Prasad G V Ramesh, Nash M M, Yuan W, Beriault D, Yazdanpanah M, Connelly P W
Department of Medicine, University of Toronto, ON, Canada.
Kidney Transplant Program, St. Michael's Hospital, Toronto, ON, Canada.
Can J Kidney Health Dis. 2023 Apr 18;10:20543581231168085. doi: 10.1177/20543581231168085. eCollection 2023.
Post-transplant diabetes mellitus (PTDM) encompasses new-onset and previously unrecognized type 2 diabetes. Kidney failure masks type 2 diabetes. Branched-chain amino acids (BCAA) are closely associated with glucose metabolism. Therefore, understanding BCAA metabolism both in kidney failure and after kidney transplantation may inform PTDM mechanisms.
To understand the impact of present or absent kidney function on plasma BCAA concentrations.
Cross-sectional study of kidney transplant recipients and kidney transplant candidates.
Large kidney transplant center in Toronto, Canada.
We measured plasma BCAA and aromatic amino acid (AAA) concentrations in 45 pre-kidney transplant candidates (15 with type 2 diabetes, 30 without type 2 diabetes) and 45 post-kidney transplant recipients (15 PTDM, 30 non-PTDM), along with insulin resistance and sensitivity by 75 g oral glucose loading for those in each group without type 2 diabetes.
Plasma AA concentrations were analyzed using MassChrom AA Analysis and compared between groups. The insulin sensitivity for oral glucose tolerance tests or Matsuda index (a measure of whole-body insulin resistance), Homeostatic Model Assessment for Insulin Resistance (a measure of hepatic insulin resistance), and Insulin Secretion-Sensitivity Index-2 (ISSI-2, a measure of pancreatic β-cell response) was calculated from fasting insulin and glucose concentrations, and compared with BCAA concentrations.
Each BCAA concentration was higher in post-transplant subjects than pre-transplant subjects ( < .001 for leucine, isoleucine, valine). In post-transplant subjects, each BCAA concentration was higher in PTDM versus non-PTDM (odds ratio for PTDM 3-4 per 1 SD increase in BCAA concentration, < .001 for each). Tyrosine concentrations were also higher in post-transplant subjects than pre-transplant subjects, but tyrosine did not differ by PTDM status. By contrast, neither BCAA nor AAA concentrations were different in pre-transplant subjects with or without type 2 diabetes. Whole-body insulin resistance, hepatic insulin resistance, and pancreatic β-cell response did not differ between nondiabetic post-transplant and pre-transplant subjects. Branched-chain amino acid concentrations correlated with the Matsuda index and Homeostatic Model Assessment for Insulin Resistance ( < .05 for each) only in nondiabetic post-transplant subjects-not in nondiabetic pre-transplant subjects. Branched-chain amino acid concentrations did not correlate with ISSI-2 in either pre-transplant or post-transplant subjects.
The sample size was small, and subjects were not studied prospectively for the development of type 2 diabetes.
Plasma BCAA concentrations are higher post-transplant in type 2 diabetic states, but do not differ by diabetes status in the presence of kidney failure. The association of BCAA with measures of hepatic insulin resistance among nondiabetic post-transplant patients is consistent with impaired BCAA metabolism as a characteristic of kidney transplantation.
移植后糖尿病（PTDM）包括新发和既往未被识别的2型糖尿病。肾衰竭会掩盖2型糖尿病。支链氨基酸（BCAA）与葡萄糖代谢密切相关。因此，了解肾衰竭及肾移植后的BCAA代谢情况可能有助于揭示PTDM的发病机制。
了解肾功能存在或缺失对血浆BCAA浓度的影响。
对肾移植受者和肾移植候选者进行横断面研究。
加拿大多伦多的大型肾移植中心。
我们测量了45例肾移植候选者（15例2型糖尿病患者，30例非2型糖尿病患者）和45例肾移植受者（15例PTDM患者，30例非PTDM患者）的血浆BCAA和芳香族氨基酸（AAA）浓度，并对每组无2型糖尿病的患者进行75g口服葡萄糖负荷试验，以评估胰岛素抵抗和敏感性。
采用MassChrom AA分析法分析血浆氨基酸浓度，并在各组间进行比较。根据空腹胰岛素和葡萄糖浓度计算口服葡萄糖耐量试验的胰岛素敏感性或松田指数（衡量全身胰岛素抵抗的指标）、胰岛素抵抗稳态模型评估（衡量肝脏胰岛素抵抗的指标）以及胰岛素分泌-敏感性指数-2（ISSI-2，衡量胰腺β细胞反应的指标），并与BCAA浓度进行比较。
移植后受试者的每种BCAA浓度均高于移植前受试者（亮氨酸、异亮氨酸、缬氨酸的P值均<0.001）。在移植后受试者中，PTDM患者的每种BCAA浓度均高于非PTDM患者（BCAA浓度每增加1个标准差，PTDM的优势比为3 - 4，每种的P值均<0.001）。移植后受试者的酪氨酸浓度也高于移植前受试者，但酪氨酸浓度在PTDM状态下无差异。相比之下，移植前有或无2型糖尿病的受试者的BCAA和AAA浓度均无差异。非糖尿病移植后和移植前受试者的全身胰岛素抵抗、肝脏胰岛素抵抗和胰腺β细胞反应无差异。支链氨基酸浓度仅在非糖尿病移植后受试者中与松田指数和胰岛素抵抗稳态模型评估相关（每种的P值均<0.05），而在非糖尿病移植前受试者中无相关性。移植前或移植后受试者的支链氨基酸浓度与ISSI-2均无相关性。
样本量较小，且未对受试者进行2型糖尿病发生情况的前瞻性研究。
2型糖尿病状态下移植后血浆BCAA浓度较高，但在肾衰竭患者中，其浓度不受糖尿病状态影响。非糖尿病移植后患者中BCAA与肝脏胰岛素抵抗指标的相关性与BCAA代谢受损作为肾移植的一个特征相符。
