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Review |

Bariatric Surgery:  A Systematic Review and Meta-analysis FREE

Henry Buchwald, MD, PhD; Yoav Avidor, MD; Eugene Braunwald, MD; Michael D. Jensen, MD; Walter Pories, MD; Kyle Fahrbach, PhD; Karen Schoelles, MD
[+] Author Affiliations

Author Affiliations: Department of Surgery, University of Minnesota, Minneapolis (Dr Buchwald); Ethicon Endo-Surgery Inc, a Johnson & Johnson company, Cincinnati, Ohio (Dr Avidor); Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (Dr Braunwald); Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minn (Dr Jensen); Department of Surgery, East Carolina University School of Medicine, Greenville, NC (Dr Pories); and MetaWorks Inc, Medford, Mass (Drs Fahrbach and Schoelles).

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JAMA. 2004;292(14):1724-1737. doi:10.1001/jama.292.14.1724.
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Published online

Context About 5% of the US population is morbidly obese. This disease remains largely refractory to diet and drug therapy, but generally responds well to bariatric surgery.

Objective To determine the impact of bariatric surgery on weight loss, operative mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea).

Data Sources and Study Selection Electronic literature search of MEDLINE, Current Contents, and the Cochrane Library databases plus manual reference checks of all articles on bariatric surgery published in the English language between 1990 and 2003. Two levels of screening were used on 2738 citations.

Data Extraction A total of 136 fully extracted studies, which included 91 overlapping patient populations (kin studies), were included for a total of 22 094 patients. Nineteen percent of the patients were men and 72.6% were women, with a mean age of 39 years (range, 16-64 years). Sex was not reported for 1537 patients (8%). The baseline mean body mass index for 16 944 patients was 46.9 (range, 32.3-68.8).

Data Synthesis A random effects model was used in the meta-analysis. The mean (95% confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%) for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding; 61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and 70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative mortality (≤30 days) in the extracted studies was 0.1% for the purely restrictive procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch. Diabetes was completely resolved in 76.8% of patients and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more of patients. Hypertension was resolved in 61.7% of patients and resolved or improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients and was resolved or improved in 83.6% of patients.

Conclusions Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.

Figures in this Article

The world epidemic of overweight (body mass index [BMI], calculated as weight in kilograms divided by the square of the height in meters, ≥25) and obesity (BMI ≥30) is estimated to encompass about 1.7 billion individuals,13 and the percentage of overweight adults is highest in the United States.47 Approximately two thirds of individuals living in the United States are overweight, and of those, almost half are obese.7 The BMI subgroups experiencing the most rapid growth are 35 or higher (23 million) and 40 or higher (8 million).8,9

The rise in the prevalence of obesity is associated with increases in the prevalence of obesity comorbidities (eg, type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, back and lower extremity weight-bearing degenerative problems, several forms of cancer, depression, etc).1012 These comorbidities are responsible for more than 2.5 million deaths per year worldwide.10 The loss of life expectancy due to obesity is profound—in comparison with a normal-weight individual, a 25-year-old morbidly obese man has a 22% reduction in expected remaining lifespan, representing an approximate loss of 12 years of life.13

Unfortunately, diet therapy, with and without support organizations, is relatively ineffective in treating obesity in the long term.14,15 There are currently no truly effective pharmaceutical agents to treat obesity, especially morbid obesity.14,15 In 1991, the National Institutes of Health established guidelines for the surgical therapy of morbid obesity (BMI ≥40 or BMI ≥35 in the presence of significant comorbidities), now referred to as bariatric surgery.16

The literature on postoperative weight loss and the problems associated with various bariatric surgical procedures is extensive and has been summarized elsewhere.17 The literature with respect to comorbidity outcomes of bariatric surgery is also extensive, but has not been systematically reviewed and subjected to meta-analysis. We have conducted a systematic review of published observational and interventional trials that focus on bariatric surgery. The subsequent meta-analysis has concentrated on the impact of bariatric surgery on 4 selected obesity comorbidities: diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea. For consistency, meta-analyses of weight loss outcomes were confined to the studies qualifying for the categories selected for assessment.

We used a comprehensive and current database to catalog the bariatric surgery literature. The catalog was developed as an online, navigable research adjunct. The evidence database for the catalog was assembled using established systematic review methods.18,19

The main objectives of this study were to analyze the impact of bariatric surgery on diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea, as well as on health care economics and disease impact; to analyze weight reduction efficacy outcomes in the studies selected for the comorbid conditions; and to summarize operative mortality outcomes.

Data Sources

A broad search of the English-language literature was performed incorporating both electronic and manual components. The electronic search was performed using MEDLINE, Current Contents, and the Cochrane Library databases. MEDLINE (1990-2003, cutoff date June 5, 2003) was searched using the following search terms: obesity/surgery,gastric bypass, gastroplasty, bariatric, gastric banding, “anastomosis, Roux-en-Y,” biliopancreatic diversion (including duodenal switch), or jejunoileal bypass. Prior to 1990, the literature offered little to no clinical data on the impact of bariatric surgery weight loss on diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea. The complete bibliography of accepted and rejected studies is available by request to the corresponding author.

Two strategies were used to identify recently published articles that may not have been indexed on MEDLINE by the search cutoff date. First, a search was performed that included a keyword search for the prior 6 months with no limit. Next, Current Contents was searched for the prior year using an analogous approach. Finally, manual reference checks of accepted papers in recent reviews (within the past 2 years) were performed to supplement the above electronic searches. The cutoff date for the retrieval of articles from libraries was July 2003.

Literature Screening and Catalog Construction

Study selection was accomplished through 2 levels of study screening. At level 1 screening, abstracts were reviewed for the following exclusion criteria: publication of abstracts only, case reports, letters, comments, and reviews; animal or in vitro studies; fewer than 10 patients in the study; follow-up of less than 30 days; languages other than English; no surgical intervention for obesity; and intragastric balloon therapy (experimental device).

Full articles were then obtained for all studies accepted at level 1 and for any citations for which a determination could not be made from the abstract. For level 2 screening, inclusion required that the studies dealt with at least 1 of the following categories of information: surgical outcomes (including efficacy and/or safety), guidelines, health care economics, or disease impact (utilization [eg, hospital length of stay for bariatric surgery and readmissions] and quality of life).

