang Bong Ahn
- QIMR Berghofer Medical Research InstituteHerstonAustralia
- Department of Internal MedicineEulji University School of MedicineSeoulKorea
| | - Elizabeth E. Powell
- Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneAustralia
- Department of Gastroenterology and HepatologyPrincess Alexandra HospitalBrisbaneAustralia
| | - Anthony Russell
- Department of Diabetes and EndocrinologyUniversity of QueenslandBrisbaneAustralia
| | - Gunter Hartel
- QIMR Berghofer Medical Research InstituteHerstonAustralia
| | - Katharine M. Irvine
- Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneAustralia
- Mater ResearchUniversity of QueenslandBrisbaneAustralia
| | - Chris Moser
- Statistical Services BranchQueensland HealthBrisbaneAustralia
| | - Patricia C. Valery
- QIMR Berghofer Medical Research InstituteHerstonAustralia
- Centre for Liver Disease ResearchTranslational Research InstituteFaculty of MedicineUniversity of QueenslandBrisbaneAustralia
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Lee WG, Wells CI, McCall JL, Murphy R, Plank LD. Prevalence of diabetes in liver cirrhosis: A systematic review and meta-analysis. Diabetes Metab Res Rev 2019; 35:e3157. [PMID: 30901133 DOI: 10.1002/dmrr.3157] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 03/05/2019] [Accepted: 03/19/2019] [Indexed: 12/20/2022]
Abstract
An association between diabetes mellitus (DM) and liver cirrhosis is well-known, but estimates of the prevalence of DM in patients with liver cirrhosis vary widely. A systematic review was undertaken to determine the prevalence of DM in adult patients with liver cirrhosis. The Medline, EMBASE, and Cochrane Library databases were searched for peer-reviewed studies published in English (1979-2017) that investigated the prevalence of diabetes in adult patients with cirrhosis. Pooled estimates of prevalence of DM were determined for all eligible patients and according to aetiology and severity of liver disease. Fifty-eight studies satisfied criteria for inclusion, with 9705 patients included in the pooled prevalence analysis. The overall prevalence of DM was 31%. The prevalence of DM was highest in patients with nonalcoholic fatty liver disease (56%), cryptogenic (51%), hepatitis C (32%), or alcoholic (27%) cirrhosis. For assessing prevalence of DM as a function of severity of liver disease, evaluable data were available only for hepatitis C and hepatitis B cirrhosis. DM may be more prevalent in cirrhosis than previously thought. This has implications for prognosis and treatment in these patients.
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Affiliation(s)
- Wai Gin Lee
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - John L McCall
- Section of Surgery, Department of Medical and Surgical Sciences, University of Otago, Dunedin, New Zealand
| | - Rinki Murphy
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
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Bossen L, Dam GA, Vilstrup H, Watson H, Jepsen P. Diabetes does not increase infection risk or mortality following an infection in patients with cirrhosis and ascites. JHEP Rep 2019; 1:265-269. [PMID: 32039377 PMCID: PMC7001534 DOI: 10.1016/j.jhepr.2019.07.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Revised: 07/19/2019] [Accepted: 07/29/2019] [Indexed: 12/15/2022] Open
Abstract
Both cirrhosis and diabetes are established risk factors for infections. However, it remains uncertain whether diabetes adds to the risk of infections in patients with cirrhosis who are already at high risk of infections, or increases the mortality following an infection. To answer these questions, we followed a cohort of trial participants with cirrhosis and ascites for 1 year to compare the incidence of infections and post-infection mortality between those with or without diabetes. Methods We used Cox regression to estimate the hazard ratio (HR) of any infection, adjusting for confounding by patient age, gender, MELD score, albumin, use of proton pump inhibitors and lactulose, cirrhosis aetiology, and severity of ascites. Further, we analysed the mortality after infection. Results Among 1,198 patients with cirrhosis and ascites, diabetics (n = 289, 24%) were more likely than non-diabetics (n = 909, 76%) to be old and male, to have low platelets, and to use lactulose. At inclusion, similar proportions of diabetic and non-diabetic patients were taking a quinolone antibiotic (13% vs. 12%) and they had similar median MELD scores (14 vs. 15). During the follow-up, 446 patients had an infection. Diabetes did not increase the HR of infections (adjusted HR 1.08; 95% CI 0.87–1.35). Further, diabetes did not increase the mortality following an infection (adjusted HR 0.93; 95% CI 0.64–1.35). Conclusions In patients with cirrhosis and ascites, diabetes did not increase infection risk or mortality after infection. The immune incompetence of each disease did not appear to be additive. In clinical terms, this means that particular attention to infections is not indicated in patients with cirrhosis and diabetes. Lay summary Cirrhosis and diabetes are chronic diseases that weaken the immune system and increase the risk of infections, but it is unknown whether their combined effects exceed the effect of cirrhosis alone. We showed that the risk of infections was the same in patients with cirrhosis, ascites and diabetes as in patients with cirrhosis and ascites alone. Thus, their combined effects do not exceed the effect of cirrhosis alone.
