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I S S U E 10

Conference Pearls .......... 1The ADA 68th Annual

Scientific Sessions

Letter from the Editor .. 2

NewNowNext ................ 6New meters from Abbott,

LifeScan and Bayer plus

information about special

diabetes programs

Learning Curve .............. 8ACCORD, ADVANCE, and

VADT - three big studies at

ADA

Trial Watch ...................... 10Incretins, CGM and insulin

pumps

What We’re Reading ...... 11Who will manage America’s

patients with diabetes in the

near future?

in this issue

research and product news for people with diabetes

1

®

conference pearls American Diabetes Association 68th Scientific Sessions San Francisco (June 6-10)When every fifth taxi in downtown San Francisco is carrying an ad for Byetta, FlexPen, or FreeStyle meters, you know the American Diabetes Association (ADA) is in town. Over 20,000 physicians, diabetes educators, and company representatives descended upon our beautiful city by the bay (home of diaTribe headquarters) for five intense days at the ADA’s 68th Scientific Sessions. diaTribe was right there attending sessions, talking to experts, and exploring the exhibit floor to bring you the latest news, views, and reviews from this mammoth meeting.

It is probably easiest to think of this meeting in five parts: the famous Banting Lecture (named for Nobel Laureate, Frederick Banting, a discoverer of insulin); the Presidential Lecture; the results from three landmark clinical trials (ACCORD, ADVANCE, and VADT); the many symposia with updates on progress in diabetes devices and drugs respectively; and the exhibition floor. This issue’s Learning Curve is devoted to a more detailed discussion of the three landmark trials named above. Below are some of our other Conference Pearls from the meeting.

Banting Lecture – Dr. Ralph DeFronzo shakes it up!Dr. Ralph DeFronzo of the University of Texas Health Science Center, and recipient of the 2008 Banting Medal for Scientific Achievement, had the honor of delivering this year’s Banting Lecture. There are hardly higher accomplishments in diabetes. One of Dr. DeFronzo’s key messages was the need for earlier interventions in treating diabetes. He explained that by the time people are diagnosed with type 2 diabetes, they have often already lost 80% of their beta cells, the insulin-producing cells in the pancreas. He argued that pre-diabetes should be treated more aggressively before it turns into diabetes.

In what we saw as a defining moment at the conference, Dr. DeFronzo also challenged the idea that type 2 diabetes is a distinct entity from pre-diabetes. Typically, people who are at risk of developing type 2 diabetes are thought to go through several stages of impaired glucose tolerance (i.e. pre-diabetes) before reaching the ‘disease’ state of type 2.

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diaTribe staffEditor in ChiefKelly L. Close

Managing EditorJames S. Hirsch

Contributers Kaku ArmahDaniel Belkin Dana Lewis Brendan Milliner Kerri Morrone Melissa TjotaEllen UllmanMark Yachoan

DesignGina Wilson

diaTribeadvisory board

Jennifer Block, RN, CDEDr. Zachary Bloomgarden, MDDr. Bruce Bode, MDDr. Nancy Bohannon, MDDr. Bruce Buckingham, MDDr. Wendell Cheatham, MD Dr. Steven Edelman Dr. Barry Ginsberg, MD, PhDDr. Lutz Heinemann Debbie Hinnen, CDEDr. Irl Hirsch, MDJeff HitchcockDr. Lois Jovanovic, MDDr. Francine Kaufman, MDDr. David Kendall, MDDr. Aaron Kowalski, PhDDr. Harold Lebovitz, MD, PhDDr. William H. Polonsky, PhDMichael RobintonJane Jeffrie Seley, NP, CDEDr. Jay Skyler, MD Dr. Paul Strumph, MD Virginia Valentine, CDEDr. Howard Wolpert, MDGloria Yee, RN, CDEDr. Paul Zimmet, MD, PhD Dr. Bernard Zinman, MD

from the editor

L ooking through this special issue of diaTribe about the American

Diabetes Association meeting this year, I can’t help but feel two

things – pride and trepidation.

The pride stems from how far we have come from the days of urine

testing and sharpening needles – the disease is actually being redefined

as scientists gain insight into the molecular components of type 2 and

type 1 diabetes. Some in the medical and academic community are pushing to treat diabetes

much earlier in its progression and even before pre-diabetes! With earlier recognition and

intervention, people with the disease are living longer, fuller lives.

The scary part is the numbers that define diabetes – and I’m not only talking about blood

glucose numbers. The Centers for Disease Control and Prevention (CDC) reported 2007

diabetes statistics in late June, and the numbers just keep going up. The oft-quoted figure

that 21 million Americans have diabetes is out – it’s now almost 24 million. In 2000, the

figure for pre-diabetes was 41 million (in 40-74 age range), and now it’s 57 million people

(over the age of 20).

