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Chowdhury TA, Mukuba D, Casabar M, Byrne C, Yaqoob MM. Management of diabetes in people with advanced chronic kidney disease. Diabet Med 2025; 42:e15402. [PMID: 38992927 DOI: 10.1111/dme.15402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/28/2024] [Accepted: 06/24/2024] [Indexed: 07/13/2024]
Abstract
Diabetes is the commonest cause of end stage kidney disease globally, accounting for almost 40% of new cases requiring renal replacement therapy. Management of diabetes in people with advanced kidney disease on renal replacement therapy is challenging due to some unique aspects of assessment and treatment in this group of patients. Standard glycaemic assessment using glycated haemoglobin may not be valid in such patients due to altered red blood cell turnover or iron/erythropoietin deficiency, leading to changed red blood cell longevity. Therefore, use of continuous glucose monitoring may be beneficial to enable more focussed glycaemic assessment and improved adjustment of therapy. People with advanced kidney disease may be at higher risk of hypoglycaemia due to a number of physiological mechanisms, and in addition, therapeutic options are limited in such patients due to lack of experience or license. Insulin therapy is the basis of treatment of people with diabetes with advanced kidney disease due to many other drugs classes being contraindicated. Targets for glycaemic control should be adjusted according to co-morbidity and frailty, and continuous glucose monitoring should be used in people on dialysis to ensure low risk of hypoglycaemia. Post-transplant diabetes is common amongst people undergoing solid organ transplantation and confers a greater risk of mortality and morbidity in kidney transplant recipients. It should be actively screened for and managed in the post-transplant setting.
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Affiliation(s)
| | - Dorcas Mukuba
- Department of Diabetes, The Royal London Hospital, London, UK
| | - Mahalia Casabar
- Department of Nephrology, The Royal London Hospital, London, UK
| | - Conor Byrne
- Department of Nephrology, The Royal London Hospital, London, UK
| | - M Magdi Yaqoob
- Barts and the London School of Medicine and Dentistry, London, UK
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Graňák K, Vnučák M, Beliančinová M, Kleinová P, Blichová T, Pytliaková M, Dedinská I. Regular Physical Activity in the Prevention of Post-Transplant Diabetes Mellitus in Patients after Kidney Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1210. [PMID: 39202491 PMCID: PMC11356157 DOI: 10.3390/medicina60081210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 07/15/2024] [Accepted: 07/22/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Post-transplant diabetes mellitus (PTDM) is a significant risk factor for the survival of graft recipients and occurs in 10-30% of patients after kidney transplant (KT). PTDM is associated with premature cardiovascular morbidity and mortality. Weight gain, obesity, and dyslipidemia are strong predictors of PTDM, and by modifying them with an active lifestyle it is possible to reduce the incidence of PTDM and affect the long-term survival of patients and grafts. The aim of our study was to determine the effect of regular physical activity on the development of PTDM and its risk factors in patients after KT. Materials and Methods: Participants in the study had to achieve at least 150 min of moderate-intensity physical exertion per week. The study group (n = 22) performed aerobic or combined (aerobic + strength) types of sports activities. Monitoring was provided by the sports tracker (Xiaomi Mi Band 4 compatible with the Mi Fit mobile application). The control group consisted of 22 stable patients after KT. Each patient underwent an oral glucose tolerance test (oGTT) at the end of the follow-up. The patients in both groups have the same immunosuppressive protocol. The total duration of the study was 6 months. Results: The patients in the study group had significantly more normal oGTT results at 6 months compared to the control group (p < 0.0001). In the control group, there were significantly more patients diagnosed with PTDM (p = 0.0212) and with pre-diabetic conditions (impaired plasma glucose and impaired glucose tolerance) at 6 months (p = 0.0078). Conclusions: Regular physical activity after KT provides significant prevention against the development of pre-diabetic conditions and PTDM.
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Affiliation(s)
- Karol Graňák
- Transplant-Nephrology Department, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia; (K.G.)
- Department of I. Internal Medicine, University Hospital Martin, Jessenius Faculty of Medicine of Comenius University, 03601 Martin, Slovakia
| | - Matej Vnučák
- Transplant-Nephrology Department, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia; (K.G.)
- Department of I. Internal Medicine, University Hospital Martin, Jessenius Faculty of Medicine of Comenius University, 03601 Martin, Slovakia
| | - Monika Beliančinová
- Transplant-Nephrology Department, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia; (K.G.)
| | - Patrícia Kleinová
- Transplant-Nephrology Department, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia; (K.G.)
- Department of I. Internal Medicine, University Hospital Martin, Jessenius Faculty of Medicine of Comenius University, 03601 Martin, Slovakia
| | - Tímea Blichová
- Transplant-Nephrology Department, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia; (K.G.)
- Department of I. Internal Medicine, University Hospital Martin, Jessenius Faculty of Medicine of Comenius University, 03601 Martin, Slovakia
| | - Margaréta Pytliaková
- Department of Gastroenterological Internal Medicine, University Hospital Martin, Jessenius Faculty of Medicine of Comenius University, 03601 Martin, Slovakia
| | - Ivana Dedinská
- Transplant-Nephrology Department, University Hospital Martin, Kollárova 2, 036 01 Martin, Slovakia; (K.G.)
- Department of I. Internal Medicine, University Hospital Martin, Jessenius Faculty of Medicine of Comenius University, 03601 Martin, Slovakia
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Kanbay M, Copur S, Topçu AU, Guldan M, Ozbek L, Gaipov A, Ferro C, Cozzolino M, Cherney DZI, Tuttle KR. An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management. Diabetes Obes Metab 2024; 26:2531-2545. [PMID: 38558257 DOI: 10.1111/dom.15575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/09/2024] [Accepted: 03/09/2024] [Indexed: 04/04/2024]
Abstract
OBJECTIVE Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.
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Affiliation(s)
- Mehmet Kanbay
- Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Sidar Copur
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - A Umur Topçu
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Mustafa Guldan
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Lasin Ozbek
- Department of Medicine, Koc University School of Medicine, Istanbul, Turkey
| | - Abduzhappar Gaipov
- Department of Medicine, School of Medicine, Nazarbayev University, Astana, Kazakhstan
| | - Charles Ferro
- Department of Nephrology, University Hospitals Birmingham and Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - David Z I Cherney
- Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada
| | - Katherine R Tuttle
- Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington, USA
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Du Q, Li T, Yi X, Song S, Kang J, Jiang Y. Prevalence of new-onset diabetes mellitus after kidney transplantation: a systematic review and meta-analysis. Acta Diabetol 2024; 61:809-829. [PMID: 38507083 DOI: 10.1007/s00592-024-02253-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/01/2024] [Indexed: 03/22/2024]
Abstract
AIMS Post-transplant diabetes is a prevalent and consequential complication following kidney transplantation, which significantly augments the risk of cardiovascular disease, graft loss, infection, and mortality, thereby profoundly impacting both graft and patient survival. However, the early stages of post-transplant diabetes often go unnoticed or receive inadequate management. Consequently, this study systematically assesses the incidence of new-onset diabetes after kidney transplantation with the aim to enhance medical staff awareness regarding post-transplantation diabetes and provide clinical management guidance. METHODS We conducted a comprehensive search across multiple databases including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed until September 21, 2023. Data extraction was performed using standardized tables and meta-analysis was conducted using Stata 16.0 software. A random effects model was employed to estimate the combined prevalence along with its corresponding 95% confidence interval. The source of heterogeneity was explored using subgroup analysis and sensitivity analysis, while publication bias was assessed through funnel plot and Egger's test. This study has been registered with PROSPERO under the registration number CRD42023465768. RESULTS This meta-analysis comprised 39 studies with a total sample size of 16,584 patients. The prevalence of new-onset diabetes after transplantation was found to be 20% [95% CI (18.0, 22.0)]. Subgroup analyses were conducted based on age, gender, body mass index, family history of diabetes, type of kidney donor, immunosuppressive regimen, acute rejection episodes, hepatitis C infection status and cytomegalovirus infection. CONCLUSIONS The incidence of post-kidney transplantation diabetes is substantial, necessitating early implementation of preventive and control measures to mitigate its occurrence, enhance prognosis, and optimize patients' quality of life. CLINICAL TRIAL REGISTRATION PROSPERO: CRD42023465768.
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Affiliation(s)
- Qiufeng Du
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Tao Li
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Xiaodong Yi
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Shuang Song
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Jing Kang
- College of Nursing, Chengdu University of Traditional Chinese Medicine, No.37 Shi-er-qiao Road, Chengdu City, 610075, Sichuan Province, China
| | - Yunlan Jiang
- Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu City, 610072, Sichuan Province, China.
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Serna-Higuita LM, Isaza-López MC, Hernández-Herrera GN, Serna-Campuzano AM, Nieto-Rios JF, Heyne N, Guthoff M. Development and Validation of a New Score to Assess the Risk of Posttransplantation Diabetes Mellitus in Kidney Transplant Recipients. Transplant Direct 2023; 9:e1558. [PMID: 37954683 PMCID: PMC10635612 DOI: 10.1097/txd.0000000000001558] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 09/20/2023] [Indexed: 11/14/2023] Open
Abstract
Background Posttransplantation diabetes mellitus (PTDM) is a serious complication of solid organ transplantation. It is associated with major adverse cardiovascular events, which are a leading cause of morbidity and mortality in transplant patients. This study aimed to develop and validate a score to predict the risk of PTDM in kidney transplant recipients. Methods A single-center retrospective cohort study was conducted in a tertiary care hospital in Medellín, Colombia, between 2005 and 2019. Data from 727 kidney transplant recipients were used to develop a risk prediction model. Significant predictors with competing risks were identified using time-dependent Cox proportional hazard regression models. To build the prediction model, the score for each variable was weighted using calculated regression coefficients. External validation was performed using independent data, including 198 kidney transplant recipients from Tübingen, Germany. Results Among the 727 kidney transplant recipients, 122 developed PTDM. The predictive model was based on 5 predictors (age, gender, body mass index, tacrolimus therapy, and transient posttransplantation hyperglycemia) and exhibited good predictive performance (C-index: 0.7 [95% confidence interval, 0.65-0.76]). The risk score, which included 33 patients with PTDM, was used as a validation data set. The results showed good discrimination (C-index: 0.72 [95% confidence interval, 0.62-0.84]). The Brier score and calibration plot demonstrated an acceptable fit capability in external validation. Conclusions We proposed and validated a prognostic model to predict the risk of PTDM, which performed well in discrimination and calibration, and is a simple score for use and implementation by means of a nomogram for routine clinical application.