Cirrhosis and diabetes both increase the risk of infections. In patients with cirrhosis, diabetes does not increase the risk of infection. In patients with cirrhosis, diabetes does not increase mortality among those infected.
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Affiliation(s)
- Lars Bossen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Gitte A Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Hugh Watson
- Evotec ID, Lyon, France.,Department of Clinical Pharmacology, Aarhus University, Aarhus, Denmark
| | - Peter Jepsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.,Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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9
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Tergast TL, Laser H, Gerbel S, Manns MP, Cornberg M, Maasoumy B. Association Between Type 2 Diabetes Mellitus, HbA1c and the Risk for Spontaneous Bacterial Peritonitis in Patients with Decompensated Liver Cirrhosis and Ascites. Clin Transl Gastroenterol 2018; 9:189. [PMID: 30250034 PMCID: PMC6155293 DOI: 10.1038/s41424-018-0053-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/06/2018] [Accepted: 08/11/2018] [Indexed: 12/15/2022] Open
Abstract
Introduction Type 2 diabetes mellitus (DM) is a frequent comorbidity among patients with liver cirrhosis. However, data regarding the impact of DM on spontaneous bacterial peritonitis (SBP) are quite limited. Our aim was to analyze the impact of DM and HbA1c values on the incidence of SBP and mortality in patients with liver cirrhosis and ascites. Methods A number of 475 consecutive patients with liver cirrhosis and ascites were analyzed. Presence of DM as well as HbA1c was assessed at the time of the first paracentesis. Patients were followed up for a mean of 266 days. Primary endpoints were SBP development and mortality. Results Overall, 118 (25%) patients were diagnosed with DM. DM patients had an increased risk for developing a SBP during follow-up (HR: 1.51; p = 0.03). SBP incidence was particularly high in DM patients with HbA1c values ≥6.4%, significantly higher than in DM patients with HbA1c values <6.4% (HR: 4.21; p = 0.0002). Of note, DM patients with HbA1c <6.4% at baseline had a similar risk for SBP as those without DM (HR: 0.93; p = 0.78, respectively). After excluding all patients who were eligible for secondary antibiotic prophylaxis, HbA1c ≥6.4% but neither bilirubin nor ascites protein level were associated with primary SBP development in the multivariate analysis (p = 0.003). Conclusions Individuals with liver cirrhosis and concomitant DM have a higher risk for developing a SBP. HbA1c values may be useful to further stratify the risk for SBP among DM patients, which may help to identify those who benefit from antibiotic prophylaxis.
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Affiliation(s)
- Tammo L Tergast
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - Hans Laser
- Centre for Information Management (ZIMt), Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - Svetlana Gerbel
- Centre for Information Management (ZIMt), Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany.,German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.,Centre for Individualised Infection Medicine (CIIM), c/o CRC Hannover, Feodor-Lynen-Str. 15, 30625, Hannover, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany. .,German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany. .,Centre for Individualised Infection Medicine (CIIM), c/o CRC Hannover, Feodor-Lynen-Str. 15, 30625, Hannover, Germany.
| | - Benjamin Maasoumy
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany. .,German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung DZIF), Partner-site Hannover-Braunschweig, Hannover, Germany.
