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in this issue
From the Editor .............. 1 A healthy, happy baby shows how far we’ve come Learning Curve ............... 2 Why we like to pump it up! Logbook.......................... 5 Jackie Robinson’s secret Test Drive ........................ 8 Putting on the OmniPod diaTribe Dialogue ........... 11 Speaking with the CEO of insulin maker Novo Nordisk Profile.............................. 14 The woman who’s been on insulin longer than anyone NewNowNext ................ 16 What’s out: Janumet and FreeStyle Lite approved FingerSticks ................... 17 Jurassic variability? Conference Pearls .......... 18 To Seattle and back with new information What We’re Reading ...... 19 The latest research on inhaled insulin and stem cell therapy

research and product news for �������������������������������������������������� people with diabetes from the editor
Last week, my husband, John, and I had a beautiful baby named Lola. The experience has reminded me of how challenging diabetes is, but also how fortunate I am to have a great health care team and a supportive husband. We all know that diabetes is a family affair, but that is never truer than during pregnancy. Years ago, women with diabetes were discouraged from having children. Those days, thank goodness, are long gone. But while successful pregnancies are now fairly routine, I can attest that they are not necessarily easy. Maintaining normal blood sugars this time around took a lot of adjustments. And I would be lying if I wrote that we’ve had no uncertainties about the baby’s health. But the point is: we’ve come a long way. Fittingly, this issue’s loose theme is about just that. Pump therapy is considered by many experts as much better than its alternatives, and yet it’s underused. It is really just our sort of topic. A great Learning Curve describes how pumps have improved over the years and what they offer today, namely continuous insulin delivery that is much closer to the way a pancreas works than multiple daily injections. In a very personal Test Drive, I share with you not only my experiences on the fabulous OmniPod, but also the way I stumbled upon pumps years ago and how they changed my life. The first thing to look at in this issue may be the incredible Profile on Gladys Dull, who has been on insulin therapy longer than any other person in history. Where better to start than the early days of diabetes treatment? No pumps here – she spent most of her life using glass syringes and measuring her blood sugar by boiling her urine. Almost miraculously, she is now 90 and for the most part independent. Gladys, thank you, for inspiring us. Danish company Novo Nordisk is now the largest insulin maker. We are very impressed with this company, which has taken a leading role in urging the world to recognize diabetes as an epidemic and to curb it. Our discussion with the CEO of Novo Nordisk, Lars Rebien Sorensen, was quite revealing, about how governments must recognize that health care is not about treating diseases but about investing in the future, about Novo’s next generation of insulins, and more. Finally, I just want to say thanks again to all of you on our Patient Advisory Board. Just as we pride ourselves in having an excellent expert advisory board with the top educators, doctors, and other players in the diabetes community, we also pride ourselves in having a terrific Patient Advisory Board who keeps us on our toes. As always, we invite you to let us know how diaTribe can better serve you (team@diaTribe.us). We are, after all, one big family… plus one!

To subscribe to diaTribe, visit www.diaTribe.us.

Kelly L. Close

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learning curve
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Pumping Insulin: New Technology May Spur Greater Acceptance

By Daniel Trecroci and Kelly Close

diaTribe staff
Editor in Chief Kelly L. Close Managing Editor James S. Hirsch Contributers Daniel Belkin John Close Jenny Jin Daniel Trecroci Design Gina Wilson

he insulin pump has long been heralded as a revolutionary product in diabetes care – a brilliant delivery system that relieves patients of injections, a technology that can be programmed, manipulated, and tweaked to mimic a healthy pancreas. Pumps have their own evangelists who are mystified why any insulin-dependent patient would not use one, and in many ways their faith has been rewarded: the technology keeps getting better. Pumps are now more like powerful information-management systems than simple drug-delivery devices. They are small and discreet, they are being integrated with glucose meters and continuous glucose sensors, and they are central to the high-tech Holy Grail in diabetes management: the artificial pancreas. (Or, as some like to call it, the Artificial Pancreas.) But for all their improvements, pumps have never become more than a niche product. In the US, only about 21 percent of type 1 patients use a pump, according to Diabetes Care, and very few insulin-dependent type 2 patients wear one. The numbers are even worse abroad: in the United Kingdom and in Denmark, for example, pumps are worn by about one to two percent of type 1 patients.

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diaTribe advisory board
Jennifer Block, RN, CDE Dr. Zachary Bloomgarden, MD Dr. Bruce Bode, MD Dr. Nancy Bohannon, MD Dr. Bruce Buckingham, MD Dr. Wendell Cheatham, MD Dr. Barry Ginsberg, MD, PhD Debbie Hinnen, ARNP , BC-ADM, CDE Dr. Irl Hirsch, MD Jeff Hitchcock Dr. Lois Jovanovic, MD Dr. Francine Kaufman, MD Dr. Aaron Kowalski, PhD Mirasol Panlilio Dr. William H. Polonsky, PhD Michael Robinton Jane Jeffrie Seley, NP CDE , Virginia Valentine, CNS, BC-ADM, CDE Dr. Howard Wolpert, MD Gloria Yee, RN, CDE

Reasons for Poor Acceptance The product has never made greater inroads for several reasons. For one, many physicians are reluctant to prescribe them, let alone advocate for them. Clinicians must spend additional time to understand the pumps, additional time to train their patients, and additional time to handle the paperwork – but unbelievably, for the most part, they receive no extra compensation for their labor. What is that about?! Many patients themselves are not willing to invest the additional effort that pumps require. Money is also a factor. The pumps are expensive – about $6,000 for each device, excluding all the supplies – and some employer-sponsored health plans are cutting back on durable medical equipment coverage. No matter that pumps can improve our health dramatically over time. Some experts blame the pump companies for not educating patients on why they should use the product and for not training their existing customers on how to take full advantage of its many features. Those are valid points. Some observers contend that the pump companies don’t understand what they are promoting. We don’t go that far, but we definitely believe not all patients receive the right information about what pumps can do, so they are operating in the dark. To increase the use of pump therapy (which in the medical literature is called “continuous subcutaneous insulin infusion”), patient training and reimbursement will have to improve. But so too will the technology. Like any sophisticated machine, pumps occasionally break down, and while the companies will replace them, there is nothing like a “dead pump” to throw a family vacation into turmoil. Temporary glitches require immediate troubleshooting, and serious problems can arise if the patient is unaware that – for whatever reason – the insulin is not reaching its destination. The true price of any pump is eternal vigilance that must start and end with the patient. Pump Technology Continues to Improve Continued improvement in pump technology may not guarantee a surge in sales, but pumps that are easier, smarter, and safer – and those that are integrated with meters and
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The Accu-Chek Spirit

sensors – will stand a better chance. And the companies are spending their money accordingly. The MiniMed Paradigm REAL-Time System, for example, is the first to integrate an insulin pump with real-time continuous glucose monitoring. The new Animas 2020 has a flat-panel, high contrast color screen, the ability to store the previous 500 blood glucose values, and a food database. The Roche Accu-Chek Spirit has side-mounted tactile buttons for “no-look delivery” (you don’t have to withdraw the pump from your pocket, waistband, or bra). Deltec’s CozMore has a glucose meter attached to its back. And the one pump that does not rely on a tube – the OmniPod – consists of a lightweight device worn on the skin (like an infusion set), which delivers insulin according to signals from a handheld, wireless Personal Diabetes Manager.

Whatever its configuration, the pump’s aim is to replicate a healthy pancreas, which continuously secretes a low level of “background” insulin.