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Affiliation(s)
- Lina Maria Serna-Higuita
- Department of Clinical Epidemiology and Applied Biostatistics, University Hospital Tübingen, Germany
| | | | | | | | - John Fredy Nieto-Rios
- Faculty of Medicine, University of Antioquia, Medellín, Colombia
- Department of Nephrology, Hospital Pablo Tobón Uribe, Medellín, Colombia
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, University of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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Gibson CA, Gupta A, Naik A, Sullivan DK, Doshi M, Backes J, Harvey S, Lee J, Mount R, Valentine H, Shaffer K. Developing a Healthy Lifestyle Program for Recent Kidney Transplant Recipients. Prog Transplant 2023; 33:193-200. [PMID: 37469164 DOI: 10.1177/15269248231189878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
INTRODUCTION Many kidney transplant recipients experience weight gain in the first year after transplantation. RESEARCH QUESTION The objective of this research study was to assess the desires of recent kidney transplant patients about the design features of a healthy lifestyle program to counter unnecessary weight gain. DESIGN In this descriptive study, recent recipients at 2 transplant centers were invited to participate in an online survey. Survey items included sociodemographic information, current medications, health conditions, weight change posttransplant, diet behaviors, physical activity participation, and desired features of a lifestyle program. RESULTS Fifty-three participants, mean age 60.5 (11.2) years, primarily males, completed surveys. Forty percent gained weight posttransplantation with many indicating struggling with their diet. Physical activity levels stayed the same (17%) or decreased (40%) posttransplantation. Eighty-seven percent of participants indicated they would participate in an online lifestyle program and 76% wanted online physical activity and nutrition sessions to meet at least once weekly. Suggestions about the type of information and activities, included eating strategies (eg, how to eat healthfully at restaurants, grocery shopping tips, and recipes), resources for at-home physical activities, access to cooking classes, and apps to track both activity and food intake. CONCLUSION Recent kidney transplant recipients would benefit from and desired to join a lifestyle program featuring tailored nutrition education and physical activity coaching. Gathered information will be used to inform and tailor a lifestyle program. Identifying features for the prevention of unnecessary weight gain with patients' input is essential for promoting and sustaining healthy behaviors.
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Affiliation(s)
- Cheryl A Gibson
- Division of General Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Aditi Gupta
- Division of Nephrology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Abhijit Naik
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Debra K Sullivan
- Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, USA
| | - Mona Doshi
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Jim Backes
- Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS, USA
| | - Susan Harvey
- Department of Health, Sports, and Exercise Sciences, University of Kansas, Robinson Center, Lawrence, KS, USA
| | - Jaehoon Lee
- Department of Educational Psychology, Leadership, and Counseling, Texas Tech University, Lubbock, TX, USA
| | - Rebecca Mount
- Division of General Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Heather Valentine
- Division of General Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA
| | - Kelly Shaffer
- Division of Nephrology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
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Febles RM, Miranda DM, Perera CDLCC, Martín LD, Rodríguez-Rodríguez AE, González Martín AR, Sánchez Báez DJ, Porrini E. Therapeutic Exercise on Metabolic and Renal Outcomes in Patients with Chronic Kidney Disease: A Narrative Review. Nephron Clin Pract 2023; 148:85-94. [PMID: 37611542 DOI: 10.1159/000531921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 06/28/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) affects 11-13% of the world population. The main risk factors for CKD include diabetes, hypertension, and obesity. Metabolic syndrome (MS) is associated with the onset of CKD in the nondiabetic population. Obesity and MS are also risk factors for a worse progression of established CKD. Therapeutic exercise is an effective option to treat and manage obesity, MS, and diabetes in the general population. However, the evidence on the effect of exercise on patients with CKD, obesity, and MS is scarce. SUMMARY We evaluated available evidence on the effect of therapeutic exercise in patients with CKD, excluding dialysis, particularly in improving the metabolic risk factors and main renal outcomes: renal function loss and albuminuria/proteinuria. This review includes prospective studies and clinical trials. A total of 44 studies were analysed in 1,700 subjects with renal disease (2-5), including patients with renal transplantation. Most studies did not prove a major effect of exercise on albuminuria/proteinuria, glomerular filtration rate (GFR), obesity, or MS. These results are intriguing and deserve attention. The exploratory nature of most studies, including a low number of cases and short follow-up, might explain the lack of efficacy of exercise in our analysis. Specific aspects like the type of exercise, frequency, intensity, duration, accommodation during follow-up, individualization, safety, and adherence are crucial to the success of therapeutic exercise. The beneficial role of exercise in patients with CKD remains to be determined. KEY MESSAGES Key messages of this review are as follows. (1) The effect of therapeutic exercise on renal and metabolic outcomes in patients with CKD remains to be determined. (2) According to the evidence selected, therapeutic exercise seems to be safe to treat patients with CKD. (3) Most studies are exploratory by nature, with results that need further investigation. (4) Therapeutic exercise is a complex procedure that must be specifically designed to treat patients with CKD.
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Affiliation(s)
- Raúl Morales Febles
- Faculty of Medicine, University of La Laguna, Tenerife, Spain,
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Tenerife, Spain,
| | - Domingo Marrero Miranda
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, Tenerife, Spain
| | - Coriolano de la Concepción Cruz Perera
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Tenerife, Spain
- Nephrology Unit, Hospital Universitario de Canarias (HUC), La Laguna, Spain
| | - Laura Díaz Martín
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Tenerife, Spain
| | | | | | | | - Esteban Porrini
- Faculty of Medicine, University of La Laguna, Tenerife, Spain
- Nephrology Unit, Hospital Universitario de Canarias (HUC), La Laguna, Spain
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Morales Febles R, Marrero Miranda D, Jiménez Sosa A, González Rinne A, Cruz Perera C, Rodríguez-Rodríguez AE, Álvarez González A, Díaz Martín L, Negrín Mena N, Acosta Sørensen C, Pérez Tamajón L, Rodríguez Hernández A, González Rinne F, Dorta González A, Ledesma Pérez E, González Delgado A, Domínguez-Rodríguez A, García Baute MDC, Torres Ramírez A, Porrini E. Exercise and Prediabetes After Renal Transplantation (EXPRED-I): A Prospective Study. SPORTS MEDICINE - OPEN 2023; 9:32. [PMID: 37202497 DOI: 10.1186/s40798-023-00574-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/25/2023] [Indexed: 05/20/2023]
Abstract
BACKGROUND Post-transplant diabetes mellitus (PTDM) beyond 12 months (late PTDM) is a severe complication after renal transplantation. Late PTDM develops mostly in subjects with prediabetes. Although exercise may have a potential role in preventing late PTDM, there are no previous data on the effect of exercise in patients with prediabetes. MATERIAL AND METHODS The design was a 12-month exploratory study to test the capacity of exercise in reverting prediabetes in order to prevent late-PTDM. The outcome was the reversibility of prediabetes, assessed every 3 months with oral glucose tolerance tests (OGTT). The protocol included an incremental plan of aerobic and/or strength training as well as an active plan for promoting adherence (telephone calls, digital technology, and visits). A priori, a sample size cannot be calculated which makes this an exploratory analysis. Based on previous studies, the spontaneous reversibility of prediabetes was 30% and the reversibility induced by exercise will account for another 30%, a total reversibility of 60% (p value < 0.05, assuming a potency of 85%). Ad interim analysis was performed during follow-up to test the certainty of this sample calculation. Patients beyond 12 months after renal transplantation with prediabetes were included. RESULTS The study was interrupted early due to efficacy after the evaluation of the follow-up of 27 patients. At the end of follow-up, 16 (60%) patients reverted to normal glucose levels at fasting (from 102.13 mg/dL ± 11 to 86.75 ± 6.9, p = 0.006) and at 120 min after the OGTTs (154.44 mg/dL ± 30 to 113.0 ± 13.1, p = 0.002) and 11 patients had persistent prediabetes (40%). Also, insulin sensitivity improved with the reversibility of prediabetes, compared to those with persistent prediabetes: 0.09 [0.08-0.11] versus 0.04 [0.01-0.07], p = 0.001 (Stumvoll index). Most needed at least one increment in the prescription of exercise and compliance. Finally, measures aimed at the improvement of compliance were successful in 22 (80%) patients. CONCLUSION Exercise training was effective to improve glucose metabolism in renal transplant patients with prediabetes. Exercise prescription must be conducted considering both the clinical characteristics of the patients and pre-defined strategy to promote adherence. The trial registration number of the study was NCT04489043.
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Affiliation(s)
- Raúl Morales Febles
- Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Spain
- Research Unit, University Hospital of Canary Islands, La Laguna, Spain
| | | | | | - Ana González Rinne
- Nephrology Department, University Hospital of Canary Islands, La Laguna, Spain
| | | | | | | | - Laura Díaz Martín
- Research Unit, University Hospital of Canary Islands, La Laguna, Spain
| | | | | | | | | | - Federico González Rinne
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Spain
| | | | | | | | - Alberto Domínguez-Rodríguez
- Cardiology Department, University Hospital of Canary Islands, La Laguna, Spain
- CIBER of Cardiovascular Diseases (CIBERCV), Madrid, Spain
- Faculty of Health Science, European University of Canary Islands, La Laguna, Tenerife, Spain
| | | | - Armando Torres Ramírez
- Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Spain
- Nephrology Department, University Hospital of Canary Islands, La Laguna, Spain
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Spain
| | - Esteban Porrini
- Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Spain.
- Research Unit, University Hospital of Canary Islands, La Laguna, Spain.
- Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, La Laguna, Tenerife, Spain.
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Raven LM, Muir CA, Macdonald PS, Hayward CS, Jabbour A, Greenfield JR. Diabetes medication following heart transplantation: a focus on novel cardioprotective therapies-a joint review from endocrinologists and cardiologists. Acta Diabetol 2023; 60:471-480. [PMID: 36538088 DOI: 10.1007/s00592-022-02018-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 12/10/2022] [Indexed: 12/25/2022]
Abstract
There is accumulating evidence that novel glucose-lowering agents infer potent cardiovascular and renal benefits. Therefore, it is imperative to reassess the management of post-transplant diabetes mellitus and consider the role of newer agents. With improved transplant-related survival and high prevalence of post-transplant diabetes, management of long-term complications such as diabetes are increasingly important. There are limited guidelines to assist in choice of appropriate agents after solid organ transplantation. Traditional therapies including insulin and sulfonylureas may still have a role; however, other agents should be considered prior. The evidence of novel glucose-lowering agents in post-transplant care is limited, and most studies have focused on kidney transplant recipients. While there are some parallels between renal and cardiac transplant recipients, the potential cardiovascular benefits, particularly on cardiac fibrosis are unique to cardiac transplantation. The treatment of diabetes, with a focus on additional cardiac and renal benefits, needs to be brought to the forefront of post-transplant care with incorporation of recent evidence outside of transplantation. The role for novel glucose-lowering agents in cardiac transplant recipients will be explored, with a summary of available evidence.
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Affiliation(s)
- Lisa M Raven
- Department of Diabetes and Endocrinology, St Vincent's Hospital, Sydney, Australia.
- Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, Australia.
