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Diabetes Core Update
Diabetes Core Update 7/10/2012
00:20:23
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 Diabet
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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 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 week, beginning with an article from the June edition of Diabetes Care on trends in mortality from 1997 to 2006 in patients with diabetes. Then an article on change in fitness and improvement in risk factors in patients with diabetes, also from the June edition of Diabetes Care, followed by an article on genetic testing for maturity onset diabetes of the young, then a review of an article on lixisenatide as monotherapy for diabetes, also in the June edition of Diabetes Care, and finally an article on the impact of non compliance with treatment and its effect on mortality in patients with diabetes. Our first article is from the June issue of Diabetes Care on trends in death rates of among US adults with and without diabetes between 1997 and 2006. It's clear that diabetes is associated with increased mortality for individuals having diabetes. This article looked at the change in mortality over a 10 year span and they used the National Health Interview Survey linked to mortality data to look at this question. What they found was that among diabetic adults, the cardiovascular death rate declined by 40% from 1997 to 2006 and all cause mortality declined by 23%. There was no difference in the rate of decline in mortality between diabetic men and women. The excess cardiovascular mortality rate associated with diabetes decreased by 60% while the excess all cause mortality rate declined by 44%. While there was a decline in mortality among non diabetic individuals, the decline among those individuals was small.
- [02:56]
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Shawn so the question is why is this happening? And certainly we've seen a decrease in cardiovascular deaths over the last 30 years due to better technology, stenting, angioplasties, etc. But when you compare this to a non diabetic group, you really haven't seen the same decrease. So what really happened? Well, if you think back to the ATP3. In 2003 we had a LDL goal of 100 and then the white paper that followed the successive year had a high risk group that should have LDLs as less than 70. Perhaps that's what we're seeing. This paper really didn't specify the LDLs of the patient population they looked at, but I would think that we are much more enlightened with regard to diabetic diabetes being a cardiac equivalent, and we are much more aggressive now, I think of getting people's LDLs lower. And certainly we have found if we get people's LDLs lower we can certainly have a decrease in cardiovascular events. Our next article is from the June edition of Diabetes Care and it looks at changes in physical fitness predicting improvements in modifiable cardiovascular risk factors independently of body weight loss in Subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Trial. Large studies have shown that physical activity provides significant health benefits by reducing cardiovascular disease and all cause mortality in the general population and also in subjects in type 2 diabetes. A recent meta analysis has shown that aerobic and resistance exercises are both effective in reducing A1C in diabetic individuals.
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To address this issue, the researchers looked.
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At changes in physical and fitness and improvement in modifiable cardiovascular risk factors and in Subjects with type 2 diabetes participating in the Italian Diabetes Exercise trial. This involved 22 outpatient diabetes clinics throughout Italy over a six month period between 2005 and 2006. Each center was connected with a metabolic fitness Center, a dedicated facility where patients trained under the supervision of an exercise professional. Patients were eligible for the subject if they met the International Diabetes criteria for metabolic syndrome. Patients were randomized to supervised training plus structured exercise counseling versus a control group that received counseling alone as a part of standard care. Study groups from both groups received structured individual counseling aimed at achieving the currently recommended amount of physical activity by encouraging any type of commuting, occupational, home and leisure time physical activity. The exercise group consisted of 150 minutes per week in two supervised sessions consisting of 150 minutes per week of progressive mixed aerobic and resistance training. The results showed a change in upper and lower body strength and flexibility were significantly associated with the variation in the volume of physical activity Hemoglobin A1C BMI, waist circumference, highly sensitive CRP, coronary heart.
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Disease risk score and inversely HDL cholesterol.
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Changes in fitness predicted improvement in a 1C waist circumference, HDL highly sensitive CRP cardiovascular reduced score independent of the study.
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Arm BMI and in case of strength, also waist circumference.