How Far We’ve Come It’s worth noting how far these pumps have come. The first models, in the 1960s, were mounted on backpacks. By the early 1980s, a pump could be attached to a belt, but it still weighed more than a pound, had flashing red lights, and was nicknamed “the blue brick” (though it was also reminiscent of a World War II-era walkie-talkie). Over the next two decades, the device became smaller, safer, more functional, more durable, and less uncomfortable. Pumps today are about the size of a pager or even smaller, and we know size drives sales and uptake, so we can’t stress enough to the companies how critical it is to continue to reduce the size. Most pumps are composed of a reservoir that stores insulin, which is continuously delivered to the body through a tube that connects the reservoir to the cannula. The cannula is inserted underneath the skin at the site where insulin enters the body, and this “infusion set” is usually changed every three days. (Type 2 patients need more insulin so they may change the set closer to once every two days, while many type 1 patients can push the change to once every four days, which is possible with most pumps.) The battery-operated pump delivers the insulin according to how the patient programs it. How a Healthy Pancreas Works Whatever its configuration, the pump’s aim is to replicate a healthy pancreas, which continuously secretes a low level of “background” insulin. But when the beta cells detect rising glucose levels, their insulin production goes into overdrive until glycemic order is restored. Imagine a graph with a flat production line interrupted by sharp spikes – that’s a healthy pancreas secreting background and mealtime insulin. People with diabetes try to recreate that graph through multiple daily injections of long- and shortacting insulins. This “basal-bolus therapy” is considered the gold standard for intensively managed patients, but an insulin pump is a more powerful, more flexible tool. It can be programmed to deliver a continuous amount of background, or basal, insulin, it can deliver a high-volume bolus dose before eating (typically, fast-acting insulin is used), a lower basal rate can be used during exercise, and “correction” doses can also be taken. “Pumps allow us to vary basal insulin levels to match the liver’s varying secretion of glucose through the day and night, and boluses delivered by the pump can be given with extreme specificity or delivered over a controlled period of time for slowly-digesting foods,” says Gary Scheiner, author of “Think Like A Pancreas,” in an interview with diaTribe. 1
1 We strongly recommend Gary Scheiner’s book, Think Like a Pancreas..

The Animas 2020

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Insulet’s OmniPod

Compelling “Smart” Features Become Standard Some of the more compelling “smart” features on the pump have become standard, and “insulin on board” is one of the most important. When you give an injection, the insulin remains in the body for a number of hours, but you don’t know how much is still active and for how long. Pumps now come with software programs that make that information available. The feature deters patients from “stacking insulin” – or giving a correction bolus for a high blood sugar when the existing insulin (“insulin on board”) may return glucose levels to normal. “One of the complexities of pumping insulin is that people give multiple [boluses] through the day, and the current rapid insulins have a duration of action that is far longer than most people realize,” says John Walsh, co-author of “Pumping Insulin.” “A conservative estimate is that it lasts at least five hours. The average time between boluses is probably less than four hours. So there is a lot of overlapping of bolus activity.” Several pumps will recommend how much insulin to deliver based on numerous criteria: your target range, your sensitivity to insulin, how many carbs you’re about to eat, and your current glucose level. The pumps have safety features to alert users when the insulin is not flowing properly or when the reservoir is low. They also have “multiple bolus options” – the “square-wave” and “dual-wave” boluses can spread the delivery of bolus insulin over time and are helpful when eating high-fat meals or when taking insulin with Symlin (See last issue’s Learning Curve for more information on this new drug for type 1 and type 2 patients who take insulin). Next Generation: Smaller and More Integrated with Other Technology What will the next generation of pumps look like? They will continue to become smaller, perhaps with more concentrated insulins in micro reservoirs. The tubeless, disposable OmniPod, which is easier to attach and has fewer “moving parts” than conventional pumps, appears to be a glimpse into the future: Other new pumps currently under development promise to be miniaturized devices taped directly onto the skin that deliver insulin subcutaneously. Like the OmniPod, other new pumps may be operated and programmed through remote control devices. Pumps will also become more “customizable” with personal alarms, reminders, and delivery options, and there will be a continued push to integrate with glucose meters and continuous glucose sensors. We also look forward to dual-chamber pumps that will allow us to infuse other drugs such as Symlin and perhaps Byetta (currently prescribed for type 2 patients). Better Pumps are Central to an Artificial Pancreas The ultimate prize is the artificial pancreas. In that scenario, a continuous sensor would signal to a pump how much insulin to deliver based on the current glucose level and its rate of change, and the pump would deliver the insulin without any human intervention. Some have called this closed-loop system a “technological” or a “mechanical” cure, or at least a way to ensure normal blood sugars regardless of how many pancakes you eat. The closest product to an artificial pancreas that is available is the MiniMed Paradigm REAL-Time Insulin Pump and Continuous Glucose Monitoring system. The sensor essentially “talks to” the Paradigm 522 or 722 pump, giving the user access to real-time glucose readings every five minutes and recommendations on boluses. It is still an openloop system, because the patient delivers the insulin, and we believe open-loop systems will
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MiniMed’s Paradigm pump and continuous glucose transmitter

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From the expert: John Walsh, author of Pumping Insulin, on the

closed loop: Pumps have a tremendous advantage in accuracy of dosing boluses. Just the fact that you are wearing a pump and giving boluses, which are easier than taking injections, suggests that you are going to more accurately cover your carbs.

continue to improve and that, in fact, the power of the open loop may be underestimated. Getting to a true closed loop requires more than a more perfect sensor. It also requires the right algorithms and probably glucagon (what’s known as a counter-regulatory hormone), which in turn may require a dual-chamber pump. Studies at Yale University have demonstrated the feasibility of a fully closed loop system, though they’re being done in the clinic and with significant monitoring. The trials are part of the JDRF’s (Juvenile Diabetes Research Foundation) Artificial Pancreas Project. The biggest hurdle right now is that the insulin, sent by pumps into subcutaneous fat, takes too long to take effect and then takes too long to stop working. This is true even for the fastestacting insulin; and even if a more rapid-acting insulin becomes available, that might still be too slow. This is why, in addition to progress with new pumps, we are also closely following developments where faster-acting insulins, more concentrated insulins, and other valuable hormones could be infused, all with the goal of making a diabetic’s body more closely resemble that of a healthy person without diabetes.

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Jackie Robinson, Diabetes, and an Opportunity Lost
By James S. Hirsch

The tragedy is not simply that diabetes killed a great man who still had so much to give. It is that Robinson himself - who spoke out forcefully on civil rights, politics, and business - wanted to keep his disease quiet, and those who carry on his name have continued that legacy.

full-page newspaper ad, celebrating the sixtieth anniversary of Jackie Robinson’s first Major League baseball game, said: “He was a soldier, a writer, an activist, a politician, a voice, a leader, a father, a husband, and a friend.” He was all of those, and he was something else. He was a diabetic. Last month’s anniversary of Jackie Robinson’s historic achievement allowed America to remember his extraordinary life. In 1947, when he played his first game for the Brooklyn Dodgers, he shattered some of the country’s most pernicious, yet deeply held, biases toward black Americans. During his career, he withstood racial epithets from opposing players, threatened boycotts from his own teammates, hostile boos from fans, and death threats from enemies. But he played with daring, skill, and courage, amassing a Hall of Fame career while also serving as a front-runner for the modern civil rights era. As the author Jonathan Eig wrote, “Robinson showed black America what was possible. He showed white America what was inevitable.” Accordingly, Robinson has been celebrated in books, movies, documentaries, songs, short stories, poems, term papers, and sermons. Yet precious little has been written or said about the role of diabetes in Robinson’s life – how it may have cut short his baseball career and how it certainly cut short his life. The tragedy is not simply that diabetes killed a great man who still had so much to give. It is that Robinson himself – who spoke out forcefully on civil rights, politics, and business – wanted to keep his disease quiet, and those who carry on his name have continued that legacy.

