Near-Euglycemia Can Be Achieved Safely in Pediatric Total Pancreatectomy Islet Autotransplant Recipients Using an Adapted Intravenous Insulin Infusion Protocol

Abstract

Background: Children with severe chronic pancreatitis may undergo total pancreatectomy with islet autotransplantation (TPIAT) to relieve pain while minimizing the risk of postsurgical diabetes. Because overstimulation of transplanted islets by hyperglycemia can result in b-cell loss, we developed a specialized intravenous insulin infusion protocol (IIP) for pediatric TPIAT recipients to maintain euglycemia or near-euglycemia posttransplant. Subjects and Methods: Our objective was to review glucose control using an IIP specific for TPIAT recipients at a single institution. We reviewed postoperative blood glucose (BG) levels for 32 children 4-18 years old with chronic pancreatitis who underwent TPIAT between July 2011 and June 2013. We analyzed the proportion of BG values in the range of 70-140 mg/dL, mean glucose, glucose variability, and occurrence of hypoglycemia during the IIP; we also evaluated the transition to subcutaneous therapy (first 72 h with multiple daily injections [MDI]). Results: During IIP, the mean patient BG level was 116 -27 mg/dL, with 83.1% of all values in the range of 70-140 mg/dL. Hypoglycemia was rare, with only 2.5% of values <70 mg/dL. The more recent era (n = 16) had a lower mean BG and less variability than the early era (first 16 patients) (P £ 0.004). Mean glucose level (116 vs. 128 mg/dL) and glucose variability were significantly lower during the IIP compared with MDI therapy (P < 0.0001). Conclusions: Tight glycemic control without excessive severe hypoglycemia was achieved in children undergoing TPIAT using an IIP specifically designed for this population; the ability to maintain BG in target range improved with experience with the protocol.

Pediatric Autologous Islet Transplantation

“…Therefore, the newly infused islets require at least several weeks, up to 3 months, to engraft and revascularize in the liver [33, 34]; during this time, beta-cell apoptosis is common and is exacerbated by hyperglycemia [35, 36]. Care must be taken to provide appropriate insulin therapy—by intravenous drip and then by subcutaneous injections—in order to maintain normal or near-normal blood glucose levels while the islets engraft [37•]. Patients should be followed closely by a multidisciplinary team, including the surgery, gastroenterology, endocrinology, and pain management services.…”

Successful Application of Closed-Loop Artificial Pancreas Therapy After Islet Autotransplantation

“…All participants underwent total pancreatectomy consisting of partial duodenectomy, Roux-en-Y duodenojejunostomy, choledochojejunostomy, and splenectomy as previously described (12, 21, 22). Isolation and purification of the patient’s own islet cells was performed in the UMN Molecular and Cellular Therapeutics Good Manufacturing Practices Facility.…”

“…In the immediate post-operative period, intravenous continuous insulin infusion therapy is the standard of care and it is relatively easy to successfully achieve a narrow range of euglycemia (12). After several days, however, the patient must be transitioned to subcutaneous insulin therapy, and it becomes more challenging to maintain strict euglycemia without risk of hypoglycemia.…”

Role of Automated Insulin Delivery (Artificial Pancreas) in Islet Transplantation: An In Silico Assessment

“…Nevertheless, AID could become an appealing alternative to increase the chances for success during engraftment period because maintaining normoglycemia favors the survival of the transplanted β-cells [60]. This is particularly relevant beyond the immediate postoperative period during which intravenous continuous insulin infusion is the standard of care [61].…”