Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus
Association of Inflammation prior to Kidney Transplantation with Post-Transplant Diabetes Mellitus
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DOI：
10.1159/000446294
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发表时间：
2016-01-01
影响因子：
3.8
通讯作者：
Falkner, Bonita
中科院分区：
文献类型：
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作者：
Cantarin, Maria P. Martinez;Keith, Scott W.;Falkner, Bonita
背景/目的：肾移植后糖尿病（PTDM）是肾移植术后常见且预后不良的疾病。我们的目的是检查尿毒症相关炎症和脂联素与PTDM的关系。方法：非糖尿病肾移植患者与供体对照。移植前后分别测定炎症因子和脂联素。取脂肪组织进行基因表达分析。细胞因子暴露后，C2C12细胞体外葡萄糖转运定量。对患者进行长达12个月的PTDM监测。结果：我们研究了36例对照和32例移植患者，其中11例（35%）发展为PTDM。与对照组相比，移植患者血浆TNF α、IL-6、MCP-1和CRP水平较高（p < 0.01）。在多变量分析中，移植前血浆TNF α水平与PTDM的发生相关（OR = 2.03, p = 0.04）。移植患者内脏脂肪组织TNF α mRNA表达高于对照组（倍数变化1.33;p < 0.05）。发生PTDM的患者TNF α mRNA表达也高于未发生PTDM的患者（翻倍变化1.42,p = 0.05），脂联素mRNA表达较低（翻倍变化0.48,p < 0.05）。对C2C12细胞的研究表明，暴露于脂联素后葡萄糖摄取增加，而单独暴露于TNF α后无显著变化。同时暴露于TNF α和脂联素使脂联素诱导的葡萄糖摄取减弱（减少11%；p < 0.001）。结论：我们的体外和临床观察表明TNF α可能通过影响脂联素而导致PTDM。我们的研究表明，炎症参与了肾移植后的葡萄糖调节。(C) 2016 S. Karger AG，巴塞尔
Background/Objective: Post-transplant diabetes mellitus (PTDM) is both common and associated with poor outcomes after kidney transplantation. Our objective was to examine relationships of uremia-associated inflammation and adiponectin with PTDM. Methods: Nondiabetic kidney transplant patients were enrolled with donor controls. Inflammatory cytokines and adiponectin were measured before and after transplantation. Adipose tissue was obtained for gene expression analysis. Glucose transport was quantified in vitro in C2C12 cells following cytokine exposure. The patients were monitored up to 12 months for PTDM. Results: We studied 36 controls and 32 transplant patients, of whom 11 (35%) developed PTDM. Compared to controls, plasma TNF alpha, IL-6, MCP-1, and CRP levels were higher in transplant patients (p < 0.01). In multivariable analysis, TNF alpha plasma levels before transplantation were associated with development of PTDM (OR = 2.03, p = 0.04). Visceral adipose tissue TNF alpha mRNA expression was higher in transplant patients than controls (fold change 1.33; p < 0.05). TNF alpha mRNA expression was also higher in patients who developed PTDM than in those who did not (fold change 1.42; p = 0.05), and adiponectin mRNA expression was lower (fold change 0.48; p < 0.05). The studies on the C2C12 cells demonstrated an increase in glucose uptake following exposure to adiponectin and no significant change after exposure to TNF alpha alone. Concomitant TNF alpha and adiponectin exposure blunted adiponectin-induced glucose uptake (11% reduction; p < 0.001). Conclusion: Our in vitro and clinical observations suggest that TNF alpha could contribute to PTDM through an effect on adiponectin. Our study proposes that inflammation is involved in glucose regulation after kidney transplantation. (C) 2016 S. Karger AG, Basel