Islet autotransplantation to preserve beta cell mass in selected patients with chronic pancreatitis and diabetes mellitus undergoing total pancreatectomy

Abstract

Objectives: Islet autotransplantation (IAT) is performed in nondiabetic patients with chronic pancreatitis at the time of total pancreatectomy (TP) to minimize risk of postoperative diabetes. The role of TP-IAT in patients with chronic pancreatitis and C-peptide-positive diabetes is not established. We postulate that IAT can preserve beta cell mass and thereby benefit patients with preexisting diabetes undergoing TP.

Methods: Preoperative metabolic testing, islet isolation outcomes, and subsequent islet graft function were reviewed for 27 patients with diabetes mellitus and chronic pancreatitis undergoing TP-IAT. The relationships between the results of preoperative metabolic testing and islet isolation outcomes were explored using regression analysis.

Results: Mean islet yield was 2060 (SD, 2408) islet equivalents/kg. Peak C-peptide (from mixed meal tolerance testing) was the strongest predictor of islet yield, with higher stimulated C-peptide levels associated with greater islet mass. Half of the patients who had C-peptide levels measured after transplantation demonstrated C-peptide production at a level that conveys protective benefit in type 1 diabetes (≥ 0.6 ng/mL).

Conclusions: These findings provide proof of concept that significant islet mass can be isolated in patients with chronic pancreatitis and C-peptide-positive diabetes mellitus undergoing TP-IAT. Stimulated C-peptide may be a useful marker of islet mass before transplantation in these patients.

Figure 1

Islet equivalents per kilogram body weight (IEQ/kg) isolated and transplanted in diabetic IAT recipients versus the pre-surgical peak C-peptide (stimulated value from mixed meal tolerance testing). The solid line indicates the predicted IEQ/kg based on preoperative C-peptide, predicted from the equation: IEQ/kg = -937.6 + 573.5 * Peak C-peptide. Pearson's correlation coefficient (r) = 0.76, p-value = 0.0004.