No evidence for progressive deterioration in stimulated insulin secretion in renal transplant recipients after 12Â years tacrolimus exposure

- Tacrolimus inhibits insulin secretion in a Tac-trough blood level dependent way early post-transplant.
- Age is significantly related to stimulated insulin secretion, but use of Tacrolimus for many years is not.
- Chronic Tac exposure for more than 10 years does not lead to a progressive decrease in insulin secretion post renal transplant.

AimsTacrolimus (Tac) inhibits insulin secretion in a Tac-trough blood level dependent way early post-transplant in renal transplant recipients (Rtx). It is unknown whether long-term exposure results into a progressive beta cells dysfunction.MethodsTwo independent cohorts of Tac-treated non-diabetic Rtx, previously participating in glucose metabolism studies using intravenous Glucose Tolerance Test (ivGTT) were included: Fifty-eight Rtx were tested by ivGTT cross-sectional between 0.25 and 12.6 years post-transplant. Factors related to glucose metabolism parameters were explored by multilinear regression analysis. Eighteen non-diabetic Rtx tested by ivGTT 6 months post-transplant were retested at 12 years. The glucose metabolism outcome parameters were also adjusted according to the results of the cross-sectional study.ResultsMultivariate analysis showed 'Age', 'BMI' and 'use of steroids' to be significantly related, in different combinations, to the glucose metabolism parameters 'insulin resistance', 'fasting insulin level' and 'stimulated insulin secretion'. However 'time on tacrolimus' wasn't related to any parameter.In the longitudinal study, none of the glucose metabolism parameters (either analyzed crude or adjusted) deteriorated clinically or statistically significant. Numerically, 'stimulated insulin secretion' even increased.ConclusionsChronic Tac exposure does NOT lead to a progressive decrease in 'stimulated insulin secretion' between 6 months and 12 years post renal transplant in our population of 18 patients.