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Why Robinson’s Diabetes Matters Why does it matter that Jackie Robinson had diabetes? Because perceptions matter, and Robinson could have blunted some of the misperceptions that existed during his life and to some extent still remain: that the disease only affects people who are old or overweight, or that the discovery of insulin has either cured the disorder or at least made it not that serious.
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Jackie Robinson

Patients, of course, have always known the realities of diabetes, but over the years, they rarely advocated for themselves. On the contrary, they were more apt to conceal or even lie about their condition, either out of misplaced shame or genuine concerns about discrimination. The landscape changed somewhat with the founding of the Juvenile Diabetes Foundation in 1970, which became an energetic voice for diabetic children and enlisted several celebrities (most notably, Mary Tyler Moore) to the cause. But even as diabetes became a mainstream disease, it’s had difficulty gaining traction as a serious public health threat. In a recent speech, President Bill Clinton acknowledged that he didn’t understand the scope of the epidemic until after he got out of office. Between 1980 and 1994, NIH’s research dollars for diabetes – as a percentage of its entire budget – declined slightly even as the number of diabetics had doubled. What the diabetes community has lacked is urgency (see: AIDS activists), public figures (see: Michael J. Fox, Parkinson’s), and national commitments (see: polio, 1930s). Why does it matter that Jackie Robinson had diabetes? Because his story, if known, could be a rallying cry for better care, for more research dollars, for greater understanding – and a poignant reminder of the true costs of this disease.

ILLUSTRATION: DANIEL BELKIN

What the diabetes community has lacked is urgency (see: AIDS activists), public figures (see: Michael J. Fox, Parkinson’s), and national commitments (see: polio, 1930s).

Hyperglycemic While Still in Uniform Robinson’s health problems began while he was still playing for the Dodgers. His knees and ankles chronically hurt, and his arm was often sore. He also struggled with his weight. After his rookie season, he went on a celebration tour through the Deep South, “ate like pigs,” and gained 25 pounds. His weight would fluctuate throughout his career. Robinson retired at age 37. After 10 seasons, his performance had begun to decline, and his health was also poor, though it’s unclear if he was diagnosed with diabetes while he was still playing or immediately after. In what’s considered the most definitive account of his life, “Jackie Robinson: A Biography,” Arnold Rampersad wrote that he was diagnosed “about the time of his retirement.” If nothing else, it’s safe to assume that Robinson was hyperglycemic while still in uniform. Robinson discovered his diagnosis on a routine visit to his physician. “He left in high spirits,” said his friend, Jack Gordon. “But when he came back … he was very quiet. He said that the doctor had told him that for someone who had played sports for so long and didn’t smoke or drink, he had never seen a body so badly deteriorated. Jack found out he had diabetes. It was very, very sad.” His diagnosis could not have come as a complete shock. Two of Robinson’s brothers, Edgar and Mack, already had diabetes. Jackie was immediately prescribed insulin. He initially practiced his injections on tomatoes, then he took the shots himself. His biggest challenge was his diet. As his wife, Rachel, told Rampersad, “He used to put away a pint of ice cream at one sitting. That stopped, along with the pies and cakes.” A Painful Connection to His Mentor In a painful twist of history, diabetes would forge another link with the man most responsible for Robinson’s fame. Branch Rickey, as the president and part-owner of the Brooklyn Dodgers, signed Robinson with the team and then became Robinson’s beloved mentor and father figure. Unfortunately, Rickey’s eldest son, Branch Jr., also had diabetes, and he died from complications in 1961 at age 47. In his retirement, Robinson was involved in business and politics, he wrote a newspaper
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When a fan asked him to sign a baseball, he said, “I’m sorry. I can’t see it. ”

column (tackling subjects ranging from housing to migrant workers to trade unions), and he was active in the civil rights movement. His biographies cite no examples of his speaking out on diabetes, but the disease hospitalized him on several occasions. His heart was balking, his sight was beginning to cloud, and his decline was irreversible. By 1969, he was still seen as a paragon of strength and courage, but his doctor could not discover a pulse in his legs. He told Rachel Robinson that her husband would be dead in two or three years. “Jack did not want to hear that news,” Rachel told Rampersad. “He would not talk about death. Denial was his greatest prop, and he denied that he was dying.” The following year, Robinson suffered two mild strokes that left him unsteady and with numbness on his left side. Blood vessels continued to rupture in his eyes. In 1971, he received experimental laser surgery, but the vision in his right eye was almost completely gone; and his left eye was badly impaired. By 1972, walking had become increasingly difficult, and his doctors knew that both legs, lacking sufficient blood supply, needed to be amputated. Robinson, however, refused to succumb to self-pity or even acknowledge his own mortality. As his doctor noted after one visit, “The patient, as always, says he feels great.”

Now, at a time when type 2 diabetes is ravaging the African American community, some medical leaders recognize that Robinson’s secretiveness represents a lost opportunity.

An Autobiography, and a Missed Opportunity In 1972, Robinson’s autobiography, “I Never Had It Made,” was published. By then, he knew what diabetes had done to his life – he couldn’t even read the galleys – and he (or his ghostwriter) could have used the book as a platform to raise awareness of diabetes and urge improvement in care. Just as he walked onto Major League ball fields to clear the path for future generations, he could have spoken out for patients who would follow his footsteps. Instead, Robinson only made two fleeting references to diabetes, in ways that completely misrepresented the condition. “Although I have lost one eye and have impaired sight with the other,” he wrote, “there has been remarkable improvement recently. I’ve always been a fighter, but this is one fight I could have never won alone.” The fight didn’t last long. On June 4, 1972, he attended an Old Timers’ Game at Dodger Stadium, and – as one observer wrote – “when he walked out on the field to be introduced to the wildly cheering crowd, he walked like a man of 80.” Then on October 15, he was honored before a World Series game, and he gave a speech most remembered for his plea that Major League baseball hire a black manager. When a fan asked him to sign a baseball, he said, “I’m sorry. I can’t see it.” Jackie Robinson died nine days later, at age 53. A Hole in a Hero’s Legacy Around the time of his death, at a public meeting sponsored by the American Diabetes Association, then president Max Ellenberg cited Robinson as one of those famous figures who kept their disease “in the closet.” Now, at a time when type 2 diabetes is ravaging the African American community, some medical leaders recognize that Robinson’s secretiveness represents a lost opportunity. Former ADA president Ronald Arky, for example, vividly remembers radio announcer Red Barber’s description of Jackie Robinson dancing off first base as he prepared to steal second; Arky says he’s always wanted to speak with Rachel Robinson about the onset of Jackie’s disease, his family history, and his treatment, but he never has. It’s possible that Robinson didn’t talk about his health because he didn’t want people to feel sorry for him. He may also have felt shame or embarrassment. He wouldn’t be the first, nor last, to feel that way. And how much more could we expect from Jackie Robinson? A hero only has so much heroism to give. But we can expect more from others. To sustain her husband’s legacy, Rachel founded
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the Jackie Robinson Foundation, which provides college scholarship money and mentoring to minority youths. The Web site, which includes a biography of Jackie’s life, makes no reference to diabetes. Mrs. Robinson, who is now in her 80s, looked radiant during her speech at Dodger Stadium last month to celebrate the anniversary of Jackie’s arrival in the Major Leagues. But asked to be interviewed for this column, a spokeswoman, Barbara Tribble-Sawyer, said: “She does not want to be interviewed on this subject.”

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Test Driving Insulet’s OmniPod System
By Kelly Close

I foresee OmniPod making a difference in how many diabetics use pumps.

I’ve said that I would sacrifice my cell phone for an OmniPod – and those who know me will tell you that is huge. For me, it’s the best product that has come along in a decade. Symlin actually comes close, and then the other pumps are way up there, but the quality- of-life improvements that OmniPod offers have been enormous. It truly is a breakthrough, and really, so few breakthroughs come along in this diabetic life. The OmniPod, of course, is by definition an insulin pump, and there are many important reasons for using a pump (see this issue’s Learning Curve). As a group here at diaTribe, we think it’s fantastic that insulin therapy can be more physiologic, or more similar to the body’s natural functions. In other words, the pump, continuously supplying small amounts of insulin, approximates a functioning pancreas much more closely than do multiple daily injections of insulin. Honestly, it’s crazy to me that only 20% of type 1s and a very small percentage of insulin-using type 2s are using pumps. Insulet, which makes OmniPod, was until recently a small private company; in May, it went public with the goal of expanding capacity, and I foresee OmniPod making a difference in how many diabetics use pumps.

