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Sanchez-Baya M, Bolufer M, Vázquez F, Alonso N, Massó E, Paul J, Coll-Brito V, Taco O, Anton-Pampols P, Gelpi R, DaSilva I, Casas Á, Rodríguez R, Molina M, Cañas L, Vila A, Ara J, Bover J. Diabetes Mellitus in Kidney Transplant Recipients: New Horizons in Treatment. J Clin Med 2025; 14:1048. [PMID: 40004579 PMCID: PMC11856796 DOI: 10.3390/jcm14041048] [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: 01/10/2025] [Revised: 02/02/2025] [Accepted: 02/05/2025] [Indexed: 02/27/2025] Open
Abstract
Diabetes mellitus (DM) in kidney transplant recipients (KTR) is a risk factor for mortality, increases the risk of infections and, in the long term, can lead to graft loss due to diabetic kidney disease. A preventive approach applied to those on the waiting list could decrease the incidence of post-transplant DM (PTDM) by detecting those patients at risk, thus allowing strategies to minimize the probability of developing a New Onset Diabetes After Transplant (NODAT). On the other hand, modifications of immunosuppressive therapy may improve glucose control in patients with KTR. In recent years, two new classes of antidiabetic drugs and non-steroidal mineralocorticoid receptor antagonists have demonstrated cardiovascular and renal benefits in randomized clinical trials where the transplant population has not been represented. Because of the potential benefit expected in this population, the clinical use of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i) and finerenone is increasing in the kidney transplant setting. This review focuses on comprehensive pharmacological interventions in KTR with glucose metabolism disorders. In-depth knowledge in this area will allow prevention and identification of potential adverse effects or drug interactions in the clinical course of KTR with DM.
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Affiliation(s)
- Maya Sanchez-Baya
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Mónica Bolufer
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Federico Vázquez
- Department of Endocrinology and Nutrition, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain
| | - Nuria Alonso
- Department of Endocrinology and Nutrition, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain
- Germans Trias i Pujol Health Sciences Research Institute (IGTP), 08916 Badalona, Spain
- Department of Medicine, Autonomous University of Barcelona (UAB), 08193 Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases, Instituto de Salud Carlos III, 08041 Barcelona, Spain
| | - Elisabet Massó
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Javier Paul
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Veronica Coll-Brito
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Omar Taco
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Paula Anton-Pampols
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Rosana Gelpi
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Iara DaSilva
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Ángela Casas
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Rosely Rodríguez
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Maria Molina
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Laura Cañas
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Anna Vila
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Jordi Ara
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, Spain
| | - Jordi Bover
- Department of Nephrology, Hospital Universitario Germans Trias i Pujol, 08916 Barcelona, Spain (V.C.-B.); (M.M.)
- Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2040, 28029 Badalona, 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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American Diabetes Association Professional Practice Committee, ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Ebekozien O, Echouffo-Tcheugui JB, Ekhlaspour L, Gaglia JL, Garg R, Khunti K, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Selvin E, Stanton RC, Bannuru RR. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S27-S49. [PMID: 39651986 PMCID: PMC11635041 DOI: 10.2337/dc25-s002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 09/12/2024] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Kim J, Joh JW, Lee KW, Choi DL, Wang HJ. Safety and efficacy of early corticosteroid withdrawal in liver transplant recipients: A randomized controlled trial. Ann Hepatobiliary Pancreat Surg 2024; 28:238-247. [PMID: 38484785 PMCID: PMC11128783 DOI: 10.14701/ahbps.23-129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 02/04/2024] [Accepted: 02/04/2024] [Indexed: 05/25/2024] Open
Abstract
Backgrounds/Aims Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.
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Affiliation(s)
- Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Korea
| | - Hee-Jung Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
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American Diabetes Association Professional Practice Committee, ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Gaglia JL, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Selvin E, Stanton RC, Gabbay RA. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S20-S42. [PMID: 38078589 PMCID: PMC10725812 DOI: 10.2337/dc24-s002] [Citation(s) in RCA: 519] [Impact Index Per Article: 519.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Crannage EF, Nguyen KL, Ellebrecht MD, Challen LM, Crannage AJ. Use of Sodium-Glucose Cotransporter-2 Inhibitor for Diabetes Management in Patients Following Kidney Transplantation. J Pharm Technol 2023; 39:147-155. [PMID: 37323766 PMCID: PMC10268042 DOI: 10.1177/87551225231169620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023] Open
Abstract
Objective: To evaluate data sources pertaining to the safety and efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitor use for diabetes management in patients following kidney transplantation. Data Sources: A literature search was conducted through PubMed (1966-January 2023), EMBASE (1973-January 2023), and clinicaltrials.gov databases using the search terms kidney transplantation, diabetes mellitus, and SGLT2 inhibitor or empagliflozin, dapagliflozin, and canagliflozin. Study Selection and Data Extraction: Studies evaluating human kidney transplant recipients (KTR) receiving SGLT2 inhibitors treatment and published in the English language were included. Eight case series or retrospective analyses, 4 prospective observational studies, and 1 randomized controlled trial were identified. Data Synthesis: Available literature provides evidence that the addition of SGLT2 inhibitors may provide modest benefits on glycemic control, body weight, and serum uric acid levels in certain KTR. Various studies and case reports found that incidence of urinary tract infections was low, but still present. Overall, there are limited data on mortality and graft survival; however, one study reported a benefit of SGLT2 inhibitor use in KTR relative to these outcomes. Conclusions: The current literature evaluated demonstrates that there may be benefit to the addition of SGLT2 inhibitors for diabetes management in select KTR. However, the limited evidence within a large diverse population and extended duration of treatment makes it difficult to definitively identify the true efficacy and safety of SGLT2 inhibitor use in this population.
