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Simó-Servat O, Amigó J, Ortiz-Zúñiga Á, Sánchez M, Cuadra F, Santos MD, Rojano A, Abadías MJ, Roman A, Hernández C, Simó R. SMART DIABETES HOSPITAL: CLINICAL IMPACT IN COMPLEX SURGICAL UNITS OF A TERTIARY HOSPITAL. Acta Diabetol 2025; 62:423-428. [PMID: 39240308 PMCID: PMC11872769 DOI: 10.1007/s00592-024-02370-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 08/21/2024] [Indexed: 09/07/2024]
Abstract
AIM To evaluate the impact of a proactive action of a specialized diabetes team (SDT) on different health outcomes in patients hospitalized in high complexity surgery units, including solid organ transplant surgical units, of a tertiary hospital. METHODS Nested case control study matched (1:1) by age and gender. The control group consisted of patients (n = 120) who were under the standard of care diabetes management admitted three months' prior the cases. The cases were admitted in the same surgical units (n = 120) and were treated in the setting of the so called "Smart Diabetes Hospital" (SDH) consisting in a SDT that prioritized their actions through a digital map showing blood glucose levels obtained during the previous 24 h. RESULTS SDH implementation resulted in a significant reduction in both blood glucose levels (mean 162.1 ± SD 44.4 vs. mean 145.5 ± SD 48.0; p = 0.008) and hypoglycaemic episodes (19.7% vs. 8.4%: p = 0.002). Furthermore, a reduction of 3 days in the length of stay (LOS) was observed (15.6 ± 10.3 vs. 12.4 ± 6.0), which represents a significant cost-saving. Moreover, more new cases of diabetes were detected during the SDT period (2.5% vs. 6.7%, p = 0.04). CONCLUSION SDH is effective in diabetes management and reduce LOS in complex surgical units.
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Affiliation(s)
- Olga Simó-Servat
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain.
| | - Judit Amigó
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
| | - Ángel Ortiz-Zúñiga
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
| | - Mónica Sánchez
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
| | - Fátima Cuadra
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
| | - Marcos Dos Santos
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
| | - Alba Rojano
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
| | - Maria José Abadías
- Health Services Research Group, Vall d'Hebron Research Institute and Vall d'Hebron University Hospital, Barcelona, Spain
| | - Antonio Roman
- Health Services Research Group, Vall d'Hebron Research Institute and Vall d'Hebron University Hospital, Barcelona, Spain
| | - Cristina Hernández
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain
- Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Rafael Simó
- Endocrinology and Nutrition Department, Vall d'Hebron University Hospital and Vall d'Hebron Research Institute, Barcelona, Spain.
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), Madrid, Spain.
- Universitat Autònoma de Barcelona, Barcelona, Spain.
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Popović L, Bulum T. New Onset Diabetes After Organ Transplantation: Risk Factors, Treatment, and Consequences. Diagnostics (Basel) 2025; 15:284. [PMID: 39941214 PMCID: PMC11816453 DOI: 10.3390/diagnostics15030284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/15/2025] [Accepted: 01/23/2025] [Indexed: 02/16/2025] Open
Abstract
New onset diabetes mellitus after organ transplantation (NODAT) is a frequent and serious complication of solid organ transplantation. It significantly impacts graft function, patient survival, and quality of life. NODAT is diagnosed based on the criteria for type 2 diabetes, with the oral glucose tolerance test (OGTT) serving as the gold standard for diagnosis. The development of NODAT is influenced by a range of risk factors, which are classified into modifiable and non-modifiable categories. Post-transplant, regular glycemic monitoring at specific intervals is essential for timely diagnosis and initiation of therapy. Early intervention can help prevent or delay the onset of diabetes-related complications. The treatment strategy for NODAT involves lifestyle modifications and pharmacological interventions. These include medications such as metformin, sulfonylureas, glinides, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and insulin. Adjusting immunosuppressive therapy-either by reducing dosages or substituting drugs with lower diabetogenic potential-is a common preventative and therapeutic measure. However, this must be performed cautiously to avoid acute graft rejection, which poses a greater risk to the patient compared to NODAT itself. In addition to managing diabetes, addressing comorbidities such as hypertension and dyslipidemia is crucial, as they elevate the risk of cardiovascular events and mortality. Patients with NODAT are also prone to developing common diabetes-related complications, including diabetic nephropathy, neuropathy, retinopathy, and peripheral vascular disease. Therefore, regular follow-ups and appropriate treatment are vital to maintaining quality of life and improving long-term outcomes.
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Affiliation(s)
- Lucija Popović
- Department of Emergency Medicine, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia
| | - Tomislav Bulum
- School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia
- Department of Diabetes and Endocrinology, Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Dugi dol 4a, 10000 Zagreb, Croatia
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3
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Ahmed M, Ahmed MH. Ramadan Fasting in Individuals with Metabolic Dysfunction-Associated Steatotic Liver Disease, Liver Transplant, and Bariatric Surgery: A Narrative Review. J Clin Med 2024; 13:3893. [PMID: 38999457 PMCID: PMC11242100 DOI: 10.3390/jcm13133893] [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: 05/22/2024] [Revised: 06/25/2024] [Accepted: 07/01/2024] [Indexed: 07/14/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease is a growing worldwide pandemic. A limited number of studies have investigated the potential effect of Ramadan fasting on metabolic dysfunction-associated steatotic liver disease (MASLD). There is no single medication for the treatment of MASLD. There is a growing interest in dietary intervention as potential treatment for metabolic diseases including MASLD. The aim of this study was to discuss the epidemiology, pathogenesis, and risk factors of MASLD and the potential effects of Ramadan fasting on MASLD, liver transplant, and bariatric surgery. We searched PubMed and SCOPUS databases using different search terms. The literature search was based on research studies published in English from the year 2000 to the 2024. Thirty-two studies were included in this review. Ramadan fasting reduced body weight and improved lipid profile, anthropometric indices, fasting plasma glucose, plasma insulin, and inflammatory cytokines. Ramadan fasting improved risk factors of nonalcoholic fatty liver disease and might improve MASLD through weight reduction. However, further studies are needed to assess the safety and effectiveness of Ramadan fasting in liver transplant recipients and bariatric surgery.
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Affiliation(s)
- Musaab Ahmed
- College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Mohamed H Ahmed
- Department of Medicine and HIV Metabolic Clinic, Milton Keynes University Hospital NHS Foundation Trust, Eagelstone, Milton Keynes MK6 5LD, UK
- Department of Geriatric Medicine, Milton Keynes University Hospital NHS Foundation Trust, Eagelstone, Milton Keynes MK6 5LD, UK
- Honorary Senior Lecturer of the Faculty of Medicine and Health Sciences, University of Buckingham, Buckingham MK18 1EG, UK
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4
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Alajous S, Budhiraja P. New-Onset Diabetes Mellitus after Kidney Transplantation. J Clin Med 2024; 13:1928. [PMID: 38610694 PMCID: PMC11012473 DOI: 10.3390/jcm13071928] [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: 02/01/2024] [Revised: 03/19/2024] [Accepted: 03/24/2024] [Indexed: 04/14/2024] Open
Abstract
New-Onset Diabetes Mellitus after Transplantation (NODAT) emerges as a prevalent complication post-kidney transplantation, with its incidence influenced by variations in NODAT definitions and follow-up periods. The condition's pathophysiology is marked by impaired insulin sensitivity and β-cell dysfunction. Significant risk factors encompass age, gender, obesity, and genetics, among others, with the use of post-transplant immunosuppressants intensifying the condition. NODAT's significant impact on patient survival and graft durability underscores the need for its prevention, early detection, and treatment. This review addresses the complexities of managing NODAT, including the challenges posed by various immunosuppressive regimens crucial for transplant success yet harmful to glucose metabolism. It discusses management strategies involving adjustments in immunosuppressive protocols, lifestyle modifications, and pharmacological interventions to minimize diabetes risk while maintaining transplant longevity. The importance of early detection and proactive, personalized intervention strategies to modify NODAT's trajectory is also emphasized, advocating for a shift towards more anticipatory post-transplant care.