The Device There are two pieces to the system: one is a Personal Diabetes Manager, or “PDM,” which is kind of like a Palm Pilot or a big Blackberry. This controls the other piece, the pod, which is attached to the patient. The PDM has a FreeStyle blood glucose meter built in. It’s about three by four by one inch, bigger than most meters, but not significantly. When you get the PDM, you work with your healthcare team to program it. • Basal rates (mine varied between 0.5 – 0.7 mg/hour until I got pregnant recently – then they were 1.0 – 1.5 mg/hour!) • Target glucose levels (mine was 100 mg/dL until pregnancy, then it went to 80 mg/dL – hypoglycemia was very rare for me in pregnancy, so it was safe to reduce this) • Insulin-to-carb ratio (mine was 14 units per carb pre-pregnancy, and five during the last few months of pregnancy!) • Insulin sensitivity (this means how much 1 unit of insulin lowers your blood glucose – mine was over 50 mg/dL pre-pregnancy and 45 mg/dL during pregnancy) • You can also program a bunch of other choices, like whether you want a reminder an hour (or two or three) after you eat to tell you to check your blood glucose, if you’ve missed a bolus dose, or whether you want any sound at all on your meter The programming takes about 5-10 minutes, and then you’re ready to start your OmniPod. When you take the pod out of the packaging, you fill it with insulin, which takes about 30 seconds. Then the PDM (it is so friendly!) asks you if you’d like to put on a pod. Why, yes! So it instructs you – just like that! – to fill the pod with insulin. You receive a syringe with every pod, and you just withdraw the amount of insulin (minimum
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The OmniPod

I really get the impression, crazy as it sounds, that [the OmniPod] cares about me...

I’ve only had to call the [customer service] desk a few times, but when I have, the reps were extremely knowledgeable and efficient. Turns out they are all type 1 diabetics!

85 units - maximum 200 units) you require for three days and fill the pod through a fill port on the underside of the pod. Two hundred units of insulin is the maximum, which is a drawback – I never used to use so much insulin, but I found in pregnancy, it barely lasted the three days, so for some type 2 patients, this wouldn’t be enough. Then the PDM asks if you are ready (again, so friendly! I really get the impression, crazy as this sounds, that it cares about me…), and you take off the pod’s adhesive backing and place it on your stomach, back of arm, or leg – plenty of flexibility because you aren’t constrained by tubing. You can put it anywhere there is fat tissue. Then you press “start” on the PDM – and I always do this gleefully, because I never feel it – “go!” You hear a little “click, click, click…” which I find reassuring, and then the needle goes in at 1/200 of a second and then comes right back out, leaving the cannula under your skin. I’m not sure if it is because I don’t see it go in, or because it’s so fast, or because it’s automated, but for such a long time, this “auto-insertion” was my favorite thing about the pod. I didn’t feel it, while the insertion of my other pumps had always been my least favorite thing about them. After insertion, you’re off and running with your basal insulin. You wear the pod continuously for three days (it tells you when it’s time or insulin is running out) and then remove it and throw it away. Swapping to another pod only takes about 90 seconds – super fast and easy – basically just filling the new pod with insulin and saying “go.” This device is very easy to maintain – you don’t need to clean anything. You do get in trouble if you forget to take a pod – and you need to switch your existing one – because the alarm is very, very loud and you can only quiet the alarm intermittently, but if the pod wants to get your attention, you can’t ignore it! While you’re wearing the pod, you use the wireless PDM to program doses or adjust basal rates. To program a bolus, you first take a blood glucose test, just like with a regular FreeStyle meter, and you get your result, and then press next. I love how all this works. My husband is very technical, and he was helping me and he said “Nice UI…” approvingly the first time I tried it. “ Thanks!” I said, pleased with my score of 122 mg/dL. “No, sweetie,” he laughed. “You’re lovely, but I was talking about the PDM. Nice UI. That means nice user interface. This means I like how it’s so logical. Press ‘next!’” I did, and the PDM asked if I was planning on eating, which I was – enter 30 carbs! Then there appeared the bolus dose it was telling me to take. This wasn’t unlike my old pumps – I also think the “bolus estimator” function on pumps has been a breakthrough – but the screen on this is pretty big, and I just liked the PDM’s personality. Then I hit “go” and a wireless signal was sent to the pod, which delivered my bolus dose of insulin. Insulet is working on combining the OmniPod with FreeStyle’s soon-to-be-available continuous glucose monitoring system, Navigator – I think this holds a lot of promise, but I imagine that will take a couple of years. Even though the interface on the PDM is easy to set up and learn, the PDM still has all the sophisticated options that a serious patient would want, like a bolus wizard (which determines your bolus) and an “insulin on board” feature (which deters overdosing). The PDM also has a food database, reminders, a quiet alarm (some like it loud, but I don’t); and, best of all, it doesn’t need to be connected to me! It’s also worth noting that Insulet’s customer service desk is excellent – perhaps because all its members are type 1 patients who also wear the pod. (Now, that’s standing behind your product.) I’ve only had to call the desk a few times, but when I have, the reps were extremely knowledgeable and efficient.

PHOTO: DANIEL BELKIN

An evolution in pumps As I described in an interview with a top teen Web site for diabetes (diabetesteentalk. com), over the past 10 years I have worn both the MiniMed and Animas pumps. The
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...I can still vividly feel what it was like to wake up in the ambulance. It always felt the same – ‘Oh, not this again’ – and I would close my eyes and hope it was a dream.

With a way to mimic my pancreas’ insulin secretion every minute, four shots a day suddenly seemed like a very blunt tool.

I was intrigued by the ‘no tubing’ concept, but the idea of leaving it on for three days seemed like a deal breaker.

MiniMed 507 was the first series of pumps I started on – life changing. I cringe when I think of what I did before that from the late 1980s to the mid 1990s – on a fixed insulin dose for most of that time, mainly NPH and regular. I was in and out of the emergency room for hypoglycemia at least once a year, and I can still vividly feel what it was like to wake up in the ambulance. It always felt the same – “Oh, not this again” – and I would close my eyes and hope it was a dream. It was in the mid-1990s, when I was working on Wall Street, that I was asked to develop an opinion for investors on MiniMed as a small public company. I had been very against pump therapy – probably, I was just against thinking actively about my diabetes. The body-image stuff really bugged me, and I didn’t want a constant reminder of my diabetes anywhere, much less to wear. My A1c at the time was 7 percent or so, and my doctors would assure me that below 8 percent was “very good” – this was before everyone was so focused on the importance of tight control! Anyway, I said I would go on the pump for a week to determine whether MiniMed was a positive investment. Going to MiniMed to meet the leaders, I learned about the benefits of physiologic therapy – the more you can mimic an actual pancreas, the better. With a way to mimic my pancreas’ insulin secretion every minute, four shots a day suddenly seemed like a very blunt tool. Inside a day, I vowed never to go off pump therapy. I felt so much better on it, almost immediately. Life was more flexible: I could exercise without fears of hypos, I could eat more, I could give a “shot” just by pushing a few buttons. Now, not all was rosy – I found the insertion painful, I hated when my infusion set pulled out accidentally, and sometimes I just wanted people to stop asking about it. When MiniMed was bought by Medtronic in 2002, I started having problems with customer service and stumbled upon Animas at a conference. I used Animas all through the 1200 series. I thought the pumps were sleek and worked well, and I loved the “insulin on board” and the other “smart pump” features. At this time, there seemed to be so much innovation – more than we had seen in years. So why the move to OmniPod? When I volunteered for the clinical trial – I love clinical trials – I didn’t think anything could prompt me to change permanently from Animas. I was intrigued by the “no tubing” concept, but the idea of leaving it on for three days seemed like a deal breaker. To my surprise, I loved it. It was more discreet than other pumps, which for me was so key. It was faster and easier than my other pumps, and it really was as smart as my old pump. It was a good time for change – I had just had my daughter, Coco, who would pull out my infusion sets, which was incredibly depressing. It was nothing I couldn’t get over, but putting those in was the worst part of being on a pump, and the OmniPod’s autoinsertion is so much less stressful for me. Because it has no tubing, it is easily hidden. I’ve worn it nearly everywhere, though I’ve noticed that my abdomen has the best absorption (this varies from person to person). Many wear it on the back of the arm, possibly the least cumbersome location. I love hiding it. Even though I’m pretty glass-half-full about my diabetes, I do get sick sometimes of telling my story whenever someone asks about my pump (before that, my pen, or syringe). I am still asked sometimes, and typically I’m pretty upbeat about it because I feel lucky, but I’m not now answering in response to my pump, because it’s never really visible. It’s small – about half the size of a regular pump – and of course I’m hoping it gets even smaller – and it’s always hidden under my clothes. Since the OmniPod is always attached to me, some people ask whether I can suspend the flow of insulin, for exercise, for example. Yes, you can. I walk a lot and I always suspend it half an hour before my walk. If I don’t, my BG drops 50 points minimum. I would do that with any pump. The pod is waterproof, so there’s no issue with showering or swimming. Apparently, the insulin in the pod may have problems in hot tubs, but you can prepare for that by putting it in your upper arm. Technically, the company says it can only be immersed
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8 feet for 30 minutes, but that’s not really very restrictive unless you’re a scuba diver, which I’m not (I made the mistake of admitting I was diabetic when going for training a couple of years back – I’ll have to not tell the truth next time!) — Continue reading about Kelly’s experience with the Omnipod online at www.diaTribe. us/issues/4/test-drive.php with the device and how to sample one.

