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Budhiraja P, Smith BH, Kukla A, Kline TL, Korfiatis P, Stegall MD, Jadlowiec CC, Cheungpasitporn W, Wadei HM, Kudva YC, Alajous S, Misra SS, Me HM, Rios IP, Chakkera HA. Clinical and Radiological Fusion: A New Frontier in Predicting Post-Transplant Diabetes Mellitus. Transpl Int 2025; 38:14377. [PMID: 40248509 PMCID: PMC12003133 DOI: 10.3389/ti.2025.14377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/24/2025] [Indexed: 04/19/2025]
Abstract
This study developed a predictive model for Post-Transplant Diabetes Mellitus (PTDM) by integrating clinical and radiological data to identify at-risk kidney transplant recipients. In a retrospective analysis across three Mayo Clinic sites, clinical metrics were combined with deep learning analysis of pre-transplant CT images, focusing on body composition parameters like adipose tissue and muscle mass instead of BMI or other biomarkers. Among 2,005 nondiabetic kidney recipients, 335 (16.7%) developed PTDM within the first year. PTDM patients were older, had higher BMIs, elevated triglycerides, and were more likely to be male and non-White. They exhibited lower skeletal muscle area, greater visceral adipose tissue (VAT), more intermuscular fat, and higher subcutaneous fat (all p < 0.001). Multivariable analysis identified age (OR: 1.05, 95% CI: 1.03-1.08, p < 0.0001), family diabetes history (OR: 1.55, CI: 1.14-2.09, p = 0.0061), White race (OR: 0.43, CI: 0.28-0.66, p < 0.0001), and VAT area (OR: 1.37, CI: 1.14-1.64, p = 0.0009) as predictors. The combined model achieved C-statistic of 0.724 (CI: 0.692-0.757), outperforming the clinical-only model (C-statistic 0.68). Patients with PTDM in the first year had higher mortality than those without PTDM. This model improves predictive precision, enabling accurate identification and intervention for at risk patients.
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Affiliation(s)
- Pooja Budhiraja
- Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Byron H. Smith
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States
| | - Aleksandra Kukla
- Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Timothy L. Kline
- Department of Radiology, Mayo Clinic, Rochester, MN, United States
| | | | - Mark D. Stegall
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
| | | | | | - Hani M. Wadei
- Department of Transplant, Mayo Clinic Florida, Jacksonville, FL, United States
| | - Yogish C. Kudva
- Department of Medicine, Mayo Clinic, Rochester, MN, United States
| | - Salah Alajous
- Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Suman S. Misra
- Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Hay Me Me
- Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, United States
| | - Ian P. Rios
- Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, United States
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Abdelrahman Z, Maxwell AP, McKnight AJ. Genetic and Epigenetic Associations with Post-Transplant Diabetes Mellitus. Genes (Basel) 2024; 15:503. [PMID: 38674437 PMCID: PMC11050138 DOI: 10.3390/genes15040503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/10/2024] [Accepted: 04/12/2024] [Indexed: 04/28/2024] Open
Abstract
Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT). The task of diagnosing PTDM continues to pose challenges, given the potential for diabetes to manifest at different time points after transplantation, thus demanding constant clinical vigilance and repeated testing. Interpreting HbA1c levels can be challenging after renal transplantation. Pre-transplant risk factors for PTDM include obesity, sedentary lifestyle, family history of diabetes, ethnicity (e.g., African-Caribbean or South Asian ancestry), and genetic risk factors. Risk factors for PTDM include immunosuppressive drugs, weight gain, hepatitis C, and cytomegalovirus infection. There is also emerging evidence that genetic and epigenetic variation in the organ transplant recipient may influence the risk of developing PTDM. This review outlines many known risk factors for PTDM and details some of the pathways, genetic variants, and epigenetic features associated with PTDM. Improved understanding of established and emerging risk factors may help identify people at risk of developing PTDM and may reduce the risk of developing PTDM or improve the management of this complication of organ transplantation.
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Affiliation(s)
- Zeinab Abdelrahman
- Centre for Public Health, Queen’s University of Belfast, Belfast BT12 6BA, UK; (Z.A.); (A.P.M.)
| | - Alexander Peter Maxwell
- Centre for Public Health, Queen’s University of Belfast, Belfast BT12 6BA, UK; (Z.A.); (A.P.M.)
- Regional Nephrology Unit, Belfast City Hospital, Belfast BT9 7AB, UK
| | - Amy Jayne McKnight
- Centre for Public Health, Queen’s University of Belfast, Belfast BT12 6BA, UK; (Z.A.); (A.P.M.)
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Malik RF, Jia Y, Mansour SG, Reese PP, Hall IE, Alasfar S, Doshi MD, Akalin E, Bromberg JS, Harhay MN, Mohan S, Muthukumar T, Schröppel B, Singh P, Weng FL, Thiessen Philbrook HR, Parikh CR. Post-transplant Diabetes Mellitus in Kidney Transplant Recipients: A Multicenter Study. KIDNEY360 2021; 2:1296-1307. [PMID: 35369651 PMCID: PMC8676388 DOI: 10.34067/kid.0000862021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/01/2021] [Indexed: 02/06/2023]
Abstract
Background De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. Methods In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. Results Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P<0.001) and higher BMI (P=0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM. Conclusions PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time.
