Hybrid Closed-Loop System Demonstrates Effectiveness in Controlling Glucose Levels in Children and Adults with Type 1 Diabetes

SAN DIEGO, June 12, 2017 /PRNewswire-USNewswire/ -- For people with type 1 diabetes, continuous glucose monitoring (CGM) devices provide around-the-clock information on blood glucose levels. Insulin pumps allow insulin to be administered subcutaneously throughout the day. Over the recent past, researchers combined the technology of CGM and insulin pumps to form closed-loop systems, which allow people with diabetes to receive insulin through a pump continuously throughout the day and night based on the glucose measurements provided every five minutes by the CGM. The performance of closed-loop systems and their ability to prevent hypoglycemia is highlighted in two studies presented at the American Diabetes Association's 77th Scientific Sessions^® at the San Diego Convention Center.

Safety and Feasibility of Omnipod Hybrid Closed-Loop in Children Aged 6-12 Years with Type 1 Diabetes Using a Personalized Model Predictive Control Algorithm

Children with type 1 diabetes have increased insulin sensitivity compared to adolescents and adults, and are at increased risk of severe hypoglycemia (low blood glucose levels) overnight. This inpatient, research center study investigated the safety and feasibility of a new hybrid closed-loop system. Researchers combined an Omnipod^® patch pump, Dexcom^, G4 CGM sensor with Bluetooth technology built into the receiver, and a personalized model, predictive control algorithm. "Hybrid closed-loop," indicates that the system is continuously adjusting insulin delivery. However, at mealtime, the patient enters the amount of carbohydrates they are eating in order for the insulin pump to determine the meal dose of insulin.

The study included 12 children, aged 6-12 years with type 1 diabetes, with an average age of nine years, and an average diabetes duration of four years. The trial consisted of a 36-hour, inpatient, closed-loop assessment with meals ranging from 30-90 grams of carbohydrates and limited physical activity to examine glycemic outcomes.

The continuous monitoring data indicated that 69.2 percent of the overall glucose values were between the desired range of 70-180 mg/dl; and overnight, 82 percent of values were within range. The participants' average glucose level was 157 mg/dl, and two percent of readings were <70 mg/dl with use of the system compared to four percent of readings < 70 mg/dl when at home and not using the hybrid-closed loop system. The mean fasting glucose level following overnight use of the closed-loop system was 136±24 mg/dL. These findings indicate that the Omnipod^® automated glucose control algorithm performed well and was safe during day and night use in children with type 1 diabetes.

"Hybrid closed-loop systems do a great job improving glucose control overnight, significantly lowering the risk of hypoglycemia, thus allowing patients and their families to get a good night's sleep," said chief investigator Bruce A. Buckingham, MD, professor of pediatrics (endocrinology) at the Lucile Salter Packard Children's Hospital, Stanford University. "These systems also assist patients during the day in decreasing the magnitude of both high- and low-glucose fluctuations. And, many patients prefer wearing an 'untethered' patch pump, which provides more flexibility to enjoy physical activities without worrying about infusion set detachments, and a hybrid system provides some additional protection to prevent low blood glucose levels, resulting in improved quality of life for children with diabetes."

"Longer outpatient studies are needed with subjects using the system under their home living conditions. The device is being tested in many age groups and under many different conditions," Dr. Buckingham concluded.

Single and Dual-Hormone Closed-Loop Glucose Control with Automated Exercise Detection to Prevent Hypoglycemia in Type 1 Diabetes

People with type 1 diabetes have difficulty controlling their blood glucose levels while exercising. Aerobic exercise can cause sharp drops in blood sugar leading to hypoglycemia. Single- and dual-hormone closed-loop systems automate the dosing of insulin, or insulin plus glucagon, to a person with type 1 diabetes to help them better manage their blood sugar levels. Automated delivery of insulin and glucagon during exercise can help people avoid exercise-induced hypoglycemia by reducing insulin delivery and increasing glucagon in response to exercise.

