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Diabetes Core Update
Diabetes Core Update December 2014
00:20:33
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. Skolmik.
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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 discussing the economic burden of diabetes in 2012, followed by an article from Diabetes on GLP1 receptor agonists and their activity on modulating appetite and reward areas of the brain, then an article from Diabetes Care on the effect of phentermine topiramate on patients with diabetes, and then an article on hypoglycemia and macrovascular deaths, and finally an article on the incidence of remission of diabetes in a community setting.
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Our first article looks at the economic burden of elevated blood glucose levels in 2012, diagnosed and undiagnosed diabetes, gestational diabetes and prediabetes. This study estimated the healthcare use and medical expenditures in excess of expected levels occurring in the absence of diabetes or pre diabetes. Data sources included Optum medical claims for approximately 4.9 million commercially insured patients who were continuously enrolled from 2010 to 2012 Medicare files containing medical claims for approximately 2.6 million Medicare patients in 2011 and 2012 and nationwide inpatient sampling which contained another 7.8 million hospital discharge records. The indirect economic burden includes reduced labor force participation, missed workdays, reduced productivity. State level estimates reflect geographic variation, prevalence, risk factors and prices. The economic burden associated with diabetes at all ages and undiagnosed diabetes, gestational diabetes and prediabetes in adults exceeded over $322 billion in 2012. That consisted of 244 billion in excess medical costs and $78 billion in reduced productivity. Combined. This amounts to an economic burden exceeding $1,000 for each American in 2012. The national estimate is 48% higher than the 218 billion that was estimated in 2007.
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Neil John, what this article says is that we are in trouble. The increased cost going up over 45% over a five year period of time is not hard but impossible for this country to sustain. Of that increase, it's felt that approximately 27% is attributed to growth in the prevalence of diabetes and 14% of that is a growth in the average cost per per case of diabetes. The CDC estimates that 86 million adults had either prediabetes in 2012 or another, which has increased from 57 million adults with prediabetes in 2007. Currently, nearly half 47% of adults in the United States have either diabetes or or prediabetes. And as you went over nicely, the data, based on a huge data set, suggests over $300 billion in cost or essentially a tax on every American of $1,000 per person that goes just to the treatment of diabetes. The authors in their discussion estimate that for a typical American family in 2012 with three members and a median income of 64,000 DOL, the burden from diabetes equates to almost 5% of their income, which is up from 3.4% in 2007. It's clear, as we've talked about many times on these podcasts, that long term the answer isn't going to be in better meds, though meds are currently important for treating patients with diabetes, but it's going to be in primary prevention lifestyle modification for people in the primary prediabetes group and even before they get prediabetes. Our next article is from the December edition of diabetes on GLP1 receptor activation modulating appetite and reward related brain areas in humans. In this study, the author's hypothesis was that food intake reduction after GLP1 receptor activation is mediated through appetite and reward related brain areas. The way they studied this is that they took obese type 2 patients and normal glycemic obese and lean individuals and studied them in a randomized crossover placebo controlled trial using functional mri. Using that functional mri, they determined the acute effects of IV administration of the GLP1 receptor agonist exenatide with or without prior GLP1 receptor blockade using exendin 9, which is a blocker of the GLP1 receptor. And they looked at the effect on functional MRI. Brain responsors to pictures of food obese type 2 patients and normoglycemic obese patients versus lean subjects showed increased brain responses to food pictures in appetite and reward related brain regions, the insulin amygdala, suggesting that their response in response to food pictures was greater than those of individuals who were lean. Exenatide versus placebo decreased food intake, not surprising and Food related brain responses. In type 2 patients and obese subjects, the effects were largely blocked by prior administration of a GLP1 receptor blocker.