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Affiliation(s)
- Erica F. Crannage
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Katherine L. Nguyen
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Morgan D. Ellebrecht
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Laura M. Challen
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
| | - Andrew J. Crannage
- St. Louis College of Pharmacy, University of Health Sciences & Pharmacy in St. Louis, St. Louis, MO, USA
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7
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S19-S40. [PMID: 36507649 PMCID: PMC9810477 DOI: 10.2337/dc23-s002] [Citation(s) in RCA: 1209] [Impact Index Per Article: 604.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Quintana-Pérez JC, García-Dolores F, Valdez-Guerrero AS, Alemán-González-Duhart D, Arellano-Mendoza MG, Rojas Hernández S, Olivares-Corichi IM, García Sánchez JR, Trujillo Ferrara JG, Tamay-Cach F. Modeling type 2 diabetes in rats by administering tacrolimus. Islets 2022; 14:114-127. [PMID: 35348048 PMCID: PMC8966987 DOI: 10.1080/19382014.2022.2051991] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
The prevalence of diabetes is rapidly increasing. The current number of diagnosed cases is ~422 million, expected to reach ~640 million by 2040. Type 2 diabetes, which constitutes ~95% of the cases, is characterized by insulin resistance and a progressive loss of β-cell function. Despite intense research efforts, no treatments are yet able to cure the disease or halt its progression. Since all existing animal models of type 2 diabetes have serious drawbacks, one is needed that represents the complete pathogenesis, is low cost and non-obese, and can be developed relatively quickly. The aim of this study was to evaluate a low-cost, non-obese model of type 2 diabetes engendered by administering a daily high dose of tacrolimus (an immunosuppressant) to Wistar rats for 4 weeks. The biochemical and antioxidant markers were measured at basal and after the 4-week tacrolimus treatment. At week 4, the values of these parameters closely resembled those observed in human type 2 diabetes, including fasting blood glucose at 141.5 mg/dL, blood glucose greater than 200 mg/dL at 120 min of the glucose tolerance test, blood glucose at varied levels in the insulin tolerance test, and elevated levels of cholesterol and triglyceride. The tacrolimus treatment produced hypoinsulinemia and sustained hyperglycemia, probably explained by the alteration found in pancreatic β-cell function and morphology. This model should certainly be instrumental for evaluating possible type 2 diabetes treatments, and for designing new immunosuppressants that do not cause pancreatic damage, type 2 diabetes, or new-onset diabetes after transplantation (NODAT).
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Affiliation(s)
- JC Quintana-Pérez
- Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas,Miguel Hidalgo, Ciudad de México, México
| | - F García-Dolores
- Departamento de Patología, Instituto de Servicios Periciales y Ciencias Forenses, Tribunal Superior de Justicia de la Ciudad de México, Ciudad de México, México
| | - AS Valdez-Guerrero
- Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas,Miguel Hidalgo, Ciudad de México, México
| | - D Alemán-González-Duhart
- Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas,Miguel Hidalgo, Ciudad de México, México
| | - MG Arellano-Mendoza
- Laboratorio de Investigación en Enfermedades Crónico Degenerativas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Miguel Hidalgo, Ciudad de México, México
| | - S Rojas Hernández
- Laboratorio de Inmunología Celular y Molecular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Miguel Hidalgo, Ciudad de México, México
| | - IM Olivares-Corichi
- Laboratorio de Estrés Oxidativo, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Ciudad de México, México
| | - JR García Sánchez
- Laboratorio de Estrés Oxidativo, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Ciudad de México, México
| | - JG Trujillo Ferrara
- Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas,Miguel Hidalgo, Ciudad de México, México
| | - F Tamay-Cach
- Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas,Miguel Hidalgo, Ciudad de México, México
- CONTACT F Tamay-Cach Laboratorio de Investigación en Bioquímica Aplicada, Sección de Estudios de Posgrado e Investigación y Departamento de Formación Básica Disciplinaria, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomas, Miguel Hidalgo, Ciudad de México11340, México. JG TrujilloFerrara
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Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes. Nat Med 2022; 28:999-1005. [PMID: 35393535 DOI: 10.1038/s41591-022-01758-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 02/24/2022] [Indexed: 12/13/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients (n = 1,581) and their donors (n = 1,555), and kidney recipients (n = 2,062) and their donors (n = 533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1-71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8-65.8%) for the clinical characteristics model (P = 0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07-5.00) (P = 1.92 × 10-7) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted.
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10
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Axelrod DA, Cheungpasitporn W, Bunnapradist S, Schnitzler MA, Xiao H, McAdams-DeMarco M, Caliskan Y, Bae S, Ahn JB, Segev DL, Lam NN, Hess GP, Lentine KL. Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients. Kidney Med 2022; 4:100377. [PMID: 35072042 PMCID: PMC8767140 DOI: 10.1016/j.xkme.2021.08.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
RATIONALE & OBJECTIVE Posttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients. STUDY DESIGN Retrospective database study. SETTING & PARTICIPANTS Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. EXPOSURES Various immunosuppression regimens in the first 3 months after transplant. OUTCOMES Development of DM >3 months-to-1 year posttransplant. ANALYTICAL APPROACH We used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting. RESULTS 12.7% of kidney transplant recipients developed posttransplant DM with higher incidences in older (≥55 years vs <55 years: 16.7% vs 10.1%) and obese (body mass index [BMI] ≥ 30 kg/m2 vs BMI < 30 kg/m2: 17.1% vs 10.9%) patients. The incidence of posttransplant DM was lower with steroid avoidance [TMG/ALEM + no prednisone (8.4%) and IL2rAb + no prednisone (9.7%)] than TMG/ALEM with triple therapy (13.1%). After adjustment for donor and recipient characteristics, TMG/ALEM with steroid avoidance was beneficial for all groups [age < 55 years: adjusted HR (aHR), 0.63 (95% confidence interval [CI], 0.54-0.72); age ≥ 55 years: aHR, 0.69 (95% CI, 0.60-0.79); BMI < 30 kg/m2: aHR, 0.69 (95% CI, 0.60-0.78); BMI ≥ 30 kg/m2: aHR, 0.67 (95% CI, 0.57-0.79)]. However, IL2rAb with steroid avoidance was beneficial only for older patients (aHR, 0.76; 95% CI, 0.58-0.99) and for those with BMI < 30 kg/m2 (aHR, 0.63; 95% CI, 0.46-0.87). LIMITATIONS Retrospective study and lacked data on immunosuppression levels. CONCLUSIONS The beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.