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Affiliation(s)
- Rubab F. Malik
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Yaqi Jia
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sherry G. Mansour
- Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut,Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Peter P. Reese
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania,Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Isaac E. Hall
- Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
| | - Sami Alasfar
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Mona D. Doshi
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
| | - Enver Akalin
- Kidney Transplant Program, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Jonathan S. Bromberg
- Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland,Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Meera N. Harhay
- Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania,Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, Pennsylvania,Tower Health Transplant Institute, Tower Health System, West Reading, Pennsylvania
| | - Sumit Mohan
- Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York,Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, New York, New York
| | - Thangamani Muthukumar
- Department of Medicine, Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York,Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, New York
| | | | - Pooja Singh
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Francis L. Weng
- Saint Barnabas Medical Center, RWJBarnabas Health, Livingston, New Jersey
| | | | - Chirag R. Parikh
- Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Pham Vu T, Nguyen Thi Thuy D, Truong Quy K, Nguyen Thi Thu H, Nguyen Van D, Diem Thi V, Do Manh H, Nguyen Trung K, Do Q, Tran Viet T, Do Nhu B, Pham Quoc T, Can Van M, Le Viet T. Serum hs-CRP measured prior transplantation predicts of new-onset diabetes after transplantation in renal transplant recipients. Transpl Immunol 2021; 66:101392. [PMID: 33838297 DOI: 10.1016/j.trim.2021.101392] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/29/2021] [Accepted: 04/04/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND To assess the incidence of new-onset diabetes after transplantation (NODAT) for the first year post-transplantation and the predictive value of high-sensitivity C-reactive Protein (hs-CRP) before transplantation for NODAT prediction in kidney transplantation patients. MATERIAL AND METHODS A study of 251 consecutive adult end-stage kidney disease patients transplanted kidneys from living donors, follow-up during the first year to find NODAT. We diagnosed NODAT based on blood glucose or HbA1c following to the criteria of the American Diabetes Association. RESULTS The ratio of NODAT was 12.4%. The mean age, mean BMI, the proportion of arteriosclerosis, and the median hs-CRP level in NODAT group were significantly higher than those of non-NODAT group with p < 0.05. Age, BMI and serum hs-CRP had a predictive value for NODAT (Age: AUC = 0.62, p < 0.05, BMI: AUC = 0.626, hs-CRP: AUC = 0.748, p < 0.001). CONCLUSION Serum hs-CRP level measured prior transplantation is a good predictor for NODAT in renal transplant recipients.
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Affiliation(s)
- Thuy Pham Vu
- Kinh 7 Charity Clinic, Kien Giang, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Dung Nguyen Thi Thuy
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Kien Truong Quy
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | | | - Duc Nguyen Van
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Van Diem Thi
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Ha Do Manh
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Kien Nguyen Trung
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Quyet Do
- Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Tien Tran Viet
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Binh Do Nhu
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Toan Pham Quoc
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Mao Can Van
- Vietnam Military Medical University, Ha Noi, Viet Nam
| | - Thang Le Viet
- Military Hospital 103, Ha Noi, Viet Nam; Vietnam Military Medical University, Ha Noi, Viet Nam.
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Jahromi M, Al-Otaibi T, Ashry Gheith O, Farouk Othman N, Mahmoud T, Nair P, A-Halim M, Aggarwal P, Messenger G, Chu P, De Serres SA, Azzi JR. Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant. Sci Rep 2021; 11:6014. [PMID: 33727573 PMCID: PMC7966742 DOI: 10.1038/s41598-021-84400-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 01/13/2021] [Indexed: 12/03/2022] Open
Abstract
New Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet β-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (- 174)C, macrophage mediator; IL-4 C (- 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF β1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (- 174) C, IL-4 C (- 590) T, interferon-γ T (+ 874) A gene and transforming growth factor β1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.
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Affiliation(s)
- Mohamed Jahromi
- Clinical Research, Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait.
- Sehatek Awal, Manama, Bahrain.
