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Diabetes Core Update
Diabetes Core Update April 2014
00:25:43
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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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 Skolnick, 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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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 great issue this month, starting with an article from Diabetes Care looking at pragmatic approaches to diabetes prevention, then an article from Diabetes Care on physical activity in patients with diabetes and its effect on all cause mortality, followed by an article on prevention of diabetes in patients with prediabetes who received phentermine and topiramate extended release, then an article from Diabetes on spontaneous pancreatic lesions in normal and diabetic rats, followed by a discussion of subthreshold depression and diabetes and finally, really interesting counterpoints on the effect of sugar on body fat.
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Our first article in this edition is from the April 2014 edition of Diabetes Care and it looked at diabetes prevention in the real world, the effectiveness of pragmatic lifestyle interventions for the prevention of type 2 diabetes and the impact of adherence to guideline recommendations. This systemic review and meta analysis looked at studies through July 2012. It included studies that had a follow up of greater than 12 months and outcomes comparing change in body composition, glycemic control or progression to diabetes. The lifestyle interventions were aimed to translate evidence from previous efficacy trials of diabetes preventions into real world intervention programs. 25 studies met the inclusion criteria and the preliminary Meta analysis included 22 studies with outcome data for weight loss at 12 months. The pooled result of the direct pairwise meta analysis showed that lifestyle intervention resulted in a mean weight loss of 2.12kg and adherence to guidelines was significantly associated with greater weight loss.
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Neal John, I think this is an important study. We know from the Diabetes Prevention Program trial as well as from the Finnish Diabetes Prevention Program that well done controlled studies show that lifestyle intervention diet plus exercise decreased the chance of developing diabetes. Remember in DPPT usual care compared to metformin850 bid compared to lifestyle intensive lifestyle modification showed that you could decrease in a group of patients with prediabetes with progression to diabetes by 30% with metformin, but about double that 60% with lifestyle modification. The problem is how to translate those really great studies into real life at a level of cost that's sustainable. So what this study does is look at programs like those done in the at YMCAs and other places where they use ancillary health personnel, personal trainers, people like that, to implement pragmatically the same sort of protocols for people in real life with reasonable follow ups. And what this shows is that the outcomes are about half as good as what you see in the intensive control trials. Nonetheless, there clearly is better weight loss with lifestyle modification than without. Important to realize with the over 2 kg of weight loss here compared to the non intervention programs is that in the control trials like DPI we saw a 16% decrease in the incidence of diabetes with each 1 kg of weight loss. So it is accomplishing something real. We know what to do essentially now what we need to learn is how to do it. The next article, also from the April edition of Diabetes Care is titled Physical Activity and Risk of all cause and cause Cardiovascular Disease mortality in Diabetic adults from Great Britain. This trial looked at over 3,000 participants among whom there were eventually 675 deaths, all of whom had diabetes in the Health Survey for England and Scottish Health surveys that was conducted between 1997 and 2008. Participants were over 50 years of age at baseline and were followed for an average of greater than six years and they were followed for all cause and cardiovascular disease mortality. Data was collected on self reported frequency, duration and intensity of participation in sports and exercise, walking and other physical activity. There was an inverse association with all cause and cardiovascular disease mortality observed for both overall physical activity in a dose response manner after adjusting for covariates. Compared with those individuals who were inactive, participants who had some activity had a 26% lower all cause mortality and those who had the recommended amount of physical activity had a 35% decrease in all cause mortality.
