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Diabetes Core Update
Diabetes Core Update June 2015
00:18:28
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]
Host
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. Skolmik.
- [00:38]
Dr. Neal Skolnik
Thank you. It's a pleasure to be here.
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Host
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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Dr. John Russell
Thank you. I'm looking forward to going over this week's articles.
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Host
And now for the articles.
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Dr. Neal Skolnik
We have another excellent issue this month, beginning with an article on cardiorespiratory fitness and the development of diabetes over time care, and then two articles from Diabetes Care examining whether there is an association between the increase mimetics and the development of pancreatitis, followed by a discussion from an article on the impact of fat, protein and carbohydrates on diabetes control and insulin needs, and concluding with an article that discusses changes in muscle gene expression in responders and in non responders to low levels of exercise.
- [01:39]
Dr. John Russell
Our first article is from the June edition of Diabetes Care and it looked at cardiorespiratory fitness and incident diabetes. The FIT project this particular study looked at 46,000 patients who did not have diabetes at baseline who were seen at the Henry Ford Exercise Testing FIT Project Fitness was measured from a treadmill stress test that was performed between the years 1991 and 2009. Folks were followed with regard to whether they developed incident diabetes. The mean age of the patients was 53 years of age with 52% of the participants being men and 27% of the patients being African American. The metabolic equivalence or METS achieved was 9.5. During a median follow up period of 5.2 years, there were 6,851 new diabetes cases which was 14% of the patients. After adjustment, the patients who were able to achieve more than 12 Mets had a 54% lower risk of incident diabetes compared with patients who could only achieve less than 6 Mets. The relationship was preserved across strata of age, sex, race, obesity, hypertension and hyperlipidemia.
- [02:52]
Dr. Neal Skolnik
Neil John, once again I love this study because it further confirms and increases the reach of what we've seen in many of the studies that we discuss, which is if you're going to pick one intervention in life to prevent anything, including Diabetes, it's going to be exercise. The Henry Ford Exercise Testing Project has published a great deal in this area over the years. One of their previous publications looked at the relationship between fitness and cardiovascular disease and of course showed those who are more fit and to have a lower incidence of cardiovascular disease and in fact even mortality over time. Another one of the interesting pieces of data on fitness and cardiovascular outcomes is there was a time when we used to think that maybe people who were more fit were simply healthier and healthier people have better cardiovascular outcomes. A previous study also looked at change in fitness in middle age and in fact people who were not fit but then started exercising had better outcomes with regard to cardiovascular incidence of cardiovascular disease, MI and mortality than people who remained non exercisers in middle age. What this study does is look at that with the fitness issue with regard to development of diabetes across an incredibly broad cohort of people. And as you went over with very large numbers, this study shows that regardless of age, sex, race, obesity, hypertension, hyperlipidemia, there's a strong relationship between fitness as rigorously measured not just by historical data but by exercise testing and the development of diabetes. One of the interesting things here that I that also piqued my interest was that this was true regardless of obesity, so that exercise appears to be protective. And we're going to talk about this a little bit in terms of the outcomes of exercise, that the outcomes of exercise with regard to cardiometabolic parameters are not the same for everyone. We'll talk about this a little more later in the podcast, but that even for people who were obese, individuals who were obese and fit had a lower incidence of diabetes than those who were not obese and unfit. So it adds to the strength of our data regarding the importance of exercise. We're now going to discuss two articles from the June issue of Diabetes Care. The first is Is there a link between liraglutide and pancreatitis? A post hoc review of pancreatic pooled and patient level data from completed liraglutide type 2 diabetes clinical trials. This study looked at data from Novo Nordisk sponsored trials with liraglutide phase 2 and 3 completed by 19 April 2013. All pancreatitis cases were reviewed. Total exposure to liraglutide and active comparators was 5,000 and 1,300 patient years, respectively. Eight cases of acute pancreatitis with liraglutide and one with any comparator lamipuride were found. The incidence of pancreatitis was 1.6 cases per thousand patient years of exposure for liraglutide versus 0.7 cases per thousand patient years for total active comparators. One of the eight pancreatitis cases reported with liraglutide did not meet diagnostic criteria. In six of these eight cases, recognized risk factors for pancreatitis were present or the onset of pancreatitis occurred greater than six months after liraglutide initiation.
- [07:08]
Dr. John Russell
JOHN so in this particular study they looked at a cohort of folks who were on liraglutide and kind of followed them out to see if they developed pancreatitis. And looking at 5000 patients and 1300 patient years over a period of time, found perhaps 8 cases of pancreatitis with liraglutide in 1 cases in someone who was on glimepramide. They were able to kind of tease out some of the cases that not all of the one cases were met the criteria for pancreatitis. There were a few more cases of pancreatitis seen in the liraglutide group. As we're going to see in the next study. It certainly seems like pancreatitis is associated with diabetes in general. So I think this is something that I would be mindful of. Just like for all diabetics I would be mindful of, but it would not be a reason for me not to use these medicines. I think if I had a patient who had chronic pancreatitis at the beginning, it probably would not. I probably wouldn't pick incredibly based therapies to start with, but it would not be one of those things that, geez, when I'm sitting down with patients I would spend a lot of time on, I would certainly start talking about some of the GI side effects that people will get with this class of medicine, but I probably would not have a super high worry about pancreatitis.
