Prevalence of the metabolic syndrome in 337 severely obese patients across quintiles of body mass index, age, and waist-hip ratio.
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Lee W, Huang M, Wang W, Lin C, Chen T, Lai I. Effects of Obesity Surgery on the Metabolic Syndrome. Arch Surg. 2004;139(10):1088–1092. doi:10.1001/archsurg.139.10.1088
Individuals with the metabolic syndrome (MS), a clustering of risk factors (high levels of triglycerides and serum glucose, low level of high-density-lipoprotein cholesterol, high blood pressure, abdominal obesity) defined by the Third Report of the National Cholesterol Education Program Expert Panel of Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (ATPIII), are at high risk of developing coronary heart disease and type 2 diabetes mellitus and may benefit from surgically induced weight loss.
Prospectively controlled clinical study.
A tertiary referral center.
From December 1, 1999, to March 31, 2002, 645 consecutive morbidly obese patients were enrolled in a surgically supervised weight loss program, and the efficacy of weight loss 1 year after surgery was examined.
Laparoscopic weight reduction surgery.
Main Outcome Measures
Prevalence of the MS as defined by the ATPIII (>3 of the following): waist circumference greater than 102 cm in men and 88 cm in women; serum triglyceride level of at least 150 mg/dL (1.70 mmol/L); high-density lipoprotein cholesterol level less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.30 mmol/L) in women; blood pressure of at least 130/85 mm Hg; and serum glucose level of at least 110 mg/dL (6.11 mmol/L).
Of 645 individuals, 337 (52.2%) met the ATPIII definition of the MS. Individuals with the MS had significant differences in age (31.5 years vs 28.1 years), sex (127 [37.7%] of 337 men vs 81 [26.3%] of 308 women), and many metabolic abnormalities compared with patients without the MS. Laparoscopic vertical banded gastroplasty was performed in 528 patients (81.9%) and laparoscopic gastric bypass in 117 (18.1%). A significant decrease in weight was found in both groups, but individuals who underwent laparoscopic gastric bypass lost significantly more weight (mean ± SD, 38.4 ± 14.4 kg vs 35.1 ± 16.8 kg) and achieved a lower body mass index (29.3 ± 4.8 vs 32.0 ± 5.4) than individuals who underwent laparoscopic vertical banded gastroplasty. Substantial mean weight reduction (31.9%) of patients with the MS resulted in a substantial reduction of systolic (11.0 mm Hg) and diastolic (11.4 mm Hg) blood pressure and levels of glucose (46.1 mg/dL [2.56 mmol/L]), triglycerides (196.6 mg/dL [2.22 mmol/L]), and total cholesterol (33.7 mg/dL [0.88 mmol/L]) 1 year after surgery. These improvements resulted in a 95.6% resolution of the MS 1 year after surgery. There was no difference between operations (laparoscopic vertical banded gastroplasty or laparoscopic gastric bypass) in the resolution rate of the MS 1 year after surgery (95.0% vs 98.4%, respectively).
The MS is prevalent in 52.2% of morbidly obese individuals enrolling in an obesity surgery program. Significant weight reduction 1 year after surgery markedly improved all aspects of the MS and resulted in a cure rate of 95.6%. Obesity surgery performed by laparoscopic surgery is recommended for obese patients with the MS.
Obesity and its associated comorbidities are an ongoing health care problem worldwide. It is well known that obese patients are at increased risk for the development of diabetes, hypertension, hyperlipidemia, sleep apnea, osteoarthritis, and other degenerative diseases. The combination of hypertension, dyslipidemia, glucose intolerance, and obesity, particularly central obesity, has been termed the metabolic syndrome (MS).1 The key feature of the MS is an increased insulin resistance; therefore, the MS is frequently associated with obesity. People with the MS are at increased risk for developing diabetes mellitus and cardiovascular disease and, as a result, have increased mortality.2,3 There has been a marked increase in the number of individuals diagnosed with type 2 diabetes mellitus and a dramatic increase in obesity.4 These trends are likely to continue through the next half century.5
The recently released Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)6 (ATPIII) has drawn attention to the importance of the MS and provides a working definition of this syndrome for the first time. Individuals must have at least 3 of the following 5 risk factors to be diagnosed with the MS: abdominal obesity or waist circumference greater than 102 cm in men and 88 cm in women; serum triglyceride level of at least 150 mg/dL (1.70 mmol/L); high-density lipoprotein cholesterol level less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.30 mmol/L) in women; blood pressure of at least 130/85 mm Hg; and serum glucose level of at least 110 mg/dL (6.11 mmol/L).