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Affiliation(s)
| | | | | | - Mark A. Schnitzler
- Saint Louis University Center for Abdominal Transplantation, Saint Louis, Missouri
| | - Huiling Xiao
- Saint Louis University Center for Abdominal Transplantation, Saint Louis, Missouri
| | | | - Yasar Caliskan
- Saint Louis University Center for Abdominal Transplantation, Saint Louis, Missouri
| | - Sunjae Bae
- Johns Hopkins School of Medicine, Baltimore, Maryland
| | - JiYoon B. Ahn
- Johns Hopkins School of Medicine, Baltimore, Maryland
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American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S17-S38. [PMID: 34964875 DOI: 10.2337/dc22-s002] [Citation(s) in RCA: 1351] [Impact Index Per Article: 450.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Gul W, Naem E, Elawad S, Elhadd T. Successful use of the sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with renal transplant and diabetes: a case series and literature review. Cardiovasc Endocrinol Metab 2021; 10:222-224. [PMID: 34765893 PMCID: PMC8575439 DOI: 10.1097/xce.0000000000000246] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Accepted: 02/01/2021] [Indexed: 01/10/2023]
Abstract
Management of patients with diabetes and renal transplant could be challenging. Transplant patients use multiple immune suppressants that can worsen or even trigger hyperglycemia. There are no data about the use of the new class of sodium-glucose co-transporter-2 (SGLT-2) inhibitor dapagliflozin in patients with renal transplant and diabetes. CASE SERIES Four patients, with diabetes, who are attending the diabetes clinic at our institution, are presented here. They were all counseled to be started on dapagliflozin 10 mg to improve diabetes control as they were on multiple agents and not achieving targets. All four patients showed significant improvement in hemoglobin A1c, with no adverse effects on renal parameters and had favorable effect on weight and blood pressure (BP). CONCLUSION Use of the SGLT-2 inhibitor dapagliflozin in the standard dose of 10 mg helped to achieve satisfactory control with favorable effects on BP and weight with no adverse effects on renal function.
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Affiliation(s)
- Wajiha Gul
- Department of Medicine, Endocrinology Section & Qatar Metabolic Institute, Hamad Medical Corporation
| | - Emad Naem
- Department of Medicine, Endocrinology Section & Qatar Metabolic Institute, Hamad Medical Corporation
| | - Safa Elawad
- Department of Medicine, Section of Nephrology, Hamad General Hospital, Doha, Qatar
| | - Tarik Elhadd
- Department of Medicine, Endocrinology Section & Qatar Metabolic Institute, Hamad Medical Corporation
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13
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Zhang K, Zheng S. The need for deepened molecular mechanism exploration in new onset diabetes after transplantation (NODAT). Hepatobiliary Surg Nutr 2021; 10:896-898. [PMID: 35004966 PMCID: PMC8683927 DOI: 10.21037/hbsn-2021-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Accepted: 10/21/2021] [Indexed: 08/30/2023]
Affiliation(s)
- Ke Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
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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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15
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Wachholz LF, Knihs NDS, Sens S, Paim SMS, Magalhães ALP, Roza BDA. Good Practices in Transitional Care: continuity of care for patients undergoing liver transplantation. Rev Bras Enferm 2021; 74:e20200746. [PMID: 34037143 DOI: 10.1590/0034-7167-2020-0746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 11/21/2020] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVES to develop a guide of care recommendations for good practices in care transition for adult patients undergoing liver transplantation. METHODS a methodological study, based on the Appraisal of Guidelines for Research & Evaluation in the updated version, II. Care recommendations were sustained by conducting an integrative literature review and qualitative research. RESULTS from evidence, three topics emerged: Care Transition Planning; Health Education for Self-Care; Care Management. Each of the central topics has respective subtopics, totaling six, giving rise to 30 care recommendations. Concerning evaluators' scores, in all domains the scores were higher than 90%. FINAL CONSIDERATIONS the proposed guide assists professionals in conducting care transition in liver transplantation, ensuring greater safety for patients in continuity of home care.
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Affiliation(s)
| | | | - Suyan Sens
- Universidade Federal de Santa Catarina. Florianópolis, Santa Catarina, Brazil
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16
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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17
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Poltronieri NVG, Moreira RSL, Schirmer J, Roza BDA. Medication non-adherence in heart transplant patients. Rev Esc Enferm USP 2020; 54:e03644. [PMID: 33295526 DOI: 10.1590/s1980-220x2019009203644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Accepted: 01/30/2020] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE To measure medication non-adherence in patients after heart transplantation using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and the Visual Analogue Scale (VAS); to compare the results of biopsies performed with the prevalent comorbidities and survival. METHOD Quantitative historical cohort. The population consisted of patients undergoing transplantation between 2009 and 2016. RESULTS Participation of 60 patients. The measurement using the BAASIS was 46.7% of non-adherence and 53.3% of patient adherence. The group with greater difficulty in non-adherence reported up to 2 hours delay of medication intake in relation to the prescribed time (25%), although there was no interruption in medications. The initial diagnosis was Chagas disease (33.3%). The studied comorbidities were systemic arterial hypertension (SAH), diabetes mellitus (DM), dyslipidemia (DLP) and chronic renal failure (CRF). CONCLUSION Assessment using the BAASIS showed medication non-adherence in 46.7% of heart transplant patients. The VAS according to patients' self-report and nurse's assessment showed high values (93.3% vs 83.3%). The BAASIS tends to address the difficulties reported by patients, when there is a change in doses, delays or anticipations of time and dose.
