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Diabetes Core Update
Diabetes Core Update April 2016
00:25:46
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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And now for the articles.
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We have another excellent issue this month, beginning with an article from Diabetes Care on the metabolic consequences of fatty liver in patients with type 2 diabetes. Then an article from Diabetes Care on community health centers delivering lifestyle modification for Hispanic women. Then an article from Diabetes Care on bariatric surgery and its effect on glucose metabolism, followed by an article from Diabetes Spectrum on obstructive sleep apnea and diabetes, then an article on the effect of meal fat quality on glucose response, and finally an article from Clinical Diabetes on new insulin choices. Our first article this month is on the metabolic impact of non alcoholic steatohepatitis in obese patients with type 2 diabetes, published in Diabetes Care. Non alcoholic steatohepatitis, or NASH, is an increasingly common occurrence in obese patients. However, its metabolic consequences in patients with type 2 diabetes are currently unknown. The authors studied 154 obese patients and divided them into two groups controls, I.e. people who had neither type 2 diabetes nor alcoholic fatty liver. Then the second group were individuals with type 2 diabetes without non alcoholic fatty liver disease. The third group were those with type 2 diabetes with isolated steatosis and the fourth group were type 2 diabetes with NASH. They evaluated triglycerides and other aspects of glucose metabolism. There were no significant differences in the group at baseline with regard to BMI or total body fat. Metabolic parameters worsened progressively with the presence of type 2 diabetes and the development of hepatic steatosis with worse hyperinsulinemia, insulin resistance and dyslipidemia, primarily hypertriglyceridemia and low HDL in those with nash.
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Sean so I think this is very interesting and fatty liver certainly goes hand in hand with a large, large percentage of our diabetics and studies here, talking about anywhere from 25 to 69% of folks with type 2 diabetes also having some fatty liver. So what would be interesting for me is what am I going to do different with those diabetics if I identify them? So if, if there was a different algorithm to say, boy, someone has fatty liver and I'm going to use a TZD earlier, I'm going to use some other product earlier, I think that's going to be very interesting to identify. I think it also pointed out in the article that folks with elevated triglycerides and certainly elevated triglycerides can go hand in hand with poor glycemic control. But maybe those patients who have not yet pumped their liver enzymes but have some elevated triglycerides might be some folks you might think about getting an ultrasound for the liver, but short of weight loss, we really do not have that quintessential treatment for fatty liver. And we might get to the point that there is going to be a different algorithm and if we find that someone has type 2 diabetes and fatty liver, we're going to do X instead of Y I think so. I think this is the start and the takeoff of something that we might be doing different with our patients in the Future with type 2 diabetes. Our next article is from Diabetes Care and it looked at an effective translation of an intensive lifestyle intervention to Hispanic women with prediabetes in a community health center setting. Women diagnosed with pre diabetes on a screening oral glucose tolerance test were recruited from a community health center. The participants that were 90% Hispanic were randomized to either usual care or intensive lifestyle intervention. Their mean age were in the mid-40s and their BMIs were around 35. It was structured as 14 weeks of group sessions focused on food choices, behavioral change, physical activity and weight loss and they followed these women for one year. The groups had similar baseline weight, BMI, fasting and two hour glucose. One year later the intensive lifestyle group had lost 3.8kg while the usual care had gained 1.4kg. Two hour glucose excursion decreased 15mg in intensive lifestyle intervention and 1mg in the usual care group. There were significant decreases favoring the intensive lifestyle intervention noted in bmi, body fat, weight circumference and fasting insulin.
