Ali Khawla F, San Martin Vicente T, Hatipoğlu Betül
Cleveland Clinic, Endocrinology and Metabolism Institute, Cleveland, OH, USA.
Turk Klin Immunol Alerji. 2019;2019:39-44. Epub 2019 Apr 12.
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，旨在保留患者的胰岛素分泌功能。尽管三分之一的患者在接受全胰切除术和自体胰岛移植（TPAIT）后实现了胰岛素自主分泌，但随着时间的推移，许多患者仍需要添加胰岛素治疗以维持血糖控制。我们通过这项研究旨在调查TPAIT后胰岛素自主分泌患者的早期代谢特征，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年间接受TPAIT的受试者。使用混合餐耐量试验数据（MMTT）评估代谢参数，并使用胰岛素与胰岛素原指数比作为β细胞应激的标志物。使用Wilcoxon符号秩检验评估代谢变量之间的差异。所有比较均假定显著性水平为0.05。在TPAIT后平均（±标准差）随访37.7±17个月时，11名患者（30%）实现了胰岛素自主分泌，平均糖化血红蛋白（HbA1C）为5.85±0.42%。尽管后一组患者血糖控制良好，但与TPAIT前的MMTT相比，我们观察到TPAIT后的MMTT中，中位数峰值血糖显著更高（180.5对115.0 mg/dL；p=0.031），中位数空腹C肽更低（0.95对1.5 ng/mL；p=0.008）。此外，与TPAIT前相比，TPAIT后胰岛素与胰岛素原指数AUC比显著更低（p=0.022）。在TPAIT后的胰岛素自主分泌患者中，观察到胰岛素与胰岛素原指数比降低，这表明胰岛素原加工能力下降。应进一步开展研究以探索这些发现背后的病理生理学机制。