- [08:31]
Dr. Neal Skolnik
Our next study looks also at incretin based therapy and risk of acute pancreatitis, but through a different methodology. A nationwide population based case control study. The goal of this study was to investigate whether the use of incretin based drugs, GLP1 receptor agonists and DPP4 inhibitors are associated with acute pancreatitis. It was a nationwide population based case control trial using medical databases in Denmark. Participants were 12,000 patients with first time hospitalization for acute pancreatitis between 2005 and 2012 and a population of over 120,000 matched controlled patients. The main outcome measure was the odds ratio for acute pancreatitis associated with different antihyperglycemic drugs. A total of 89 pancreatitis patients, that's 0.69% and 684 control subjects, which equals 0.53%, were ever users of incretins. The crude odds ratio for acute pancreatitis among incretin users was 1.36, which did not meet statistical significance while it was 1.44among users of other anti hyperglycemic drugs. After co founder adjustment, the risk of acute pancreatitis was not increased among incretin users, including DPP4 inhibitors or GLP1 receptor agonists, or among non incretin antihyperglycemic drug users compared with non users of any antihyperglycemic drug.
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Dr. John Russell
So this study is kind of opposite. The other study is they're actually starting with folks with pancreatitis and then kind of working backwards. The study happened during a time where there weren't a whole lot of people on GLP1. So of the hundred patients in this study who had ever been on incredin based therapy, only 30 of them had ever been on a GLP1. So I think this study for the most part is looking more at the DPP4s and in this particular study they didn't find that folks were any more likely to be on incredin based therapy than other things. But one of the things I thought was interesting in all these studies that an early onset use of any of the diabetic medicines was associated with pancreatitis. So if we actually looked at several groups of medicine, the early starts of lots of different medicines, be it insulin, be it sulfonylureas, be it metformin, not so much so, or any incredin based therapy. So I think if we are going to think about pancreatitis, which really was not found more often in the incredin based therapy, but if we are going to think about pancreatitis, perhaps we are going to think about people who are earlier on in their therapy. Our next article is from the June edition of Diabetes Care and it looked at the impact of fat, protein and glycemic index on postprandial glucose control in patients with type 1 diabetes. Implications for the intensive diabetes management in the continuous glucose monitoring era. So in this particular study the researchers looked at all the studies that examined the effects of fat, which were seven studies, protein, which were seven studies in glycemic index. And they looked at these after researching Medline, Cochrane databases, different research databases to see is there a particular effect of certain things in someone's diet for postprandial glucose control? And can we look at those particular facets of someone's diet to determine how we should dose their insulin? So some of the things that they found that lace postprandial hyperglycemia was a predominant effect of dietary fat, although in some studies glucose concentrations were reduced in the first two to three hours. They also found that studies that indicated that high fat and high protein meals required more insulin than lower fat, lower protein meals that both had the same carbohydrate content. So perhaps all the carb counting we do might have to be looked at a little different.
- [12:54]
Dr. Neal Skolnik
Neil John this is a really interesting study in that it questions our carb centric model of the effects of food food on glucose response and insulin needs. And it really raises some very good points that both carbohydrates, proteins and fats in aggregate come together to determine both glucose response and insulin needs. But the timing of those needs may be influenced by the mix of diet. The authors discussed that the impact of a three hour postprandial glucose concentration on the addition of 35 grams of fat and 40 grams of protein to a meal, for instance, is the equivalent that results from consumption of 20 grams or half as much carbs without insulin. And that the addition of 50 grams of fat to a meal, or to say it a different way, that big rib eye I had the other night can increase insulin requirements by more than two fold. Basically what it says is that to optimize postprandial glucose control, our decisions about how much insulin to use have to be based not just on carb counting and glycemic index, but also include some adjustments for fat and protein. It really reflects how complicated really true matching of insulin needs to dietary intake is and I think for me also reminds me of the importance of diabetes educators and dietitians in our team management of patients with diabetes. Our next article is on changes in gene expression in responders and non responders to a low intensity walking intervention. We know that the response to exercise is variable. We know that some people can exercise a little bit and seem to shed pounds and other people try really hard and don't lose a lot of weight. What this study did was investigated 14 overweight individuals with impaired glucose tolerance before and after a four month low intensity unsupervised walking exercise intervention. What they found was that waist circumference and work capacity during cycle ergometry were improved in individuals who achieved normal glucose tolerance after exercise training. But waist circumference and work capacity did not improve in individuals who remained with impaired glucose tolerance. Then they looked at messenger RNA expression of mitochondrial markers and transcription factors of different things related to the efficiency of energy use. And they found that that was increased in those that began with impaired glucose tolerance and became normal glucose tolerance with exercise. And it normalized actually to levels measured in a separate cohort of individuals who did not have impaired glucose tolerance. But those markers, those MRNA markers, were unaltered after exercise intervention in those that remained glucose intolerant.
- [16:19]
Dr. John Russell
JOHN so in thinking about this particular study, I don't think I'm going to be having patients exercise and say, we'll come back, you know, in half a year and we'll do a muscle biopsy to see if you've been exercising correctly. But I think it's an interesting construct. We talk about neuroplasticity, we talk about kind of changes in the brain that will happen at a cellular level in young brains who are learning things or young brains who are exposed to drugs and alcohol. We talk about remodeling in asthma. So suddenly someone who has untreated asthma and suddenly the ciliary, ciliated epithelium becomes very chaotic looking and very crazy. And that's what we want to prevent because we do not want asthma to turn from a reversible condition to irreversible changes. So I think this is basically the same thing, that we're not going to necessarily go forward and do muscle biopsies, but there can be changes if people do go and make some changes. If you can change and go from being a diabetic to a non diabetic at a cellular level, we can show changes that hopefully will make a long term outcome in our patients.
- [17:32]
Dr. Neal Skolnik
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.