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John so this is not especially surprising. I think we would guess that people who have more activity do better. We've looked at lots of papers in the last year that looked at fitness versus fatness and showed really that fitness was helpful. I think one of the things that's helpful in this is it really pointed out that domestic activity really does not make a difference. So we all see patients who say, well I do a lot around the house that really doesn't count. What was also really helpful for me in seeing is the people who walk, who walk above an average amount did just as well as the people who participated in a little bit more vigorous exercise. So for the people who don't really want to join a gym, who don't really want to do something quite as intense, just walking above average, probably about five miles a week, seem to do just as well as the people who had more vigorous exercise. So when patients have to decide do I need to just walk and walk a good amount or do a very vigorous exercise, I would quote them baseball great Yogi Berra who says when you come to a fork in the road, take it. Our next article is also from Diabetes Care and it looked at prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. This randomized placebo controlled double blind study of overweight obese subjects who had a BMI between 27 and 45 with two or more comorbidities. The patients were randomized to placebo a combination of phenteramine 7.5mg or extended release topiramate 46mg or phentermine 15mg with topiramate extended release 92mg plus. Lifestyle modifications the patients were followed for 108 weeks and were followed for percentage of weight loss, annualized incidence, rate of progression to type 2 diabetes, changes in glycemia, lipid parameters, blood pressure and waist circumference. At baseline there were 475 subjects who met the criteria for prediabetes and or metabolic syndrome. After 108 weeks the patients in the placebo lost 2.5% weight loss. In the lower group of phentermine topiramate lost 10.9% and in the higher dose lost 12.5%. The reduction in going on to diabetes was 70.5% decreased in the lower dose and 78.7 in the higher dose of the combination medicine. The ability of phentermine topiramate at extended release was related to the degree of weight loss and was accompanied by significant improvements in all the cardiometabolic parameters. The medicines were well tolerated in this group who took medicines for over two years.
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Neil John I think this is really an important study and in truth it's been a pretty phenomenal one to two years with regard to obesity. Remember in the last year and a half there have been two new guidelines that have come out addressing obesity and In June of 2013 the American Medical association voted to classify obesity as a disease which has important implications with regard to our ability as clinicians to be able to see patients who are obese and be able to bill for a medically related visit. In addition, two new medicines have been approved over the last two years and have come to market over the last year, both of which lead to significant weight loss. One of the medicines 4% weight loss, the other about 12% weight loss. There's some real questions and debate then about where medicines fit into our approach. It's clear that everyone who's overweight or obese should have counseling about lifestyle modifications, specifically diet and exercise. It's equally clear that the large majority of patients who attempt lifestyle modification are unsuccessful in sustaining long term outcomes. The question then becomes what is the place of medicines and what is the place? The other thing on the map is bariatric surgery. Let's focus on medicines. Until this study, the real question is we knew medicines led to weight loss, but did it really lead to a sustained decrease in the likelihood of developing one of the feared outcomes of obesity, which is diabetes? This study pretty convincingly shows in almost 500 patients that use of phentermine and topiramate led to a 70 to 80% decrease in the development of diabetes, which is important, impressive and very relevant. It's important to remember that both groups got lifestyle modification, so this is not compared to lifestyle modification. The placebo group and the medication group got lifestyle. And it's important if we choose to use medications for weight loss to remember that. It's important to also emphasize lifestyle modification if we want to get these sort of results along with using medicines. But this study is important in that it really does show that phentermine and topiramate works to accomplish one of the important goals that we would hope it would, which is in addition to weight loss, improving metabolic parameters and specifically decreasing progression from pre diabetes to diabetes. Our next study is from Diabetes April edition titled Occurrence of spontaneous pancreatic lesions in normal and diabetic rats a potential confounding factor in the non clinical assessment of GLP1 based therapies. Glucagon, like peptide 1 based therapies, collectively described as incretins, produce important glycemic benefits. Recent publications though have raised concern for potential increase in the risk of pancreatitis as well as pancreatic cancer with incretins, based in part on findings from a small number of rodents. However, extensive toxicology assessments in a number of animals dosed up to two years at high multiples of human exposure don't support these concerns. The authors hypothesized that the lesions being attributed to incretins are commonly observed. Background Findings Findings and looked to characterize the incidence of spontaneous pancreatic lesions in three different rat strains. What they found was pancreatic findings in all groups, diabetic rats and non diabetic rats included focal exocrine degeneration, atrophy, inflammation, ductal cell proliferation and observations of large pancreatic ducts similar to those described in the literature. With the incidence of exocrine atrophy and inflammation seen in the rats ranging from 6 to 42%. These data indicated that the pancreatic findings attributed to incretins were common background findings observed without drug treatment and independent of diet or glycemic status, suggesting a need to exercise caution when interpreting the relevance of some recent reports regarding incretance.