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Neil John I love this study. Back in 2002 in the New England Journal, what is perhaps one of the most important studies in the field of diabetes. The Diabetes Prevention Program trial was published showing that intensive lifestyle modification led to a decrease a significant decrease in progression from prediabetes to diabetes. In fact, in this trial they looked at usual care versus metformin 850 bid versus intensive lifestyle modification in over 3,000 individuals with prediabetes. And what they showed was that metformin decreased progression to diabetes by approximately 30%, but intensive lifestyle modification decreased progression to diabetes by approximately twice as much as metformin. Incredibly important. But the question that was asked after that trial was they were able to do that in the population they looked at with intensive work. But could this be generalized to other populations over the next 10 years? This has been shown their methodology or variations of that methodology have been shown to be able to be carried out in community programs. The Finnish diabetes prevention trial showed that it could be carried out in primary care offices. The CDC has now rolled out this program or a variation of the program in many communities throughout the United States. And now the trial that you just went over wonderfully shows that this can be carried out in community health centers, in people from lower socioeconomic circumstances, and specifically in a Hispanic population, which in the near future will account for almost 30% of our population. There is no question that many physicians feel that lifestyle modification doesn't work because that's their experience when they don't address it in an avid, passionate way and when they don't have patients either within their office having multiple contacts over the year or refer them to formal programs. But there's equally no question when we approach patients with prediabetes with well thought out programs that have multiple contacts, we can decrease progression substantially from prediabetes to diabetes. And this trial that you just went over shows that it can be done in again another important population. Our next study from Diabetes Care is on weight change adjusted effects of gastric bypass surgery on glucose metabolism. From the Swedish obese subjects the SOS study, it's been suggested that weight change independent effects on fasting insulin and glucose levels are present after gastric bypass surgery but not after banding and vertical banded gastroplasty. These authors evaluated weight change effects and compared restrictive surgical procedures versus gastric bypass on long term changes in glucose metabolism. Participants who completed the two year and or 10 year follow up over 1000 patients in each were divided into three weight change classes. Weight loss greater than 30%, 20 to 30% or less than or equal to 20% and by surgical method, banding, vertical banded gastroplasty or gastric bypass surgery within weight class changes, reductions in glucose, insulin and insulin resistance were similar in the three surgery groups. Both at 2 and 10 years, reductions in glucose, insulin and insulin resistance increased with increasing weight loss and the changes were typically related to weight change within each surgery group. Moreover, the association between weight change and change in glucose, insulin or insulin resistance did not differ between the different surgery groups at either two or ten years. John.
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So I find this to be very interesting and I think we had been told that it kind of depended on what type of procedure you had, whether it was going to have that impact on your diabetes. And I think what we've learned from this particular study that really is how much weight loss, not necessarily how you get there. Bariatric surgery is still a very exciting thing in the realm of diabetes. And certainly our patients who BMI have found themselves north of 35 and 40, we really should be considering doing bariatric surgery in this particular population as part of their care for their diabetes. So I think that this is a very interesting thing. It should be something that we really do not necessarily wait before we refer people on. And certainly any bariatric program worth its salt is still going to want people to have gone through lifestyle, diet changes, lots of programs, before they jump to do surgery. But I think that needs to be part of our treatment algorithm. Our next article is from Diabetes Spectrum and it looked at sleep apnea and type 2 diabetes. This was a review article. So obstructive sleep apnea, or OSA has a prevalence about 2 to 4% in the general population. OSA has been shown to increase the risk and severity of type 2 diabetes independent of age and obesity. So how does some of this stuff happen? Well, OSA leads to intermittent hypoxia and sleep fragmentation that leads to sympathetic activation, oxidative stress, systemic inflammation, HPA axis activation and adipokine dysregulation. These all lead to insulin resistance, glucose intolerance and type 2 diabetes, which is outlined very nicely in this particular article. So what about the treatment of OSA? Well, in treatment of OSA, the weight loss related to lifestyle interventions in type 2 diabetics has been shown to significantly improve OSA severity. It's unclear, however, if the improvement in the OSA is a result of weight loss in these studies and had an independent effect on the control of the type 2 diabetes. So data regarding the effect of treatment interventions for osa on type 2 diabetes are limited. In this particular article, it looked at CPAP and looked at various parameters for diabetes control. Of five studies that they looked at, one had no change in hemoglobin A1c. One found hemoglobin A1c was significantly lower in the CPAP treated group. And in three other studies they found a decrease in insulin resistance decrease in 24 hour, meaning blood glucose and decrease in insulin resistance by oral glucose tolerance and CPAP treated group. So overall I think the data is mixed but is promising that there could be some impact with better control of OSA and better control of diabetes.