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John so I think this is interesting and I think this is one of the ways that we're starting to rethink the paradigm on how we look at diabetes. So in 2009, Dr. DeFronzo won the Banting Award. And in winning the Banting Award, he talked about the ominous octet. So going back, once upon a time, you and I really thought about diabetes in the context of it being having to do with hepatic glucose production, had to do with resistance of uptake of sugar in muscles and had to do with beta cell function. And they're all still important. But now we're starting to see five other parts of the body that are parts of this the relationship of glucagon, the SGLT2s, free fatty acid metabolism, etc. And one of those eight now is the brain and satiety. So looking at medicines that can impact satiety, so bromocriptine has been one of these medicines that impacts the brain. Never really used all that much. The GLP LPs as we see in this study, actually have some function on decreasing satiety. So I think this will show that the people who are overweight and obese in this particular study, their brain waves respond a little bit different to food than some of the normal weight people. And the GLP1 medications can help impact that a little bit. So I think this is part of the ominous octet and this is one of the reasons that the GLPs have kind of a pleomorphic effect on many of these eight parts of the octet. Our next article is from Diabetes Care and it looked at weight loss therapy and type 2 diabetes, the effect of phentermine and topiramate extended release. This study was a 56 week phase 2 clinical trial that had randomized subjects to receive one Stanley placebo or the combination of phentermine and topiramate extended release 15 and 92 milligrams respectively. The primary endpoint was a change in A1C, a post hoc analysis of a subpopulation with type 2 diabetes from a second study Conquer was also presented. All the study subjects made lifestyle modifications and comorbidities were managed by standard care. The Study groups combined 130 subjects with type 2 diabetes enrolled in the original study and they had a mean A1C of 8.7 in 388 subjects with type 2 diabetes in the Concord trial who had a A1C of 6.8 at wheat 56. The change in weight in the patients in the first study was 2.7% for placebo and 9.4 in the combination drug trial. The change in A1C level was minus 1.2 for placebo and minus 1.6% for the phentermine topiramate group. In both trials there were a greater number of patients randomized to receive the phentermine topiramate treatment achieved A1C targets with reduced need for diabetes medicines when compared with a placebo group. The adverse events we're seeing include paresthesias, constipation and insomnia.
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Neil John the results here are interesting and important, though not surprising, so that we have phentermine and topiramate available FDA approved as a weight loss drug and it's important that we have drugs available for weight loss. They achieve a approximately 10% or so weight loss when used in obese individuals, but the question remained with that weight loss would you get improvement in metabolic parameters and would that improvement be to an important degree in patients 1 with prediabetes and then with diabetes? We reviewed an article on our April podcast of phentermine and topiramate in patients with prediabetes showing that progression to diabetes was decreased by approximately approximately 80% in the higher dose of phentermine and topiramate, an important outcome in addition to weight loss. In this trial, looking at just patients with diabetes, we see that not only do they achieve weight loss, which of course is desirable, but they also achieve what we would hope they would with that weight loss is significantly better A1C control in the range that we see with some of the newer diabetes medicines. The difference between placebo and the treated group was approximately a difference of negative 0.6% decrease in a 1C. So we really are seeing this medicine work well not just to achieve significant weight loss, but also to achieve improvement in metabolic parameters, decreased progression of diabetes in patients with prediabetes as well as improvement in age. Our next article from Diabetes Care is on the association between severe hypoglycemia, adverse macrovascular events and inflammation in the Idenberg type 2 diabetes study. This study looked at a cohort of over a thousand adults aged 60 to 75 years of age with type 2 diabetes underwent a prospective evaluation. Baseline history of severe hypoglycemia. Plasma levels of inflammatory markers including C reactive protein and fibrinogen were looked at. Their association with incident macrovascular events after four years was explored at baseline. 87 participants or 8.2% reported one or more episodes of severe hypoglycemia within the preceding year. And at follow up, 99 participants, 9.3% had suffered a new macrovascular event. Hypoglycemia was associated with increased odds of macrovascular events with an odds ratio of 2.1, which reached statistical significance largely due to increased myocardial infarction rate with an odds ratio of 4. Hypoglycemia was also associated with increased levels of inflammatory markers, including general inflammation factors derived using principal component analysis. However, the significant association between hypoglycemia and macrovascular events persisted even after adjustment for inflammatory markers.
