A Two Hormone Artificial System Improved Patient’s Time in Target Range and Decreased Hypoglycemia

A recent publication reported on a study of the efficacy of a closed-loop bi-hormonal system for controlling glucose levels in adults with T1D. The study involved 15 adults comparing their use of continuous glucose monitoring and conventional insulin pump therapy with a closed-loop delivery system of insulin and glucagon. Patients were admitted two times to the hospital’s clinical research facility for overnight stays where they received each treatment in random order. During the artificial pancreas test visits, the hormones were delivered based on predictive dosing software that made decisions every 10 minutes based on CGM readings. During the conventional therapy visits, the patients used standard insulin pump therapy. The study found that the bi-hormonal artificial pancreas delivery system increased the percentage of time spent in the target blood glucose range (72-180mg/dl) to 70.7% from 57.3% on conventional therapy. The time spent in the hypoglycemic range (<72mg/dl) was 0.0% with the artificial pancreas system compared with 2.8% with conventional therapy. Eight participants in the conventional therapy group had at least one hypoglycemic event (<54mg/dl) compared to only a single event during artificial pancreas system treatment. In a separate commentary in the journal, Dr. David Nathan noted that although this study was neither the first nor the longest investigation using a dual hormone artificial pancreas system, it was the first to compare such a system to conventional intensive therapy in a rigorous, randomized design. He also noted that treatment with the artificial pancreas system increased the amount of time patients spent in the target range of blood glucose levels and decreased hypoglycemia.

Ramifications for Individuals with T1D:
The clinical study described here adds to the extensive JDRF-funded research by Dr. Ed Damiano at Boston University and Dr. Ken Ward in Oregon and others to accelerate the development and delivery of bi-hormonal artificial pancreas systems, an advanced generation design concept. Such two hormone artificial pancreas systems will move a step closer to reproducing natural blood glucose control in individuals with T1D. These findings underscore the need for the development of a stable, liquid form of glucagon that is suitable for pumps and for bi-hormonal pumps that can deliver both insulin and glucagon (or another hormonal drug). Towards this end, JDRF is funding research to identify a pumpable liquid glucagon and has recently announced a partnership with Tandem to develop and deliver a dual chamber pump.

JDRF Involvement:
JDRF did not fund this study, however assistance was provided by the Jaeb Center for Health Research which receives JDRF support for the Artificial Pancreas Project. Dr. Ahmad Haidar and Dr. Remi Rabasa Loret are new recipients of a JDRF postdoctoral fellowship and an Innovative grant respectively.

Investigators and Institutions:
Ahmad Haidar1,2, Laurent Legault3, Maryse Dallaire1, Ammar Alkhateeb1, Adele Coriati1, Virginie Messier1, Peiyao Cheng6, Maude Millette3, Benoit Boulet2 and Remi Rabasa-Lhoret1,4,5, 1Institut de Recherches Cliniques de Montreal; 2Centre for Intelligent Machines. Montreal Children’s Hospital, 4Nutrition Department, Universite de Montreal; and 5Endocrinology Division, Montreal University Hospital, Montreal Quebec Canada; and 6Jaeb Center for Health Research, Tampa Fl.

Reference:
Haidar A, Legault L, Dallaire M, Alkhateeb A, Coriati A, Messier V, Cheng P, Millette M, Boulet B, Rabasa-Lhoret R.(2013) Glucose-responsive Insulin and Glucagon Delivery (Dual-Hormone Artificial Pancreas) in Adults with T1D: a Randomized Crossover Controlled Trial. CMAJ. 2013 Mar 5;185(4):297-305. doi: 10.1503/cmaj.121265. Epub 2013 Jan 28.

Accompanying commentary by Drs. David Nathan and Steven Russell (Massachusetts General Hospital, Harvard Medical School, Boston MA)