Emerging Diabetes Technology
The "artificial pancreas" will soon be a reality. Lately there has been an inordinate amount of publicity in light of the FDA's decision to increase the pace in the development of a safe product. I thought I would take the opportunity to review recent evidence-based literature leading up to the FDA's welcome news.
In Diabetes Care, Volume 34, September 2011, Choudhary et. al, published "Insulin Pump Therapy with Automated Insulin Suspension in Response to Hypoglycemia," which demonstrated a decrease in nocturnal hypoglycemia in those people with diabetes at greatest risk. The authors evaluated the sensor-augmented pump (Minimed Paridigm Veo) with the "low glucose suspend" (LGS) feature. The objective was to see if this feature did indeed automatically suspend basal insulin delivery for up to 2 hours in response to "sensor detected hypoglycemia." This study involved 31 adults with type 1 diabetes.
Did it work?
The Veo with the LGS feature was associated with a reduced nocturnal hypoglycemia. Most importantly, the low glucose suspend feature did reduce anxiety about overnight lows. This study was an important first step involving the Veo and prompted the development of randomized controlled trials to evaluate hypoglycemia and quality of life in type 1 diabetes using the LGS feature versus insulin pump therapy with or without the sensor.
Enter the ASPIRE study. The ASPIRE (Automation to Simulate Pancreatic Insulin Response) study was a multicenter, in-clinic, randomized, crossover study to examine "the efficacy of LGS in exercise-induced hypoglycemia." Brazg et. al published the results in the Journal of Diabetes Science and Technology, 2011 Nov
1: 5(6). In this study, 50 adults and teenagers (17-58) with type 1 diabetes were randomized into two separate exercise sessions:
1. With the LGS feature to suspend insulin when the CGM detected blood sugars less than 70 mg/dl
2. Without the LGS feature turned on
Exercise sessions occurred after an overnight fast with blood sugars ranging from 100-140. The study subjects then exercised until BS dropped to less than or equal to 85 mg/dl. Subsequent blood sugars of less than 70 mg/dl were recorded for up to 4 hours to measure the duration and degree of blood sugar drop. (If blood sugars were less than 50 or greater than 300, patients were treated with either carbs or insulin appropriately.) The primary endpoint was comparison of the duration and severity of hypoglycemia between the group with LGS feature-on and LGS feature-off groups.
The ASPIRE study results were published in Diabetes Technology Therapy 2012 March; 14 (3) by Garg et al. and the conclusions were very promising and statistically significant. It was demonstrated that "automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia." Thus the ASPIRE study met its "efficacy" endpoints and demonstrated a 19 percent reduction in time spent below the low glucose threshold in patients using the MiniMed Paradigm system with the LGS automation versus insulin pump therapy without LGS.
What are some possible weaknesses of the trials? The studies were financially supported by the Metronic Minimed corporation, which always brings up the potential possibility of bias. However, keep in mind that many rigorous randomized controlled trials are supported by pharmaceutical companies.
In January of 2012, the FDA agreed to accelerate artificial pancreas technology!
Last week on March 23, it was publicized that the FDA released approval for an artificial pancreas developed by the University of Virginia. These clinical trials are the first outpatient clinical trials and are led by Drs. Patrick Keith-Hynes and Boris Kovatchev. The device is hand-held and was created by reconfiguring a smart phone. It automatically monitors blood glucose levels and provides insulin as needed (therefore apparently decreasing the need for people with diabetes to have to check blood sugars as often). Earlier inpatient trials at the University of Virginia and Europe, as well as ongoing outpatient trials in 2011 (Italy and France), have demonstrated encouraging results in which the first eight type one diabetes patients that participated in the outpatient trial in Europe were able to maintain safe blood glucose levels outside the hospital. According to Dr. Kovatchev, it is possible that the first outpatient trials will begin within the next 2 months.
All the above evidence-based studies are precursors to the development of the best care until the cure. Research also will aggressively pursue the cure as well. However, until there is prevention of diabetes or a cure, the development of an "artificial pancreas" will not only improve diabetes control by reducing significant glucose fluctuations, but will improve quality of life for both the person with diabetes and his/her caregivers. Parents and family members may finally enjoy a full night of sleep for the very first time!