Clinical Diabetes Technology Meeting 2006
The second annual Clinical Diabetes Technology Meeting was held in Boston from April 21 to 22, 2006. In attendance were over 400 scientists, engineers, and doctors from government, industry, academia, and clinical practice. During the two days of sessions, speakers shared information on a variety of topics, including many aspects of continuous glucose monitoring, the danger of glycemic variability, new drug therapies (Symlin and Byetta), the challenge of reimbursement, the importance of glucose control in the hospital setting, and MDI vs. pump therapy, just to name a few. Here is a summary of some of the sessions:
- David Klonoff, MD, the meeting organizer, opened the sessions with the first of two sessions under the topic of Benefits and Limitations of Intermittent Blood Glucose, A1c, and Ketone Testing. Dr. Klonoff summarized data from several studies that showed a significant decline in HbA1c with increasing frequency of home glucose checks. One study showed a drop of 0.25% for each daily check, while others showed a drop of 0.3% and 0.4%. A Kaiser study of adults with type 2 showed a drop of 0.3% for each daily check. These studies demonstrate the importance of knowing your blood glucose level and that "SMBG educates, motivates, and protects."
- Laurie Laffel, MD, discussed the benefits of blood ketone testing compared with urine ketone testing. Using slides from studies in which pump patients were purposely disconnected, she showed a steep rise in both blood glucose and 3-beta-hydroxy butyrate, the ketone body of importance in diabetes care. Other slides showed an equally steep decline in the level of this ketone after reinitiation of insulin therapy. Urine testing conducted during these studies were significantly less effective. In one case, after five hours of no insulin, more than 25% of the patients showed no urine ketones but all had significant blood ketone levels.
- Lawrence Blonde, MD, spoke about HbA1c, Glycemic Variability (Stability) and Other Outcome Markers - What is the Most Telling?. Echoing some of the data presented at the 2005 Clinical Diabetes Technology Meeting by Dr. Irl Hirsh, Dr. Blonde explored glucose variability and its potential impact on the development of complications. He explored the concept of metabolic memory, in which good control early after diagnosis seems to have lasting benefits even if control worsens over the years. He also reported on a study which showed that patients with diabetes who took pramlintide (Symlin) had a marked reduction in oxidative stress.
- Howard Wolpert, MD, taught us about Using CGM in Diagnosing and Managing Hypoglycemia Unawareness - Discussion and Demonstration. Beginning with slides illustrating the hierarchy of physiological responses to hypoglycemia, Dr. Wolpert explained how repeated hypoglycemia leads to reduced neuroendocrine responses and results in what is called "hypoglycemia unawareness." He noted that continuous sensors, which measure interstitial fluid rather than blood, correlate better with the glucose levels in the brain and can help patients and doctors detect hypoglycemia unawareness, which is the first step to reversing it through scrupulous avoidance of lows for several weeks. Dr. Wolpert also noted that patients need to understand the difference between the pharmacokinetics (speed of onset of action) and pharmacodynamics (duration of action) of insulin to reduce the risk of stacked boluses.
- Darrell Wilson, MD, spoke on Impact of Real-Time Continuous Readings on Children and Their Families, a topic near and dear to CWD readers. Beginning with the question, "How low is too low, and how long is too long?", Dr. Wilson shared a slide that showed a CGMS tracing of a young man who had a severe nighttime low that ended in a seizure. He noted that the depth and duration of the low was significant -- 40 mg/dl or below (sensor had flatlined) for several hours -- indicating that the risk of seizure may be lower than people might think and that continuous sensors, even with today's limitations, may be good enough to make a big difference.
- Irl Hirsch, MD, presented Algorithms for Care in Adults Using CGM. Dr. Hirsch reiterated the need to reduce glycemic excursions. He also noted that reactive oxygen species, created in the presence of high glucose, are the key to complications. Dr. Hirsch's also noted that continuous sensors have taught us that insulin corrections have to take into account the velocity of change in glucose to prevent incorrect dosing, especially when the glucose levels are dropping. (Episodic monitoring can rarely generate enough data to offer direction data, much less velocity data.)
- Three people addressed What Will it Take to Get CGM Reimbursed - Examining Compelling Factors: Claudia Graham, PhD (Medtronic MiniMed), Charles Raine, MD, and Virginia Tobiason, RN (Abbott Diabetes Care). Each presented a slightly different perspective. Dr. Raine told a story about his own experience providing improved care that resulted in higher reimbursement rates for patient visits but an overall cost reduction for those patients. The three presenters agreed that new diabetes technology, from pumps to continuous sensors, have the potential to reduce the overall costs associated with diabetes by preventing complications (long term and from hypoglycemia), but the challenge remains to get them paid for within a health care system that rewards episodic encounters and which is ill equipped to cover the costs of long term care for chronic illnesses like diabetes.