On the economic side, half of the money spent to directly treat diabetes ($116 billion) is

actually spent treating complications ($58 billion). Including the estimates for indirect

costs, such as loss of productivity, the disease costs us $174 billion a year.

Are there any quick fixes? Of course not, but I will make one suggestion: autopilot and

cruise control may work for modes of transportation, but they do not work with diabetes.

In other words, diabetes is not just about following instructions from doctors and nurses –

it requires constant patient involvement. As patients, we must be conscious of how various

therapies are affecting us and take note of changes. Most important, we must then talk

about these changes with our healthcare team. I’m not a scientist and I don’t claim to know

anything about cytokines and signaling pathways, but that cannot stop me from asking my

doctor or educator to explain (time and again) why I need to follow a particular regimen if I

don’t think it’s working. Communication is key, especially with your diabetes educator.

Sometimes my doctor will point out some striking trend she’s noticed, and I’ll have what

she calls an “A-ha!” moment. These moments help my management. Diabetes isn’t about

adopting a therapy and sticking to it. Hardly! As patients, we need to understand why we’re

doing what we’re doing. We must work to recognize when it’s working and when it’s failing.

I’m off to add a new question to my list for my next visit. I hope you’ll do the same – and

remember, if you don’t have a diabetes educator yet, that should be the very next thing on

your list! Just check out www.diabeteseducator.org or call 1-800-877-AADE (2233).

Yours truly,

Kelly

www.diaTribe.us

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Glucose tolerance is an indication of how quickly glucose that is ingested is cleared from the blood either into muscle (or other) cells for usage, or into liver cells (or fat cells) for storage. Insulin is a hormone that helps these cells take up glucose from the blood. Impaired glucose tolerance has been associated with insulin resistance – a condition in which normal amounts of insulin are unable to cause these cells to take up glucose from the blood. This condition often leads to elevated levels of glucose (and insulin) in the blood, resulting in type 2 diabetes and a host of other conditions known as the metabolic syndrome.

However, Dr. DeFronzo believes that labeling these stages as a stepwise progression from normal glucose tolerance, to impaired glucose tolerance, and finally to type 2 diabetes, is rather arbitrary. He proposed thinking of the process as a continuous progression and argued that patients should be treated much earlier in the process and with interventions that can help prevent the death of insulin-producing beta cells. In summary, strive for normal glycemia as early as possible.

Finally, in a provocative conclusion, Dr. DeFronzo criticized the ADA’s treatment guidelines, which recommend lifestyle changes and metformin as initial therapy for type 2 diabetes. He suggested instead that we should begin treatment with a triple combination of drugs: metformin, exenatide (Byetta), and a thiazolidinedione (TZD; such as Actos or Avandia). Dr.

DeFronzo’s rationale for multiple drug therapy was to simultaneously treat the multiple organ dysfunctions that contribute to diabetes and at the same time protect surviving beta cells, and possibly augment them. In combination, the three drugs he recommends may help to slow the progression of diabetes and may work without causing weight gain (Byetta prompts weight loss in about 80% of patients who take it, and this may “cancel out” weight gain caused by the TZD). None of the drugs used in Dr. DeFronzo’s combination cause hypoglycemia, a major benefit from his perspective. Dr. DeFronzo’s personal treatment algorithm was controversial since there are no studies showing long-term effects of Byetta – it is a relatively new drug. Additionally, TZDs have been criticized for their association with increased risk of swelling, heart failure, weight gain and bone fractures. Research suggests that these problems are reduced when the drugs are taken earlier and in lower doses. We await information on Dr. DeFronzo’s ongoing clinical study on this subject.

When we asked Dr. Jay Skyler of the University of Miami, one of the leading thinkers in diabetes, for his opinion on the lecture, he gave it high praise for blending science with potential clinical implications in a scientifically sound and understandable way. “Although I have not been a TZD user (because I don’t like weight gain), the arguments persuaded me to re-think that in the context of early treatment with triple therapy of metformin, exenatide, and a TZD, a circumstance in which metformin and exenatide might prevent TZD weight gain. If scientific evidences from an ongoing trial proves that Dr. DeFronzo’s approach is better, it may profoundly influence the future treatment of type 2 diabetes.” See Learning Curve in issue #1 and #8 for more on exenatide, and #6 for more on TZDs.

The grand foyer at the

Moscone Center

Since the 1950’s,

diabetes has been

transformed from a

disease of disability

and death to a disease

that is treatable and

has a relatively good

prognosis.

