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Diabetes Core Update
Diabetes Core Update Special Edition - Diabetes is Primary 2015 Part 2
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Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and...
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A
Hello, I'm Dr. Neal Skolnick and I'd like to welcome you to this special edition of Diabetes Corps. Update on this special series of podcasts. We will be interviewing faculty who presented during the American Diabetes Association's Scientific Sessions Diabetes Primary Conference on June 6, 2015. In part one of this series, we heard Dr. Andrew Reinhart discussing and updating us on the standards of Care, and Dr. John Buesse discussing new medications for diabetes. In today's podcast, which is part two of this series, we will hear Dr. Charles Schaefer discussing what to do after basal insulin is no longer sufficient, and Dr. Jim Chamberlain discussing data on the importance of and the management of hypoglycemia. Next month, in part three of this series, we'll hear Dr. Jay Shubra discussing atypical diabetes, Dr. Henry Rodriguez discussing diabetes in adolescents, and Dr. Eric Johnson discussing continuous glucose monitoring and insulin pump therapy for primary care. Please visit www.professional.diabetes.org CE to access the full webcasts of these lect. Our next speaker is Charles Schaefer, who.
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Is in practice in Augusta, Georgia. Charles is an internist who focuses almost exclusively on type 2 diabetes who just spoke on the topic of when basal Insulin doesn't work.
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Welcome, Dr. Schaefer.
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Thank you, Neil. It's a pleasure to be with you this morning.
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Could you give us some overview of your talk and some of the high points for our listeners?
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C
Sure. It's an interesting topic, I think. What to do when Basal Insulin Doesn't Fully Work we're so accustomed to starting basal insulin sort of as the last thing. When all of the orals don't work, then we think about starting basal insulin. And we, we work and work and work toward trying to get that morning sugar down to our established target. And yet, interestingly, when you look at the large spectrum of people taking basal insulin, only 42% of them ever get to a target A1C. So in fact, basal insulin doesn't work more than it does. And the question that's begged by that circumstance is what do you do next? So obviously there are several answers. One is, well, you can add mealtime insulin. That's what we've been taught. There are a variety of ways to do that. Fortunately, I think some of the exciting news over recent years is that we've learned, particularly in our type 2 patients, that you don't have to go to the full monty. You don't have to go to three injections of mealtime insulin a day to get the effect you're looking for. In fact, there's several studies that show that a single injection of basal insulin at the largest meal of the day may in fact get you that a 1C reduction that you're looking for. So that's one way to go about improving upon what we can traditionally accomplish with basal insulin alone. Unfortunately, even in that circumstance, only slightly more than 50% of people receive the kind of A1C coverage that we would like to get to restore them back to their target levels of glycemic control. So in the last several years, a group of new options have popped up that are very compelling, very interesting. Adding the DPP4 inhibitors to basal insulin have been shown to be effective not only in reducing a 1C by around a half a percentage point or maybe slightly more, but we're able now to do that without the problem we have with mealtime insulin, which is no hypoglycemia, no and no weight gain. So again, a simpler way to go about achieving the same outcome. In addition, we've seen some studies done and there's a lot of work in a future type way going on looking at the possibility of using Rapid Acting GLP1 substances to try to get us better mealtime control. John Buse has done some excellent work with exenatide twice daily and shows substantial A1C reductions of around seven to eight tenths of a percentage point. And again, not only no weight gain, he actually showed weight loss in that setting, an ability to reduce basal insulin, total dosing, and also no introduction of increased hypoglycemia. So another sort of novel way to go about approaching mealtime control. And similar studies have been done with liraglutide that show similar results. A third way that's come up recently has been the introduction of SGLT2 inhibitors to basal insulin. And again, we see substantial A1C drops of 7 to 8/10 of a percentage point, weight reduction, no hypoglycemia, in fact a little bit of improved blood pressure control, which isn't a bad thing because 75% of our type 2 patients are going to come to us with hypertension anyway. So this looks like a very substantial option to add to basal insulin. That's not getting our patients to go. Now, let me add a quick caveat. On May 15, the FDA said, oh, by the way, we're now seeing some random cases of diabetic ketoacidosis in patients taking SGLT2 inhibitors. So this may suggest that something is going on at some elementary level that's affecting glucose metabolism. I think we just need to throw out a warning that these drugs should be used. With that in the back of our mind, these cases of DKA were not just in type 1 patients. In fact, we believe that most of these 20 reported cases occurred in patients with type 2, many of whom were on insulin therapy. So that needs to be used with a reasonable measure of caution. And then just in the what's new arena, we have inhaled insulin technosphere, insulin