| | - Torki Al-Otaibi
- Nephrology Department, Hamad Al-Essa Organ Transplantation Center, Kuwait City, Kuwait
| | - Osama Ashry Gheith
- Nephrology Department, Hamad Al-Essa Organ Transplantation Center, Kuwait City, Kuwait
- Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | - Nashwa Farouk Othman
- Community department, Faculty of Nursing, Manoura University, Mansoura, Egypt
- Education, Clinical Services Division, Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Tarek Mahmoud
- Nephrology Department, Hamad Al-Essa Organ Transplantation Center, Kuwait City, Kuwait
| | - Parasad Nair
- Nephrology Department, Hamad Al-Essa Organ Transplantation Center, Kuwait City, Kuwait
| | - Medhat A-Halim
- Nephrology Department, Hamad Al-Essa Organ Transplantation Center, Kuwait City, Kuwait
| | | | - Grace Messenger
- Podiatry Department, Dasman Diabetes Institute, Kuwait City, Kuwait
| | | | | | - Jamil R Azzi
- Kidney Division, Transplantation Research Center, Harvard Medical School, Brigham and Women's Hospital, Boston, USA
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Xia M, Yang H, Tong X, Xie H, Cui F, Shuang W. Risk factors for new-onset diabetes mellitus after kidney transplantation: A systematic review and meta-analysis. J Diabetes Investig 2021; 12:109-122. [PMID: 32506801 PMCID: PMC7779280 DOI: 10.1111/jdi.13317] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 05/20/2020] [Accepted: 06/02/2020] [Indexed: 12/15/2022] Open
Abstract
AIMS/INTRODUCTION To systematically review the risk factors for new-onset diabetes mellitus after kidney transplantation, and to provide a theoretical basis for the prevention and management of new-onset diabetes mellitus after kidney transplantation. MATERIALS AND METHODS We searched PubMed, Web of Science, Embase, the Cochrane Library databases and other databases for case-control studies related to risk factors for new-onset diabetes mellitus after kidney transplantation published between January 2005 and July 2019. A meta-analysis of data on risk factors for new-onset diabetes mellitus after kidney transplantation from the included studies was carried out. A narrative review of risk factors for new-onset diabetes mellitus after kidney transplantation was also carried out. RESULTS A total of 24 case-control studies were included in the meta-analysis, with a total of 7,140 patients. There were 1,598 patients with new-onset diabetes mellitus after kidney transplantation, and 5,542 patients without new-onset diabetes mellitus after kidney transplantation. The meta-analysis results showed that age, polycystic kidney disease, family history of diabetes, body mass index, acute rejection, tacrolimus use, hepatitis B virus infection, hepatitis C virus infection and hypertension were associated with new-onset diabetes mellitus after kidney transplantation, whereas sex, sirolimus use, cyclosporin A use, steroid use and cytomegalovirus infection were not associated with new-onset diabetes mellitus after kidney transplantation. CONCLUSIONS Older age, body mass index, family history of diabetes, tacrolimus use, history of hypertension, polycystic kidney disease, acute rejection, hepatitis B virus infection and hepatitis C virus infection are risk factors for new-onset diabetes mellitus after kidney transplantation. Therefore, the clinical implications of these factors warrant attention.
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Affiliation(s)
- Mancheng Xia
- First Clinical Medical CollegeShanxi Medical UniversityTaiyuanChina
| | - Haosen Yang
- Kidney Transplantation CenterShanxi Second People’s HospitalTaiyuanChina
| | - Xunan Tong
- Kidney Transplantation CenterShanxi Second People’s HospitalTaiyuanChina
| | - Hongjie Xie
- First Clinical Medical CollegeShanxi Medical UniversityTaiyuanChina
| | - Fan Cui
- First Clinical Medical CollegeShanxi Medical UniversityTaiyuanChina
| | - Weibing Shuang
- Department of UrologyThe First Hospital of Shanxi Medical UniversityTaiyuanChina
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Gomes V, Ferreira F, Guerra J, Bugalho MJ. New-onset diabetes after kidney transplantation: Incidence and associated factors. World J Diabetes 2018; 9:132-137. [PMID: 30079149 PMCID: PMC6068739 DOI: 10.4239/wjd.v9.i7.132] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 05/24/2018] [Accepted: 06/13/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To determine the incidence and associated factors of new-onset diabetes after transplantation (NODAT) in a Portuguese central hospital.
METHODS This single-center retrospective study involved consecutive adult nondiabetic transplant recipients, who had undergone kidney transplantation between January 2012 and March 2016. NODAT was diagnosed according to the criteria of the American Diabetes Association. Data were collected from an institutional database of the Nephrology and Kidney Transplantation Department (Santa Maria Hospital, Lisbon, Portugal) and augmented with data of laboratorial parameters collected from the corresponding patient electronic medical records. Exclusion criteria were preexisting diabetes mellitus, missing information and follow-up period of less than 12 mo. Data on demographic and clinical characteristics as well as anthropometric and laboratorial parameters were also collected. Patients were divided into two groups: With and without NODAT - for statistical comparison.
RESULTS A total of 156 patients received kidney transplant during the study period, 125 of who were included in our analysis. NODAT was identified in 27.2% of the patients (n = 34; 53% female; mean age: 49.5 ± 10.8 years; median follow-up: 36.4 ± 2.5 mo). The incidence in the first year was 24.8%. The median time to diagnosis was 3.68 ± 5.7 mo after transplantation, and 76.5% of the patients developed NODAT in the first 3 mo. In the group that did not develop NODAT (n = 91), 47% were female, with mean age of 46.4 ± 13.5 years and median follow-up of 35.5 ± 1.6 mo. In the NODAT group, the pretransplant fasting plasma glucose (FPG) levels were significantly higher [101 (96.1-105.7) mg/dL vs 92 (91.4-95.8) mg/dL, P = 0.007] and pretransplant impaired fasting glucose (IFG) was significantly more frequent (51.5% vs 27.7%, P = 0.01). Higher pretransplant FPG levels and pretransplant IFG were found to be predictive risk factors for NODAT development [odds ratio (OR): 1.059, P = 0.003; OR: 2.772, P = 0.017, respectively].