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JOHN so I think there are kind of two disparate things that they talked about in this One is the inflammatory markers and you know, the inflammatory markers I think overall, if you're looking with regard to treatment of lipids, I think are helpful in people who are in that intermediate risk group. We know that diabetic patients tend to be in a high risk group, not an intermediate risk group. So really, a patient, whether a patient has elevated inflammatory markers or not, every diabetic patient over the age of 40 per guideline should be on a statin. And the reason they should be on a statin as opposed to other drugs that lower cholesterol, not just for better outcomes. Part of the reason for the better outcomes is the anti inflammatory effect of the statins. So really, regardless of whether a patient had elevated inflammatory markers with their hypoglycemia, I would still treat all diabetic patients because they're all at risk with regard to hypoglycemia. Once again, looking in a senior citizen population, I know the lower age of the study was 60. We saw hypoglycemia being associated with increased poor events, increased death rates, increased cardiovascular events. So we need to be very mindful when we are choosing agents and senior citizens to really think about picking agents that don't cause hypoglycemia. And the agents I especially thinking about are the sulfonylureas, medicines like glyburide, which are renally metabolized as people get older, as their GFR goes down, which invariably will happen to all of us as we age. The glyburide is going to hang around a lot longer. If you look at studies with regard to amounts of hypoglycemia, the sulfonylureas have almost twice as much hypoglycemia as basal insulin. So I think we need to be very mindful of what our A1C targets are for our senior citizens patients and they probably do not necessarily need to be under seven. And I think if we're going to use agents, I think the rate of hypoglycemia of any individual agent we give to a particular patient really needs to be paramount. And our last article is from Diabetes Care and it looked at the incidence of remission in adults with type 2 diabetes. The diabetes and Aging Study so this study quantified the incidence of diabetes remission and examined its correlates among over 122,000 adults who had type 2 diabetes that were part of an integrated healthcare delivery system. Remission required the absence of ongoing drug therapy and was defined as the 1 partial at least one year of sub diabetic hyperglycemia which would be an A1C level of 5.7 to 6.4, 2 complete remission, at least one year of normoglycemia with an A1C of less than 5.7 and 3 prolonged complete remission for at least five years. The incidence density per thousand person years of partial, complete or Prolonged remission was 2.8, 0.24 and 0.04 respectively. The 7 year cumulative incidence of partial, complete or Prolonged remission was 1.47, 0.14 and 0.07 respectively. The seven year cumulative incidence of achieving any remission was 1.6 in the whole cohort and 4.6 in the subgroup with new onset diabetics, those who had less than two years since diagnosis after adjusting for demographic and clinical characteristics. Correlates of remission included age over 65, African American, race under 2 years since diagnosis, and a baseline A1C level of less than 5.7 and no diabetes medication at baseline.
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Neil John this study is enough to make one cry. Remission rates under 2% in a community setting are really disappointing and are very different than what was achieved, for instance, in the Look Ahead trial. So that remember in the look ahead trial at one year you had remission of about 11%, at 4 years, 7%. The numbers here were in the same range as that seen in the standard control group that received diabetes education. I think what it's saying is that we're just not doing a terribly good job at promoting lifestyle change in our usual practices. What's also interesting is if you compare that to the remission rates after bariatric surgery, again there's no comparison. You have something like a 70% remission rate with bariatric surgery, which isn't to argue that everyone ought to get bariatric surgery, but clearly appropriate candidates. We should be thinking of bariatric surgery. Equally clearly, in my opinion, we ought to be more forceful with our recommendations, more thoughtful with how to motivate our patients to carry out sustained lifestyle changes, and be aware that some patients are able to make those changes and might be able to have medicines withdrawn. 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.