which can be inhaled either as 4, 8 or 12 units at the time of meals. The advantage of this insulin is almost an immediate uptake in the system, almost an immediate onset of action. And I think in the end the real benefit is you puff this rather than injecting it. So for patients who may be needle phobic, this is an exciting alternative to taking shots. And in fact we're seeing that there's at all stages, both immediately after you take it within the first couple of hours and from the 2 to 5 hour mark of reduction in hypoglycemia. So the good news is lots of stuff to do when basal insulin isn't enough. I would throw out a little challenge to the, to the primary care community here and that is, I'm not sure we always know when basal insulin isn't enough. We've been taught that you fix fasting first and by gosh, we often go about that with a zeal that's remarkable. We're going to get that fasting sugar less than 130 despite all odds. And in fact if you look at treat to target trials that targeted fasting sugars of less than 100, generally they got to about 127. So even under the best of circumstances we, we don't fix fasting first. And in fact if you look at what happens with basal insulin, progressive use produces less and less benefit in reducing the morning sugar. So I think one thing we've learned, and in fact our group, including you of course, Neil, are presenting a poster today in the ADA poster sessions that have shown that once you reach a basal insulin use of about 4, 10 to 5, 10 of a unit per kilo, you're very unlikely in a population basis way to further reduce fasting insulin. And it is time to turn to one of these alternatives we've just talked about.
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Dr. Schaefer, that was a fantastic overview. That's probably the most concise, organized overview of what to do after basal fails that I've ever heard. And it really points out how much the landscape has changed over the last few years. There used to be one Shaw ice.
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Add Some insulin with every meal.
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Now there's lots of choices as you went over. Thank you so much for joining us, Neil.
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Thank you. I appreciate it.
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The next speaker that we're talking to.
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Is Jim Chamberlain from St. Mark's Hospital in Salt Lake City, and he is the medical director of Diabetes services there. Welcome, Dr. Chamberlain.
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Thank you.
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And Dr. Chamberlain just gave a wonderful talk on hypoglycemia. And can you give us a overview of the most important points in your talk about what has really become a critical emerging topic?
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Sure, yeah. It's, I think, my favorite talk to give. It's certainly a very hot topic in diabetes and probably has been, I'd say, one of the hottest topics in probably in the last five years since some of the big glycemic control trials were published in type 2 diabetes. So I started by telling the audience that hypoglycemia is frequent. It's under recognized, it has a lot of significant clinical impacts on our patients, and that they need to make sure they're screening for it, that they understand the significance of it, that they're communicating that to their patients, and that they're doing things in their clinics on a daily basis to. To try to identify and minimize hypoglycemia. So we talked about the frequency of hypoglycemia first, which the important points to me to make to the crowd was that sulfonylureas are not necessarily safer than insulin. We have this sort of assumption, I think, that pills are safer than injections. Sometimes they're not. So we talked about the severe hypoglycemia rate being very similar between sulfonylurea use and insulin use. We moved on to sort of recognizing the symptoms of hypoglycemia, the dividing those into the autonomic symptoms, which are the good ones, those are sort of the warning system for our patients. So the feelings of the palpitations, the anxiety, the sweats and shakes and all of that is a good thing. What we lose sometimes, we call that hypoglycemia unawareness, when we lose those symptoms. And that feedback mechanism, type 1 diabetics, type 2s, who've had diabetes for a long time, and people that have frequent hypoglycemia can develop hypoglycemia unawareness. So we talked about that and the fact that that increases your risk for severe hypoglycemia about 6. So when patients are not feeling the symptoms of hypoglycemia, it puts them at risk for further hypoglycemia So I mentioned this concept that hypoglycemia begets or leads to further hypoglycemia because you're just simply not feeling it and your body can't help you come out of hypoglycemic events. From there, we spent a lot of time talking about the clinical consequences of hypoglycemia. So mortality, cardiovascular events, driving mishaps, quality of life issues and actually cognitive dysfunction. So we went over the mortality data from the three big studies, the type 2 control trials I mentioned from a few years ago, Advance Accord and the VA trials, and they showed about a two to three fold increase in in mortality risk in patients who had severe hypoglycemia. During those studies I showed a couple other large community based trials with tens of thousands of patients that showed very similar numbers. So essentially a two to three fold increased risk of death in patients who are suffering severe hypoglycemia. We talked about the cardiovascular events that we saw in the Origin trial. So that was a six year old study looking at insulin glargine versus standard care. The good news is overall, in that study with