In order to test if exercise-related hypoglycemia can be reduced through a closed-loop system that responds automatically to physical activity, researchers in this trial developed and evaluated single-hormone and dual-hormone closed-loop systems. The study included 20 adults with type 1 diabetes who used wearable, wireless sensors, including heart rate and accelerometer sensors, to automatically detect the onset of aerobic exercise and to communicate, calculate and deliver the appropriate insulin and/or glucagon dose needed to avoid hypoglycemia.

In random order, the study participants used various systems, including: a single-hormone closed-loop system that doses insulin only; a dual-hormone closed-loop system that doses both insulin and glucagon; a predictive, low-glucose suspend system that shuts off insulin if glucose is predicted to go too low; and the patients' usual current standard of care whereby they controlled their glucose levels using their own methods.

Participants underwent four, 4-day outpatient visits, exercising for 45 minutes at 60 percent VO₂max on day one and day four in a human performance lab, and completing at least one at-home exercise session to determine the amount of time in hypoglycemia. Subjects entered estimated carbohydrate intake into the insulin pump, which automatically delivered a portion of the estimated pre-meal insulin dose. Blood glucose levels were measured four times daily.

The study found that incorporation of glucagon, along with insulin, into automated dosing during and after exercise reduced exercise-induced hypoglycemia from 6.3 percent to 1.0 percent when compared to insulin-only usage. The dual-hormone closed-loop system was also more effective than both the predictive low-glucose suspend dosing system and current care therapy. Results across all four days from a subset of the 20 adult subjects from 17 visits show that time spent in hypoglycemia (<70 mg/dl) was 1.0 percent for the dual-hormone system; 3.4 percent for single-hormone; 1.2 percent for the predictive low glucose suspend system; and 2.1 percent for current care. However, participants undergoing current care prevented exercise-induced hypoglycemia by keeping their blood sugar levels significantly higher leading up to the start of exercise. The mean glucose level after exercise was significantly lower for single-hormone compared with dual-hormone, 67±6 mg/dL and 100±9 mg/dL, respectively.

"Our findings show that fully automated insulin and glucagon delivery, combined with wearable physical activity sensors that detect exercise, effectively controlled glucose levels, reduced exercise-induced hypoglycemia and can safely be used in a home environment," said investigator Peter G. Jacobs, PhD, assistant professor in the department of biomedical engineering at Oregon Health & Science University in Portland. "These results suggest that a dual-hormone closed-loop system with automated detection of aerobic exercise can be used as a tool to adjust dosing of insulin and glucagon during and after exercise."

"We plan to explore migrating our system from a smart-phone platform to a smart watch, where exercise can be more easily detected," Jacobs explained. "These exercise-enabled automated dosing systems may soon be able to help people with type 1 diabetes exercise safely without fear of hypoglycemia."

To speak with Dr. Buckingham or Dr. Jacobs, please contact the Association's media relations team on-site at the San Diego Convention Center on June 9 - 13, by phone at 619-525-6250 or by email at [email protected].

The American Diabetes Association's 77th Scientific Sessions, to be held June 9-13, 2017, at the San Diego Convention Center, is the world's largest scientific meeting focused on diabetes research, prevention and care. During the five-day meeting, health care professionals have exclusive access to more than 2,500 original research presentations, participate in provocative and engaging exchanges with leading diabetes experts, and can earn Continuing Medical Education (CME) or Continuing Education (CE) credits for educational sessions. The program is grouped into eight interest areas: Acute and Chronic Complications; Behavioral Medicine, Clinical Nutrition, Education and Exercise; Clinical Diabetes/Therapeutics; Epidemiology/Genetics; Immunology/Transplantation; Insulin Action/Molecular Metabolism; Integrated Physiology/Obesity; and Islet Biology/Insulin Secretion. Brenda Montgomery, RN, MSHS, CDE, President of Health Care and Education[1], will deliver her address on Saturday, June 10, and Alvin C. Powers, MD, President of Medicine and Science, will present his address on Sunday, June 11. Eight abstracts were selected by the Scientific Sessions Meeting Planning Committee to be presented on Tuesday, June 13, in the President's Oral Session. These abstracts represent important research being conducted in the field of diabetes today. In total, the 2017 Scientific Sessions includes 378 abstracts in 49 oral sessions; 2,152 poster presentations including 50 moderated poster discussions; and 360 published-only abstracts. Join the Scientific Sessions conversation on Twitter, #2017ADA. 

