Coronary calcium scores 6 years after bariatric surgery.

BACKGROUND: Obesity is associated with elevated coronary artery calcium (CAC), a marker of coronary atherosclerosis that is strongly predictive of cardiovascular events. We evaluated the effects of marked weight loss achieved through Roux-en-Y gastric bypass surgery (GBS) on CAC scores. METHODS: We performed echocardiography and computed tomography of the heart in 149 subjects 6 years after enrollment in a prospective registry evaluating the cardiovascular effects of GBS. Coronary calcium scores, left ventricular ejection fraction, and left ventricular mass were measured. RESULTS: At baseline, most coronary risk factors were similar between the GBS and nonsurgical groups including current smoking, systolic blood pressure, LDL-C, HDL-C, and TG. However, GBS patients were younger (4.7 years), less likely to be diabetic, and less likely to be postmenopausal. At 6 years after enrollment, CAC score was significantly lower in patients who underwent GBS than those without surgery (p < 0.01). GBS subjects had a lower likelihood of having measureable coronary calcium (odds ratio of CAC > 0 = 0.39; 95 % CI of (0.17, 0.90)). Significant predictors of 0 CAC were GBS, female gender, younger age, baseline BMI, and baseline LDL-C. Substituting change in BMI for group status as a predictor variable showed that BMI change also predicted CAC (p = 0.045). Changes in LDL-C did not predict the CAC differences between groups (p = 0.67). CONCLUSIONS: Sustained weight loss achieved through bariatric surgery is associated with less coronary calcification. This effect, which appears to be independent of changes in LDL-C, may contribute to lower cardiac mortality in patients with successful GBS.

Health benefits of gastric bypass surgery after 6 years.

CONTEXT: Extreme obesity is associated with health and cardiovascular disease risks. Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term, long-term outcomes are uncertain. OBJECTIVE: To examine the association of Roux-en-Y gastric bypass (RYGB) surgery with weight loss, diabetes mellitus, and other health risks 6 years after surgery. DESIGN, SETTING, AND PARTICIPANTS: A prospective Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese (body mass index [BMI] ≥ 35) participants aged 18 to 72 years (82% women; mean BMI, 45.9; 95% CI, 31.2-60.6) who sought and received RYGB surgery (n = 418), sought but did not have surgery (n = 417; control group 1), or who were randomly selected from a population-based sample not seeking weight loss surgery (n = 321; control group 2). MAIN OUTCOME MEASURES: Weight loss, diabetes, hypertension, dyslipidemia, and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment. RESULTS: Six years after surgery, patients who received RYGB surgery (with 92.6% follow-up) lost 27.7% (95% CI, 26.6%-28.9%) of their initial body weight compared with 0.2% (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, -1.2% to 1.2%) in control group 2. Weight loss maintenance was superior in patients who received RYGB surgery, with 94% (95% CI, 92%-96%) and 76% (95% CI, 72%-81%) of patients receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after surgery, respectively. Diabetes remission rates 6 years after surgery were 62% (95% CI, 49%-75%) in the RYGB surgery group, 8% (95% CI, 0%-16%) in control group 1, and 6% (95% CI, 0%-13%) in control group 2, with remission odds ratios (ORs) of 16.5 (95% CI, 4.7-57.6; P < .001) vs control group 1 and 21.5 (95% CI, 5.4-85.6; P < .001) vs control group 2. The incidence of diabetes throughout the course of the study was reduced after RYGB surgery (2%; 95% CI, 0%-4%; vs 17%; 95% CI, 10%-24%; OR, 0.11; 95% CI, 0.04-0.34 compared with control group 1 and 15%; 95% CI, 9%-21%; OR, 0.21; 95% CI, 0.06-0.67 compared with control group 2; both P < .001). The numbers of participants with bariatric surgery-related hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for the RYGB surgery group and 2 control groups, respectively. CONCLUSION: Among severely obese patients, compared with nonsurgical control patients, the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years.

Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects.