– Dr. Buse“

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Presidential Lecture – Dr. John Buse defends the ADA During his lecture, Dr. John Buse, of the University of North Carolina, Chapel Hill and cur-rent president of the ADA, defended the ADA’s conservative approach to setting the treat-ment standards for diabetes care in the US. He acknowledged the tremendous progress we have made thanks to the expanded toolbox of drugs and devices now available to assist with diabetes management. He said, “Since the 1950’s, diabetes has been transformed from a disease of disability and death to a disease that is treatable and has a relatively good progno-sis.” This is evidenced in the 2007 diabetes statistics from the Centers for Disease Control and Prevention (CDC) that note that diabetes moved from seventh place to sixth place in terms of leading causes of death in the US.

Dr. Buse explained that it is the ADA’s responsibility to clearly identify which of its recommendations are based on scientific evidence and which are based on “expert opinion” – medical practices based on singular experiences of physicians and not on larger, formal studies. For example, the current ADA guidelines are ambivalent about self-monitoring of blood glucose (SMBG) in type 2s not on insulin. The fine print notes that it “may be useful.” This is because there are few studies conclusively showing the value of testing in this patient population. This doesn’t mean that it is not useful – in fact, Dr. Buse condemned some poorly designed studies that have suggested that SMBG in type 2s should be used less frequently – but it does mean that on this topic the ADA has only expert opinion to rely on. If patients don’t know present blood sugar levels, they will be hard-pressed to plan food, exercise and medication to obtain suitable future blood sugar levels. That said we take the point that more good studies are needed in this area.

He concluded his presentation with a discussion of rapidly increasing diabetes costs and the pressure to contain them. The ADA, being the nation’s leading voluntary diabetes health organization, has a responsibility to stick to incontrovertible facts in its recommendations and to avoid being influenced by marketing evidence. Nonetheless, the argument is not just about cost, but also about quality of care. “We need to change the dialog from restricting dollars to increasing care.” diaTribe certainly agrees with this sentiment particularly since we are using half of the $116 billion spent to directly treat diabetes, on treating complications. We urge more spending on earlier treatments so as to avoid the costly long-term complications seen today. What’s new with Diabetes Devices?This year’s meeting had a greater focus on diabetes drugs than devices. Many working in the field of diabetes devices are eagerly awaiting the results of the Juvenile Diabetes Research Foundation (JDRF) CGM trial. The hope is that positive results from this trial will prove conclusively what many of us have believed for ages – the value of CGM and the need for better reimbursement for the technology and for education to teach patients how best to use it. We hope to see some preliminary results later this summer.

In a compelling presentation, Dr. Lois Jovanovic of the Sansum Diabetes Research Institute suggested that the ADA should consider stress as a fourth focus point in diabetes management, in addition to exercise, diet, and insulin. She named three different types of stress – psychological, physical, and hormonal – that vary in intensity from person to person. She asked that physicians take this into account when dosing insulin for their patients. Stress reduction is difficult to address for many, but it might help to give it some extra thought as part of your diabetes management.

A recurring message on the subject of CGM was the need for both patients and healthcare providers to set realistic goals and expectations. Dr. Bruce Buckingham of Stanford

We need to change

the dialog from

restricting dollars to

increasing care,

said Dr. Buse. diaTribe

urges more spending on

earlier treatments so as

to avoid the costly long-

term complications

seen today.

If you can measure it,

you can improve it –

but if you measure it,

you must do

something about it.

This highlights the idea

that self-monitoring of

blood glucose is only

effective when patients

are empowered to act

based on their results.

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University characterized CGM as a behavior modification tool – not a magic cure for diabetes. Many presenters emphasized that patients must interact frequently with the device and take appropriate actions based on their readings to benefit from CGM data. One tip: if you have a CGM, try using your receiver as a replacement for your watch so you interact with it more often. Studies have shown greater benefit in patients who interact more frequently with the device and make appropriate changes based on the readings.

To cap off the device section, we were very excited about a poster presented at the meeting showing that safe and reliable use of the DexCom SEVEN CGM sensor for up to 10 days. We hope to see this device receive FDA approval for 10-day use soon.

Update on Diabetes Drugs - New Incretins and MoreThere was a tremendous amount of excitement about the class of diabetes drugs called incretins (see Learning Curve in issue #1 and #9, and Test Drive in issue #3). In fact, there were so many sessions devoted to this topic that ADA President Dr. Buse opened one of his incretin talks saying, “If you haven’t heard of the word exenatide [Byetta] by now, you should contact the ADA organizers and ask for your money back.”

