A large federal trial, looking at lifestyle--diet and exercise--for the treatment of diabetes was just terminated because, after 11 years, it wasn't working as intended. The Look AHEAD study was stopped early because it was not reducing the rate of heart attack and stroke in the intervention group relative to the control. The termination was reported in a press release by the National Institutes of Health, and picked up by mainstream media. The findings suggest that diet and exercise are not effective for reducing the cardiovascular complications of diabetes.
And so, AHEAD, or at least the media coverage of it, is inviting us to look back, and doubt what we thought we knew about diet as the best medicine we've got--for diabetes, at least. We thought we knew that lifestyle was among the most powerful determinants of health outcomes. We thought we knew that diet and exercise together could prevent heart attacks in high-risk people. Participants in the AHEAD intervention lost 8 percent of their body weight by the end of the first year of the trial and were still down 5 percent from their baseline weight at the four-year mark. We thought we knew that diet, exercise, and weight management like this exerted important influences on the course of diabetes. Now, the AHEAD findings suggest we were wrong. Right? Not so fast.
For one thing, the trial did generate many noteworthy benefits. Prior papers in the Archives of Internal Medicine and the New England Journal of Medicine have reported significant benefits of lifestyle intervention related to weight loss, fitness, blood glucose levels, blood pressure, cholesterol levels, and mobility. The study was terminated for failing to prevent heart attacks and strokes, but it did reduce medication use, and conferred other benefits--such as a significant reduction in sleep apnea.
The AHEAD methodology also helps account for the putatively disappointing results of the long-term study. Diabetes requires treatment--so all patients in AHEAD were treated. Those in the lifestyle intervention group reduced their reliance on medication, while those in the control group took more. But since failing to treat diabetes with state-of-the-art medication is unethical, everyone was provided that. The study was actually comparing feet and forks to pharmacotherapy. When both intervention and control groups are being treated, differences between them diminish, an occurrence known in research as "bias toward the null." This exerted a profound effect in the AHEAD trial, making the positive findings more noteworthy still.
But to the extent that the negative results, with regard to cardiovascular event prevention, remain both surprising and disappointing, there is a fundamental explanation for them: too little, too late. What works for prevention may not always work nearly as well for treatment.
Need an image to help that notion really resonate? Let's talk about jumping out of an airplane. A parachute is great for preventing a high-velocity collision with the ground,but it's of no use at all if opened after the landing. Sometimes, timing is everything.
The Diabetes Prevention Program (DPP)--the precursor to AHEAD, in fact, and based on the very same lifestyle intervention--showed that diet, exercise, and modest weight loss could prevent the development of diabetes in 58 percent of high-risk adults. The best drug we've got, metformin, was only half that good. And let's be clear: complications of diabetes don't happen when the diabetes doesn't happen.
The DPP was not a warm-up band for AHEAD. It was a huge federal trial in its own right, run by many of the same people who ran AHEAD. It enrolled thousands of pre-diabetic adults and was supported with a budget of $174 million. The DPP administered the lifestyle intervention adapted for AHEAD. We can't toss out the original DPP results just because AHEAD didn't serve up a repeat. The results of prior trials don't vanish just because new results come along. Whatever we need to learn from AHEAD needs to be reconciled with what we learned before.
We have long had evidence that a comprehensive lifestyle intervention can shrink plaque in coronary arteries. We have evidence that it can prevent heart attacks in high-risk individuals. And we have evidence that it can even change gene expression, and potentially reduce the risk of cancer occurrence, recurrence, and progression.
How do we reconcile such findings with the latest from AHEAD? As a case of a bit too little, quite a bit too late.
See more here:
Diet, Diabetes, and Doubt: Is Preventive Medicine Lost in Space?
