• Politics is making us miss some really amazing research news

    A longtime reader of the blog laments to me that it’s too bad politics is overshadowing clinical and policy news right now. I couldn’t agree more. I’ve posted on a number of interesting studies recently, but they’re just not going to get eyeballs until the election is over. Here’s another:

    An intensive diet and exercise program resulting in weight loss does not reduce cardiovascular events such as heart attack and stroke in people with longstanding type 2 diabetes, according to a study supported by the National Institutes of Health.

    The Look AHEAD (Action for Health in Diabetes) study tested whether a lifestyle intervention resulting in weight loss would reduce rates of heart disease, stroke, and cardiovascular-related deaths in overweight and obese people with type 2 diabetes, a group at increased risk for these events.

    Researchers at 16 centers across the United States worked with 5,145 people, with half randomly assigned to receive an intensive lifestyle intervention and the other half to a general program of diabetes support and education. Both groups received routine medical care from their own health care providers.

    This study took people with type 2 diabetes, and ran half of them through a lifestyle intervention to help them lose weight. The hope was that people who lost weight would have fewer heart attacks and cardiovascular events. Seems like a no-brainer.

    Unfortunately, it didn’t work. Yes, participants lost weight: 8% in the first year and about 5% at four years. That’s pretty good. But they still had the same number of bad cardiovascular events.

    Things were so obviously not working that the researchers and NIH decided to end the study early. Some participants had been going for 11 years.

    This doesn’t mean that weight loss is useless. It still could have other health benefits. Lifestyle modification have also been shown to help prevent type 2 diabetes. That’s especially important, because if this study shows us anything, it’s that once you get diabetes, it doesn’t seem like you can reduce your risk of heart attack by losing weight after.

    A larger point is that we don’t actually know the stuff we think we know. I would have assumed that weight loss would work here. It doesn’t. It took millions of dollars, and years of work to find that out. Research is hard and expensive. We need to keep funding it, and doing it.

    @aaronecarroll

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    • This research is very expensive, and it indeed takes a long, long time.

      A good example is the IMPROVE-IT Trial that Merck is running to see whether ezetimibe in combination with simvastatin reduces cardiovascular events more than simvastatin alone. It started in 2005, and is scheduled to end when 5,250 cardiovascular events have occurred. Merck has increased total enrollment several times, and its now up to 18,000 patients. The projected end date keeps getting pushed back, since actual event rates in this population have been lower than planned. Currently, Merck is hoping for a mid-2014 conclusion to the trial.

      Some people suspect that Merck is intentionally slowing things down, to preserve sales if the results are negative. I honestly don’t think that’s true. The criteria for ending the trial are very clear, and have not changed from the original protocol. It is just a reality that studies with sufficient statistical power and relatively uncommon endpoints take a really long time.

      I don’t know what Merck is paying clinical investigators per patient, but over a 9-year trial it has to be tens of thousands of dollars. It wouldn’t shock me if the total cost started to approach a billion dollars. And that’s just ONE trial.

      This kind of research is enormously expensive. I believe sincerely that we should still do it — but we have to be selective to insure that investments like these have an adequate return.

    • Looking at the study it’s hard to see that there was any serious weight loss. 5% over 4 years is never going to be a significant factor.

      The study was probably canned because there wasn’t much weight loss involved.

      • I tend to agree. They didn’t lose much weight and probably kept on eating junk food and high cholesterol meat and dairy so why would you expect it would have any effect?

      • A 5% weight loss sustained over four years is actually pretty impressive. Not many programs can show that kind of success.

        • I agree that a 5% weight loss sustained over 5 years is a “good” result as far as weight loss programs go.
          However, in order to have some effect on disease, these people need a much greater change. Someone going from 200 pounds to 190 pounds just can’t expect to gain any health benefit, especially if they continue to eat a typical diet containing saturated fat and empty sugar calories (which is why they probably had such a small weight loss).

          • A lifestyle modification program isn’t just about losing weight. I imagine it’s also about healthier eating. Moreover, this is a real-world test. It’s entirely possible that encouraging (even strongly) people to enter such a program doesn’t work.

            Two other points: (1) This was the average weight loss. I imagine some had much more, some less. (2) I’m betting that many people weighed significantly more than 200 pounds, and 5% of weight would be a larger amount.

            • It may be helpful to compare the degree of weight loss to that experienced in whatever trial(s) demonstrated an effect in pre-diabetics. Was 5% enough in that case? If so, this recent study is really telling us something important.

            • (Actually replying to Austin here since we’ve maxed out nesting levels.)
              This study is on the cardiovascular effects of weight loss in diabetics. While there are a lot of studies showing improvements in diabetes with weight loss, I can’t find any that looked at cardiovascular effects.
              Even the studies of weight loss and diabetes had much larger weight changes. There is a good summary (with references) on this ADA page:
              http://care.diabetesjournals.org/content/25/2/397.full
              However, the weight loss amount they report to have a good effect are very large (gastric band surgery: 40 pounds, 27 kg, 100 pounds in different studies) although one study showed a (non-surgical) loss of 4.2 kg sustained for 3 years can lower the progression of diabetes by 50%.
              However, no results specifically for cardiovascular effects (although this study did show an inverse correlation of “fitness” and “all cause mortality”: doi: 10.2337/diacare.27.1.83 Diabetes Care January 2004 vol. 27 no. 1 83-88 )

          • Mark
            A 5% weight loss, even in your example (relative vs absolute does not matter) is significant. Search around on google. Even what seem like trivial drops in weight can change insulin resistance, allowing many patients to forgo insulin or oral meds. Better health ensues. In fact, a long term loss of 5% is a victory.

