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Impact of immunosuppression on incidence of post-transplant diabetes mellitus in solid organ transplant recipients:Systematic review and meta-analysis

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World Journal of transplantation 2021年第10期11卷 432-442页

作者： Sreelakshmi Kotha Bishoy Lawendy Saira Asim Charlene Gomes Jeffrey Yu Ani Orchanian-Cheff George Tomlinson Mamatha Bhat Department of Gastroenterology Guy's and St Thomas'HospitalLondon SE17JDUnited Kingdom Department of Multi-Organ transplantation Toronto General HospitalToronto M5G 2C4Canada Multi Organ transplant Program Toronto General HospitalToronto M5G 2C4Canada Dalla Lana School of Public Health Department of MedicineUniversity Health Network-Toronto General HospitalUniversity of TorontoToronto M5G 2C4Canada Multi-organ transplant Toronto General HospitalToronto M5G 2C4Canada

BACKGROUND Solid organ transplantation is a life-saving intervention for end-stage organ disease.post-transplant diabetes mellitus(PTDM)is a common complication in solid organ transplant recipients,and significantly compromises long-term survival beyond a year.AIM To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM.METHODS Two hundred and six eligible studies identified 75595 patients on Tacrolimus,51242 on Cyclosporine and 3020 on Sirolimus.Random effects meta-analyses was used to calculate incidence.RESULTS Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus(OR=1.495%CI:1.0–2.0)and sirolimus(OR=1.8;95%CI:1.5–2.2)than with Cyclosporine.The overall incidence of PTDM at years 2-3 was 17%for kidney,19%for liver and 22%for heart.The risk factors for PTDM most frequently identified in the primary studies were age,body mass index,hepatitis C,and African American descent.CONCLUSION Tacrolimus tends to exhibit higher diabetogenicity in the short-term(2-3 years post-transplant),whereas sirolimus exhibits higher diabetogenicity in the longterm(5-10 years post-transplant).This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.

关键词： post-transplant diabetes mellitus solid organ transplantation Tacrolimus Cyclosporin Sirolimus

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Sodium-glucose cotransporter-2 inhibitor use in kidney transplant recipients

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World Journal of transplantation 2023年第5期13卷 239-249页

作者： Pavithra Ramakrishnan Neetika Garg Samantha Pabich Didier A Mandelbrot Kurtis J Swanson Department of Medicine University of MinnesotaMinneapolisMN 55455United States Department of Medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States

Sodium-glucose cotransporter-2 inhibitors(SGLT2i)are novel oral hypoglycemic agents garnering much attention for their substantial benefits.These recent data have positioned SGLT2i at the forefront of diabetic chronic kidney disease(CKD)and heart failure management.SGLT2i use post-kidney transplant is an emerging area of research.Highlights from this mini review include the following:Empagliflozin is the most prescribed SGLT2i in kidney transplant recipients(KTRs),median time from transplant to initiation was 3 years(range:0.88-9.6 years).Median baseline estimated glomerular filtration rate(eGFR)was 66.7 mL/min/1.73 m2(range:50.4-75.8).Median glycohemoglobin(HgbA1c)at initiation was 7.7%(range:6.9-9.3).SGLT2i were demonstrated to be effective short-term impacting HgbA1c,eGFR,hemoglobin/hematocrit,serum uric acid,and serum magnesium levels.They are shown to be safe in KTRs with low rates of infections,hypoglycemia,euglycemic diabetic ketoacidosis,and stable tacrolimus levels.More data is needed to demonstrate long-term outcomes.SGLT2i appear to be safe,effective medications for select KTRs.Our present literature,though limited,is founded on precedent robust research in CKD patients with diabetes.Concurrent research/utilization of SGLT2i is vital to not only identify long-term patient,graft and cardiovascular outcomes of these agents,but also to augment management in KTRs.

关键词： Sodium glucose cotransporter-2 Sodium glucose cotransporter-2 inhibitor Kidney transplantation diabetes post-transplant diabetes mellitus New onset diabetes after transplant

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肝脏移植术后糖尿病患者肠道微生物组的变化

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Engineering 2023年第12期31卷 98-111页

