B (3:03)

Neil John, what I liked about this study is a few things. 1. It showed that efforts to help people change their behavior work when it's carried out in a systematic multimodal fashion and it works in a real way. People doubled their exercise amount roughly they dropped their A1Cs by about 0.3% and they decreased their BMIs by 1 compared to the group that just got usual care, which was, hey, why don't you try and exercise basically. And then what they did was they looked at what's needed. What does that multimodal approach involve from an office setting? Basically, what they determined was that you have to be specific with regard to what you want people to do, not just why don't you try and exercise more, but set clear behavioral goals. Here's what we want to achieve. Here's what we want you to do by next visit. The second thing they saw that worked was follow up, whether that was phone follow up or in office follow up, that having clear methods for follow up and encouraging sustained behavior helps. The next thing they talked about is important is enlisting social supports. No one can do it alone. Figuring out who your patient's main supports are and getting them to help carry out the encouragement for those behavioral changes, because behavioral changes aren't easy to begin with and they're even harder to sustain. And then anticipatory guidance, talking to patients about how are they going to manage their time, when are they going to fit in their exercise and focus on past success, successes and failures, what has allowed you in the past to be successful when you were successful in changing your behavior, and where were the rocky points in the road? So using a number of different behavioral theories and strategies as we just outlined, allows one to actually achieve, and their studies looked at over 1900 people, so there's a lot of validity to them in 17 different studies allows you to achieve sustained behavioral change. John Joining us today is the editor of diabetes care, Dr. William Cefalou, who's been kind enough to share some of his thoughts on two important articles. Dr. Cefalu is Associate Executive Director of Clinical Research, Douglas L. Manship, Sr. Professor of Diabetes, Chief Joint Program on Diabetes, Endocrinology and Metabolism, Pennington Biomedical Research center and LSUHSC School of Medicine. Will the first article that you were going to talk to us about is the review by David Sack on the measurement of hemoglobin A1C. Measuring A1C is something that's become so ordinary that we don't think much anymore about the details of its measurement, and we forget that the first commercial assay for A1C only became available about 35 years ago. Would you mind going over some of the information in this review article about the history of A1C, the measurement of A1C, and most importantly, how and why we're going to be seeing new units of measurement showing up in the reported A1C values.

D (6:28)

Well, perfect actually. It's because we were so comfortable with assay that it's important that we now talk about it. All the individual patients, physicians have been quite comfortable with our current reporting for the hemoglobin A1C generally as a percent for years have done a very good job in making sure individuals know their percent A1C. And actually this reference unit goes back to the DCCT and UK PDS as far as it becoming standardized. However, many years ago there's been a push around the world to actually reference the hemoglobin A1c more to more specified units. Again, the International Federation for Clinical Chemistry wanted it referenced to to a more definite endpoint. So over the past many years there's been discussion, ada, esd, idf, as far as the best way to report these particular values. And many of the countries across the world are actually going to the FI unit or the international unit. Essentially this is not a percent, but really bases the unit on a completely different unit in millimoles of A1C expressed per mole of the hemoglobin A. Now what this essentially does, it really creates a disconnect between those countries who are reporting one unit versus the other. First and foremost, those of us who publish and are editors of journals, and yet we read journals from different, different countries, there would be no way to really compare one unit versus the other. Even though they would be equivalent, they're actually different units and they're 1% unit linear, but at the same time they are completely different units. And it's not as easy to convert percent or international units. You actually have to use an equation and these equations are listed on website, but it needs to be corrected. So that's the first thing. The second thing is that if you compare a publication that was done in one unit versus a different publication in a new unit, there's really no way to compare. So what we are suggesting at Diabetes Care is that for a time we report in dual units, essentially meaning that papers come in and they have to report report in the percent, which is the O unit, and the SI unit, which is the milling unit, which is what we're suggesting. This would allow us at Diabetes Care and the readers at Diabetes Care to essentially compare any publication in the world back to what we are currently publishing, in the sense that if a unit publication is presenting in percent, you'll be able to relay it back to the article you're reading. If another journal's publishing in SI units, you'll be able to relay it back to the particular journal article. And again, this review is extremely timely because it talks about the history of the A1C. It talks about the comparison. For example, there's a nice table in this review that looks at the old unit versus the new unit and you'll see that it's not similar. For example, an old A1C in the National Glycohemoglobin Standardization Program of 4% related to a new SI unit of about 20. However, if the percent now goes up to 12, which is a threefold increase by the old standard, it goes up almost five fold with the new standard. Even though it's linear, its different reference ranges are relative at the low versus the high level. You really can't do a quick conversion. You actually have to use the equation that's on the website and calculate one to the other. So this is going to be great education for physicians, for researchers, and it's going to be even more education for patients. But I think at this point, as far as dual reporting the A1C, we'll still be able to compare what we're doing in diabetes care with what's done around the world. And again, the important thing is that some countries are now reporting only the SI unit, whereas other countries are reporting both or still reporting the percent unit. So it's a very important review for those interested in either research or care of the patient with diabetes.

