Khawla F Ali, Vicente T San Martin, Betül Hatipoğlu
In patients with chronic pancreatitis (CP), autologous islet transplantation (AIT) is often coupled with total pancreatectomy (TP) in aims to preserve patients' insulin secretory function. Despite a third of patients achieving insulin independence post-total pancreatectomy and autologous islet transplantation (TPAIT), many will require the addition of insulin therapy for maintenance of glycemic control overtime. We aimed through this study to investigate the early metabolic profile signature of insulin independent subjects post-TPAIT, specifically exploring markers of beta cell stress in this cohort. In a prospective study design, we identified 37 subjects who underwent TPAIT between 2008 and 2017. Metabolic parameters were assessed using mixed meal tolerance test data (MMTT), and the insulin-to-proinsulin index ratio, a marker of beta cell stress. Assessments between metabolic variables were evaluated using the Wilcoxon signed rank test. A significance level of 0.05 was assumed for all comparisons. At a mean (±standard deviation) follow up duration of 37.7±17 months post-TPAIT, 11 patients (30%) were insulin independent with a mean HbA1C of 5.85±0.42%. Despite adequate glycemic control in the latter cohort, we observed significantly higher median peak glucose (180.5 versus 115.0 mg/dL; p=0.031), and lower median fasting C-peptide (0.95 versus 1.5 ng/mL; p=0.008) on post-TPAIT MMTT compared to pre-TPAIT MMTT. Additionally, significantly lower insulin-to-proinsulin index AUC ratio was seen post-TPAIT compared to pre-TPAIT (p=0.022). A decline in the proinsulin processing capacity, expressed by a lower insulin-to-proinsulin index ratio was seen in insulin independent subjects post-TPAIT. Further studies exploring the pathophysiology underlying these findings should be attained.
在慢性胰腺炎(CP)患者中，自体胰岛移植(AIT)常与全胰切除术(TP)联合进行，目的是保护患者的胰岛素分泌功能。尽管三分之一的患者在全胰腺切除术和自体胰岛移植(TPAIT)后实现了胰岛素独立，但许多患者仍需要额外的胰岛素治疗来维持血糖控制。我们旨在通过本研究调查胰岛素独立受试者在tpait后的早期代谢特征，特别是探索该队列中β细胞应激的标志物。在一项前瞻性研究设计中，我们确定了37名在2008年至2017年期间接受TPAIT的受试者。代谢参数通过混合膳食耐受试验数据(MMTT)和胰岛素与胰岛素原指数比值(β细胞应激的标志)进行评估。代谢变量间的评估采用Wilcoxon符号秩检验。假设所有比较的显著性水平为0.05。tpait后平均(±标准差)随访时间为37.7±17个月，11例(30%)患者为胰岛素独立患者，平均HbA1C为5.85±0.42%。尽管后一组患者血糖得到了适当的控制，但我们观察到血糖峰值中位数明显更高(180.5 vs 115.0 mg/dL;p=0.031)，空腹c肽中位数较低(0.95 vs 1.5 ng/mL;p=0.008) tpait后MMTT与tpait前相比。此外，与tpait前相比，tpait后胰岛素-胰岛素原指数AUC比值显著降低(p=0.022)。胰岛素独立受试者在tpait后胰岛素原处理能力下降，表现为胰岛素与胰岛素原指数比值降低。进一步的研究探索这些发现背后的病理生理学应该得到。
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