- School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia.
| | - Christopher A Muir
- Department of Diabetes and Endocrinology, St Vincent's Hospital, Sydney, Australia
- School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
| | - Peter S Macdonald
- School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
- Department of Heart and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Victor Chang Cardiac Research Institute, Sydney, Australia
| | - Christopher S Hayward
- School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
- Department of Heart and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Victor Chang Cardiac Research Institute, Sydney, Australia
| | - Andrew Jabbour
- School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
- Department of Heart and Lung Transplantation, St Vincent's Hospital, Sydney, Australia
- Victor Chang Cardiac Research Institute, Sydney, Australia
| | - Jerry R Greenfield
- Department of Diabetes and Endocrinology, St Vincent's Hospital, Sydney, Australia
- Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, Australia
- School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
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10
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Van Oosterwyck A, Lauwers N, Pauwels N, Vanuytsel T. Nutrition in intestinal transplantation: centre stage or supporting act? Curr Opin Clin Nutr Metab Care 2023; 26:105-113. [PMID: 36728936 DOI: 10.1097/mco.0000000000000901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE OF REVIEW Intestinal transplantation (ITx), whether isolated or combined with other organs, is now a valid treatment option in some patients with chronic intestinal failure or extensive venous mesenteric thrombosis. The aim in these patients is not only to restore nutritional autonomy, but also to minimize the risk of complications, both short and long term. Despite parenteral nutrition playing a central part in the management of intestinal failure patients, there are little data about the perioperative and postoperative nutritional management of ITx patients, due to small patient populations per centre. In this review, we collected the scientific data available to date. RECENT FINDINGS In this review, we will bundle the limited scientific information about diet after intestinal and multivisceral transplantation combined with recommendations from our own clinical practice in 28 ITx patients in University Hospitals Leuven, Belgium. We will discuss the immediate preoperative period, surgical complications necessitating dietary interventions and the late postoperative phase in a stable outpatient transplant recipient. SUMMARY Although no specific research has been done in the field of ITx, we can extrapolate some findings from other solid organ transplants. Prehabilitation might prove to be of importance; Preserving kidney and liver function in the pretransplant period should be pursued. Transition from parenteral to enteral and oral nutrition can be complex due to inherent surgical procedures and possible complications. Ultimately, the goal is to give patients nutritional autonomy, while also minimizing the risk of foodborne infections by teaching patients well tolerated food practices.
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Affiliation(s)
- Aude Van Oosterwyck
- Leuven Intestinal Failure and Transplantation (LIFT)
- Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | | - Nelle Pauwels
- Leuven Intestinal Failure and Transplantation (LIFT)
| | - Tim Vanuytsel
- Leuven Intestinal Failure and Transplantation (LIFT)
- Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
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11
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Sharif A. Interventions Against Posttransplantation Diabetes: A Scientific Rationale for Treatment Hierarchy Based on Literature Review. Transplantation 2022; 106:2301-2313. [PMID: 35696695 DOI: 10.1097/tp.0000000000004198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Posttransplant diabetes (PTD) is a common medical complication after solid organ transplantation. Because of adverse outcomes associated with its development and detrimental impact on long-term survival, strategies to prevent or manage PTD are critically important but remain underresearched. Treatment hierarchies of antidiabetic therapies in the general population are currently being revolutionized based on cardiovascular outcome trials, providing evidence-based rationale for optimization of medical management. However, opportunities for improving medical management of PTD are challenged by 2 important considerations: (1) translating clinical evidence data from the general population to underresearched solid organ transplant cohorts and (2) targeting treatment based on primary underlying PTD pathophysiology. In this article, the aim is to provide an overview of PTD treatment options from a new angle. Rationalized by a consideration of underlying PTD pathophysiological defects, which are heterogeneous among diverse transplant patient cohorts, a critical appraisal of the published literature and summary of current research in progress will be reviewed. The aim is to update transplant professionals regarding medical management of PTD from a new perspective tailored therapeutic intervention based on individualized characteristics. As the gap in clinical evidence between management of PTD versus type 2 diabetes widens, it is imperative for the transplant community to bridge this gap with targeted clinical trials to ensure we optimize outcomes for solid organ transplant recipients who are at risk or develop PTD. This necessary clinical research should help efforts to improve long-term outcomes for solid transplant patients from both a patient and graft survival perspective.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.,Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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12
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Górska M, Kurnatowska I. Nutrition Disturbances and Metabolic Complications in Kidney Transplant Recipients: Etiology, Methods of Assessment and Prevention-A Review. Nutrients 2022; 14:nu14234996. [PMID: 36501026 PMCID: PMC9738485 DOI: 10.3390/nu14234996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/20/2022] [Accepted: 11/21/2022] [Indexed: 11/25/2022] Open
Abstract
Nutrition disturbances occur at all stages of chronic kidney disease and progress with the decrease of the kidney filtration rate. Kidney transplantation (KTx) as the best form of kidney replacement therapy poses various nutritional challenges. Prior to transplantation, recipients often present with mild to advanced nutrition disturbances. A functioning allograft not only relieves uremia, acidosis, and electrolyte disturbances, but also resumes other kidney functions such as erythropoietin production and vitamin D3 metabolism. KTx recipients represent a whole spectrum of undernutrition and obesity. Since following transplantation, patients are relieved of most dietary restrictions and appetite disturbances; they resume old nutrition habits that result in weight gain. The immunosuppressive regimen often predisposes them to dyslipidemia, glucose intolerance, and hypertension. Moreover, most recipients present with chronic kidney graft disease at long-term follow-ups, usually in stages G2-G3T. Therefore, the nutritional status of KTx patients requires careful monitoring. Appropriate dietary and lifestyle habits prevent nutrition disturbances and may improve kidney graft function. Despite many nutritional guidelines and recommendations targeted at chronic kidney disease, there are few targeted at KTx recipients. We aimed to provide a brief review of nutrition disturbances and known nutritional recommendations for kidney transplant recipients based on the current literature and dietary trends.
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13
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Blonde L, Umpierrez GE, Reddy SS, McGill JB, Berga SL, Bush M, Chandrasekaran S, DeFronzo RA, Einhorn D, Galindo RJ, Gardner TW, Garg R, Garvey WT, Hirsch IB, Hurley DL, Izuora K, Kosiborod M, Olson D, Patel SB, Pop-Busui R, Sadhu AR, Samson SL, Stec C, Tamborlane WV, Tuttle KR, Twining C, Vella A, Vellanki P, Weber SL. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract 2022; 28:923-1049. [PMID: 35963508 PMCID: PMC10200071 DOI: 10.1016/j.eprac.2022.08.002] [Citation(s) in RCA: 221] [Impact Index Per Article: 73.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
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Affiliation(s)
| | | | - S Sethu Reddy
- Central Michigan University, Mount Pleasant, Michigan
| | | | | | | | | | | | - Daniel Einhorn
- Scripps Whittier Diabetes Institute, La Jolla, California
| | | | | | - Rajesh Garg
- Lundquist Institute/Harbor-UCLA Medical Center, Torrance, California
| | | | | | | | | | | | - Darin Olson
- Colorado Mountain Medical, LLC, Avon, Colorado
| | | | | | - Archana R Sadhu
- Houston Methodist; Weill Cornell Medicine; Texas A&M College of Medicine; Houston, Texas
| | | | - Carla Stec
- American Association of Clinical Endocrinology, Jacksonville, Florida
| | | | - Katherine R Tuttle
- University of Washington and Providence Health Care, Seattle and Spokane, Washington
| | | | | | | | - Sandra L Weber
- University of South Carolina School of Medicine-Greenville, Prisma Health System, Greenville, South Carolina
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14
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Cuomo G, Cioffi G, Di Lorenzo A, Iannone FP, Cudemo G, Iannicelli AM, Pacileo M, D’Andrea A, Vigorito C, Iannuzzo G, Giallauria F. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients. J Clin Med 2022; 11:jcm11113247. [PMID: 35683632 PMCID: PMC9180971 DOI: 10.3390/jcm11113247] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/03/2022] [Accepted: 06/04/2022] [Indexed: 01/27/2023] Open
Abstract
Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering LDL levels, consequently increasing cardiovascular risk. Monoclonal antibody PCSK9 inhibitors demonstrated remarkable efficacy in the general population in reducing LDL cholesterol levels and preventing cardiovascular disease. In transplant patients, these drugs are still poorly used, despite having comparable efficacy to the general population and giving fewer drug interactions with immunosuppressants. Furthermore, there is enough evidence that PCSK9 also plays a role in other pathways, such as inflammation, which is particularly dangerous for graft survival. In this review, the current evidence on the function of PCSK9 and the use of its inhibitors will be discussed, particularly in transplant patients, in which they may provide additional benefits.
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Affiliation(s)
- Gianluigi Cuomo
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Giuseppe Cioffi
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Anna Di Lorenzo
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Francesca Paola Iannone
- Department of Clinical Medicine and Surgery, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (F.P.I.); (G.I.)
| | - Giuseppe Cudemo
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Anna Maria Iannicelli
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Mario Pacileo
- Unit of Cardiology and Intensive Care, Umberto I Hospital, 84014 Nocera Inferiore, Italy; (M.P.); (A.D.)
| | - Antonello D’Andrea
- Unit of Cardiology and Intensive Care, Umberto I Hospital, 84014 Nocera Inferiore, Italy; (M.P.); (A.D.)
| | - Carlo Vigorito
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Gabriella Iannuzzo
- Department of Clinical Medicine and Surgery, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (F.P.I.); (G.I.)
| | - Francesco Giallauria
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
- Correspondence:
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15
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Analysis of risk factors and establishment of a risk prediction model for post-transplant diabetes mellitus after kidney transplantation. Saudi Pharm J 2022; 30:1088-1094. [PMID: 36164572 PMCID: PMC9508626 DOI: 10.1016/j.jsps.2022.05.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 05/30/2022] [Indexed: 11/22/2022] Open
Abstract
Introduction Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Methods Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Results Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14–3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29–5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41–7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86–8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05–2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79–4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862–0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. Conclusions Risk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.
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16
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Abstract
CONTEXT Though posttransplant diabetes mellitus (PTDM, occurring > 45 days after transplantation) and its complications are well described, early post-renal transplant hyperglycemia (EPTH) (< 45 days) similarly puts kidney transplant recipients at risk of infections, rehospitalizations, and graft failure and is not emphasized much in the literature. Proactive screening and management of EPTH is required given these consequences. OBJECTIVE The aim of this article is to promote recognition of early post-renal transplant hyperglycemia, and to summarize available information on its pathophysiology, adverse effects, and management. METHODS A PubMed search was conducted for "early post-renal transplant hyperglycemia," "immediate posttransplant hyperglycemia," "post-renal transplant diabetes," "renal transplant," "diabetes," and combinations of these terms. EPTH is associated with significant complications including acute graft failure, rehospitalizations, cardiovascular events, PTDM, and infections. CONCLUSION Patients with diabetes experience better glycemic control in end-stage renal disease (ESRD), with resurgence of hyperglycemia after kidney transplant. Patients with and without known diabetes are at risk of EPTH. Risk factors include elevated pretransplant fasting glucose, diabetes, glucocorticoids, chronic infections, and posttransplant infections. We find that EPTH increases risk of re-hospitalizations from infections (cytomegalovirus, possibly COVID-19), acute graft rejections, cardiovascular events, and PTDM. It is essential, therefore, to provide diabetes education to patients before discharge. Insulin remains the standard of care while inpatient. Close follow-up after discharge is recommended for insulin adjustment. Some agents like dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have shown promise. The tenuous kidney function in the early posttransplant period and lack of data limit the use of sodium-glucose cotransporter 2 inhibitors. There is a need for studies assessing noninsulin agents for EPTH to decrease risk of hypoglycemia associated with insulin and long-term complications of EPTH.