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Neal John this article is a nice reminder that we need to think about obstructive sleep apnea in our patients with diabetes and probably have a low threshold for sending them for evaluation. Remember, OSA is defined by daytime sleepiness, excessive snoring and apnea, along with at least five obstructive respiratory events per hour of sleep during evaluation. It also can be defined as greater than 15 apneic events per hour in the absence of symptoms. There are certain patients who are clearly at high risk and that includes individuals who are obese who have chf, AFIB resistant hypertension or as we talked about today, type 2 diabetes. Also, certain physical features should make us think about obstructive sleep apnea, including in men a neck circumference greater than 17 inches and greater than 16 inches in women. Guidelines from the American Academy of Sleep Medicine suggest that home evaluation can be done for patients in whom we have a low suspicion of sleep apnea but feel they should have an evaluation because home monitors may underestimate the severity of hypotenic events compared to a full evaluation. This was reconfirmed just this month in an article published in American Journal of Medicine, which showed that home monitors miss a small but significant proportion of people with sleep apnea. So the bottom line with this article is that one we ought to have a low threshold for doing an evaluation in patients who have diabetes if we think they may also have sleep apne because finding that they have sleep apnea can improve both their quality of life, decrease their risk of hypertension or their blood pressure, and potentially even improve their metabolic parameters with regard to treatment of their diabetes. Our next article is from Diabetes Care titled Extra Virgin olive oil reduces glycemic response to a high glycemic index meal in type 1 diabetes. The authors sought to evaluate whether fat quality in the context of meals with either high glycemic index or low glycemic index influences the postprandial glucose response in patients with type 1 diabetes. They used a randomized crossover design with 13 patients given either a high or low glycemic index meal with the same quantity of carbohydrate but differing in the amount and quality of fat, either low fat or high saturated fat in the form of butter or high monounsaturated fat in the form of extra virgin olive oil postprandial glucose was significantly different, of course, between the high and low glycemic index meals, being significantly higher during the first three hours after the high glycemic index meal. In the context of a high glycemic index meal, postprandial glucose was significantly lower after extra virgin olive oil than after low fat or butter. No significant differences were observed in any of the groups between the three low glycemic index meals.
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John So I think this is an interesting study. So a couple thoughts on this particular study. So I think this would go along with the Mediterranean diet. So when we think of the Leon Hartz trial that randomized people to a regular cardiac diet versus a Mediterranean diet and showed a 70% reduction in cardiac events happening when people were on a Mediterranean diet and when Mediterranean diet is going to not purely be an olive oil, but it's going to have olive oil, it's going to have more nuts, it's going to have more wine, it's going to have more fish. But clearly it's something I think we should be recommending to our cardiac patients. And certainly this might be part of it. It might be a little bit of this glycemic excursion as a mechan for that, because certainly the fish oil trials over the last few years have really not shown that fish oil, either in a high risk, medium risk or low risk population, has that huge impact on cardiovascular events that we think. So perhaps it could be the olive oil and how it impacts glycemic excursion. So I think that that's an interesting thing. The second thing is this whole concept of extra virgin olive oil. And if you're a reader of magazines that have been coming out lately, if you saw 60 Minutes at the beginning of the year, a lot of the things that we are purchasing in our homes that we think is extra virgin olive oil is really olive oil and really not extra virgin olive oil. So there was a whole fraud that is going out there in some of the people who are producing extra virgin olive oil. So and probably olive oil is fine and certainly is going to be much better than butter or other fat sources for our patients. Our next article is from Clinical Diabetes and it looked at the role of emerging insulin technologies in the initiation and intensification of insulin therapy for diabetes patients in primary care. So insulin is often initiated late in the natural history of type 2 diabetes. Despite recommendations the treatment should be intensified with three to six months of failure to meet glycemic targets by bodies including the ADA. International guidelines recommend an A1C target of less than 7. But despite these recommendations, the average A1C level at which insulin is initiated has been shown to be greater than nine in several studies. Furthermore, there's not only reluctance to initiate insulin treatment, but the intensification of treatment may be delayed for several years. As the diabetes disease progresses, beta cell function declines and the response to insulin and skeletal muscle liver cell reduces. Our patients will eventually reach a point where the target blood glutose levels cannot be maintained on oral agents alone. With continued disease progression or if the