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Diabetes Core Update
Diabetes Core Update November 2015
00:19:45
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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- [00:04]
A
Welcome to the American Diabetes Association Diabetes Core Update, where we will regularly keep you up to date on the latest clinically relevant articles from the American Diabetes Association's core science and medical journals Diabetes, Diabetes Care, Clinical Diabetes and Diabetes Spectrum. Joining us for this program are Dr. Neal Skolnik, who is a Professor of Family Medicine at Temple University School of Medicine and Associate Director in the Family Medicine Residency Program at Abington Memorial Hospital. Welcome Dr. Skolnick.
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B
Thank you. It's a pleasure to be here.
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And Dr. John Russell, who is a Professor of Family Medicine at Temple University School of Medicine and Director in the Family Medicine Residency Program at Abington Memorial Hospital.
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C
Thank you. I'm looking forward to going over this week's articles.
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A
And now for the articles.
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B
We have another excellent issue this week, beginning with an article discussing the development of a new weekly DPP inhibitor, Then an article on vaccination rates in patients with diabetes, followed by an article that looks at triple therapy with dapagliflozin, saxagliptin and metformin. Then an article looking at sleep disturbances and the relationship of sleep disturbance including sleep apnea and insomnia and snoring to glucose metabolism and fat. Finally, individual variations in energy expenditure in response to fasting and overfeeding.
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C
Our first article is from the November 2015 edition of Diabetes Care and it looked at safety and efficacy of a novel DPP4 inhibitor, omegliptin for the treatment of patients with type 2 diabetes. This was a multi center double blind 12 week dose range finding study that looked at 685 hyperglycemic naive patients who had type 2 diabetes were randomized to 1 of 5 weekly doses of omerogliptin. The primary efficacy endpoint was changed from baseline A1C and the secondary endpoints were a two hour postprandial meal glucose and fasting blood glucose. What the researchers found is that once weekly treatment for 12 weeks with omerogliptin provided dose related reduction in a 1C 2 hour post meal glucose fasting blood glucose and at 12 weeks the omerogliptin 25 milligram dose provided the greatest glycemic efficacy. Roughly it equated to an A1C decrease of 0.72% decrease. The incidence of adverse events was similar across all the dose groups and there was a low incidence of symptomatic hypoglycemia. There was no effect found on body weight.
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Neil John, this is exciting the advent of once a week treatments for diabetes. We have two GLP1 agonists that are available for weekly injection. And now the prospect in the future of a Once weekly oral DPP. 4. One of the big issues in any chronic disease, and certainly in diabetes, is the issue of compliance. When you look at compliance data in diabetes, and this is data that is obtained from pharmacy reports that look at how many months out of 12 months do patients refill their medicines. It turns out that patients on the average with diabetes only fill 60 to 80% of the prescriptions that are prescribed for them. What is the main issue when it comes to adherence with medication taking? It appears to be motivation and complexity of medical regimen. We know that once daily medicines are taken more frequently or are adhered to better than for instance, three or four time a day medicines which are hard to take. It's not entirely clear that once weekly will be taken more as prescribed than once daily, but hopefully that'll be the case. And the other, I think, important thing that this brings up for all of us, taking care of patients, is that one of the critical things that we do with patients, in addition to picking the right medicine for them, is helping keep them motivated to take their medicines to get as best outcomes as possible. Our next article is on adherence to guidelines for hepatitis B, pneumococcal vaccination and influenza vaccination in patients with diabetes. This was a single center cross sectional study designed to assess adherence to national guidelines that was published in Clinical Diabetes. The authors looked at a hundred patients admitted to the inpatient service in a single hospital and assessed vaccination rates. What they found was that vaccination compliance for influenza was 41%. For pneumococcal vaccine, specifically pneumovax was 37%. And none of the patients had had hepatitis B vaccine.