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John I think this has been more than a whisper. In fact we've talked about this in this very same forum a few months ago about kind of a pro and con about whether this was a true thing. I think it's, it's very reassuring from this. And, and my takeaway point is when you're looking at this rat population, a lot of the things that they were finding and attributing to these medicines were basically rat incidentalomas. You know, if we're going to find, if we had a new medicine and suddenly we did CAT scans on a large percentage of the population and we saw that 1% of people had small adrenal masses, we'd say oh my goodness. But the truth is that's kind of the human experience and this is a bit of the rat experience. Interestingly Enough, in the February 27th edition of New England Journal there was a report from the FDA and the European Medication Agency which basically came out for the DPP4s and the GLP1s that really a lot of these safety concerns was noise, but really what did not have a whole lot of validity to them. So certainly I think when we're making our decisions on medicines to use and to use medicines from either of these classes, I think we can be reassured that some of these safety whispers really have not played themselves out. Our next article is from Diabetes Care and it looked to recurrent subthreshold depression and in type 2 diabetes, an important risk factor for poor health outcomes. This prospective community study was done in Quebec, Canada and was carried out between 2008 and 2013. Over 1,000 patients were interviewed and followed for five years with follow up assessments by telephone. The researchers looked at baseline and follow up assessments used to identify recurrent subthreshold depressive episodes, patients overall level of function and health related quality of life. They also looked at the percentage of unhealthy days that patients had over this four to five year study. Nearly half of the participants suffered from at least one episode of subthreshold depression symptoms. After adjusting for potentially confounding factors, the risk of poor functioning or impaired health related quality of life was nearly three times higher. Relative risk of 2.86 for participants who had four subthreshold depressive episodes compared with participants with no to minimal depression. The results suggested a dose response relationship and the results of poor functioning. Impaired health increased with the number of recurrent subthreshold depression episodes even after controlling for potentially confounding variables.
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Neil John it's interesting. This study adds to the body of literature about chronic disease and depression. We know that most chronic diseases, including diabetes, have a higher instance of concomitant depression than seen in the population at large. If we look at the population at large, there's about a 10 to 12% prevalence of depression. If we look at patients with diabetes, that prevalence goes up to 20 to 25%. Other studies have shown that patients who have depression and diabetes have poorer self care, poor adherence to medicines and worse A1Cs. Last month we talked about a study from Diabetes Care that addressed depression and diabetes utilizing cognitive behavioral therapy and actually showed improvement in self care skills and decreased A1Cs in the group that got CBT by about 0.6%, about the amount that you often get with some of the new diabetes medicines. This study expands on that idea and looks at subthreshold depression. In fact, when we look at subthreshold depression, the prevalence in this study was up to 50% of patients and the outcomes for these patients with regard to impaired health related quality of life and other parameters were significantly worse than in patients who did not have sub threshold depression. It emphasizes the importance of addressing depression, sub threshold depression and other quality of life issues. In fact, in the Alaskan Inuit health system, putting mental health professionals on site in primary care offices decreased health care costs. It wasn't just about improving the way people felt, but those people would in turn take their medicines more often, adhere better to diet, exercise, felt better and actually had better health outcomes. So I think this is one worth remembering and underscores the importance of addressing psychosocial issues. Next we're going to discuss two articles that argue in the first case that while sugar is important, it isn't the sole cause of the obesity epidemic. And the second article takes the stance that sugar is a significant contributor to the obesity epidemic and needs to be very directly addressed. In the first article, the author states that while there is a rise in the prevalence of overweight and obesity in the 1980s, it doesn't and it's related to the increase in availability of added sugars. That's an epidemiologic