Q and A Session

Moderator: Our first question today comes from our planning committee. In your opinion, what is the most important action clinicians can take to prevent CVD in patients with diabetes? Dr. Goldstein?

Dr. Barry Goldstein: Well, I think that is really the highlight of what we are trying to communicate in this presentation. And as we were discussing the many factors, it is really this attention to the multiple risk factors that contribute. We know that blood pressure control and lipid control is very important in nondiabetic individuals, but also it has been proven now in diabetes. These are important things to get under control according to the guidelines, besides glycemic control. I think the final answer is really still out on how much glycemic control will help to prevent macrovascular disease, but it is likely that it is playing a role. We certainly know that microvascular complications are tightly connected to glucose control in diabetes, and there is a relationship between micro- and macrovascular disease in that people that get renal failure certainly are more susceptible to cardiovascular end points.

So, it is really this multiple approach. And the compliance issues and the managed care perspective that Dr. Cardarelli presented are really important from a more practical and systems point of view to help patients really cover all of these multiple aspects of their disease management.

Moderator: Thank you. Dr. Cardarelli, would you like to comment?

Dr. William Cardarelli: Well, I agree with Dr. Goldstein’s comments. This is a very complex disease state, with a lot of comorbidities that are naturally associated with it. And, as Dr. Goldstein pointed out, both the control of hypertension, the control of lipid levels, risk minimization in terms of both heart attack and stroke are critically important in this space.

I think as a care deliverer—it is a system that delivers care—it is really important that we marshal all of our available resources to make sure that we are taking care of these patients in total. So while it is critically important to manage their diabetes, it is equally important to manage their lipid issues or hypertension issues, to prevent the onset of both macrovascular and microvascular complications, all of which ultimately end up with a much healthier patient who does not suffer any of these complications, or hopefully does not.

Moderator: Thank you. Our next question today comes from the VA Medical Center. Please go ahead with your question.

Participant: Yes, I wanted to get some more insight from either of you on the ACCORD trial—if you think that those results are going to really pan out or if that is changing your practice in any way? And also, one other question, if you could talk about the differences between using detemir or glargine insulin?

Dr. Goldstein: Yes, I think they are 2 important questions.

The ACCORD trial, actually I am quite involved with that, and really know what limited information has been made public in the sense that it is not really clear what seems to account for the increased deaths in the intensively treated group. What may not be as widely known, there is a similar study that was done in Australia called the ADVANCE trial, which was also looking at cardiovascular outcomes and intensive control, getting to try to get to a normal A1c level. That study has also recently completed, and they did not find the same issue with increased deaths with intensive treatments. So, I think we are all looking toward the ADA meeting; it is actually going to have a symposium with investigators from both of these trials in talking about what the issues are and we will get some more insight at that point.

Whether it relates practically to how we manage patients—I think the media has really gotten this wrong, because the ACCORD study is not a typical clinical-practice scenario. They are patients who are at risk of cardiovascular events. The intensity of the treatment was really very aggressive with lots of prandial insulin, aggressive use of basal insulin, and combination with oral agents. And, as you would expect, hypoglycemia and lots of things going on, because the target A1c was even less than 6%, trying to get people on average in that group to have an A1c of about 6.5%. So normally, especially in people that may be at risk, we are looking at an A1c toward 6.5%, certainly less than 7%. So, the typical guidelines, I do not think, have really changed with these new results, and we are still going to get more information.

The other question about glargine and detemir—there are some pharmacologic differences, one is that some of the studies have shown that detemir seems to be associated with less weight gain, and it may have different action in the body. It may actually get into some of the sites in the brain that regulate appetite or weight control, because structurally it is different than glargine. Detemir is a fatty acid coupled to insulin that is carried around the body in albumin. It may get through the blood-brain barrier, we are not really sure, but it is possible.

Glargine is a derivative of the insulin structure that precipitates after you inject it. So, it is sort of the opposite of NPH, which you inject as a precipitate. Glargine is slowly absorbed; but once it is absorbed, it acts like any other insulin. It is just the kinetics of the time course of absorption are prolonged. Glargine is longer in its duration of action, probably working 18 to 24 hours, whereas detemir is really a 12- to 14-hour insulin, and if you give a higher dose, it could have a longer time of action. But, most of the time, people are using detemir either to provide overnight coverage—which may be appropriate in some patients—or if it is used in type 1 and many type 2 patients, it is given twice a day, whereas glargine would be expected to act more like a once-a-day preparation.