You may have heard about or even used Byetta or Januvia - the only two FDA-approved incretin drugs on the market in the United States for the treatment of type 2 diabetes. A large part of the excitement at ADA centered on long-awaited test results from a newer set of incretins that require less frequent administration. These drugs are formulated to enter the bloodstream more slowly once they are injected. Currently, exenatide (Byetta) is injected twice daily, but the new formulation of exenatide being developed by Amylin/Eli Lilly will only require a once-weekly injection. Data presented on this new drug, which we expect to be out in 2010, showed a 2% reduction in A1c. Liraglutide (Novo Nordisk), another incretin drug in development, will require a once-daily injection with a smaller needle than for once-weekly exenatide. We are always happy about new, safe, and effective alternatives for improving diabetes management.

Data presented at ADA suggested that both exenatide once-weekly and liraglutide provide significant decreases in A1c and body weight with minimal hypoglycemia. Nausea was reported as the predominant side effect. Note that neither is yet FDA approved.

Another presentation that we thought was interesting was on type 2 use of Symlin, in combination with basal insulin. Though this combination isn’t yet approved, the weight loss and A1c reductions were impressive. See Test Drive in issue #2 and #8 for more on Symlin. We also enjoyed learning more at the meeting about a new drug called alogliptin. This drug is a DPP-4 inhibitor (like Januvia), and from the data we saw at the meeting, we think that it may offer similar benefit as Januvia. Of course, whether its safety profile is similar to Januvia’s will need to be evaluated over time. The drug is currently being reviewed by the FDA, and could be on the market in about a year.

The meeting was also an excellent opportunity to learn about some of the new types of drugs that are being developed to treat diabetes. Most of these drugs are being studied for type 2 diabetes only, but a few drugs in development including SGLT-2 inhibitors could potentially be used to treat type 1 diabetes as well (as an add-on to insulin). To learn more about SGLT-2 inhibitors, see Learning Curve in issue #8. Because most of

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If you haven’t heard

of the word exenatide

[Byetta] by now, you

should contact the ADA

organizers and ask for

your money back.

– Dr. Buse “

The exhibit hall at the 2008

ADA meeting

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these new drugs are in earlier stages of development, we think that it is too soon to know whether they will prove to be safe and effective for treating diabetes. Nonetheless, we were happy to see so much progress in diabetes research, and after hearing about all of the new drugs in development we are very optimistic that even better therapies for diabetes are on the way. Stay tuned…

NewNowNext The New OneTouch Ping New from J&J’s Animas/OneTouch is the OneTouch Ping Glucose Management System. This represents a positive step in pump convenience and (dare we say) “cool” fac-tor. The new, exciting element is that the OneTouch Ping pump is wirelessly linked to the OneTouch Ping glucose meter via a remote control. This means that after you test your blood sugar with the meter, you can send insulin dosage information wirelessly to the pump without ever having to touch the pump – very similar to the OmniPod System though the pump is traditional rather than disposable. Equally impressive, blood glucose and pump data can be downloaded either from the pump or the meter to a Mac or a PC – big plus for Apple fans! Finally, being able to use our Mac to analyze our numbers – thank you! Like the 2020, the pump is waterproof and has the hip color screen - the system will eventually be available in a range of colors. Come August, you can get a Ping system, either an upgrade at reasonable (still undisclosed) cost or as a brand new system. See www.animascorp.com for more details.

The Meter Monitor Patients who would prefer a larger display and larger buttons on their blood glucose meter may want to give the FreeStyle Freedom Lite a try. This meter from Abbott was released in the US in mid-April and shown at ADA. It has similar features to the other meters in the FreeStyle family: no coding, alternate site testing, very small blood sample required, five second testing, and uses FreeStyle test strips.

The OneTouch UltraLink is a recently launched meter from LifeScan that transmits wire-lessly to the Medtronic Paradigm insulin pump and CGM and Guardian CGM. One idea driving this development was the need to minimize errors in entering blood glucose data, which in turn minimizes insulin bolus dosing errors. The meter was approved for use in the US in April, and the first units were shipped at no cost to “eligible customers” over the last couple of months. As a bonus Medtronic customers were offered another free LifeScan meter (UltraMini, Ultra 2, or UltraSmart). We look forward to improvements suggested by patients, such as further miniaturization, a backlight, and larger screen readings on the next generation UltraLink Outside the US, the previously released Bayer Contour Link is the meter available which communicates wirelessly with the Medtronic Paradigm and Guardian.