Study Selection for Data Extraction

For inclusion in the subset of studies for data extraction, the screened studies had to report outcomes for one or more of the following comorbid conditions: diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea, or on health care economics. Extracted studies could be of any design, published from 1990 to 2003, and had to have enrolled at least 10 patients undergoing bariatric surgery. All outcomes were preferentially extracted at the time points for which the comorbidity outcomes were available or the latest time point available for follow-up of at least 50% of the population. In studies reporting morbidity improvement, an effort was made to determine both the number of patients evaluated and the time point of evaluation. In some studies, however, the number of patients with a condition at baseline was the only denominator available. Time points for comorbidity improvement were imputed for some studies based on the time point at which other outcomes were reported (principally weight loss). Kin relationships, defined as multiple publications describing the same or overlapping series of patients, were identified and entered into our catalog only once to avoid the double counting of patients.

Definitions

Surgical Procedures. Surgical procedures were grouped into the following categories: gastric banding (including adjustable and nonadjustable bands), gastric bypass (principally Roux-en-Y variations), gastroplasty (principally vertical banded gastroplasty), biliopancreatic diversion or duodenal switch (including a variety of modifications), and mixed and other (biliary intestinal bypass, ileogastrostomy, jejunoileal bypass, and unspecified bariatric). Procedures that included a gastric bypass component (eg, gastroplasty with gastric bypass, biliopancreatic diversion with gastric bypass, and banding with gastric bypass) were classified as gastric bypass surgery. The history and evolution of the procedures discussed, by open and laparoscopic techniques, have been described.20

Results are reported individually for gastric banding, gastric bypass, gastroplasty, and biliopancreatic diversion or duodenal switch procedure groups, as well as for the total population, which included gastric banding, gastric bypass, gastroplasty, and biliopancreatic diversion or duodenal switch, plus mixed groups and other less common bariatric surgery procedures (biliary intestinal bypass, ileogastrostomy, jejunoileal bypass, and unspecified bariatric surgery).

Resolved and Resolved or Improved. Outcomes of the selected comorbidities were grouped into categories of resolved and resolved or improved. For the calculation of the percentage resolved, we included those studies reporting the number of patients in which comorbid conditions disappeared or no longer required therapy. We preferentially extracted the number of patients evaluated as the denominator wherever possible. For the calculation of the percentage resolved or improved, we included studies reporting numbers of patients in both of these 2 categories (in which case, the 2 were summed), as well as studies that only used the term improved, but not the studies reporting only resolution. Consequently, the percentage resolved or improved may be lower than the percentage deemed resolved due to different study cohorts and, therefore, different denominators for the percentage calculations. Improved in lipid disorders was defined as normalization of laboratory values or the reduction or discontinuation of medical therapy.

Weight Loss. Weight loss is reported as the mean percentage of excess weight loss, which is the standard in the bariatric surgery nomenclature. This calculation is derived from the formula: percentage of excess weight loss = (weight loss/excess weight) × 100, where excess weight = total preoperative weight – ideal weight. Changes in absolute weight (kilograms), BMI, and percentage of initial weight are also reported when appropriate.

Safety Data. Operative mortality (≤30 days) is reported. Complication rates were difficult to catalog because they were variably reported, dependent on duration of follow-up, and were procedure specific, as well as a function of open compared with laparoscopic technique. They are not included in this article.

Statistical Analysis

Analyses were performed only on the data from the studies in the data extraction subset. Study, patient, and treatment-level data were summarized using basic descriptive statistics (simple counts and means). The number of patients enrolled or randomized was used in the calculation of study and patient demographics.

Efficacy outcomes of interest were synthesized via meta-analytic pooling of similar surgery group results across studies with stratification by the type of surgery. In addition, meta-analysis of within-study surgery effects on weight loss and diabetes-related outcomes were stratified by studies with extractable outcomes for a general population compared with subgroups of patients with diabetes or impaired glucose tolerance.

Meta-analyses of all efficacy outcomes were conducted using a random-effects model, estimated by using the restricted maximum likelihood method.21,22 Efficacy outcomes included both proportions (eg, response rates) and raw mean before and after changes (eg, absolute weight changes). The random-effects model meta-analyses take into account both study sample size and the estimate of between-study variation (ie, study heterogeneity) when weighting study effects. Meta-analytic means and mean changes are expressed with 95% confidence intervals (CIs).

Weighted means (ie, weighting results by sample size) were calculated for all studies for a given outcome to provide a non–meta-analytic comparison for each result. A drawback of the weighted means analysis is that it ignores between-study variations, providing a result similar to that found by a fixed-effects analysis. There are, however, positive aspects of the use of weighted means. In the analysis of continuous data, some outcomes had exceedingly wide fluctuations in within-study variation, allowing certain studies of the same size to be weighted quite differently.

All calculations were performed using SAS (version 8.1, SAS Institute Inc, Cary, NC) and SPSS (version 11.0, SPSS Inc, Chicago, Ill) statistical software.

Data Retrieval

A flow diagram outlining the systematic review process is provided (Figure). The initial literature review identified 2738 citations for screening. Of these, 1772 were rejected after reviewing the abstracts and 5 publications could not be retrieved prior to the retrieval cutoff date of July 18, 2003. Of the remaining 961 articles, 253 did not meet inclusion criteria for the catalog, and 572 studies met inclusion criteria only for the catalog but not for further analysis. Therefore, 136 fully extracted primary studies (for which there were 91 “kin” or linked publications) were available for meta-analysis.

Figure. Study Attrition Diagram
Graphic Jump Location

Asterisk indicates 2 health care economics studies without efficacy or safety data are included in the 136 primary studies.

Decisions about relationships among publications were made to maximize information on the comorbidities of interest without double counting patients. Several important studies had numerous kin publications. Outcomes of interest were typically presented in the more recently published articles in which longer periods of follow-up were reported for some or all of the patients. On the other hand, in some large studies only small subgroups of patients with outcomes relevant to the comorbidities of interest were reported and these articles were again dealt with to avoid counting patients more than once.

There were a total of 136 studies, within which there were 179 treatment groups and 22 094 patients either enrolled or analyzable in the data set, including those in comparator control groups. Health care economic outcomes were varied and not amenable to meta-analysis. We did, however, include the weight loss efficacy and operative mortality data from those studies in these respective analyses.

Study Characteristics

After excluding 2 health care economics studies with no weight loss or mortality data, 134 studies were extracted. Fifty-six of the extracted studies were based in North America, 58 in Europe, and 20 were conducted in other locations throughout the world (Australia, New Zealand, South America, Japan, Israel, Saudi Arabia, and Taiwan) (Table 1 and Table 2). Included were 5 randomized controlled trials, 28 nonrandomized controlled trials or series with comparison groups, and 101 uncontrolled case series. The majority of studies were conducted at single centers (n = 126) and only a few were multicenter studies (n = 5). At least 1 categorical outcome of interest (eg, proportion of patients with resolution or improvement in diabetes, hyperlipidemia, hypertension, or obstructive sleep apnea) or 1 continuous outcome of interest (change in a laboratory or physiological measure) was reported by each of the extracted studies.

