Prediabetes in Pediatric Recipients of Liver Transplant: Mechanism and Risk Factors

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To investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths. This was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL). Corrected insulin response (CIR) was calculated as measure of insulin secretion, corrected for glucose (CIR30, CIR60, CIR120). Subjects were aged 8.1-30.0 years and 1.1-24.7 years post-transplant; 44% had prediabetes-27% IGT, 14% IFG, and 3% both. IGT was characterized by insulin hyposecretion, with lower CIR60 and CIR120 in IGT than subjects with normal glucose tolerance. Subjects with tacrolimus trough >6 µg/mL at study visit had lower CIR120 than those with trough ≤6 µg/mL and those off calcineurin-inhibitors. Mean of tacrolimus troughs preceding the study visit, years since transplant, and rejection episodes were not associated significantly with lower CIR. CIR suppression by tacrolimus was most pronounced >6 years from transplant. Overweight/obese subjects and adolescents who retained normal glucose tolerance had greater CIR than those who were IGT. IGT after pediatric liver transplant is driven by inadequate insulin secretion. It is quite common but not detectable with fasting laboratory values-the screening recommended by current guidelines. Calcineurin inhibitors suppress insulin secretion in these patients in a dose-dependent manner. Given the recent focus on long-term outcomes and immunosuppression withdrawal in these children, longitudinal studies are warranted to investigate whether IGT is reversible with calcineurin inhibitor minimization.