Lars Sjöström

Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden.

A longitudinal population study of 1462 women aged 38-60 was carried out in Gothenburg, Sweden, in 1968-9. In univariate analysis the ratio of waist to hip circumference showed a significant positive association with the 12 year incidence of myocardial infarction, angina pectoris, stroke, and death. The association with incidence of myocardial infarction remained in multivariate analysis and was independent of age, body mass index, smoking habit, serum cholesterol concentration, serum triglyceride concentration, and systolic blood pressure. The relation between the ratio of waist to hip circumference and the end points of myocardial infarction, angina pectoris, stroke, and death was stronger than for any other anthropometric variable studied.

Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution.

The distribution of adipose tissue thickness, fat cell weight (FCW), and number (FCN) were studied in four regions in randomly selected middle-aged men and women and in 930 obese individuals. Both the obese and the randomly selected men were found to have the largest adipose tissue thickness in the abdominal region. Women, however, showed a relative preponderance for the gluteal and femoral regions. FCW increased with expanding body fat up to a maximal size of approximately 0.7-0.8 micrograms/cell in each region. After this increase in FCW, a more rapid increase in FCN was found. For the same degree of relative overweight, men had higher triglyceride, fasting glucose, and insulin levels; higher sums of glucose and insulin levels during an oral glucose tolerance test; and higher blood pressure. Furthermore, elevated fasting glucose levels (greater than 7.4 mM) occurred twice as often in the males. These differences between males and females persisted even after body fat matching. A male risk profile was seen in women characterized by abdominal obesity (high waist/hip circumference ratio) as compared to women with the typical peripheral obesity. Stepwise multiple regression analyses in both women and men showed the obesity complications to be associated in a first step to waist/hip circumference or body fat and in a second to abdominal fat cell size. It may thus be concluded that: (a) In both obese and nonobese subjects, regional differences exist between the sexes with regard to adipose tissue distribution. (b) Moderate expansion of body fat is mainly due to FCW enlargement, which is subsequently followed by increased FCN. (c) Men and women with a male abdominal type of obesity are more susceptible to the effect of excess body fat on lipid and carbohydrate metabolism.

Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients

BACKGROUND We undertook a randomised controlled trial to assess the efficacy and tolerance of orlistat, a gastrointestinal lipase inhibitor, in promoting weight loss and preventing weight regain in obese patients over a 2-year period. METHODS 743 patients (body-mass index 28-47 kg/m2), recruited at 15 European centres, entered a 4-week, single-blind, placebo lead-in period on a slightly hypocaloric diet (600 kcal/day deficit). 688 patients who completed the lead-in were assigned double-blind treatment with orlistat 120 mg (three times a day) or placebo for 1 year in conjunction with the hypocaloric diet. In a second 52-week double-blind period patients were reassigned orlistat or placebo with a weight maintenance (eucaloric) diet. FINDINGS From the start of lead-in to the end of year 1, the orlistat group lost, on average, more bodyweight than the placebo group (10.2% [10.3 kg] vs 6.1% [6.1 kg]; LSM difference 3.9 kg [p < 0.001] from randomisation to the end of year 1). During year 2, patients who continued with orlistat regained, on average, half as much weight as those patients switched to placebo (p < 0.001). Patients switched from placebo to orlistat lost an additional 0.9 kg during year 2, compared with a mean regain of 2.5 kg in patients who continued on placebo (p < 0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein ratio, and concentrations of glucose and insulin decreased more in the orlistat group than in the placebo group. Gastrointestinal adverse events were more common in the orlistat group. Other adverse symptoms occurred at a similar frequency during both treatments. INTERPRETATION Orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight regain in obese patients over a 2-year period. The use of orlistat beyond 2 years needs careful monitoring with respect to efficacy and adverse events.

Bariatric Surgery and Long-term Cardiovascular Events

CONTEXT Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking. OBJECTIVE To study the association between bariatric surgery, weight loss, and cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals. MAIN OUTCOME MEASURES The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined. RESULTS Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P < .001). CONCLUSION Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

Review of the key results from the Swedish Obese Subjects (SOS) trial – a prospective controlled intervention study of bariatric surgery

Obesity is a risk factor for diabetes, cardiovascular disease events, cancer and overall mortality. Weight loss may protect against these conditions, but robust evidence for this has been lacking. The Swedish Obese Subjects (SOS) study is the first long‐term, prospective, controlled trial to provide information on the effects of bariatric surgery on the incidence of these objective endpoints. The SOS study involved 2010 obese subjects who underwent bariatric surgery [gastric bypass (13%), banding (19%) and vertical banded gastroplasty (68%)] and 2037 contemporaneously matched obese control subjects receiving usual care. The age of participants was 37–60 years and body mass index (BMI) was ≥34 kg m−2 in men and ≥38 kg m−2 in women. Here, we review the key SOS study results published between 2004 and 2012. Follow‐up periods varied from 10 to 20 years in different reports. The mean changes in body weight after 2, 10, 15 and 20 years were −23%, −17%, −16% and −18% in the surgery group and 0%, 1%, −1% and −1% in the control group respectively. Compared with usual care, bariatric surgery was associated with a long‐term reduction in overall mortality (primary endpoint) [adjusted hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.54–0.92; P = 0.01] and decreased incidences of diabetes (adjusted HR=0.17; P < 0.001), myocardial infarction (adjusted HR = 0.71; P = 0.02), stroke (adjusted HR=0.66; P = 0.008) and cancer (women: adjusted HR = 0.58; P = 0.0008; men: n.s.]. The diabetes remission rate was increased severalfold at 2 years [adjusted odds ratio (OR) = 8.42; P < 0.001] and 10 years (adjusted OR = 3.45; P < 0.001). Whereas high insulin and/or high glucose at baseline predicted favourable treatment effects, high baseline BMI did not, indicating that current selection criteria for bariatric surgery need to be revised.