Table Graphic Jump LocationTable 1. Characteristics of Total Population and Gastric Banding and Gastric Bypass Studies*
Table Graphic Jump LocationTable 2. Characteristics of Gastroplasty and Biliopancreatic Diversion or Duodenal Switch Studies*
Patient Characteristics

In studies reporting sex (150 treatment groups), 19.4% (n = 3769) of patients were men and 72.6% (n = 14 082) were women (Table 3). Sex was not reported for 1537 patients (8%). The overall mean age was 38.97 years (range, 16.20-63.60 years) in studies for which this was reported. The BMI for 16 944 patients at baseline was 46.85 (range, 32.30-68.80). Patient characteristics such as mean age and BMI at baseline were relatively similar across surgical procedure types.

Weight Loss

Given the emphasis on comorbidities, weight loss efficacy outcomes were preferentially extracted at time points for which comorbidity changes were reported. In addition, whenever possible, outcome time points representing at least 50% of the patient population undergoing surgery were used.

Substantial weight reduction was observed in this study set by both meta-analytic techniques and simple pooling across studies using weighted means (Table 4). The mean (95% CI) percentage of excess weight loss by meta-analysis at the outcome time point for which comorbidities were assessed was 47.5% (40.7%-54.2%) for gastric banding, 61.6% (56.7%-66.5%) for gastric bypass, 68.2% (61.5%-74.8%) for gastroplasty, and 70.1% (66.3%-73.9%) for biliopancreatic diversion or duodenal switch. The overall percentage of excess weight loss for 10 172 patients for all surgery types was 61.2% (95% CI, 58.1%-64.4%). Although less common, weight loss outcomes were also reported as a decrease in BMI (mean [95% CI], 14.2 [13.3-15.1] in 8232 patients) and a decrease in absolute weight (mean [95% CI], 39.7 kg [37.2-42.2 kg] in 7588 patients). In most cases, weight loss outcomes did not differ significantly for assessments at 2 years or less compared with those at more than 2 years. All of the weight loss reductions reported in Table 4 are significant at the P<.001 level.

Table Graphic Jump LocationTable 4. Efficacy Outcomes for Weight Reduction*
Operative Mortality

Operative mortality—mortality at 30 or less days—was 0.1% for the purely restrictive procedures (2297 patients undergoing banding and 749 patients undergoing gastroplasty), 0.5% in 5644 patients undergoing gastric bypass procedures, and 1.1% in 3030 patients undergoing biliopancreatic diversion or duodenal switch procedures.

Comorbidity Outcomes

Diabetes. When defined as the ability to discontinue all diabetes-related medications and maintain blood glucose levels within the normal range, strong evidence for improvement in type 2 diabetes and impaired glucose tolerance was found across all the surgery types. Within studies reporting resolution of diabetes, 1417 (76.8% [meta-analytic mean, 76.8%; 95% CI, 70.7%-82.9%]) of 1846 patients experienced complete resolution. Within studies reporting both resolution and improvement or only improvement of diabetes, 414 (85.4% [meta-analytic mean, 86.0%; 95% CI, 78.4%-93.7%]) of 485 patients experienced resolution or improvement of diabetes. The changes in glycosylated hemoglobin (HbA1c), fasting glucose, and fasting insulin are also reported in Table 5 and Table 6.

Table Graphic Jump LocationTable 5. Efficacy for Improvement in Diabetes-Related Outcomes for All Patients
Table Graphic Jump LocationTable 6. Efficacy for Improvement in Diabetes-Related Outcomes for Diabetic and Glucose-Intolerant Patients*

In patients selected for diabetes or impaired glucose tolerance at baseline, the mean change in percentage of excess weight loss was 57.25% (95% CI, 46.21%-68.30%) and the reduction in the BMI was 14.03 (95% CI, 10.77-17.30), both of which are close to the values for unselected populations. Reductions in HbA1c and fasting glucose levels were much greater in groups selected for baseline diabetes or impaired glucose tolerance. The reduction in fasting glucose levels was significantly different for the total diabetic population (mean change, 71.53 mg/dL; 95% CI, 49.37-93.69 mg/dL [3.97 mmol/L; 95% CI, 2.74-5.20 mmol/L]; n = 296 by meta-analysis) compared with unselected populations (mean change, 13.33 mg/dL; 95% CI, 10.81-15.86 mg/dL [0.74 mmol/L; 95% CI, 0.60-0.88 mmol/L]; n = 2092 by meta-analysis).

There was a difference in diabetes outcomes analyzed according to the 4 categories of operative procedures. With respect to diabetes resolution, there was a gradation of effect from 98.9% (95% CI, 96.8%-100%) for biliopancreatic diversion or duodenal switch to 83.7% (95% CI, 77.3%-90.1%) for gastric bypass to 71.6% (95% CI, 55.1%-88.2%) for gastroplasty, and to 47.9% (95% CI, 29.1%-66.7%) for gastric banding. The percentage of patients with diabetes resolved or improved showed different results (Table 5); this variation from the trend solely for diabetes resolved may be due to the far greater number of patients assessed for this variable (n = 1846) compared with the number assessed for the combined variable (n = 485) in the total population.

Hyperlipidemia. By both meta-analysis and by weighted means, the outcome categories of hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia were significantly improved across all surgical procedures (including the mixed and other bariatric surgery groups; Table 7). The percentage of patients improved was typically 70% or higher, with some variation as a function of the measure used and the procedure performed. The maximum improvements in hyperlipidemia by meta-analysis occurred with the biliopancreatic diversion or duodenal switch procedure (99.1%; 95% CI, 97.6%-100%) and with gastric bypass (96.9%; 95% CI, 93.6%-100%).

Table Graphic Jump LocationTable 7. Efficacy for Improvement in Hyperlipidemia by Surgical Procedure

In the total population, meta-analysis of the continuous measures demonstrated a significant decrease in total cholesterol level (mean change, 33.20 mg/dL; 95% CI, 23.17-43.63 mg/dL [0.86 mmol/L; 95% CI, 0.60-1.13 mmol/L]; n = 2573), low-density lipoprotein cholesterol level (mean change, 29.34 mg/dL; 95% CI, 17.76-40.93 mg/dL [0.76 mmol/L; 95% CI, 0.46-1.06 mmol/L]; n = 879), and level of triglycerides (mean change, 79.65 mg/dL; 95% CI, 64.60-95.58 mg/dL [0.90 mmol/L; 95% CI, 0.73-1.08 mmol/L]; n = 2149). While there was not a significant increase in high-density lipoprotein cholesterol level in the total population, significant improvements were seen with gastric banding (mean change, 4.63 mg/dL; 95% CI, 1.54-7.72 mg/dL [0.12 mmol/L; 95% CI 0.04-0.20 mmol/L]; n = 623) and with gastroplasty (mean change, 5.02 mg/dL; 95% CI, 0.77-9.27 mg/dL [0.13 mmol/L; 95% CI, 0.02-0.24 mmol/L]; n = 253).

