Beta Cell Stress in Insulin Independent Subjects Following Total Pancreatectomy and Autologous Islet Transplantation.

Abstract

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.