The Diabetes Self-Care Specialists

1 333 E. Lancaster Avenue Suite 204 Wynnewood, PA 19096 Phone Fax The Diabetes Self-Care Specialists Greetings! The following is a summary of my observations and information gathered from the research posters, scientific presentations, and exhibits at the American Diabetes Association s Scientific Sessions in Chicago, IL, June 20-24, 2013. My personal slant/opinions are noted in blue with an OP/ED heading. - Gary Scheiner MS, CDE Owner and Clinical Director, Integrated Diabetes Services Artificial Pancreas Development Having demonstrated the safety and efficacy of its low glucose suspend feature (an important first step in bringing closed loop technology to market), Medtronic s Veo insulin pump and Enlite glucose sensors are on the verge of FDA approval in the In its closed loop research, Medtronic has also devised an innovative hyperglycemia correction feature based on current basal rates.

2 In closed loop systems using the Animas Ping insulin pump and (previous generation) Dexcom 7+ CGM, 20 adults had an average blood sugar of 135 mg/dl. Most participants had no glucose levels above 180. Overnight glucose levels were consistently within target ranges. Studies involving the OmniPod and Dexcom found that glucose levels could be held very steady overnight but were peaking quite high after breakfast. Similar results were produced in closed loop studies conducted in Spain. In a fully patient-controlled home use closed-loop system developed in Israel, the user had the ability to switch from manual control to fully automated control at the flip of a switch. The automated control (where a computer algorithm determined all insulin deliveries) reduced time spent in a hypoglycemic range by 50% and significantly increased the percentage of time spent within target ranges.

3 OP-ED: As CGM quality and computer algorithms continue to improve, the pathway to a cure for type-1 Diabetes appears to be headed in a technological rather than biological direction. Whole-organ pancreas transplant outcomes are improving due to better immunosuppression therapies, but the availability of pancreases (pancreata?) continues to be a major limiting factor. Many experts believe that an effective closed loop system will require the use of multiple hormones. A JDRF-funded group in Portand, Oregon has been using two OmniPod systems simultaneously (one with aspart rapid-acting insulin, one with glucagon) and the Dexcom sensor. Rapid infusion of glucagon when glucose was dropping reduced the incidence of hypoglycemia to near 0%.

4 However, post-meal glucose spikes continued to be an issue. BG rose an average of 90mg/dl after breakfast, 20mg/dl after lunch, and 60mg/dl after dinner. Researchers concluded that manual pre-bolusing at mealtimes will be needed to eliminate the peaks. This was validated in separate research (using OmniPod and the Navigator CGM). Manually pre-bolusing approximately 50% of the normal meal bolus lowered the overall average glucose level by 10-15 mg/dl. The relatively slow action of subcutaneously infused insulin has been a major limiting factor in preventing post-meal spikes. Investigators at the Sansum Diabetes Research Center In California have studied the use of intraperitoneal insulin delivery, whereby a catheter infuses the insulin into the abdominal cavity rather than the fatty layer.

5 They found that this route of delivery greatly accelerates insulin action to near insulin levels. Using the Dexcom 7+ sensor and Spirit insulin pump with intraperitoneal delivery, they were able to reduce post-meal peaks by 15 to 105 mg/dl. Progress in Pregnancy Closed loop studies with pregnant type-1 women in the United Kingdom showed that while insulin requirements change dramatically during pregnancy, the patterns ( peak/valley times) do not. It was also shown that because CGM sensors become somewhat less accurate during exercise conditions, sensor performance may suffer during labor. Frequent fingerstick testing during labor is recommended. Because insulin absorption becomes slower as pregnancy progresses, earlier mealtime bolusing and/or post-meal walking may be necessary to reduce post-meal peaking in later phases of pregnancy.

6 Staff at the Joslin Diabetes Center in Boston found that preeclampsia (elevated BP & proteinuria in the later stages of pregnancy, sometimes referred to as toxemia) is much more common in women whose A1c was elevated at the time of conception and during 1st trimester. High glucose levels early in pregnancy may interfere with the development of a healthy placenta. A poorly developed placenta secretes endothelial growth factors that contribute to preeclampsia. Further confirmation has been received that insulin lispro (Humalog) does not pass into cord blood and does not affect a developing baby. No increase in complication risk has been found in women using lispro. OP-ED Insulin aspart (Novolog) has very similar properties to lispro and has been used for many years without reports of problems.

7 Both are now considered class B in terms of safety during pregnancy. Insulin glargine (lantus) has not been studied intensively enough to warrant class B status, but small studies and countless individual reports have suggested its safety and efficacy. Unfortunately, many clinicians continue to recommend a known hindrance to quality metabolic control (multi-dose NPH) rather than use glargine which carries a very small potential risk but well-established benefits. I prefer to educate the patient on the benefits/risks so that she can make her own educated decision. Exercise Experiments Researchers at the University of Tennessee found that exercise is a more powerful tool for improving insulin sensitivity than metformin. Adding exercise to metformin offers additional benefit (better than taking metformin alone), but adding metformin to the regimen of those already exercising leads to a decrease in improvement in insulin sensitivity.

8 It is unclear why this is the case, but it speaks volumes about the importance of physical activity, particularly for those with type-2 Diabetes as well as insulin-resistant type-1s. OP/ED I attended as many exercise-related presentations as possible. Interesting to note that there was more than twice the attendance at presentations on medications that can simulate some of the effects of exercise (exercise mimetics ) as there were at presentations on exercise itself. Speaks volumes about trends in society. Despite the fact that diet/exercise are still considered first, front-line treatments for type-2 Diabetes , it appears that the majority of clinicians would rather prescribe pills than do what it takes to promote physical activity among their patients.

9 Researchers at the Mayo Clinic showed that cardiovascular exercise produces significant improvement in peripheral/muscle insulin sensitivity. One hour of moderate-intensity exercise led to nearly 100% more insulin sensitivity. Improved insulin sensitivity is one of the major benefits of physical activity in people with Diabetes . Research has shown that this improvement is completely gone 48 hours post-activity, particularly when glycogen stores are replenished due to carb intake following exercise. In addition, studies that involved cycling with one leg or both legs revealed that only exercised muscles demonstrate improved insulin sensitivity. Likewise, muscular exercise only effects muscle insulin sensitivity; the liver s sensitivity to insulin is unaffected.

10 OP/ED Because the reduction in insulin sensitivity takes place mainly during the 24-48 hour timeframe following exercise, I stand by my ongoing recommendation that people with Diabetes should strive for some form of exercise on a daily basis. Research showed that cardiovascular fitness and quality of life measures improve in direct proportion to amount of exercise performed. The more minutes per week spent exercising, the greater the improvement. In general, at least 75 minutes cardiovascular exercise per week, or two strength training workouts per week are needed to significantly reduce cardiac risks. The best results are seen from performing a combination of the two. Adding 30 minutes of strength training per week to one s usual cardiovascular workouts reduces cardiovascular risk an additional 23%.