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Affiliation(s)
| | | | - Janine Schirmer
- Universidade Federal de São Paulo, Escola Paulista de Enfermagem, São Paulo, SP, Brasil
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18
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Man Kim J, Hwang S, Lee KW, Lee JG, Ryu JH, Kim BW, Choi DL, You YK, Kim DS, Nah YW, Kang KJ, Cho JY, Hong G, Choi IS, Yu HC, Choi D, Kim MS, The Korean Organ Transplantation Registry Study Group. New-onset diabetes after adult liver transplantation in the Korean Organ Transplantation Registry (KOTRY) study. Hepatobiliary Surg Nutr 2020; 9:425-439. [PMID: 32832494 PMCID: PMC7423540 DOI: 10.21037/hbsn.2019.10.29] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Accepted: 08/05/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication following liver transplantation (LT). The present study aimed to investigate the incidence of and risk factors for NODAT using the Korean Organ Transplantation Registry (KOTRY) database. METHODS Patients with history of pediatric transplantation (age ≤18 years), re-transplantation, multi-organ transplantation, or pre-existing diabetes mellitus were excluded. A total of 1,919 non-diabetic adult patients who underwent a primary LT between May 2014 and December 2017 were included. Risk factors were identified using Cox regression analysis. RESULTS NODAT occurred in 19.7% (n=377) of adult liver transplant recipients. Multivariate analysis showed steroid use, increased age, and high body mass index (BMI) in recipients, and implantation of a left-side liver graft was closely associated with NODAT in adult LT. In living donor liver transplant (LDLT) patients (n=1,473), open donor hepatectomy in the living donors, steroid use, small for size liver graft (graft to recipient weight ratio ≤0.8), increased age, and high BMI in the recipient were predictive factors for NODAT. The use of antimetabolite and basiliximab induction reduced the incidence of NODAT in adult LT and in adult LDLT. CONCLUSIONS Basiliximab induction, early steroid withdrawal, and antimetabolite therapy may prevent NODAT after adult LT. High BMI or advanced age in liver recipients, open donor hepatectomy in living donors, and small size liver graft can predict the occurrence of NODAT after adult LT or LDLT.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae-Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
| | - Dong Lak Choi
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
| | - Young Kyoung You
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
| | - Geun Hong
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
| | - In Seok Choi
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
| | - Hee Chul Yu
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
| | - Dongho Choi
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - The Korean Organ Transplantation Registry Study Group
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
- Department of Surgery, Asan Medical Center, College of Medicine University of Ulsan, South Korea
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
- Department of Surgery, Pusan National University College of Medicine, Busan, South Korea
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, South Korea
- Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, South Korea
- Department of Surgery, College of Medicine, Catholic University of Korea, Seoul, South Korea
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, South Korea
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
- Department of Surgery, Keimyung University School of Medicine, Daegu, South Korea
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, South Korea
- Department of Surgery, Ewha Woman’s University School of Medicine, Seoul, South Korea
- Department of Surgery, Konyang University Hospital, Daejon, South Korea
- Department of Surgery, Chonbuk National University School of Medicine, Jeonju, South Korea
- Department of Surgery, Hanyang University College of Medicine, Seoul, South Korea
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Lo C, Toyama T, Oshima M, Jun M, Chin KL, Hawley CM, Zoungas S. Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients. Cochrane Database Syst Rev 2020; 8:CD009966. [PMID: 32803882 PMCID: PMC8477618 DOI: 10.1002/14651858.cd009966.pub3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.
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Affiliation(s)
- Clement Lo
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Australia
| | - Tadashi Toyama
- The George Institute for Global Health, UNSW, Sydney, Australia
- Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
- Innovative Clinical Research Center (iCREK), Kanazawa University Hospital, Kanazawa, Japan
| | - Megumi Oshima
- The George Institute for Global Health, UNSW, Sydney, Australia
- Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, Japan
- Innovative Clinical Research Center (iCREK), Kanazawa University Hospital, Kanazawa, Japan
| | - Min Jun
- The George Institute for Global Health, UNSW, Sydney, Australia
| | - Ken L Chin
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- Melbourne Medical School, The University of Melbourne, Melbourne, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Australia
- Australasian Kidney Trials Network, Diamantina Institute, The University of Queensland, Brisbane, Australia
- Translational Research Institute, Brisbane, Australia
| | - Sophia Zoungas
- School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
- The George Institute for Global Health, UNSW, Sydney, Australia
- Diabetes and Vascular Medicine Unit, Monash Health, Clayton, Australia
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Zhao T, Zhao Y, Zong A, Tang Y, Shi X, Zhou Y. Association of body mass index and fasting plasma glucose concentration with post-transplantation diabetes mellitus in Chinese heart transplant recipients. J Int Med Res 2020; 48:300060520910629. [PMID: 32216552 PMCID: PMC7132567 DOI: 10.1177/0300060520910629] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Objective Post-transplantation diabetes mellitus (PTDM) is a frequent complication
after heart transplantation. We investigated the specific predictors of PTDM
in Chinese heart transplant recipients and the prognostic value of these
predictors. Methods We retrospectively analyzed 122 adult patients who underwent heart
transplantation. Comparisons were made between patients with PTDM (n = 44)
and those without PTDM (n = 78). Results During the median follow-up of 44 months, the cumulative incidence of PTDM
was 19.7% at 1 year after transplantation and 36.1% at the endpoint. PTDM
was associated with a significantly higher preoperative body mass index
(BMI) (odds ratio [OR] = 1.349), fasting plasma glucose (FPG) concentration
(OR = 2.538), and serum uric acid concentration (OR = 1.005) after
transplantation. The area under the receiver operating characteristic curve
was 0.708 and 0.763 for the BMI and FPG concentration, respectively. The
incidence of acute rejection and infection were higher and the all-cause
mortality rate was considerably greater in patients with than without
PTDM. Conclusions A higher preoperative BMI (>23 kg/m2), FPG concentration
(>5.2 mmol/L), and uric acid concentration could potentially predict PTDM
in Chinese heart transplant recipients. PTDM influences long-term survival
after heart transplantation.
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Affiliation(s)
- Tian Zhao
- Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China
| | - Yinan Zhao
- Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China
| | - Ailun Zong
- Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China
| | - Yadi Tang
- Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China
| | - Xiaopeng Shi
- Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China
| | - Yingsheng Zhou
- Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing, PR China
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Health Needs of Patients Undergoing Liver Transplant From the Context of Hospital Discharge. Transplant Proc 2020; 52:1344-1349. [PMID: 32199651 DOI: 10.1016/j.transproceed.2020.02.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 02/05/2020] [Accepted: 02/13/2020] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To identify the health needs of the patient and family facing the perspectives of discharge, health care, and adaptation to the new reality at home. METHODS This was a quantitative and qualitative, exploratory, descriptive study conducted at a reference hospital for liver transplantation. The participants were patients undergoing liver transplant in this hospital unit from 2011 to June 2019. A semistructured interview script was used for data collection, and data were analyzed according to guidelines proposed for content analysis. RESULTS Twenty patients participated, with a mean age of 40.2 years; 76% were men. The interview data enabled the development of 3 categories: daily health care, warning signs, and adaptation to the new health care routine. The data obtained from the categories showed that the main health needs include difficulties in blood glucose management, insulin administration, the importance of awareness of the warning signs, and obtaining support from the health care team to deal with food restrictions and high doses of medication. CONCLUSION The health needs are focused on identifying strategies to develop daily care, in addition to seeking better strategies to adapt to the new reality. The study showed the need for individualized discharge planning by the health care team, based on the health needs of each patient.