glycemic targets are not met with basal insulin alone, we might need to move on to basal bolus insulin in which the basal insulin supplemented by mealtime bolus insulin. Alternatives to the basal bolus approach include incretin, such as the GLP receptor agonist, which might help achieve a 1C target without weight gain or an increase in hypoglycemia or switching to a premixed insulin. Premixed insulin may be administered two to three times a day to improve convenience may cause a Greater decrease in a 1C compared with basal insulin alone, according to some studies. Barriers to insulin initiation experienced by patients with diabetes are mainly psychological, include concern over safety, the efficacy of insulin. Other misperceptions include that insulin itself is associated with complications or even death, that it causes hypoglycemia or weight gain, and it results in a loss of independence. The need for insulin therapy is also perceived as a personal failure by the patient to effectively manage their weight, nutrition and physical activity. Clinical inertia, which is defined as the failure of primary care physicians to initiate or intensify therapy when indicated, arises for several complex interrelated factors including a need for education about the benefits of insulin, how and when to start this therapy, interpretations of patient beliefs by primary care physicians, and limited resources for initial and ongoing patient education and following up in the primary care setting. Our interpretation of patient beliefs can be a barrier to starting insulin. Many primary care physicians believe that patients would not accept injection therapy. The perception of patient resistance to new oral and insulin therapies due to fear related to the therapy was reported by almost two thirds of primary care physician to be one of the main reasons for not initiating insulin therapy. Almost 90% of primary care physicians agreed that injection router administration is the greatest barrier to patients acceptance of insulin therapy. Although many primary care physicians believe that reluctance injection therapy is a barrier to insulin initiation for their patients, the number of patients with true needle phobia is indeed small. The primary care physicians did not feel that training in the administration of insulin use was too complicated for most patients. 40% felt that providing this training was too time consuming for their staff and it speaks to the lack of time and resources in busy primary care practices. Other things to improve basal insulin initiation in primary care settings Looking at some of the new basal insulins so there was a new insulin glargine 300 units per milliliter. This new insulin formation that delivers the same number of insulin units as our standard 100 unit glargine but a third of the injection volume. It's been found that at a steady state in type 1 diabetes, the 300 unit glargine was associated with a more constant pharmacokinetic profile compared with the Glargine 100 with longer and tighter blood glucose control and a duration of action of more than 24 hours. This prolonged pharmacokinetic profile of the new 300 unit glargine may allow for various variations in times of administration. The safety and efficacy studies demonstrated comparable effective glycemic control with both the 300 and 100 unit glargine in type 2 diabetes patients at 6 months. However, the 6 month extension studies of these two showed that A1C reduction was maintained or improved for the glargine 300 compared to the glargine 100 over 12 months. In both studies, the percentage of patients experiencing more than one confirmed or severe nocturnal hypoglycemic event was lower for the glargine 300 than for the 100. A meta analysis of trials confirmed no Difference in mean A1C change between the glargine 300 and glargine 100. As seen in individual studies, the proportion of patients experiencing more than one confirmed or severe hypoglycemic event at any time of the day and during the night over the six month period was significantly lower for the 300 glargine.
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Neil John When I think about treatment of diabetes after the use of oral hypoglycemic agents, I actually often think of Charles Dickens A Tale of Two Cities where he started by saying it was the best of times and it was the worst of times. We are really fortunate to live in a time where we have an increasing array of choices. We've had new insulins come out, new injectable GLP1s. You went over U300 deglodeq. We have a lot of GLP1 choices, we have a choice of injections or pens. We in the future will have choices of additional insulin products and in that way it's the best of times with the greatest of promise. But it's also the worst of times, because in a study that we went over on this podcast about two years ago, we found that after one or two or three oral agents are no longer sufficient. It takes over seven years on the average till a patient is started on injectable therapy. And that's really far from ideal. And the reasons for that that you alluded to, things like clinical inertia, things like patients hesitancy to use injectables, are real and important. Also concerns over weight gain. We talk to patients for many years about the importance of weight loss. Then we start insulin, which can cause weight gain. We have lots of choices with regard to medicines. This is truly the best of times. It is then incumbent upon us to then embrace new technologies, new developments and, and move forward in a steady fashion to make sure this continues to be the best of times for our patients with diabetes. 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. Sam.