diaTribe dialogue
Lars Rebien Sorensen does not have diabetes, but he may be the most important business leader in the field today. As president and chief executive officer of Novo Nordisk, he heads the world’s largest insulin company – its products are used by 15 million people around the globe each day – and Novo has taken the lead on raising awareness of the epidemic. Most recently, it sponsored the Global Changing Diabetes Leadership Forum in New York, which we attended in early March, and former President Bill Clinton was the keynote speaker. He emphasized that three things are needed to slow down the pandemic: vision, leadership, and money. Right now, Mr. Sorensen and his company are providing all three. In a conversation with Kelly Close and Jim Hirsch, Mr. Sorensen discussed the need for governments to recognize that health care is not about treating diseases but about investing in the future, the development of Novo’s next generation of insulins, and the reasons why the pharmaceutical industry needs to repair its reputation. Kelly: Thank you so much for taking the time to speak with us. What steps would you like to see industry, government, and health care professionals take to improve diabetes care? Mr. Sorensen: I think we’re basically talking about a problem of chronic disease, which is the biggest public health threat we have in many societies. And we believe diabetes is a model that can be used for how to deal with it, how to monitor it, how to treat it. But no single institution is able to solve this problem on its own, and therefore, we need to come together – patient associations, health professionals, governments, NGOs (nongovernmental aid organizations), and industry – because otherwise we can’t solve this.

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Lars Rebien Sorensen

Lars Rebien Sorensen

Jim: But once everyone comes together, what should they be doing? Mr. Sorensen: Well, I think we need to recognize that we each can play a role, and if we work together, I think there’s a win/win situation possible. For example, ideally, we should create health care systems that are capable of preventing chronic disease, but if that’s not possible, health care systems should diagnose and treat early rather than treating late. Then it’s a win/win situation for everybody because diabetes is not costly if diagnosed and treated early, but it’s very, very costly if it’s left untreated. So there’s an industry interest, looking upon it from our perspective: more awareness will lead to more diagnoses, which will lead to more advanced and more aggressive therapies, which leads to more business for the pharmaceutical industry. This would also reduce patients’ suffering and complications. It would help society with reduced health care costs in the long run. So I think there is legitimate interest on behalf of all stakeholders in working together. Kelly: How has the global diabetes epidemic affected Novo Nordisk – its product line, its research and development, or its mission?
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...Ideally, we should create health care systems that are capable of preventing chronic disease...

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Insulin had a bad connotation. But clinical studies have shown that diabetes needs to be treated as aggressively and as early as possible, to reach near-normal glycemic levels.

Mr. Sorensen: Therapies today are not sufficient for people with diabetes to live normal lives. So there is a lot more that we can do from the research side – there are still new drugs, and Levemir and GLP-1 therapy in particular are ways of addressing this. (Note: Liraglutide, Novo’s GLP-1 mimetic, is currently in phase 3 clinical trials. It works through the same mechanism as Amylin’s Byetta.) There are a lot of therapies that are being promoted today – DPP-4 inhibitors from Merck (Januvia) and Novartis (Galvus, not yet approved) in the future, as well. These are all new therapies, including inhaled insulins, which are more convenient for the patient. And then there is still a lot that can be done in terms of developing clinical practice guidelines and dietary guidelines so our people can appropriately treat themselves. There’s an amazing lot of work that can still be done. Kelly: It’s fair to say that your biggest product, insulin, is under prescribed or under used, certainly in the US, because there’re so many people who are taking it who are not at glycemic target. What do you think Novo or the other insulin companies should do to increase the use of the product? Mr. Sorensen: It is interesting that diabetes and severe diabetes have often been associated with insulin therapy, so physicians would often encourage patients to treat themselves properly, otherwise they would be put on insulin. So historically insulin was used as a threat in some ways, and to many patients, it was viewed as the end stage of the disease. Insulin had a bad connotation. But clinical studies have shown that diabetes needs to be treated as aggressively and as early as possible, to reach near-normal glycemic levels. That is where the new therapies, like GLP-1, are important, because patients are concerned about going directly from oral agents to insulin. Insulin has traditionally had the side effects that you’d gain weight and that there may be hypoglycemia, though the latter is not very significant as it relates to type 2 diabetes - it’s more significant for type 1 diabetes. So GLP-1 has presented itself recently as an intermediate step between oral therapy and insulin. So we expect these new therapies will all find their own niche, and it’s up to the physician and the patients themselves to decide how aggressively do they want to treat themselves, because we have to understand that the more aggressively the patients treat themselves, the more they infringe on their personal and private life in terms of either having to monitor blood sugar or having to take injections or multiple injections. And so it is a balance between the patient wanting to have a quality of life and the risk of developing complications long term. Kelly: What has to happen to make diabetes the urgent issue that it should be? Mr. Sorensen: Well, I think you’re touching on a very central thing, which is also one thing that I asked President Clinton about. It’s going to be interesting to see how we will make significant change unless we also look at the financing of the health care system. In my country, where we have a public health system, we view prevention and early intervention as investments – long-term investments in the future well-being of the population. Whereas in insurance-based systems, it’s often difficult to see how they are able to invest, because people keep moving to different companies. And therefore the interest in investing in long-term prevention and health is significantly less. So in the US context, I think the main thing we need to get is major employers involved. We need to get the government involved because the government at the end will have the responsibility when uninsured individuals develop the complications of diabetes. And large employers will often carry the responsibility of their workforce for an extended period of time.
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In my country, where we have a public health system, we view prevention and early intervention as investments – longterm investments in the future well-being of the population. Whereas in insurance-based systems, it’s often difficult to see how they are able to invest, because people keep moving to different companies.

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Talking with the chief medical officer of Novo Nordisk, Dr. Alan Moses Q: For some very poor people in the US and around the world, insulin is too expensive to purchase. Do you believe that an insulin company has a responsibility to provide insulin – for free – to any diabetic who cannot afford it? A: Access to health is something Novo Nordisk has worked actively to address for a number of years. Among other things, we helped found the independent non-profit organization, the World Diabetes Foundation (WDF), in 2001 with a grant of 500 million Danish crowns (about 67 million euros or 90 million dollars) to be spent over 10 years. The WDF works to build capacity, infrastructures and access to diabetes care in the poorest parts of the world. To date the WDF has started 57 ongoing projects in more than 65 countries with an estimated direct impact on 24 million people in the developing world. Novo Nordisk also offers human insulin to the public health systems in the 50 least developed countries (LCDs), as defined by the UN, at prices not to exceed 20% of the average price in North America, Europe and Japan. In 2005, Novo Nordisk offered this pricing policy to all 50 countries and sold human insulin in a total of 32 countries at or below this price. Compared to many other drugs, insulin is already a low cost medication that most health care systems can afford. However, lowering costs of medicine or giving away free products are not the sustainable answer to a long-term problem. Indeed, in some countries it is not the cost of the insulin but the distribution systems within the country that prevent access for patients in need of this life-saving treatment. We need initiatives that address the root cause of the problem of limited access to health care providers and medications.

