Diabetes Technology Meeting and FDA/NIH Workshop on the Artificial Pancreas
by joseph shivers
We recently traveled to Maryland for back-to-back meetings on the future of diabetes devices, drugs, and communication technologies. First was the FDA/NIH Public Workshop on the Clinical Development of the Artificial Pancreas, where we sat in on a day of lively discussion among clinicians, members of industry, and FDA officials. This was followed by the 10th Annual Diabetes Technology Meeting (DTM), which (among updates on every other major aspect of glucose monitoring and insulin delivery) also prominently featured the artificial pancreas. The basic idea of the artificial pancreas is a computerized system that uses devices to maintain blood sugar at a healthy level for people with diabetes, without any user input. Such a “closed-loop” system involves a CGM (to take glucose readings), a software algorithm (to analyze the data and predict how much insulin is needed), and an insulin pump (to actually deliver the recommended dose). As we’ve written about in Conference Pearls in diaTribe #11 and Conference Pearls in diaTribe #26, researchers have conducted many promising closed-loop experiments, usually in hospitals over short time frames. Expectations for the future are high; however, as we saw at the two recent meetings in Maryland and share below, the pace of progress in this field is something we would always like to see go faster.
low glucose suspend
One pump feature that has growing interest is Medtronic’s Low Glucose Suspend (LGS), a safety feature that allows integrated pump-CGM systems to automatically stop insulin delivery before sensor glucose readings fall below a dangerously low value. According to Dr. Aaron Kowalski, who heads the Artificial Pancreas Project at JDRF, LGS represents the first step toward “closing the loop.” In fact, the technology is already available in Europe as part of Medtronic’s Paradigm Veo system. However, the FDA has not approved the Veo for the United States, so the Paradigm Revel (the US equivalent of the Veo; please see Test Drive in diaTribe #23) does not include this feature. At the FDA/NIH workshop on the artificial pancreas, regulatory officials emphasized their concerns that LGS could turn off insulin delivery at inappropriate times due to sensor error, which would lead to hyperglycemia. Meanwhile several top physicians (including diaTribe Advisory Board members Dr. Bruce Buckingham and Dr. William Tamborlane) argued that the hyperglycemia risk is minor compared to the benefits of avoiding serious hypoglycemia – an attitude shared by the several people with diabetes who spoke during the public comments section of the meeting, including our own Adam Brown. Low Glucose Suspend came up again later in the week at DTM, where Dr. Pratik Choudhary presented results from a month-long British study of Veo use in 29 people with diabetes. Impressively, people in the study who used LGS spent almost two-thirds less time per day with blood sugar less than 70 mg/dl, 0.6 hours compared to 1.7 hours when LGS was turned off. Automated pump suspension was in fact not associated with rebound hyperglycemia; in cases where the pump suspension lasted two hours, glucose ranged from 88 mg/dl to 160 mg/dl upon basal resumption. Hopefully, ongoing research will satisfy the FDA's concerns about the Veo's LGS feature so that people in the US can move one step closer to closing the loop.
better continuous glucose monitoring sensors
Dr. Charles Zimliki, Chair of the FDA’s Artificial Pancreas Critical Path Initiative and someone who has had type 1 diabetes for 27 years, said at DTM that he believes an Artificial Pancreas system within the next four-to-five years is “definitely possible.” Very exciting in our view. However, he also identified several crucial areas for technological improvement, with sensor inaccuracy foremost among them. Fortunately, two major talks at DTM addressed this very topic, and better CGM sensors are indeed on their way. Rajiv Shah presented Medtronic’s new Enlite sensor, which improves on the current Sof-Sensor in a variety of ways. The Enlite promises to be much more accurate, more reliable (with a 60% reduction in temperature response and a 40% reduction in drug interference), easier to insert (with a 27-gauge, 10.5 mm needle instead of the 22-gauge, 17.5 mm needle on the current Sof-Sensor), and – with a seven-day sensor life – significantly longer-lasting than Medtronic’s current sensor of three days. Peter Simpson, Dexcom’s Senior Director of R&D, had good news as well: DexCom’s fourth-generation sensor has been shown to be significantly more accurate than the current SEVEN PLUS, and the fifth-generation sensor is ambitiously being designed for accuracy on par with traditional glucose meters. Although all three of these sensors have begun or even completed clinical trials, it’s difficult to forecast when they will receive FDA approval and come to market in the US. Still, seeing companies prioritize greater sensor accuracy by developing such impressive technologies is really encouraging.
Another common concern with closed-loop systems is the speed of insulin action. Dr. Edward Damiano explained that for many people using insulin pumps, Humalog – one of the three rapid-acting insulin analogs currently available (Novolog and Apidra are the other two and the three are generally considered to work very similarly) – takes more than an hour to reach its peak level in the body. This is slower than the speed that blood glucose rises after meals, meaning that if insulin is given after starting to eat, hyperglycemia is likely to occur. Currently, people with diabetes can avoid this problem by using pre-meal boluses (hard to remember and plan for many people!), but the ideal closed-loop system would not require users to pre-announce the meal. However, Dr. Damiano is now conducting a trial of partially closed-loop control that involves pre-meal “priming” boluses, and early results are impressive. Still, Dr. Damiano believes they would be even better with ultra-rapid-acting insulin such as Biodel’s Linjeta, which could theoretically eliminate the need for pre-meal boluses altogether. Linjeta is currently facing serious regulatory setbacks and likely won't be approved until 2012 at the earliest (please see New Now Next in diaTribe #27), and the FDA has yet to comment on other insulins that may be faster; Halozyme’s PH20 (please see New Now Next in diaTribe #14) and MannKind’s Afrezza (please see Conference Pearls in diaTribe #20) are still in development and late this month, the FDA said it would give a decision on Afrezza in late January (as a reminder, Afrezza is inhaled; some think it could provide a “chaser” for some who use the closed loop).
telemedicine and social media
Most discussions of the artificial pancreas are about closing the loop: automating the current version of pump-CGM control. However, Dr. David Klonoff, the Chair of the Diabetes Technology Meeting, gave a presentation on “expanding the loop”: incorporating other sensors and communication technologies to make diabetes management safer and more sophisticated than ever. For example, he proposed that sensors might one day be able to monitor variables such as insulin sensitivity, time that carbohydrates appear in the bloodstream, and even stress – this would be quite valuable! The same system could also link with emergency medical response systems to enable rescue during extreme hypoglycemia or hyperglycemia. Although these technologies would likely appear far in the future, if at all, we were reminded at DTM that people with diabetes have been using the Internet and mobile devices for some time to cooperatively manage their diabetes. For example, Dr. Suzanne Boren noted that of the 15 largest Facebook groups related to diabetes, 66% of posts included unsolicited sharing of diabetes management strategies, 29% involved emotional support, and 27% featured product promotion. She also listed some of the biggest online communities and social networking sites, including: Children With Diabetes, dLife, Diabetes Daily, Diabetes Friends, Diabetes Sisters, Diabetes Talkfest, Diabetic Connect, Juvenation, My Diabetes, TuDiabetes, We Are Diabetic, and Diabetic Rockstar. Dr. David Kerr, a highly regarded British endocrinologist, encouraged healthcare providers and companies to familiarize themselves with these sites as well, so that they can better reach out to and help people with diabetes by recommending valuable online resources.