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Affiliation(s)
| | - Pooja Budhiraja
- Division of Medicine, Mayo Clinic Arizona, Phoenix, AZ 85054, USA;
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Taneja S, Roy A, Duseja A. NASH After Liver Transplantation: Impact of Immunosuppression. J Clin Exp Hepatol 2023; 13:835-840. [PMID: 37693259 PMCID: PMC10483005 DOI: 10.1016/j.jceh.2023.03.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Accepted: 03/28/2023] [Indexed: 09/12/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the common causes of cirrhosis and hepatocellular carcinoma (HCC) and is a leading indication for liver transplantation (LT). Patients with NAFLD-related cirrhosis and HCC are at high risk for the development of recurrent NAFLD after LT. NAFLD can also develop de novo post-transplantation in patients subjected to LT for other indications. Besides the pretransplant presence of various components of metabolic syndrome (MS) use of immunosuppressive agents in the post-LT setting forms one of the major drivers for the development of post-LT NAFLD. Individual components of conventional immunosuppressive regimens (corticosteroids, calcineurin inhibitors, and m-TOR inhibitors) are all implicated in the development of post-LT metabolic derangement and follow unique mechanisms of action and degree of disturbances. The development of cardiovascular risk is associated with post-LT NAFLD, although graft outcomes do not seem to be influenced only by the presence of post-LT NAFLD. Measures in consonance with the management of NAFLD, in general, including lifestyle modifications and control of metabolic risk factors, hold true for post-LT NAFLD. Tailoring immunosuppression strategies with early corticosteroid withdrawal and calcineurin inhibitor minimization balancing against the risk of graft rejection constitutes important nuances in the individualized management of post-LT NAFLD.
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Affiliation(s)
- Sunil Taneja
- Department of Hepatology, Postgraduate Institute on Medical Education & Research, Chandigarh, India
| | - Akash Roy
- Institute of Gastrosciences and Liver Transplantation Apollo Multispeciality Hospitals, Kolkata, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute on Medical Education & Research, Chandigarh, India
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6
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Zhang Z, Sun J, Guo M, Yuan X. Progress of new-onset diabetes after liver and kidney transplantation. Front Endocrinol (Lausanne) 2023; 14:1091843. [PMID: 36843576 PMCID: PMC9944581 DOI: 10.3389/fendo.2023.1091843] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/27/2023] [Indexed: 02/11/2023] Open
Abstract
Organ transplantation is currently the most effective treatment for end-stage organ failure. Post transplantation diabetes mellitus (PTDM) is a severe complication after organ transplantation that seriously affects the short-term and long-term survival of recipients. However, PTDM is often overlooked or poorly managed in its early stage. This article provides an overview of the incidence, and pathogenesis of and risk factors for PTDM, aiming to gain a deeper understanding of PTDM and improve the quality of life of recipients.
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Affiliation(s)
- Zhen Zhang
- Department of Urology, The People's Hospital of Linyi, Linyi, Shandong, China
| | - Jianyun Sun
- Department of Gastroenterology, The People's Hospital of Linyi, Linyi, Shandong, China
| | - Meng Guo
- National Key Laboratory of Medical Immunology &Institute of Immunology, Navy Medical University, Shanghai, China
| | - Xuemin Yuan
- Department of Gastroenterology, The People's Hospital of Linyi, Linyi, Shandong, China
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Dos Santos Q, Hornum M, Terrones-Campos C, Crone CG, Wareham NE, Soeborg A, Rasmussen A, Gustafsson F, Perch M, Soerensen SS, Lundgren J, Feldt-Rasmussen B, Reekie J. Posttransplantation Diabetes Mellitus Among Solid Organ Recipients in a Danish Cohort. Transpl Int 2022; 35:10352. [PMID: 35449717 PMCID: PMC9016119 DOI: 10.3389/ti.2022.10352] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/15/2022] [Indexed: 12/15/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0–45 days; 46–365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46–365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16–2.69 and aHR: 1.89, 95% CI: 1.17–3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients.
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Affiliation(s)
- Quenia Dos Santos
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Mads Hornum
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Cynthia Terrones-Campos
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Cornelia Geisler Crone
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Neval Ete Wareham
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Soeborg
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Allan Rasmussen
- Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen, Denmark
| | - Finn Gustafsson
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | - Michael Perch
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | | | - Jens Lundgren
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Bo Feldt-Rasmussen
- Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Joanne Reekie
- Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Ouni A, Sahtout W, Hadj Brahim M, Azzabi A, Aicha NB, Mrabet S, Fradi A, Zallema D, Guedri Y, Achour A. New-Onset Diabetes as a Complication After Kidney Transplant: Incidence and Outcomes. EXP CLIN TRANSPLANT 2022; 20:129-131. [PMID: 35384822 DOI: 10.6002/ect.mesot2021.p56] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Diabetes after kidney transplant is a common complication. It may increase the risk of cardiovascular disease and mortality after kidney transplant. The aim of this study was to examine the effects of diabetes that developed after transplant on outcomes in kidney transplant recipients. MATERIALS AND METHODS This study included renal allograft recipients without diabetes who received transplants from 2008 to 2019 in our Department of Nephrology at Sahloul Hospital (Tunisia). Demographic and clinical data at transplant time and clinical events during the study period were collected. Patient and graft survival rates were analyzed. Patients with and without diabetes after transplant were compared. RESULTS In the 257 patients (median age of 36 years) included in our study, the overall incidence of diabetes after transplant was 21.8%. Laboratory data (serum cholesterol, serum creatinine at discharge, and 24-hour proteinuria) were similar in those with and without diabetes after transplant. We observed no significant differences in cardiovascular diseases and infectious complication rates between patients with and without diabetes after transplant. There was also no significant difference in graft loss at 5 years between those with and without diabetes after transplant (P = .582). The 5-year patient survival rate in kidney transplant recipients with diabetes after transplant was 87.5%. There was no significant difference in death rate between those with and without diabetes after transplant (P = .566). CONCLUSIONS Diabetes after transplant affected graft and patient survival and increased the incidence of posttransplant cardiovascular disease. The incidence and impact of diabetes after transplant can be minimized through pre- and posttransplant screening to identify patients at higher risk.
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Affiliation(s)
- Amal Ouni
- From the Department of Nephrology, Sahloul Hospital, Sousse, Tunisia
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Bashier AM, Kumar D, Alalawi FJ, Al Nour H, Al Hadari AK, Bin Hussain AA. Post-Transplant Diabetes: Prevalence, Risk, and Management Challenges. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2022. [DOI: 10.1159/000522092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The prevalence of diabetes and diabetic nephropathy is increasing, especially in middle eastern countries. Many patients reach end-stage renal disease and either start dialysis or consider preemptive transplantation. Even a higher number of patients develop post-transplant diabetes, which imposes an even higher risk on graft survival and outcomes post-transplantation. Recently, in the UAE, a renal transplant service has been initiated. Because the population is considered at high risk for post-transplant diabetes, we wrote this review article to discuss the prevalence, risk factors, diagnostic criteria, and management, including lifestyle interventions, manipulation of immunosuppressant agents, and suggested algorithms for the use of oral hypoglycemic agents used in the management of post-transplantation diabetes mellitus. We also discussed the specific indications for each of the oral hypoglycemic agents.
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Strategies to Improve Immune Suppression Post-Liver Transplantation: A Review. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2040042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Since the first liver transplantation operation (LT) in 1967 by Thomas Starzl, efforts to increase survival and prevent rejection have taken place. The development of calcineurin inhibitors (CNIs) in the 1980s led to a surge in survival post-transplantation, and since then, strategies to prevent graft loss and preserve long-term graft function have been prioritized. Allograft rejection is mediated by the host immune response to donor antigens. Prevention of rejection can be achieved through either immunosuppression or induction of tolerance. This leads to a clinical dilemma, as the choice of an immunosuppressive agent is not an easy task, with considerable patient and graft-related morbidities. On the other hand, the induction of graft tolerance remains a challenge. Despite the fact that the liver exhibits less rejection than any other transplanted organs, spontaneous graft tolerance is rare. Most immunosuppressive medications have been incriminated in renal, cardiovascular, and neurological complications, relapse of viral hepatitis, and recurrence of HCC and other cancers. Efforts to minimize immunosuppression are directed toward decreasing medication side effects, increasing cost effectiveness, and decreasing economic burden without increasing the risk of rejection. In this article, we will discuss recent advances in strategies for improving immunosuppression following liver transplantation.
