7.0.0.0 POST­TRANS­PLAN­TA­TION DI­A­BETES MEL­LI­TUS

Rec­om­men­da­tions

2.23 Pa­tients should be screened after organ trans­plan­ta­tion for hy­per­glycemia, with a for­mal di­ag­no­sis of posttrans­plan­ta­tion di­a­betes mel­li­tus being best made once a pa­tient is sta­ble on an im­muno­sup­pres­sive reg­i­men and in the ab­sence of an acute in­fec­tion. E

2.24 The oral glu­cose tol­er­ance test is the pre­ferred test to make a di­ag­no­sis of posttrans­plan­ta­tion di­a­betes mel­li­tus. B

2.25 Im­muno­sup­pres­sive reg­i­mens shown to pro­vide the best out­comes for pa­tient and graft sur­vival should be used, irre­spective of posttrans­plan­ta­tion di­a­betes mel­li­tus risk. E

Sev­er­al terms are used in the lit­er­a­ture to de­scribe the pres­ence of di­a­betes fol­low­ing organ trans­plan­ta­tion. “New-‍onset di­a­betes after trans­plan­ta­tion” (NODAT) is one such des­ig­na­tion that de­scribes in­di­vid­u­als who de­vel­op new-‍onset di­a­betes fol­low­ing trans­plant. NODAT ex­cludes pa­tients with pretrans­plant di­a­betes that was undi­ag­nosed as well as posttrans­plant hy­per­glycemia that re­solves by the time of dis­charge (103). An­oth­er term, “posttrans­plan­ta­tion di­a­betes mel­li­tus” (PTDM) (103,104), de­scribes the pres­ence of di­a­betes in the posttrans­plant set­ting irre­spective of the tim­ing of di­a­betes onset.

Hy­per­glycemia is very com­mon dur­ing the early posttrans­plant pe­ri­od, with ˜90% of kid­ney al­lo­graft re­cip­i­ents ex­hib­iting hy­per­glycemia in the first few weeks fol­low­ing trans­plant (103-106). In most cases, such stress-‍ or steroidin­duced hy­per­glycemia re­solves by the time of dis­charge (106,107). Al­though the use of im­muno­sup­pres­sive ther­a­pies is a major con­trib­u­tor to the de­vel­op­ment of PTDM, the risks of trans­plant re­jec­tion out­weigh the risks of PTDM and the role of the di­a­betes care pro­vider is to treat hy­per­glycemia ap­pro­pri­ately re­gard­less of the type of im­muno­sup­pres­sion (103). Risk fac­tors for PTDM in­clude both gen­er­al di­a­betes risks (such as age, fam­i­ly his­to­ry of di­a­betes, etc.) as well as trans­plant-‍specific fac­tors, such as use of im­muno­sup­pres­sant agents (108). Whe­re­as posttrans­plan­ta­tion hy­per­glycemia is an im­por­tant risk fac­tor for sub­se­quent PTDM, a for­mal di­ag­no­sis of PTDM is op­ti­mally made once the pa­tient is sta­ble on main­te­nance im­muno­sup­pres­sion and in the ab­sence of acute in­fec­tion (106-108). The OGTT is con­sid­ered the gold stan­dard test for the di­ag­no­sis of PTDM (103,104,109,110). How­ev­er, screen­ing pa­tients using fast­ing glu­cose and/‍or A1C can iden­tify high-‍risk pa­tients re­quir­ing fur­ther as­sess­ment and may re­duce the num­ber of over­all OGTTs re­quired.

Few ran­domized con­trolled stud­ies have re­port­ed on the short-‍ and long-‍term use of antihy­per­glycemic agents in the set­ting of PTDM (108,111,112). Most stud­ies have re­port­ed that trans­plant pa­tients with hy­per­glycemia and PTDM after trans­plan­ta­tion have high­er rates of re­jec­tion, in­fec­tion, and re­hos­pi­tal­iza­tion (106,108,113).

In­sulin ther­a­py is the agent of choice for the man­age­ment of hy­per­glycemia and di­a­betes in the hos­pi­tal set­ting. After dis­charge, pa­tients with pre­ex­ist­ing di­a­betes could go back on their pretrans­plant reg­i­men if they were in good con­trol be­fore trans­plan­ta­tion. Those with pre­vi­ous­ly poor con­trol or with per­sis­tent hy­per­glycemia should con­tin­ue in­sulin with fre­quent home self-‍mon­i­tor­ing of blood glu­cose to de­ter­mine when in­sulin dose re­duc­tions may be need­ed and when it may be ap­pro­pri­ate to switch to nonin­sulin agents.

No stud­ies to date have es­tab­lished which nonin­sulin agents are safest or most effica­cious in PTDM. The choice of agent is usu­al­ly made based on the side ef­fect profile of the med­i­ca­tion and pos­si­ble in­ter­ac­tions with the pa­tient’s im­muno­sup­pres­sion reg­i­men (108). Drug dose ad­just­ments may be re­quired be­cause of de­creases in the glomeru­lar filtra­tion rate, a rel­a­tively com­mon com­pli­ca­tion in trans­plant pa­tients. A small short-‍term pilot study re­port­ed that met­formin was safe to use in renal trans­plant re­cip­i­ents (114), but its safe­ty has not been de­ter­mined in other types of organ trans­plant. Thi­a­zo­lidine­diones have been used suc­cess­ful­ly in pa­tients with liver and kid­ney trans­plants, but side ef­fects in­clude fluid re­ten­tion, heart fail­ure, and os­teope­nia (115,116). Dipep­tidyl pep­ti­dase 4 in­hibitors do not in­ter­act with im­muno­sup­pres­sant drugs and have demon­strat­ed safe­ty in small clin­i­cal tri­als (117,118). Well-‍de­signed in­ter­ven­tion tri­als ex­am­in­ing the efficacy and safe­ty of these and other antihy­per­glycemic agents in pa­tients with PTDM are need­ed.