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C
John So a very important concept. It might not necessarily been the really kind of the right way to investigate this. So certainly looking at a single hospital, looking at 100 diabetics and just asking them which of these vaccines they've gotten without trying to tie this to their outpatient records, does not really seem to give the answer, you know, as perfectly as we'd like to give. But probably the truth is that people are not as good at getting these vaccines. So remember, we're in the beginning of flu season. Everyone over the age of 6 months should be getting a flu shot. Certainly there's not a whole lot of question about that. And I think when you ask patients, did they get a flu shot this year? I think people probably remember whether they got a flu shot this year because of, you know, it's every Annual type thing. So flu shot's real important. The pneumococcal vaccine. So certainly we're faced now with two pneumococcal vaccines. We have the Pneumovax, the polysaccharide vaccine as well as the conjugate vaccine. It's a little bit confusing. Who needs to get what? So when you look at Healthy People 2010 we did a pretty good job at vaccinating folks over 65 for pneum. The question is the folks who are under the age of 65. So folks under the age of 65 do not need the conjugate vaccine, do not need the Prevnar 13. They do need a single dose of the Pneumovax that they should get before the age of 65 and then their second one would be given five years later, as long as it's after the age of 65. So if I get the Pneumovax at 22, my next Pneumovax as a diabetic would be at 65 and I would not need the Prevnar 13. I would only need the Prevnar 13 if I found myself on dialysis or with a cancer, etc. So I think that that's important to do, although I think kind of living as consumers. The direct to consumer vaccination market, as you walk through the local drugstore and it says remember to get your every five year pneumococcal vaccine. Not necessarily true. And there might be a small subset of people who should get three pneumovacs in their life, but it's a very, very, very small subset of folks who are the asplenics, the people who are immunocompromised. E and the folks who should get the prevnar 13 under the age of 65 are the people who are at risk for bacteremia for the most part. Now the hepatitis B vaccine is kind of an interesting thing and it's one of these recommendations that doesn't make the backstory, doesn't make as much inherent sense as one would expect. So when they looked over a 20 year period of hepatitis B outbreaks, a large percentage of these happened at some kind of group setting where someone was going around and using lancets on multiple people for assessing blood glucose and actually spread hepatitis B that way. And then so that led to us vaccinating all of our folks against hepatitis B. So I don't think necessarily the diabetic population is that much more at risk for a sexually transmitted infection as well as a bloodborne infection. But I do think our diabetic patients have a higher likelihood of finding them at the working end of a dialysis machine later in life. So certainly it's a relatively innocuous vaccine to give. We probably don't do as good a job with taking sexual histories on people. So there's. It kind of makes a lot of sense that way to get the vaccine and it doesn't really carry a whole lot of side effects. Remember, if someone is on the other side of dialysis and they have CKD5 and they're receiving dialysis, they need a higher dose of the hepatitis B vaccine. Our next article is from the November edition of Diabetes Care. And it was a randomized double blind phase three trial triple therapy with dapagliflozin as an add on to saxagliptin plus metformin in patients with type 2 diabetes. So this particular study looked at a total of 320 patients. 160 patients were on stable metformin doses. The second 160 were on metformin and a stable dose of DPP4. And in both groups the average A1C found themselves in the low eights. Patients were randomized to go on a metformin plus saxagliptin at 5mg per day or plain metformin and they had an add on of dapagliflozin and patients were followed for A1C over 24 weeks. The secondary endpoints including fasted glucose, 2 hour postprandial glucose, body weight changes and the proportion of patients achieving an A1C level of less than 7. What the researchers found is that treatment with the dapagliflozin add on to the saxagliptin plus metformin resulted in a greater mean A1C reduction, a decrease of 0.82 versus 0.2 for placebo. There were significantly greater reductions in fasting blood glucose level. The two hour postprandial glucose and body weights were observed. There was a low risk of hypoglycemia. The gentle infections developed in more patients with dopagliflozin which was 5% versus the placebo which is 0.6%.
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Neil John it's interesting when we look at the combination of dapagliflozin, saxagliptin and metformin. What I think about is this is very similar to when we treat patients with hypertension that we become used to there using multiple medicines that work through different mechanisms. And that's the model that we've now moved to with diabetes and this is a combination of mechanisms that makes sense. So if we think back to DeFronzo's ominous octet here, with this combination we're hitting five of the eight potential mechanisms. So metformin, we're addressing liver issues in glucagon where and gluconeogenesis, we're addressing resistance with saxagliptin, we're addressing the incretins as well as satiety. And then of course with dapagliflozin we're addressing the kidney. And when we think about adding medicines going from single to double to triple oral therapies, it is helpful to think about it with regard to using medicines that address complementary mechanisms. And what we see as we saw this study, is that it works and it helps us and our patients achieve better A1C control. Our next article is titled Sleep Disturbances and Glucose Metabolism in Older Adults from Diabetes Care. And in this study they looked at the patients from the Cardiovascular Health study, that's almost 6,000 participants greater than 65 years of age from four U.S. communities. And they looked at the participants reports of sleep disordered breathing, specifically insomnia, snoring or sleep apnea. And then they determined the cross sectional association of sleep symptoms with fasting glucose levels, two hour glucose levels, insulin sensitivity and insulin secretion. What they found was that apnea, snoring and daytime sleepiness were associated with higher fasting glucose levels, higher two hour glucose levels and lower insulin sensitivity and higher insulin secretion. The risk of the development of type 2 diabetes was associated with observed sleep apnea with an increase of 80%, snoring, an increase of 27% and daytime sleepiness an increase of 54%. There was not a consistent association of between insomnia symptoms and glucose metabolism or diabetes.