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Ramkanth S, Anitha P, Gayathri R, Mohan S, Babu D. Formulation and design optimization of nano-transferosomes using pioglitazone and eprosartan mesylate for concomitant therapy against diabetes and hypertension. Eur J Pharm Sci 2021; 162:105811. [PMID: 33757828 DOI: 10.1016/j.ejps.2021.105811] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 02/28/2021] [Accepted: 03/16/2021] [Indexed: 12/16/2022]
Abstract
Hypertension, a form of cardiovascular diseases, is considered a major risk factor associated with deaths in type 2 diabetes patients. The current medication systems for treating such chronic coexisting diseases are limited and challenging due to the difficulties in overcoming the side effects from complex therapeutic and treatment regimen. The objective of the present study is to design and optimize pioglitazone (PIO) and eprosartan mesylate (EM)-loaded nano-transferosomes (NTs) using Design-Expert software, aiming its transdermal delivery as a novel combination therapy for concomitant treatment of hypertensive diabetic patients. The developed formulations were characterized for various parameters, including in-vitro skin permeation, skin irritation, in-vivo antidiabetic, and antihypertensive activities. NTs were prepared using PIO and EM as the two model drugs and optimized using Box-Behnken design by considering phospholipid (X1), surfactant (X2), ratio of solvents (X3), and sonication time (X4), as independent variables, each at three levels. Entrapment efficiency (Y1 and Y2) and flux (Y3 and Y4) of PIO and EM, respectively, were selected as dependent variables. Among all the prepared formulations, one optimized formulation was chosen by the point prediction method and evaluated for drug-polymer compatibility, particle size, and surface charge analysis, followed by skin permeation and pharmacodynamic studies. The optimized nano-transferosomal gel (ONTF) showed all responses which confirm with the values predicted by the design. Pharmacodynamic studies showed improved and prolonged management of diabetes and hypertension in Wistar rats after the ONTF was applied, compared to oral and drug-loaded NT formulations. Results of the current study suggest that the development of such combinational delivery system can result in a rational therapeutic regimen for effective treatment of concomitant disease conditions of diabetic hypertensive patients.
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Affiliation(s)
- S Ramkanth
- Department of Pharmaceutics, Karpagam College of Pharmacy, Coimbatore, 641032, Tamilnadu, India.
| | - P Anitha
- Department of Pharmaceutics, Annamacharya College of Pharmacy, Rajampet, 516126, Andhra Pradesh, India
| | - R Gayathri
- Department of Pharmaceutics, Karpagam College of Pharmacy, Coimbatore, 641032, Tamilnadu, India
| | - S Mohan
- Department of Pharmaceutics, Karpagam College of Pharmacy, Coimbatore, 641032, Tamilnadu, India
| | - Dinesh Babu
- Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy & Health Research, University of Alberta, Edmonton, AB, Canada.
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Ahmed M, Ahmed MH. Nonalcoholic fatty liver disease and COVID-19: An epidemic that begets pandemic. World J Clin Cases 2021; 9:4133-4142. [PMID: 34141776 PMCID: PMC8173420 DOI: 10.12998/wjcc.v9.i17.4133] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/24/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, affecting all the individuals across the planet. COVID-19 has gained significant attention due to its high prevalence among individuals with diabetes, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome. NAFLD is the hepatic manifestation of metabolic syndrome and can be associated with a high risk of developing type 2 diabetes. The association of COVID-19 and NAFLD has also gained more attention because NAFLD is highly associated with the epidemic of obesity. NAFLD is a potential risk factor for SARS-CoV-2 infection and severe COVID-19, independent of metabolic syndrome. Importantly, it is not yet clear whether the epidemics of obesity and NAFLD have perpetuated the current pandemic of COVID-19. Further research is urgently needed to assess the following: (1) Whether NAFLD is a high risk factor for SARS-CoV-2 infection; (2) Whether NAFLD is associated with the severe form of COVID-19; and (3) Whether the presence of NAFLD can explain the racial variation in the morbidity and mortality associated with COVID-19. This review summarizes the interactions between COVID-19 and NAFLD, mechanism of liver injury by COVID-19, and effect of lockdown due to COVID- 19 on patients with NAFLD.
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Affiliation(s)
- Musaab Ahmed
- College of Medicine, Ajman University, Ajman 346, United Arab Emirates
| | - Mohamed H Ahmed
- Department of Medicine and HIV Metabolic Clinic, Milton Keynes University Hospital NHS Foundation Trust, Milton Keynes MK5 6LD, United Kingdom
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13
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Topaloğlu Ö, Cengiz M, Cengiz A, Evren B, Yoloğlu S, Yılmaz S, Şahin İ. New-onset diabetes mellitus after liver transplantation in the patients with acute liver failure. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00922-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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14
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Bhadada SK, Pal R. Post-liver transplantation diabetes mellitus — a clinical challenge for diabetologists? Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00955-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Acosta-Gualandri A, Blydt-Hansen T, Islam N, Amed S. Risk Factors for Developing Posttransplant Diabetes After Pediatric Kidney Transplant in a Canadian Tertiary Care Children's Hospital Between 1995 and 2016. Can J Diabetes 2021; 45:481-489. [PMID: 34176612 DOI: 10.1016/j.jcjd.2021.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 04/07/2021] [Accepted: 05/10/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Posttransplant diabetes mellitus (PTDM) is a serious complication in kidney transplant recipients (KTRs) due to its negative impact on graft and patient survival. Although reported in 3% to 20% of pediatric KTRs, it has not been as well characterized in adults. In this study we describe incidence and risk factors associated with development of PTDM in pediatric KTRs. METHODS This work is a retrospective cohort study of nondiabetic pediatric patients, aged 6 months to 19 years, who underwent a first kidney transplant during 1995 to 2016. We estimated the cumulative incidence rate and used multivariable logistic regression to identify the diabetogenic risk factors for PTDM. RESULTS A total of 142 KTRs were included in this study. The cumulative incidence of PTDM was 31% and 14.1% in the first and second year posttransplant, respectively. Significant risk factors for PTDM in the first year after transplant included: dysglycemia in the first 8 to 30 days posttransplant (adjusted odds ratio [aOR], 3.02; 95% confidence interval [CI], 1.21 to 7.53; p=0.018) and use of sirolimus in the first 30 days posttransplant (aOR, 5.33; 95% CI, 1.16 to 24.35; p=0.031). No significant association was found with typical diabetogenic factors. CONCLUSIONS The incidence of PTDM is high among pediatric KTRs. Independent risk factors associated with PTDM included meeting the criteria for dysglycemia or diabetes and sirolimus use in the first month posttransplant. Typical diabetogenic risk factors for type 2 diabetes were not associated with increased risk. This study provides valuable information for posttransplant medical care and future research.
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Affiliation(s)
- Alejandra Acosta-Gualandri
- Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada
| | - Tom Blydt-Hansen
- Division of Nephrology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada
| | - Nazrul Islam
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Shazhan Amed
- Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada.
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16
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Ponticelli C, Favi E, Ferraresso M. New-Onset Diabetes after Kidney Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:250. [PMID: 33800138 PMCID: PMC7998982 DOI: 10.3390/medicina57030250] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/25/2021] [Accepted: 03/05/2021] [Indexed: 02/07/2023]
Abstract
New-onset diabetes mellitus after transplantation (NODAT) is a frequent complication in kidney allograft recipients. It may be caused by modifiable and non-modifiable factors. The non-modifiable factors are the same that may lead to the development of type 2 diabetes in the general population, whilst the modifiable factors include peri-operative stress, hepatitis C or cytomegalovirus infection, vitamin D deficiency, hypomagnesemia, and immunosuppressive medications such as glucocorticoids, calcineurin inhibitors (tacrolimus more than cyclosporine), and mTOR inhibitors. The most worrying complication of NODAT are major adverse cardiovascular events which represent a leading cause of morbidity and mortality in transplanted patients. However, NODAT may also result in progressive diabetic kidney disease and is frequently associated with microvascular complications, eventually determining blindness or amputation. Preventive measures for NODAT include a careful assessment of glucose tolerance before transplantation, loss of over-weight, lifestyle modification, reduced caloric intake, and physical exercise. Concomitant measures include aggressive control of systemic blood pressure and lipids levels to reduce the risk of cardiovascular events. Hypomagnesemia and low levels of vitamin D should be corrected. Immunosuppressive strategies limiting the use of diabetogenic drugs are encouraged. Many hypoglycemic drugs are available and may be used in combination with metformin in difficult cases. In patients requiring insulin treatment, the dose and type of insulin should be decided on an individual basis as insulin requirements depend on the patient's diet, amount of exercise, and renal function.