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Neil John, this is an interesting study. We've known for a long time that people who exercise more do better. They have a lower incidence of diabetes, they have less depression, osteoporosis, hypertension, and in fact less live longer. What we have only recently begun to accumulate is an evidence base that says this doesn't just correlate with people who are fit, because it might have been that simply people who tend to be more healthy, who are going to live longer, tend to stay more fit. But there are a number of studies, and this adds to those studies that now show that a change in fitness yields improvement in outcomes. And those improvement in outcomes really appear to be across the board. This study really shows the change in fitness and improvement in fitness over just a year had beneficial effects on most of the modifiable cardiovascular risk factors, including a 1C. What was also interesting in this study is that the improvement in risk factors correlated with exercise but were not associated necessarily with a change in bmi. So there were people who lost weight that didn't improve their A1Cs as much as people who had exercise. The other thing here that was interesting is there seemed to be a correlation with both aerobic and resistance training. And this is consistent with other studies out there that have shown independent effects of both aerobic training and resistance training and additive effects of both. What's the take home point for us? Well, I think the take home point is a simple one and a straightforward one. We need to constantly remind our patients of the importance of exercise and in fact it appears that exercise may be one of the most important ways to modify other existent risk factors and that we ought to view a lack of exercise simply as a modifiable risk factor which if addressed, can yield substantial improvement in outcomes. Our next article is from the June edition of Diabetes Care on a systematic assessment of the etiology in adults with a clinical diagnosis of young onset type 2 diabetes and a successful strategy for identifying maturity onset diabetes of the young. Clinicians who manage diabetes that occurs in young adults often are faced with figuring out the type of diabetes that that person has. In a previous podcast we reviewed an article from Clinical Diabetes on distinguishing type 1 from type 2 diabetes when they occur in young adults. This article talks about maturity onset diabetes and genetic testing far less common than either type 1 or type 2 diabetes, but important because it's a distinct subset typically characterized by an autosomal dominant inheritance, young age of onset in the second to fourth decade, and continued secretion of endogenous insulin often best addressed with the use of sulfonylureas. There are existing guidelines about when to look, and the authors of this article contend that genetic testing should be more widespread in looking for maturity onset diabetes of the young. So what they did was that they looked at 247 cases clinically labeled as type 1 diabetes and sequenced genetic sequencing to look for maturity onset diabetes of the Young. And similarly, 322 individuals who were clinically labeled with type 2 diabetes. What they found was that in these two groups, in the type 1 diabetic group, approximately 1% of patients had genetic mutations that were consistent with maturity onset diabetes of the young. In the type 2 diabetes group, approximately 4% of patients had genetic mutations consistent with maturity onset diabetes of the young. Of those that were identified, less than half of them would have been identified under current guidelines about when to use genetic testing.
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Sean so this is a subset we.
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Should be thinking about a little bit.
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So, you know, once upon a time, when many of us trained, if you were young, you had type 1 diabetes, and if you were 2, you were older and you were heavier, you had type 2 diabetes. And we certainly see the blurring of that. So it's important to remember for us that there is entities like late onset autoimmune diabetes of adults where people can have more or less something that looks very much like a type 1 diabetes at a type 2 age. And certainly this is something this mature onset diabetes of the young, where people who are not necessarily heavy can have something that can behave a little bit like a type 2 diabetes that might present looking like a type 1 diabetes. And really the only benefit of really figuring out that someone would have maturity onset diabetes of the young is there's a possibility that these folks don't have to be committed to insulin for the.
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Rest of their lives.
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So it's certainly something we should put in our armamentarium when we're trying to figure out if folks have diabetes and if they do have diabetes, what type of diabetes. Our next article is from the June edition of Diabetes Care and it looked at efficacy and safety of the once daily GLP1 receptor agonist, lixisenatide in monotherapy. GLP1 receptor agonists possess a number of favorable clinical characteristics in addition to their glucose lowering effects, including a low propensity to cause hypoglycemia and promotion of weight loss. GLP1 receptor agonists have the potential to preserve pancreatic islet beta cells, which may help to provide more stable metabolic control long term. As of today, three representatives of the GLP1 receptor agonist class have been marketed exenatide, liraglutide and naloxenatide, which is a new selective once daily GLP receptor agonist in development for the treatment of type 2 diabetes.
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Lixisenatide is highly sex selective for the.