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Gulsoy Kirnap N, Bozkus Y, Haberal M. Analysis of Risk Factors for Posttransplant Diabetes Mellitus After Kidney Transplantation: Single-Center Experience. EXP CLIN TRANSPLANT 2020; 18:36-40. [PMID: 32008491 DOI: 10.6002/ect.tond-tdtd2019.o8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Posttransplant diabetes mellitus may severely affect the short-term and long-term outcomes of grafts and patient survival in kidney transplant recipients. The annual incidence rate of posttransplant diabetes mellitus ranges from 4% to 25%. In this study, our aim was to determine the possible risk factors in patients diagnosed with this disease. MATERIALS AND METHODS From November 1975 to May 2019, our transplant team performed 3012 kidney transplant procedures at different units within Baskent University Transplantation Centers. We retrospectively analyzed data of patients who were diagnosed with posttransplant diabetes mellitus between 2010 and 2019. The diagnosis was made according to the 2001 American Diabetes Association criteria (fasting plasma glucose level ≥ 126 mg/dL [7 mmol/L] in 2 measurements or random blood glucose level ≥ 200 mg/dL [11.1 mmol/L] within 12 months posttransplant). RESULTS For this study, 400 patients (292 male, 108 female) with end-stage renal disease and without diabetes met the initial inclusion criteria; 270 received hemodialysis, 26 received peritoneal dialysis, and 104 underwent preemptive kidney transplant. In this patient group, 62 patients (15.5%) developed post-transplant diabetes mellitus. When we compared patients who developed and did not develop posttransplant diabetes mellitus, cause of end-stage renal disease, dialysis type and duration, type of donor (living or deceased), and graft survival posttransplant were similar between groups. Baseline fasting plasma glucose level was significantly higher in patients who developed posttransplant diabetes mellitus (90 vs 85 mg/dL; P = .034). Patients who developed the disease were significantly older. CONCLUSIONS In our study, recipient age was the only risk factor for posttransplant diabetes mellitus. Older recipients should be examined more carefully for posttransplant diabetes mellitus, and less diabetogenic immunosuppressive drugs may be preferred.
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Samji NS, Heda R, Satapathy SK. Peri-transplant management of nonalcoholic fatty liver disease in liver transplant candidates . Transl Gastroenterol Hepatol 2020; 5:10. [PMID: 32190778 PMCID: PMC7061181 DOI: 10.21037/tgh.2019.09.09] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 09/23/2019] [Indexed: 12/12/2022] Open
Abstract
The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly growing, affecting 25% of the world population. Non-alcoholic steatohepatitis (NASH) is the most severe form of NAFLD and affects 1.5% to 6.5% of the world population. Its rising incidence will make end-stage liver disease (ESLD) due to NASH the number one indication for liver transplantation (LT) in the next 10 to 20 years, overtaking Hepatitis C. Patients with NASH also have a high prevalence of associated comorbidities such as type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, and chronic kidney disease (CKD), which must be adequately managed during the peritransplant period for optimal post-transplant outcomes. The focus of this review article is to provide a comprehensive overview of the unique challenges these patients present in the peritransplant period, which comprises the pre-transplant, intraoperative, and immediate postoperative periods.
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Affiliation(s)
- Naga Swetha Samji
- Tennova Cleveland Hospital, 2305 Chambliss Ave NW, Cleveland, TN, USA
| | - Rajiv Heda
- University of Tennessee Health Science Center, College of Medicine, Memphis, TN, USA
| | - Sanjaya K. Satapathy
- Division of Hepatology and Sandra Atlas Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee (https://doi.org/10.2337/dc20-SPPC), a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc20-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Wachholz LF, Knihs NDS, Martins SR, Magalhães ALP, Brehmer LCDF, Martins MDS. Alta hospitalar do paciente transplantado hepático: revisão integrativa. ESCOLA ANNA NERY 2020. [DOI: 10.1590/2177-9465-ean-2019-0346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
Abstract
Resumo Objetivo Analisar evidências disponíveis na literatura capazes de subsidiar o planejamento da alta hospitalar do paciente submetido ao transplante hepático. Método Revisão integrativa a partir das bases Scopus, LILACS, SciELO, MEDLINE/PubMed, CINAHL, BDENF, Web of Science. Utilizou-se os descritores Transplante hepático e Alta hospitalar, em inglês, espanhol e português, identificando-se 1.152 artigos, sendo que a amostra foi composta por 13 artigos. Resultados As publicações concentram-se entre 2014 (n=4; 30,7%) e 2016 (n=3; 23%), tendo como origem o Brasil (n=5; 38,4%) e os Estados Unidos (n=3; 23%). Os resultados foram organizados nas categorias: Sinais de alerta para possíveis alterações que possam surgir no domicílio; Recomendações para o uso de medicamentos-promoção do autogerenciamento e adesão ao tratamento; Atividades e cuidados diários em domicílio – apoio e autoconfiança; Mudanças na imagem corporal e vida diária – importância da rede de apoio. Conclusão A alta hospitalar do paciente submetido ao transplante hepático é um desafio, visto a complexidade do procedimento. Os achados apresentam cuidados direcionados à educação em saúde no sentido de minimizar complicações, apoiar a equipe multiprofissional e o paciente no autocuidado, em especial quanto aos sinais e sintomas de complicações, cuidados com o uso de medicação e as mudanças que ocorrem no retorno ao domicílio.