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Affiliation(s)
- Claudio Ponticelli
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Evaldo Favi
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, 20122 Milan, Italy
| | - Mariano Ferraresso
- Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, 20122 Milan, Italy
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17
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Kim HD, Chang JY, Chung BH, Kim CD, Lee SH, Kim YH, Yang CW. Effect of Everolimus with Low-Dose Tacrolimus on Development of New-Onset Diabetes After Transplantation and Allograft Function in Kidney Transplantation: A Multicenter, Open-Label, Randomized Trial. Ann Transplant 2021; 26:e927984. [PMID: 33479188 PMCID: PMC7836319 DOI: 10.12659/aot.927984] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background This randomized controlled trial aimed to investigate the effect of everolimus (EVL) with low-dose tacrolimus (Tac) on the development of post-transplantation diabetes mellitus (PTDM) in kidney transplantation (KT). Material/Methods Seventy-seven kidney transplant patients from 4 transplant centers were included. Patients were randomized to the “EVL group” (n=38) and the “TAC group” (n=39). The target Tac trough level was 2 to 5 ng/mL in the EVL group and 5 to 10 ng/mL in the TAC group. Results The 1-year cumulative incidence of PTDM in all patients was 7.8%, and no difference was found between the 2 groups (P=0.0819). Insulin resistance measured with the homeostatic model assessment for insulin resistance showed a significant increase only in the TAC group (1.11 to 1.30, P=0.0492). Allograft rejection rate and estimated glomerular filtration rate (eGFR) follow-ups every 3 months were not significantly different between the 2 groups. However, the EVL group showed a significant increase in the mean eGFR at 9 months and 12 months after KT compared to the baseline value (P=0.0242 and 0.0491, respectively). The EVL group showed lower insulin resistance and higher allograft function in comparison to the TAC group. Conclusions EVL-based immunosuppressive therapy with lower Tac exposure could be a safer alternative for maintenance treatment.
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Affiliation(s)
- Hyung Duk Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Ji-Yeun Chang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Byung Ha Chung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, Kyungpook National University School of Medicine, Deagu, South Korea
| | - Sang-Ho Lee
- Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, South Korea
| | - Yeong Hoon Kim
- Department of Internal Medicine, College of Medicine, Inje University, Pusan, South Korea
| | - Chul Woo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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18
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Spiritos Z, Abdelmalek MF. Metabolic syndrome following liver transplantation in nonalcoholic steatohepatitis. Transl Gastroenterol Hepatol 2021; 6:13. [PMID: 33409407 DOI: 10.21037/tgh.2020.02.07] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/16/2019] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome is a major clinical disorder involving metabolic dysregulation characterized clinically with features of central obesity, insulin resistance (IR), type 2 diabetes, hypertension, and dyslipidemia. Metabolic syndrome is strongly associated with the rising prevalence nonalcoholic steatohepatitis, a leading indication for orthotopic liver transplantation in the Western world. The presence or recurrence of metabolic syndrome following liver transplantation can contribute to the development and recurrence of nonalcoholic fatty liver disease (NAFLD) in the liver allograft. In this review, we discuss the endogenous and exogenous drivers of post-transplant metabolic syndrome, role of chronic immunosuppression, and the prevalence and clinical significant of post-transplant metabolic syndrome on nonalcoholic steatohepatitis.
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Affiliation(s)
- Zachary Spiritos
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
| | - Manal F Abdelmalek
- Division of Gastroenterology and Hepatology, Duke University, Durham, NC, USA
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19
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Treatment of cyclosporine induced hypertension: Results from a long-term observational study using different antihypertensive medications. Vascul Pharmacol 2019; 115:69-83. [DOI: 10.1016/j.vph.2018.06.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 06/04/2018] [Accepted: 06/14/2018] [Indexed: 11/21/2022]
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20
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Grancini V, Resi V, Palmieri E, Pugliese G, Orsi E. Management of diabetes mellitus in patients undergoing liver transplantation. Pharmacol Res 2019; 141:556-573. [PMID: 30690071 DOI: 10.1016/j.phrs.2019.01.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 01/24/2019] [Accepted: 01/24/2019] [Indexed: 02/07/2023]
Abstract
Diabetes is a common feature in cirrhotic individuals both before and after liver transplantation and negatively affects prognosis. Certain aetiological agents of chronic liver disease and loss of liver function per se favour the occurrence of pre-transplant diabetes in susceptible individuals, whereas immunosuppressant treatment, changes in lifestyle habits, and donor- and procedure-related factors contribute to diabetes development/persistence after transplantation. Challenges in the management of pre-transplant diabetes include the profound nutritional alterations characterizing cirrhotic individuals and the limitations to the use of drugs with liver metabolism. Special issues in the management of post-transplant diabetes include the diabetogenic potential of immunosuppressant drugs and the increased cardiovascular risk characterizing solid organ transplant survivors. Overall, the pharmacological management of cirrhotic patients undergoing liver transplantation is complicated by the lack of specific guidelines reflecting the paucity of data on the impact of glycaemic control and the safety and efficacy of anti-hyperglycaemic agents in these individuals.
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Affiliation(s)
- Valeria Grancini
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Veronica Resi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Eva Palmieri
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea University Hospital, Rome, Italy
| | - Emanuela Orsi
- Diabetes Service, Endocrinology and Metabolic Diseases Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, and Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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21
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Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
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Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
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22
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Santos AH, Chen C, Casey MJ, Womer KL, Wen X. New-onset diabetes after kidney transplantation: can the risk be modified by choosing immunosuppression regimen based on pretransplant viral serology? Nephrol Dial Transplant 2018; 33:177-184. [PMID: 29045704 DOI: 10.1093/ndt/gfx281] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Indexed: 12/14/2022] Open
Abstract
Background This study aimed to analyze adult kidney transplant recipients (KTRs) for the risk of new-onset diabetes after transplantation (NODAT) associated with viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac]. Methods Cox regression models were used to examine the risk of NODAT in the first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or -; hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the viral serology found significant in the main analysis. Results Adult KTRs (n = 97 644) from January 1995 through September 2015 were studied. HCV+ [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.31-1.68] or CMV+ (HR 1.12, 95% CI 1.06-1.19) serology was a risk factor and HBc+ (HR 1.04, 95% CI 0.95-1.15) or EBV+ (HR 1.06, 95% CI 0.97-1.15) serology was not a risk factor for NODAT. Regardless of associated HCV or CMV serology, risk of NODAT relative to the reference regimen (Tac + MPA) was lower with CSA + MPA [HCV-: HR 0.74, 95% CI 0.65-0.85; HCV+: HR 0.47, 95% CI 0.28-0.78; CMV-: CSA + MPA HR 0.68, 95% CI 0.54-0.86; CMV+: (CSA + MPA) HR 0.73, 95% CI 0.63-0.85] and similar with SRL + CSA or SRL + MPA. In KTRs with HCV- or CMV+ serology, SRL + Tac was associated with a higher risk of NODAT relative to reference [HCV- (HR 1.43, 95% CI 1.17-1.74) and CMV+ (HR 1.44, 95% CI 1.14-1.81), respectively]. The risk for NODAT-free graft loss was lower with Tac + MPA than the other regimens. Conclusions Tailoring immunosuppression regimen based on HCV or CMV serology may modify the risk of developing NODAT in KTRs.
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Affiliation(s)
- Alfonso H Santos
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Chao Chen
- Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Michael J Casey
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Karl L Womer
- Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Xuerong Wen
- Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, RI, USA
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Manzia TM, Angelico R, Toti L, Angelico C, Quaranta C, Parente A, Blasi F, Iesari S, Sforza D, Baiocchi L, Lerut J, Tisone G. Longterm Survival and Cost-Effectiveness of Immunosuppression Withdrawal After Liver Transplantation. Liver Transpl 2018; 24:1199-1208. [PMID: 30129171 DOI: 10.1002/lt.25293] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 04/15/2018] [Indexed: 02/05/2023]
Abstract
Lifelong immunosuppression (IS) after liver transplantation is associated with severe adverse effects and increased recipients' morbidity and mortality. Clinical operational tolerance has been reported in up to 40% in very well-selected recipients. Longterm survival and cost savings within the Italian national health system in operational tolerant recipients is reported. Seventy-five liver recipients were enrolled for IS withdrawal at our institution during the period from April 1998 to December 2015. The study population comprised 32 (42.7%) tolerant patients; 41 (54.7%) nontolerant patients needing uptake of IS after clinical or biopsy-proven rejection; and 2 (2.7%) immediate nontolerant patients who developed early rejection after the first drug reduction. The primary endpoint of the study was to assess the longterm patients and graft outcome; the secondary endpoint was the assessment of cost savings in the context of IS withdrawal. The follow-up was 95.0 months (interquartile range, 22.5-108.5 months). IS withdrawal did not result in patient nor graft loss and resulted in a major cost savings reaching about €630,000. In conclusion, longterm IS withdrawal represents a remarkable cost savings in the health care of liver recipients without exposing them to graft loss.