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John so a study that in many ways not especially surprising. So I don't think any of us would wrap our heads around saying if you have diabetes you're more likely to have insomnia. And this study in fact showed it. I think we would all kind of think that that person who has OSA or pre OSA certainly would be at increased risk for diabetes. When we think about someone having Pickwickian syndrome, we think about someone who is so large that they their OSA is manifesting itself 24 hours a day, kind of. And the term the Pickwickian syndrome comes from the Pickwick Papers, which was Dickens first foray into writing. And there was a character Joe in there who would kind of just fall asleep at the table. And the first write up of the Pickwickian syndrome was in the 1950s about a gambler who was basically kind of falling asleep from his hypoventilation. So certainly I think we would think if someone has defined OSA or maybe pre osa, that they would have an increased risk for diabetes. Just like we would say if someone has diabetes and obesity that they probably would be an increased risk for having some sleep disorder. Certainly we should think about treating the two. And interestingly enough, when we do bariatric procedures to have people lose a large amount of weight, which can be very, very helpful in diabetes, not everyone loses their osa. So it's not necessarily something that, geez, if we can do the surgery and have you lose £100, you're not going to need the CPAP anymore. So an interesting study that reaffirms things that I think logically we would guess our next article is from diabetes and it looked at energy expenditure responses to fasting and overfeeding to identify phenotypes associated with with weight change. So in this particular study, volunteers were recruited from the Phoenix, Arizona area between 2007 and 2013 and they were admitted to a clinical research unit for 25 days to participate in an inpatient study looking at their metabolic responses to either fasting or overfeeding. Overall, 79 folks were admitted to the study and 59 folks completed the study. In the particular study, the groups were randomized to five particular groups and on any given day they were either fasted, given a low protein over calorie diet, a standard over calorie diet, a high fat over calorie diet, or a high carb over calorie diet. And they were followed through a whole series of studies that looked at their energy expenditure, caloric intake, caloric burn, and then they were followed and they were reevaluated six months later. And it was to examine to how do people respond to either fasting or overfeeding and overfeeding with individual things. What they found they found two independent things associated with weight gain, an ability to conserve energy during caloric and protein deprivation, or a increased response energy wise to large amounts of carbohydrates.
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B
Neil John, I like this article because it teaches us again that there's an enormous amount of individual variability when it comes to things like dieting and weight control. We'd seen in a previous article that we reviewed on this podcast about two years ago a study that looked at functional MRI results in patients who were exposed to tasty food stimulus. And what that study showed was that in obese individuals the lighting up on the functional mri and the part of the brain that drives you to get food was far more intense and spread out more quickly than the similar response to tasty food stimulus in lean individuals. Showing that people who are already obese have a stronger desire to have more food when exposed to food stimulus. Again, we're all different. We're all dealing with different responses to often the same stimuli. This study shows that individual variability in a different way. And what it shows is that there are essentially different phenotypes, different responses to food restriction. And I think the clearest one here is on fasting. And what it showed is that some people, when fasting, decrease their energy expenditure more than others. And what it showed in six months follow up is that if you're the type of person who, without even thinking about it, decreases your energy expenditure. And remember, energy expenditure is a combination of how much you move around and your basal metabolic rate. If you decrease your energy expenditure more during caloric restriction, then they showed by six months later, you tend to gain more weight, you gain more weight easily and it's more difficult to take off weight when you diet because you're decreasing, decreasing your energy expenditure. The relationship between overfeeding, particularly with carbohydrates, and I won't go into detail on that. Also showed a lot of individual variability and suggested that there might be some people who actually do better on low carb diets than high carb diets. We know this from our clinical experience, but had not yet had the scientific data to support that hypothesis. So the bottom line is when we advise patients to diet and to exercise, we ought to do so recognizing the individual challenges and differences in outcome that they might expect from achieving similar behaviors. 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 it.
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Sam.