Speaking of Bayer, the new Bayer Contour meter, anticipated later this summer, will allow patients to choose ‘basic’ or ‘advanced’ levels, as they prefer. The advanced setting now enables users to view 30-day averages in addition to 7- and 14-day averages. User-settable features are great in our view as they enable more “individualization of therapy,” a key ADA meeting theme. Users can set adjustable timers to alert them when it’s time to test. Unlike the basic setting, the advanced setting includes pre- and post-meal markers as well

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(from top to bottom) new

FreeStyle Freedom LIte

(Abbott Diabetes Care), and

new UltraLink communicates

wirelessly with Paradigm

New OneTouch Ping Glucose

Monitoring System (Animas/

LifeScan)

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as programmable pre- and post-meal reminders. Following a stylish trend started last year with meters and pumps, the new Contour will come in dark grey, purple, and green, in addition to the traditional blue color. It’s great that the company is thinking in the shoes of patients to create a medical device that need not look like one.

The Online Bolus Calculator Integrated Diabetes Services (http://www.integrateddiabetes.com/tools.shtml) has put together a mealtime insulin-dosing calculator. This is a great tool to help patients learn how to “optimize” the amount of insulin taken for meals, which can be pretty tough. The idea is that you can download the calculator as a spreadsheet, insert your target blood glucose levels, sensitivity factors, carb-to-insulin ratio, and/or exercise factor, and have a customized spreadsheet. This is a great opportunity to work with your diabetes educator to establish or refine what these levels should be! They recommend printing off the chart, and we think this will be particularly helpful for newly diagnosed patients. For patients with a bit more experience with carb-counting, we think the calculator at the top of the chart will be the most useful component – this is a very user-friendly insulin-on-board calculator with a simple “this is how much you should dose” box. We hope someone takes the time to write the code for the calculator into a small application for computer desktops, Blackberrys, iPhones, and other PDA devices, for people with diabetes living their lives on the go! Insulin for Life and Life for a Child diaTribe got the opportunity to learn a lot about these two programs by spending time speaking to International Diabetes Federation (IDF) leaders during this year’s ADA meeting. Too often we take for granted the availability of life-saving insulin. People in numerous countries around the world cannot access insulin – let alone afford it! Insulin For Life is an amazing non-profit organization dedicated to collecting and distributing unopened and insulin and test strips (at least five months to expiry) that would otherwise be discarded. Learn more at http://insulinforlife.org/.

Life for a Child is a sister program to Insulin for Life. It was established in 2001 as a sustainable sponsorship program where people can help children in developing countries get the supplies, support, and education needed to survive with diabetes. The program supports over 1,000 children in 17 countries by providing supplies for insulin injections, blood glucose monitoring, A1c testing, technical support for health care professionals, and diabetes education. Donate and find out more: http://lifeforachild.org/pages/donate. We suggest you talk to local diabetes camps and programs that receive donated supplies and recommend sending the leftovers to the US shipping centers for these programs!

“The vision for Life for a Child is that no child should die of diabetes. diaTribe readers could help by becoming financial sponsors of the program - a dollar a day supports the ongoing care of a child - see www.lifeforachild.org and then www.lifeforachild.org/pages/tax-deductibility” - Dr. Graham Ogle,Manager, International Diabetes Federation “Life for a Child” Program

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learning curve ACCORD, ADVANCE, and the VADT: What do they Mean, and for Whom?“Psssst. Have you heard? Three large clinical trials presented this month show that lowering your blood sugar to near-normal levels produces no cardiovascular health benefits and may even be harmful.”

“Psssst. Have you heard? Even the reputable New York Times had a front page article called “Tight Rein on Blood Sugar Yields No Heart Benefits.””

These are the type of misleading headlines circulating after the presentation of results from three large clinical studies involving about 23,000 patients at this year’s ADA meeting in San Francisco. But what do these three trials really mean, and for whom? The answer is not as simple as suggested in sensational headlines, and the studies actually raise many more questions than they answer.

What are ACCORD, ADVANCE, and the VADT?First, some background: ACCORD, ADVANCE, and the VADT were three large clinical trials that compared the rates of heart disease in patients receiving either “intensive” diabetes treatment (targeting near-normal average blood glucose levels – A1c closer to 6%), or “conventional” diabetes treatment (targeting somewhat higher blood glucose levels – A1cs of 7.5% or above. These studies were designed to test the theory that extremely tight control of blood glucose would help reduce heart disease. ACCORD tested approximately 10,000 people in North America and Canada, while ADVANCE tested 11,1400 people internationally. The VADT tested a more limited sample of 2,000 veterans in the US.

