{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:47:55Z","timestamp":1792626475083,"version":"4.5.0"},"reference-count":125,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Post-transplant diabetes mellitus (PTDM) affects 7\u201339% of kidney transplant recipients and substantially worsens cardiovascular, infectious, and allograft outcomes. Although PTDM shares core pathophysiological features with type 2 diabetes\u2014peripheral insulin resistance and impaired \u03b2-cell secretion\u2014its etiology is fundamentally shaped by immunosuppressive therapy. Calcineurin inhibitors suppress insulin gene transcription via NFAT inhibition and exacerbate lipotoxicity; corticosteroids drive hepatic gluconeogenesis and impair GLUT4-mediated glucose uptake; and mTOR inhibitors reduce \u03b2-cell mass through mTORC1-dependent mechanisms. Chronic NF-\u03baB\/JNK-driven inflammation further amplifies insulin resistance and promotes \u03b2-cell apoptosis. Beyond these established mechanisms, we propose a unifying \u201cgut\u2013immune\u2013metabolic axis\u201d in which immunosuppression-induced gut microbiota dysbiosis\u2014characterized by depletion of short-chain fatty acid-producing taxa (Roseburia, Faecalibacterium prausnitzii) and Akkermansia muciniphila\u2014drives intestinal barrier dysfunction, endotoxemia, impaired FXR\/TGR5-mediated GLP-1 secretion, and TMAO-associated metabolic inflammation, collectively perpetuating glucose dysregulation. Risk stratification integrates non-modifiable factors (advanced age, African American\/Hispanic\/South Asian ethnicity, TCF7L2 polymorphisms, autosomal dominant polycystic kidney disease) with modifiable determinants (pre-transplant dysglycemia, obesity, hypomagnesemia, hepatitis C and cytomegalovirus infections, acute rejection, and diuretic use). Diagnosis requires OGTT-centered assessment per the 2024 International Consensus guidelines, with cautious interpretation of HbA1c during the early post-transplant period. Management encompasses personalized immunosuppression (corticosteroid minimization, tacrolimus trough levels &amp;lt;10 ng\/mL, and belatacept-based regimens in high-risk patients), structured lifestyle interventions, and emerging pharmacotherapies\u2014particularly SGLT2 inhibitors and GLP-1 receptor agonists\u2014which offer cardiometabolic benefits beyond glycemic control. Microbiome-targeted strategies, including prebiotics, probiotics, and fecal microbiota transplantation, represent a conceptually compelling frontier warranting prospective investigation. This framework reframes PTDM as a multi-hit, immunometabolic syndrome and provides a translational roadmap toward precision prevention and improved long-term transplant outcomes.<\/jats:p>","DOI":"10.3389\/fendo.2026.1829579","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:10:17Z","timestamp":1777425017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Post-transplant diabetes mellitus after kidney transplantation: pathogenesis, risk factors, and management strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianhua","family":"Long","sequence":"first","affiliation":[{"name":"Department of Urology, Chunlei Huang Chuiyangliu Hospital Affiliated to Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, Chunlei Huang Chuiyangliu Hospital Affiliated to Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianen","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Urology, Chunlei Huang Chuiyangliu Hospital Affiliated to Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, Chunlei Huang Chuiyangliu Hospital Affiliated to Tsinghua University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina57030250","article-title":"New-onset diabetes after kidney transplantation","volume":"57","author":"Ponticelli","year":"2021","journal-title":"Med (Kaunas)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000495081","article-title":"Trends in the causes of death among kidney transplant recipients in the United States (1996-2014)","volume":"48","author":"Awan","year":"2018","journal-title":"Am J Nephrol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-1230","article-title":"New-onset diabetes after renal transplantation: risk assessment and management","volume":"35","author":"Ghisdal","year":"2012","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0004042021","article-title":"New onset diabetes mellitus after transplant: The challenge continues","volume":"2","author":"Aziz","year":"2021","journal-title":"Kidney360"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/db18-1267","article-title":"HDL cholesterol efflux predicts incident new-onset diabetes after transplantation (NODAT) in renal transplant recipients independent of HDL cholesterol levels","volume":"68","author":"Szili-Torok","year":"2019","journal-title":"Diabetes"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.09310819","article-title":"Metabolic disorders with kidney transplant","volume":"15","author":"Cohen","year":"2020","journal-title":"Clin J Am Soc Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.059002732.x","article-title":"Post-transplant diabetes mellitus: increasing incidence in renal allograft recipients transplanted in recent years","volume":"59","author":"Cosio","year":"2001","journal-title":"Kidney Int"},{"key":"B8","doi-asserted-by":"publisher","first-page":"SS3","DOI":"10.1097\/01.TP.0000069952.49242.3E","article-title":"New-onset diabetes after transplantation: 2003 International consensus guidelines. 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