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Affiliation(s)
- Anira Iqbal
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Keren Zhou
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Sangeeta R Kashyap
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio
| | - M Cecilia Lansang
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, Cleveland, Ohio
- Corresponding author: M. Cecilia Lansang, MD, MPH, Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic Foundation, 9500 Euclid Avenue, F-20, Cleveland, Ohio 44195 Phone: 216-445-5246 x 4, Fax: (216) 445-1656,
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17
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Wilkinson TJ, Bishop NC, Billany RE, Lightfoot CJ, Castle EM, Smith AC, Greenwood SA. The effect of exercise training interventions in adult kidney transplant recipients: a systematic review and meta-analysis of randomised control trials. PHYSICAL THERAPY REVIEWS 2021. [DOI: 10.1080/10833196.2021.2002641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Thomas J. Wilkinson
- Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK
- Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK
| | - Nicolette C. Bishop
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - Roseanne E. Billany
- Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
| | - Courtney J. Lightfoot
- Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK
- Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Ellen M. Castle
- Therapies Department, King’s College Hospital NHS Trust, London, UK
- Renal Medicine, School of Life Course Sciences, King’s College London, London, UK
| | - Alice C. Smith
- Leicester Kidney Lifestyle Team, Department of Health Sciences, University of Leicester, Leicester, UK
- Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Sharlene A. Greenwood
- Therapies Department, King’s College Hospital NHS Trust, London, UK
- Renal Medicine, School of Life Course Sciences, King’s College London, London, UK
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18
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Abstract
Cardiovascular disease remains a leading cause of death and morbidity in kidney transplant recipients and a common reason for post-transplant hospitalization. Several traditional and nontraditional cardiovascular risk factors exist, and many of them present pretransplant and worsened, in part, due to the addition of immunosuppression post-transplant. We discuss optimal strategies for identification and treatment of these risk factors, including the emerging role of sodium-glucose cotransporter 2 inhibitors in post-transplant diabetes and cardiovascular disease. We present common types of cardiovascular disease observed after kidney transplant, including coronary artery disease, heart failure, pulmonary hypertension, arrhythmia, and valvular disease. We also discuss screening, treatment, and prevention of post-transplant cardiac disease. We highlight areas of future research, including the need for goals and best medications for risk factors, the role of biomarkers, and the role of screening and intervention.
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Affiliation(s)
- Kelly A. Birdwell
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Meyeon Park
- Division of Nephrology, Department of Medicine, University of California, San Francisco, California
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19
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Abstract
PURPOSE OF REVIEW Posttransplant diabetes mellitus (PTDM) is a prevalent complication in kidney transplant recipients, and has been associated with worse short-term and long-term outcomes. RECENT FINDINGS While hyperglycemia is frequently seen in the early posttransplant period because of surgical stress, infection, and use of high-dose steroids, the diagnosis of PTDM should be established after patients are clinically stable and on stable maintenance immunosuppression. In the early posttransplant period, hyperglycemia is typically treated with insulin, and pilot data have suggested potential benefit of lower vs. higher glycemic targets in this setting. Growing data indicate lifestyle modifications, including dietary interventions, physical activity, and mitigation of obesity, are associated with improved posttransplant outcomes. While there are limited data to support a first-line antidiabetic medication for PTDM, more established pharmacotherapies such as sulfonylureas, meglitinides, and dipetidyl peptidase IV inhibitors are commonly used. Given recent trials showing the benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists upon kidney outcomes in nontransplant patients, further study of these agents specifically in kidney transplant recipients are urgently needed. SUMMARY Increasing evidence supports a multidisciplinary approach, including lifestyle modification, obesity treatment, judicious immunosuppression selection, and careful utilization of novel antidiabetic therapies in PTDM patients.
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20
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Martinez Cantarin MP. Diabetes in Kidney Transplantation. Adv Chronic Kidney Dis 2021; 28:596-605. [PMID: 35367028 DOI: 10.1053/j.ackd.2021.10.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 10/11/2021] [Accepted: 10/12/2021] [Indexed: 11/11/2022]
Abstract
Diabetes mellitus (DM) is one of the most common complications after kidney transplantation and is associated with unfavorable outcomes including death. DM can be present before transplant but post-transplant DM (PTDM) refers to diabetes that is diagnosed after solid organ transplantation. Despite its high prevalence, optimal treatment to prevent complications of PTDM is unknown. Medical therapy of pre-existent DM or PTDM after transplant is challenging because of frequent interactions between antidiabetic and immunosuppressive agents. There is also frequent need for medication dose adjustments due to residual kidney disease and a higher risk of medication side effects in patients treated with immunosuppressive agents. Sodium-glucose cotransporter 2 inhibitors have demonstrated a favorable cardio-renal profile in patients with DM without a transplant and hence hold great promise in this patient population although there is concern about the higher risk of urinary tract infections. The significant gaps in our understanding of the pathophysiology, diagnosis, and management of DM after kidney transplantation need to be urgently addressed.
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21
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Li J, Chong A, Carey S. Dietary interventions on the prevention and management of diabetes in post-kidney transplantation - A systematic review. Nephrology (Carlton) 2021; 27:269-280. [PMID: 34610191 DOI: 10.1111/nep.13982] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 09/07/2021] [Accepted: 10/02/2021] [Indexed: 12/24/2022]
Abstract
Post-transplant diabetes mellitus is associated with long-term immunosuppression and weight gain, and is related to an increased risk of cardiovascular disease, accelerated loss of graft and increased mortality. There is an absence of strong evidence-based dietary guidelines for the prevention and management of post-transplant diabetes mellitus in kidney transplant recipients. The aim of this study was to systematically review all dietary evidence for kidney transplant recipients on clinical outcomes relating to diabetes, patient-reported outcomes and economic outcomes. A comprehensive literature search was conducted in August 2020 using the databases Medline, Embase, CENTRAL and CINAHL. Studies were critically appraised using Cochrane risk of bias tools and GRADE. A total of 12 studies and 1928 participants were included. Four papers focused on diet and exercise, one paper on diet only, two papers on magnesium supplementation, one paper on magnesium and fibre intake, two papers on Mediterranean diet, one paper on marine n-3 fatty acid supplementation and one paper on fruit and vegetable intake. There were no significant effects on outcomes relating to dietary counselling, magnesium supplementation, magnesium and fibre intake or marine n-3 fatty acid supplementation. Low-quality evidence supports the Mediterranean diet in reducing the risk of post-transplant diabetes mellitus and fasting plasma glucose levels. Low-quality evidence suggests vegetable intake being associated with a lower risk of post-transplant diabetes mellitus. This review demonstrates limited evidence for dietary interventions in the prevention and management of diabetes in post-kidney transplantation. The findings suggest that further high-quality research with robust study designs is required.
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Affiliation(s)
- Joanne Li
- Nutrition and Dietetics Group, School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia
| | - Arian Chong
- Department of Nutrition and Dietetics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
| | - Sharon Carey
- Department of Nutrition and Dietetics, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
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22
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Grottenthaler JM, Füger JK, Mahling M, Königsrainer A, Malek NP, Birkenfeld AL, Nadalin S, Berg CP, Heyne N, Guthoff M. Dynamics of glucose metabolism after liver transplantation: Prediabetes as a window of opportunity for patient survival and long-term kidney function. Transpl Int 2021; 34:1959-1970. [PMID: 34214208 DOI: 10.1111/tri.13967] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/30/2021] [Accepted: 06/28/2021] [Indexed: 12/01/2022]
Abstract
Posttransplantation diabetes mellitus (PTDM) is a relevant complication following liver transplantation with profound impact on morbidity and mortality. To date, little is known about the evolution and dynamics of glucose metabolism and the impact of prediabetes in long-term follow-up. To address this issue, all consecutive adult liver transplant recipients (n=429) from a European university hospital transplant center between 2007 and 2017 were analyzed retrospectively. In patients without pre-existing diabetes (n=327), we conducted a longitudinal characterization of glucose metabolism. Median follow-up was 37 [9-64, IQR] months. Median prevalence of prediabetes was 39 [37-39]% and of PTDM 21 [17-22]%. Throughout follow-up, intra-individual glucose regulation of patients was highly variable, continuously fluctuating between different states of glucose metabolism (normal glucose tolerance, prediabetes, PTDM). Whereas overall survival and long-term kidney function of patients with PTDM were significantly lower than that of patients with normal glucose metabolism, prediabetes was not associated with adverse outcome. This study provides new insight into the dynamics and impact of glucose metabolism after liver transplantation. Unlike PTDM, prediabetes is not associated with adverse outcome, providing a window of opportunity for targeted intervention. The results underline the need for constant screening and intervention in post-transplant care of liver allograft recipients.
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Affiliation(s)
- Julia M Grottenthaler
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Judith K Füger
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany
| | - Moritz Mahling
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Alfred Königsrainer
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Nisar P Malek
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Andreas L Birkenfeld
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Silvio Nadalin
- Department of General-, Visceral- and Transplant Surgery, University of Tuebingen, Tuebingen, Germany
| | - Christoph P Berg
- Department of Gastroenterology, Gastrointestinal Oncology, Hepatology, Infectiology, and Geriatrics, University of Tuebingen, Tuebingen, Germany
| | - Nils Heyne
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, University of Tuebingen, Tuebingen, Germany.,Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen, Tuebingen, Germany.,German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
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23
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Cyrino LG, Galpern J, Moore L, Borgi L, Riella LV. A Narrative Review of Dietary Approaches for Kidney Transplant Patients. Kidney Int Rep 2021; 6:1764-1774. [PMID: 34307973 PMCID: PMC8258457 DOI: 10.1016/j.ekir.2021.04.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 03/16/2021] [Accepted: 04/12/2021] [Indexed: 12/19/2022] Open
Abstract
A healthy eating pattern has proven to lower the risk of metabolic and cardiovascular diseases. However, there are sparse dietary recommendations for kidney transplant recipients, and the ones available focus only on single nutrients intake, such as sodium, potassium, and proteins, and not on the overall eating pattern. Considering that individuals do not typically consume nutrients in isolation, but as part of a complete dietary pattern, it is challenging for the average transplanted patient to understand and implement specific dietary recommendations. Also, single-nutrient interventions demonstrate largely inconclusive effects, and it seems improbable that they could have a strong enough impact on transplant outcomes. Dietary trends such as plant-based diets, intermittent fasting, low-carb diet/keto-diet, and juicing, have gained major attention from the media. Herein, we review the potential risks and benefits of these diets in kidney transplant recipients and provide an updated dietary recommendation for this population with consideration of current nutritional trends. Overall, the Mediterranean and DASH diets have demonstrated to be the most beneficial dietary patterns to the post kidney transplant population by focusing on less meat and processed foods, while increasing the intake of fresh foods and plant-based choices. We believe that to maintain a healthy lifestyle posttransplant, patients should be educated about the scientific evidence of different diets and choose a dietary pattern that is sustainable long-term.
