Doctors spend a lot of time recommending diet and exercise for weight loss. If you’re my patient, unless you’re quite fit, you've probably heard me ask you to exercise more and eat less. There is good reason for this. Many short term studies have convinced us of multiple benefits of weight loss – better sugar control in diabetics, lower blood pressure, improved mood, higher quality of life.
Nevertheless, there is little data about the long term benefits of weight loss. If you were to design a trial looking to measure the cardiovascular benefits of weight loss you would want to focus on a group of people who would benefit most, a group at high risk for strokes and heart attacks. Overweight diabetics would be a great choice.
Last week the New England Journal of Medicine (NEJM) published the results of a long term trial testing whether intensive lifestyle modification aimed at weight loss would prevent strokes and heart attacks in overweight patients with type 2 diabetes.
Over 5,100 middle aged and elderly patients with type 2 diabetes were enrolled. They were all overweight or obese (BMI 25 or over). They were randomized to two groups. One group was counseled about diet and exercise. They were educated to exercise for about 3 hours per week and consume 1,200 to 1,800 calories daily with less than 30% of the calories from fat. The control group was not given specific targets for calories or exercise. Both groups had their diabetes and other medical problems managed by their own physicians, and their medications were not controlled by the study.
Both groups were followed for an average of 9.6 years to see if one group had fewer strokes, heart attacks, or death due to cardiovascular causes.
Not surprisingly, the lifestyle intervention group lost more weight than the control group. After one year the intervention group lost on average 8.6% of body weight, compared to 0.7% in the control group. After the first year, the intervention group regained some weight, a common occurrence in weight-loss studies (and in the personal experience of dieters). Still, by the end of the study the intervention group lost 6% of their initial body weight, compared to 3.5% in the control group. The intervention group had lower glucose levels (i.e. better diabetes control), was on less medication, and had less serious kidney disease, depression, and sleep apnea.
That’s not bad, right? If I had diabetes I would exercise regularly and eat less for those benefits.
So you would think that with all those benefits including the pretty impressive weight loss, the intervention group would have had fewer strokes and heart attacks. They didn’t. The numbers of strokes, heart attacks, and deaths in the two groups were not significantly different.
Across the scientific land there was wailing and gnashing of teeth. What happened? Surely, we can’t throw in the towel on diet and exercise.
An editorial in the same NEJM issue suggests possible explanations. Perhaps the weight loss achieved in the study was simply too small to decrease cardiovascular risk. That would be a very depressing explanation since the weight loss achieved in the study is greater than most people are able to maintain. Hoping that a larger weight loss is needed for cardiovascular benefits would not be very realistic for real patients. Another possibility is that the cardiovascular benefits only accrue after a longer delay, and that following the patients for longer than 10 years is needed to measure this benefit.
The explanation I find most plausible has to do with the medications the patients were taking. Again, the medications taken by the patients were not controlled by the study; they were left up to each patient’s physician. As it turned out, blood pressure medicines, statins (a family of cholesterol-medicines), and insulin were used more frequently in the control group than in the intervention group. One result of this is that LDL (the most important cholesterol molecule) was lower in the control group.
It’s easy to see how this might have happened. Imagine two overweight diabetics with elevated cholesterol. One is in the control group. He’s not making much progress losing weight, so his doctor starts him on a statin. Statins have solid evidence that they prevent strokes and heart attacks. The other patient is in the intervention group. He’s making good progress losing weight with diet and exercise, so the doctor delays starting the statin, choosing instead to recheck his cholesterol in a few months. Maybe his cholesterol eventually drops or maybe it doesn’t but the proven statin therapy is delayed despite the high cholesterol because of the optimism generated by the impressive weight loss. The delayed statin use negates whatever benefit the weight loss would have caused, and the two groups end up with equal numbers of strokes and heart attacks.
To put it another way, I think current medical treatment for high blood pressure, diabetes, and high cholesterol is so effective in preventing strokes and heart attacks that it is very difficult to find an intervention that will decrease cardiovascular risk even further. Perhaps the most positive thing that can be said about the weight-loss group is that it had the same cardiovascular outcomes as the control group which was taking more medications.
So my lesson is that overweight diabetics should diet and exercise, but medications to aggressively lower their blood pressure, sugar and cholesterol should not be delayed due to optimism about their weight loss. Lose some weight, but take your statin.
Disappointing Results for Weight Loss and Diabetes (Wall Street Journal)
Weight loss, exercise didn't affect heart outcomes in Look AHEAD (Internal Medicine News)
Weight loss does not lower heart disease risk from type 2 diabetes (National Institutes of Health)
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes (NEJM article)
Do Lifestyle Changes Reduce Serious Outcomes in Diabetes? (NEJM editorial)
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