Hypertension. By both meta-analysis and by weighted proportions, hypertension significantly improved in the total patient population and across all surgical procedures (Table 8). The percentage of patients in the total population whose hypertension resolved was 61.7% (95% CI, 55.6%-67.8%). The percentage of patients in the total population whose hypertension resolved or improved was 78.5% (95% CI, 70.8%-86.1%). The rank order of efficacy among the surgical groups was variable for both resolution and resolution or improvement.

Table Graphic Jump LocationTable 8. Efficacy for Improvement in Hypertension and Obstructive Sleep Apnea by Surgical Procedure

Obstructive Sleep Apnea. Diagnoses of sleep apnea, sleep-disordered breathing, and pickwickian syndrome were combined as representative of obstructive sleep apnea. By both meta-analysis and by weighted means, the combined outcome category of obstructive sleep apnea was significantly improved in the total patient population group and in each surgical procedure group (Table 8). The percentage of patients in the total population whose obstructive sleep apnea resolved was 85.7% (95% CI, 79.2%-92.2%). The percentage of patients in the total population whose obstructive sleep apnea resolved or improved was 83.6% (95% CI, 71.8%-95.4%).

Evidence for changes in obstructive sleep apnea was primarily available for gastric bypass patients. This was particularly so for the continuous objective variable of apneas or hypopneas per hour (4 available studies), which decreased by 33.85 per hour (95% CI, 17.47-50.23 per hour) in the total population, including 2 gastric bypass groups.

Randomized Controlled Trials

Data from the 5 randomized controlled trials were examined separately for weight loss and, when feasible, for the impact on mortality for 30 or fewer days and the 4 comorbidities (Table 9). These outcomes were within the range of values and the trends found for the overall meta-analysis.

Table Graphic Jump LocationTable 9. Surgical Outcomes for the 5 Randomized Controlled Trials*

Bariatric surgery in morbidly obese individuals reverses, eliminates, or significantly ameliorates diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea. These benefits occur in the majority of patients who undergo surgery.

With respect to type 2 diabetes, more than three quarters of the patients experienced complete resolution of their diabetes following bariatric surgery. Of those patients not experiencing complete resolution, more than half showed demonstrable improvement. Thus, about 85% of patients with diabetes experienced improvement in their diabetes course after bariatric surgery.

A landmark article on bariatric surgery was published in 1995.28 Provocatively titled, “Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus,” this article inspired more than 30 studies demonstrating resolution or marked improvement in type 2 diabetes after bariatric surgery. Two recently published series (after our cut-off date for inclusion) by Schauer et al29 and Sugerman et al30 report almost identical rates of resolution as our meta-analysis, 83% and 86%, respectively. In addition, at 2-year follow-up, a 60% decrease in plasma insulin and a 20% decrease in the plasma glucose were seen in the surgical weight loss group in the Swedish Obesity Subjects study.31 The control group at 2 years had a 3.7-fold higher risk of diabetes onset.

Resolution of diabetes often occurred days following bariatric surgery, even before marked weight loss was achieved.28 Resolution of diabetes was more prevalent following the predominantly malabsorptive procedures (biliopancreatic diversion or duodenal switch) and the mixed malabsorptive/restrictive gastric bypass in contrast to the purely restrictive gastroplasty and gastric banding procedures. In addition, there appeared to be a gradation of diabetes resolution as a function of the operative procedure itself: 98.9% for biliopancreatic diversion or duodenal switch, 83.7% for gastric bypass, 71.6% for gastroplasty, and 47.9% for gastric banding.

The putative extent and time relationships of the different operative procedures to diabetes resolution or improvement after bariatric surgery may be related to some of the changes in the gut-related hormones. The hormonal milieu, or the relative balance of foregut mediators, is differently affected when the distal stomach is bypassed, or a partial gastrectomy is performed, and the enteric contents are separated from the biliopancreatic stream in the upper small intestinal tract. The study of the impact of the various bariatric procedures on leptin, ghrelin, resistin, acylation-stimulating protein, adiponectin, entroglucagon, cholecystokinin, and other gastrointestinal satiety mediators is receiving increasing attention.3236

Current metabolic studies of patients with diabetes undergoing bariatric surgery have shown a recovery of acute insulin response37; significant decreases of inflammatory indicators (C-reactive protein and interleukin 6)38; improvement in insulin sensitivity correlated with increases in plasma adiponectin32,39; significant changes in the enteroglucagon response to glucose40; significant reduction in ghrelin levels following gastric bypass41 but not gastric banding42; and significant improvement in beta cell function following gastric banding.43

Considerable attention recently has focused on the Swedish Obesity Subjects study, in which 2010 patients after gastric bypass, gastroplasty, or gastric banding were compared with 2037 matched-pair controls who underwent conventional nonoperative obesity management. After 2 years, the incidence of hyperlipidemia was lower by 10-fold in the surgical weight loss group compared with the control group.31 Similar findings have been reported by others.4447 In 1990, the Program on the Surgical Control of the Hyperlipidemias reported marked reductions in the levels of total (23%) and low-density lipoprotein cholesterol (38%), in association with increases in high-density lipoprotein cholesterol (4%) after a surgical distal ileal malabsorptive procedure.48 In the current meta-analysis, the improvement in hyperlipidemia also was more prevalent with the malabsorptive procedures.

Resolution or improvement of hypertension by weight reduction is well-known. Even a modest weight loss (eg, 10%) can lower blood pressure significantly. As a generalization, a decrease of 1% in body weight will decrease systolic blood pressure by 1 mm Hg and diastolic blood pressure by 2 mm Hg.4951 The bariatric surgery literature extracted for this analysis is replete with reports of the resolution or improvement in hypertension postoperatively. This reduction in blood pressure, in distinction to the effect of weight loss on type 2 diabetes and hyperlipidemia, seems to be independent of the operative procedure performed.