B (11:26)

Thanks for going over this issue in detail. This information helps clarify a potentially confusing issue, and I'm sure our listeners appreciate your input here. The next article that we're going to discuss is titled projection of type 1 and type 2 diabetes burden in the United States Population aged less than 20 years through 2050. The article discusses frightening projections of increases in diabetes in the youth over the next 30 to 40 years. Can you tell us about this article and its implications?

D (12:00)

Well, actually, you said the operative word. This is scary. And again, this is an article that was really well done. Essentially looked at the database from the census report. It looks at the incidence of type 1 and type 2 diabetes currently. It looked at changes that we can expect in migration patterns and percent changes that we can see in ethnic backgrounds. And clearly we've had a lot of information on the prevalence of diabetes in the adult population. Again, essentially since 2000, the increase in number of new cases up to over 23 million. The CDC now reports even higher cases. So for the adult population, we've had some frightening trends for many, many years as far as type 2 diabetes. What's real interesting about this particular as we're now seeing the impact of these changes in the US and the rising rates of obesity among kids. And now we're seeing real projections of what this is going to be like for our children 40 years from now. There's no question when we look at the morbidity and mortality from diabetes in adult population, and now we're suggesting that kids or individuals below the age of 18 have this disease, what impact is that going to be on health related outcomes for these individuals 20 years from now at a time when we would think they would normally start developing the disease? But this particular study actually estimates that for type 1 diabetes, a 23% increase in type 1 diabetes by 2050 and almost a 49% increase in type 2 diabetes in this particular age range over the next 40 years. So this is pretty frightening. And what it does tell us is that at this particular time that even though we've done a great job managing micro and macrovascular complications for diabetes, the sheer number of new cases is going to be really increasing. Even though we've reduced, we think, the micro and microvascular complications, the fact that the population's getting larger, the fact that we're seeing these increasing trends is still going to be a huge problem. Now, what it means as far as management of type 1 diabetes, clearly there's going to be a shift in the ethnic groups that have type 1 diabetes. So what's going to be important from the clinical standpoint is knowing the presentation, the rates of control, how this different ethnic population, as far as having type 1 diabetes, what will be the difference in presentation and treatment for type 2? It speaks to the fact now, can we now expect the strategies that we use in adults to be working in kids as far as addressing the obesity epidemic, which we know is one of the main reasons we're seeing the increase in type 2 diabetes. So we have a lot of work cut out for us as far as this particular projections and more importantly, what we can do to address the prevention. I know Bob Ratner, who's now the chief medical officer ADA also point out his editorial and talked about just, he put it in a very good light as far as what we need to do and what we need to address and how imperative it is now that we start addressing prevention strategies not only in adults, but it's really frightening what's happening in children right now. Thanks. It really is a point worth emphasis that the biggest impact that we stand to have now is really in primary prevention and, and back to fundamentals, it's diet, it's exercise, and for kids it's got to be done in a way that they enjoy because unlike adults, they don't set their goals necessarily and go after it. They do what feels right and perhaps video games feel too right and sports and eating well doesn't feel right enough. But clearly there's a lot that we need to do. The other thing is children. If I can make one more point, it's a little bit more difficult than adults in the sense that now we have to worry about. So in children it's not going to be as easy because we have other things to worry about. We have these children are still actively growing. So how do you actually implement weight reducing measures in someone who is still in an active growth birth? And so these are important issues and there's a lot of again, peer pressure and how you relate to changes for the child and yet maintain these healthy lifestyle behavior is going to be a challenge. That's a great point. Thank you so much for joining us.

B (17:19)

Our next study is from the December issue of Diabetes Care. A randomized placebo controlled comparison of amitriptyline, duloxetine and pregabalin in patients with chronic diabetic peripheral neuropathic pain. This was a double blind randomized parallel group investigation of type 1 and type 2 diabetic patients with diabetic peripheral neuropathy. Each treatment group had a single blind 8 day placebo run in followed by 14 days of lower dose and then 14 days of higher dose medication at the end of each dose titration interview period, subjective pain, sleep and daytime functioning were assessed. All medications reduced pain by about 50% compared with placebo, but no one treatment was better than any of the others for sleep. Pregabalin improved sleep continuity, but duloxetine increased wake and reduced total sleep time. Pregabalin seemed to make people a little bit more sleepy during the day. Duloxetine improved wakefulness and attentiveness during the day.