            This study looked at macrovascular complications, but like AC points out, other potential benefits accrue, including QOL, reduced costs, and less microvascular complications. The paradoxical findings are still darn interesting.
            Brad

    • I am a bit confused about the result. How many of these people still had type 2 diabetes even after the weight loss? I was under the impression in some cases it could more or less “go away” with enough weight loss. It seems intuitive to me that the diabetes plays more of a role in increasing your risk of cardiovascular events than the additional weight in a vacuum. Could this result be driven by the fact that many participants didn’t lose enough weight to “cure” their diabetes? The abstract wasn’t clear to me on this front. Still an interesting finding though.

    • I think that this is an extremely important result. The sustained loss of 5% of weight is clearly in the range we expect with most weight loss interventions. Consider this trial:

      Wadden TA, Volger S, Sarwer DB, Vetter ML, Tsai AG, Berkowitz RI, Kumanyika S, Schmitz KH, Diewald LK, Barg R, Chittams J, Moore RH. A two-year randomized trial of obesity treatment in primary care practice. N Engl J Med. 2011 Nov 24;365(21):1969-79.

      “We randomly assigned 390 obese adults in six primary care practices to one of three types of intervention: usual care, consisting of quarterly PCP visits that included education about weight management; brief lifestyle counseling, consisting of quarterly PCP visits combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral weight control; or enhanced brief lifestyle counseling, which provided the same care as described for the previous intervention but included meal replacements or weight-loss medication (orlistat or sibutramine), chosen by the participants in consultation with the PCPs, to potentially increase weight loss.”

      “Initial weight decreased at least 5% in 21.5%, 26.0%, and 34.9% of the participants in the three groups, respectively.”

      Now this is a random pick, but other studies have seen similar results in terms of the efficacy of behavioral intervention on diet (we can talk about surgical intervention separately). So a loss of 5% of weight (which was possible for only a third of patients in the most intensive group) is a pretty decent outcome.

      I am happy to conclude that modern dietary interventions are not effective. But that would have the same inference as “expected effects from these interventions are not improving vascular outcomes”.

      It’s also possible that, by the time patients are type 2 diabetes, the level of Atherosclerosis is advanced and irreversible (now I am guessing, without evidence). There is a lot that can learned here. But dismissing the results as being too low is also dismissing behavioral interventions, as currently formulated, at the same time.

    • Wouldn’t it be NICE if there were an agency in the U.S. whose responsibility it was to keep track of these sorts of studies and findings and periodically evaluate and intergrate them into synthesized guidance for physicians and patients?

    • Did this study look at other risk factors associated with obesity/type-2 diabetes and cardiovascular disease (CVD) such as tobacco use? I didn’t see any mention of such in the link provided (or I missed it). And I also agree with the majority. Even though 5% weight loss may be high for some, these individuals were still heavy set, and so still at an increased risk for CVD. The results to me don’t seem too generalizable. It would be interesting if this study was conducted using NBC’s Biggest Loser contestants as study participants – everyone sees the dramatic weight loss those individuals go through and maybe their numbers could give more reliable data. Just a thought.

    • On a separate note. Please consider posting something about medical bankruptcy. The warren study is criticized. Don’t know if that’s just political bias.

      Thank you

    • I think your post is a bit misleading (as are most press releases of this particular study). There are, after all, many ways to LOSE Weight. Rather than say “weight loss” “didn’t work”, you need to be more specific. What method was used to be “lose weight”.

      Here is the link to the protocol for the above study: https://www.lookaheadtrial.org/public/LookAHEADProtocol.pdf

      The intervention (aside from exercise):

      “Restriction of caloric intake is the primary method of achieving weight loss. In order to aim for a weight loss of 10% of initial weight, the calorie goals are 1200-1500 kcal/day for individuals weighing 250 lbs (114 kg) or less at baseline and 1500-1800 kcal/day for individuals who weigh more than 250 lbs. These goals can be reduced to 1000-1200 kcal/day and 1200-1500 kcal/day, respectively, if participants do not lose weight satisfactorily. These calorie levels should promote a weight loss of approximately one to two lbs/week.

      The composition of the diet is structured to enhance glycemic control and to minimize cardiovascular risk factors. The recommended diet is based on guidelines of the ADA and National Cholesterol Education program and includes a maximum of 30% of total calories from total fat, a maximum of 10% of total calories from saturated fat, and a minimum of 15% of total calories from protein.”

      That means 55% of the diet was achieved from carbohydrate.

      Essentially, a “Low Fat, calorie restricted diet”.

      So instead of saying weight loss did not work regarding cardiovascular events, let’s say the diet “fat-restricted, calorie restricted diet (restricted through calorie counting rather than through more natural calorie restriction such as letting feedback) with exercise coaching that results in weight loss did not work.”

      The Null Hypothesis. Science.

      Indeed, there are other ways to “lose weight” that might improve cardiovascular risk factors. A low carbohydrate diet has consistently been proven superior to low fat diets in terms of weight loss (using RCT).

      http://www.dietdoctor.com/science

      I really enjoy your blog. Regards.