A 5-year study reveals that the properly constructed diet, along with exercise aimed at muscle maintenance, can achieve long-term weight loss results.
Osama Hamdy, MD, PhD, has spent much of the past few years presenting study data that dispute conventional wisdom about the futility of diet and exercise and suggest that lifestyle intervention may be the key to fighting type 2 diabetes mellitus (T2DM).
Each year, he reports another 12 months of follow-up information on 129 patients who spent 12 weeks in the Weight Achievement and Intensive Treatment (Why WAIT) program, based at the Joslin Diabetes Center. Each year, the information indicates that a majority of patients have maintained significant weight loss and enjoyed significant health benefits.1,2 Each year, audiences tell Hamdy that the results are extremely promising but too preliminary to justify any major shift in treatment paradigm.
There are some indications that things may change this year, with the publication of a full 5 years of follow-up data. The study abstract that Hamdy and his colleagues prepared for the annual meeting of the American Diabetes Association (ADA) in June generated only moderate coverage in the specialty press, but it did win the Michaela Modan Memorial Award for its contribution to the understanding of T2DM,3 and Hamdy hopes that many researchers and clinicians will come to appre-ciate the significance of its findings. (Medscape included the study among its top 5 from the 2015 Scientific Ses-sions of the ADA.)4 So many previous studies have found that patients regain whatever weight they lose via short-term diet-and-exercise5 and often end up sicker than they started—that many physicians have come to see bariatric surgery as the only path to long-term weight loss. The new study, however, basically falsifies that belief. Indeed, considering that the me-dian weight loss at the 5-year mark was 6.4% of baseline body weight, it suggests that savvy lifestyle management may work better than surgery. Around 53% were even able to maintain 9% weight loss from baseline.
Better still, the study also found that sustained weight loss can reduce the bur-den of diabetes far more than most experts had believed possible. Hamdy said earlier studies showed that with weight loss of 7% or more, insulin sensitivity improved by an average of 57%. In this recent study, patients who maintained 7% weight loss or more after 1 year were more likely to maintain their weight loss for 5 years, and maintain good diabetes control as reflected by their glycated hemoglobin (A1C) reduction.
Results were particularly good for patients who had been diagnosed with T2DM less than 5 years before the study began and had consistently managed to keep A1C levels below 7.5% with oral medication alone. Many patients with these characteristics showed partial or complete remission from diabetes. This information was presented in another poster at ADA; Hamdy and his colleagues also compared their model of Why WAIT in comparison to bariatric surgery (gastric banding). Their randomized controlled study showed no difference between the 2 interventions on diabetes control after 1 year; but the Why WAIT group showed better im-provement in quality of life, especially in mental health. This study was pub-lished in the Journal of Clinical Endocrinology and Metabolism.6
The full details of the 5-year study will only become available on its publication, but such results appear to be a personal and professional triumph for Hamdy, who has devoted his career to fighting a disease that claimed the lives of many of his family members and then spent much of that career arguing to skeptical audiences that T2DM is less an independent disease than a complex symptom of obesity.
“Diabetes is to obesity as fevers are to infectious disease, yet diabetes research has typically focused on blood sugar and ignored body fat. Those priorities were always questionable, but now that many drugs can reduce blood sugar without the extra insulin that hastens disease progression, it’s absurd to keep spending 80% of our research dollars de-veloping more,” said Hamdy, who runs the Obesity Clinical Program at Joslin Diabetes Center and teaches at Harvard Medical School.
Hamdy hopes that the 5-year Why WAIT data demonstrate the potential of fighting the underlying cause of T2DM rather than just managing the symptoms associated with the condition, both to research organizations that devote relatively little money to weight-loss studies and to clinicians who treat T2DM patients.
“Doctors have it drummed into their heads that long-term weight loss is impossible without surgery, so they often spend all of 30 seconds talking about nutrition and exercise before they turn their attention to medication. This study gives them a roadmap for using lifestyle modification to achieve much better outcomes over the long run.”
INTENSITY OF THE WHY WAIT INTERVENTION
Participants in the Why WAIT study underwent only 12 weeks of lifestyle intervention, but that program was very intense but doable. It included a structured diet, regular exercise, cognitive therapy, group counseling, and medication adjustment. As for the 5-year study period that followed, it mandated no particular lifestyle, though it did pro-vide some support and required periodic check-ups, medication adjustments, and other routine care.
Many older studies had already tried something similar, and almost all of them reported depressing news. Patients lost significant amounts of weight while they followed specific diet-and-exercise programs, but once those programs ended, patients regained all the weight they lost (or more) and some-times ended up in worse condition than they began.7,8
The design of the new study hypothesized that these failures stemmed largely from overmedication, muscle loss, and lackluster advice about weight maintenance.