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Affiliation(s)
- Tommaso Maria Manzia
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Roberta Angelico
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
- Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy
| | - Luca Toti
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | | | - Claudia Quaranta
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Alessandro Parente
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Francesca Blasi
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Samuele Iesari
- Department of Economics, Bocconi University, Milan, Italy
| | - Daniele Sforza
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Leonardo Baiocchi
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
| | - Jan Lerut
- Starzl Unit of Abdominal Transplantation, Université Catholique de Louvain, Brussels, Belgium
| | - Giuseppe Tisone
- Transplant and Hepatobiliary Unit, Department of Surgery, University of Rome Tor Vergata, Rome, Italy
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Paka P, Lieber SR, Lee RA, Desai CS, Dupuis RE, Barritt AS. Perioperative glucose management and outcomes in liver transplant recipients: A qualitative systematic review. World J Transplant 2018; 8:75-83. [PMID: 29988867 PMCID: PMC6033739 DOI: 10.5500/wjt.v8.i3.75] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 02/20/2018] [Accepted: 04/01/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the relationship between post-liver transplantation (LT) glycemic control and LT outcomes. METHODS A qualitative systematic review on relevant prospective interventions designed to control glucose levels including insulin protocols. Studies investigating an association between glycemic control and post-LT outcomes such as mortality, graft rejection, and infection rate were reviewed. PubMed, EMBASE, and other databases were searched through October 2016. RESULTS Three thousands, six hundreds and ninety-two patients from 14 studies were included. Higher mortality rate was seen when blood glucose (BG) ≥ 150 mg/dL (P = 0.05). BG ≥ 150 mg/dL also led to higher rates of infection. Higher rates of graft rejection were seen at BG > 200 mg/dL (P < 0.001). Mean BG ≥ 200 mg/dL was associated with more infections (P = 0.002). Nurse-initiated protocols and early screening strategies have shown a reduction in negative post-LT outcomes. CONCLUSION Hyperglycemia in the perioperative period is associated with poor post-LT outcomes. Only a few prospective studies have designed interventions aimed at managing post-LT hyperglycemia, post-transplant diabetes mellitus (PTDM) and their impact on post-LT outcomes.
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Affiliation(s)
- Prani Paka
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Sarah R Lieber
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Ruth-Ann Lee
- Division of Abdominal Transplant, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, United States
| | - Chirag S Desai
- Division of Abdominal Transplant, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, United States
| | - Robert E Dupuis
- Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States
| | - Alfred Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States
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Mitić B, Paunović G, Dimitrijević Z, Veličković-Radovanović R. PREVALENCE OF NEW ONSET DIABETES IN PATIENTS AFTER KIDNEY TRANSPLANTATION – THE PROSPECTIVE STUDY. ACTA MEDICA MEDIANAE 2017. [DOI: 10.5633/amm.2017.0415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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26
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Cen C, Fang HX, Yu SF, Liu JM, Liu YX, Zhou L, Yu J, Zheng SS. Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation. Hepatobiliary Pancreat Dis Int 2017; 16:602-609. [PMID: 29291779 DOI: 10.1016/s1499-3872(17)60069-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 08/07/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation (LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients. METHODS A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom MassARRAY. Modified clinical models in predicting NODAT were established and evaluated. RESULTS The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients (56% vs 39%, P=0.014). Dominant model (GG vs GT+TT, P=0.030) and recessive model (GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age (OR=1.048, P=0.004), BMI (OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT (OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT (AUROC=0.743, P<0.001). CONCLUSION ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.
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Affiliation(s)
- Chao Cen
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Hai-Xing Fang
- Department of Hepatobiliary Surgery, the First People's Hospital of Fuyang, Hangzhou 311400, China
| | - Song-Feng Yu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Ji-Min Liu
- Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton CAN L8N 3Z5, Canada
| | - Yuan-Xing Liu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jun Yu
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Benedict M, Zhang X. Non-alcoholic fatty liver disease: An expanded review. World J Hepatol 2017; 9:715-732. [PMID: 28652891 PMCID: PMC5468341 DOI: 10.4254/wjh.v9.i16.715] [Citation(s) in RCA: 504] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 02/08/2017] [Accepted: 04/18/2017] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the "magic bullet" in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients.
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Affiliation(s)
- Mark Benedict
- Mark Benedict, Xuchen Zhang, Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, United States
| | - Xuchen Zhang
- Mark Benedict, Xuchen Zhang, Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, United States
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Pisano G, Fracanzani AL, Caccamo L, Donato MF, Fargion S. Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study. World J Gastroenterol 2016; 22:8869-8882. [PMID: 27833378 PMCID: PMC5083792 DOI: 10.3748/wjg.v22.i40.8869] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/27/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation (OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk (i.e., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT (i.e., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage, which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.
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Han E, Kim MS, Kim YS, Kang ES. Risk assessment and management of post-transplant diabetes mellitus. Metabolism 2016; 65:1559-69. [PMID: 27621191 DOI: 10.1016/j.metabol.2016.07.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/13/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023]
Abstract
The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.
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Affiliation(s)
- Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center; Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Kubo F, Takahara M, Yasuda T, Shimo N, Matsuoka TA, Shimomura I. A case of diabetic ketoacidosis after everolimus treatment. Acta Diabetol 2016; 53:861-2. [PMID: 26972800 DOI: 10.1007/s00592-016-0849-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 02/22/2016] [Indexed: 11/25/2022]
Affiliation(s)
- Fumiyo Kubo
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan
| | - Mitsuyoshi Takahara
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
- Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.
| | - Tetsuyuki Yasuda
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan
| | - Naoki Shimo
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan
| | - Taka-Aki Matsuoka
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan
| | - Iichiro Shimomura
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan
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Xue M, Lv C, Chen X, Liang J, Zhao C, Zhang Y, Huang X, Sun Q, Wang T, Gao J, Zhou J, Yu M, Fan J, Gao X. Donor liver steatosis: A risk factor for early new-onset diabetes after liver transplantation. J Diabetes Investig 2016; 8:181-187. [PMID: 27511316 PMCID: PMC5334314 DOI: 10.1111/jdi.12560] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 07/26/2016] [Accepted: 08/04/2016] [Indexed: 01/01/2023] Open
Abstract
AIMS/INTRODUCTION To investigate whether donor liver steatosis increases the incidence of new-onset diabetes after transplantation (NODAT) in liver transplant recipients. MATERIALS AND METHODS We retrospectively analyzed liver transplant recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December 2014. The final analysis involved 763 patients. The cumulative incidence of NODAT at 1, 3, 5 and 10 years after liver transplantation was investigated. Furthermore, according to the findings of donor liver biopsy before transplantation, patients were divided into steatotic and non-steatotic donor liver groups, and NODAT incidence was compared between these groups. Multivariate Cox regression was used to explore the risk factors for NODAT in the patients. RESULTS Of the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an incidence that exceeded that in the non-steatotic donor liver group (P = 0.001). The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years after transplantation was 33, 43, 50 and 56%, respectively. The cumulative incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group were significantly higher than those in the non-steatotic donor liver group (P = 0.003). Multivariate Cox regression analyses showed that donor liver steatosis was an independent risk factor for NODAT among liver transplant recipients, after other potential risk factors were adjusted for (hazard ratio 1.774, 95% confidence interval: 1.025-3.073; P = 0.041). CONCLUSIONS Donor liver steatosis increases NODAT incidence among liver transplant recipients.
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Affiliation(s)
- Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.,Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chenhe Zhao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Fudan University, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
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Nel JD, Epstein S. Metabolic Bone Disease in the Post-transplant Population: Preventative and Therapeutic Measures. Med Clin North Am 2016; 100:569-86. [PMID: 27095646 DOI: 10.1016/j.mcna.2016.01.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Post-transplant bone disease contributes significantly to patients' morbidity and mortality after transplantation and has an impact on their quality of life. This article discusses the major contributors to mechanisms causing bone loss, highlighting the role of preexisting disease in both kidney and liver failure and contributions from glucocorticoids and calcineurin inhibitors. Suggested monitoring and investigations are reviewed as well as treatment as far as the current literature supports, emphasizing the difference between kidney and liver recipients.
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Affiliation(s)
- Johan Daniël Nel
- Division of Nephrology, Department of Medicine, Tygerberg Hospital and University of Stellenbosch, PO Box 241, Cape Town, Western Cape 8000, South Africa.
| | - Sol Epstein
- Mt Sinai School of Medicine, New York, NY, USA; University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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Wang J, Yao M, Xu JH, Shu B, Wang YJ, Cui XJ. Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials. Osteoporos Int 2016; 27:1683-90. [PMID: 26733377 DOI: 10.1007/s00198-015-3465-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 12/15/2015] [Indexed: 12/19/2022]
Abstract
We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy. Osteopenic-osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16-1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03-0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.