CONCLUSION NODAT incidence was high in our renal transplant recipients, particularly in the first 3 mo posttransplant, and higher pretransplant FPG level and IFG were risk factors.
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Affiliation(s)
- Vânia Gomes
- Endocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
| | - Florbela Ferreira
- Endocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
| | - José Guerra
- Nephrology and Kidney Transplantation Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
| | - Maria João Bugalho
- Endocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, Lisbon 1649-035, Portugal
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Dubois-Laforgue D. [Post-transplantation diabetes mellitus in kidney recipients]. Nephrol Ther 2017; 13 Suppl 1:S137-S146. [PMID: 28577736 DOI: 10.1016/j.nephro.2017.01.011] [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: 12/22/2016] [Revised: 01/15/2017] [Accepted: 01/17/2017] [Indexed: 10/19/2022]
Abstract
Post-transplantation diabetes mellitus is defined as diabetes that is diagnosed in grafted patients. It affects 20 to 30 % of kidney transplant recipients, with a high incidence in the first year. The increasing age at transplantation and the rising incidence of obesity may increase its prevalence in the next years. Post-transplantation diabetes mellitus is associated with poor outcomes, such as mortality, cardiovascular events or graft dysfunction. Its occurrence is mainly related to immunosuppressive agents, affecting both insulin secretion and sensibility. Immunosuppressants may be iatrogenic, and as such, induce an early and transient diabetes. They may also precociously determine a permanent diabetes, acting here as a promoting factor in patients proned to the development of type 2 diabetes. Lastly, they may behave, far from transplantation, as an additional risk factor for type 2 diabetes. The screening, management and prognosis of these different subtypes of post-transplantation diabetes mellitus will be different.
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Affiliation(s)
- Danièle Dubois-Laforgue
- Service de diabétologie, hôpital Cochin-Port Royal, 123, boulevard Port-Royal, 75014 Paris, France; Inserm U1016, institut Cochin, 22, rue Méchain, 75014 Paris, France.
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Tarnowski M, Słuczanowska-Głabowska S, Pawlik A, Mazurek-Mochol M, Dembowska E. Genetic factors in pathogenesis of diabetes mellitus after kidney transplantation. Ther Clin Risk Manag 2017; 13:439-446. [PMID: 28435278 PMCID: PMC5388273 DOI: 10.2147/tcrm.s129327] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Posttransplant diabetes mellitus (PTDM) is one of the major metabolic complications after transplantation of solid organs including the kidney. This type of diabetes mellitus affects allograft survival, cardiovascular complications and overall patient survival. The modifiable risk factors that contribute to PTDM include obesity, some viral infections (eg, hepatitis C virus, cytomegalovirus) and especially immunosuppressive drugs including corticosteroids, tacrolimus, cyclosporine and sirolimus. Currently, predisposing genetic factors have been considered important in PTDM development. The commonly evaluated genetic determinants include genes encoding transcription factors, cytokines, chemokines, adipokines, ionic channels, glucose transporters, cytochrome P450 enzymes and other enzymes metabolizing drugs, drug transporters. Unfortunately, the results of studies are inconclusive and differ between populations. There is a need for large genome-wide association study to identify the genetic risk factors associated with PTDM development.
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Affiliation(s)
| | | | | | | | - Elżbieta Dembowska
- Department of Periodontology, Pomeranian Medical University, Szczecin, Poland
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Pharmacogenetics of posttransplant diabetes mellitus. THE PHARMACOGENOMICS JOURNAL 2017; 17:209-221. [DOI: 10.1038/tpj.2017.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 12/04/2016] [Accepted: 01/09/2017] [Indexed: 02/08/2023]
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The incidence of new onset diabetes after transplantation and related factors: Single center experience. Nefrologia 2017; 37:181-188. [PMID: 28262264 DOI: 10.1016/j.nefro.2016.11.022] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Revised: 10/27/2016] [Accepted: 11/17/2016] [Indexed: 12/17/2022] Open
Abstract
AIM New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication and is considered a risk factor for patients undergoing renal transplant. The aim of this study was to evaluate the incidence and developing duration of new-onset diabetes after transplant (NODAT) and influencing factors. METHODS All patients' data was investigated retrospectively. Diabetics, follow-up period<6 months, age<18years were excluded. Demographic, clinical and laboratory data was recorded. Patients were divided into two groups: with/without NODAT. NODAT group was divided into four subgroups according to the time of developing NODAT, which were 0-3, 3-6, 6-12 and 12 months later. Two groups were compared, to investigate the incidence of NODAT and risk factors associated with the occurrence of NODAT. RESULTS We retrospectively analyzed the records of 570 patients, of which 420 patients were included. Seventy (16.6%) patients had NODAT (36 female, mean age 51.7±8.2 years, mean follow-up 41.6±21.5 months), 52.8% of patients developed NODAT within the first three months of being diagnosed. 350 patients (116 female, mean age 43.2±12.5 years, mean follow-up 41.6±21.5 months) were without NODAT. The incidence of impaired fasting glucose (IFG) during the first week after transplant was found to be higher in the patients with NODAT (p<0.001). There was positive correlation between NODAT and older age, obesity, family history of diabetes, presence of IFG, fasting plasma glucose, total and LDL-cholesterol, triglycerides, parathormone. Old age, obesity, presence of IFG, pretransplant hypertriglyceridemia and hyperparathyroidism were predictors of development of NODAT. CONCLUSION Incidence of NODAT, especially the first six months, was high. All patients should be screened for IFG within the first week. Patients with dyslipidemia, elderly and obese patients should be closely monitored for the risk of development of NODAT.
