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

AIMS: Tacrolimus (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.

METHODS

Two 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 12.6years post-transplant. Factors related to glucose metabolism parameters were explored by multilinear regression analysis. Eighteen non-diabetic Rtx tested by ivGTT 6months post-transplant were retested at 12years. The glucose metabolism outcome parameters were also adjusted according to the results of the cross-sectional study.

RESULTS

Multivariate 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.

CONCLUSIONS

Chronic Tac exposure does NOT lead to a progressive decrease in 'stimulated insulin secretion' between 6months and 12years post renal transplant in our population of 18 patients.