Abstract
Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (≥18 y) with a functioning graft for ≥1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 ± 13.6 y (53.6% men) and plasma BCAA was 377.6 ± 82.5 µM. During median follow-up of 5.3 (IQR, 4.2–6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08–1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c < 5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM.
Highlights
Post-transplant diabetes after transplantation (PTDM), often a result of insulin resistance and deficient insulin production [1], is a serious complication in renal transplant recipients [2]
No differences were seen in medication, except for use of statins, which was more common in the diabetic renal transplant recipients than in the non-diabetic renal transplant recipients
When we divided the non-diabetic renal transplant recipients in patients with prediabetes (HbA1c ≥ 5.7%) and without prediabetes (HbA1c < 5.7%), we found a positive correlation in the prediabetic renal transplant recipients (r = 0.23, p = 0.002), but not in renal transplant recipients without prediabetes (r = 0.003, p = 0.96)
Summary
Post-transplant diabetes after transplantation (PTDM), often a result of insulin resistance and deficient insulin production [1], is a serious complication in renal transplant recipients [2]. PTDM develops in 10–20% of renal transplant recipients during the first year post-transplantation [3], some studies reported incidences of up to 50% [4]. PTDM is an important risk factor for cardiovascular disease (CVD) and infections, contributing to impaired graft and patient survival [5,6,7]. Previous studies have shown that PTDM is an important risk factor for premature mortality in renal transplant recipients [8,9,10]. Non-modifiable risk factors for the development of PTDM are patient’s age, race, genetic background, and family history of diabetes. It should be noted that if a renal transplant recipient is diagnosed with diabetes, it is considered PTDM, irrespective whether this occurs one-year post-transplantation or 10 years later [16]
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