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10
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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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Salvianolate Reduces Glucose Metabolism Disorders in Dimethylnitrosamine-Induced Cirrhotic Rats. Chin J Integr Med 2017; 24:661-669. [PMID: 29209957 DOI: 10.1007/s11655-017-2773-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/11/2016] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the preventive effect of salvianolate (Sal B) on glucose metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats. METHODS Fifty-five Wistar rats were randomly divided into a control group (n=10) and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups (n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B (50 mg/kg), metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline (HYP) and liver function were detected at the end of the treatment. Area under the curve (AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining (HE), Sirius Red staining and Masson's trichrome staining, respectively. Hepatic expression of α-smooth muscle actin (α-SMA) and collagen (Col I) were evaluated by immunohistochemical staining. RESULTS Compared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently than Sal B (P<0.05). CONCLUSIONS Sal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.
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12
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Ramachandran TM, Rajneesh AHR, Zacharia GS, Adarsh RP. Cirrhosis of Liver and Diabetes Mellitus: The Diabolic Duo? J Clin Diagn Res 2017; 11:OC01-OC05. [PMID: 29207749 DOI: 10.7860/jcdr/2017/30705.10529] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 08/08/2017] [Indexed: 12/26/2022]
Abstract
Introduction Cirrhosis of the liver and diabetes mellitus are two chronic illnesses with significant impact on the quality of life. Studies from different part of the world have shown the combination to be associated with higher incidence of complications of cirrhosis and reduced survival. However, data on the impact of pre-cirrhotic and post-cirrhotic diabetes on cirrhosis is minimal. Aim The aim of the study was to determine the complications of cirrhosis patients with and without co-existent DM and to compare the relation between cirrhosis patients with antecedent DM and hepatogenous DM. Materials and Methods The present prospective study was conducted at a tertiary care hospital in Kerala, India, over a period of three years. Cirrhosis patients with and without diabetes, along with subcategorization as antecedent and hepatogenous diabetes, were studied for various complications and outcome including death. Chi-square and Mann-whitney tests were used for comparing data. Results Patients with cirrhosis and diabetes had higher incidence of gall stones (27.6% versus 13.2%; p=0.008) and urinary infection (29.3% versus 7.5%; p=<0.001). Incidence of hepatocellular carcinoma and mortality were similar between the groups. Patients with antecedent diabetes and hepatogenous diabetes were similar with respect to complications and mortality. Child-Turcotte-Pugh (CTP) score, Model for End stage Liver Disease (MELD) score, urinary tract and respiratory infections and duration of cirrhosis were independent predictors of mortality in patients with cirrhosis. Conclusion Coexistent diabetes mellitus increases the incidence of complications and hospitalizations in cirrhosis patients but without impact on mortality rates. There is no significant morbidity or mortality difference between cirrhotics with antecedent diabetes and hepatogenous diabetes.
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Affiliation(s)
- Thazhath Mavali Ramachandran
- Additional Professor, Department of Medical Gastroenterology, Government Medical College, Kozhikode, Kerala, India
| | | | - George Sarin Zacharia
- Senior Resident, Department of Medical Gastroenterology, Government Medical College, Kozhikode, Kerala, India
| | - Rajendran P Adarsh
- Senior Resident, Department of Medical Gastroenterology, Government Medical College, Kozhikode, Kerala, India
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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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14
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Li X, Xu H, Gao Y, Pan M, Wang L, Gao P. Diabetes mellitus increases the risk of hepatocellular carcinoma in treatment-naïve chronic hepatitis C patients in China. Medicine (Baltimore) 2017; 96:e6508. [PMID: 28353605 PMCID: PMC5380289 DOI: 10.1097/md.0000000000006508] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
We investigated the link between diabetes mellitus (DM) and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) risk in treatment-naïve chronic hepatitis C (CHC) patients in China.To examine the association between DM and HCC, we conducted a case-control study of 300 Chinese CHC patients with HCC, compared to an age- and sex-matched control group of 517 CHC patients not diagnosed with HCC.We found that DM was more prevalent in the HCC patient group (18.7%) than in the CHC-only patient group (10.8%). We conducted logistic regression analyses adjusting for demographics features and other HCC risk factors and found that DM increased the risk of HCC development nearly 2-fold [adjusted odds ratio (AOR), 95% confidence interval (95% CI), 1.80 (1.17-2.75)]. Meanwhile, the proportion of HCC patients and CHC-only patients with liver cirrhosis were 79.3% and 46.2%, respectively, yielding an AOR of 4.62 (95% CI, 3.31-6.46). Multivariate analyses comparing the risk of HCV-related HCC development in DM patients with and without liver cirrhosis revealed that the estimated AOR (95% CI) for those with liver cirrhosis was 5.60 (2.25-13.96). However, the HCC risk decreased significantly with a later age of diabetes onset (AOR [95% CI], 0.94 [0.89-0.99]).DM was associated with an increased risk for HCC development in treatment-naïve CHC patients in China. Furthermore, liver cirrhosis and an early DM diagnoses further increased the risks of HCC development in patients diagnosed with both CHC and DM.