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Han E, Kim MS, Kim YS, Kang ES. Risk assessment and management of post-transplant diabetes mellitus. Metabolism 2016; 65:1559-69. [PMID: 27621191 DOI: 10.1016/j.metabol.2016.07.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 07/13/2016] [Accepted: 07/21/2016] [Indexed: 02/06/2023]
Abstract
The success rate of organ transplantation has been increasing with advances in surgical and pharmacological techniques. However, the number of solid organ transplant recipients who require metabolic disease management is also growing. Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation and is associated with risks of graft loss, cardiovascular morbidity, and mortality. Other risk factors for PTDM include older age, genetic background, obesity, hepatitis C virus infection, hypomagnesemia, and use of immunosuppressant agents (corticosteroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitor). Management of PTDM should be started before the transplantation plan to properly screen high-risk patients. Even though PTDM management is similar to that of general type 2 diabetes, therapeutic approaches must be made with consideration of drug interactions between immunosuppressive agents, glucose-lowering medications, and graft rejection and function.
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Affiliation(s)
- Eugene Han
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center
| | - Myoung Soo Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Yu Seun Kim
- Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea
| | - Eun Seok Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Hospital Diabetes Center; Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Benson KA, Maxwell AP, McKnight AJ. A HuGE Review and Meta-Analyses of Genetic Associations in New Onset Diabetes after Kidney Transplantation. PLoS One 2016; 11:e0147323. [PMID: 26789123 PMCID: PMC4720424 DOI: 10.1371/journal.pone.0147323] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 12/31/2015] [Indexed: 12/11/2022] Open
Abstract
PURPOSE New onset diabetes after transplantation (NODAT) is a serious complication following solid organ transplantation. There is a genetic contribution to NODAT and we have conducted comprehensive meta-analysis of available genetic data in kidney transplant populations. METHODS Relevant articles investigating the association between genetic markers and NODAT were identified by searching PubMed, Web of Science and Google Scholar. SNPs described in a minimum of three studies were included for analysis using a random effects model. The association between identified variants and NODAT was calculated at the per-study level to generate overall significance values and effect sizes. RESULTS Searching the literature returned 4,147 citations. Within the 36 eligible articles identified, 18 genetic variants from 12 genes were considered for analysis. Of these, three were significantly associated with NODAT by meta-analysis at the 5% level of significance; CDKAL1 rs10946398 p = 0.006 OR = 1.43, 95% CI = 1.11-1.85 (n = 696 individuals), KCNQ1 rs2237892 p = 0.007 OR = 1.43, 95% CI = 1.10-1.86 (n = 1,270 individuals), and TCF7L2 rs7903146 p = 0.01 OR = 1.41, 95% CI = 1.07-1.85 (n = 2,967 individuals). CONCLUSION Evaluating cumulative evidence for SNPs associated with NODAT in kidney transplant recipients has revealed three SNPs associated with NODAT. An adequately powered, dense genome-wide association study will provide more information using a carefully defined NODAT phenotype.
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Affiliation(s)
| | - Alexander Peter Maxwell
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
- Regional Nephrology Unit, Belfast City Hospital, Belfast, United Kingdom
| | - Amy Jayne McKnight
- Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom
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Khan IIA, Jahan P, Hasan Q, Rao P. Validation of the association of TCF7L2 and SLC30A8 gene polymorphisms with post-transplant diabetes mellitus in Asian Indian population. Intractable Rare Dis Res 2015; 4:87-92. [PMID: 25984427 PMCID: PMC4428192 DOI: 10.5582/irdr.2015.01008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Revised: 04/11/2015] [Accepted: 04/16/2015] [Indexed: 12/17/2022] Open
Abstract
The rs7903146 and rs13266634 polymorphisms in the TCF7L2 and SLC30A8 genes, respectively, have been reported to be associated with type 2 diabetes. However, little is known about the association of these polymorphisms with post-transplant diabetes mellitus (PTDM). To study this linkage, we determined a distribution of allele and genotype frequencies in Asian Indians. 42 PTDM and 98 non-PTDM subjects were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect for rs7903146 and rs13266634 polymorphisms. The clinical details and statistical analysis for PTDM and non-PTDM subjects were recorded. Our results observed higher frequencies of the minor alleles in rs7903146 and rs13266634 polymorphisms in the PTDM group compared to the non-PTDM subjects. The allele frequencies also found to be significantly associated with PTDM (rs7903146: T vs C: OR-2.6; (95%CI: 1.2-5.6); p = 0.01; rs13266634: T vs C: OR-2.0; (95%CI: 1.1-3.4); p = 0.01). These findings suggest that rs7903146 and rs13266634 polymorphisms are associated with PTDM in the Asian Indian population despite a relatively small study group.