Study diets typically restrict total calories, particularly calories from simple carbohydrates, so they raise blood sugar levels far less than standard patient diets. What’s more, by reducing body fat, they steadily make patients more sensitive to their own insulin. In theory, therefore, dieting patients should need ever-decreasing amounts of medication to control blood sugar and those who have completed the diet should need less medication than they did at baseline. Yet previous studies rarely adjusted medication levels in any systematic way, said Hamdy, if they adjusted them at all. This failure created a systematic risk of overmedication, mild hypoglycemia, and intense cravings that led patients to eat themselves back to a weight that justified so much medication.
Among the key features of the new study was a custom-built algorithm that monitored how patients responded to the study regimen and adjusted their medication usage accordingly. By the end of the Why WAIT program, patients were, on average, using slightly less than half as much medication as they were before the study began. That reduction translated into an average annual cost savings of $561 per year. More importantly, it kept blood sugar levels from falling too low and encouraging patients to eat more.
Another key feature of the new study was its muscle-maintenance program. Prior studies have successfully combined diet and exercise to cause a rapid reduction in body weight, but, according to Hamdy, dieting patients typically lost almost a pound of muscle for every 3 pounds of fat they manage to shed. This muscle loss does nothing to reduce the burden of diabetes. To the contrary, research indicates that muscle loss is associated with disease progression, so Hamdy and his colleagues designed a study protocol that would minimize it. The Why WAIT study’s exercise program included strength training, and its dietary guidelines called for plenty of protein. They succeeded in reducing muscle mass loss to only 10% of the total weight loss. Maintenance of the muscle mass is critical for maintaining higher basal en-ergy expenditure (Basal Metabolic Rate, or BMR). This BMR typically goes down after weight loss and is one of the main causes of weight rebound.
Men who participated in the study ate 1800 calories a day, while women ate 1500 calories a day, which is not a drastic cut in caloric intake. Protein consumption, on the other hand, varied along with body weight: everyone received 1.5 to 2 grams of daily protein per kilogram of baseline body weight. This formula led to very protein-rich diets for heavy patients. A 250-pound woman would receive one-third of her day’s calories from protein, or 150 to 200 grams a day. The diet also limited total carbohydrate consumption to no more than 40% to 45% and delivered most of them from low glycemic index carbs and fiber, rather than from sugar or starch.
The exercise program that patients performed during the initial 12 weeks of the study featured a mix of aerobic exercise and stretching, along with enough strength training to prevent muscle loss. Given the relatively poor condition of most patients at baseline, light work with resistance bands, performed for 10 or 15 minutes a day, was generally sufficient to maintain or increase strength. The exercise program progressed gradually to 300 minutes per week by the end of the 12 weeks.
The initial regimen helped patients shed about as much weight as programs used in other trials. Patients lost an average of 23.8 pounds, which translated into 9.7% of body weight. Their body fat as content and percentage dropped significantly but ratio of lean muscle mass to fat mass went up, indicating a great preservation of lean muscle mass. Hamdy said, “this is a key indicator of successful and healthy weight loss and dif-ferentiates us from any other program.”
Analysis of the study showed markedly different outcomes for the 61 patients who failed to remain at least 7% below baseline body weight for a full year (Group A) and the 68 patients who did not (Group B). Both groups dispelled the myth that long-term weight loss was impossible, but the average 5-year loss for Group A members was a modest 8.4 pounds (3.5%), while the average 5-year loss for Group B members was 23.1 pounds (9.0%), more than enough to create substantial health benefits.9
That weight loss had little apparent effect on simple health metrics, which may be why the abstract results did not generate much media coverage. Improvement to lipid profiles were significant and lasted the full 5 years,even among patients who regained the weight they initially lost. On the other hand, the passing of time reversed initial declines in blood pressure, even among patients who maintained significant weight loss the entire 5 years. As for A1C levels, average measurements for Group A members fell from 7.5% to 6.7% during the first 12 weeks of the study, but rose to 8% by the end of the 5 years. Group B members essentially stood still. Their average A1C level fell from 7.4% to 6.4% but climbed back to 7.3% by the end of the study, but patients were taking few-er medications.10
“Keep in mind that diabetes is a progressive disease, so to stop its progression or reverse it is considered a revolution in management,” Hamdy said.
Such figures suggest that the effort required to keep off the extra pounds produced virtually no payoff for study patients, but other figures indicate that weight reduction rewarded patients handsomely. Not only did they enjoy the dramatic increase in insulin sensitivty—an indication that weight reduction reverses the course of T2DM—but they also enjoyed dramatically better health. According to Hamdy, the overall healthcare costs of study patients fell by an average of 27%, while the costs associated with diabetes care fell by 44%.
“No study, to our knowledge, has ever found any of this, not at the 5-year mark,” Hamdy said. “We’re the first to show this degree of weight loss (without surgery), this degree of disease reversal, and this degree of health and cost benefit in real-world clinical practice.”