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Affiliation(s)
- LG Cyrino
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jennie Galpern
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Lori Moore
- Division of Nephrology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Lea Borgi
- Division of Nephrology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Leonardo V. Riella
- Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
- Division of Nephrology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
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24
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Acosta-Gualandri A, Blydt-Hansen T, Islam N, Amed S. Risk Factors for Developing Posttransplant Diabetes After Pediatric Kidney Transplant in a Canadian Tertiary Care Children's Hospital Between 1995 and 2016. Can J Diabetes 2021; 45:481-489. [PMID: 34176612 DOI: 10.1016/j.jcjd.2021.05.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 04/07/2021] [Accepted: 05/10/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Posttransplant diabetes mellitus (PTDM) is a serious complication in kidney transplant recipients (KTRs) due to its negative impact on graft and patient survival. Although reported in 3% to 20% of pediatric KTRs, it has not been as well characterized in adults. In this study we describe incidence and risk factors associated with development of PTDM in pediatric KTRs. METHODS This work is a retrospective cohort study of nondiabetic pediatric patients, aged 6 months to 19 years, who underwent a first kidney transplant during 1995 to 2016. We estimated the cumulative incidence rate and used multivariable logistic regression to identify the diabetogenic risk factors for PTDM. RESULTS A total of 142 KTRs were included in this study. The cumulative incidence of PTDM was 31% and 14.1% in the first and second year posttransplant, respectively. Significant risk factors for PTDM in the first year after transplant included: dysglycemia in the first 8 to 30 days posttransplant (adjusted odds ratio [aOR], 3.02; 95% confidence interval [CI], 1.21 to 7.53; p=0.018) and use of sirolimus in the first 30 days posttransplant (aOR, 5.33; 95% CI, 1.16 to 24.35; p=0.031). No significant association was found with typical diabetogenic factors. CONCLUSIONS The incidence of PTDM is high among pediatric KTRs. Independent risk factors associated with PTDM included meeting the criteria for dysglycemia or diabetes and sirolimus use in the first month posttransplant. Typical diabetogenic risk factors for type 2 diabetes were not associated with increased risk. This study provides valuable information for posttransplant medical care and future research.
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Affiliation(s)
- Alejandra Acosta-Gualandri
- Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada
| | - Tom Blydt-Hansen
- Division of Nephrology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada
| | - Nazrul Islam
- Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Shazhan Amed
- Division of Endocrinology, Department of Pediatrics, British Columbia Children's Hospital and the University of British Columbia, Vancouver, British Columbia, Canada.
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25
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Madziarska K, Hap K, Mazanowska O, Sutkowska E. Comprehensive lifestyle modification as
complementary therapy to prevent and manage
post-transplant diabetes mellitus*. POSTEP HIG MED DOSW 2021. [DOI: 10.5604/01.3001.0014.8311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is one from the most common metabolic complications
after kidney transplantation. PTDM develops in the early period after transplantation.
The risk factors of PTDM are carbohydrate imbalances occurring in the patient prior to
transplantation, surgery and the inclusion of immunosuppressive treatment. Kidney transplant
patients tend to gain weight, which is associated with an increased risk of post-transplant
diabetes, cardiovascular diseases and abnormal transplanted kidney function.
Patients after kidney transplantation should be advised to adopt a lifestyle based on a proper
diet, exercise, weight control and smoking cessation. The strategy to reduce the risk factors
for PTDM development should start before transplantation and continue after kidney
transplantation. A targeted, non-pharmacological approach to patients already during the
dialysis period may have a significant impact on reducing post-transplantation diabetes.
Lifestyle interventions can effectively reduce the risk of development and inhibit the progression
of post-transplantation diabetes. The article describes elements of comprehensive
non-pharmacological management based on available knowledge of rehabilitation, dietetics
and psychology.
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Affiliation(s)
- Katarzyna Madziarska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland
| | - Katarzyna Hap
- Department and Division of Medical Rehabilitation, Wroclaw Medical University, Poland
| | - Oktawia Mazanowska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Poland
| | - Edyta Sutkowska
- Department and Division of Medical Rehabilitation, Wroclaw Medical University, Poland
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26
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Current Pharmacological Intervention and Medical Management for Diabetic Kidney Transplant Recipients. Pharmaceutics 2021; 13:pharmaceutics13030413. [PMID: 33808901 PMCID: PMC8003701 DOI: 10.3390/pharmaceutics13030413] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/16/2021] [Accepted: 03/16/2021] [Indexed: 01/02/2023] Open
Abstract
Hyperglycemia after kidney transplantation is common in both diabetic and non-diabetic patients. Both pretransplant and post-transplant diabetes mellitus are associated with increased kidney allograft failure and mortality. Glucose management may be challenging for kidney transplant recipients. The pathophysiology and pattern of hyperglycemia in patients following kidney transplantation is different from those with type 2 diabetes mellitus. In patients with pre-existing and post-transplant diabetes mellitus, there is limited data on the management of hyperglycemia after kidney transplantation. The following article discusses the nomenclature and diagnosis of pre- and post-transplant diabetes mellitus, the impact of transplant-related hyperglycemia on patient and kidney allograft outcomes, risk factors and potential pathogenic mechanisms of hyperglycemia after kidney transplantation, glucose management before and after transplantation, and modalities for prevention of post-transplant diabetes mellitus.
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27
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Bhat M, Usmani SE, Azhie A, Woo M. Metabolic Consequences of Solid Organ Transplantation. Endocr Rev 2021; 42:171-197. [PMID: 33247713 DOI: 10.1210/endrev/bnaa030] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Indexed: 12/12/2022]
Abstract
Metabolic complications affect over 50% of solid organ transplant recipients. These include posttransplant diabetes, nonalcoholic fatty liver disease, dyslipidemia, and obesity. Preexisting metabolic disease is further exacerbated with immunosuppression and posttransplant weight gain. Patients transition from a state of cachexia induced by end-organ disease to a pro-anabolic state after transplant due to weight gain, sedentary lifestyle, and suboptimal dietary habits in the setting of immunosuppression. Specific immunosuppressants have different metabolic effects, although all the foundation/maintenance immunosuppressants (calcineurin inhibitors, mTOR inhibitors) increase the risk of metabolic disease. In this comprehensive review, we summarize the emerging knowledge of the molecular pathogenesis of these different metabolic complications, and the potential genetic contribution (recipient +/- donor) to these conditions. These metabolic complications impact both graft and patient survival, particularly increasing the risk of cardiovascular and cancer-associated mortality. The current evidence for prevention and therapeutic management of posttransplant metabolic conditions is provided while highlighting gaps for future avenues in translational research.
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Affiliation(s)
- Mamatha Bhat
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Shirine E Usmani
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
| | - Amirhossein Azhie
- Multi Organ Transplant program and Division of Gastroenterology & Hepatology, University Health Network, Ontario M5G 2N2, Department of Medicine, University of Toronto, Ontario, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Minna Woo
- Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.,Division of Endocrinology and Metabolism, Department of Medicine, University Health Network, Ontario, and Sinai Health System, Ontario, University of Toronto, Toronto, Ontario, Canada
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28
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Sanyal D, Biswas M, Chaudhari N. Long-term efficacy and safety of anti-hyperglycaemic agents in new-onset diabetes after transplant: Results from outpatient-based 1-year follow-up and a brief review of treatment options. Diabetes Metab Syndr 2021; 15:13-19. [PMID: 33278690 DOI: 10.1016/j.dsx.2020.11.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 10/14/2020] [Accepted: 11/20/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Evaluation of long-term efficacy and safety of various anti-hyperglycaemic agents (AHA) for glycaemic control in NODAT, in stable kidney transplant recipients (KTRs) during 1-year outpatient follow-up. METHODS We collected FPG, PPG, HbA1c, serum creatinine, eGFR, blood tacrolimus level, hypoglycaemia and body weight values from an existing database of KTRs diagnosed to have NODAT. Those newly initiated on AHA over 3 months post-transplant; received standard triple immunosuppressive therapy; and followed up for 1-year after referral, were included. RESULTS In ninety-five patients' (Male = 65), mean decrease at 1-year from baseline in FPG (185.01 ± 62.11 mg/dL), PPG (293.21 ± 85.23 mg/dL) and HbA1c (8.48 ± 1.08%) was 67.09, 126.11 and 1.4 respectively (p < 0.0001). At 1-year, mean HbA1c was 7.08 ± 0.38%, ninety-one patients achieving HbA1c ≤ 7.5%. Fifty-two patients received oral combination therapy based on linagliptin/metformin/repaglinide/gliclazide, 19 received insulin-based regimen, and 24 received linagliptin monotharapey. Thirty patients reported hypoglycaemia (10 with gliclazide and 15 with insulin) and fifty patients gained body-weight at 1-year. Mean serum creatinine and eGFR significantly improved by 0.29 and 15.77 from baseline of 1.56 ± 0.62 mg/dL and 53.95 ± 16.10 mL/min/1.73 m2 respectively. CONCLUSIONS Significant proportion of NODAT patients achieved long-term glycemic control with improved renal function. Combination therapy was needed in most within 1-year. Linagliptin monotherapy was effective, without producing hypoglycaemia or weight gain.
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Affiliation(s)
- Debmalya Sanyal
- Department of Endocrinology, KPC Medical College and Hospital, RN Tagore International Institute of Cardiac Sciences, Kolkata, India.
| | - Mansij Biswas
- Department of Medical Affairs, Boehringer Ingelheim, Mumbai, India
| | - Nayan Chaudhari
- Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, India
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29
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Hecking M, Sharif A, Eller K, Jenssen T. Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics. Transpl Int 2021; 34:27-48. [PMID: 33135259 PMCID: PMC7839745 DOI: 10.1111/tri.13783] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/20/2020] [Accepted: 10/29/2020] [Indexed: 12/12/2022]
Abstract
Post-transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus-based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium-glucose-linked transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1-RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1-RAs that have not brought forth major concerns, likely indicating that GLP1-RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.