association and that while such ecological findings are intriguing, they don't define a causality. And the author in fact mentions that at the same time there's been a rise in consumption of bottled water, that these associations are hypothesis generating but not conclusion finding. The author then goes on to talk about. Over the last decade, numerous randomized trials on the effect of sugar consumption have been performed. And some of those trials looked at whether an isocaloric exchange of added sugar, purified fructose, with other macronutrients would affect body weight in adults. Analyses of these studies showed no significant effect of sugar or pure fructose on body weight when it was substituted in an equal caloric fashion for other calories. Another approach in randomized trials has been to examine the effect on weight when calories from sugar are reduced relative to consumption in a control group. What this showed is that there's no significant change in weight with reduction in calories from sugar. When eight trials of children and adults were analyzed, all three meta analyses of this issue found major inner study heterogeneity, implying that there were difficulties with many of the trials that were done. The author goes on to state that while all the prospective cohort studies examine the relationship between sugar and weight, adjusted for various potentially confounding variables, almost none adjusted for energy consumption. So in these studies, as in the randomized trials, the association between increased sugar consumption and weight would be due to excess energy intake, but not to unique effect of sugar. John, do you want to go over the article that talks about the problems with sugar?
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So in the next article, it looked at dietary sugar and body weight. Have we reached a crisis in the epidemic of obesity and diabetes? So this particular study really points out that our increase in sugar has really been a big part of our downfall. So if you go back to the signing of the Declaration of Independence, the average American ate about 4 pounds of sugar a day. If you get to the early 2000s, it's about 120 pounds of sugar a day. Since in the early 1970s, we've seen a huge uptick in obesity and we've seen over that period of time a huge uptick in the consumption of sugar, sweetened beverages, the United States, which is now the second fattest country in the world, has the largest consumption of sugar sweetened beverages in the world. We're almost double the next closest country, which would be Ireland. When McDonald's first opened, a standard soda was 7 ounces. Now a standard soda is 16 ounces. And certainly we've seen interventions in New York City to try to limit the size of soft drinks, etc. So the authors really want to talk about high fructose corn syrup and actually being associated with a lot of bad things, including fatty liver. There really is not satiety that happens when people are taking in high amounts of sugar to ask people to stop drinking. There's often caffeine that has a little bit of a wearing off effect and kind of signals us to take in more of sugar sweetened beverages. In fact, the National Academy of Sciences in the early 1980s said sugar is probably not all that bad, it certainly causes tooth decay, but really did not have such a damning effect. But now we're at a point that we're seeing so many health effects that are linked to the consumption of high fructose drinks that are in so many sugar sweetened beverages. 75% of the foods we eat right now contain some added sugar. So certainly were some recommendations to have people choose water, unsweetened coffee or tea. We really should be eating fruit rather than drinking fruit drinks. When you look at some of the fruit drinks, there actually can be more calories and almost just as much sugar as compared to the same volume of soda. If we're going to drink calorically sweetened beverages, we should really try to get down to 6 ounces a day for adults and that's 7 ounces for kids 2 to 18 years of age, which was really the amount in the pre-70s. We should be thinking about alternative things to take in and we should be mindful that there's caffeine and lots and lots of drinks that kind of reinforces the cycle. But I did mention that the United States was the second fattest country. And I think the interesting thing is if you look to see what's happened in Mexico, so Mexico now, in the entire world, Mexico's per capita consumption of Coca Cola equals that of the United States, Britain and Germany combined. And they're consuming about 300 servings of coca Cola per annum. And actually they've taken over from the United States States as the fattest country in the world. I don't know if this is coincidence, but certainly it's worth thinking about.
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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.
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SA Sam.