- Patient Panel: Continuous Glucose Monitors -- What We Like and Don't Like was the final session of the first day and was chaired by Marilyn Ritholz, PhD and Stuart Weinzimer, MD, joined by a group of adults who wear continuous glucose sensors. The consensus of the group was that, while the current generation of sensors have their problems -- mostly related to sensitivity and specificity of alarms -- they are worth the effort and the price because use of the continuous sensors result in better diabetes care and better quality of life.
- Chan Cooppan, MD, opened the second day with a talk entitled Treatment Goals and Strategies for Type 2 Diabetes -- The Changing Landscape. He summarized the results of the EDIC Study, noting that good control early has lasting implications -- a phenomenon called metabolic memory. He stressed the importance of aiming for good control right away for patients diagnosed with type 2 diabetes, and noted that the use of insulin in type 2 diabetes should never be a threat, is not due to non-compliance, and is not a last resort.
- Robert Vigersky, MD, moderated a discussion about Algorithms for Intensive Insulin Therapy of Diabetes in the Hospital -- In the ICU and the Wards. He was joined by Stephen Clement, MD and Jeffrey Joseph, DO. A subsequent session entitled Eliminating Sliding Scale Insulin in the Hospital covered a similar topic. To summarize, good blood sugar control makes a huge difference in outcomes in the hospital setting, and the old sliding scale approach is not acceptable. Patients with diabetes who go to the hospital should insist on the best diabetes care to ensure the best possible outcome.
- In Exenatide (Byetta®) and Other Incretin Mimetic Therapies -- A Look at Changing Treatment Paradigms, John Buse, MD, PhD, explained the importance of the first in a new class of drugs. People with diabetes not only have a lack of insulin, but also exhibit an abnormal rise in glucagon levels after a meal, contributing to spikes in post prandial blood glucose levels. Exenatide, marketed as Byetta® by Amylin, counteracts this rise and can result in essentially flat post prandial blood glucose levels in adults with type 2 diabetes. Based on several slides presented, the result was better with regular insulin injected 30 minutes prior to eating compared with a fast-acting insulin analog taken immediately prior to eating.
- Diane Karl, MD, presented Therapeutics of Pramlintide (Symlin®) in Type 1 Diabetes. Symlin is also by Amylin, but unlike Byetta®, Symlin® is for people with type 1 diabetes. Like Dr. Buse, Dr. Karl noted that post prandial increases in blood glucose are the result not only of the food eaten but also an increase in the production of glucagon in people with diabetes. Simply increasing the insulin dose is not enough to counteract this effect (see The Role of Amylin and Glucagon in the Dampening of Glycemic Excursions in Children With Type 1 Diabetes [Diabetes 54:1100-1107, 2005]). Pramlintide, however, effectively blunts this response and can lead to nearly flat post prandial blood glucose levels. Dosing Symlin requires care to prevent low blood sugars after meals, however.
- Moderator Robert Gabbay, MD, presided over a spirited Debate -- Pump vs. Basal Insulin / Advantages vs. Disadvantages. Satish Garg, MD, assumed the role of Devil's Advocate, arguing against pump therapy mostly from an economic standpoint, noting that the cost of pump therapy was significantly higher than MDI. He also noted that pump therapy is rare in Europe, yet their average A1c readings are 1% lower than in the US, which has the highest use of pumps. Steven Wittlin, MD, assumed the role of pump advocate. He noted that there are two distinct types of patients with type 1 diabetes, those with residual C-peptide production under 0.2 mmol and those with higher levels. Patients with higher levels of C-peptide have a lower of hypoglycemia and tend to do well on MDI as compared with patients with lower levels. Dr. Wittlin noted that only pump therapy can deal effectively with the dawn phenomenon in a reliable and predictable way, and that data suggests that glucose variability is lowest among pump users. Given presentations about the importance of reducing glucose variability to reduce the risk of complications, pump use wins out, according to Dr. Wittlin. Finally, Dr. Wittlin noted that pump users have a marked reduction in automobile accidents compared with MDI users.
Dr. David Klonoff (left) with Dr. Jeffrey Joseph. Dr. Klonoff leads the Diabetes Technology Society, and Dr. Joseph serves on the planning committee.
Dr. Laurie Laffel spoke about the limitations of episodic glucose monitoring to a full house
Dr. Howard Wolpert spoke about the use of continuous sensing in treating hypoglycemic unawareness
Dr. Irl Hirsh (left) fielded questions from Dr. Barry Ginsberg (right) after his talk about algorithms for continuous sensing in adults
Claudia Graham from Medtronic MiniMed took part in a panel exploring the challenges of securing reimbursement for new diabetes technology
Dr. Satish Garg, assuming the role of Devil's Advocate, smiles as he takes the microphone from moderator Dr. Robert Gabbay and prepares to argue against the use of insulin pumps and advanced technology, mainly from an economic perspective
Drs. Stuart Weinzimer, Darrell Wilson, Michael Bryer-Ash, and Daniel Crowe offer insights into the future of diabetes technology during the final session