Kelly: Maybe you could talk a little bit about your mission to defeat diabetes and what that means to you and what you think it means to your employees. Mr. Sorenson: Well, it comes from a simple recognition, and that is if we align ourselves with the interests of people with diabetes, they’re interested in getting rid of that disease. If I could just brush aside that wish by saying it’s not technically or scientifically feasible, then we could go on selling our products. But I can’t do that. We know there is scientific progress that seems to indicate there might be something we can do – stem cells and other therapies. And therefore we also have to engage in this and do our part, and as I tell my employees, it’s better that we eradicate diabetes than somebody else. And we’ll find another business as part of the process. Or if nothing else, we just made the final commitment to the disease. So if it can be done, it will be done. Kelly: In light of that, what keeps you up at night? What do you worry about the most in terms of your business? Mr. Sorensen: Well, I just spoke to a lot of our employees today [about this]. And one of the things I worry the most about is the quality of our products. We service about 15 million people with their daily needs of insulin, and if we don’t make the proper quality and have the proper controls of our product, somebody is going to get hurt, and that’s the worst thing that could happen. We know there are risks involved in drug research, and that’s a publicly understood risk. It’s a risk that people that enter into these clinical trials understand, and they commit to that risk because they want to further research. So there are problems, of course. We try to avoid it but that’s an inevitable risk we run. But not being able to supply adequate quantities of a high-quality product … could affect millions of people’s lives. That’s the worse fear I have. Jim: Regarding your products, can the insulins get better than where we are now, or is it now just a matter of finding smarter ways of dosing? Mr. Sorensen: That is the most exciting thing. Right now we are working on developing yet another generation of insulins. So Levemir, when you look at it, is fantastic basal insulin, but it still has a duration of action which is slightly less than 24 hours. It has the benefit that you’re not gaining as much weight as the traditional NPH or long-acting insulin. When we look at our research portfolio, we have in early research and clinical trials new and further improved basal insulins, which might even be formulated as premixes. This may not be available for another five years, but it’s very, very encouraging research that we’re seeing at the moment. Kelly: This would be even beyond the rapid-acting analogs like Novolog and Humalog, like a super analog or something like that? Mr. Sorensen: Yes. Whether we can improve it even further from that, I don’t know at this point, but this will give significant benefit to those that use our products. I’m quite certain about that. Kelly: There’s been a lot of coverage in the media about obesity as the driving force behind diabetes. What do you think can be done about that?

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Mr. Sorensen: I don’t believe that obesity prevention and treatment is a medical problem, in general. It’s a social and cultural and societal problem that we need to deal with from a different perspective. But when we then see that there are groups of individuals having had unsuccessful attempts to diet or exercise or at counseling then we start to talk about medical intervention. And in that case, I think that perhaps GLP-1s might play a significant role in the future because we know the GLP-1 product actually reduces weight. But treating people who are just slightly overweight is absolutely not something that we want to do. — Continue reading online about developing countries, the pharmaceutical industry’s reputation, and inhaled insulin online at http://www.diaTribe.us/issues/4/diabetesdialogue.php.

profile
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The Durable Diabetic: Gladys Dull Relies On The Basics To Make Medical History

By James S. Hirsch

Gladys Dull

She has been on insulin therapy for 83 years – longer than any person in history.

She was three years old when both her parents died from the Great Influenza. Her four siblings scattered to live with relatives, but she was taken in by neighbors in Granville, North Dakota. She grew up on a wheat farm, which fell on hard times during the Great Depression. The Dust Bowl finally drove the family off the land. Gladys Dull ended up in Walla Walla, Washington, and now at 90 years old, she is an American survivor – but not just for the hardships endured by so many of her generation. In November of 1924, at age seven, Gladys became deathly ill and was diagnosed with diabetes. Her doctor didn’t know how to treat it, other than to instruct the girl to eat meat. (Carbohydrates would further raise her blood sugar.) Insulin had been discovered two years earlier, but very few clinics had the drug and certainly none on the wind-swept plains of North Dakota. Her parents scraped up the money for a train to Rochester, Minnesota, where they took their adopted daughter to the Mayo Clinic. There, Gladys received her first insulin shot. Since then, she’s taken 60,000 more and has been on insulin therapy for 83 years – longer than any person in history. “I’ve never missed a shot in all those years,” she says. “Not one shot.2” Gladys Dull’s longevity is partly attributed to genetics, which can play a role in protecting against diabetic complications. Dull has virtually none, so her genes have clearly served her well. But other long-time patients have taken full advantage of the new tools and technology in diabetes care, giving them maximum opportunities to reduce their health risks and extend their twilight years. Oddly enough, Gladys has avoided therapeutic advancements for most of her life. She began using disposable syringes only five years ago – she was still using glass syringes with replaceable steel needles – and she began homeglucose monitoring only five years ago as well. (She was still testing her urine.) So for 78 years, Dull had little idea what her actual blood sugar was and, truth be told, she would just as soon go back to the urine tests. “I liked that more,” she says. “The finger sticks don’t feel so good, and you can’t get the blood out.” Her durability is a tribute to her rigorous self-discipline, a commitment to an oldfashioned ethic that is easily lost in the high-tech age of downloadable glucose meters, synthetic analogs, and continuous sensors. What’s her secret? A strict diet, regular injections, and a healthy lifestyle.
2 All quotes from Gladys Dull came from an interview with Dr. Irl Hirsch; the interview was filmed by her son, Norman, and sponsored in part by the Animas Corporation.

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Gladys as a child

The doctor said I would never have any children, but I showed him.