Neither the initial program nor the follow-up treatment relies on any recent discovery or technology, except perhaps the software used to keep adjusting each patient’s medication. It’s no secret that excessive medication leads to excessive eating,8 that dieters tend to lose muscle, or that resistance training and protein consumption protects muscle. The diet-and-exercise regimen merely combined existing knowledge in what Hamdy considered to be a logical way when he oversaw its design. The counseling program was much the same, a collection of research-backed strategies—imperfect strategies that reflect our very imperfect understanding of self-control—for effecting long-term lifestyle changes: daily weigh-ins, meal replacements, brief spurts of exercise sprinkled throughout the day, and others.
In theory, researchers could have built a similar program and performed a similar study decades ago and, in so doing, reduced the need for gastric bypass surgery and shifted some diabetes research from A1C control to weight control. In practice, however, efforts to understand and combat diabetes have pursued what Hamdy considers a frustrating number of false leads and counterproductive strategies over the past 50 years.
“We understood the basics of type 2 diabetes a century ago: the disease is a form of carbohydrate intolerance that arises when people who are pre-disposed to develop it become obese,” Hamdy said. “The obvious treatment, therefore, is to lose fat while reducing carbohydrates enough to control blood sugar. The creation of medical insu-lin moved the focus of treatment from lifestyle to medication, which seemed reasonable at the time because many people thought that diligent insulin use would be almost as good as a cure. The real problem is that after it became clear that insulin was no panacea, the focus of both treatment and research stayed fixed so completely on controlling blood sugar with insulin and, eventually, sub-stitutes for insulin. We currently have more than 40 different drugs for diabetes management.”
Those research choices affected a relatively small number of Americans while obesity remained rare, but diabetes research has become a major health issue thanks to the ongoing surge in obesity rates—a surge that Hamdy attributes in part to medical research gone wrong.
“There are a lot of reasons that we are getting fatter, but bad science did contribute,” Hamdy said. “A few dubious studies led directly to bad nutritional guidelines, and from there to media coverage and advertising that spurred people to eat worse in the name of eating better. Sales records from the time show the consumption of meat and eggs and butter plummet, never to recover. Had we given obesity and nutrition the attention they deserved we would have known that replacing protein with sugar would make more people obese, but the evidence was limited and the prevailing dogma was that all calories were equal. We’re still feeling the consequences, decades later, both because it takes forever to correct mistakes that get fixed in the public’s imagination and because we failed to study obesity properly for so long that we don’t really have all the information we need to provide clear ad-vice about what’s best.”
Hamdy’s obvious contempt for the food pyramid that advised Americans to subsist mainly on white flour does not indicate any support for diets that consist entirely of bacon. Up to 40% of the calories in the Why WAIT diet come from carbohydrates, albeit carbohydrates with low glycemic index values. The diet tries to keep calories from satu-rated fat significantly below 10% of daily intake. That said, Hamdy believes that excessive carbohydrates are the biggest problem for most T2DM patients, and he struggles to understand why many doc-tors still recommend that such patients get up to 60% of their calories from carbohydrates.
From the beginning of the 17th century until the last part of the 20th century, diabetes was treated with a low carbohydrate diet, but over the last 4 decades we were giving our patients the wrong dietary advice that 50% to 60% carbohydrates is not a problem. It really is the problem.”
Hamdy hopes that the 5-year figures from the Why WAIT study convince more of his colleagues about the virtues of eating carbohydrates with minimal effect on blood sugar and keeping carbohydrates well below 40% of total calories. He also hopes those results will spur many physicians to think more seriously about muscle preservation. Research has yet to prove that muscle loss causes disease progression or that muscle gain can reverse it, but many studies have demonstrated that muscle loss and disease progression are strongly associated. The Why WAIT study, moreover, provided another indication of the importance of muscle mass: the best predictor of whether a patient would sustain fat loss and enjoy disease reversal was the con-tinuation of strength training.
“Each new piece of evidence helps us understand a little bit more about the mechanisms of both diabetes and obesity, but we still have an incredible amount to learn,” Hamdy said. “It’s frustrating to think that we could know so much more if we had avoided a few serious mistakes and made better research choices. On the other hand, it is a great relief to have hard evidence that we do already know enough to put together a plan that produces very significant long-term weight loss in a large percentage of diabetes patients. Now the only trick is convincing the world and, of course, learning all the stuff we need to know to make it work even better.” References
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2. From ADA 2012: Diabetes and obesity—Why WAIT? Ameri-can College of Cardiology website. www.acc.org/latest-in-cardiology/articles/2012/07/12/10/09/from-ada-2012. Published July 2012. Accessed August 22, 2015.
3. Dr Osama Hamdy, medical director of Joslin Diabetes Center’s Obesity Program, to receive ADA’s Michaela Modan Memorial Award [press release]. Boston, MA: Joslin News; May 4, 2015. www.joslin.org/news/Osama-hamdy-%20to-receive-michaela-modan-memorial-award%20.html. Accessed August 22, 2015.
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