Bariatric Surgery — Quick Fix or Long-Term Solution?
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《新英格兰医药杂志》
More than 30 percent of the U.S. population is obese (body-mass index [the weight in kilograms divided by the square of the height in meters], 30 or greater), and 4.9 percent is morbidly obese (body-mass index, 40 or greater).1 The associated risks are substantial. Obese persons have more than 10 times the risk of type 2 diabetes2 and 3 times the risk of coronary heart disease3 of those who are lean, and the risks of these and other coexisting conditions rise with increasing obesity. Mortality increases correspondingly; the risk of death among persons with a body-mass index of 40 or greater is double that among persons who are not overweight.4
Although attempts to lose weight are common, doing so is not easy, and maintaining weight loss is even more difficult. Moderate caloric reduction combined with increased physical activity typically results in 5 to 10 percent reductions in body weight over a six-month period, and these moderate losses are rarely sustained.5 Diets severely restricted in carbohydrates are popular, but in one study such a diet resulted in no weight-loss advantage relative to a conventional diet (involving reduced intake of fat and calories) at one year.6 Very-low-calorie diets (400 to 800 kcal daily) result in more rapid weight loss but are associated with serious potential risks requiring medical supervision, and weight regain is no less likely than it is with more moderate caloric restriction. The currently approved pharmacotherapies, including the anorexiant sibutramine and orlistat (which inhibits dietary-fat absorption), moderately improve weight loss as compared with caloric restriction alone, but estimates of efficacy are confounded by high rates of noncompliance, in part owing to side effects of the medications.5 Furthermore, these medications have not been approved for indefinite use, despite the chronic nature of obesity.
The disappointing results of these approaches have led to a burgeoning interest in bariatric surgery. Commonly performed procedures include Roux-en-Y gastric bypass (whereby a small pouch that is isolated from the rest of the stomach empties into a loop of small intestine), gastric banding, and vertical gastroplasty (both of which involve the creation of a small gastric pouch, which then empties through a narrow outlet to the remainder of the stomach). The number of bariatric surgeries performed in the United States each year has increased by a factor of five during the past seven years, to more than 100,000 procedures in 2003.7 A recent meta-analysis evaluating the effects of these procedures among more than 22,000 patients found that the average loss of excess weight was 61 percent; diabetes mellitus, hypertension, and sleep apnea resolved and dyslipidemia improved in the majority of patients.8 However, the majority of the studies included were uncontrolled case series, and a minority involved more than two years of follow-up. Since some weight is gradually regained over time even after surgically induced weight loss, a crucial question has been what happens in the long term.
In this issue of the Journal, Sj?str?m et al.9 report the results of up to 10 years of follow-up in the Swedish Obese Subjects Study, a large prospective study that included men and women with body-mass indexes of at least 34 and 38, respectively, who underwent bariatric surgery (gastric banding, vertical banded gastroplasty, or gastric bypass) or no surgery. The criteria for surgery in this cohort differed from current U.S. guidelines, which recommend that surgery be considered for patients with a body-mass index of 40 or greater or, if obesity-associated conditions are present, 35 or greater.10 The study was not randomized, because several institutional review boards considered the high postoperative mortality rate initially observed (1 to 5 percent through the 1980s) to preclude randomization. However, an appropriate comparison group of subjects who did not undergo surgery was assembled by computerized matching of such subjects to subjects in the surgery group on the basis of sex, age, and anthropomorphic, metabolic, and psychosocial measures. The current study included 3505 subjects evaluated at 2 years and 1268 evaluated at 10 years. The follow-up rates — 87 percent and 74 percent, respectively, of the initial cohort — compare favorably with the high attrition rates typical of weight-loss studies.
The mean weight losses from baseline in the surgical group were 23 percent at 2 years and 16 percent at 10 years, as compared with weight gains of less than 1 percent and 2 percent, respectively, in the control group. Weight losses were greatest among the patients who underwent gastric bypass. At the 10-year follow-up, "recovery" from diabetes, hypertension, hypertriglyceridemia, and hyperuricemia (but not hypercholesterolemia) was significantly more likely in the surgery group than in the control group; in addition, the new development of diabetes, hypertriglyceridemia, and hyperuricemia was significantly less common in the surgery group. For example, 36 percent of the subjects who underwent surgery had recovered from diabetes at 10 years (as compared with 13 percent of the controls), and 7 percent of those who underwent surgery had newly developed diabetes (as compared with 24 percent of the controls). However, the rates at which these obesity-associated complications were eliminated or avoided were less impressive at 10 years than at 2 years; the temporal changes are probably explained by the regaining of some of the lost weight and the advancing age of the participants. Caloric intake remained lower and physical activity greater in the surgical group than in the control group throughout follow-up, suggesting that a weight-loss advantage among those who underwent surgery is likely to be maintained.