thousands of patients, there was no significant difference in mortality or cardiovascular events. But if you look at the subset of patients who had severe hypoglycemia, there were dramatic increases in mortality, cardiovascular events, arrhythmia, deaths approaching 70 to 80% increase in those outcomes. So bad things happening. I showed a study from Japan that was just published recently showing that when patients are brought to the emergency room with severe hypoglycemia, and These were type one and type two diabetics, about 400 patients, they looked at things like QT interval prolongation, the fact that these patients were hypokalemic and had severe hypertension. So, and so when you combine that with the fact that we know epinephrine, which is one of the main kind of regulatory hormones when you're hypoglycemic, is also a nice vasoconstrictor and platelet aggregator. So now you've got tachycardia, vasoconstriction platelet aggregation, QT interval prolongation, hypokalemia and severe hypertension, that's a pretty good recipe for killing people, in particular ischemic and fatal ventricular arrhythmias, which is what we think a lot of these people are dying from. So we talked about that, we talked about cognitive dysfunction. So several studies now showing that even one or two severe hypoglycemic events increases risk for dementia two to three fold, typically about twofold. So some pretty severe long term effects on the brain, probably especially in older patients with severe hypoglycemia. We talk about driving mishaps. Over 50% of type 1 diabetics in an observational trial suffered at least one driving mishap during a 12 month period. And that can be from as severe as crashing or getting a reckless driving ticket to simply having to pull over and treat a low blood sugar reaction or have somebody else take over the driving. A fair number of patients didn't remember driving home, having no recall of driving home. So those are, again, the clinical impact on patients is significant. Then we talked about just the anxiety and worry and fear of hypoglycemia. So several studies recently showing that over 50% of people with diabetes worry about hypoglycemia most or all of the time. And we actually have a poster here at the ADA showing that CGM might actually be able to significantly reduce that. So we covered all of that. We finish by talking about just the approach in the clinic to hypoglycemia. So obviously the first thing you have to do is you have to ask about it and you have to download glucometers. I made the point to the audience that if they're seeing any significant number of diabetics at all in their clinics, they have to be downloading glucometers and continuous glucose monitors if their patients are using those. Very simple to do. And the data that you can extract is obviously very helpful. Quizzing patients about hypoglycemia is only done about 30% of the time in primary care visits in people with diabetes. So we have to be asking, we have to be trying to get data from glucometers. And we talked about the fact that every hypoglycemic event happens for a reason. So I think you have to ask patients, what were you doing? When did you last take your medication? When did you last take insulin? You have to try to figure out was this from long acting insulin or sulfonylurea, which typically causes hypoglycemia. When patients are fasting for extended periods of time, so early in the morning, late in the night or just before waking up or late afternoon, or patients are skipping meals and getting low in the middle part of the day, that's typically basal insulin or sulfonylurea. Hypoglycemia occurring within about three hours of meals most typically is going to be from the rapid acting insulins. And or activity level. So we talked about that. We talked about treating hypoglycemia with commercial products. Glucose tabs and gels and whatnot are easy to carry around. They work quickly, they don't have fat to slow absorption. And I think it really helps patients not be tempted to over treat their hypoglycemia. So we talked about the concept of the 1515 rule, which is when you're hypoglycemic, eat or drink 15 grams of carbohydrate, wait 15 minutes, check your blood sugar again, give it a chance to have come up. If you're still below 70 or 80, treat again with 15 carb grams, wait 15 minutes and just bring your sugar up in a stepwise approach so you don't drive your blood sugar from 50 to 400, which patients do frequently.
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Well, that was great, Dr. Chamberlain. And it really has become a critical issue. We've all become sick attentive to getting those A1Cs down, partly because quality measures. Look at that. I know there's talk about quality measures beginning to look at our assessment of hypoglycemia. As you said, it's really an astonishing number. 30% of people are asking about hyperglycemia. And I think you've nicely summarized the reasons we ought to be paying attention. Thank you so much.
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That was some wonderful information. Again Today we heard Dr. Charles Schaefer discussing what to do after basal insulin is no longer Safe sufficient and Dr. James Chamberlain discussing data on the importance of and management of hypoglycemia. Remember, in part one of this special series that came out last month, we heard Dr. Reinhart discussing an update on the standards of Care and Dr. Buce discussing new medications for diabetes. Next month, in part three of this special series, we will hear Dr. Jay Shubrook discussing atypical diabetes, Dr. Rodriguez discussing diabetes in adolescents, and Drs. Johnson discussing continuous glucose monitoring and insulin pump therapy for primary care. Please visit www.professional.diabetes.org CE to access the full version of these lectures via webcast.
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Thank you, Sam.