C (18:31)

John so this is certainly a problem we have in many of our patients with diabetes. And for me, taking away from this paper is it's nice to know that amitriptyline and duloxetine and pregabalin all worked pretty equivalently. I also would have been interested in the study if they had thrown gabapentin in as a potentially another generic medicine to use for this. Some of the takeaway points is, you know, a study that has 80 people in it. I'm not so sure. I'm going to base a ton of things on it, but overall it seemed that the numbers were fairly equivalent. The authors seem to really not emphasize that the people got pregabalin did worse on daytime cognitive functions than the people who did duloxetine and amitriptyline. And I also think we have to remember that was not pointed out in this article that amitriptyline is an old drug, a good drug, but often not the best drug to give, especially in our elderly patients, with regard to orthostatic hypotension and other side effects that can come from that medicine. So I think really one of our things is really try to prevent peripheral neuropathy by better glycemic control as best we can. Our next article is from diabetes spectrum, the November 2012 edition, and it looked at the use of the dietary approaches to stop hypertension or the DASH eating plan for diabetes management. The DASH trial, Originally published in 1997, reviewed the impact of eating patterns on blood pressure management. Specifically, the study subjects were fed either a diet rich in fruits and vegetables or a combination diet that was both rich in fruits and vegetables and low fat dairy foods and low in saturated fat. And this study really found that diet could have a remarkable impact on hypertension. So in this particular paper the researchers looked and said how about the DASH trial for diabetes and some of the studies they looked at. One was a randomized trial. The Premier trial that looked at 52 subjects revealed that the DASH eating plan was beneficial for improving a variety of factors in the Medolach syndrome, including blood pressure, lipid levels and insulin resistance. And the authors concluded that the addition of the DASH eating plan led to statistically improvements in insulin sensitivity compared to the control group. Another trial, the Encore trial, was a randomized controlled trial of 144 hypertensive subjects that showed different results. This trial suggested that the DASH eating plan alone may help to reduce blood pressure in hypertensive individuals who are overweight, but may not significantly improve insulin sensitivity unless combined with a lifestyle modification program that includes weight and exercise reduction.

B (21:29)

Neil John this study was interesting. This review was interesting in terms of introducing us and reminding us about the DASH approach toward hypertension and potentially its utility with patients with diabetes. It's important to remember that the main thing with diabetes is still going to be weight management, and lifestyle approaches are best off emphasizing a combination of diet and exercise. There are two real interesting articles about three years ago in the New England Journal, one in July of 2008, the second in February of 2009 that compared different diets high fat versus low fat, high protein versus low protein. Now, these trials were not in all diabetic patients, but what the trial showed that was interesting was that really the different types of diets worked equally to achieve weight loss and that the thing that was the best predictor of weight loss in patients wasn't the type of diet that they were on, but their degree of motivation in adhering to the diet so that it really is about calories. Dash is a reasonable plan. It has a lot of evidence with regard to decreasing blood pressure, with regard to other aspects of management. It's on the map. But it's important to make use of our diabetic nurse educators, have patients see them and find dietary plans that patients will most comfortably adhere to. Our next study from the December issue of Diabetes Care is titled moderate Intensity physical activity ameliorates the Breast Cancer risk in Diabetic Women. Previous studies have shown that there's a relationship between breast cancer and decreasing breast cancer incidence in those who exercise more. This study looked at the relationship among patients with diabetes. It was a population based case controlled study using 1,000 incident cases and over 1,000 control subjects. The association between diabetes and breast cancer risk decreased with increasing tertiles of moderate intensity physical activity with an odds ratio of 4.93 and 1 respectively for each tertile.

C (23:55)

JOHN so certainly this is not breaking completely new ground and certainly some of the cancers do have a behavioral component. So obesity has been linked with breast cancer, obesity has been linked with colon cancer, and it would certainly follow that people who exercise perhaps can decrease some of that risk. I think it was interesting in this particular study that they did use some serum markers, C peptide, IGF1 and IGF binding protein 3 levels, to actually seem as a bit of its proof of evidence that if you could change these markers, you could change someone's breast cancer risk. So when I was taking math class in junior high and high school, you'd have to show your work and I clearly think the authors came to the right answer. I'm not sure I completely agree with the work they did along the way.

B (24:50)

For more information and links to the articles that we discussed in this issue, just go to www. Diabetesjournals.org until next week, keep listening and keep learning.

D (25:07)

Sam.