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Affiliation(s)
- Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
- Jilin Province Key Laboratory of Infectious Disease, Laboratory of Molecular Virology
| | - Yang Gao
- Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun, China
| | - Meng Pan
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Le Wang
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University
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15
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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] [MESH Headings] [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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Isoda H, Takahashi H, Eguchi Y, Kojima M, Inoue K, Murayama K, Matsuda Y, Anzai K. Re-evaluation of glycated hemoglobin and glycated albumin with continuous glucose monitoring system as markers of glycemia in patients with liver cirrhosis. Biomed Rep 2016; 6:51-56. [PMID: 28123707 PMCID: PMC5244784 DOI: 10.3892/br.2016.808] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 09/22/2016] [Indexed: 12/20/2022] Open
Abstract
Liver cirrhosis (LC) is frequently accompanied by glucose intolerance. The present study was designed to determine whether glycated hemoglobin A1c (HbA1c) and glycated albumin (GA) were predictive markers of glycemia, as determined by a continuous glucose monitoring system (CGMS), in patients with LC. A total of 30 patients with LC, including 3, 19, 5, 2 and 1 with LC due to hepatitis B virus, hepatitis C virus, non-alcoholic steatohepatitis, alcohol and unknown causes, respectively, were assessed by CGMS. The average, maximum and minimum blood glucose (BG) levels were measured by CGMS, and correlated with HbA1c and GA. The average, maximum and minimum BG in these individuals were 142±38.7, 209.3±65.7 and 85.1±25.4 mg/dl, respectively. HbA1c was significantly correlated with average BG (r=0.447, P=0.015) and maximum BG (r=0.523, P=0.004). In addition, GA was significantly correlated with average BG (r=0.687, P<0.001) and maximum BG (r=0.648, P<0.001). Neither HbA1c nor GA was significantly correlated with minimum BG. Correlation analysis yielded formulas by which HbA1c and GA were predictive of average BG in individuals with LC: Average BG=19.2 × HbA1c (%) + 36.5 and average BG=6.6 × GA (%) + 13.0, respectively. In conclusion, HbA1c and GA showed significant correlations with average and maximum BG, as determined by CGMS. The derived formulas allow for estimates of average BG based on HbA1c and GA, and may contribute to the control of glycemia in patients with LC.
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Affiliation(s)
- Hiroshi Isoda
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
| | - Hirokazu Takahashi
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
| | - Yuichiro Eguchi
- Division of Hepatology, Liver Center, Saga Medical School, Saga 8498501, Japan
| | - Motoyasu Kojima
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
| | - Kanako Inoue
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
| | - Kenichiro Murayama
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
| | - Yayoi Matsuda
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
| | - Keizo Anzai
- Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga 8498501, Japan
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Liu TL, Trogdon J, Weinberger M, Fried B, Barritt AS. Diabetes Is Associated with Clinical Decompensation Events in Patients with Cirrhosis. Dig Dis Sci 2016; 61:3335-3345. [PMID: 27480088 DOI: 10.1007/s10620-016-4261-8] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Accepted: 07/20/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Liver cirrhosis is a leading cause of morbidity and mortality in the USA. Diabetes is common and increasing in incidence. Patients with compensated cirrhosis and diabetes may be at greater risk of clinical decompensation. We examined the risk of decompensation among a large sample of working-aged insured patients dually diagnosed with compensated cirrhosis and diabetes. METHODS This retrospective study used MarketScan® Commercial Claims and Encounters and Medicare Supplemental Databases (2000-2013). Decompensation events included incident ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, acute renal failure, and hepatocellular carcinoma. Dually diagnosed patients were defined as patients with cirrhosis and diabetes using previously published ICD-9 coding strategies. Adjusted odds ratios (ORs), hazard ratios (HRs), and confidence intervals (CI) were estimated using logistic regression and Cox proportional hazard models. RESULTS Of 72,731 patients with compensated cirrhosis, 20,477 patients (28.15 %) were diagnosed with diabetes. After controlling for patient characteristics and medication usage, the odds of developing any decompensation event were 1.14 times higher for patients with cirrhosis and diabetes than for patients with cirrhosis only (95 % CI 1.08-1.21, P value <0.01). In the Cox proportional hazard model, patients who were dually diagnosed with diabetes had a 1.32 times higher HR (95 % CI 1.26-1.39, P value <0.01) after controlling for time-to-event. CONCLUSIONS Patients dually diagnosed with compensated cirrhosis and diabetes had a higher risk of having decompensation events. Careful management of diabetes in patients with liver disease may reduce the risk of clinical decompensation in this population.
