Glucose Disorders Induced by Tacrolimus on Pre Transplantation Endstage Renal Disease Patients
Status:
Recruiting
Trial end date:
2023-07-01
Target enrollment:
Participant gender:
Summary
Diabetes after kidney transplantation is a frequent complication, the incidence of which
varies from 7 to 45% depending on the studies and on the diagnostic criteria used.
Post-transplant diabetes is an early complication, most often occurring in the first month
after transplantation.
In addition to the additional health costs generated by the appearance of post-transplant
diabetes, the risk of graft loss is increased by 60% and the overall mortality risk by 90%.
Similarly, the development of glucose intolerance after transplantation is associated with
higher mortality.
Tacrolimus treatment is therefore currently one of the most important risk factors for
diabetes at the time of transplantation.
Indeed, several in vitro and in vivo animal studies have shown that tacrolimus alters
pancreatic endocrine function.
In the final stage, this cellular toxicity leads to diabetes, most often diagnosed on the
rise in capillary or venous blood sugar levels after transplantation. This diabetes often
requires hypoglycemic treatment with insulin or oral anti-diabetic drugs. for a variable
period. The pro-diabetogenic effect of tacrolimus is sometimes irreversible, justifying
preventive treatment.
No clinical studies have looked at "sub-clinical" changes in insulin secretion or insulin
resistance under tacrolimus prior to the onset of diabetes. The static indices HOMA-β% and
HOMA-IR (Homeostasis Model Accessment of insulin resistance) make it possible to estimate
insulin secretion and insulin resistance in fasting patients respectively, while the oral
glucose disposition index (IDO) makes it possible to study insulin secretion and action
dynamically (after a 75 g glucose load), and are calculated as follows:
HOMA IR= Fasting blood glucose (mmol/L) x Fasting insulin (mU/L)/ 22.5 HOMAβ% = 20 x fasting
insulinemia (mU/L) / fasting plasma glucose (mmol/L) - 3.5 IDO = (delta insulinemia T30-T0/
delta blood glucose T30-T0)/insulinemia T0
These indices have already been studied in dialysis patients (diabetic and non-diabetic) and
may allow a more detailed study of pancreatic response and insulin resistance under
tacrolimus in patients prior to renal transplantation. Determining the "pancreatic response"
to tacrolimus in patients prior to transplantation would prevent diabetes by adapting
immunosuppressive treatment and post-transplant screening modalities in the event of
pre-transplant subclinical abnormalities identified in our study. The development of
tacrolimus-induced diabetes in pre-transplantation in our study will be a contraindication to
tacrolimus at the time of transplantation and ciclosporin therapy will be preferred.