The result has been a full and rich life. Growing up, she farmed wheat and rode horses, motorcycles, and snowmobiles; later she held a full-time job at a photo studio and helped found a humane society in Walla Walla. In 1943, she married George Dull (he would work in construction after the war), and four years later Gladys delivered their only child, Norman. “The doctor said I would never have any children, but I showed him,” she says. And she remained physically active, tending to a family cottage in the Blue Mountains. “Hiking and camping – that was her greatest love,” Norm says. Dull is part of dwindling cadre of “insulin pioneers” who were among the first to use the drug in the years following its discovery in 1922. There are only five patients in the US who have been taking insulin for at least 75 years, according to Eli Lilly, which manufactured the product after its discovery. Lilly only found out about its most loyal customer last year after Dull’s principal caretaker contacted the company. Lilly confirmed her medical history by investigating the records at the Mayo Clinic; she then received a Lilly for Life Award for 75 years on insulin. Never mind that she passed that milestone the previous decade. “The award doesn’t go high enough,” Norm says. That she survived her childhood is itself a miracle. Had she developed diabetes even one year earlier, the Mayo Clinic may not have had the insulin to save her. When she was 9 years old, she had her appendix removed, after which she went into a coma. Few diabetics survived surgery in that era. “They took me back to Rochester,” Dull says. “I think I was in a coma for a couple of days. I still remember my good old doctor, Russell M. Wilder. He picked me up and kissed me after I came out of that coma. I’ll always remember that, I guess.” Her mother played a large role in helping Gladys adjust. By today’s standards, for example, the early needles were large and painful, but they do not inspire bad memories for Dull. “A 7-year-old doesn’t like shots,” she says, “but my mother wouldn’t let me have one bite to eat unless she gave me that shot. And I got on to it . . . It didn’t hurt that bad, I guess.” From the outset, Mayo’s clinicians emphasized a strict low-carb diet. Wax figures of food demonstrated portion size. Scales were used at every meal. Thick books gave calorie counts. “I followed the whole deal,” Dull says. “But I’ve done it for so long, I don’t weigh anymore. I don’t even have the scales. But I can look at something and know how many grams.” While she likes ice cream – “I will cheat every once in awhile” – she rarely strays from her diet, nor does she drink alcohol or smoke. As Norm says, “In 1993, for her fiftieth anniversary, I saw her eat one piece of cake, and I just about fell to the floor.” Most striking is how rigid Dull’s care has been over the years. As a girl, her mother would test her urine by mixing it with Benedict’s solution, bringing it to a boil, and observing the color. “You’re supposed to stay blue, but if it’s a brick color, you’re loaded with sugar,” Gladys says. But the family couldn’t adjust her insulin without consulting the doctors at the Mayo Clinic, and even as an adult, Dull says she never really changed her regimen – two shots a day, same insulin doses. By the time she was in her eighties, she began experiencing more hypoglycemia, but she was reluctant to adjust. Then five years ago, her husband died, and three days later, she suffered a stroke. Things had to change. When a doctor asked Norm what her mother’s blood sugar was, he said, “Grayish-brick.” “He couldn’t understand what I was talking about,” Norm says. “He couldn’t believe that she had never taken a blood test.” The home glucose monitoring has helped stabilize Gladys’s blood sugars; the glass syringes were also discarded. She continues to live by herself, in the house that she and George had shared for most of their married lives. And she remains fiercely independent.
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She does her own laundry, occasionally gardens, and does not use a cane. Her walker stays in the bedroom. She does acknowledge some limitations: with impaired vision from nondiabetic causes, a caretaker comes twice a day to prepare her meals, give her injections, and straighten up. “I’m not a very good house keeper anymore,” she concedes. Her black dog, a Schipperke named Coalie, is her protector. Her four siblings have all passed away, so Norm, who runs a video production company in a nearby town, takes her to dinner each Tuesday, and Gladys calls him each evening at 9 p.m., to tell him her blood sugar and confirm she’s eaten her snack. Says Norm: “It’s peanut butter and jelly – sugarless – and it holds her through the night.”

NewNowNext
An easier way to take Lantus For those on or considering the basal insulin Lantus, a new disposable pen is out. Approved by the FDA on April 30, this new option for Lantus – called the SoloStar – will be made available across the US this year. Lantus users now deliver with the refillable pen OptiClik or with the traditional vial and syringe. We think it’s great to see this new pen, since the OptiClik has had various delivery problems, and we’re waiting to see how patients like the SoloStar and whether it’s covered by insurance. The pen is pre-filled with Lantus and can dose up to 80 units per injection, which is more than any other disposable pen. According to Sanofi-Aventis, which makes the pen, it requires less “injection force,” which may be good for those with limited hand strength, though we can’t verify yet that you can really tell the difference. A SoloStar pre-filled with the rapid-acting insulin Apidra has already been approved in Europe; we may see that in the US in the next few years.
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The SoloStar for Lantus

Januvia + metformin = Janumet Less is more with this new diabetes pill out from Merck. It combines two favorites in one formulation – one is metformin, a veteran of diabetes drugs, and the other is Januvia, a promising rookie. If it’s appropriate for you to be on both these drugs, this new combination pill means one co-pay and an easier routine. Metformin and Januvia, a DPP-4 inhibitor, target different areas of the body: metformin decreases glucose production by the liver and Januvia increases insulin secretion by the pancreas, both acting in different ways against hyperglycemia. We’ve heard from doctors that the drugs work better together. The pill is taken twice a day, rather than Januvia’s once a day, though metformin is also once or twice a day. Doctors may prefer you start with metformin, as they may want to determine your optimal dose of that drug first (metformin dosing differs person to person), and insurance may not cover starting directly on the combination. Insurers may change, as more health care professionals are calling for earlier and more aggressive therapy.

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The combination pill, Janumet

Lights, camera, cure: Health fairs spread across America Jenna Scarsi, a diabetes educator from the Chicago area with type 1 diabetes, recently won the Bayer Dream Fund, an annual $100,000 fellowship to help people accomplish something “that might not have been possible unless they were in control of their diabetes.” The fund is helping Jenna expand a program she created a few years ago called Lights, Camera, Cure. What was an annual, mostly local event can now be bimonthly and in various cities across the US. Scarsi’s events are geared toward kids and consist of small diabetes health fairs followed by family movies, for which the events are themed.
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Winner of the Dream Fund, Jenna Scarsi

For example, the next event, in Philadelphia in June, will show Surf’s Up, a mockumentary slated for release this summer about surfing penguins, so activities at the event will include a hula-hoop contest and other island-inspired adventures. Two aspects we love differentiate Scarsi’s events. The people providing information at each of the fair’s stations (“what is diabetes,” pumping, exercise, BG monitoring, and so on) are not educators or doctors, but “youth advocates,” or young people ages five to 21 with diabetes. Also, the money raised stays in the city in which it was raised – a hospital’s diabetes unit, a diabetes center, or anything that “does something positive for the diabetes community” in that city, says Scarsi. Scarsi says she created the program because it’s “one thing to know what we have to do to intensively manage our diabetes, and it’s another thing to do it on a daily basis.” Upcoming events will also be in Philadelphia in June, Portland (with a Grease sing-along), Nashville (likely with an IMAX showing of Polar Express), and San Antonio. Details can be found at www.lightscameracure.com, and if you’re interested in applying for your own Dream Fund, applications are now being accepted at www.bayerdreamfund.com/ tellusurdrea_form.php.

A no-coding meter out from FreeStyle In April, the FDA approved the FreeStyle Lite meter, which requires no coding. It’s similar to the very small FreeStyle Flash, though apparently won’t be replacing it at this stage. Only Bayer meters had “no-coding” (or auto-calibration) before now. The Freestyle Lite is supposed to be simple and easy-to-use, two descriptors we love to hear for devices. Jane Seley, a member of our advisory board and a noted educator from New York Presbyterian Hospital, praised the meter for its “killer combination” of no-coding, smallest blood drop size, and an excellent backlight, which she thought really does make a difference in speed and convenience.
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The FreeStyle Lite

FingerSticks

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conference pearls
The American Association of Clinical Endocrinologists (AACE) 16th Annual Meeting & Clinical Congress took place in early April in Seattle. The main themes, we found, were the lowering of glycemic targets (like A1c) and the growing recognition of the harmful effects of glycemic variability (when blood glucose fluctuates). • Better, tighter glycemic control is always a theme at this meeting. This year, the focus was on postprandial glucose management and the greater use of combination therapy to push A1c values below 6.5 percent. The American College of Endocrinology (ACE) and AACE will soon publish a joint “roadmap” for the prevention and care of diabetes. We were able to get a preview: Compared to the ADA’s guidelines, it will emphasize a lower A1c target as well as the need for patients to receive different treatments depending on their A1c level. • Fasting and postprandial glucose make different contributions to overall hyperglycemia. We note that this is based on the work of Dr. Louis Monnier, who published an important paper in 2003 that showed that post-meal glucose spikes are a bigger contributor to overall hyperglycemia for patients at lower A1c, while high fasting glucose is a bigger contributor for patients at higher A1c. For example, for patients with A1c <7.3 percent, postprandial glucose accounts for 70 percent of overall hyperglycemia while fasting glucose accounts for only 30 percent . The contributions are reversed for patients with A1c >10.3 percent. For patients with A1c between 7.4 percent and 10.3 percent, postprandial and fasting glucose make equal contributions to overall hyperglycemia. • Combination therapy is needed to treat both fasting and postprandial glucose. The logic, then, is that in order for patients to achieve lower A1c targets, they need a combination of treatments that target both fasting and postprandial plasma glucose levels. Examples of drugs that focus on fasting plasma glucose are: basal insulin (Lantus and Levemir), metformin (generic), and sulfonylureas (generic). Examples of drugs that focus on postprandial plasma glucose are: rapid-acting insulin analogs (Novalog, Humalog, and Apidra), pramlintide (Symlin), exenatide (Byetta), DPP-4 inhibitors (Januvia), and thiazolidinediones (Actos and Avandia). ACE/AACE recommends that diabetic patients achieve fasting plasma glucose <110 mg/dL (pre-meal) and postprandial plasma glucose <140 mg/dL (post-meal). • The ACE/AACE roadmap will include newer drugs. The ADA currently recommends metformin and lifestyle intervention (diet and exercise) as first-line therapy for patients diagnosed with type 2 diabetes, in order to achieve a target A1c <7 percent. For patients who still remain uncontrolled on metformin alone, it recommends adding a sulfonylurea, thiazolidinedione (TZD), or basal insulin. The ADA’s algorithm does not endorse newer drugs like Januvia or Byetta. However, in sessions at AACE this year we learned that the ACE/AACE roadmap will likely include more options for first-line therapy, including Januvia, and that it will also include other postprandial-specific drugs like Byetta and Symlin as additional therapeutic options for patients who are not at A1c goal on one drug alone. • There was a lot of focus on earlier insulin use as well as moving toward more use of meal-time insulin. Some research suggests that early use of insulin – at diagnosis of type 2 diabetes, even – can have long-term effects on reducing complications. Sanofi-Aventis is currently conducting a 12,500-patient 5-year trial called ORIGIN to determine whether early use of its basal insulin, Lantus, can delay the development of type 2 diabetes in people with prediabetes, or whether basal insulin can delay the development