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GLP1 receptor and exerts about a four fold higher affinity for the GLP1 receptor than native human GLP1. Lixenatide undergoes renal metabolism but mild or moderate renal impairment does not appear to influence its pharmakinetics.
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In this phase 3 clinical trial they assessed the safety and efficacy of 20 micrograms lixisenatide once daily in a 12 week multi center randomized double blind placebo controlled parallel group monotherapy trial in patients with type 2 diabetes who were not currently receiving glucose lowering therapy. The study population comprise both males and females between 20 and 85 years of age with type 2 diabetes not currently receiving glucose lowering therapy who had an A1C between 7 and 10. This 12 week multinational randomized parallel group placebo controlled trial was conducted at 61 centers in 12 different countries. 361 patients were randomized and treated from the 791s that were screened. Lixisenatide once daily significantly reduced A1C from baseline to week 12. The mean changes at endpoint in A1C were 0.19 and 0.73 and 0.85 from a baseline of 8, 7.97 and 8.06 for the combined placebo 2 step and 1 step dose increase groups respectively. The goal A1C was achieved by significantly more patients in both the lixenatide 2 steps in lixenatide 1 step group compared with placebo. Body weight decreased by 2 kg in all groups with no significant differences between lixisenatide and placebo. Treatment with lixisenatide also decreased fasting plasma glucose compared with the combined placebo group for tolerability. The most common side effects were gastrointestinal nature with nausea being the most common. The nausea was reported more frequently in patients treated with lixisenatide compared with placebo 24 versus 4%. One placebo controlled patient and eight lixatinetide patients discontinued treatment because of side effects and the gastrointestinal disorders were at least partly responsible for the discontinuation in all eight lixisenatide treated patients.
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Neil John it continues to be an exciting time with regard to new therapies becoming available being studied for diabetes. This is A nice example of a well run phase 3 trial of a new GLP1 receptor agonist, lixisenatide and the results are not surprising. In this treatment naive group, lixisenatide was effective decreasing a 1C by about 0.5% to 0.6%. Remember, we can't compare the efficacy in this group to other studies of GLP1 receptor agonists because there are different groups that are studied. All we can say is that it appears to be effective and the side effects are again what we have come to See with other GLP1 receptor agonists. We have a high incidence of nausea that seems to diminish over time, some weight loss and a low incidence of hypoglycemia. So it's nice to see again new drugs that are being studied that will likely add to our armamentarium for treatment. The next study is from the June edition of Diabetes Care on the impact of treatment non compliance on mortality in people with type 2 diabetes. We know that treatment non compliance or non adherence to medications is common among all patients with chronic disease. In fact, some studies have shown that up to half of patients prescribe medications for modifiable risk factors discontinue their therapy within 12 months of treatment initiation. This study looked at data from the UK General Practice Records and included over 15,000 patients who had diagnosis codes consistent with type 2 diabetes and who had received a prescription for an oral anti diabetic agent and were treated with insulin. Records in the 30 months before the index date were looked at for clinical codes that were recorded during the office visit that indicated medication non compliance or medical appointments being missed. Non compliance was defined as missing more than one scheduled visit or having at least one provider code for not taking medications as prescribed. After adjustment for confounding factors, medication non compliance increased mortality by 57%, clinic non attendance of one or two missed appointments increased mortality by 16% and clinic non attendance for greater than two appointments increased mortality by 60% and were all independent risk factors for all cause mortality.
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John so certainly there were some flaws in this study with regard to who they said had non adherence. They didn't actually count pills themselves to see if someone wasn't taking their pills. My takeaway from the study is this is any study I've seen lately a great argument for a medical home. So in a medical home we're going to be assessing our diabetics and we're going to be calling our diabetics and we're going to be making sure they're coming in for appointments because clearly by this study, if we can get people in for their visits, we can significantly impact their mortality. So, you know, when people are starting to invest money in primary care and say, you know, is that really going to make a difference? Well, certainly this study would say if we can get people to the doctors, we can get them to take their medicines, we can get them to live longer.
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So that's all of the articles for this week and until next week, keep.
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Listening and keep learning.