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

Abstract

Total pancreatectomy with islet auto-transplantation (TPIAT) may relieve the pain of chronic pancreatitis while avoiding post-surgical diabetes. Minimizing hyperglycemia after TPIAT limits beta cell apoptosis during islet engraftment. Closed loop (CL) therapy combining an insulin pump with a continuous glucose monitor (CGM) has never previously been investigated in islet transplant recipients. Our objective was to determine the feasibility and efficacy of CL therapy to maintain glucose profiles close to normoglycemia following TPIAT. Fourteen adult subjects (36% male; age 35.9±11.4 years) were randomized to subcutaneous insulin via CL pump (n=7) or multiple daily injections with blinded CGM (n=7) for 72 hours at transition from IV to subcutaneous insulin. Mean serum glucose values were significantly lower in the CL pump than the control group (111±4 v. 130±13 mg/dL; p=0.003 without increased risk for hypoglycemia (% time <70 mg/dl: CL pump 1.9%, control 4.8%, p=0.46). Results from this pilot study suggest that CL therapy is superior to conventional therapy in maintaining euglycemia without increased hypoglycemia. This technology shows significant promise to safely maintain euglycemic targets during the period of islet engraftment following islet transplantation. (clinicaltrials.gov #: NCT01945138)

Insulin therapy in organ donation and transplantation

“…Within transplantation, pancreas and islet recipients are likely to benefit from better training in relation to optimal insulin therapy and from greater understanding of the benefits of good glycaemic control. These patients also have an unprecedented opportunity to benefit from technological advances such as continuous glucose monitoring and closed‐loop insulin delivery introduced within closely monitored and heavily supervised hospital settings. Flash glucose monitoring boasts high accuracy, user‐friendliness and patient engagement, but is not currently licensed for use with insulin sliding scales in hospital settings.…”

Is islet transplantation a realistic approach to curing diabetes?

“…This pilot study showed significant promise for safely maintaining euglycemic targets during the period of islet engraftment following islet transplantation with closed-loop insulin delivery. Moreover, the results of this study suggest that islet transplantation and closed-loop insulin delivery can be mutually complementary approaches, rather than competitive therapies [17]. …”

Accuracy of Continuous Glucose Monitoring in Patients After Total Pancreatectomy with Islet Autotransplantation

“…26 This study marked the first clinical trial using the Medtronic Enlite 2 subcutaneous glucose sensors as part of a CL system. It was also one of the first studies to use CGM in a postsurgical patient population and in patients with some level of endogenous islet function.…”