Effect of Everolimus with Low-Dose Tacrolimus on Development of New-Onset Diabetes After Transplantation and Allograft Function in Kidney Transplantation: A Multicenter, Open-Label, Randomized Trial

Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients

“…36 Although tacrolimus and sirolimus have been associated with increased risks of posttransplant DM, data on steroid avoidance/withdrawal as a strategy to decrease posttransplant DM risk are conflicting. [22][23][24][25][26][37][38][39][40][41][42][43] Because the use of regimens that reduced the risk of posttransplant DM [cyclosporine (CsA)-based regimens or steroid avoidance] have historically been associated with an increasing risk of rejection, recommendations published in 2014 following an international consensus meeting on posttransplant DM suggested that the immunosuppression regimens should fully optimize patient and allograft survival without concern for enhancing the risk of posttransplant DM. 5,44 Similar recommendations were issued by the British Clinical Diabetologists and Renal Association and American Diabetes Association in 2021.…”

“…5,44,45 These guidelines drew on data mainly from the CsA era, often without effective induction therapy. [22][23][24][25][26][37][38][39][40][41][42][43] In contrast, transplantation guidelines now recommend that tacrolimus and mycophenolate mofetil be used as first-line maintenance immunosuppression agents with appropriate induction medications, mitigating the risk of rejection associated with steroid avoidance. 46,47 Previous studies evaluating the risk of posttransplant DM have not assessed the benefits of alternative immunosuppression strategies, such as steroid avoidance/withdrawal, to reduce the risk of posttransplant DM among older and obese recipients, who are more at risk of metabolic complications.…”

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

“…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 (143) risks (such as age, family history of diabetes, etc.) as well as transplant-specific factors, such as use of immunosuppressant agents (148)(149)(150). 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 (146)(147)(148)151).…”

Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

“…Os inibidores da calcineurina, incluindo o tacrolimus, têm sido associados ao comprometimento da função secretora de insulina e à redução da sensibilidade à insulina, contribuindo para o desenvolvimento de RI e diabetes de início recente em pacientes com TR 13 . Os mecanismos fisiopatológicos ainda não estão claros, mas estratégias como o uso de baixas doses de tacrolimus ou everolimus têm sido propostas como uma alternativa para reduzir distúrbios no metabolismo de carboidratos 14 . A associação de IMC, tecido adiposo subcutâneo abdominal e tecido adiposo visceral com RI é bem conhecida 15…”