In the current analysis, improvement in obstructive sleep apnea was dramatic—in the 80% or higher range. The extracted bariatric surgery literature is quite prolific on this subject. In association with the clinical findings, improvements in oxygen saturation, decreases in arterial carbon dioxide, and increases in arterial oxygen content have been demonstrated.52,53 These favorable physiological changes in the blood contents, which in turn affect the neurological pathways and cerebral centers responsible for respiration, are primarily the result of an increase in diaphragmatic excursion. This increase is brought about by a reduction in intra-abdominal pressure after successful bariatric surgery.54,55

Reversal of or marked improvement in diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, and obesity itself, should markedly increase life expectancy. A large, prospective, observational study, which controlled for unintentional weight loss and for smoking, of 43 457 women had a 12-year follow-up and showed that a weight loss of at least 9 kg was associated with a 53% reduction in all obesity-related deaths.56 A growing amount of evidence relates increased longevity with successful bariatric surgery. The Swedish Obesity Subjects study in diabetic patients has shown an 80% decrease in the annual mortality in the surgical weight loss group.31 Specifically, the obese diabetic patients in the surgical group had a 9% mortality at 9 years, whereas, the control group had a 28% mortality, with most deaths related to cardiovascular disease. In a comparable study, MacDonald et al57 reported that diabetic patients treated with an oral hypoglycemic had a 4.5% mortality rate for every 9 years of follow-up compared with a 1% mortality rate in diabetic patients who underwent gastric bypass. Christou et al58 demonstrated that weight-loss surgery in 1035 patients compared with 5746 controls with a 5-year follow-up reduced the relative risk of death by 89% (95% CI, 73%-96%), with an absolute mortality reduction of 5.49% (P<.001).

All therapeutic interventions need to have efficacy balanced against risk. In such an assessment, bariatric surgery does well. The operative 30-day mortality rates of 0.1% for the restrictive procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch compare favorably with the accepted operative mortality rates for other major surgical procedures.

The heterogeneity of the immediate postoperative and long-term morbidity data did not allow for meta-analysis. However, although these data are diverse, operation-specific reports of adverse outcomes are available for gastric banding,5961 gastric bypass,28,30,62 gastroplasty,23,63,64 and biliopancreatic diversion or duodenal switch.6567

Even after accounting for the pain and anxiety of surgery, the inconveniences of dietary restrictions, and possible complications including reoperation, quality of life should improve for the majority of bariatric surgery patients. A weight loss often in excess of 45 kg, relief from fatal comorbid diseases, improved appearance, and improved social and economic opportunities should markedly enhance quality of life and several studies support this contention.6873 The perception of well-being, social function, body self-image, self-confidence, ability to interact with others, and time spent in recreational and physical activities increases after successful bariatric surgery. Productivity and economic opportunities are enhanced, including new employment and more lucrative employment.

In summary, in addition to the effective weight loss achieved by patients undergoing bariatric surgical procedures, a substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement of their comorbid condition.

Corresponding Author: Henry Buchwald, MD, PhD, University of Minnesota, 420 Delaware St SE, MMC 290, Minneapolis, MN 55455 (buchw001@umn.edu).

Author Contributions: Dr Buchwald had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Buchwald, Avidor, Pories, Fahrbach, Schoelles.

Acquisition of data: Buchwald, Avidor, Pories, Schoelles.

Analysis and interpretation of data: Buchwald, Avidor, Braunwald, Jensen, Pories, Fahrbach, Schoelles.

Drafting of the manuscript: Buchwald, Avidor, Pories, Fahrbach.

Critical revision of the manuscript for important intellectual content: Buchwald, Avidor, Braunwald, Jensen, Pories, Schoelles.

Statistical expertise: Buchwald, Fahrbach.

Obtained funding: Avidor.

Administrative, technical, or material support: Buchwald, Avidor, Jensen, Pories, Schoelles.

Study supervision: Buchwald, Avidor, Schoelles.

Funding/Support: Sponsored by Ethicon Endo-Surgery Inc, a Johnson & Johnson Company, Cincinnati, Ohio.

Role of the Sponsor: Ethicon Endo-Surgery Inc, paid for the services of MetaWorks (Medford, Mass). The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Acknowledgment: We thank the following individuals at MetaWorks Inc, who were instrumental in performing the literature search and subsequent preparation of data and meta-analysis: Diana Frame, MEM, Catherine Cella, BA, and Rhonda Estok, RN, CNOR. We also thank Jane Buchwald, MA, MEDWRITE Medical Communications, Minneapolis, Minn, for performing substantive editing of the manuscript.