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Affiliation(s)
- IImran Ali Khan
- Department of Genetics and Molecular medicine, Kamineni Hospitals, Hyderabad, India
- Department of Genetics, Vasavi Medical and Research Centre, Khairathabad, Hyderabad, India
- Department of Genetics and Biotechnology, Osmania University, Tarnaka, Hyderabad, India
| | - Parveen Jahan
- Department of Genetics and Biotechnology, Osmania University, Tarnaka, Hyderabad, India
| | - Qurratulain Hasan
- Department of Genetics and Molecular medicine, Kamineni Hospitals, Hyderabad, India
- Department of Genetics, Vasavi Medical and Research Centre, Khairathabad, Hyderabad, India
| | - Pragna Rao
- Department of Biochemistry, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
- Address correspondence to: Dr. Pragna Rao, Department of Biochemistry, Kasturba Medical College, Manipal University, SH 65, Madhav Nagar, Manipal, Karnataka 576104, India. E-mail:
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Ivarsson KM, Clyne N, Almquist M, Akaberi S. Hyperparathyroidism and new onset diabetes after renal transplantation. Transplant Proc 2015; 46:145-50. [PMID: 24507041 DOI: 10.1016/j.transproceed.2013.07.076] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Accepted: 07/30/2013] [Indexed: 12/23/2022]
Abstract
BACKGROUND Secondary hyperparathyroidism persists after renal transplantation in a substantial number of patients. Primary hyperparathyroidism and secondary hyperparathyroidism are both associated with abnormalities in glucose metabolism, such as insufficient insulin release and glucose intolerance. The association of hyperparathyroidism and diabetes after renal transplantation has, as far as we know, not been studied. Our aim was to investigate whether hyperparathyroidism is associated with new-onset diabetes mellitus after transplantation (NODAT) during the first year posttransplantation. STUDY DESIGN In a retrospective study, we analyzed data on patient characteristics, treatment details, and parathyroid hormone (PTH) in 245 adult nondiabetic patients who underwent renal transplantation between January 2000 and June 2011. RESULTS The first year cumulative incidence of NODAT was 15%. The first serum PTH value after transplantation was above normal range in 74% of the patients. In multiple logistic regression analysis, PTH levels above twice normal range (>13.80 pmol/L) were significantly associated with NODAT (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.13-15.92; P = .03) compared with PTH within normal range (≤6.9 pmol/L). Age between 45 and 65 years (OR, 2.80; 95% CI, 1.07-7.36; P = .04) compared with age <45 years was also associated with NODAT. CONCLUSION We found a strong association between hyperparathyroidism and NODAT in the first year after renal transplantation. Both conditions are common and have a negative impact on graft and patient survivals. Our results should be confirmed in prospective studies.
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Affiliation(s)
- K M Ivarsson
- Department of Nephrology, Clinical Sciences Lund, Lund University, Lund, Sweden
| | - N Clyne
- Department of Nephrology, Clinical Sciences Lund, Lund University, Lund, Sweden
| | - M Almquist
- Department of Surgery, Clinical Sciences Lund, Lund University, Lund, Sweden
| | - S Akaberi
- Department of Nephrology, Clinical Sciences Lund, Lund University, Lund, Sweden.
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Musavi Z, Azarpira N, Sangtarash MH, Kordi M, Kazemi K, Geramizadeh B, Malek-Hosseini SA. Polymorphism of Transcription Factor-7-Like 2 (TCF7L2) Gene and New-Onset Diabetes after Liver Transplantation. Int J Organ Transplant Med 2015; 6:14-22. [PMID: 25737773 PMCID: PMC4346459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication in transplant recipients. Transcription factor-7-like 2 (TCF7L2) is a Wnt signaling-associated transcription factor that plays an important role in β-cell proliferation and insulin secretion. The association between TCF7L2 SNP rs7903146 and NODAT was documented in renal transplant patients. OBJECTIVE To determine the association between TCF7L2 rs7903146 variants and the risk of NODAT after liver transplantation. METHODS This study was conducted on 140 liver transplant recipients who had received tacrolimus-based immunosuppressive drugs. The patients were divided into NODAT (n=70) and non-NODAT (n=70) groups and were genotyped using PCR-RFLP. In addition, 100 normal subjects were considered as the comparison group. RESULTS There was a significant difference (p<0.05) between the two study groups regarding donor and recipient age, recipient body mass index, and recipient fasting plasma glucose before the transplantation. No significant relationship was observed between TCF7L2 rs7903146 genotypes and development of NODAT. No significant difference was also found between the two groups in terms of the tacrolimus and mycophenolate mofetil daily dosage as well as tacrolimus blood level. However, the prednisolone daily dosage was significantly (p=0.01) higher in the NODAT group compared to those without NODAT. The majority of the patients in the NODAT group also had an episode of acute rejection. Furthermore, a significant difference was found between the transplant recipients and the comparison subjects regarding T allele (p<0.001, OR=1.96) and TT genotype (p<0.001, OR=3.47) frequencies. CONCLUSION No correlation was found between TCF7L2 genotypes and development of NODAT. Acute rejection and prednisolone pulse therapy predisposed the susceptible patients to NODAT.
