PDF(Pubmed)
Abstract：
The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.
摘要：
即时血液介导的炎症反应（IBMIR）导致胰岛丢失，并在胰岛自体移植全胰腺切除术（TPIAT）后损害糖尿病结局。我们先前报道了依那西普在TPIAT后3个月维持胰岛素分泌的可能益处。这里,我们报告了一项在TPIAT中使用依那西普和α-1抗胰蛋白酶(A1AT)的随机试验的2年糖尿病结局和围手术期炎症谱.我们将43名TPIAT接受者随机分为A1AT（90mg/kgIVx6剂量，n=13),依那西普（50毫克，然后25毫克SQx5剂量，n=14),或标准护理(n=16)。炎性细胞因子,在围手术期多次抽取血清A1AT和未甲基化的胰岛素DNA。TPIAT后2年采用混合餐耐量试验评估胰岛功能,静脉葡萄糖耐量试验和葡萄糖强化精氨酸诱导的胰岛素分泌。细胞因子,特别是IL-6，IL-8，IL-10和MCP-1在TPIAT期间和之后升高。然而,只有TNFα在组间有显著差异，依那西普组的水平最高（p=0.027）。所有组的A1AT在IAT后增加（p<0.001），提示内源性上调。三组中未甲基化的胰岛素DNA比率（胰岛丢失的标志）和2年胰岛功能测试相似。最后，我们发现在围手术期使用依那西普或A1AT没有持续获益.
