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Diabetes Core Update
Diabetes Core Update November 2014
00:19:37
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 four 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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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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Thank you. I'm looking forward to going over this week's articles.
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And now for the articles.
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We have another excellent issue this month, beginning with an article from Diabetes Care on high intensity statin therapy and its effect on regression of coronary plaque in patients with diabetes. Then an article from Diabetes Care on the contribution of liraglutide in fixed dose combination with insulin deglodeq, followed by an article from Clinical Diabetes on practical use of GLP1 receptor agonists in primary care, then an article from Diabetes Care on functional MRI and exaggerated brain response to food images in obese adolescents, and finally the article that we've all been waiting for on pistachio consumption and glucose metabolism, insulin resistance and metabolic markers from Diabetes Care. Our first study is from Diabetes Care on high intensity statin therapy altering the natural history of diabetic coronary atherosclerosis. Insights from the Statin trial the statin trial used serial intravascular ultrasound as a measure of coronary atheroma volume in patients treated with rosuvastatin 40 or atorvastatin 80 mg 24 months. The analysis compared changes in biochemistry and coronary percent atheroma volume in patients with and without diabetes. At baseline, patients with diabetes had lower LDL cholesterol and HDL cholesterol but higher triglycerides and CRP levels compared to patients without diabetes. At follow up, diabetic patients had lower levels of ldl, HDL as well, but higher levels of triglycerides and crp. Both patients with and without diabetes demonstrated regression of coronary atheroma as measured by changes in pav. Ultrasound measurements of regression were less in diabetic patients compared with non diabetic patients when LDL levels were greater than 70, but importantly were similar when when LDL levels were less than 70.
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John so as we've seen a change in the cholesterol guidelines over the last year or so we've really seen kind of going away from this targeted LDL to whether someone needs high intensity statin or a medium intensity or low intensity statin. And basically when we look at previous studies, things like the ASTEROID trial, et cetera, we really see regression when we really get LDLs below 70. And in this particular study, in both groups, the diabetic and the non diabetic group, that's really where they saw regression. I'm not completely sure why seeing a little bit of regression in the non diabetic patients, a little higher than 70 went on. But I think if we're really looking to have some regression, probably getting it below 70. And in both groups they were given high intensity stats. Our next article is from the November edition of Diabetes Care and it looked at the contribution of liraglutide in the fixed ratio combination of insulin, deglutec and liraglutide. So this was a 26 week double blind placebo controlled trial in patients with type 2 diabetes who had a 1Cs ranging between 7.5 and 10. They were already on basal insulin somewhere between 20 and 40 units daily and metformin with or without a combination of sulfonylure and glynides. And they were randomized to one to one to once daily degludec, which is a basal insulin not yet released in the United States, or a combination of deglutec and the GLP1 liraglutide. They were titrated up, but there was a maximal dose of the equivalent of 50 units of insulin that you could be on in either group. A total of 413 patients were randomized and their mean A1C was 8.8. The Deglutec dose alone or part of the deglutec liraglutide was equivalent to 45 units in the groups. The A1C decreased by 1.9 with the combination of the daglutec and the liraglutide and 0.9 in the deglutec alone. Mean weight reduction with the combination was 2.7 kg versus no weight change in the deglutec by itself. Hypoglycemia was comparable in Both groups, about 24%. Overall adverse events were similar and the incidence of nausea was low in both groups.
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Neil John, the advent of weekly GLP1 agonists I think are really going to change the landscape for treatment of diabetes. And here we're seeing a combination pro of a long acting basal insulin with a long acting GLP1 agonist. We've reviewed in some of our previous podcasts articles from Diabetes care looking at GLP1 agonists versus short acting insulin for treatment of patients who are uncontrolled on Basilinsin alone. Last month we looked at a GLP1 receptor agonist exenatide versus bolus insulin and what we saw was that compared to bolus insulin on top of basal insulin, addition of a GLP1 receptor agonist axenatide had equivalent blood glucose control equivalent decreases in A1C but the GLP1 group lost weight where the group with Lispro gained weight a few months ago in the in the August issue of Diabetes Care we looked at adding albiglutide, a weekly GLP1 receptor agonist versus three times daily PRANDTL insulin Lispro and again saw equivalent results with regard to A1C control. But weight loss with albiglutide compared to weight gain on Lispro. Here we're seeing a combination product of a very long acting insulin, insulin Deglodeq, which has a half life of over 48 hours, so very flat basal insulin delivery along with liraglutide and we're seeing again an important contribution of the GLP1 agonists to A1C control here about a 1% improvement. But compared to just basal insulin we see weight loss as well. I think the GLP1s and we'll talk about this a little more in a review of GLP1 agonists later in this podcast really are presenting an increasingly exciting option for were physicians to be used very commonly in patients who are not controlled on basal insulin alone in the studies we just reviewed. Our next article is from Clinical Diabetes on the practical use of GLP1 receptor agonist therapy in primary Care. At the time of writing of this article, there were three GLP1 receptor agonists available Exenatide for twice daily administration or Byeta exenatide for once weekly administration, bidurion and liraglutide for one's daily administration Victoza since the article was written and this is a rapidly changing field, there are two other weekly GLP1 agonists that have been approved LinkedIn albiglutide weekly or Tanzium and dulaglutide weekly or trulicity, which was just approved a few weeks ago. The GLP1 receptor agonist class has five important actions for patients with type 2 diabetes. The first is an increase in glucose mediated insulin production by pancreatic beta cells. As a consequence, there's a low incidence of hypoglycemia. Because we the medicines are glucose mediated, gastric emptying rate is also slowed, thereby slowing the absorption of carbohydrates, leading to a lower rise in plasma glucose. GLP1 receptor agonists also act via a central nervous system mechanism, resulting in a sensation of satiety and thereby, along with slowed gastric emptying, reducing food intake. Because of this