Weight Loss and Mortality
A number of studies of “generic weight loss” (cause of weight loss unknown), “weight cycling” (cycles of weight loss followed by weight regain), and mortality have been published. In most, but not all, of these studies, generic weight loss and weight cycling are associated with increases in mortality. None of these studies, however, differentiated between intentional and unintentional weight loss. With the exception of the studies below, very little is currently known about factors related to intentional and unintentional weight loss in the general population or about the relationship between weight loss intention and mortality.
Two studies of factors related to weight loss intention have been carried out in the general population: French and colleagues assessed correlates of intentional and unintentional weight loss of > 20 lb in the Iowa Women’s Health Study, a cohort study of approximately 29,000 women with a mean age of about 65 years; and Meltzer and Everhart analyzed data on 1-year self-reported weight change from approximately 9,000 participants in the nationally representative U.S. National Health Interview Survey, aged 45 years and above. The results of these two studies suggest the following:
- In cross-sectional studies of weight loss recall, heavier persons are more likely to report intentional weight loss than unintentional weight loss, while the reverse is true for leaner persons;
- Intentional and unintentional weight losses occur with similar frequency in the U.S. population and contribute similarly to long-term weight fluctuation;
- The frequency of intentional weight loss is lower at older ages, while the frequency of unintentional weight loss is higher at older ages; and
- Unintentional weight loss occurs more often in persons who report that their health status is poor, who use medications for chronic health conditions, and who smoke.
To date, only three studies have examined the relationship between intentional weight loss and mortality. Singh and colleagues published results from a 1-year randomized controlled trial of a “cardio protective diet” in East Indian patients hospitalized with recent myocardial infarction (mean age 50 years, mean BMI about 24 kg/m2 ). Although this study was not designed to specifically test the efficacy of intentional weight loss on lower mortality, the authors found that those who lost at least 0.5 kg (1.1 lb) had a 50 percent lower incidence of cardiac events and a 54 percent lower risk of overall mortality compared with counterparts who lost < 0.5 kg (1.1 lb). 317
Williamson and colleagues published a 12-year prospective observational study of weight loss and mortality that directly assessed weight loss intention. They analyzed data from 43,457 overweight (BMI > 27), never-smoking, white women ages 40 to 64 years. Mortality ratios were compared for women who intentionally lost weight with those for women who had no change in weight. In women with obesity-related comorbidities, intentional weight loss of any amount was associated with a statistically significant 20 percent reduction in all-cause mortality, primarily due to a significant 40 to 50 percent reduction in mortality from obesity-related cancers; diabetes-related mortality was also significantly reduced by 30 to 40 percent in those who intentionally lost weight. In women with no comorbidities, intentional weight loss was generally unrelated to mortality; however, after subdividing intentional weight loss by time interval, it was found that a loss of at least 20 lb that occurred within the previous year was associated with small to modest increases in mortality. The authors concluded that the association between intentional weight loss and longevity in middle age overweight women depends on health status. In addition, preliminary evidence suggests that intentional weight loss in middle-age overweight men may be associated with a similar reduction of diabetes-related mortality as was observed in the overweight women.
The ongoing Swedish Obesity Study is a controlled trial of surgically induced weight loss and subsequent morbidity and mortality over a 10-year follow-up period (1,006 participants aged 37 to 57 years; initial BMI of 34 in men and 38in women). Although the study is not randomized (participants self-select for surgery), the controls (who receive a behavioral weight loss program) are computer-matched to surgical participants on a large number of potential confounders including weight. In a preliminary abstract, the study reported the 2-year incidence rates. These results for disease and risk factor incidences suggest that 10-year mortality will ultimately be lower in the surgical intervention group. Definitive mortality results have not been reported to date.
ENVIRONMENT
The environment is a major determinant of overweight and obesity. Environmental influences on overweight and obesity are primarily related to food intake and physical activity behaviors. In countries like the United States, there is an overall abundance of palatable, calorie-dense food. In addition, aggressive and sophisticated food marketing in the mass media, supermarkets, and restaurants, and the large portions of food served outside the home, promote high calorie consumption. Many of our sociocultural traditions promote overeating and the preferential consumption of high calorie foods.