Identification of these high-risk individuals is crucial to provide the appropriate therapy with the available disease-modifying treatments. Weight loss is recommended as first-line management of the MS, and benefits of moderate weight loss with conservative treatment have been described.7 However, few treatments have been effective in severely obese patients in the long term. At present, only surgery results in sustained weight loss for seriously obese patients.8
In this study, we determined the prevalence and characteristics of individuals enrolling in a surgically supervised weight loss program who met ATPIII criteria for the MS and the predicting factors for its development in morbidly obese patients. Furthermore, we examined the efficacy of surgically induced weight loss for the treatment of the MS and its defining components.
We studied 645 morbidly obese patients requiring surgical treatment (208 men, 437 women; median age, 29.9 (range, 18-63 years), with a mean body mass index (BMI) of 43.4 (range, 35.4-72.1). The inclusion criteria for these patients were BMI higher than 40 or higher than 35 with associated high-risk comorbidities for which nonsurgical treatment failed.8
Baseline demographic data were collected on each patient and are listed in Table 1. The individual components of the MS (waist circumference; levels of serum glucose, high-density lipoprotein cholesterol, and triglycerides; and blood pressure) as well as levels of total cholesterol, uric acid, aspartate aminotransferase, alanine aminotransferase, and albumin and complete blood cell count were assessed at the initial physical examination before surgery. Body weight was measured in light clothing without shoes to the nearest 0.1 kg and body height to the nearest 0.1 cm. Body mass index was calculated as weight in kilograms divided by the height in meters squared. The waist circumference was measured at the level midway between the lateral lower rib margin and the superior anterior iliac crest. Criteria used to define metabolic comorbidities were listed earlier. Patients were considered to have the MS according to ATPIII definition.6 At 1 year after surgery, BMI, blood pressure, and other blood test values were assessed. Individuals who were receiving pharmacological therapy for diabetes mellitus or high blood pressure were counted as meeting the glucose level and blood pressure criteria, respectively.
Descriptive data are expressed as mean ± SD. Group characteristics were compared by unpaired t tests, and differences between proportions were tested by χ2 tests. A multivariate analysis using logistic regression was performed to assess the correlation between clinical factors and occurrence of the MS. The statistic analysis was performed using SPSS version 8.0 for Windows (SPSS Inc, Chicago, Ill). Statistical significance was inferred at a 2-tailed P value of less than .05.
All the patients in the study group received laparoscopic weight reduction surgery at our center. The surgical procedures performed were laparoscopic vertical banded gastroplasty (LVBG) and laparoscopic gastric bypass (LGBP). The techniques of LVBG and LGBP are described in detail elsewhere.9,10 We performed LVBG in 528 patients (81.9%) and LGBP in 117 (18.1%). We performed LVBG only before 2000 and started to perform LGBP in 2001. Patients could choose either procedure. There was no operation mortality in this series. Nine patients (1.4%) developed major complications and 21 (3.3%), minor complications. Mean ± SD operation time was 123 ± 46 minutes, and mean ± SD hospital stay was 4.2 ± 3.2 days. One year after surgery, 2 patients had died (1 patient of fulminate hepatitis due to hepatitis B and the other of hemorrhagic pancreatitis). There were 34 patients (5.3%) lost to follow-up at 1 year.
Of 645 consecutive individuals enrolled in the obesity surgery program, 337 (52.2%) had at least 3 of the 5 defining criteria and were classified as having the MS. Approximately 148 individuals (23%) had 4 defining components, and 77 (12%) had all 5 components. Individuals with the MS had significant differences in sex (127 [37.7%] of 339 men vs 81 [26.3%] of 308 women), age (31.5 years vs 28.1 years), blood pressure (140/90 mm Hg vs 131/82 mm Hg), and levels of glucose (132 mg/dL [7.33 mmol/L] vs 98 mg/dL [5.44 mmol/L]), total cholesterol (214 mg/dL [5.54 mmol/L] vs 182 mg/dL [4.71 mmol/L]), high-density lipoprotein cholesterol (40 mg/dL [1.04 mmol/L] vs 50 mg/dL [1.30 mmol/L]), triglycerides (275 mg/dL [3.11 mmol/L] vs 138 mg/dL [1.56 mmol/L]), aspartate aminotransferase (37 U/L vs 30 U/L), and alanine aminotransferase (51 U/L vs 39 U/L) compared with individuals without the MS (Table 1). Both groups had similar baseline BMI, levels of uric acid and albumin, and white blood cell count. The prevalence in individuals with the MS across quintiles for BMI, waist-hip ratio, and age are depicted in Figure 1. The number of patients affected by the MS was found to steadily increase with increasing age or waist-hip ratio but not BMI. Multivariate analyses confirmed an increased prevalence of the MS associated with male sex, increased age, and abnormal liver function. Body mass index and hyperuricemia were not significant predictors for the MS as presented in Table 2.