As a reminder, the A1c is a measure of average blood glucose. An A1c of 7.0% is equivalent to an estimated average blood glucose level of 154 mg/dl (8.5 mmol/l), whereas an A1c of 6.0% is equivalent to an average blood glucose level of 126 mg/dl (7 mmol/l). Roughly two-thirds of people with type 2 diabetes die from heart disease, a much higher rate than in the general population. As such, researchers for these three studies wanted to see if reducing blood sugar to near-normal levels would reduce the risk of heart disease. For more background, see diaTribe issue #9 What We’re Reading.

The three trials differed in the precise blood glucose levels targeted, as well as in their patient populations. Patients were mostly over 60 years old with a long duration of type 2 diabetes. Thus, the results may not be relevant to people less than 60 years of age, people with type 1 diabetes, or people with either newly diagnosed or well-managed type 2 diabetes. If you have type 2 diabetes and are at high risk of heart disease, or have had a heart attack, then these results are more likely to relate to you.

Contrary to many researchers’ expectations, none of the three trials showed a clear benefit of tight glucose control on heart disease risk over the study periods. In ADVANCE, which lasted five years, and the VADT, which lasted seven and a half years, the rate of heart attacks, stroke, and heart disease was similar between the intensive and standard glucose arms of the studies. In contrast, the intensive glucose control arm of the ACCORD study was famously discontinued in February, long before its expected completion date. This happened after a committee responsible for overseeing the study found that the intensive glucose control arm had significantly more deaths than the standard control arm (257 versus 203).

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So what is (are) the answer(s)?Why was intensive glucose control associated with poorer outcomes in ACCORD, but not in the other two studies? Nobody knows for sure, but several speakers at the ADA meeting offered possible explanations. One theory is that glucose was lowered too quickly in the ACCORD trial. Whereas average glucose levels were lowered slowly in ADVANCE and the VADT, glucose levels were lowered very quickly and aggressively in ACCORD – from an average of 8.3% to 6.4% in four months. Some research presented at the meeting by Dr. Eric Kilpatrick (Hull Royal Infirmary, UK) and colleagues suggests that rapid changes in average blood glucose may increase the risk of heart disease. Patients in the intensive treatment arm of the ACCORD trial were also treated to reach a blood glucose level below current international guidelines – many think this was too aggressive. Whereas the ADA recommends that patients try to achieve an A1c level of less than 7.0%, patients in ACCORD were treated to target an A1c level of less than 6.0%.

To achieve lower blood glucose levels, many patients in ACCORD were treated with multiple medications that cause significant weight gain, including Avandia or Actos, sulfonylureas, and insulin. Whereas patients in ADVANCE did not gain weight, almost 30% of patients in the intensive treatment arm of ACCORD gained 10 kg (22 pounds) or more during the study. This weight gain may have contributed to the increased incidence of heart failure in the intensive arm of that study.

Another theory proposed is that unrecognized or “silent” hypoglycemia (possibly due to insulin or sulfonylurea use) may have occurred more often in the intensive treatment arm of the study, leading to more heart disease and increased deaths. This easily gets very complicated since it’s impossible to study something that can’t really even be identified.

No medication in the ACCORD study was associated with poorer health outcomes. This included Avandia, which some previous studies have suggested could be linked to increased heart attacks (see Learning Curve in diaTribe issue #6). Notably, the drug Byetta was linked to significantly fewer deaths than any other medication. This was especially significant in our view because Byetta is not usually associated with hypoglycemia or weight gain – in fact, it is known to cause weight loss. That said, the study was not designed to assess the safety of different drugs, so it is difficult to draw conclusions about any specific drug in the study. It would be very enlightening if these drug effects were formally studied.

Notably, there were actually fewer cardiovascular deaths in both ACCORD patient groups (intensive and standard) than expected, possibly due to the better overall control of blood pressure, cholesterol, and blood glucose. According to diaTribe advisory board member Dr. Barry Ginsberg, a number of doctors and researchers believe a longer study would have shown greater benefits of intensive glucose control on heart disease. He characterized the assumption that having more people in a study allows you to run the study for a shorter time as a potential design flaw.

What does all of this mean? And for whom? Here is our list of conclusions – and as always, we remind readers that we aren’t medical doctors, so please consult your healthcare team before making any changes:

1. For older people with a long duration of type 2 diabetes who are at high risk for heart disease, very aggressive treatment of blood glucose may not necessarily reduce heart disease risk over the span of a few years. It remains unclear whether aggressive treatment of blood glucose will reduce heart disease risk over a longer time frame. Previous

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It remains unclear

whether aggressive

treatment of blood

glucose will reduce

heart disease risk over

a longer time frame.