Participant: But, do you prefer one over the other?

Dr. Goldstein: Well, there are a couple of considerations. One is the glargine people have come out with a much better pen device recently. I think if you want a single injection for patients with type 2 diabetes, for convenience, you definitely would go with glargine; we probably use more glargine. There are many patients that have a high fasting blood sugar, because the pancreas cannot respond to the glucose overnight. But, during the day, they are responding to their metformin, and maybe their sulfonylurea. So, if you are really just targeting fasting, and maybe before-dinner blood sugar is okay, I think then detemir would be a good choice.

Moderator: Thank you. Dr. Cardarelli, do you have any thoughts on this topic?

Dr. Cardarelli: Well, I think Dr. Goldstein did an excellent job talking about the insulin. So, I cannot add anything to that conversation.

With regard to the pen devices, I think that managed care is very slowly but certainly coming around to a more universal acceptance of these. If you look at the utilization of pen devices in the United States versus the use of them in Europe, you will find that Europe uses them very extensively, and yet the uptake in the United States has been very slow. There is no question that they contribute positively to adherence and persistence in therapy. So, I think overall that there is a good return on your investment there, and I would support that.

In terms of the ACCORD trial, the problem with trials and the subsequent publicity, is that sometimes the publicity is a little bit out of proportion with their importance. I would simply caution everyone to look at all of the studies that are available, and to really evaluate them. There is the European study, which basically said the opposite of what ACCORD said. There are several other studies that look at treatment of type 2 diabetes that come up with differing responses. You really have to take the body of evidence in its totality versus looking at one specific, very highly publicized survey. So, I would just caution the group on that specifically.

Dr. Goldstein: The other thing that I would add to your comment about the pen—glargine insulin is recommended to only be used for 30 days once the vial is open, and this seems to be related to the way that it is made. It is an acidic solution that gets neutralized when it is injected. And, many patients have also told me that they see that if they try to use it more than a month, it loses its effectiveness. So, if you have a vial that contains 1000 units, and the patient is only using a couple of hundred units, at the end of the month it is really a waste. And, I do not know how this factors into the costs in terms of managed care, but the pens have only 300 units, and just saving the product, it seems like a good way to go.

Dr. Cardarelli: I agree.

Moderator: Thank you. Our next question today comes from University of Pittsburgh Presbyterian Shady Side. Please go ahead with your question.

Participant: Yes, we understand that you are working in the EpiCare Medical Record. We are just starting on it, and we were wondering if there was anything we needed to work with specifically, maybe a diabetic flow sheet, or something that would help us monitor the patients more accurately?

Dr. Cardarelli: We actually created what EpiCare now refers to as a diabetes dashboard, and it is essentially a flow sheet, which I believe EpiCare has put into its latest release.

Participant: Great.

Dr. Cardarelli: One of the things about working with EpiCare is that they do a lot of benchmarking of different institutions, and we are one of the larger users of EpiCare within their system right now. And there is a lot of utility and a lot of capability within the EpiCare Electronic Medical Record System around tracking patients, building rosters so that you can outreach to them, and actually generating electronic letters to patients. There is a feature where the patient can connect directly, electronically, and view portions of their electronic medical record, all of which improves the connectivity between the physician and his or her patient. So, we have had a very good experience with the EpiCare system up here.

Moderator: Our next question today comes from St. Tammany Parish Hospital. Please go ahead with your question.

Participant: Some of our cardiologists have changed their practice, and are no longer holding metformin after the administration of a contrast. Would you agree with that practice?

Dr. Goldstein: Well, I think what has been unusual about the recommendations with metformin has been this idea that you should stop it 2 days before a procedure.

Participant: Well, 2 days after, not before.

Dr. Goldstein: Yes, because it does not accumulate, you take it more than once a day. But, I do think that still it would be prudent that after a contrast—iodinated contrast—which in patients with diabetes can cause some transient renal insufficiency, you are supposed to document the normal creatinine after the procedure. And, the way that radiologists handle this is the patients should be well-hydrated, and there is still a small risk that the patient may end up with a reduced creatinine clearance. Then if they go back on their metformin, even though we know that the risk of lactic acid doses is very low, it is still worth doing that. It is just holding it before the procedure that patients are always calling us. They tell us the doctor recommends that they stop their drug for 2 days before surgery. That does not really make sense. But, once you have the contrast, or a major procedure, I think you really should check the creatinine again.