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Affiliation(s)
- Tsai-Ling Liu
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 1101 McGavran-Greenberg Hall, CB #7411, Chapel Hill, NC, 27599-7411, USA
| | - Justin Trogdon
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 1101B McGavran-Greenberg Hall, CB #7411, Chapel Hill, NC, 27599-7411, USA
| | - Morris Weinberger
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 1105B McGavran-Greenberg Hall, CB #7411, Chapel Hill, NC, 27599-7411, USA
- Durham VAMC Center for Health Services Research, Durham, NC, USA
| | - Bruce Fried
- Department of Health Policy and Management, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 1104E McGavran-Greenberg Hall, CB #7411, Chapel Hill, NC, 27599-7411, USA
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill, 8004 Burnett Womack, CB #7584, Chapel Hill, NC, 27599-7584, USA.
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18
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Zhang X, Harmsen WS, Mettler TA, Kim WR, Roberts RO, Therneau TM, Roberts LR, Chaiteerakij R. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology 2014; 60:2008-16. [PMID: 24798175 PMCID: PMC4218882 DOI: 10.1002/hep.27199] [Citation(s) in RCA: 140] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Accepted: 04/29/2014] [Indexed: 12/07/2022]
Abstract
UNLABELLED The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment. This study investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with diabetes. Diabetic patients diagnosed with cirrhosis between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were identified (n = 250). Data were retrospectively abstracted from the medical record. Survival of patients who continued versus discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox's proportional hazards analysis. Overall, 172 patients continued metformin whereas 78 discontinued metformin. Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11.8 vs. 5.6 years overall, P < 0.0001; 11.8 vs. 6.0 years for Child A patients, P = 0.006; and 7.7 vs. 3.5 years for Child B/C patients, P = 0.04, respectively). After adjusting for other variables, continuation of metformin remained an independent predictor of better survival, with an HR of 0.43 (95% CI: 0.24-0.78; P = 0.005). No patients developed metformin-associated lactic acidosis during follow-up. CONCLUSION Continuation of metformin after cirrhosis diagnosis reduced the risk of death by 57%. Metformin should therefore be continued in diabetic patients with cirrhosis if there is no specific contraindication.
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Affiliation(s)
- Xiaodan Zhang
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - William S. Harmsen
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, College of Medicine, Mayo Clinic and Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Teresa A. Mettler
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - W. Ray Kim
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Rosebud O. Roberts
- Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, and Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Terry M. Therneau
- Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, College of Medicine, Mayo Clinic and Mayo Clinic Cancer Center, Rochester, Minnesota, USA
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
- Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
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Abstract
Cirrhosis patients’ comorbidities are their other diseases than cirrhosis. Comorbidities are neither causes nor consequences of cirrhosis, but they can increase mortality and are therefore clinically important. They are also an important source of confounding in epidemiologic studies. Comorbidity scoring systems have been developed as tools to measure the cirrhosis patient’s total burden of comorbidity, and they are useful in the clinic and for epidemiologic studies. The recently developed CirCom score is the only comorbidity scoring system developed specifically for cirrhosis patients, and it may be preferred over the older, generic, and more complex Charlson comorbidity index. Studies of individual comorbid diseases can provide insight into the interactions between cirrhosis and other diseases and thus into the pathophysiology of cirrhosis. This article reviews the literature on comorbidity in cirrhosis.
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