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Affiliation(s)
- J Wang
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - M Yao
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
- Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - J-h Xu
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - B Shu
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
- Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Y-j Wang
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
- Institute of Spine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - X-j Cui
- Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
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Abstract
Immunosuppression use for prevention of allograft recognition/rejection has evolved to reflect an expanded understanding of the immune system, as well as a fine tuning of the goals of therapy. Immunosuppression in organ transplantation represents a balance between the desire to improve the health status of an individual affected by chronic conditions versus not imposing an unintended immunodeficiency leading to iatrogenic morbidity/mortality. This article discusses the selection and general dosing of immunosuppression in organ allograft recipients to allow providers to be comfortable in monitoring immunosuppressive therapy long term and the associated, expected posttransplant complications in allograft recipients.
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Affiliation(s)
- Gregory Malat
- Solid Organ Transplantation, Hahnemann University Hospital, Drexel University College of Medicine, 216 North Broad Street, MS 417, 5th Floor Feinstein Building, Philadelphia, PA 19102, USA.
| | - Christine Culkin
- Solid Organ Transplantation, Hahnemann University Hospital, Philadelphia, PA, USA
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35
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Ling Q, Xu X, Xie H, Wang K, Xiang P, Zhuang R, Shen T, Wu J, Wang W, Zheng S. New-onset diabetes after liver transplantation: a national report from China Liver Transplant Registry. Liver Int 2016; 36:705-712. [PMID: 26681557 DOI: 10.1111/liv.13042] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 12/04/2015] [Indexed: 02/05/2023]
Abstract
BACKGROUND/AIMS New-onset diabetes after transplantation (NODAT) is a serious complication of liver transplantation (LT). The present study aimed to investigate the risk factors of NODAT by a national survey using the China Liver Transplant Registry database. PATIENTS A total of 10 204 non-pre-existing diabetic patients undergone primary LT between January 2000 and December 2013 were included. Risk factors were identified by logistic regression analysis. RESULTS NODAT occurred in 24.3% of liver recipients with a median follow-up time of 2.6 years, and was associated with a significantly lower patient survival. NODAT increased not only diabetes related complications (e.g., infection, kidney failure) but also biliary stricture and cholangitis. NODAT patients who received hypoglycaemic treatment had a worse prognosis and a higher hepatocellular carcinoma recurrence compared with those without treatment. New-onset hyperglycaemia (<30 days) was the major predictor of NODAT. Other risk factors included cold ischaemia time >9 h, recipient age >50 years, body mass index >25 kg/m(2) , other hepatitis (mainly hepatitis C), post-transplant intensive care unit stay >15 days, cytomegalovirus infection and corticosteroid at discharge. CONCLUSIONS The incidence of NODAT in China is similar to that in Western countries. However, the NODAT-related complications are more common and severer in China compared with those in Western countries. The major risk factors are different.
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Affiliation(s)
- Qi Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haiyang Xie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Penghui Xiang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Runzhou Zhuang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tian Shen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weilin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant. Int J Mol Sci 2016; 17:490. [PMID: 27049380 PMCID: PMC4848946 DOI: 10.3390/ijms17040490] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 03/25/2016] [Accepted: 03/28/2016] [Indexed: 02/07/2023] Open
Abstract
Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.
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Goldmannova D, Karasek D, Krystynik O, Zadrazil J. New-onset diabetes mellitus after renal transplantation. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016; 160:195-200. [PMID: 26927467 DOI: 10.5507/bp.2016.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Accepted: 02/02/2016] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND AND AIM Diabetes mellitus is a very common metabolic disease with a rising incidence. It is both a leading cause of chronic renal disease and one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. The aim of this paper is to review current knowledge of NODAT including risk factors, diagnosis and management. METHODS A MEDLINE search was performed to retrieve both original and review articles addressing the epidemiology, risk factors, screening and management of NODAT. We also focused on microRNAs as potential biomarkers of NODAT. RESULTS AND CONCLUSION Understanding the risk factors (both modifiable-e.g. obesity, viruses, and unmodifiable-e.g. age, genetics) may help reduce the incidence and impact of NODAT using pre- and post-transplant management. This can lead to better long-term graft function and general transplant success.
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Affiliation(s)
- Dominika Goldmannova
- Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - David Karasek
- Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Ondrej Krystynik
- Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
| | - Josef Zadrazil
- Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
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Abstract
BACKGROUND Liver transplantation is a treatment of choice for both acute and chronic liver failure. Accompanied with the increase of long-term survival rates of recipients, metabolic syndrome and its individual components, including obesity, hyperglycemia, hypertension and hyperlipidemia, have become more frequent post liver transplantation. Here we reviewed the literature concerning the risk factors for the development of metabolic complications in liver recipients. DATA SOURCES PubMed was searched for English-language articles published from January 2000 to June 2015. The search criteria focused on risk factors for metabolic syndrome after liver transplantation. RESULT The risk factors of metabolic syndrome in liver recipients include older age, obesity, pre-transplantation diabetes mellitus, hepatitis C virus infection, certain genetic polymorphisms and the use of immunosuppressive drugs. CONCLUSION Active intervention of the risk factors will reduce the occurrence rate of metabolic syndrome after liver transplantation and improve the recipients' quality of life.
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Affiliation(s)
- Jun Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China.
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Boloori A, Saghafian S, Chakkera HA, Cook CB. Characterization of Remitting and Relapsing Hyperglycemia in Post-Renal-Transplant Recipients. PLoS One 2015; 10:e0142363. [PMID: 26551468 PMCID: PMC4638338 DOI: 10.1371/journal.pone.0142363] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Accepted: 10/21/2015] [Indexed: 01/08/2023] Open
Abstract
Background Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT). Objective To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications). Methods We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia. Results Age (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (P<0.0001) are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001), non-White race (P = 0.002), BMI (P = 0.002), HDL cholesterol (P = 0.003), uric acid (P = 0.012), and using steroid (P = 0.007) are the significant risk factors for the recurrent cases of hyperglycemia. Discussion This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.
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Affiliation(s)
- Alireza Boloori
- Department of Industrial Engineering, School of Computing, Informatics and Decision Systems Engineering, Arizona State University, Tempe, Arizona, United States of America
| | - Soroush Saghafian
- Harvard Kennedy School, Harvard University, Cambridge, Massachusetts, United States of America
- * E-mail:
| | - Harini A. Chakkera
- Division of Nephrology and Transplantation, Mayo Clinic School of Medicine, Scottsdale, Arizona, United States of America
| | - Curtiss B. Cook
- Division of Endocrinology, Mayo Clinic School of Medicine, Scottsdale, Arizona, United States of America
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Lv C, Zhang Y, Chen X, Huang X, Xue M, Sun Q, Wang T, Liang J, He S, Gao J, Zhou J, Yu M, Fan J, Gao X. New-onset diabetes after liver transplantation and its impact on complications and patient survival. J Diabetes 2015; 7:881-90. [PMID: 25676209 DOI: 10.1111/1753-0407.12275] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Revised: 01/13/2015] [Accepted: 01/27/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The aim of the present study was to investigate the incidence and risk factors of new-onset diabetes after transplantation (NODAT) in liver transplant recipients and the influence of NODAT on complications and long-term patient survival. METHODS We examined 438 patients who underwent liver transplantation between April 2001 and December 2008 and were not diabetic before transplantation. RESULTS The mean (± SD) follow-up duration was 2.46 ± 1.62 years. The incidence of NODAT 3, 6, 9, 12, 36, and 60 months after transplantation was 44.24%, 25.59%, 23.08%, 25.17%, 17.86%, and 18.18%, respectively. Multifactor analysis indicated that preoperative fasting plasma glucose (FPG) levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an interleukin-2 receptor (IL-2R) antagonist reduced the risk of NODAT. Compared with the no NODAT group (N-NODAT), the NODAT group had a higher rate of sepsis and chronic renal insufficiency. Mean survival was significantly longer in the N-NODAT than NODAT group. Cox regression analysis showed that pre- and/or postoperative FPG levels, tumor recurrence or metastasis, and renal insufficiency after liver transplantation were independent risk factors of mortality. Pulmonary infection or multisystem failure were specific causes of death in the NODAT group, whereas patients in both groups died primarily from tumor relapse or metastasis. CONCLUSIONS Preoperative FPG levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an IL-2R antagonist reduced the risk of NODAT. Patients with NODAT had reduced survival and an increased incidence of sepsis and chronic renal insufficiency. Significant causes of death in the NODAT group were pulmonary infection and multisystem failure.