In individuals with the MS, the average weight loss 1 year after surgery was 38.2 kg or 31.9% of their initial body weight. The mean ± SD BMI declined from 43.3 ± 6.0 to 29.9 ± 8.7. There was no difference in types of surgery and weight lost between individuals with the MS and individuals without the MS. Individuals who underwent LGBP lost significantly more weight (38.4 ± 14.4 kg vs 35.1 ± 16.8 kg) and achieved a lower BMI (29.3 ± 4.8 vs 32.0 ± 5.4) than individuals who underwent LVBG.
Blood pressure was significantly reduced 1 year after surgery in individuals with the MS (Table 3). Average systolic blood pressure decreased from 139.6 mm Hg to 128.6 mm Hg and diastolic blood pressure decreased from 89.8 mm Hg to 78.4 mm Hg (P<.001). Systolic and diastolic blood pressure decreased an average of 11.0 mm Hg or 7.9% and 11.4 mm Hg or 12.7%, respectively.
Lipid and glucose levels were also significantly reduced in individuals with the MS (Table 3). Total cholesterol levels decreased from 214.3 mg/dL (5.55 mmol/L) to 180.6 mg/dL (4.68 mmol/L) (P<.001), representing a 15.7% reduction from baseline, and triglyceride levels decreased from 275.3 mg/dL (3.11 mmol/L) to 78.7 mg/dL (0.89 mmol/L) (P<.001), representing a reduction of 71.4%. Glucose levels decreased from 132.3 mg/dL (7.35 mmol/L) to 86.1.0 mg/dL (4.78 mmol/L) (P<.001), representing a reduction of 34.8%. In addition, the reduction of uric acid (7.85 to 6.31 mg/dL [466.92 to 375.32 µmol/L]), aspartate aminotransferase (36.9 to 20.4 U/L), and alanine aminotransferase levels (50.8 to 21.3 U/L) and white blood cell count (8.95 to 7.05 103/µL) were all statistically significant.
Overall, there was a reduction in the number of individuals who met the criteria for the MS. After 1 year of surgery, only 14 (4.4%) of 315 individuals still had the MS. The overall resolution rate of the MS was 95.6% 1 year after surgery. There was no difference between the different operations (LVBG or LGBP) in the resolution rate (95.0% vs 98.4%, respectively).
Individuals without the MS as defined by ATPIII criteria had an average weight loss of 38.4 kg 1 year after surgery. In these individuals, weight loss resulted in a less dramatic but statistically significant change in levels of glucose (96.5 to 83.9 mg/dL [5.4 to 4.7 mmol/L]), average total cholesterol (182.4 to 172.2 mg/dL [4.7 to 4.5 mmol/L]), triglycerides (128.8 to 65.5 mg/dL [1.5 to 0.7 mmol/L]), uric acid (7.6 to 6.2 mg/dL [452.1 to 368.8 µmol/L]), and alanine aminotransferase (41.5 to 23.1 U/L) and white blood cell count (8.90 to 6.77 103/µL). The average blood pressure (134/84 to 132/79 mm Hg) was not statistically significant.
Using the new ATPIII definition, the prevalence of the MS in this single-center obesity surgery program was 52.2%. Previous estimates of the prevalence of the MS in severely obese individuals have varied because of differences in definitions and populations.2,11-14 A recent estimate of the prevalence of the MS suggests that 20% to 25% of US adults have the syndrome.14 The unrelenting increase in the prevalence of obesity in the United States suggests that the prevalence of the MS will very likely grow higher.15
Insulin resistance is thought to be an underlying feature of the MS.16 Genetic abnormalities, fetal malnutrition, and visceral adiposity may play roles in the pathophysiologic process of insulin resistance and the MS.17 Although obesity appears to be the central component of the MS,18 significant proportions of severely obese patients do not have the MS. Our study discovered that male sex and increased age were the 2 significant predicting factors for the MS in this group of patients. A recent report19 found that male sex and age were predictors of surgical morbidity and mortality in Roux-en-Y gastric bypass, which corroborates with our results. However, the prevalence of the MS in US men and women is similar.15 A possible bias does exist to explain the discrepancy. Because women are more willing to receive surgical treatment than men, the female patients in our study tended to be younger and healthier than the male patients in our study and other studies.9,10,20-23 Therefore, the significance of sex may be the result of biased patient selection. Further study is needed to clarify the role of sex in severely obese patients. Nonetheless, the finding that the occurrence of the MS is closely related to increased age highlights the importance of early effective treatment of weight reduction in severely obese patients.