property, many patients lose weight on these medicines. By comparison, DPP4 inhibitors which also act on the incretin system, don't slow gastric emptying and don't promote satiety or reduce food intake, so don't have the same associated weight loss. A reduction in A1C of about a half to 1.5% has been reported in most studies with GLP1 receptor agonists as monotherapy. Another benefit of GLP1 receptor agonists is their impact on cardiovascular risk factors and biomarkers. GLP1 receptor agonists cause a reduction of approximately 1 to 7 millimeters of mercury in systolic pressure. Improvement in lipid profiles are also observed, notably a reduction in triglycerides of about 10-40mg per deciliter. Limitations of GLP1 receptor agonists the occurrence of hypoglycemia with GLP1 receptor agonists is generally low. Focusing on the limitations that patients are more likely to experience transient GI adverse events and how these limitations will be addressed is helpful when we talk to patients to minimize their concerns if they experience these each of the GLP1 agonists to varying degrees can cause transient nausea and diarrhea as monotherapy. Nausea occurs in 11 and 28% of patients treated with exenatide twice a day, exenatide weekly and liraglutide respectively. Diarrhea is experienced by 2, 11 and 17% respectively. GI events are usually self limiting and improve over time. Nausea is usually mild and peaks within eight weeks of starting the medication. The most common approach to minimizing the risk and severity of nausea includes using a dose escalation strategy. Patients should be educated to avoid administering GLP1 receptor agonists close to large or high fat meals because doing so is likely to make the nausea worse. The other adverse experience that patients may find is the development of nodule formation at the site of the injection. So there are both many advantages as well as limited adverse experience.
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John so this is an exciting new class of medicine in this kind of new time of diabetes. We've seen kind of emergence over the last few years of some newer medicines that we can use beyond metformin, beyond insulin, beyond the sulfonylureas. I think a lot of exciting things about this class of medicine, namely the very effective A1C reduction, so probably getting at least one point plus for A1C reduction. Not having hypoglycemia I think is a big thing. I think the other thing that is exciting is now if we're starting to see the ability to give a shot once a week, it becomes hard to argue for a newer medicine, medicines that are more expensive to say I'm going to trade your two two to three a day insulin shots for two or three a day GLP1 shots that might be more expensive. But I think now as we're seeing medicines that we could use potentially once a week, I find that very exciting and I think that will be a much easier sell to patients who often we have a difficult time getting them to transition to insulin when they really need it. Our next article is from Diabetes Care and it looked at the association of leptin with exaggerated brain reward and emotion response to food images in adolescent obesity. In the United States we've reached a point where we have 12.5 million obese children and adolescent making up 17% of our nation's youth. This particular study looked at 25 obese children whose BMI on average was 34 and paired them with 15 lean children whose BMI was 21. They underwent functional MRI during exposure to high calorie food, low calorie food and non food visual stimuli two hours after eating an isocaloric meal. The brain responses to high calorie foods relative to non food cues increased in obese versus lean adolescents in various regions of the brain that are involved in motivational reward and emotion processing. There were higher endogenous leptin levels correlated with increasing neural activation to high calorie images in all subjects.
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Neil John I really like these functional MRI studies because they inform us about a fundamental idea which is that we all experience stimuli differently. Essentially we occupy the same space but we live in different worlds. So this study shows that simply images of high caloric density foods lead to different brain responses on functional MRI in emotional and satiety related areas of the brain in obese adolescents compared to what those images elicit in lean adolescents. So that when we tell and the take home message from this is that when we tell our patients, our adolescent patients who are obese just to make good decisions, the the stimuli and the response that obese individuals experience is very different than that which lean individuals experience. So the strategies that they need to use, that they need to learn have to be more practiced and more carefully thought out strategies than those used by people who don't suffer from issues around overweight. The whole issue of leptin is I think, an evolving one. Remember, leptin leads to increase in satiety, but in obese individuals, patients, people who are obese develop leptin resistance. So that's an area where I think we're going to continue to see evolution of our knowledge. But I think the take home point here is that things like advertising and its effect on people who are obese is very different than its effect on people who are lean. And this is supported by functional MRI imaging. Last article of this issue that we're going to review is on the beneficial effects of pistachio consumption on glucose metabolism, insulin resistance, inflammation and related metabolic risk markers. In a randomized clinical trial of pistachio use, pre diabetic subjects were recruited in a crossover manner. 54 individuals consumed two diets each for four months. Pistachio supplemented diet and the control diet. Diets were isocaloric and matched for protein, fiber and saturated fatty acids. Fasting glucose Insulin measures of insulin resistance decreased significantly after the pistachio diet compared to the control diet. Other cardiometabolic risk markers such as fibrinogen and oxidized LDL significantly decreased under the pistachio diet compared with the control diet.
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John so Neil, pistachios have been around since ancient times in the Middle east as part of the diet we've been growing in the United states since the mid-70s. Pistachio is one of the categories of nuts that are more low calorie, along with almonds and cashews. But if you look at our nut brothers that are kind of highest in calories, which would be macadamias and pecans, there's still not a whole lot of swing between the highest and lowest categories. I think there's probably benefits from all the particular nuts and I think nuts are good snacks for people, especially when we're not dry roasting them or covering them with salt, especially when we're eating them in the raw state. I think overall nuts are good snacks in that we're not eating things that are higher calorie, that are more devoid of any other nutrients. I'm not so sure. I would kind of take this particular study and ascribe to my patients that they should particularly eat nuts and kind of forego other nuts. And I think there are other studies that show benefits from all the different members of the NUT family.
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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. SA.