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Affiliation(s)
- Chaoyang Lv
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Xianying Chen
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
- Department of Endocrinology and Metabolism, Hainan Provincial Nong Ken Hospital, Hainan, China
| | - Xiaowu Huang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mengjuan Xue
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Ting Wang
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Jing Liang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Shunmei He
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jian Gao
- Center of Clinical Epidemiology and Evidence-based Medicine, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Mingxiang Yu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery, Zhongshan Hospital, Shanghai, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Shanghai, China
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Tafazoli A. Cyclosporine use in hematopoietic stem cell transplantation: pharmacokinetic approach. Immunotherapy 2015; 7:811-36. [DOI: 10.2217/imt.15.47] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Cyclosporine is one of the most vital agents in the process of successful allogeneic hematopoietic stem cell transplantation. Despite a long history and worldwide extent of cyclosporine use for prevention of graft versus host disease, currently there are lots of uncertainties about its optimal method of application to reach the best clinical outcome. A major portion of this problem stems from complicated cyclosporine pharmacokinetics. Study of cyclosporine pharmacokinetic behavior can significantly help recognition of its effectiveness and consequently, optimization of dosing, administration, monitoring and management of adverse effects. In this review, highly accredited but sparse scientific data are gathered in order to provide a better insight for preparation of practice guidelines and directing future studies for allogeneic hematopoietic cell recipients.
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Affiliation(s)
- Ali Tafazoli
- Clinical Pharmacy Department, School of Pharmacy, Shahid Beheshti University of Medical Sciences (SBMU), Vali-e-Asr Avenue, Niayesh Junction, PO Box: 14155/6153 Tehran, Iran
- Taleghani Bone Marrow Transplantation Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences (SBMU), Vali-e-Asr Avenue, Niayesh Junction, PO Box 14155/6153 Tehran, Iran
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Hoehn RS, Singhal A, Wima K, Sutton JM, Paterno F, Steve Woodle E, Hohmann S, Abbott DE, Shah SA. Effect of pretransplant diabetes on short-term outcomes after liver transplantation: a national cohort study. Liver Int 2015; 35:1902-9. [PMID: 25533420 DOI: 10.1111/liv.12770] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 12/15/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We sought to analyse the effect of pretransplant diabetes on post-operative outcomes and resource utilization following liver transplantation. METHODS A retrospective cohort study was designed using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases. We identified 12 442 patients who underwent liver transplantation at 63 centres from 2007-2011 and separated cohorts of patients with diabetes (n = 2971; 24%) and without (n = 9471; 76%) at the time of transplant. We analysed transplant related outcomes and short-term survival. RESULTS Diabetic recipients were more likely to be male (70% vs 67%), non-white (32% vs 26%), older (age ≥60; 41% vs 28%), and have a higher BMI (29 vs 27; P < 0.001). More diabetic patients were on haemodialysis (10% vs 7%), had cirrhosis caused by NASH (24% vs 9%; P < 0.001), and received liver allografts from older donors (≥ 60 years; 19% vs 15%) with a higher donor risk index (>1.49; 46% vs 42%; P < 0.001). Post-transplant, diabetic recipients had longer hospital length of stay (10 vs 9 days), higher peri-transplant mortality (5% vs 4%) and 30-day readmission rates (41% vs 37%), were less often discharged to home (83% vs 87%; P < 0.05), and had inferior graft and patient survival. Liver transplant was more expensive for type 1 vs type 2 diabetics ($105 078 vs $100 624, P < 0.001). Poorly controlled diabetic recipients were less likely discharged home following transplant (75% vs 82%, P < 0.01). CONCLUSIONS This national study indicates that pretransplant diabetes is associated with inferior post-operative outcomes and increased resource utilization after liver transplantation.
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Affiliation(s)
- Richard S Hoehn
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Ashish Singhal
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Koffi Wima
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Jeffrey M Sutton
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Flavio Paterno
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - E Steve Woodle
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Sam Hohmann
- University Health Consortium and Department Health Systems Management, Rush University, Chicago, IL, USA
| | - Daniel E Abbott
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
| | - Shimul A Shah
- Cincinnati Research in Outcomes and Safety in Surgery (CROSS), Department of Surgery, University of Cincinnati School of Medicine, Cincinnati, OH, USA
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Sadhu AR, Schwartz SS, Herman ME. THE RATIONALE FOR USE OF INCRETINS IN THE MANAGEMENT OF NEW ONSET DIABETES AFTER TRANSPLANTATION (NODAT). Endocr Pract 2015; 21:814-22. [PMID: 25786557 DOI: 10.4158/ep14569.ra] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Owing to advances in transplant science, increasing numbers of patients are receiving solid organ transplantation. New onset diabetes after transplantation (NODAT) frequently develops in transplant patients and requires acute and often ongoing management of hyperglycemia. The metabolic derangements of NODAT are similar to those of classic type 2 diabetes, and treatment has typically followed diabetes standards of care. Best practices for NODAT management remain to be developed. METHODS The mechanistic suitability of incretins to treat NODAT pathogenesis has been hitherto underappreciated. This review details the specific mechanistic value of incretins in patients with immunosuppression-associated hyperglycemia. RESULTS Corticosteroids have long been known to exert their effects on glucose metabolism by decreasing glucose utilization and enhancing hepatic gluconeogenesis. Corticosteroids also significantly and directly reduce insulin secretion, as do calcineurin inhibitors (CNIs), another commonly used group of immunosuppressive drugs that cause hyperglycemia and NODAT. The ability of incretins to counteract immunosuppressant-induced disruptions in insulin secretion suggest that the insulinotropic, glucagonostatic, and glucose-lowering actions of incretins are well suited to treat immunosuppressant-induced hyperglycemia in NODAT. Additional benefits of incretins include decreased glucagon levels and improved insulin resistance. In the case of glucagon-like peptide-1 (GLP-1) receptor agonists, weight loss is another benefit, countering the weight gain that is a common consequence of both hyperglycemia and transplantation. These benefits make incretins very attractive and deserving of more investigation. CONCLUSION Among diabetes treatment options, incretin therapies uniquely counteract immunosuppressant drugs' interference with insulin secretion. We propose an incretin-based treatment paradigm for NODAT management.
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Abstract
BACKGROUND Dysglycemia and dyslipidemia are important metabolic complications of organ transplantation. Statins are widely used to control dyslipidemia; however, long-term use of statins is related to diabetes mellitus (DM) and impaired fasting glucose (IFG). The aim of this study was to evaluate the influence of statins on the development of dysglycemia (IFG and/or DM) in renal allograft recipients. METHODS A total of 394 patients without previously known DM or IFG who underwent kidney transplantation were enrolled. Patients were grouped into the two groups according to the use of statin (control, n=149; statin, n=245). The major statins used were fluvastatin (80 mg/d, n=134) and atorvastatin (20 mg/d, n=111). We compared the incidence of IFG or DM during the follow-up period. RESULTS The incidence of IFG was higher in the statin group than that in the control group (28.6% vs. 8.7%, P<0.001). The incidence of dysglycemia was significantly higher in the statin group (40.0% vs. 15.4%, P=0.001). Time to development of dysglycemia after transplantation was shorter in the statin group than in the control group (38.8±29.7 vs. 47.2±23.3 months, P=0.002). Statin use was associated with an increased risk for dysglycemia after adjustment for age, sex, body mass index, hypertension, cholesterol levels, hepatitis C infection, and type of immunosuppressant (hazard ratio=3.08, 95% confidence interval=1.91-4.98). The dysglycemic effect was more profound in the patients who used atorvastatin than in those who used fluvastatin (hazard ratio=2.21, 95% confidence interval=1.02-4.76). CONCLUSION Statin treatment is associated with an elevation in fasting plasma glucose and in the development of dysglycemia in renal allograft recipients.
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Portero McLellan KC, Wyne K, Villagomez ET, Hsueh WA. Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus. Ther Clin Risk Manag 2014; 10:173-88. [PMID: 24672242 PMCID: PMC3964168 DOI: 10.2147/tcrm.s39564] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Clinical trials have demonstrated that it is possible to prevent diabetes through lifestyle modification, pharmacological intervention, and surgery. This review aims to summarize the effectiveness of these various therapeutic interventions in reducing the risk of progression of prediabetes to diabetes, and address the challenges to implement a diabetes prevention program at a community level. Strategies focusing on intensive lifestyle changes are not only efficient but cost-effective and/or cost-saving. Indeed, lifestyle intervention in people at high risk for type 2 diabetes mellitus (T2DM) has been successful in achieving sustained behavioral changes and a reduction in diabetes incidence even after the counseling is stopped. Although prediabetes is associated with health and economic burdens, it has not been adequately addressed by interventions or regulatory agencies in terms of prevention or disease management. Lifestyle intervention strategies to prevent T2DM should be distinct for different populations around the globe and should emphasize sex, age, ethnicity, and cultural and geographical considerations to be feasible and to promote better compliance. The translation of diabetes prevention research at a population level, especially finding the most effective methods of preventing T2DM in various societies and cultural settings remains challenging, but must be accomplished to stop this worldwide epidemic.