作者： Qi Ling Yuqiu Han Yue Ma Xiaosen Wang Zheng Zhu Jingyu Wang Jiaying Cao Lin Xiaohan Jun Wang Baohong Wang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China Department of Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Lab of Combined Multi-Organ transplantation Ministry of Public HealthHangzhou 310003China CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Shandong First Medical University&Shandong Academy of Medical Sciences Jinan 250117China Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China

post-transplant diabetes mellitus(PTDM)increases the risk of graft failure and death in liver transplant(LT)recipients.Experimental studies have indicated that enteric dysbiosis mediated by immunosuppressive tacrolimus(TAC)could contribute to glucose disorders,but no data on human recipients with PTDM have been reported.Here,by combining high-throughput shotgun metagenomics sequencing and metabolomics profiling,we characterized the intestinal microbiome(IM)in LT recipient cohort with or without PTDM and deciphered the potential relationship among IM,TAC dosage,and diabetes.By comparing with both non-PTDM and classical type 2 diabetes mellitus(T2DM),we identified microbial signatures of PTDM,which was characterized by the enriched Proteobacteria and decreased Bacteroidetes.Additionally,the altered microbes,as well as the microbial metabolomics,correlated with the dosage of TAC.Specifically,the levels of beneficial microbes associated with PTDM were lowered in recipients with the high TAC trough concentrations(>5 ng·mL^(-1))than those with low ones(<5 ng·mL^(-1)),which was accompanied by reduced faecal metabolites involved in the biosynthesis of a-linolenic acid and arachidonic acid-lowering factors of developing T2DM.Moreover,these microbial signatures linked with the extent of glucose disorders in LT recipients.In summary,the faecal microbiome and metabolome differed between PTDM and non-PTDM patients,which were linked with TAC dosage.This study was the first to explore taxonomic alterations and bacterial gene functions to better understand the contribution of the IM to PTDM.

关键词： post-transplant diabetes mellitus Tacrolimus Metagenomics Metabolomics

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Recent advances in new-onset diabetes mellitus after kidney transplantation

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World Journal of diabetes 2021年第5期12卷 541-555页

作者： Tess Montada-Atin G V Ramesh Prasad Kidney transplant Program St.Michael's HospitalToronto M5C 2T2OntarioCanada Department of Medicine University of TorontoToronto M5C 2T2Canada

A common challenge in managing kidney transplant recipients(KTR)is posttransplant diabetes mellitus(PTDM)or diabetes mellitus(DM)newly diagnosed after transplantation,in addition to known pre-existing DM.PTDM is an important risk factor for post-transplant cardiovascular(CV)disease,which adversely affects patient survival and quality of life.CV disease in KTR may manifest as ischemic heart disease,heart failure,and/or left ventricular hypertrophy.Available therapies for PTDM include most agents currently used to treat type 2 diabetes.More recently,the use of sodium glucose co-transporter 2 inhibitors(SGLT2i),glucagon-like peptide-1 receptor agonists(GLP-1 RA),and dipeptidyl peptidase 4 inhibitors(DPP4i)has cautiously extended to KTR with PTDM,even though KTR are typically excluded from large general population clinical trials.Initial evidence from observational studies seems to indicate that SGLT2i,GLP-1 RA,and DPP4i may be safe and effective for glycemic control in KTR,but their benefit in reducing CV events in this otherwise high-risk population remains unproven.These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status,pre-existing burden of peripheral vascular disease,urinary tract infections due to immunosuppression and a surgically altered urinary tract,erythrocytosis from calcineurin inhibitors,and reduced kidney function from acute or chronic rejection.

关键词： Cardiovascular disease Glucagon-like peptide-1 receptor agonists Kidney transplantation Oral antihyperglycemic drugs post-transplant diabetes mellitus Sodium glucose co-transporter 2 inhibitors Dipeptidyl peptidase-4 inhibitors

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Chances and risks of sodium-glucose cotransporter 2 inhibitors in solid organ transplantation:A review of literatures

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World Journal of transplantation 2021年第7期11卷 254-262页

作者： Marlene Schwarzenbach Flavia Elena Bernhard Cecilia Czerlau Daniel Sidler Department of Nephrology and Hypertension University Hospital Insel BernBern 3010Switzerland

Solid organ transplantation offers life-saving treatment for patients with endorgan dysfunction.Patient survival and quality of life have improved over the past few decades as a result of pharmacological development,expansion of the donor pool,technological advances and standardization of practices related to transplantation.Still,transplantation is associated with cardiovascular complications,of which post-transplant diabetes mellitus(PTDM)is one of the most important.PTDM increases mortality,which is best documented in patients who have received kidney and heart transplants.PTDM results from traditional risk factors seen in patients with type 2 diabetes mellitus,but also from specific posttransplant risk factors such as metabolic side effects of immunosuppressive drugs,post-transplant viral infections and hypomagnesemia.Oral hypoglycaemic agents are the first choice for the treatment of type 2 diabetes mellitus in non-transplanted patients.However,the evidence on the safety and efficacy of oral hypoglycaemic agents in transplant recipients is limited.The favourable risk/benefit ratio,which is suggested by large-scale and long-term studies on new glucoselowering drug classes such as glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors,makes studies warranted to assess the potential role of these agents in the management of PTDM.

关键词： Solid organ transplantation post-transplant diabetes mellitus Antidiabetic treatment Sodium-glucose cotransporter 2 inhibitors Renoprotection

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