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Affiliation(s)
- Z. Musavi
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Genetic, Sistan and Baluchestan University of Sciences, Zahedan, Iran
| | - N. Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - M. H. Sangtarash
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Genetic, Sistan and Baluchestan University of Sciences, Zahedan, Iran
| | - M. Kordi
- Department of Genetic, Sistan and Baluchestan University of Sciences, Zahedan, Iran
| | - K. Kazemi
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - B. Geramizadeh
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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New onset of diabetes after transplantation - an overview of epidemiology, mechanism of development and diagnosis. Transpl Immunol 2013; 30:52-8. [PMID: 24184293 DOI: 10.1016/j.trim.2013.10.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 10/21/2013] [Accepted: 10/21/2013] [Indexed: 12/12/2022]
Abstract
New onset of diabetes after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported to occur in 2% to 53% of renal transplant recipients. Several risk factors are associated with NODAT, however the mechanisms underlying were unclear. Renal transplant recipients who develop NODAT are reported to be at increased risk of infections, cardiovascular events, graft loss and patient loss. It has been reported that the incidence of NODAT is high in the early transplant period due to the exposure to the high doses of corticosteroids, calcineurin inhibitors and the physical inactivity during that period. In addition to these risk factors the traditional risk factors also play a major role in developing NODAT. Early detection is crucial in the management and control of NODAT which can be achieved through pretransplant screening there by identifying high risk patients and implementing the measures to reduce the development of NODAT. In the present article we reviewed the literature on the epidemiology, risk factors, mechanisms involved and the diagnostic criteria in the development of NODAT. Development of diagnostic tools for the assessment of β-cell function and determination of the role of glycemic control would include future area of research.
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Chakkera HA, Weil EJ, Pham PT, Pomeroy J, Knowler WC. Can new-onset diabetes after kidney transplant be prevented? Diabetes Care 2013; 36:1406-12. [PMID: 23613600 PMCID: PMC3631828 DOI: 10.2337/dc12-2067] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Because the negative consequences of new-onset diabetes mellitus after transplantation (NODAT) diminish the significant gains of kidney transplantation, it is imperative to develop clinical interventions to reduce the incidence of NODAT. In this review, we discuss whether intensive lifestyle interventions that delay or prevent type 2 diabetes mellitus may decrease the incidence of NODAT. We examine the literature pertaining to incidence and timing of onset of NODAT, as well as the risk factors and pathophysiology that NODAT shares with type 2 diabetes mellitus, namely pathways related to increased insulin resistance and decreased insulin secretion. Our central hypothesis is that NODAT results from the same metabolic risk factors that underlie type 2 diabetes mellitus. These risk factors are altered and enhanced by transplantation, "tipping" some transplant recipients with seemingly normal glucose homeostasis before transplant toward the development of NODAT. We describe the diabetogenic properties of transplant immunosuppressive drugs. We describe novel methods of prevention that are being explored, including resting the pancreatic β-cells by administration of basal insulin during the period immediately after transplant. On the basis of the current evidence, we propose that intensive lifestyle modification, adapted for individuals with chronic kidney disease or end-stage renal disease, as well as resting pancreatic β-cells during the immediate postoperative period, may lower the incidence of NODAT.
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Phillips S, Heuberger R. Metabolic Disorders Following Kidney Transplantation. J Ren Nutr 2012; 22:451-60.e1. [DOI: 10.1053/j.jrn.2012.01.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2011] [Revised: 01/05/2012] [Accepted: 01/14/2012] [Indexed: 11/11/2022] Open
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Dong M, Parsaik AK, Eberhardt NL, Basu A, Cosio FG, Kudva YC. Cellular and physiological mechanisms of new-onset diabetes mellitus after solid organ transplantation. Diabet Med 2012; 29:e1-12. [PMID: 22364599 DOI: 10.1111/j.1464-5491.2012.03617.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
New-onset diabetes after transplantation is recognized as one of the metabolic consequences which may increase the risk of morbidity and mortality after solid organ transplantation. The pathophysiology of new-onset diabetes after transplantation has not been clearly defined and may resemble that of Type 2 diabetes, characterized by predominantly insulin resistance or defective insulin secretion, or both. This review aims to summarize the current state of knowledge regarding the prevalence, consequences, pathogenesis, and management of new-onset diabetes after transplantation, with a major focus on the possible mechanisms involved in the pathogenesis of the disorder. The aetiology of new-onset diabetes after transplantation is multifactorial, with diabetogenic immunosuppressive drugs playing a major role. Multiple cellular and physiologic mechanisms are involved in the process. Selection of an appropriate maintenance immunosuppressive regimen should involve balancing the risk of patient and graft survival vs. the potential for new-onset diabetes after transplantation.