Deitel M. Overweight and obesity worldwide now estimated to involve 1.7 billion people.  Obes Surg. 2003;13:329-330
PubMed   |  Link to Article
International Obesity Task Force.  Call for obesity review as overweight numbers reach 1.7 billion [press release]. London, England: International Obesity Task Force; March 17, 2003. Available at: http://www.iotf.org/media/iotfmar17.htm. Accessed September 12, 2004
 Worldwatch Institute Web site. Available at: http://www.worldwatch.org. Accessed September 9, 2002
Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994.  Int J Obes Relat Metab Disord. 1998;22:39-47
PubMed   |  Link to Article
Mokdad AH, Serdula MK, Dietz WH, Bowman BS, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991-1998.  JAMA. 1999;282:1519-1522
PubMed   |  Link to Article
Monteforte MJ, Torkelson CM. Bariatric surgery for morbid obesity.  Obes Surg. 2000;10:391-401
PubMed   |  Link to Article
 National Center for Health Statistics NHANES IV Report. Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/obese/obse99.htm Accessed September 9, 2002
Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000.  JAMA. 2002;288:1723-1727
PubMed   |  Link to Article
Sturm R. Increases in clinically severe obesity in the United States, 1986-2000.  Arch Intern Med. 2003;163:2146-2148
PubMed   |  Link to Article
World Health Organization.  World Health Report 2002. Available at: http://www.iotf.org. Accessed January 13, 2004
Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity.  JAMA. 1999;282:1523-1529
PubMed   |  Link to Article
 Overweight, obesity, and health risk: National Task Force on the Prevention and Treatment of Obesity.  Arch Intern Med. 2000;160:898-904
PubMed   |  Link to Article
Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity.  JAMA. 2003;289:187-193
PubMed   |  Link to Article
North American Association for the Study of Obesity and the National Heart, Lung, and Blood Institute.  The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, Md: National Institutes of Health; 2000. NIH publication 00-4084
North American Association for the Study of Obesity (NAASO) and the National Heart.  Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, Md: National Institutes of Health; 1998. NIH publication 98-4083
National Institutes of Health Consensus Development Panel.  Gastrointestinal surgery for severe obesity.  Ann Intern Med1991;115:956-961
Buchwald H. A bariatric surgery algorithm.  Obes Surg. 2002;12:733-746
PubMed   |  Link to Article
Cook DJ, Mulrow CD, Haynes RB. Systematic reviews: synthesis of best evidence for clinical decisions.  Ann Intern Med. 1997;126:376-380
PubMed   |  Link to Article
Mulrow CD, Oxman ADCochrane Collaboration Handbook. Oxford, England: Cochrane Library, Update Software; 1997;issue 1
Buchwald H, Buchwald JN. Evolution of operative procedures for the management of morbid obesity: 1950-2000.  Obes Surg. 2002;12:705-717
PubMed   |  Link to Article
DerSimonian R, Laird N. Meta-analysis in clinical trials.  Control Clin Trials. 1986;7:177-188
PubMed   |  Link to Article
Hedges L, Olkin I. Statistical Methods for Meta-analysis. Orlando, Fla: Academic Press; 1985:230-257
Ashy AR, Merdad AA. A prospective study comparing vertical banded gastroplasty versus laparoscopic adjustable gastric banding in the treatment of morbid and super-obesity.  Int Surg. 1998;83:108-110
PubMed
Hall JC, Watts JM, O'Brien PE.  et al.  Gastric surgery for morbid obesity: the Adelaide Study.  Ann Surg. 1990;211:419-427
PubMed   |  Link to Article
Mingrone G, Greco AV, Giancaterini A, Scarfone A, Castagneto M, Pugeat M. Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery.  Atherosclerosis. 2002;161:455-462
PubMed   |  Link to Article
Nguyen NT, Goldman C, Rosenquist CJ.  et al.  Laparoscopic versus open gastric bypass: a randomized study of outcomes, quality of life, and costs.  Ann Surg. 2001;234:279-289
PubMed   |  Link to Article
Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding.  Int J Obes Relat Metab Disord. 2002;26:193-199
PubMed   |  Link to Article
Pories WJ, Swanson MS, MacDonald KG.  et al.  Who would have thought it? an operation proves to be the most effective therapy for adult-onset diabetes mellitus.  Ann Surg. 1995;222:339-352
PubMed   |  Link to Article
Schauer PR, Burguera B, Ikramuddin S.  et al.  Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.  Ann Surg. 2003;238:467-484
PubMed
Sugerman HJ, Wolfe LG, Sica DA, Clore JN. Diabetes and hypertension in severe obesity and effects of gastric bypass-induced weight loss.  Ann Surg. 2003;237:751-756
PubMed
Sjostrom CD, Lissner L, Wedel H, Sjostrom L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study.  Obes Res. 1999;7:477-484
PubMed   |  Link to Article
Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects.  J Clin Endocrinol Metab. 2003;88:1594-1602
PubMed   |  Link to Article
Yannakoulia M, Yiannakouris N, Blüher S, Matalas AL, Klimis-Zacas D, Mantzoros CS. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans.  J Clin Endocrinol Metab. 2003;88:1730-1736
PubMed   |  Link to Article
Pories WJ, Albrecht RJ. Etiology of type 2 diabetes mellitus: role of the foregut.  World J Surg. 2001;25:527-531
PubMed   |  Link to Article
Hickey MS, Pories WJ, MacDonald KG.  et al.  A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?  Ann Surg. 1998;227:637-644
PubMed   |  Link to Article
Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease.  Ann Surg. 2004;239:1-11
PubMed   |  Link to Article
Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, Alexandrides TK. Restoration of euglycemia and normal acute insulin response in obese subjects with type 2 diabetes following bariatric surgery.  Diabetes. 2003;52:1098-1103
PubMed   |  Link to Article
Kopp HP, Kopp CW, Festa A.  et al.  Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients.  Arterioscler Thromb Vasc Biol. 2003;23:1042-1047
PubMed   |  Link to Article
Geloneze B, Pereira JA, Pareja JC.  et al.  Circulating Concentrations of Adiponectin Increase in Parallel With Enhancement of Insulin Sensitivity During Weight Loss in Humans. Alexandria, Va: American Diabetes Association; 2003. Abstract 1707-P
Kellum JM, Kuemmerle JF, O’Dorisio TM.  et al.  Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty.  Ann Surg. 1990;211:763-770