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Riou M, Renaud-Picard B, Munch M, Lefebvre F, Baltzinger P, Porzio M, Hirschi S, Dégot T, Schuller A, Santelmo N, Reeb J, Olland A, Falcoz PE, Massard G, Kessler L, Kessler R. Organized Management of Diabetes Mellitus in Lung Transplantation: Study of Glycemic Control and Patient Survival in a Single Center. Transplant Proc 2019; 51:3375-3384. [DOI: 10.1016/j.transproceed.2019.07.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 05/31/2019] [Accepted: 07/09/2019] [Indexed: 12/27/2022]
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Jeddi M, Aghasadeghi F, Ranjbar Omrani G, Malek-Hosseini SA, Lakarani KB. Incidence, Risk Factors, and Follow-Up of Diabetes Mellitus After Liver Transplant: A Prospective Study From Iran. EXP CLIN TRANSPLANT 2019; 19:928-934. [PMID: 31580241 DOI: 10.6002/ect.2019.0158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Diabetes mellitus is one of the metabolic consequences of solid-organ transplant. Most reports on this condition are from cross-sectional or retrospective studies. In this prospective study, we evaluated the incidence, risk factors, and short-term follow-up of diabetes mellitus in recipients of liver transplant at the Shiraz Liver Transplant Center (Shiraz, Iran). MATERIALS AND METHODS Recipients of liver transplant who were ≥ 16 year old and were seen from February 2017 until February 2018 were included. Anthropologic measurements and diabetes history were taken between 2 and 4 weeks after transplant. Fasting blood sugar and 75-g oral glucose tolerance test were measured. We diagnosed patients with diabetes mellitus and patients with impaired fasting glucose or impaired glucose tolerance test based on American Diabetes Association criteria. These patients were promptly followed for at least 6 months. RESULTS Of the 397 recipients who were included in this study, 35.5% were female and 64.5% were male. Overall, the most common reason for transplant was primary sclerosing cholangitis (22.5%). We had 42 living donors and 355 deceased donors, with none being unrelated donors. At first visit (3.8 ± 1.6 wk posttransplant), 20.4% of recipients did not have diabetes, 24.2% were diagnosed with preexisting diabetes mellitus, 31.2% had impaired fasting blood sugar or oral glucose tolerance test, and 24.2% were determined to have posttransplant diabetes mellitus. At last visit (13.6 ± 4.9 mo posttransplant), prevalence for posttransplant diabetes mellitus was 10.8%. Multivariate regression analysis showed that age correlated with development of impaired glucose tolerance test or posttransplant diabetes mellitus (odds ratio 1.060; 95% confidence interval, 1.026-1.095; P < .001). CONCLUSIONS In this prospective cohort study, we followed recipients posttransplant and reevaluated the prevalence of posttransplant diabetes mellitus. We found significant recovery for this type of diabetes mellitus. Further larger and multicenter studies are necessary to monitor and manage diabetes mellitus posttransplant.
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Affiliation(s)
- Marjan Jeddi
- From the Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Abstract
Advancement in kidney transplantation has led to prolonged survival in our population with kidney disease. Newer agents of immunosuppression have made this possible with less rejections and lesser opportunistic infections and transplant related deaths. Preventative care like timely vaccines, cancer screenings, aggressive blood pressure, blood sugar, lipid control, timely referral to consultants is required in these patient population to provide quality care and to prolong their survival. Primary care physicians are the best advocate for our transplant populations. To care for these complex transplant patients, it is vital for primary care physicians to be familiar with the overall approach on our patients.
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Affiliation(s)
- Kavitha Ramaswamy
- Thomas Jefferson University Hospital, Division of Nephrology, 833 Chestnut St, Suite 700, Philadelphia, PA 19107, USA.
| | - Hector M Madariaga
- Good Samaritan Medical Center, Department of Medicine, 235N Pearl St, Brockton, MA 02301, USA
| | - Beje S Thomas
- Georgetown University Medical Center, MedStar Georgetown Transplant Institute, 3800 Reservoir Road, Washington, DC 20007 USA
| | - Edgar V Lerma
- University of Illinois at Chicago College of Medicine/ Advocate Christ Medical Center, Oak Lawn, IL, USA
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Efficacy and Safety of Empagliflozin in the Management of Diabetes Mellitus in Heart Transplant Recipients. Transplant Direct 2019; 5:e450. [PMID: 31165085 PMCID: PMC6511439 DOI: 10.1097/txd.0000000000000885] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Accepted: 02/15/2019] [Indexed: 12/27/2022] Open
Abstract
Background Type 2 diabetes mellitus (T2DM) is prevalent in patients undergoing heart transplant, and in those without preexisting T2DM, posttransplant diabetes mellitus may develop. Both T2DM and posttransplant diabetes mellitus have been associated with increased morbidity and mortality following heart transplantation. Empagliflozin is an effective glucose-lowering therapy that reduces the incidence of major cardiovascular events in patients with T2DM. The safety and efficacy of empagliflozin in transplant patients with diabetes mellitus has yet to be established. Methods Clinical outcomes were retrospectively examined in 22 heart transplant recipients treated with empagliflozin and compared with those of 79 heart transplant patients with diabetes mellitus receiving alternative glucose-lowering therapies. Results Three adverse events were recorded in empagliflozin-treated patients, leading to treatment discontinuation in 1. There were no genitourinary infections. Treatment with empagliflozin for 12 months was associated with reductions in weight, body mass index, glycated hemoglobin, and frusemide dose that were not seen in the control group. There were no large changes observed in blood pressure (systolic or diastolic) or renal function (serum urea, creatinine, or estimated glomerular filtration rate) after 12 months of treatment with empagliflozin or alternative glucose-lowering therapies. Conclusions Empagliflozin appears safe and effective in the management of selected patients with diabetes mellitus following heart transplantation.
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Lieber SR, Lee RA, Jiang Y, Reuter C, Watkins R, Szempruch K, Gerber DA, Desai CS, DeCherney GS, Barritt AS. The impact of post-transplant diabetes mellitus on liver transplant outcomes. Clin Transplant 2019; 33:e13554. [PMID: 30927288 DOI: 10.1111/ctr.13554] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 02/26/2019] [Accepted: 03/24/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Post-transplant diabetes mellitus (PTDM) is common after liver transplantation (LT). Yet, how PTDM relates to graft outcomes and survival needs elucidation as more individuals are transplanted for nonalcoholic fatty liver disease (NAFLD). METHODS This single-center, retrospective study of adult LT recipients (2003-2016) identified PTDM incidence and associations with graft steatosis, rejection, and post-LT patient survival. Multivariable analysis investigated predictors of PTDM. Kaplan-Meier curves depicted patient survival 5 years post-LT. RESULTS Among 415 adult LT recipients, 23% had pre-LT DM and 13% were transplanted for NAFLD. PTDM incidence was 34.7%, 46.9%, and 56.2% and overall survival was 90%, 80.9%, and 71.7% at 1, 3, and 5 years, respectively. Over a third of non-NAFLD patients developed PTDM. Half of PTDM cases developed by 6 months and 75% by 12 months. The PTDM group had more rejection episodes compared to no PTDM (31.9% vs 21.8%, P = 0.055), with trends toward worse patient survival 5 years post-LT (log-rank test P = 0.254). Age was the only significant predictor of PTDM. CONCLUSIONS Post-transplant diabetes mellitus occurs rapidly in the post-LT period and is a significant problem for both NAFLD and non-NAFLD LT recipients. Age is a significant risk factor for PTDM. Outcomes trended toward increased rejection and worse survival among PTDM individuals, suggesting the benefit of early strategies targeting glucose control.