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Affiliation(s)
- Manfred Hecking
- Department of Internal Medicine IIIClinical Division of Nephrology & DialysisMedical University of ViennaViennaAustria
| | - Adnan Sharif
- Department of Nephrology and TransplantationQueen Elizabeth HospitalBirminghamUK
| | - Kathrin Eller
- Clinical Division of NephrologyMedical University of GrazGrazAustria
| | - Trond Jenssen
- Department of Organ TransplantationOslo University HospitalRikshospitaletOsloNorway
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30
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Morales Febles R, Negrín Mena N, Rodríguez-Rodríguez AE, Díaz Martín L, González Rinne F, Marrero Miranda D, González Rinne A, Álvarez González A, Pérez Tamajón L, Acosta Sørensen C, Rodríguez Hernández A, Domínguez-Rodríguez A, García Baute MDC, Torres Ramírez A, Porrini E. Exercise and Prediabetes after Renal Transplantation (EXPRED): Protocol Description. Nephron Clin Pract 2020; 145:55-62. [PMID: 33264770 DOI: 10.1159/000511320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 09/02/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Post-transplant diabetes mellitus (PTDM) is a frequent and severe complication after renal transplantation. In fact, PTDM is a risk factor for both infection and cardiovascular diseases. The prevalence and incidence of PTDM have a bimodal evolution: early (up to 3 months) and late PTDM (beyond 12 months). The majority of late PTDM occurs in subjects with prediabetes after transplantation. So, treating patients with prediabetes, a potentially reversible condition, might help preventing PTDM. In the general population, exercise prevents the evolution from prediabetes to diabetes. However, in renal transplantation, not enough evidence is available in this field. OBJECTIVES We designed an exploratory analysis to evaluate the feasibility of exercise to reverse prediabetes as a first step in the design of a trial to prevent PTDM. METHODS Only patients with prediabetes beyond 12 months after transplantation with capacity to perform exercise will be included. Prediabetes will be diagnosed based on fasting glucose levels and oral glucose tolerance tests (OGTTs). Patients will be treated with a stepped training intervention, starting with aerobic exercise training (brisk walking, swimming, and cycling) 5 times per week and 30 min/day. Aerobic exercise training will be gradually increased to 60 min/day or eventually combined with anaerobic exercise training in case of persistent prediabetes. The reversibility/persistence of prediabetes will be measured with fasting glucose and OGTTs every 3 months. This study will last for 12 months.
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Affiliation(s)
- Raúl Morales Febles
- Faculty of Medicine, University of La Laguna, Tenerife, Spain.,UCICEC (Unidad Central de Investigación Clínica y Ensayos Clínicos), Research Unit, Hospital Universitario de Canarias, La Laguna, Spain
| | - Natalia Negrín Mena
- UCICEC (Unidad Central de Investigación Clínica y Ensayos Clínicos), Research Unit, Hospital Universitario de Canarias, La Laguna, Spain
| | | | - Laura Díaz Martín
- UCICEC (Unidad Central de Investigación Clínica y Ensayos Clínicos), Research Unit, Hospital Universitario de Canarias, La Laguna, Spain
| | - Federico González Rinne
- Laboratory of Renal Function (LFR), Faculty of Medicine, University of La Laguna, Tenerife, Spain
| | | | - Ana González Rinne
- Nephrology Unit, Hospital Universitario de Canarias (HUC), La Laguna, Spain
| | | | | | | | | | - Alberto Domínguez-Rodríguez
- Department of Cardiology, Hospital Universitario de Canarias (HUC), La Laguna, Spain.,CIBER of Cardiovascular diseases (CIBERCV), Madrid, Spain.,Faculty of Health Science, Europe university of Canary Island, Tenerife, Spain
| | | | - Armando Torres Ramírez
- Faculty of Medicine, University of La Laguna, Tenerife, Spain.,Nephrology Unit, Hospital Universitario de Canarias (HUC), La Laguna, Spain.,Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, Tenerife, Spain
| | - Esteban Porrini
- Faculty of Medicine, University of La Laguna, Tenerife, Spain, .,Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, University of La Laguna, Tenerife, Spain,
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31
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IMC, tour de taille et transplantation rénale : contraintes, réalités et enjeux pour un centre spécialisé de l’obésité. Revue de la littérature. NUTR CLIN METAB 2020. [DOI: 10.1016/j.nupar.2020.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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32
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Comparing Glycaemic Benefits of Active Versus Passive Lifestyle Intervention in Kidney Allograft Recipients: A Randomized Controlled Trial. Transplantation 2020; 104:1491-1499. [PMID: 31568390 DOI: 10.1097/tp.0000000000002969] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND New-onset diabetes is common after kidney transplantation, but the benefit of lifestyle intervention to improve glucose metabolism posttransplantation is unproven. METHODS We conducted a single-center, randomized controlled trial involving 130 nondiabetic kidney transplant recipients with stable function between 3 and 24 months post-transplantation. Participants were randomly assigned in a 1:1 ratio to receive active intervention (lifestyle advice delivered by renal dietitians using behavior change techniques) versus passive intervention (leaflet advice alone). Primary outcome was 6-month change in insulin secretion, insulin sensitivity, and disposition index. Secondary outcomes included patient-reported outcomes, cardiometabolic parameters, clinical outcomes, and safety endpoints. RESULTS Between August 17, 2015 and December 18, 2017, 130 individuals were recruited, of whom 103 completed the study (drop-out rate 20.8%). Active versus passive intervention was not associated with any change in glucose metabolism: insulin secretion (mean difference, -446; 95% confidence interval [CI], -3184 to 2292; P = 0.748), insulin sensitivity (mean difference, -0.45; 95% CI, -1.34 to 0.44; P = 0.319), or disposition index (mean difference, -940; 95% CI, -5655 to 3775; P = 0.693). Clinically, active versus passive lifestyle intervention resulted in reduced incidence of posttransplantation diabetes (7.6% versus 15.6%, respectively, P = 0.123), reduction in fat mass (mean difference, -1.537 kg; 95% CI, -2.947 to -0.127; P = 0.033), and improvement in weight (mean difference, -2.47 kg; 95% CI, -4.01 to -0.92; P = 0.002). No serious adverse events were noted. CONCLUSIONS Active lifestyle intervention led by renal dietitians did not improve surrogate markers of glucose metabolism. Further investigation is warranted to determine if clinical outcomes can be improved using this methodology.
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33
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Abstract
Post-transplant diabetes mellitus (PTDM) is common following solid organ transplantation, and is a risk factor for graft failure and patient mortality. In addition to standard diabetes risk factors such as obesity and ethnicity, patients undergoing transplantation also have the additional risk factors of immunosuppressive agents and infections such as hepatitis C. Patients undergoing transplant assessment should be screened for diabetes. If non-diabetic, but deemed at high risk, they should be offered careful lifestyle advice to reduce risk of post-transplant weight gain and therefore reduce risk of PTDM. Hyperglycaemia in the early post-operative period should be managed ideally with insulin therapy. Once clinically stable, there may be an opportunity to reduce or stop insulin, and consider oral hypoglycaemic agents. Despite lack of evidence from randomised trials, PTDM should be actively screened for in all transplant recipients, and actively managed with structured education, screening for complications, cardiovascular risk reduction and anti-hyperglycaemic therapy.
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34
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Conte C, Maggiore U, Cappelli G, Ietto G, Lai Q, Salis P, Marchetti P, Piemonti L, Secchi A, Capocasale E, Caldara R. Management of metabolic alterations in adult kidney transplant recipients: A joint position statement of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID). Nutr Metab Cardiovasc Dis 2020; 30:1427-1441. [PMID: 32605884 DOI: 10.1016/j.numecd.2020.05.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/01/2020] [Accepted: 05/06/2020] [Indexed: 12/21/2022]
Abstract
Chronic metabolic alterations such as post-transplant diabetes mellitus (PTDM), dyslipidaemias and overweight/obesity significantly impact on kidney transplant (KT) outcomes. This joint position statement is based on the evidence on the management of metabolic alterations in KT recipients (KTRs) published after the release of the 2009 KDIGO clinical practice guideline for the care of KTRs. Members of the Italian Society of Nephrology (SIN), the Italian Society for Organ Transplantation (SITO) and the Italian Diabetes Society (SID) selected to represent professionals involved in the management of KTRs undertook a systematic review of the published evidence for the management of PTDM, dyslipidaemias and obesity in this setting. The aim of this work is to provide an updated review of the evidence on the prevention, diagnosis and treatment of metabolic alterations in KTRs, in order to support physicians, patients and the Healthcare System in the decision-making process when choosing among the various available options.
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Affiliation(s)
- Caterina Conte
- Università Vita-Salute San Raffaele, Milan, Italy; IRCCS San Raffaele Hospital, Milan, Italy.
| | - Umberto Maggiore
- Dipartimento di Medicina e Chirurgia, University Hospital of Parma, Parma, Italy.
| | - Gianni Cappelli
- University of Modena and Reggio Emilia, Azienda Ospedaliero - Universitaria Policlinico, Modena, Italy.
| | - Giuseppe Ietto
- Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy.
| | - Quirino Lai
- Hepato-Biliary Surgery and Organ Transplantation Unit, Sapienza University of Rome, Umberto I Polyclinic of Rome, Rome, Italy.
| | - Paola Salis
- IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy.
| | | | - Lorenzo Piemonti
- Università Vita-Salute San Raffaele, Milan, Italy; IRCCS San Raffaele Hospital, Milan, Italy; Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Antonio Secchi
- Università Vita-Salute San Raffaele, Milan, Italy; IRCCS San Raffaele Hospital, Milan, Italy.
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35
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Abstract
Solid organ transplantation (SOT) is an established therapeutic option for chronic disease resulting from end-stage organ dysfunction. Long-term use of immunosuppression is associated with post-transplantation diabetes mellitus (PTDM), placing patients at increased risk of infections, cardiovascular disease and mortality. The incidence rates for PTDM have varied from 10 to 40% between different studies. Diagnostic criteria have evolved over the years, as a greater understating of PTDM has been reached. There are differences in pathophysiology and clinical course of type 2 diabetes and PTDM. Hence, managing this condition can be a challenge for a diabetes physician, as there are several factors to consider when tailoring therapy for post-transplant patients to achieve better glycaemic as well as long-term transplant outcomes. This article is a detailed review of PTDM, examining the pathogenesis, diagnostic criteria and management in light of the current evidence. The therapeutic options are discussed in the context of their safety and potential drug-drug interactions with immunosuppressive agents.
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Affiliation(s)
| | - Kathryn Biddle
- St George's University Hospitals NHS Foundation Trust, London, UK
| | | | - Shazli Azmi
- Manchester University NHS Foundation Trust, Manchester, UK
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36
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de Lucena DD, de Sá JR, Medina-Pestana JO, Rangel ÉB. Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study. J Diabetes Res 2020; 2020:1938703. [PMID: 32258163 PMCID: PMC7109550 DOI: 10.1155/2020/1938703] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 03/04/2020] [Indexed: 02/07/2023] Open
Abstract
Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2 ± 1.3vs. 40.7 ± 0.6 years old, OR 1.04; P = 0.001) and pretransplant hyperglycaemia and BMI ≥ 25 kg/m2 (32.8% vs. 21.6%, OR 0.54; P = 0.032 and 57.4% vs. 27.7%, OR 3.5; P < 0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03; P = 0.0001), acute rejection (P = 0.021), calcium channel blockers (P = 0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol) ratio ≥ 3.5 at 1 year (P = 0.01) and at 3 years (P = 0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P = 0.035), pretransplant BMI ≥ 25 kg/m2 (P = 0.0001), posttransplant transient hyperglycaemia (P = 0.0001), and TG/HDL ratio ≥ 3.5 at 3-year posttransplant (P = 0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.