About the American Diabetes Association
More than 29 million Americans have diabetes, and every 23 seconds another person is diagnosed with diabetes. The American Diabetes Association (Association) is the global authority on diabetes and since 1940 has been committed to its mission to prevent and cure diabetes and to improve the lives of all people affected by diabetes. To tackle this global public health crisis, the Association drives discovery in research to treat, manage and prevent all types of diabetes, as well as to search for cures; raises voice to the urgency of the diabetes epidemic; and provides support and advocacy for people living with diabetes, those at risk of developing diabetes and the health care professionals who serve them. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit diabetes.org. Information from both of these sources is available in English and Spanish. Find us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn). 

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Safety and Feasibility of Omnipod Hybrid Closed-Loop in Children Aged 6-12 Years with Type 1 Diabetes Using a Personalized Model Predictive Control Algorithm

77th Scientific Sessions
News Briefing: Novel Therapies, Monday, June 12, 1:15 p.m. PT

Presentation: Late Breaking Poster Session
Location: Hall B
Session Time: Sunday, June 11, 12:00 - 1:00 p.m.

Authors: BRUCE A. BUCKINGHAM, GREGORY P. FORLENZA, JENNIFER SCHNEIDER, THOMAS A. PEYSER, EYAL DASSAU, JOON BOK LEE, JASON O'CONNOR, JENNIFER E. LAYNE, TRANG LY, Stanford, CA, Denver, CO, Palo Alto, CA, Cambridge, MA, Billerica, MA

Children have enhanced insulin sensitivity compared to adolescents and adults with type 1 diabetes. We investigated the performance of an automated glucose control algorithm using the Omnipod^® Insulin Management System in children with type 1 diabetes. The system included a modified version of Omnipod, Dexcom® G4 sensor and a personalized model predictive control algorithm. The study consisted of a 36-hour inpatient closed-loop assessment with announced meals ranging from 30-90 g of carbohydrates and limited physical activity. Subjects aged 6-12 y and A1C between 6.0-10.0% were eligible. Endpoints included sensor glucose percentage of time <70, 70-180, >180, >250 mg/dL and mean glucose. Clinical demographics for 12 subjects included (mean±SD): age 8.9±1.6 y, diabetes duration 4.3±2.3 y, A1C 7.8±0.8% and TDD 0.8±0.1 U/kg. Glycemic outcomes are reported in the Table. The mean percentage of time in range, 70-180 mg/dL, was 69.2% overall and 82.0% overnight. The mean fasting glucose following overnight closed-loop was 136±24 mg/dL. The Omnipod automated glucose control algorithm performed well and was safe during day and night use in children with type 1 diabetes.

Author Disclosures: B.A. Buckingham: Consultant; Author; Dexcom, Inc., Medtronic, Sanofi, Tandem Diabetes Care, Inc., Novo Nordisk Inc. Research Support; Author; Dexcom, Inc., Medtronic, Insulet Corporation. Other Relationship; Author; Abbott Diabetes Care Inc., Dexcom, Inc., Roche Diabetes Care. G.P. Forlenza: Consultant; Author; Abbott Diabetes Care Inc.. Research Support; Author; Insulet Corporation, Medtronic, Dexcom, Inc., Bigfoot Biomedical, Tandem Diabetes Care, Inc., TypeZero Technologies, LLC, Animas Corporation, Novo Nordisk Inc. J. Schneider: Consultant; Author; Insulet Corporation. T.A. Peyser: Consultant; Author; Insulet Corporation. E. Dassau: Consultant; Author; Insulet Corporation. J. Lee: Employee; Author; Insulet Corporation. J. O'Connor: Employee; Author; Insulet Corporation. J.E. Layne: Employee; Author; Insulet Corporation. T. Ly: Employee; Author; Insulet Corporation.

