← Diabetes Core Update
Diabetes Core Update
Diabetes Core Update January 2015
00:21:57
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...
Loading summary
Transcript14 lines
- [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. Skolmik.
- [00:38]
B
Thank you. It's a pleasure to be here.
- [00:40]
A
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.
- [00:50]
C
Thank you. I'm looking forward to going over this week's articles.
- [00:53]
A
And now for the articles.
- [00:55]
B
We have another excellent issue this month, beginning with an article on automated Internet behavioral weight loss programs and their effect on weight loss, followed by an article from Diabetes Care on the microbiome and its effect on obesity, then an article from Diabetes on the mechanism for combination of metformin and SGLT2 inhibitors, followed by another article from Diabetes on coronary flow reserve and spironolactone and its effect in type 2 diabetes patients, then an article from Diabetes Care on metformin and cancer disproving some recent hypotheses and finally an article from Diabetes Care on the influence of driver's license legislation mandating loss of license with recurrent hypoglycemia and its actual effect on reporting of hypoglycemia to physicians.
- [01:58]
C
Our first article is from the January 2015 edition of Diabete and it looked at an automated Internet behavioral weight loss program by physician referral. This particular study looked at 154 patients who were between 18 and 70 years of age who had BMIs between 25 and 45. They were randomly assigned to three months of Internet behavioral intervention with 12 weekly videos teaching behavioral weight loss skills, a platform for submitting self monitored data, an automated feedback or an education only Internet delivered eating and activity control group. The outcomes measures were weight loss after three months and six months and changes in weight control behaviors. In looking at the data, there were significantly larger weight losses in the group that got the Internet behavioral intervention platform versus the people who just got information at both 3 months and 6 months, 5 kilos versus 1.3 kilos at 3 months and 5.4 kilos versus 1.3 kilros at 6 months. The participants in the more active program compared with the more passive program were also more likely to achieve a clinically significant weight loss of 5% of their initial body weight at 3 months and 6 months and they were more likely to report frequent use of weight control related strategies.
- [03:22]
B
Neil John, I love this study and the reason why I really like it is that there's no question that we're going to have to figure out novel strategies in order to combat what is really the greatest epidemic of this century, obesity and diabetes. And this program seems to do it in a well thought out and cost effective manner. We know that from studies like the Diabetes Prevention Program trial that when we have a well thought out multimodal behavioral program, we can achieve success with lifestyle modification. The problem of course with the method used in the Diabetes Prevention Program trials, it's very resource intensive. It uses dietitians, it uses personal trainers. This program that you just reviewed is purely Internet based and it's different and it was compared to simply an informational program. So its comparison group was 12 weekly videos that gave people information about what to do versus the intervention program. That was 12 weekly multimedia behaviorally oriented videos interactive with a website for submitting self monitoring data and automated feedback loops provided based on individuals progress. They had clear goals, laid out a goal of one to two pounds per week and clear caloric goals based on data that they inputted. And what it found was that this, what is probably a very cost effective automated program worked wonderfully well. So both at 3 months and 6 months, about 50% of the other participants in the intervention group achieved 5% or greater weight loss. Remember what our goal is? 5 to 7% weight loss based on the DPPT trial. So I think that this is incredibly promising. Promising something that can be easily scaled for a lot of people. And I'm looking forward to a time when programs like this are readily available. One wonders, though I haven't seen direct data, how this is probably similar to what's become very popular, the wristbands that a lot of people are wearing that interface with different programs on the net and on their mobile phone to give them direct feedback based on activities. So I think this is a very exciting area. Our next study from Diabetes Care is titled Insights into the Role of the Microbiome in obesity and type 2 diabetes. The background here is what we all know, that from 1980 to 2008, the number of people diagnosed with diabetes and obesity has increased enormously. The main cause for that has been assumed to be an increase in caloric intake along with what we know to be common, a decrease in exercise. This study reviews some data that suggests maybe something else is operative. A change in the microbiome of people that leads to obesity. The potential for the role of gut microbiome in metabolic disorders has recently been identified. Obesity is associated with changes in the composition of the intestinal microbiome and the obese microbiome seems to be interestingly more efficient at harvesting energy from the diet. The study reviewed the effects of this change on butyrate and serotonin, which in turn influences satiety signals. They also reviewed studies showing that lean male donor fecal microbiotransplantation in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with increased intestinal microbial diversity, including a distinct increase in things like serotonin and butyrate producing bacterial strains, suggesting that such differences in the gut composition might function both as early diagnostic markers for the development of type 2 diabetes, but more importantly might be the underlying cause of the obesity epidemic.