Although these results indicate some loss of the initial benefits of bariatric surgery after 10 years, they nonetheless demonstrate persistent benefits in terms of weight and associated metabolic abnormalities relative to nonsurgical treatment. However, what is not known is whether these benefits translate into reduced rates of myocardial infarction, stroke, and ultimately, death — the primary prespecified end point of this study. The authors indicate that data are currently insufficient to reveal a clear increase or decrease in overall mortality and provide no data on the rates of cardiovascular disease.
Although the risk of death is clearly higher among obese persons than among those who are not obese, randomized trials demonstrating that weight loss reduces this risk are lacking. In several observational studies, mortality rates among obese persons who have lost weight (through nonsurgical means) have not been lower — and in some cases have been higher — than among those who have not lost weight.11 (Hu et al.,12 in an article elsewhere in this issue of the Journal, likewise report no apparent reduction in mortality with weight loss. However, they emphasize that mortality was lowest among the subjects who were lean and physically active and note that even modest weight gain in adulthood increased the risk of death, independently of the physical-activity level.) The lack of an observed reduction in mortality with weight reduction has been attributed to confounding factors, such as underlying disease that causes the weight loss, or to adverse effects of repeated loss and gain of weight (weight cycling).13 An analysis limited to persons who intended to lose weight suggested that they had a lower mortality rate than persons who were not trying to lose weight, but there was no relationship between the amount of weight lost and the magnitude of benefit.14 A recent study found a lower mortality rate among patients who underwent bariatric surgery15 than among obese persons who did not, but the control group was not well matched, and confounding was likely.
Pending the availability of data on cardiovascular events and mortality after bariatric surgery, decisions regarding the appropriateness of surgery must balance expected benefits with potential risks. In the current report by Sj?str?m et al., the postoperative mortality rate was 0.25 percent. This rate was lower than that at the outset of the study and lower than that reported elsewhere,8 presumably because of a high level of experience at the participating centers. Postoperative complications occurred in 13 percent of the subjects and included infections, bleeding, and thromboembolism. Longer-term complications reported by others (depending on the procedure performed) include stomal stenosis, anastomotic ulcers, nutritional deficiencies, and bowel obstruction.
The demonstration of long-term benefits of bariatric surgery is encouraging but must be viewed in a broad context. The increasing prevalence of obesity not only in adults but also in children and adolescents — indeed, bariatric surgery is now being considered a potential pediatric intervention16 — indicate the urgent need to implement effective preventive interventions, beginning early in life, to improve dietary habits and increase physical activity. Bariatric surgery is currently the most successful approach to "rescuing" patients with severe obesity and reversing or preventing the development of several diseases associated with obesity. It would be an even greater success to make these procedures unnecessary.
References
Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004;291:2847-2850.
Carey VJ, Walters EE, Colditz GA, et al. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women: the Nurses' Health Study. Am J Epidemiol 1997;145:614-619.
Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 1990;322:882-889.
Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999;341:1097-1105.
Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002;346:591-602.
Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003;348:2082-2090.
Steinbrook R. Surgery for severe obesity. N Engl J Med 2004;350:1075-1079.
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724-1737.
Sj?str?m L, Lindroos A-K, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683-2693.
NIH conference: gastrointestinal surgery for severe obesity. Ann Intern Med 1991;115:956-961.
Pamuk ER, Williamson DF, Serdula MK, Madans J, Byers TE. Weight loss and subsequent death in a cohort of U.S. adults. Ann Intern Med 1993;119:744-748.
Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med 2004;351:2694-2703.
Lissner L, Odell PM, D'Agostino RB, et al. Variability of body weight and health outcomes in the Framingham population. N Engl J Med 1991;324:1839-1844.
Gregg EW, Gerzoff RB, Thompson TJ, Williamson DF. Intentional weight loss and death in overweight and obese U.S. adults 35 years of age and older. Ann Intern Med 2003;138:383-389.
Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416-424.
Inge TH, Krebs NF, Garcia VF, et al. Bariatric surgery for severely overweight adolescents: concerns and recommendations. Pediatrics 2004;114:217-223.(Caren G. Solomon, M.D., M)
Although attempts to lose weight are common, doing so is not easy, and maintaining weight loss is even more difficult. Moderate caloric reduction combined with increased physical activity typically results in 5 to 10 percent reductions in body weight over a six-month period, and these moderate losses are rarely sustained.5 Diets severely restricted in carbohydrates are popular, but in one study such a diet resulted in no weight-loss advantage relative to a conventional diet (involving reduced intake of fat and calories) at one year.6 Very-low-calorie diets (400 to 800 kcal daily) result in more rapid weight loss but are associated with serious potential risks requiring medical supervision, and weight regain is no less likely than it is with more moderate caloric restriction. The currently approved pharmacotherapies, including the anorexiant sibutramine and orlistat (which inhibits dietary-fat absorption), moderately improve weight loss as compared with caloric restriction alone, but estimates of efficacy are confounded by high rates of noncompliance, in part owing to side effects of the medications.5 Furthermore, these medications have not been approved for indefinite use, despite the chronic nature of obesity.
The disappointing results of these approaches have led to a burgeoning interest in bariatric surgery. Commonly performed procedures include Roux-en-Y gastric bypass (whereby a small pouch that is isolated from the rest of the stomach empties into a loop of small intestine), gastric banding, and vertical gastroplasty (both of which involve the creation of a small gastric pouch, which then empties through a narrow outlet to the remainder of the stomach). The number of bariatric surgeries performed in the United States each year has increased by a factor of five during the past seven years, to more than 100,000 procedures in 2003.7 A recent meta-analysis evaluating the effects of these procedures among more than 22,000 patients found that the average loss of excess weight was 61 percent; diabetes mellitus, hypertension, and sleep apnea resolved and dyslipidemia improved in the majority of patients.8 However, the majority of the studies included were uncontrolled case series, and a minority involved more than two years of follow-up. Since some weight is gradually regained over time even after surgically induced weight loss, a crucial question has been what happens in the long term.
In this issue of the Journal, Sj?str?m et al.9 report the results of up to 10 years of follow-up in the Swedish Obese Subjects Study, a large prospective study that included men and women with body-mass indexes of at least 34 and 38, respectively, who underwent bariatric surgery (gastric banding, vertical banded gastroplasty, or gastric bypass) or no surgery. The criteria for surgery in this cohort differed from current U.S. guidelines, which recommend that surgery be considered for patients with a body-mass index of 40 or greater or, if obesity-associated conditions are present, 35 or greater.10 The study was not randomized, because several institutional review boards considered the high postoperative mortality rate initially observed (1 to 5 percent through the 1980s) to preclude randomization. However, an appropriate comparison group of subjects who did not undergo surgery was assembled by computerized matching of such subjects to subjects in the surgery group on the basis of sex, age, and anthropomorphic, metabolic, and psychosocial measures. The current study included 3505 subjects evaluated at 2 years and 1268 evaluated at 10 years. The follow-up rates — 87 percent and 74 percent, respectively, of the initial cohort — compare favorably with the high attrition rates typical of weight-loss studies.
The mean weight losses from baseline in the surgical group were 23 percent at 2 years and 16 percent at 10 years, as compared with weight gains of less than 1 percent and 2 percent, respectively, in the control group. Weight losses were greatest among the patients who underwent gastric bypass. At the 10-year follow-up, "recovery" from diabetes, hypertension, hypertriglyceridemia, and hyperuricemia (but not hypercholesterolemia) was significantly more likely in the surgery group than in the control group; in addition, the new development of diabetes, hypertriglyceridemia, and hyperuricemia was significantly less common in the surgery group. For example, 36 percent of the subjects who underwent surgery had recovered from diabetes at 10 years (as compared with 13 percent of the controls), and 7 percent of those who underwent surgery had newly developed diabetes (as compared with 24 percent of the controls). However, the rates at which these obesity-associated complications were eliminated or avoided were less impressive at 10 years than at 2 years; the temporal changes are probably explained by the regaining of some of the lost weight and the advancing age of the participants. Caloric intake remained lower and physical activity greater in the surgical group than in the control group throughout follow-up, suggesting that a weight-loss advantage among those who underwent surgery is likely to be maintained.