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studies have suggested that the benefits of tight glucose control may not become apparent until much later.

2. For people with a shorter duration of type 2 diabetes at lower risk for heart disease, it is unclear what message (if any) to take from these studies. Arguably, many experts believe that the studies highlight the importance of treating diabetes earlier and more aggressively. By doing so, these experts suggest, it might be possible to prevent the later stages of diabetes (and complications) when aggressive interventions are less effective and potentially harmful.

3. It is impossible to draw any conclusions from these studies for people with type 1 diabetes, because only people with type 2 diabetes were studied. Previous studies of people with type 1 diabetes including the DCCT and EDIC studies showed conclusively that tight control of blood glucose significantly reduced both microvascular and macrovascular complications. In EDIC and STENO 2 (a trial investigating multiple interventions in reducing heart disease risk in type 2s), the benefit it took far longer than the average five years of ACCORD, ADVANCE, and VADT for the benefit of intensive glucose control to be shown. For more on DCCT and EDIC, see http://diabetes.niddk.nih.gov/dm/pubs/control/.

4. Treating blood glucose to current guidelines is safe and conclusive evidence has shown such treatment to be very important for reducing microvascular complications like nerve, kidney and eye disease. As such, these studies should not be viewed as supporting less aggressive guidelines. At the same time, lowering blood glucose well below treatment guidelines may not make sense for patients with longstanding diabetes at high risk for heart disease.

5. Blood glucose, as measured by A1c, is only one of several aspects of diabetes management. Managing cholesterol levels and blood pressure is also a critical part of heart disease prevention. According to 2007 CDC diabetes statistics, blood pressure control can reduce the risk of heart disease by 33% - 50%, and the risk of microvascular complications by 33%. Control of so called “bad” cholesterol can reduce cardiac risk by 20% - 50%.

We look forward to the completion of the intensive blood pressure and cholesterol management segments of the ACCORD trial, which will continue for another seven years as originally planned. Researchers will also continue to monitor patients in the intensive glycemic control arm of the study that was discontinued to see long term effects of this intervention.

trial watchThis column consists of a review of interesting diabetes-related clinical studies selected from recognized and reliable sources. Clinical studies are necessary for the development and government approval of diabetes drugs and devices and involve strict suitability, eligibility and safety criteria for participation. Please consult your healthcare team before enrolling in any clinical trial.

Increasing interest in incretins – the Duration 3 study http://clinicaltrials.gov/ct2/show/NCT00641056 Clinicaltrials.gov identifier: NCT00641056 This trial is geared toward type 2 adults (18 and older) with A1c between 7% and 11% on

Blood pressure control

can reduce the risk

of heart disease by

33% - 50%, and the

risk of microvascular

complications by 33%.

Control of so called

“bad” cholesterol can

reduce cardiac risk by

20% - 50%. (CDC, 2008)

T2

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metformin (alone or with a sulfonylurea). The study is comparing once-weekly exenatide (an incretin) and once-daily Lantus (insulin glargine). It will primarily compare the effects of these therapies on A1c in patients over 26 weeks. Additionally, researchers will compare the effects of these therapies on body weight, lipid profiles, (cholesterol etc), and frequency of hypoglycemia. Exclusion criteria include treatment with any of the following medications three months prior to enrolling in this trial: insulin, Glyset, Precose, Prandin, Starlix, Byetta, Symlin, Januvia, Actos, and Avandia. This study is enrolling approximately 456 patients at 77 centers worldwide (12 of which are located in the U.S.). For more information, please call 1-877-CTLILLY (1-877-285-4559).

Impact of insulin pump therapy vs. standard injection therapy http://clinicaltrials.gov/ct2/show/NCT00417989 Clincialtrials.gov identifier: NCT00417989This study could be an excellent way to figure out if insulin pump therapy (and continuous glucose monitoring) is (are) right for you. Researchers are looking for patients who have never used an insulin pump (or at least not within the last three years) in order to better understand the effects of pump/CGM therapy on A1c, frequency of hypoglycemia, and important health economic outcomes compared to standard insulin injection therapy. A total of 552 patients who test four or more times per day, are between the ages of 7 and 70, and have an A1c greater than 7.4% and less than 9.5% will be selected to participate in this 30-center trial. Participants will use the Medtronic Paradigm REAL-Time System. Find out more by contacting Brenda Perry at 818-576-5049 or at Brenda.perry@medtronic.com.

what we’re reading Who Will Manage American Patients with Diabetes in the Near Future?1 A Grim Prognosis for the USBy Dana M. Lewis

The diabetes pandemic is exploding in populations worldwide regardless of gender, race, social status, or age. At the same time, the number of healthcare providers who specialize in diabetes is slowly and alarmingly dwindling. Previous studies have estimated that the US has a 12-15% undersupply of endocrinologists.2,3 Let’s think about this for a second: there are fewer than 3,000 endocrinologists practicing in the US but we have over 4,000 new patients diagnosed daily. The same studies predict the shortage to expand to nearly 30% by 2020.