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Affiliation(s)
- Sarah R Lieber
- Division of Gastroenterology and Hepatology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina
| | - Ruth-Ann Lee
- Department of Pharmacy, UNC Health Care, Chapel Hill, North Carolina
| | - Yue Jiang
- Department of Biostatistics, UNC Gillings School of Public Health, Chapel Hill, North Carolina
| | - Claire Reuter
- Department of Specialty Pharmacy, Ochsner Medical Center, New Orleans, Louisiana
| | - Randall Watkins
- Department of Biostatistics, UNC Gillings School of Public Health, Chapel Hill, North Carolina
| | - Kristen Szempruch
- Department of Pharmacy, UNC Health Care, Chapel Hill, North Carolina
| | - David A Gerber
- Department of Surgery, UNC School of Medicine, Chapel Hill, North Carolina
| | - Chirag S Desai
- Department of Surgery, UNC School of Medicine, Chapel Hill, North Carolina
| | - G Stephen DeCherney
- Division of Endocrinology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina
| | - A Sidney Barritt
- Division of Gastroenterology and Hepatology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina
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Abstract
Solid organ transplantation (SOT) is a life-saving procedure and an established treatment for patients with end-stage organ failure. However, transplantation is also accompanied by associated cardiovascular risk factors, of which post-transplant diabetes mellitus (PTDM) is one of the most important. PTDM develops in 10-20% of patients with kidney transplants and in 20-40% of patients who have undergone other SOT. PTDM increases mortality, which is best documented in patients who have received kidney and heart transplants. PTDM results from predisposing factors (similar to type 2 diabetes mellitus) but also as a result of specific post-transplant risk factors. Although PTDM has many characteristics in common with type 2 diabetes mellitus, the prevention and treatment of the two disorders are often different. Over the past 20 years, the lifespan of patients who have undergone SOT has increased, and PTDM becomes more common over the lifespan of these patients. Accordingly, PTDM becomes an important condition not only to be aware of but also to treat. This Review presents the current knowledge on PTDM in patients receiving kidney, heart, liver and lung transplants. This information is not only for transplant health providers but also for endocrinologists and others who will meet these patients in their clinics.
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Affiliation(s)
- Trond Jenssen
- Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Anders Hartmann
- Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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32
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Gupta S, Pollack T, Fulkerson C, Schmidt K, Oakes DJ, Molitch ME, Wallia A. Hyperglycemia in the Posttransplant Period: NODAT vs Posttransplant Diabetes Mellitus. J Endocr Soc 2018; 2:1314-1319. [PMID: 30430145 PMCID: PMC6223248 DOI: 10.1210/js.2018-00227] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 10/10/2018] [Indexed: 12/30/2022] Open
Abstract
Objective To characterize the types of hyperglycemia that occur up to 1 year following liver transplant and to clarify the nomenclature for posttransplant hyperglycemia. Design We analyzed 1-year glycemic follow-up data in 164 patients who underwent liver transplant and who had been enrolled in a randomized controlled trial comparing moderate to intensive insulin therapy to determine if patients had preexisting known diabetes, transient hyperglycemia, persistent hyperglycemia, or new-onset diabetes after transplantation (NODAT). Results Of 119 patients with posttransplant hyperglycemia following hospital discharge, 49 had preexisting diabetes, 5 had insufficient data for analysis, 48 had transient hyperglycemia (16 resolved within 30 days and 32 resolved between 30 days and 1 year), 13 remained persistently hyperglycemic out to 1 year and most likely had preexisting diabetes that had not been diagnosed or insulin resistance/insulinopenia prior to transplant, and 4 had NODAT (i.e., patients with transient hyperglycemia after transplant that resolved but then later truly developed sustained hyperglycemia, meeting criteria for diabetes). Conclusions Distinct categories of patients with hyperglycemia following organ transplant include known preexisting diabetes, persistent hyperglycemia (most likely unknown preexisting diabetes or insulin resistance/insulinopenia), transient hyperglycemia, and NODAT. Those with preexisting diabetes for many years prior to transplant may well have very different long-term outcomes compared with those with true NODAT. Therefore, it would be prudent to classify patients more carefully. Long-term outcome studies are needed to determine if patients with true NODAT have the same poor prognosis as patients with preexisting diabetes (diagnosed and undiagnosed) undergoing transplant.
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Affiliation(s)
- Suruchi Gupta
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Teresa Pollack
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Candice Fulkerson
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Kathleen Schmidt
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Diana Johnson Oakes
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Mark E Molitch
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Amisha Wallia
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Development of a Predictive Model for Hyperglycemia in Nondiabetic Recipients After Liver Transplantation. Transplant Direct 2018; 4:e393. [PMID: 30498770 PMCID: PMC6233666 DOI: 10.1097/txd.0000000000000830] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 07/03/2018] [Indexed: 12/20/2022] Open
Abstract
Background Posttransplant hyperglycemia has been associated with increased risks of transplant rejection, infections, length of stay, and mortality. Methods To establish a predictive model to identify nondiabetic recipients at risk for developing postliver transplant (LT) hyperglycemia, we performed this secondary, retrospective data analysis of a single-center, prospective, randomized, controlled trial of glycemic control among 107 adult LT recipients in the inpatient period. Hyperglycemia was defined as a posttransplant glucose level greater than 200 mg/dL after initial discharge up to 1 month following surgery. Candidate variables with P less than 0.10 in univariate analyses were used to build a multivariable logistic regression model using forward stepwise selection. The final model chosen was based on statistical significance and additive contribution to the model based on the Bayesian Information Criteria. Results Forty-three (40.2%) patients had at least 1 episode of hyperglycemia after transplant after the resolution of the initial postoperative hyperglycemia. Variables selected for inclusion in the model (using model optimization strategies) included length of hospital stay (odds ratio [OR], 0.83; P < 0.001), use of glucose-lowering medications at discharge (OR, 3.76; P = 0.03), donor female sex (OR, 3.18; P = 0.02) and donor white race (OR, 3.62; P = 0.01). The model had good calibration (Hosmer-Lemeshow goodness-of-fit test statistic = 9.74, P = 0.28) and discrimination (C-statistic = 0.78; 95% confidence interval, 0.65-0.81, bias-corrected C-statistic = 0.78). Conclusions Shorter hospital stay, use of glucose-lowering medications at discharge, donor female sex and donor white race are important determinants in predicting hyperglycemia in nondiabetic recipients after hospital discharge up to 1 month after liver transplantation.