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Affiliation(s)
- Débora Dias de Lucena
- Nephrology Division, Universidade Federal de São Paulo/Hospital do Rim, São Paulo, SP, Brazil
| | - João Roberto de Sá
- Endocrinology Division, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - José O. Medina-Pestana
- Nephrology Division, Universidade Federal de São Paulo/Hospital do Rim, São Paulo, SP, Brazil
| | - Érika Bevilaqua Rangel
- Nephrology Division, Universidade Federal de São Paulo/Hospital do Rim, São Paulo, SP, Brazil
- Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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Byambasukh O, Osté MCJ, Gomes-Neto AW, van den Berg E, Navis G, Bakker SJL, Corpeleijn E. Physical Activity and the Development of Post-Transplant Diabetes Mellitus, and Cardiovascular- and All-Cause Mortality in Renal Transplant Recipients. J Clin Med 2020; 9:jcm9020415. [PMID: 32028662 PMCID: PMC7074375 DOI: 10.3390/jcm9020415] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 01/31/2020] [Accepted: 02/01/2020] [Indexed: 02/08/2023] Open
Abstract
(1) Background: Little is currently known about the health impacts of daily-life moderate-to-vigorous physical activity (MVPA) in relation to the development of post-transplant diabetes mellitus (PTDM) and the long-term survival of renal transplant recipients (RTRs). (2) Methods: We analyzed self-reported data on MVPA within non-occupational and occupational domains, estimated with the SQUASH questionnaire, from a prospective cohort study of RTRs (n = 650) with a functioning graft exceeding 1 year. PTDM diagnoses were based on plasma glucose levels (≥126 mg/dL), HbA1c (≥6.5%), and the use of antidiabetic medication. Mortality data were retrieved from patient files up to the end of September 2015. (3) Results: During a median follow-up period of 5.3 years, 50 patients (10%) developed PTDM and 129 (19.8%) died. Of these deaths, 53 (8.9%) were caused by cardiovascular disease. Cox regression analyses showed that higher MVPA levels among patients were associated with a lower risk of PTDM (hazard ratio (HR); 95% confidence interval (95%CI) = 0.49; 0.25–0.96, p = 0.04), cardiovascular- (0.34; 0.15–0.77, p = 0.01), and all-cause mortality (0.37; 0.24–0.58, p < 0.001) compared with No-MVPA patients, independently of age, sex, and kidney function parameters. Associations of MVPA with cardiovascular and all-cause mortality remained significant and materially unchanged following further adjustments made for transplant characteristics, lifestyle factors, metabolic parameters, medication use, and creatinine excretion (muscle mass). However, the association between MVPA and PTDM was no longer significant after we adjusted for metabolic confounders and glucose levels. (4) Conclusion: Higher MVPA levels are associated with long-term health outcomes in RTRs.
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Affiliation(s)
- Oyuntugs Byambasukh
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
- Department of Internal Medicine, Mongolian National University of Medical Sciences, 976 Ulaanbaatar, Mongolia
- Correspondence: or
| | - Maryse C. J. Osté
- Department of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.C.J.O.); (A.W.G.-N.); (E.v.d.B.); (G.N.); (S.J.L.B.)
| | - António W. Gomes-Neto
- Department of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.C.J.O.); (A.W.G.-N.); (E.v.d.B.); (G.N.); (S.J.L.B.)
| | - Else van den Berg
- Department of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.C.J.O.); (A.W.G.-N.); (E.v.d.B.); (G.N.); (S.J.L.B.)
| | - Gerjan Navis
- Department of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.C.J.O.); (A.W.G.-N.); (E.v.d.B.); (G.N.); (S.J.L.B.)
| | - Stephan J. L. Bakker
- Department of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands; (M.C.J.O.); (A.W.G.-N.); (E.v.d.B.); (G.N.); (S.J.L.B.)
| | - Eva Corpeleijn
- Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
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Yeh H, Lin C, Li YR, Yen CL, Lee CC, Chen JS, Chen KH, Tian YC, Liu PH, Hsiao CC. Temporal trends of incident diabetes mellitus and subsequent outcomes in patients receiving kidney transplantation: a national cohort study in Taiwan. Diabetol Metab Syndr 2020; 12:34. [PMID: 32368254 PMCID: PMC7189729 DOI: 10.1186/s13098-020-00541-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Accepted: 04/13/2020] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Allograft kidney transplantation has become a treatment of choice for patients with end-stage renal disease (ESRD), and post-transplant diabetes mellitus (PTDM) has been associated with impaired patient and graft survival. Taiwan has the highest incidence and prevalence rates of ESRD with many recipients and candidates of kidney transplantation. However, information about the epidemiologic features of PTDM in Taiwan is incomplete. Therefore, we aimed to investigate the prevalence and incidence of PTDM with subsequent patient and graft outcomes. METHODS Using the Taiwan National Health Insurance Research Database (NHIRD), 3663 kidney recipients between 1997 and 2011 were enrolled. We calculated the cumulative incidences of diabetes mellitus (DM) after transplantation. Cox proportional hazards model with competing risk analysis was used to calculate the hazard ratio (HR) and 95% confidence intervals (CI) between three targeted groups (DM, PTDM, non-DM). The outcomes of primary interest were the occurrence of graft failure excluding death with functioning graft, all-cause mortality, death with functioning graft and major adverse cardiovascular events (MACE) including myocardial infarction (MI), cerebrovascular accident (CVA) and congestive heart failure (CHF). Subgroup analysis for graft failure excluding death with functioning graft, MACE and all-cause mortality was performed, and interaction between PTDM and recipient age was examined. RESULTS Of 3663 kidney transplant recipients, 531 (14%) had pre-existing DM and 631 (17%) developed PTDM. Compared with non-DM group, the PTDM and DM groups exhibited higher risk of graft failure excluding death with functioning graft (PTDM: HR 1.65, 95% CI 1.47-1.85; DM: HR 1.33, 95% CI 1.18-1.50), MACE (PTDM: HR 1.51, 95% CI 1.31-1.74; DM: HR 1.64, 95% CI 1.41-1.9), all-cause mortality (PTDM: HR 1.79, 95% CI 1.59-2.01; DM: HR 2.03, 95% CI 1.81-2.18), and death with functioning graft (PTDM: HR 1.94, 95% CI 1.71-2.20; DM: HR 1.94, 95% CI 1.71-2.21). Both PTDM and DM groups had increased cardiovascular disease-related mortality (PTDM: HR 2.14, 95% CI 1.43-3.20, p < 0.001; DM: HR 1.89, 95% CI 1.25-2.86, p = 0.002), cancer-related mortality (PTDM: HR 1.56, 95% CI 1.18-2.07, p = 0.002; DM: HR 1.89, 95% CI 1.25-2.86, p = 0.027), and infection-related mortality (PTDM: HR 1.47, 95% CI 1.14-1.90, p = 0.003; DM: HR 2.25, 95% CI 1.77-2.84, p < 0.001) compared with non-DM group. The subgroup analyses showed that the add-on risks of MACE and mortality from PTDM were mainly observed in patients who were younger and those without associated comorbidities including atrial fibrillation, cirrhosis, CHF, and MI. Age significantly modified the association between PTDM and MACE (pinteraction < 0.01) with higher risk in recipients with PTDM aged younger than 55 years (adjusted HR 1.64, 95% CI 1.40-1.92, p < 0.001). A trend (pinteraction = 0.06) of age-modifying effect on the association between PTDM and all-cause mortality was also noted with higher risk in recipients with PTDM aged younger than 55 years. CONCLUSIONS In the present population-based study, the incidence of PTDM peaked within the first year after kidney transplantation. PTDM negatively impacted graft and patient outcomes. The magnitude of cardiovascular and survival disadvantages from PTDM were more pronounced in recipients aged less than 55 years. Further trials to improve prediction of PTDM and to prevent PTDM are warranted.
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Affiliation(s)
- Hsuan Yeh
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chihung Lin
- Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Yan-Rong Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Chieh-Li Yen
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Chia Lee
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jung-Sheng Chen
- Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Kuan-Hsing Chen
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ya-Chun Tian
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pi-Hua Liu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Chung Hsiao
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Nephrology, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan
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Fung SKS, Chau KF, Chow KM. Clinical practice guidelines for the provision of renal service in Hong Kong: Potential Kidney Transplant Recipient Wait-listing and Evaluation, Deceased Kidney Donor Evaluation, and Kidney Transplant Postoperative Care. Nephrology (Carlton) 2019; 24 Suppl 1:60-76. [PMID: 30900332 DOI: 10.1111/nep.13502] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | - Ka Foon Chau
- Department of Medicine, Queen Elizabeth Hospital, Hong Kong
| | - Kai Ming Chow
- Department of Medicine & Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong
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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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41
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Wissing KM, De Meyer V, Pipeleers L. Balancing Immunosuppressive Efficacy and Prevention of Posttransplant Diabetes-A Question of Timing and Patient Selection. Kidney Int Rep 2018; 3:1249-1252. [PMID: 30450448 PMCID: PMC6224669 DOI: 10.1016/j.ekir.2018.08.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Affiliation(s)
- Karl Martin Wissing
- Department of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Vicky De Meyer
- Department of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | - Lissa Pipeleers
- Department of Nephrology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
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42
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Nolte Fong JV, Moore LW. Nutrition Trends in Kidney Transplant Recipients: the Importance of Dietary Monitoring and Need for Evidence-Based Recommendations. Front Med (Lausanne) 2018; 5:302. [PMID: 30430111 PMCID: PMC6220714 DOI: 10.3389/fmed.2018.00302] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 10/11/2018] [Indexed: 12/19/2022] Open
Abstract
Many physiological properties of the renal system influence nutrient metabolism, elimination, and homeostasis. Kidney failure poses significant challenges to maintaining adequate nutrition, most of which transplantation ameliorates. Comprehensive recommendations for managing nutritional derangements for patients with chronic kidney disease and end stage renal disease exist; however, there are only sparse guidelines for post-transplant malnutrition and adverse outcomes. Not only are guidelines limited, but little is known about dietary trends of post-kidney transplant recipients. This review describes guidelines for prevalent metabolic and nutritional complications post-kidney transplantation and also evaluates changes in caloric intake and diet composition after transplantation. This topic is important because nutrition influences allograft function and a number of cardiovascular risk factors including blood pressure, dyslipidemia, weight, and diabetes. In addition, many dietary recommendations and modifiable lifestyle changes should be tailored for specific complications of transplant patients, namely immunosuppression side effects, dietary restrictions, and electrolyte imbalances.