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Single and Dual-Hormone Closed-Loop Glucose Control with Automated Exercise Detection to Prevent Hypoglycemia in Type 1 Diabetes

77th Scientific Sessions
News Briefing: Novel Therapies, Monday, June 12, 1:15 p.m. PT

Session: Pumps and Loops
Location: Ballroom 20D
Session Time: Monday, June 12, 8:00 - 10:00 a.m.

Authors: JESSICA R. CASTLE, JOSEPH EL YOUSSEF, RAVI REDDY, NAVID RESALAT, DEBORAH BRANIGAN, UMA RAJHBEHARRYSINGH, BRIAN SENF, SAMUEL SUGERMAN, NICHOLAS PREISER, PETER G. JACOBS, Portland, OR

We developed and tested single-hormone and dual-hormone closed-loop (CL) systems that automatically detect exercise and adjust dosing in response to exercise using accelerometry and heart rate inputs to help reduce exercise-related hypoglycemia in people with type 1 diabetes (T1D). We compared single hormone (SH) and dual-hormone (DH) algorithms with a predictive low glucose suspend (PLGS) system, and the person's usual current care (CC). In random order, adult subjects with T1D underwent four 4-day outpatient visits: DH, SH, PLGS, and CC. Exercise detection in both CL systems stopped insulin for 30 m, then 50% reduction for 60 m and in DH, increased glucagon by 2 fold for 1.5 h. Glucose values from a Dexcom G5 sensor were pushed every 5 m to a Google Nexus phone running the CL algorithm. Delivery commands were sent every 5 m to t:slim pumps for SC infusion of insulin and/or glucagon. Capillary blood glucose levels were measured four times daily. Subjects exercised for 45 m at 60% VO2max on day 1 and 4 in the human performance lab and completed at least one at home exercise session. Subjects estimated carbohydrate and entered estimates into the controller, which automatically delivered a portion of the estimated pre-meal insulin dose. Results from a subset of the 20 adult subjects from 17 visits show that overall sensed glucose during DH use was 152±24 mg/dL (mean±SEM) with 1.1% time in hypoglycemia (CGM<70 mg/dL). During SH, mean glucose was 134±2 mg/dL, with 4.3% time in hypoglycemia, during PLGS, mean glucose was 148±12 mg/dL, 1.4% hypoglycemia, and with CC glucose was 152±11 mg/dL, 2.9% hypoglycemia. Mean sensed glucose after exercise was significantly lower for SH compared with DH, 67±6 mg/dL and 100±9 mg/dL, respectively (p=0.002). Preliminary results show that fully automated insulin and glucagon delivery combined with automated exercise detection effectively controlled glucose levels and reduced time in hypoglycemia and can safely be used in a home environment.

Author Disclosures: J.R. Castle: Consultant; Author; Novo Nordisk Inc.. Stock/Shareholder; Author; Pacific Diabetes Technologies. J. El Youssef: None. R. Reddy: None. N. Resalat: None. D. Branigan: None. U. Rajhbeharrysingh: None. B. Senf: None. S. Sugerman: None. N. Preiser: None. P.G. Jacobs: Stock/Shareholder; Author; Pacific Diabetes Technologies.

[1] Disclosures for Brenda Montgomery. Employer: AstraZeneca Pharmaceuticals. Montgomery's role as President, Health Care & Education of the American Diabetes Association (Association) is a voluntary position to which she was elected by the members of the Association in 2015. She continues to recuse herself from any and all discussions, decisions or votes that have or could be perceived as having a conflict of interest with her employer. 

SOURCE American Diabetes Association

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