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Affiliation(s)
| | - Kathleen Wyne
- Division of Diabetes, Obesity and Lipids, Department of Medicine, The Methodist Hospital Diabetes and Metabolism Institute, and the Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA
| | - Evangelina Trejo Villagomez
- Division of Diabetes, Obesity and Lipids, Department of Medicine, The Methodist Hospital Diabetes and Metabolism Institute, and the Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA
| | - Willa A Hsueh
- Division of Diabetes, Obesity and Lipids, Department of Medicine, The Methodist Hospital Diabetes and Metabolism Institute, and the Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA
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Screening for new-onset diabetes after kidney transplantation: limitations of fasting glucose and advantages of afternoon glucose and glycated hemoglobin. Transplantation 2013; 96:726-31. [PMID: 23902993 DOI: 10.1097/tp.0b013e3182a012f3] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND The sensitivity of fasting plasma glucose (FPG) in screening for new-onset diabetes after transplantation (NODAT) has been questioned, particularly in the presence of moderate-dose prednisolone, where peak plasma glucose occurs 7 to 8 hr after administration. Oral glucose tolerance testing (OGTT) has been mooted as an alternative but is inconvenient for patients. METHODS We compared sensitivity of screening tests for NODAT at 6 weeks, 3 months, and 12 months after kidney transplantation in recipients receiving prednisolone, mycophenolate, and tacrolimus. RESULTS At 6 weeks, NODAT (capillary blood glucose [CapBG] ≥11.1 mmol/L, FPG ≥7.0 mmol/L, 2-hr plasma glucose ≥11.1 mmol/L, or glycated hemoglobin [HbA1c] ≥6.5%) was detected in 46% with CapBG versus 12% with OGTT (P=0.013), 4% with HbA1c (P<0.001), and 0% with FPG (P<0.001; n=26). At 3 months, NODAT was present in 14% with HbA1c versus 20% with OGTT (P=0.600) and 2% with FPG (P=0.059; n=50), whereas, at 12 months, NODAT was found in 4% with HbA1c versus 6% with OGTT (P=1.00) and 2% with FPG (P=0.618; n=51). Combining 3- and 12-month data, OGTT recorded NODAT in 14% and impaired glucose tolerance in 28%, whereas HbA1c detected NODAT in 10% and impaired glucose tolerance (from ≥5.7 to <6.5%) in 51%. Employing HbA1c as a screening test and reserving OGTT for those with impaired glucose tolerance would detect NODAT with a sensitivity more than 94%, avoiding the need for OGTT in 49% of patients. CONCLUSIONS This study confirms the inadequacy of FPG screening for NODAT in the first 6 weeks after transplantation, at which time 4 p.m. CapBG also outperformed OGTT. From 3 months, HbA1c had similar sensitivity to OGTT and represents a convenient alternative.
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Musgrave CR, Pilch NA, Taber DJ, Meadows HB, McGillicuddy JW, Chavin KD, Baliga PK. Improving transplant patient safety through pharmacist discharge medication reconciliation. Am J Transplant 2013; 13:796-801. [PMID: 23332093 DOI: 10.1111/ajt.12070] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2012] [Revised: 11/12/2012] [Accepted: 11/13/2012] [Indexed: 01/25/2023]
Abstract
Greater than 50% of medication errors are estimated to occur during transitions of care, and solid-organ transplant recipients are at an increased risk for errors due to significant changes in their medication regimen following transplantation. This prospective, observational study with a historical control group was conducted to evaluate the discharge process for transplant recipients and determine if transplant pharmacist involvement would improve safety. During the prospective period, a total of 191 errors were made on discharge medication reconciliations (n = 64, mean rate 3.0 per patient); however, pharmacists prevented 119 of these errors (1.9 errors per patient). In the retrospective period, none of the 430 errors identified were prevented at the time of discharge (n = 128, p < 0.0001). The 72 errors not prevented at the time of discharge in the prospective cohort were identified by the pharmacist at the patient's first clinic visit (1.1 errors per patient). In the historical cohort, all 430 errors made at discharge persisted until at least the time of the first clinic visit (3.4 errors per patient, p < 0.0001). This study demonstrates that transplant recipients are at a high risk for medication errors and that transplant pharmacist involvement leads to improved safety through the significant reduction of medication errors.
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Affiliation(s)
- C R Musgrave
- Department of Pharmacy Services, Medical University of South Carolina, Charleston, SC, USA.
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Hermayer KL, Egidi MF, Finch NJ, Baliga P, Lin A, Kettinger L, Biggins S, Carter RE. A randomized controlled trial to evaluate the effect of glycemic control on renal transplantation outcomes. J Clin Endocrinol Metab 2012; 97:4399-406. [PMID: 23074234 DOI: 10.1210/jc.2012-1979] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT Outcomes from intensive glycemic control postrenal transplant have not been studied. OBJECTIVE Our objective was to observe the optimal management of hyperglycemia in patients with diabetes or impaired glucose tolerance receiving renal transplantation. DESIGN, SETTING, AND PATIENTS We conducted a randomized controlled trial with patients undergoing renal transplantation randomized to either i.v. insulin therapy (intensive) or standard s.c. insulin therapy while the patients were admitted to the hospital. INTERVENTIONS The study consisted of a 3-day postrenal transplant group treated with intensive i.v. insulin [blood glucose (BG) = 70-110 mg/dl] or a control group treated with s.c. insulin (BG = 70-180 mg/dl). MAIN OUTCOME MEASURE The primary endpoint was delayed graft function (DGF). Secondary endpoints were glycemic control, graft survival, and acute rejection episodes. RESULTS A total of 104 patients were screened and randomized to either the intensive or control condition; however, the intention-to-treat analysis set consisted of only the 93 participants (n = 44 intensive, n = 49 control) that underwent a renal transplant. DGF was present in 18% (eight of 44) of the intensive group and 24% (12 of 49) of the control group (P = 0.46). The occurrence of severe hypoglycemia (BG < 40 mg/dl) and severe hyperglycemia (BG > 350 mg/dl) were the primary safety outcome measures. There were nine participants with hypoglycemia identified, seven of which (78%) were in the intensive treatment group (P = 0.08). There were 30 instances of hyperglycemia with five participants (11%) in the intensive group and 12 participants (24%) in the control group having at least one hyperglycemic event (P = 0.10). For the 11 rejection episodes, nine were in the intensive treatment group (P = 0.013). CONCLUSIONS The primary outcome measure of DGF was not statistically different for the two treatment groups. Regarding longer-term rejection and graft survival, the intensively treated participants were at higher risk for a rejection episode.
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Affiliation(s)
- Kathie L Hermayer
- Division of Endocrinology, Diabetes, Medical Genetics, 816 CSB, 96 Jonathan Lucas Street, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
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Singh S, Watt KD. Long-term medical management of the liver transplant recipient: what the primary care physician needs to know. Mayo Clin Proc 2012; 87:779-90. [PMID: 22763347 PMCID: PMC3498400 DOI: 10.1016/j.mayocp.2012.02.021] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2011] [Revised: 02/07/2012] [Accepted: 02/16/2012] [Indexed: 12/18/2022]
Abstract
Recognition, management, and prevention of medical complications and comorbidities after liver transplant is the key to improved long-term outcomes. Beyond allograft-related complications, metabolic syndrome, cardiovascular disease, renal dysfunction, and malignancies are leading causes of morbidity and mortality in this patient population. Primary care physicians have an important role in improving outcomes of liver transplant recipients and are increasingly relied on for managing these complex patients. This review serves to assist the primary care physician in the long-term management issues of liver transplant recipients.
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Key Words
- acei, angiotensin converting enzyme inhibitor
- arb, angiotensin receptor blocker
- ckd, chronic kidney disease
- cni, calcineurin inhibitor
- ibd, inflammatory bowel disease
- lt, liver transplant
- mmf, mycophenolate mofetil
- mtor, mammalian target of rapamycin
- nash, nonalcoholic steatohepatitis-related cirrhosis
- olt, orthotopic liver transplant
- psc, primary sclerosing cholangitis
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Affiliation(s)
| | - Kymberly D. Watt
- Correspondence: Address to Kymberly D. Watt, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905
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