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Affiliation(s)
- M Dong
- Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55902, USA
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Ghisdal L, Van Laecke S, Abramowicz MJ, Vanholder R, Abramowicz D. New-onset diabetes after renal transplantation: risk assessment and management. Diabetes Care 2012; 35:181-8. [PMID: 22187441 PMCID: PMC3241330 DOI: 10.2337/dc11-1230] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Lidia Ghisdal
- Renal Transplantation Clinic, Erasme Hospital, University of Brussels (ULB), Brussels, Belgium.
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Kurzawski M, Dziewanowski K, Kędzierska K, Wajda A, Lapczuk J, Droździk M. Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus. Pharmacol Rep 2011; 63:826-33. [PMID: 21857094 DOI: 10.1016/s1734-1140(11)70595-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Revised: 11/29/2010] [Indexed: 10/25/2022]
Abstract
New onset posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus. PTDM can adversely affect patient and graft survival. The pathophysiology of PTDM closely mimics type 2 diabetes mellitus (T2DM). One of the possible genetic factors predisposing individuals to PTDM might be a polymorphism in the transcription factor 7-like 2 gene (TCF7L2). This polymorphism has previously been associated with increased risk of T2DM in the general population. Therefore, the present study aimed to evaluate TCF7L2 polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. Non-diabetic kidney transplant patients medicated with tacrolimus (n = 234) were genotyped for the presence of TCF7L2 gene variants (rs12255372 and rs7903146) using TaqMan probes. Of the 234 patients, 66 patients had developed PTDM and 168 had not. Frequencies of the studied single nucleotide polymorphisms (SNPs) did not differ significantly between the study groups. Moreover, haplotype analyses failed to detect any associations between TCF7L2 haplotypes and PTDM. However, in late-onset PTDM (developed later that 2 weeks from transplantation), frequencies of the rs7903146 TT genotype and T minor allele were significantly increased compared to non-PTDM controls (17.9% vs. 5.9%, p = 0.017, OR: 4.13, 95% CI: 1.19-14.33 for TT genotype, 39.3% vs. 25.9%, p = 0.038 for T allele). If the application of TCF7L2 rs7903146 SNPs as a marker for PTDM is confirmed by further independent studies, replacing tacrolimus with other immunosuppressants could be warranted in patients at high risk of PTDM, as diagnosed by TCF7L2 genotyping.
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Affiliation(s)
- Mateusz Kurzawski
- Department of Pharmacology, Pomeranian Medical University, Powstańców Wlkp. 72, PL 70-111 Szczecin, Poland
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Hadj Ali I, Adberrahim E, Ben Abdelghani K, Barbouch S, Mchirgui N, Khiari K, Chérif M, Ounissi M, Ben Romhane N, Ben Abdallah N, Ben Abdallah T, Ben Maiz H, Khedher A. Incidence and Risk Factors for Post–Renal Transplant Diabetes Mellitus. Transplant Proc 2011; 43:568-71. [DOI: 10.1016/j.transproceed.2011.01.032] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Räkel A, Karelis AD. New-onset diabetes after transplantation: risk factors and clinical impact. DIABETES & METABOLISM 2011; 37:1-14. [PMID: 21295510 DOI: 10.1016/j.diabet.2010.09.003] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2010] [Revised: 09/17/2010] [Accepted: 09/21/2010] [Indexed: 02/06/2023]
Abstract
With improvements in patient and graft survival, increasing attention has been placed on complications that contribute to long-term patient morbidity and mortality. New-onset diabetes after transplantation (NODAT) is a common complication of solid-organ transplantation, and is a strong predictor of graft failure and cardiovascular mortality in the transplant population. Risk factors for NODAT in transplant recipients are similar to those in non-transplant patients, but transplant-specific risk factors such as hepatitis C (HCV) infection, corticosteroids and calcineurin inhibitors play a dominant role in NODAT pathogenesis. Management of NODAT is similar to type 2 diabetes management in the general population. However, adjusting the immunosuppressant regimen to improve glucose tolerance must be weighed against the risk of allograft rejection. Lifestyle modification is currently the strategy with the least risk and the most benefit.
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Affiliation(s)
- A Räkel
- Department of Medicine, hôpital Saint-Luc, centre de recherche, centre hospitalier, University of Montreal, René-Lévesque-Est, Québec, Canada.
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