PubMed   |  Link to Article
Cummings DE, Weigle DS, Frayo RS.  et al.  Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.  N Engl J Med. 2002;346:1623-1630
PubMed   |  Link to Article
Hanusch-Enserer U, Brabant G. Ghrelin concentrations in morbidly obese patients after adjustable gastric banding.  N Engl J Med. 2003;348:2159-2160
PubMed   |  Link to Article
Dixon JB, Dixon AF, O’Brien PE. Improvement in insulin sensitivity and beta-cell function (HOMA) with weight loss in the severely obese.  Diabet Med. 2003;20:127-134
PubMed   |  Link to Article
Brolin RE, Kenler HA, Wilson AC, Kuo PT, Cody RP. Serum lipids after gastric bypass surgery for morbid obesity.  Int J Obes. 1990;14:939-950
PubMed
Buffington CK, Cowan GSM, Hughes TA, Smith H. Significant changes in the lipid-lipoprotein status of premenopausal morbidly obese females following gastric bypass surgery.  Obes Surg. 1994;4:328-335
PubMed   |  Link to Article
Cowan GS Jr, Buffington CK. Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery.  World J Surg. 1998;22:987-992
PubMed   |  Link to Article
Gleysteen JJ. Results of surgery: long-term effects on hyperlipidemia.  Am J Clin Nutr. 1992;55:591S-593S
PubMed
Buchwald H, Varco RL, Matts JP.  et al.  Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: report of the Program on the Surgical Control of the Hyperlipidemias (POSCH).  N Engl J Med. 1990;323:946-955
PubMed   |  Link to Article
Dornfeld LP, Maxwell MH, Waks AU, Schroth P, Tuck ML. Obesity and hypertension: long-term effects of weight reduction on blood pressure.  Int J Obes. 1985;9:381-389
PubMed
Hypertension Prevention Treatment Group.  The Hypertension Prevention Trial: three-year effects of dietary changes on blood pressure.  Arch Intern Med. 1990;150:153-162
PubMed   |  Link to Article
Reisin E, Frohlich ED. Effects of weight reduction on arterial pressure.  J Chronic Dis. 1982;35:887-891
PubMed   |  Link to Article
Rajala R, Partinen M, Sane T, Pelkonen R, Huikuri K, Seppalainen AM. Obstructive sleep apnea syndrome in morbidly obese patients.  J Intern Med. 1991;230:125-129
PubMed   |  Link to Article
Rasheid S, Banasiak M, Gallagher SF.  et al.  Gastric bypass is an effective treatment for obstructive sleep apnea in patients with clinically significant obesity.  Obes Surg. 2003;13:58-61
PubMed   |  Link to Article
Sugerman H, Windsor A, Bessos M, Wolfe L. Intra-abdominal pressure, sagittal abdominal diameter and obesity comorbidity.  J Intern Med. 1997;241:71-79
PubMed   |  Link to Article
Weiner P, Walzman J, Weiner M, Rabner M, Magadle R, Zamir D. Influence of excessive weight loss after gastroplasty for morbid obesity on respiratory muscle performance.  Thorax. 1998;53:39-42
PubMed   |  Link to Article
Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C. Prospective study of intentional weight loss and mortality in never-smoking overweight US white women aged 40-64 years.  Am J Epidemiol. 1995;141:1128-1141
PubMed
MacDonald KG, Long SD, Swanson MS.  et al.  The gastric bypass operation reduces the progression and mortality on non-insulin-dependent diabetes mellitus.  J Gastrointest Surg. 1997;1:213-220
PubMed   |  Link to Article
Christou NV, Sampalis JS, Lieberman M.  et al.  Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients.  Ann Surg. 2004;240:416-423
PubMed   |  Link to Article
Ceelen W, Walder J, Cardon A.  et al.  Surgical treatment of severe obesity with a low-pressure adjustable gastric band: experimental data and clinical results in 625 patients.  Ann Surg. 2003;237:10-16
PubMed   |  Link to Article
O'Brien PE, Dixon JB, Brown W.  et al.  The laparoscopic adjustable gastric band (Lap-Band): a prospective study of medium-term effects on weight, health and quality of life.  Obes Surg. 2002;12:652-660
PubMed   |  Link to Article
Zinzindohoue F, Chevallier JM, Douard R.  et al.  Laparoscopic gastric banding: a minimally invasive surgical treatment for morbid obesity: prospective study of 500 consecutive patients.  Ann Surg. 2003;237:1-9
PubMed   |  Link to Article
Smith SC, Edwards CB, Goodman GN. Changes in diabetic management after Roux-en-Y gastric bypass.  Obes Surg. 1996;6:345-348
PubMed   |  Link to Article
Kalfarentzos F, Dimakopoulos A, Kehagias I, Loukidi A, Mead N. Vertical banded gastroplasty versus standard or distal Roux-en-Y gastric bypass based on specific selection criteria in the morbidly obese: preliminary results.  Obes Surg. 1999;9:433-442
PubMed   |  Link to Article
Nightengale ML, Sarr MG, Kelly KA, Jensen MD, Zinsmeister AR, Palumbo PJ. Prospective evaluation of vertical banded gastroplasty as the primary operation for morbid obesity.  Mayo Clin Proc. 1991;66:773-782
PubMed   |  Link to Article
Hess DS, Hess DW. Biliopancreatic diversion with a duodenal switch.  Obes Surg. 1998;8:267-282
PubMed   |  Link to Article
Marceau P, Hould FS, Simard S.  et al.  Biliopancreatic diversion with duodenal switch.  World J Surg. 1998;22:947-954
PubMed   |  Link to Article
Scopinaro N, Adami GF, Marinari GM.  et al.  Biliopancreatic diversion.  World J Surg. 1998;22:936-946
PubMed   |  Link to Article
Karlsson J, Sjöström L, Sullivan M. Swedish obese subjects (SOS): an intervention study of obesity: two-year follow-up of health-related quality of life (HRQL) and eating behavior after gastric surgery for severe obesity.  Int J Obes Relat Metab Disord. 1998;22:113-126
PubMed   |  Link to Article
Kral JG. The role of surgery in obesity management.  Int J Risk Safety Med. 1995;7:111-120
Rand CS, Macgregor AM. Morbidly obese patients’ perceptions of social discrimination before and after surgery for obesity.  South Med J. 1990;83:1390-1395
PubMed   |  Link to Article
van Gemert WG, Adang EMM, Greve JWM, Soeters PB. Quality of life assessment of morbidly obese patients: effect of weight-reducing surgery.  Am J Clin Nutr. 1998;67:197-201
PubMed
Dymek MP, LeGrange D, Neven K, Alverdy J. Quality of life and psychosocial adjustment in patients after Roux-en-Y gastric bypass: a brief report.  Obes Surg. 2001;11:32-39
PubMed   |  Link to Article
Waters GS, Pories WJ, Swanson MS, Meelheim HD, Flickinger EG, May HJ. Long-term studies of mental health after the Greenville gastric bypass operation for morbid obesity.  Am J Surg. 1991;161:154-157
PubMed   |  Link to Article