Ten-year trends in health-related quality of life after surgical and conventional treatment for severe obesity: the SOS intervention study

Objective:To examine trends and effects of weight loss treatment on health-related quality of life (HRQL) in the severely obese over 10 years.Design:Swedish obese subjects (SOS) intervention study is a controlled, longitudinal trial of the health effects of weight loss in the severely obese.Subjects:A total of 655 of 851 surgically treated and 621 of 852 conventionally treated obese men (body mass index, BMI⩾34) and women (BMI⩾38) who completed 10 years of the study.Measurements:HRQL was assessed before treatment and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years.Results:HRQL change during the 10-year observation period largely followed phases of weight loss, weight regain and weight stability. Improvements and deteriorations in HRQL were associated with the magnitude of weight loss or regain, except regarding anxiety. Peak improvements in the surgical group were observed during the first year of weight loss, whereas the weight regain phase (mainly between 1- and 6-year follow-up) was accompanied by a gradual decline in HRQL. The period from 6- to 10-year follow-up was characterized by relatively stable observations in both weight and HRQL. At 10 years, net gains were noted in all HRQL domains compared to baseline. Comparisons of treatment effects on HRQL in the surgical vs conventional group after 10 years showed significantly better outcome in the surgical group on current health perceptions, social interaction, psychosocial functioning and depression, whereas no significant differences were found for overall mood and anxiety. Long-term results of the study suggest that a maintained weight loss of about 10% is sufficient for positive long-term effects on HRQL, a limit that was reached in about two-thirds of the surgically treated patients who completed 10 years of the study.Conclusion:Long-lasting weight reduction in the severely obese has a general long-standing positive outcome on HRQL. Bariatric surgery is a favorable option for the treatment of severe obesity, resulting in long-term weight loss and HRQL improvements in a majority of patients. However, difficulties among some surgical patients to control and maintain weight loss over time should not be ignored. Future research should study if the long-term efficacy of bariatric surgery may be further enhanced by implementing lifestyle modification techniques in the postoperative management of patients.

Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels

Twenty-three healthy men (age 25 to 50 years), covering a wide range of fatness and body fat distribution, were studied. An oral glucose tolerance test was performed and adipose tissue areas were calculated from computed tomography (CT) scans made at the level of L4/L5. Visceral fat area was associated with elevated concentrations of insulin and C-peptide and with glucose intolerance before and after the oral glucose load. Concentrations of sex-hormone-binding globulin (SHBG), as well as total and free testosterone, were negatively correlated with waist/hip circumference ratio and visceral fat area and also negatively associated with increased glucose, insulin, and C-peptide concentrations. In multiple linear regression, adjusting for age, body mass index, and visceral fat area, serum concentrations of free testosterone were still negatively correlated with glucose, insulin, and C-peptide levels. Without claiming any causality in the observed associations, we conclude that, unlike in women, abdominal fat distribution, insulin, glucose, and C-peptide levels are negatively associated with serum testosterone levels in men.

Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects

BACKGROUND Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes. METHODS In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination. RESULTS During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P=0.002 for the interaction) but not by BMI (P=0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications. CONCLUSIONS Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.).

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

OBJECTIVE: To examine the effects of weight loss on health-related quality of life (HRQL) in subjects with severe obesity.DESIGN: Controlled clinical trial of the outcomes of surgical vs conventional weight reduction treatment.SUBJECTS: The first 487 surgical cases and their conventionally treated, matched controls were followed for two years in the Swedish Obese Subjects (SOS) intervention study.MEASUREMENTS:A battery of generic and study-specific self-assessment instruments or subscales was used to characterize HRQL in the severely obese (BMI) ≥34 kg/m2 for males and BMI ≥38 kg/m2 for females). Measures of general health perceptions (general health rating index; current health), mental well-being (mood adjective check list; pleasantness, activation and calmness), mood disorders (hospital anxiety and depression scale; anxiety and depression) and social interaction (sickness impact profile), were supplemented by obesity-specific modules on obesity-related psychosocial problems and eating behavior (three-factor eating questionnaire; restrained eating, disinhibition and perceived hunger). Assessments were conducted prior to treatment and repeated after 6, 12 and 24 months.RESULTS: Poor HRQL before intervention was dramatically improved after gastric restriction surgery, while only minor fluctuations in HRQL scores were observed in the conventionally treated controls. Peak values were observed in the surgical group at 6 or 12 months after intervention with a slight to moderate decrease at the two-year follow-up. The positive changes in HRQL after two years were related to the magnitude of weight loss, that is, the greater the weight reduction, the greater the HRQL improvements. Eating behavior improved accordingly.CONCLUSION: Quality of life in the severely obese is improved by substantial weight loss. Most patients benefit from weight reduction surgery, while HRQL in surgical patients with minor reduction in overweight is less positive. Further research is needed to determine outcome predictors of the surgical management of severe obesity and to ensure that HRQL improvements are maintained.

Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial

BACKGROUND Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. METHODS The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years). FINDINGS Bariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. INTERPRETATION Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. FUNDING Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.