- [07:49]
C
John, so this is a very interesting article. So our gut flora is composed of over 10 to the 14th numbers of organisms. We have over a thousand different species of bacteria. And per this paper it would say, geez, you know, what you, you know what you have in your gut is going to influence what you eat. And in certain ways. There are previous studies that looked at that. So there was a older study in 2010 that looked at germ free mice and found that these mice who had no bacteria in their gut, even when they ate 29% more calories, still did not gain weight to the same as their controls who ate less calories. So possibly there is something to this. You know, people who eat more meat are more likely to have certain flora versus people who eat more grain, more fiber. So it's a very kind of chicken and egg type thing. And certainly as we live in a world that has lots of antibiotics that are getting, especially in the western world, often unnecessarily, when we're getting antibiotics, often in our protein sources that we're eating and not even knowing about, perhaps this, this plays a role. It does seem interesting, but I do not envision a world that suddenly we take some type of probiotic tablet and it's suddenly going to kind of take away kind of bad behaviors and suddenly we're not going to want to eat Cheetos or we're going to eat Brussels sprouts because we took a certain probiotic. But of interest, and I guess more will be determined, our next article is from the January edition of Diabetes and it looked at metformin combined with SGLT2 inhibitors and suppressing endogenous glucose production in diabetic mice. The combined use of metformin and SGLT2 inhibitors is a promising treatment strategy for type 2 diabetes. The researchers investigated the physiologic mechanism by which both components lower blood glucose concentration in diabetic mice. They combined metformin with an SGLT2 inhibitor, Ave2268 alone or in combination, and looked how it mitigated hyperglycemia and modulated glucose fluxes in diabetic mice. They found that the SGLT treatment alone elicited a rapid decline in circulating blood glucose, which appeared to induce endogenous glucose production. They found supplementation of metformin dampened this counter response and therefore the combination therapy was more efficiently able to maintain glycemic control.
- [10:26]
B
Neil John I think this is just interesting and elucidating the mechanism by which two essentially new combination medicines that have come to market over the last year work. So we now have two combination metformin SGLT2 inhibitors on the market. They are a logical combination and what you just said elucidates some of the mechanism. The SGLT2 eliminates blood glucose through the through increased secretion in the kidney, but that in turn increases hepatic glucose production. Metformin acts on that part of the mechanism, so the combination seems to make sense. Studies show that the combination is effective, so it's another combination medication in our toolkit. Our next study is from Diabetes on mineral corticoid receptor blockade improving coronary microvascular function in individuals with type 2 diabetes. In patients with type 2 diabetes, coronary flow reserve is related to outcomes. So that's microvascular, not just macrovascular coronary disease. Coronary flow reserve, when reduced, is an indicator of coronary microvascular dysfunction and it's seen fairly often in type 2 diabetes since aldosterone plays a key role in vascular injury. The aim of this study was to determine whether mineral corticoid receptor blockade improved coronary flow reserve in individuals with type 2 diabetes. They looked at 64 men and women with well controlled diabetes on chronic ACE inhibitor therapy and then, then they were randomized to add on therapy of spironolactone 25 mg hydrochlorothiazide, 12.5 mg or placebo for 6 months. Coronary flow reserve was assessed by cardiac PET imaging at baseline and at the end of treatment. There were significant and similar decreases in systolic blood pressure with both treatment groups but not with placebo. Coronary flow reserve improved with treatment in the spironolactone group. As compared to either the hydrochlorothiazide group or the placebo group.
- [12:52]
C
John So I think this is an interesting study kind of going forward if we're going to add on a diuretic to patients. So spironolactone, when we think back when the first study showed what benefit it showed in congestive heart failure, certainly is something that is going to work a little bit different than our other diuretics and can be a very effective medicine. You know, one of my caveats with this study is you really did not see the hyperkalemia that I would be worried about. So all these patients received an ACE inhibitor and then had add on spironolactone. And I think there was one person who they ended up cutting both of the doses in half. So I think we're going to learn a little bit more. You'd like to see kind of more outcome based data that you actually see. You know, we put people in both arms and we don't just measure one indicator, but we actually see kind of what long term happens to patients. On just a practical level, just from my own experience, I've seen a heck of a lot more hyperkalemia with spironolactone. So the caveat if people are going to try this is I think they need to be a little bit mindful of electrolytes going forward. But I do think it's interesting and certainly warrants some more study. Our next studies from the JW edition of Diabetes Care and it looked at the comparison of sulfonygre and insulin therapies and metformin with a larger risk of cancer. It was a retrospective database analysis. This retrospective observational study used the German Disease Analyzer database that contained patient data from general practices throughout Germany. The study sample included over 22,000 patients who were diagnosed with type 2 diabetes. During the medium follow up time of approximately 5 years. Approximately 1400 some patients developed cancer. They used a Cox regression analysis with either monotherapies or first diabetes medicine as drug exposures. The users of sulfonylurea or insulin or other diabetic medicines were compared with metformin in the multivariable adjusted models. The hazard ratio was 1.09 with a confidence interval that went from 0.87 to 1.36 for sulfonylurea monotherapy a hazard ratio of 1.14 with a confidence interval of 0.85 to 1.55 for insulin monotherapy and a hazard ratio of 0.94 with a confidence interval of 0.67 to 1.33 for other diabetes medicines compared with metformin monotherapy. The results were similar for the comparison of other first diabetes medicine.