The cornerstones of treatment are the management of weight and ensuring appropriate levels of physical activity. Recent studies demonstrate that dietary modification and enhanced physical activity may delay or prevent the transition from glucose tolerance impairment to type 2 diabetes mellitus and provide relevant treatment paradigms for patients with the MS.24-26 For morbidly obese patients, a recent study7 showed that a very low-calorie diet can help patients achieve effective weight loss and resolution of the MS in 4 weeks. However, weight loss by conservative methods has proven exceedingly difficult to maintain across long periods. Based on the disappointing results of weight loss in morbidly obese patients treated using conservative methods, the National Institutes of Health, Bethesda, Md, has recommended surgical treatment for morbidly obese patients because it achieves significant and durable weight loss as well as resolution or amelioration of comorbidities.8 To the best of our knowledge, this study is the first to study the efficacy of surgical treatment for ATPIII-defined MS. The dramatic effect of obesity surgery on the MS in this study is not astonishing, because numerous studies have observed the resolution of diabetes mellitus in addition to the desired weight loss after obesity surgery.27-29 The resolution of other obesity-related conditions has also been observed, such as hypertension30 and hyperlipidemia.31 Because diabetes, hypertension, and hyperlipidemia compose the triad of MS components, a 95.6% resolution rate of the MS in severely obese patients 1 year after surgery is expected. Patients who still had the MS 1 year after surgery usually had inadequate weight loss.
In addition to resolving the MS, significant weight reduction after obesity surgery is also very effective in the reduction of uric acid levels and elevated liver function. The significant reduction of white blood cell count after obesity surgery reflects the improvement of a proinflammatory state in severely obese patients. Recent studies32,33 have showed that obese subjects have a proinflammatory state characterized by elevations of serum high-sensitivity C-reactive protein levels and leukocytes. The excess of adipose tissue apparently secretes increased amounts of several cytokines that underlie the proinflammatory state.34 Our study supports the finding that marked weight reduction after obesity surgery might reverse the proinflammatory state and reduce the risk for morbidity and mortality in these subjects.35,36
Recently, Isomaa et al2 showed that the mortality for cardiovascular conditions increases about 3-fold in subjects with the MS compared with those without the MS. In addition, a cluster of risk factors defining the MS increased cardiovascular risk more than each single component. Thus, a more integrated strategy provides better outcomes than management of the individual risks of this syndrome. Obesity surgery, therefore, should be highly recommended for the treatment of morbidly obese patients with the MS. Recent advancement in laparoscopic surgery has made laparoscopic bariatric surgery a mini-invasive procedure and renewed the interest and increased the growth of obesity surgery.9,10,20-23,29,37 In consideration of the safety and advantage of laparoscopic bariatric surgery and its dramatic effect on the MS, laparoscopic bariatric surgery might be used more freely in the treatment of the MS. Current indications for surgery in morbidly obese patients include BMI greater than 40 or greater than 35 if comorbidities are present.8 However, for patients with moderate obesity (BMI between 30-35) and the MS, laparoscopic bariatric surgery might be included in the choices of treatments. Although in some cases, weight reduction and increased physical activity may be sufficient to eliminate risk factors, most patients required long-term drug therapies to control separate risk factors. In such cases, laparoscopic bariatric surgery, which can provide an effective and integral therapy, might be a reasonable proposal. Further cost-effectiveness studies of laparoscopic bariatric surgery in the treatment of moderately obese individuals with the MS are needed before a conclusion can be made.
The metabolic syndrome, as defined by the ATPIII, was present in more than half of severely obese individuals enrolled in an obesity surgery program. Significant weight loss 1 year after laparoscopic bariatric surgery shows that the procedure was an extremely effective treatment for improving all aspects of the MS. These findings support the theory that excess adipose tissue plays a key role in all aspects of the MS. Additional clinical research is needed to evaluate the cost-effectiveness of obesity surgery in the treatment of the MS in individuals with moderate obesity.
Correspondence: Wei-Jei Lee, MD, PhD, Department of Surgery, En-Chu Kong Hospital, 399 Fuhsing Rd, San-Shia Town, Taipei Hsien 237, Taiwan (email@example.com).
Accepted for publication March 26, 2004.
This study was supported by grant 93-A-01 from En-Chu Kong Hospital, Taipei, Taiwan, and grant NSC 93-2314-B-385-001 from the National Science Council of the Republic of China, Taipei.