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Review Diabetes Research Update—Closed Loop/Artificial Pancreas Jeniece Trast Ilkowitz1 and Neesha Ramchandani2 1. Montefiore Medical Center, Bronx, New York, US; 2. New York University College of Nursing, New York, US Abstract A cure for diabetes, either biological or mechanical, has been the dream of many for a very long time. Technological advances in closed loop/ artificial pancreas (CL/AP) therapy, accompanied by an improved understanding of how the human body and the CL/AP system works, are bringing the potential for a mechanical cure for type 1 diabetes mellitus (T1DM) closer to reality. This article discusses the components of the CL/AP system, describes its limitations, and reviews recent CL/AP research studies on multihormonal CL/AP treatments, exercise, dining out, and using the CL/AP in the outpatient setting. Future directions and grassroots efforts towards an automated insulin delivery system are also addressed. Study results are encouraging, and suggest that initial CL/AP systems may be available for the general public with T1DM in the next few years, despite current limitations. Keywords Closed loop, artificial pancreas, type 1 diabetes, research update, glucagon, pramlintide, exenatide, multihormonal Disclosure: Jeniece Trast Ilkowitz has been part of a research team working with the Medtronic MiniMed ePID closed loop system on studies that were funded by the National Institutes of Health. Neesha Ramchandani is a contracted insulin pump trainer for Tandem Diabetes, is a certified pump trainer for all insulin pumps available in the US (Animas, Medtronic MiniMed, OmniPod, Roche, Tandem), and has been part of a research team working with the Medtronic MiniMed ePID closed loop system on studies that were funded by the National Institutes of Health. The information contained in this manuscript was presented as an oral presentation at the Pediatric Endocrine Nursing Society in Savannah, GA, US, on May 6, 2015. Compliance with Ethics: This article involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: August 24, 2015 Accepted: March 29, 2016 Citation: US Endocrinology 2016;12(1):31–6 Correspondence: Neesha Ramchandani, New York University College of Nursing, 140 West End Ave., 10F, New York, NY 10023, US. E: Support: Neesha Ramchandani received a small honorarium for her presentation of this topic at the Pediatric Endocrine Nursing Society 2015 meeting. No funding was received in the publication of this article. Creation of a working closed loop/artificial pancreas (CL/AP) system is one of the holy grails of type 1 diabetes mellitus (T1DM). In essence, this would be a mechanical cure for a potentially devastating chronic disease. While the CL/AP still has its limitations, the results of recent research studies are encouraging. The CL/AP system also has the attention and support of organizations such as the US Food and Drug Administration (FDA) and the Juvenile Diabetes Research Foundation (JDRF), which is a large charitable organization dedicated to funding T1DM research. 1 The JDRF has created a six-step pathway which ends in a fully automated CL/AP system, and the FDA has created a helpful guide with recommendations and instructions for those interested in developing a CL/AP. The purpose of this paper is to discuss the components of the CL/AP system, describe its limitations, and review recent CL/AP research studies and future directions. Components of the closed loop/artificial pancreas system The CL/AP system is composed of an insulin pump, a continuous glucose monitor (CGM) plus calibration fingerstick blood glucose (BG) measurements to assist with accuracy, 2 and a control algorithm (Figure 1). Initially, the TOU CH MED ICA L MEDIA control algorithm was housed on a laptop computer. Now, it can be either on a laptop computer or on a CL/AP-dedicated smartphone. The CGM, once calibrated with a fingerstick BG, checks the glucose in the interstitial fluid and sends the value to the control algorithm, which decides if insulin is needed or not. If insulin is needed, it instructs the insulin pump to deliver a bolus. All components of the system are in constant communication with each other to try to maintain glucose levels in a target range of 70–180 mg/dl (3.9–10 mmol/l). Several different control algorithms are being used in CL/AP studies. The most common ones are the Proportional-Integral-Derivative (PID, ePID) algorithm, the Model Predictive Control (MPC)/Multiple Model Predictive Control (MMPC)/Multiple Model Probabilistic Predictive Control (MMPPC) algorithms, and the Fuzzy Logic (FL) algorithm. 2,3 Each of these commonly used algorithms are described in more detail below. A comparison of the algorithms performed by Bequette and colleagues (2013) found the ePID to have the highest postprandial glucose values, followed by the MPC and MMPPC algorithms, and then open-loop basal/bolus insulin administration. The significance of the differences between algorithms was not discussed. 4 31