Abstract

Improving the maintenance of weight loss, in those who achieve it, remains a critical yet elusive goal for overweight individuals (and their practitioners). Weight regain remains the most common long-term outcome of most interventions. What makes it so hard to lose weight and keep it off? In this issue, the report (1) from a conference held at the National Institutes of Health provides an excellent summary of what is known about the challenge of long-term weight control, as viewed from the diverse perspectives of integrative physiology, genetics, endocrinology, and behavioral and cognitive sciences. The authors highlight the problem of behavioral fatigue, in which dieters grow weary of diet and exercise regimens that appear to yield little benefit after the first 6 months. Their success is thwarted, in part, by well-documented reductions in resting and (principally) non-resting energy expenditure that occur in response to caloric restriction and initial weight loss (2). The authors similarly highlight the current status of behavioral and pharmacologic methods to improve the maintenance of weight loss. One of these, monthly or twice monthly behavioral counseling sessions following initial weight reduction, delivered in person or by telephone, is efficacious (3, 4). We believe that incorporating new technology to monitor weight (e.g., cellular-connected smart scales), physical activity (e.g., low-cost accelerometers), and related behaviors will improve dieters' self-regulatory efforts, particularly if combined with frequent feedback and perhaps economic incentives (5). The challenge for health services research will be finding cost-effective methods of delivering this chronic care to the millions of Americans who could benefit from it. A particular strength of the report (1) is its call to bridge the divide between the basic and clinical sciences to further our understanding of the multiple factors, acting alone or in combination, that impair long-term weight control. Several issues were identified; the most important from our perspective was individual variability. In all weight loss trials, whether behavioral, dietary, exercise, or pharmacological, some individuals lose a great deal of weight, others the average amount, and some even gain weight. Adherence to the program is one variable; physiological adaptation of “counter-regulatory” mechanisms that stop further weight loss and enhance regain, along with individual variability, accounts for much of these differences. The report (1) says that we need to “individualize interventions or target specific populations with evidence-based strategies.” Given the wide individual variability in response to treatments, how do you get to “evidence-based population strategies” at this time? We think “individualized” strategies are more promising. Some guidance comes from genetic examination of data from the POUNDS Lost study which compared 20% and 40% fat and 15% and 25% protein diets and found identical weight loss for each diet (6). With each diet there was wide individual variability, with some people losing over 20 kg and others actually gaining weight on the diets. Several potentially predictive genes from this study have been examined including FTO, GIPR, TCF7L2, NPY, IRS-1, CRY2, MTNR1B, LIPC promoter, PPM1K, PCSK7, and APOA5A (7-9). One underlying assumption of the report (1) is that weight loss is possible and beneficial for all. In the Look AHEAD trial, 10% of participants lost on average 1% in the first year, and 25% averaged a weight loss of only 3–4% (10). This suggests that some individuals do not benefit from vigorous weight loss efforts and that we need to understand this group more thoroughly. The report (1) discusses the potential for additional drugs to treat obesity which might be combined with some that already exist. The development of new medications is very expensive, and companies need to recoup their costs. Weight loss with monotherapy has not even reached 10%, and the average is closer to 6–7% (11, 12). This magnitude of weight loss will not attract very many people. If new agents are to appear, some new thinking about drug development may be needed. Studies with leptin pose an interesting challenge. In the rare people born without leptin, marked obesity develops. When treated with leptin, their weight returns to “normal” levels. Yet when leptin is given to people born with leptin, they do not respond the same way. Unraveling this conundrum may improve therapeutic options. The use of leptin in weight-reduced individuals appears particularly promising; leptin appears to normalize their marked reductions in non-resting energy that likely contribute to weight regain (2). The report (1) focused specifically on “solutions and strategies that could be implemented at the level of the individual.” This is an essential focus but one that must be complemented by collective societal actions to change the food and activity environments, which currently only exacerbate the long-term struggles that most individuals have with their weight. Thus, as clinicians and researchers, we must also help bridge the divide between individual and collective responsibility for successful long-term weight loss maintenance.

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