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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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Cehic MG, Nundall N, Greenfield JR, Macdonald PS. Management Strategies for Posttransplant Diabetes Mellitus after Heart Transplantation: A Review. J Transplant 2018; 2018:1025893. [PMID: 29623219 PMCID: PMC5829348 DOI: 10.1155/2018/1025893] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Accepted: 12/27/2017] [Indexed: 12/23/2022] Open
Abstract
Posttransplant diabetes mellitus (PTDM) is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP-) 1 agonists and dipeptidyl peptidase- (DPP-) 4 inhibitors) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of PTDM after heart transplantation. Recently published Consensus Guidelines for the diagnosis of PTDM will hopefully lead to more consistent approaches to the diagnosis of PTDM and provide a platform for the larger-scale multicentre trials that will be needed to determine the role of these newer therapies in the management of PTDM.
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Affiliation(s)
- Matthew G. Cehic
- Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia
- Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
| | - Nishant Nundall
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, NSW, Australia
- Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Jerry R. Greenfield
- Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, NSW, Australia
- Diabetes and Metabolism Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia
| | - Peter S. Macdonald
- Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia
- Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, NSW, Australia
- Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Peled Y, Lavee J, Raichlin E, Katz M, Arad M, Kassif Y, Peled A, Asher E, Elian D, Har-Zahav Y, Shlomo N, Freimark D, Goldenberg I, Klempfner R. Metformin therapy reduces the risk of malignancy after heart transplantation. J Heart Lung Transplant 2017; 36:1350-1357. [PMID: 28736111 DOI: 10.1016/j.healun.2017.06.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 06/11/2017] [Accepted: 06/21/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Malignancy and diabetes mellitus (DM) cause significant morbidity and mortality after heart transplantation (HTx). Metformin, one of the most commonly used anti-diabetic drugs worldwide, has also been shown to exhibit anti-tumor activity. We therefore investigated the association between metformin therapy and malignancy after HTx. METHODS The study population comprised 237 patients who underwent HTx between 1991 and 2016 and were prospectively followed-up. Clinical data were recorded on prospectively designed forms. The primary outcome was any cancer recorded during 15 years of follow-up. Treatment with metformin and the development of DM after HTx were assessed as time-dependent factors in the analyses. RESULTS Of the 237 study patients, 85 (36%) had diabetes. Of the DM patients, 48 (56%) were treated with metformin. Kaplan-Meier survival analysis showed that, at 15 years after HTx, malignancy rate was 4% for DM patients treated with metformin, 62% for those who did not receive metformin and 27% for non-DM patients (log-rank test, p < 0.0001). Consistently, multivariate analysis showed that for DM patients, metformin therapy was independently associated with a significant 90% reduction (hazard ratio = 0.10; 95% confidence interval 0.02 to 0.40; p = 0.001) in the risk of the development of a malignancy. DM patients who were treated with metformin had a markedly lower risk (65%; p = 0.001) for the development of a malignancy or death after HTx as compared with non-DM patients. CONCLUSIONS Our findings suggest that metformin therapy is independently associated with a significant reduction in the risk of malignancy after HTx.
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Affiliation(s)
- Yael Peled
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Jacob Lavee
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eugenia Raichlin
- Cardiology Department, Loyola University Medical Center, Maywood, Illinois, USA
| | - Moshe Katz
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Michael Arad
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yigal Kassif
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amir Peled
- Clalit Health Services, Central Region, Israel
| | - Elad Asher
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dan Elian
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yedael Har-Zahav
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel
| | - Nir Shlomo
- Israeli Association for Cardiovascular Trials, The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel
| | - Dov Freimark
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ilan Goldenberg
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Israeli Association for Cardiovascular Trials, The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel
| | - Robert Klempfner
- The Olga and Lev Leviev Heart Center, Sheba Medical Center, Ramat Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Ryu JH, Lee TB, Park YM, Yang KH, Chu CW, Lee JH, Choi BH. Pancreas Transplantation After Liver Transplantation: A Case Report. Transplant Proc 2017; 49:225-228. [PMID: 28104144 DOI: 10.1016/j.transproceed.2016.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 11/09/2016] [Indexed: 11/30/2022]
Abstract
Our aim was to describe the clinical indications, surgical technique, and clinical outcomes of a pancreas transplantation, performed 4 years after liver transplantation, as treatment for new-onset, uncontrolled diabetes mellitus in a 53-year-old man. Liver transplantation was performed for end-stage liver disease secondary to hepatitis B virus infection and hepatocellular carcinoma. The patient had no history of diabetes prior to the liver transplantation. The decision to proceed with a pancreas transplantation was made when the patient's blood sugar levels could not be normalized despite insulin doses >100 IU/d. A modified cadaveric transplantation technique was used, with the recipient's inferior vena cava dissected for anastomosis with the portal vein of the graft, using a diamond-shaped patch procedure. Moreover, the right common iliac artery was anastomosed with a Y-graft in the pancreas graft, and the duodenum remnant of the graft was anastomosed to the recipient's duodenum using a side-to-side procedure. The 6-month postoperative follow-up included repeated endoscopic biopsy of the graft duodenum, with no evidence of thrombosis or rejection of the graft, with glucose level within normal limits without requirement for diabetic drugs. To our knowledge, this is the first reported case of pancreas transplantation after liver transplantation.
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Affiliation(s)
- J H Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - T B Lee
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Y M Park
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - K H Yang
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - C W Chu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - J H Lee
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - B H Choi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
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