Our diagnosisWe are proud to announce that diaTribe’s research into this question was selected for a poster presentation at this year’s ADA meeting (search for 864-P in Abstracts Online at www.scientificsessions.diabetes.org). We carried out a study to investigate why medical students were shying away from endocrinology, to identify what factors were deterring students from specializing in diabetes, and to determine what could be done to reverse this trend. Over five months, we sent out online surveys to medical school students across the US, yielding 524 participants (a response rate of 5-10%). All four years of medical school were represented with a small (39%) bias toward first year students.

Results confirmed that students were edging away from diabetes. While less than 1% of the students surveyed (only 4 students!) planned to specialize in or pursue diabetes care, over

The Medtronic Paradigm

insulin pump and continuous

glucose monitor

T1

T1/2

The number of

healthcare providers

who specialize in

diabetes is slowly and

alarmingly dwindling.

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D I AT R I B E • R E S E A R C H A N D P R O D U C T N E W S F O R P E O P L E W I T H D I A B E T E S

25% of students reported having considered a career in diabetes care. This is comparable to other more popular subspecialties. Students cited the social importance and the pandemic status of the disease as the two most important factors that would attract them to diabetes. The difficulties in changing patient behavior and a lack of interest in endocrinology were the two main deterrents.

Regarding students’ exposure to the disease during medical school, diaTribe found that 36% had “a little” exposure; 30.6% said they had “some” exposure; and 6.9% reported having “a lot” of exposure. Fewer than 27% had no exposure to diabetes; most of these were first year students.

Our prognosisThe diaTribe survey suggested that fewer and fewer medical school students are planning to specialize in endocrinology. So where do patients with diabetes go? To primary care providers! As students recognize that changing patient behavior is time consuming – and lies at the core of diabetes care – they also realize that treating patients with diabetes at current reimbursement levels is not necessarily lucrative. In fact, endocrinology training takes place after satisfying the training to become a pediatrician or internist. This additional “subspecialty” training adds 2-3 years of additional training. Currently salaries for endocrinologists are not meaningfully higher than for pediatricians or internists. Therefore there is expense (lost income) but no economic benefit to undertake this training. The result: fewer healthcare professionals who can treat patients with diabetes as a specialty, a future of more diabetes complications, and a future of dwindling health (and productivity) for the US.

Our prescription Increasing physician interest in diabetes will require significant changes in reimbursement for physicians’ services and the services of diabetes educators, whom the endocrinologists love, but sometimes can’t afford to pay. Maybe persuading more insurers to pay for phone and email consultations is a start? What about incentives for practices able to achieve suitable health targets for a percentage of their patients? These may not be perfect but could be a step in the right direction. Improved therapies providing alternatives to behavior modification could also increase interest in diabetes. Most importantly, patients should play a part in improving the trend. An engaged patient allows for a much smoother consultation during which, and both patients and physicians benefit from each other’s expertise.

We look forward to a larger study focusing more on senior medical students and internal medicine experts to provide information about trends in the perception of diabetes throughout a medical education.

Most importantly,

patients should play a

part in improving the

trend. An engaged

patient allows for a

much smoother

consultation during

which both patients and

physicians benefit from

each other’s expertise.

The difficulties in

changing patient behavior

and a lack of interest in

endocrinology were

the two main deterrents

for students from

specializing in diabetes.

[1] “Who Will Manage American Patients with Diabetes in the Near Future?” Kelly L. Close, Mark Yarchoan, Katelyn L. Gamson, Jenny J. Jin, Dan A. Belkin, Michael L. Dougan, and Irl B. Hirsch, MD[2] Stewart, A. F. The United States Endocrinology Workforce: A Supply-Demand Mismatch. J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1164 – 1166.[3]Erikson, C. et al. Future Supply and Demand for Oncologists: Challenges to Assuring Access to Oncology Services. J. Oncol. Pract, March 1, 2007; 3(2):79-86.

diaTribe publishes information about diabetes products and research. This information is not a substitute for medical advice and should not be used to change treatment or therapy. diaTribe urges readers to consult with professional care providers in all matters relating to their health.

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