- [15:33]
B
Neil John, I'm happy to see this study because we've reviewed two or three studies over the last two years that looked at a decreased cancer risk with metformin and I've always wondered about how well the studies were done. There are large population studies and the link between metformin and decreased cancer risk never made complete sense to me. This study was done with very careful methodology, patient matching, comparing metformin to sulfonylureas and showing no significant decrease in cancer risk with metformin. And I don't mean I'm happy to see that there isn't a decrease. It would be nice if there were, but I'm always happy when we have studies that are carefully done that potentially better reflect truth, so that the decisions we make are made with the best possible data. So we ought to be using metformin for all of the reasons that it is a good choice and a first choice in diabetes, the lack of weight gain, the low incidence of hypoglycemia. But I don't think a decreased cancer risk is one of the things we ought to be thinking of when we think of metformin. Our next study is titled the influence of new European Union driver's license Legislation Legislation on reporting of severe hypoglycemia in patients with type 1 diabetes the authors tested their hypothesis that the implementation in Denmark of new stricter laws on driver's licensing with the purpose of improving traffic safety that occurred in January 2012 reduced self reported rates of severe hypoglycemia in routine clinical settings and that anonymous reporting results in higher event rates. They looked at a cohort of over 300 patients with type 1 diabetes recruited in an outpatient clinic. Yearly numbers of severe hypoglycemic events, defined by need for treatment assistance from another person were retrieved from medical records in the years 2010 and 2012 and retrospectively reported. Also in an anonymous questionnaire. Data from 2012 were compared with those from 2010 and 2011 as well as with the questionnaire reported. Rates of severe hypoglycemia in the medical records were reduced by 55% in 2012 compared with prior years, with a significant p value. The proportion of subjects reporting recurrent episodes was grossly reduced from 5% of people to 1.5% of people, also significantly compared with anonymous reporting in the questionnaire, the rate of severe Hypoglycemia in 2012 was 70% lower when reported to their physician than on an anonymous questionnaire.
- [18:38]
C
John so I think there's two very interesting things about this study is, and I don't know how much the people of Denmark are kind of wed to their cars, but certainly taking away someone's license in the United States is really, you know, akin to a death for many people in many ways. And it is very difficult to take away people's licenses. And then when you kind of put in the added factor that people rat themselves out and what we've kind of found in this study from Denmark is, you know, when people see these consequences, they're less likely to be truthful with their physician. You don't, I don't assume that suddenly people's amount of hypoglycemia has decreased, but people see clear consequences with it. So what about the overall risk? And I think the second part is the overall risk for hypoglycemia and driving. And certainly looking at diabetes care position statement January 2012, looking at diabetics and their rate of having an accident is anywhere from 12 to 19% higher than controls. If you look at type 1 diabetes diabetics with a history of severe hypoglycemia in the last two years, their risk of having an accident is 50% to 100% greater than controls. The risks are higher in folks who are unaware of hypoglycemia. But if we look at some of the risk of some of the other groups that we let drive, compared to a 35 year old female, a 16 year old male has a 42 times higher rate of having an accident. Driving on a rural highway is over nine times higher than riding on an urban highway. Driving at 1 in the morning on Sunday morning is 142 times more likely to have an accident than Sunday morning. So I think we need to be mindful of our patients who have severe hypoglycemia and they certainly are a risk to themselves and others if they're having recurrent events. And we really should evaluate this for driving, but this well intentioned method in Denmark really seems to have failed. And certainly if I have a patient who's having hypoglycemia not just for driving issues but for a lot of other reasons, I would like them to confide that in me. And if we're going to drive them underground by feeling they're going to have their license taken away, I think there can be worse outcomes than just automobile accidents.
- [21:02]
B
For more information and links to the articles that we discussed in this issue, just go to www.diabetesjournals. until next week. Keep listening and keep learning. SA.