For many people, even when caloric intake isnot above the recommended level, the number of calories expended in physical activity is insufficient to offset consumption. Mechanization limits the necessity of physical activity required to function in society. Many people are entrenched in sedentary daily routines consisting of sitting at work, sitting in traffic, and sitting in front of a television or a computer monitor for most of their waking hours. In this obesity-promoting environment, individual attitudes and behaviors are critical in weight management. Many individuals may need extended treatment in clinical or community settings to enable them to cope with the complexities of long-term weight management, especially if there is a history of unsuccessful attempts at self-treatment. When the typical daily routine is so strongly biased towards promoting and perpetuating overweight and obesity, very high levels of knowledge, motivation, personal behavioral management skill, and lifestyle flexibility are required for an overweight or obesity-prone individual to avoid becoming overweight, or progressing to moderate or severe obesity.
Although there are undoubtedly some inter- and intrapopulation variations in the genetic predisposition to become overweight or obese, several lines of evidence suggest that genetic factors alone cannot explain the demographic and ethnic variations in overweight and obesity prevalence. For example, there is a difference in obesity prevalence among low- and high-income white women in industrialized societies. Other studies of populations, including migration studies, have shown an increase in average body weight in those who move from a traditional to a Westernized environment. Culturally determined attitudes about food, physical activity, and factors that vary with income, education, and occupation may increase the level of difficulty in weight management.
Body image concerns and other motivations for avoiding obesity or controlling weight within given limits also vary with ethnic background, age, socioeconomic status, and gender. Thus, the competence of practitioners in working with diverse sociocultural perspectives can be a critical factor in the success of obesity treatment.
GENETIC INFLUENCE IN THE DEVELOPMENT OF OVERWEIGHT AND OBESITY
Obesity is a complex multifactorial chronic disease developing from interactive influences of numerous factors-social, behavioral, physiological, metabolic, cellular, and molecular. Genetic influences are difficult to elucidate and identification of the genes is not easily achieved in familial or pedigree studies. Furthermore, whatever the influence the genotype has on the etiology of obesity, it is generally attenuated or exacerbated by nongenetic factors. A large number of twin, adoption, and family studies have explored the level of heritability of obesity; that is, the fraction of the population variation in a trait (e.g., BMI) that can be explained by genetic transmission. Recent studies of individuals with a wide range of BMIs, together with information obtained on their parents, siblings, and spouses, suggest that about to 40 percent of the individual differences in body mass or body fat may depend on genetic factors. However, studies with identical twins reared apart suggest that the genetic contribution to BMI may be higher, i.e., about 70 percent. There are several other studies of monozygotic twins reared apart that yielded remarkably consistent results. Some of the reasons behind the different results obtained from twin versus family studies have been reported. The relative risk of obesity for first-degree relatives of overweight, moderately obese, or severely obese persons in comparison to the population prevalence of the condition reaches about 2 for overweight, 3 to 4 for moderate obesity, and 5 and more for more severe obesity.
Support for a role of specific genes in human obesity or body fat content has been obtained from studies of Mendelian disorders with obesity as one of the clinical features, single-gene rodent models, quantitative trait loci from crossbreeding experiments, association studies, and linkage studies. From the research currently available, several genes seem to have the capacity to cause obesity or to increase the likelihood of becoming obese. The rodent obesity gene for leptin, a natural appetite-suppressant hormone, has been cloned as has been its receptor. In addition, other single gene mutants have been cloned. However, their relationship to human disease has not been established, except for one study describing two subjects with a leptin mutation.
This suggests that for most cases of human obesity, susceptibility genotypes may result from variations of several genes.
Severely or morbidly obese persons are, on the average, about 10 to 12 BMI units heavier than their parents and siblings. Several studies have reported that a single major gene for high body mass was transmitted from the parents to their children. The trend implies that a major recessive gene, accounting for about 20 to 25 percent of the variance, is influenced by age and has a frequency of about 0.2 to 0.3. However, no gene(s) has (have) yet been identified. Evidence from several studies has shown that some persons are more susceptible to either weight gain or weight loss than others. It is important for the practitioner to recognize that the phenomenon of weight gain cannot always be attributed to lack of adherence to prescribed treatment regimens.