Although these results indicate some loss of the initial benefits of bariatric surgery after 10 years, they nonetheless demonstrate persistent benefits in terms of weight and associated metabolic abnormalities relative to nonsurgical treatment. However, what is not known is whether these benefits translate into reduced rates of myocardial infarction, stroke, and ultimately, death — the primary prespecified end point of this study. The authors indicate that data are currently insufficient to reveal a clear increase or decrease in overall mortality and provide no data on the rates of cardiovascular disease.
Although the risk of death is clearly higher among obese persons than among those who are not obese, randomized trials demonstrating that weight loss reduces this risk are lacking. In several observational studies, mortality rates among obese persons who have lost weight (through nonsurgical means) have not been lower — and in some cases have been higher — than among those who have not lost weight.11 (Hu et al.,12 in an article elsewhere in this issue of the Journal, likewise report no apparent reduction in mortality with weight loss. However, they emphasize that mortality was lowest among the subjects who were lean and physically active and note that even modest weight gain in adulthood increased the risk of death, independently of the physical-activity level.) The lack of an observed reduction in mortality with weight reduction has been attributed to confounding factors, such as underlying disease that causes the weight loss, or to adverse effects of repeated loss and gain of weight (weight cycling).13 An analysis limited to persons who intended to lose weight suggested that they had a lower mortality rate than persons who were not trying to lose weight, but there was no relationship between the amount of weight lost and the magnitude of benefit.14 A recent study found a lower mortality rate among patients who underwent bariatric surgery15 than among obese persons who did not, but the control group was not well matched, and confounding was likely.
Pending the availability of data on cardiovascular events and mortality after bariatric surgery, decisions regarding the appropriateness of surgery must balance expected benefits with potential risks. In the current report by Sj?str?m et al., the postoperative mortality rate was 0.25 percent. This rate was lower than that at the outset of the study and lower than that reported elsewhere,8 presumably because of a high level of experience at the participating centers. Postoperative complications occurred in 13 percent of the subjects and included infections, bleeding, and thromboembolism. Longer-term complications reported by others (depending on the procedure performed) include stomal stenosis, anastomotic ulcers, nutritional deficiencies, and bowel obstruction.
The demonstration of long-term benefits of bariatric surgery is encouraging but must be viewed in a broad context. The increasing prevalence of obesity not only in adults but also in children and adolescents — indeed, bariatric surgery is now being considered a potential pediatric intervention16 — indicate the urgent need to implement effective preventive interventions, beginning early in life, to improve dietary habits and increase physical activity. Bariatric surgery is currently the most successful approach to "rescuing" patients with severe obesity and reversing or preventing the development of several diseases associated with obesity. It would be an even greater success to make these procedures unnecessary.
References
Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004;291:2847-2850.
Carey VJ, Walters EE, Colditz GA, et al. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women: the Nurses' Health Study. Am J Epidemiol 1997;145:614-619.
Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 1990;322:882-889.
Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med 1999;341:1097-1105.
Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002;346:591-602.
Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003;348:2082-2090.
Steinbrook R. Surgery for severe obesity. N Engl J Med 2004;350:1075-1079.
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724-1737.
Sj?str?m L, Lindroos A-K, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683-2693.
NIH conference: gastrointestinal surgery for severe obesity. Ann Intern Med 1991;115:956-961.
Pamuk ER, Williamson DF, Serdula MK, Madans J, Byers TE. Weight loss and subsequent death in a cohort of U.S. adults. Ann Intern Med 1993;119:744-748.
Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med 2004;351:2694-2703.
Lissner L, Odell PM, D'Agostino RB, et al. Variability of body weight and health outcomes in the Framingham population. N Engl J Med 1991;324:1839-1844.
Gregg EW, Gerzoff RB, Thompson TJ, Williamson DF. Intentional weight loss and death in overweight and obese U.S. adults 35 years of age and older. Ann Intern Med 2003;138:383-389.
Christou NV, Sampalis JS, Liberman M, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416-424.
Inge TH, Krebs NF, Garcia VF, et al. Bariatric surgery for severely overweight adolescents: concerns and recommendations. Pediatrics 2004;114:217-223.(Caren G. Solomon, M.D., M)