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ILLUSTRATION: DANIEL BELKIN

Some research suggests that early use of insulin - at diagnosis of type 2 diabetes, even - can have long-term effects on reducing complications.

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of complications in people with early type 2 diabetes. The trial results will likely be unveiled in 2010. Speakers at AACE also advocated earlier use of meal-time as well as basal insulin – this again echoes Dr. Monnier’s work, which showed that controlling mealtime glucose excursions is crucial for people at lower A1c’s. • Lots of focus on driving down A1c targets – some well-known endocrinologists recommended A1c <6 percent. This underscores the importance of achieving near-normal glucose targets – we thought it was great to hear a respected endocrinologist like Dr. William Cefalu actually say this. His whole point was that traditional drugs increase insulin action (metformin, TZDs, sulfonylureas, and insulin itself), but the new ones reduce glucose production (Byetta, Symlin, and Januvia), which should really help people achieve near-normal blood sugars. He gave a dramatic talk about how incretins are exciting because they may alter the natural history of diabetes by improving beta cell function and perhaps slowing what we used to think was the “inevitable” progression of disease in type 2 diabetes. Only time (and longer clinical trials) will tell whether these drugs can actually do this.

what we’re reading
A more detailed look at stem-cell therapy for diabetes In mid-April, the popular press was full of reports on an exciting new paper published in the Journal of the American Medical Society on a stem-cell treatment for type 1 diabetes. The phrase “stem cell research” has so many connotations that we thought it was worth taking a more detailed look at what exactly was in this widely-acclaimed paper. Published by Dr. Julio Voltarelli and colleagues from the University of Sao Paulo in Brazil, it reported the results from a small 15-patient trial that tested a method called autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) for the treatment of new type 1 patients. The method is a complex three-step procedure that is already used to treat other autoimmune diseases like sclerosis, arthritis, Crohn’s disease, and lupus: • In the first step, doctors collect a large number of hematopoietic stem cells (HSCs) from the patient’s blood. HSCs are the adult stem cells that normally reside in your bone marrow and that replenish both your red and white blood cells. Doctors have to collect a large number because at the end of the process, these pre-harvested HSCs will be reinfused in order to rebuild the patient’s immune system. • In the second step, patients receive something called “immunoablative conditioning” in order to destroy their white blood cells. This is somewhat similar to the radiation therapy that leukemia patients receive when they prepare for bone marrow transplants, except that these patients receive an antibody that specifically removes their white blood cells without exposing their bodies to harmful radiation. • In the third step, the HSCs are re-infused into the patient in order to rebuild a new immune system that (hopefully) no longer attacks their beta cells. Again, this differs from what happens in bone marrow transplants (and islet cell transplants, for that matter) in that patients are receiving their own cells, so there’s no risk of immune rejection, or any need for them to take long-term immunosuppression therapies. In Dr. Voltarelli’s trial, 14 of the 15 type 1 patients were able to stop using insulin after they received this treatment and of these, all but one were still insulin independent at the time this paper was written, in February of 2007. Because this trial was conducted over the course of three years, at that time some of the patients had been followed for as long as 36 months and others for as little as seven.

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The phrase ‘stem cell research’ has so many connotations that we thought it was worth taking a more detailed look at what exactly was in this widelyacclaimed paper.

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CHEATING DESTINY
by James S. Hirsch

“The book that people who care about diabetes have been waiting for.” —The Washington Post

Insulin Pumpers:
Support and Information for Adults and Children with Diabetes www.insulin-pumpers.org diaTribe: “A great forum for those on a pump or considering one!”

Importantly, all of these patients had been diagnosed with type 1 diabetes within six weeks of their enrollment in this trial. There is some research that suggests that even people who have had type 1 diabetes for decades are still producing some beta cells, but the underlying autoimmune condition that is responsible for type 1 destroys these new cells as soon as they are created, perpetuating the disease. In Dr. Voltarelli’s trial, the idea was that if the autoimmune condition can be removed early in the course of disease, the remaining beta cells can be rescued and recovered, thus reversing the disease. Presumably this would be much less helpful in people with longstanding type 1 diabetes, who have few if any beta cells left and thus would not benefit from having the autoimmune condition removed. The mechanism for how AHSCT restores beta-cell function is unknown. In an accompanying editorial to the Voltarelli paper, noted Miami endocrinologist Dr. Jay Skyler points out that while the goal of AHSCT is to eliminate autoimmune white cells and replace them with new, healthy white blood cells, this may not be the whole story. The process of AHSCT itself may somehow reset the immune system to be more tolerant of the body’s own beta cells. Alternatively, the re-infused HSCs may themselves be somehow growing into beta cells, or perhaps the treatment process mobilizes stem cells in the pancreas or bone marrow to become beta cells – this is a somewhat more controversial idea, but we simply don’t know enough about this exciting new technique to determine what exactly is happening. Dr. Skyler identifies a few future directions of research. Ideally, doctors and scientists will want to see Dr. Voltarelli’s results replicated in a large, randomized controlled trial with a longer follow-up period to see if patients really do remain insulin independent in the long term. Having a randomized control group is particularly important because newly diagnosed type 1 patients often have a ‘honeymoon’ period during which they can stay relatively insulin independent, and it will be important to distinguish between the effects of the honeymoon period and the effects of the AHSCT procedure. Having a longer trial will also help because the honeymoon period doesn’t last very long, whereas we would hope that a “cure” for type 1 diabetes does. Finally, Dr. Skyler would like to see biological studies carried out to discover exactly how AHSCT works – whether it eliminates autoimmune cells or helps beta cells regenerate or acts through a different mechanism altogether. We agree, and we can’t wait to see more work done in this field! Bottom line: There was a lot of hype in the press about a stem cell “cure” for diabetes in April. The study was exciting, though small and short, and it is important that more be done before we know whether this is meaningful. No embryonic stem cells were used, and no immunosuppression was required. Cells from a patient’s bone marrow were extracted, the patient underwent a sort of radiation therapy, and these cells were reintroduced. Indeed, most of the subjects of this small 15-person group did go off insulin, at least for a time. Voltarelli JC, Couri CEB, Stracieri ABPL, Oliveira MC, Moraes DA, Pieroni F, Coutinho M, Malmegrim KCR, Foss-Freitas MC, Simoes BP, Foss MC, Squiers E, Burt RK. “Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus.” JAMA 11 April 2007. 297(14):1568-76. Skyler JS. “Cellular Therapy for Type 1 Diabetes: Has the Time Come?” JAMA 11 April 2007. 297(14):1599-1600.

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