Figures

Figure. Study Attrition Diagram
Graphic Jump Location

Asterisk indicates 2 health care economics studies without efficacy or safety data are included in the 136 primary studies.

Tables

Table Graphic Jump LocationTable 1. Characteristics of Total Population and Gastric Banding and Gastric Bypass Studies*
Table Graphic Jump LocationTable 2. Characteristics of Gastroplasty and Biliopancreatic Diversion or Duodenal Switch Studies*
Table Graphic Jump LocationTable 4. Efficacy Outcomes for Weight Reduction*
Table Graphic Jump LocationTable 5. Efficacy for Improvement in Diabetes-Related Outcomes for All Patients
Table Graphic Jump LocationTable 6. Efficacy for Improvement in Diabetes-Related Outcomes for Diabetic and Glucose-Intolerant Patients*
Table Graphic Jump LocationTable 7. Efficacy for Improvement in Hyperlipidemia by Surgical Procedure
Table Graphic Jump LocationTable 8. Efficacy for Improvement in Hypertension and Obstructive Sleep Apnea by Surgical Procedure
Table Graphic Jump LocationTable 9. Surgical Outcomes for the 5 Randomized Controlled Trials*

References

Deitel M. Overweight and obesity worldwide now estimated to involve 1.7 billion people.  Obes Surg. 2003;13:329-330
PubMed   |  Link to Article
International Obesity Task Force.  Call for obesity review as overweight numbers reach 1.7 billion [press release]. London, England: International Obesity Task Force; March 17, 2003. Available at: http://www.iotf.org/media/iotfmar17.htm. Accessed September 12, 2004
 Worldwatch Institute Web site. Available at: http://www.worldwatch.org. Accessed September 9, 2002
Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994.  Int J Obes Relat Metab Disord. 1998;22:39-47
PubMed   |  Link to Article
Mokdad AH, Serdula MK, Dietz WH, Bowman BS, Marks JS, Koplan JP. The spread of the obesity epidemic in the United States, 1991-1998.  JAMA. 1999;282:1519-1522
PubMed   |  Link to Article
Monteforte MJ, Torkelson CM. Bariatric surgery for morbid obesity.  Obes Surg. 2000;10:391-401
PubMed   |  Link to Article
 National Center for Health Statistics NHANES IV Report. Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/obese/obse99.htm Accessed September 9, 2002
Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000.  JAMA. 2002;288:1723-1727
PubMed   |  Link to Article
Sturm R. Increases in clinically severe obesity in the United States, 1986-2000.  Arch Intern Med. 2003;163:2146-2148
PubMed   |  Link to Article
World Health Organization.  World Health Report 2002. Available at: http://www.iotf.org. Accessed January 13, 2004
Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity.  JAMA. 1999;282:1523-1529
PubMed   |  Link to Article
 Overweight, obesity, and health risk: National Task Force on the Prevention and Treatment of Obesity.  Arch Intern Med. 2000;160:898-904
PubMed   |  Link to Article
Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity.  JAMA. 2003;289:187-193
PubMed   |  Link to Article
North American Association for the Study of Obesity and the National Heart, Lung, and Blood Institute.  The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Bethesda, Md: National Institutes of Health; 2000. NIH publication 00-4084
North American Association for the Study of Obesity (NAASO) and the National Heart.  Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda, Md: National Institutes of Health; 1998. NIH publication 98-4083
National Institutes of Health Consensus Development Panel.  Gastrointestinal surgery for severe obesity.  Ann Intern Med1991;115:956-961
Buchwald H. A bariatric surgery algorithm.  Obes Surg. 2002;12:733-746
PubMed   |  Link to Article
Cook DJ, Mulrow CD, Haynes RB. Systematic reviews: synthesis of best evidence for clinical decisions.  Ann Intern Med. 1997;126:376-380
PubMed   |  Link to Article
Mulrow CD, Oxman ADCochrane Collaboration Handbook. Oxford, England: Cochrane Library, Update Software; 1997;issue 1
Buchwald H, Buchwald JN. Evolution of operative procedures for the management of morbid obesity: 1950-2000.  Obes Surg. 2002;12:705-717
PubMed   |  Link to Article
DerSimonian R, Laird N. Meta-analysis in clinical trials.  Control Clin Trials. 1986;7:177-188
PubMed   |  Link to Article
Hedges L, Olkin I. Statistical Methods for Meta-analysis. Orlando, Fla: Academic Press; 1985:230-257
Ashy AR, Merdad AA. A prospective study comparing vertical banded gastroplasty versus laparoscopic adjustable gastric banding in the treatment of morbid and super-obesity.  Int Surg. 1998;83:108-110
PubMed
Hall JC, Watts JM, O'Brien PE.  et al.  Gastric surgery for morbid obesity: the Adelaide Study.  Ann Surg. 1990;211:419-427
PubMed   |  Link to Article
Mingrone G, Greco AV, Giancaterini A, Scarfone A, Castagneto M, Pugeat M. Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery.  Atherosclerosis. 2002;161:455-462
PubMed   |  Link to Article
Nguyen NT, Goldman C, Rosenquist CJ.  et al.  Laparoscopic versus open gastric bypass: a randomized study of outcomes, quality of life, and costs.  Ann Surg. 2001;234:279-289
PubMed   |  Link to Article
Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding.  Int J Obes Relat Metab Disord. 2002;26:193-199
PubMed   |  Link to Article
Pories WJ, Swanson MS, MacDonald KG.  et al.  Who would have thought it? an operation proves to be the most effective therapy for adult-onset diabetes mellitus.  Ann Surg. 1995;222:339-352
PubMed   |  Link to Article
Schauer PR, Burguera B, Ikramuddin S.  et al.  Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.  Ann Surg. 2003;238:467-484
PubMed
Sugerman HJ, Wolfe LG, Sica DA, Clore JN. Diabetes and hypertension in severe obesity and effects of gastric bypass-induced weight loss.  Ann Surg. 2003;237:751-756
PubMed
Sjostrom CD, Lissner L, Wedel H, Sjostrom L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study.  Obes Res. 1999;7:477-484
PubMed   |  Link to Article
Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects.  J Clin Endocrinol Metab. 2003;88:1594-1602
PubMed   |  Link to Article
Yannakoulia M, Yiannakouris N, Blüher S, Matalas AL, Klimis-Zacas D, Mantzoros CS. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans.  J Clin Endocrinol Metab. 2003;88:1730-1736
PubMed   |  Link to Article
Pories WJ, Albrecht RJ. Etiology of type 2 diabetes mellitus: role of the foregut.  World J Surg. 2001;25:527-531
PubMed   |  Link to Article
Hickey MS, Pories WJ, MacDonald KG.  et al.  A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?  Ann Surg. 1998;227:637-644
PubMed   |  Link to Article
Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease.  Ann Surg. 2004;239:1-11
PubMed   |  Link to Article
Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, Alexandrides TK. Restoration of euglycemia and normal acute insulin response in obese subjects with type 2 diabetes following bariatric surgery.  Diabetes. 2003;52:1098-1103
PubMed   |  Link to Article
Kopp HP, Kopp CW, Festa A.  et al.  Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients.  Arterioscler Thromb Vasc Biol. 2003;23:1042-1047
PubMed   |  Link to Article
Geloneze B, Pereira JA, Pareja JC.  et al.  Circulating Concentrations of Adiponectin Increase in Parallel With Enhancement of Insulin Sensitivity During Weight Loss in Humans. Alexandria, Va: American Diabetes Association; 2003. Abstract 1707-P
Kellum JM, Kuemmerle JF, O’Dorisio TM.  et al.  Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty.  Ann Surg. 1990;211:763-770
PubMed   |  Link to Article
Cummings DE, Weigle DS, Frayo RS.  et al.  Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery.  N Engl J Med. 2002;346:1623-1630
PubMed   |  Link to Article
Hanusch-Enserer U, Brabant G. Ghrelin concentrations in morbidly obese patients after adjustable gastric banding.  N Engl J Med. 2003;348:2159-2160
PubMed   |  Link to Article
Dixon JB, Dixon AF, O’Brien PE. Improvement in insulin sensitivity and beta-cell function (HOMA) with weight loss in the severely obese.  Diabet Med. 2003;20:127-134
PubMed   |  Link to Article
Brolin RE, Kenler HA, Wilson AC, Kuo PT, Cody RP. Serum lipids after gastric bypass surgery for morbid obesity.  Int J Obes. 1990;14:939-950
PubMed
Buffington CK, Cowan GSM, Hughes TA, Smith H. Significant changes in the lipid-lipoprotein status of premenopausal morbidly obese females following gastric bypass surgery.  Obes Surg. 1994;4:328-335
PubMed   |  Link to Article
Cowan GS Jr, Buffington CK. Significant changes in blood pressure, glucose, and lipids with gastric bypass surgery.  World J Surg. 1998;22:987-992
PubMed   |  Link to Article
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