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Affiliation(s)
- Joy V Nolte Fong
- Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
| | - Linda W Moore
- Department of Surgery, Houston Methodist Hospital, Houston, TX, United States
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De Lucena DD, Rangel ÉB. Glucocorticoids use in kidney transplant setting. Expert Opin Drug Metab Toxicol 2018; 14:1023-1041. [DOI: 10.1080/17425255.2018.1530214] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Débora Dias De Lucena
- Department of Medicine, Division of Nephrology, Federal University of São Paulo/Hospital do Rim e Hipertensão, São Paulo, Brazil
| | - Érika Bevilaqua Rangel
- Department of Medicine, Division of Nephrology, Federal University of São Paulo/Hospital do Rim e Hipertensão, São Paulo, Brazil
- Instituto Israelita de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, Brazil
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Conte C, Secchi A. Post-transplantation diabetes in kidney transplant recipients: an update on management and prevention. Acta Diabetol 2018; 55:763-779. [PMID: 29619563 DOI: 10.1007/s00592-018-1137-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 03/26/2018] [Indexed: 12/14/2022]
Abstract
Post-transplantation diabetes mellitus (PTDM) may severely impact both short- and long-term outcomes of kidney transplant recipients in terms of graft and patient survival. However, PTDM often goes undiagnosed is underestimated or poorly managed. A diagnosis of PTDM should be delayed until the patient is on stable maintenance doses of immunosuppressive drugs, with stable kidney graft function and in the absence of acute infections. Risk factors for PTDM should be assessed during the pre-transplant evaluation period, in order to reduce the likelihood of developing diabetes. The oral glucose tolerance test is considered as the gold standard for diagnosing PTDM, whereas HbA1c is not reliable during the first months after transplantation. Glycaemic targets should be individualised, and comorbidities such as dyslipidaemia and hypertension should be treated with drugs that have the least possible impact on glucose metabolism, at doses that do not interact with immunosuppressants. While insulin is the preferred agent for treating inpatient hyperglycaemia in the immediate post-transplantation period, little evidence is available to guide therapeutic choices in the management of PTDM. Metformin and incretins may offer some advantage over other glucose-lowering agents, particularly with respect to risk of hypoglycaemia and weight gain. Tailoring immunosuppressive regimens may be of help, although maintenance of good kidney function should be prioritised over prevention/treatment of PTDM. The aim of this narrative review is to provide an overview of the available evidence on management and prevention of PTDM, with a focus on the available therapeutic options.
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Affiliation(s)
- Caterina Conte
- I.R.C.C.S. Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
| | - Antonio Secchi
- I.R.C.C.S. Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy
- Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy
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Hap K, Madziarska K, Zmonarski S, Kamińska D, Magott-Procelewska M, Banasik M, Jędrzejak K, Madziarski M, Hap W, Klinger M, Mazanowska O. Pretransplantation Oral Glucose Tolerance Test Can Prevent Posttransplant Diabetes Mellitus After Renal Transplantation: Preliminary Study. Transplant Proc 2018; 50:1776-1780. [PMID: 30056899 DOI: 10.1016/j.transproceed.2018.03.125] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Revised: 03/08/2018] [Accepted: 03/23/2018] [Indexed: 12/13/2022]
Abstract
Posttransplant diabetes mellitus (PTDM) adversely affects renal graft and patient survival. Fasting plasma glucose (FPG) alone underestimates diagnosis of glucose metabolism disorders (GMD) detected using the oral glucose tolerance test (OGTT-75). Prediabetes including impaired fasting glucose (IFG): 100 to 125 mg/dL (5.6-6.9 mmol/L) and impaired glucose tolerance (IGT): 140 to 199 mg/dL (7.8-11 mmol/L) 2 hours post 75-g OGTT in the pretransplant period can have a connection with the occurrence of PTDM after renal transplantation (RTx). The aim of our study was to assess the benefit of performing OGTT-75 in dialyzed chronic kidney disease (stage 5) patients on the waiting list for kidney transplantation as a useful tool to prevent PTDM. MATERIALS AND METHODS Pretransplant glucose testing using OGTT-75 was performed in nondiabetic dialyzed chronic kidney disease patients on the waiting list for renal transplantation in the southwest region of Poland. GMD were diagnosed according to current criteria. Patients with recognized prediabetic stage were recommended a low carbohydrate diet, lifestyle modification, and increased physical activity. In the 12-month posttransplant period we estimated the prevalence of PTDM in the study group based on FPG >126 mg/dL (7 mmol/L) in 2 measurements or random blood glucose >200 mg/dL (11.1 mmol/L). RESULTS A total of 80 nondiabetic dialysis patients (65 hemodialysis/15 peritoneal dialysis; 47 male/33 female) met initial entry criteria. In pretransplant glucose testing prediabetes was found in 31 out of 80 patients (39%). Among them, 5 patients (6.25%) had combined IGT/IFG, 18 patients (22.5%) had IGT, and 8 patients (10%) had IFG. One year after RTx we recognized PTDM in 14% of all analyzed patients (11/80) and noticed a significant frequency of glucose disorders status change after RTx (P = .002). CONCLUSION Our findings suggest early detection of prediabetes using the OGTT-75 test in nondiabetic dialysis patients waiting for RTx to prevent occurrence of PTDM.
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Affiliation(s)
- K Hap
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - K Madziarska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
| | - S Zmonarski
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - D Kamińska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - M Magott-Procelewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - M Banasik
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - K Jędrzejak
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | | | - W Hap
- Department of General and Oncological Surgery, Wroclaw Medical University, Wroclaw, Poland
| | - M Klinger
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland
| | - O Mazanowska
- Faculty of Medicine and Dentistry, Wroclaw Medical University, Wroclaw, Poland
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Wissing KM, Abramowicz D, Weekers L, Budde K, Rath T, Witzke O, Broeders N, Kianda M, Kuypers DRJ. Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation. Am J Transplant 2018; 18:1726-1734. [PMID: 29337426 DOI: 10.1111/ajt.14665] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 12/22/2017] [Accepted: 01/07/2018] [Indexed: 02/06/2023]
Abstract
Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared with cyclosporine A (CYC). The present 12-month, multicenter, investigator-driven, prospective, randomized study was designed to assess whether conversion from tacrolimus to CYC can reverse PTDM after renal transplantation. Predominantly white patients with PTDM according to the 2005 American Diabetes Association criteria were randomized to either replacement of TAC with CYC or continuation of their TAC-based regimen after stratification for type of glucose-lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41 patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%) in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC group decreased glycated hemoglobin level during the 12-month follow-up, resulting in significantly lower levels compared with the TAC group (6.0 ± 0.9% vs 7.1 ± 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with CYC significantly improves glucose metabolism and has the potential to reverse diabetes during the first year after conversion. (EU Clinical Trials Register No. 2006-001765-42).
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Affiliation(s)
- Karl M Wissing
- Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels, Belgium
| | - Daniel Abramowicz
- Department of Nephrology, Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium
| | - Laurent Weekers
- Department of Nephrology, Centre Hospitalier Universitaire Liège, Liège, Belgium
| | - Klemens Budde
- Department of Nephrology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Thomas Rath
- Department of Nephrology, Westpfalz Klinikum Kaiserslautern, Kaiserslautern, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Nilufer Broeders
- Department of Nephrology, Centre Universitaire de Bruxelles - Hôpital Erasme, Brussels, Belgium
| | - Mireille Kianda
- Department of Nephrology, Centre Hospitalier Universitaire Brugmann, Brussels, Belgium
| | - Dirk R J Kuypers
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
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von Düring ME, Jenssen T, Bollerslev J, Godang K, Hartmann A, Åsberg A. Arterial stiffness is associated with visceral fat mass in kidney transplanted patients-A nationwide cohort study. Clin Transplant 2018; 32:e13341. [PMID: 29957825 DOI: 10.1111/ctr.13341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2018] [Revised: 05/15/2018] [Accepted: 06/16/2018] [Indexed: 01/22/2023]
Abstract
Arterial stiffness, visceral fat, and hyperglycemia are acknowledged risk factors for adverse outcomes after transplantation, but whether arterial stiffness is associated with visceral adipose tissue and hyperglycemia is unknown. We studied 162 non-diabetic kidney transplant recipients 8-10 weeks after transplantation. Arterial stiffness was measured as pulse wave velocity (PWV) by SphygmoCor and visceral fat using a validated software applied on DXA scans. Also a standard oral glucose tolerance test was performed. Median PWV was 8.6 m/s (IQR 7.3-10.4 m/s). Patients in the upper quartile of PWV had 31%-106% higher visceral fat percentage (P < 0.001), they were older (P < 0.001) and had a fasting plasma glucose of 5.8 mmol/L that was higher than in the other quartiles (P = 0.006). In univariate analysis, visceral fat percentage and age were the parameters strongest associated with PWV (P < 0.001), but cholesterol and glucose were also significant (P < 0.05). In multivariate analysis, visceral fat was the only significant predictor of PWV along with age (P < 0.001). In conclusion, arterial stiffness is significantly associated with visceral fat but not hyperglycemia in non-diabetic kidney transplant patients. We identified age and VAT as risk variables for arterial stiffness. A potential reversibility of arterial wall stiffness with reduction in VAT needs further study.
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Affiliation(s)
- Marit Elizabeth von Düring
- Section of Nephrology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trond Jenssen
- Section of Nephrology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway
| | - Jens Bollerslev
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Kristin Godang
- Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Anders Hartmann
- Section of Nephrology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Anders Åsberg
- Section of Nephrology, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Norwegian Renal Registry, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,School of Pharmacy, University of Oslo, Oslo, Norway
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Piotti G, Gandolfini I, Palmisano A, Maggiore U. Metabolic risk profile in kidney transplant candidates and recipients. Nephrol Dial Transplant 2018; 34:388-400. [DOI: 10.1093/ndt/gfy151] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Accepted: 05/01/2018] [Indexed: 12/30/2022] Open
Affiliation(s)
- Giovanni Piotti
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Ilaria Gandolfini
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alessandra Palmisano
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Umberto Maggiore
- Department of Nephrology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
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50
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Peláez-Jaramillo MJ, Cárdenas-Mojica AA, Gaete PV, Mendivil CO. Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment. Diabetes Ther 2018; 9:521-543. [PMID: 29411291 PMCID: PMC6104273 DOI: 10.1007/s13300-018-0374-8] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Indexed: 02/08/2023] Open
Abstract
Post-liver transplantation diabetes mellitus (PLTDM) develops in up to 30% of liver transplant recipients and is associated with increased risk of mortality and multiple morbid outcomes. PLTDM is a multicausal disorder, but the main risk factor is the use of immunosuppressive agents of the calcineurin inhibitor (CNI) family (tacrolimus and cyclosporine). Additional factors, such as pre-transplant overweight, nonalcoholic steatohepatitis and hepatitis C virus infection, may further increase risk of developing PLTDM. A diagnosis of PLTDM should be established only after doses of CNI and steroids are stable and the post-operative stress has been overcome. The predominant defect induced by CNI is insulin secretory dysfunction. Plasma glucose control must start immediately after the transplant procedure in order to improve long-term results for both patient and transplant. Among the better known antidiabetics, metformin and DPP-4 inhibitors have a particularly benign profile in the PLTDM context and are the preferred oral agents for long-term management. Insulin therapy is also an effective approach that addresses the prevailing pathophysiological defect of the disorder. There is still insufficient evidence about the impact of newer families of antidiabetics (GLP-1 agonists, SGLT-2 inhibitors) on PLTDM. In this review, we summarize current knowledge on the epidemiology, pathogenesis, course of disease and medical management of PLTDM.
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Affiliation(s)
| | | | - Paula V Gaete
- Universidad de los Andes School of Medicine, Bogotá, Colombia
| | - Carlos O Mendivil
- Universidad de los Andes School of Medicine, Bogotá, Colombia.
- Endocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
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