Neuropeptide Y (NPY) is an appetite hormone that acts centrally to control feeding behavior. The 5' and exon 2 regions of NPY2R, one of five NPY receptor genes, have been weakly and inconsistently implicated with obesity. With the ATG start site of the gene at the beginning of exon 2, single-nucleotide polymorphisms (SNPs) across intron 1 may show stronger associations with obesity than expected. Two 5' SNPs, three intron 1 SNPs, and one synonymous exon 2 SNP were genotyped on 2,985 white Utah subjects. Previously associated FTO, NPY, NPY1R, MC4R, PPARGC1A, OR7D4, and four NPFFR2 SNPs were also genotyped and related to BMI. One NPY2R 5' SNP (rs12649641, P = 0.008), an exon 2 SNP (rs2880415, P = 0.009), and an intron 1 SNP (rs17376826, P = 7 × 10(-6)) were each significantly associated with BMI. All three SNPs, plus FTO (rs9939609, P = 1.5 × 10(-6)) and two NPFFR2 SNPs (rs4129733, P = 3.7 × 10(-13) and rs11940196, 4.2 × 10(-10)) remained significant in a multiple regression additive model. Diplotypes using the estimated haplotypes of NPY2R, NPFFR2, and MC4R were significantly associated with BMI (P = 1.0 × 10(-10), 3.2 × 10(-8), and 1.1 × 10(-4), respectively). Haplotypes of NPY2R, NPFFR2, and MC4R, plus the FTO SNP, explained 9.6% of the BMI variance. SNP effect sizes per allele for the four genes ranged from 0.8 to 3.5 kg/m(2). We conclude that haplotypes containing the rs17376826 SNP in intron 1 of NPY2R have strong associations with BMI, some NPFFR2 haplotypes are strongly protective against or increase risk of obesity, and both NPY2R and NPFFR2 play important roles in obesity predisposition independent of FTO and MC4R.

Favorable changes in cardiac geometry and function following gastric bypass surgery: 2-year follow-up in the Utah obesity study.

OBJECTIVES: The objective of this study was to test the hypothesis that gastric bypass surgery (GBS) would favorably impact cardiac remodeling and function. BACKGROUND: GBS is increasingly used to treat severe obesity, but there are limited outcome data. METHODS: We prospectively studied 423 severely obese patients undergoing GBS and a reference group of severely obese subjects that did not have surgery (n = 733). RESULTS: At a 2-year follow up, GBS subjects had a large reduction in body mass index compared with the reference group (-15.4 ± 7.2 kg/m(2) vs. -0.03 ± 4.0 kg/m(2); p < 0.0001), as well as significant reductions in waist circumference, systolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, and insulin resistance. High-density lipoprotein cholesterol increased. The GBS group had reductions in left ventricular (LV) mass index and right ventricular (RV) cavity area. Left atrial volume did not change in GBS but increased in reference subjects. In conjunction with reduced chamber sizes, GBS subjects also had increased LV midwall fractional shortening and RV fractional area change. In multivariable analysis, age, change in body mass index, severity of nocturnal hypoxemia, E/E', and sex were independently associated with LV mass index, whereas surgical status, change in waist circumference, and change in insulin resistance were not. CONCLUSIONS: Marked weight loss in patients undergoing GBS was associated with reverse cardiac remodeling and improved LV and RV function. These data support the use of bariatric surgery to prevent cardiovascular complications in severe obesity.

Cardiorespiratory fitness and health-related quality of life in bariatric surgery patients.

Health-related quality of life (HRQOL) is impaired in severely obese individuals presenting for bariatric surgery. Little is known about the relationship between cardiorespiratory fitness (CRF) and HRQOL in these individuals. We hypothesized that better HRQOL would be reported by those with higher CRF. In 326 gastric bypass patients (mean BMI = 46.5 ± 7.0; mean age=40.9 ± 10.1; 83.4% female), pre-surgical CRF was quantified as duration (minutes) of a submaximal treadmill test to 80% of age-predicted maximal heart rate (MHR). Patients completed both a general measure of HRQOL [the Medical Outcome Short Form 36 (SF-36)] and a weight-specific measure of HRQOL [Impact of Weight on Quality of Life--Lite]. Mean HRQOL scores were examined, controlling for age, gender, and BMI. Mean treadmill duration was 9.9 ± 3.1 min, and percent age-predicted MHR was 81.2 ± 3.0%. Higher cardiorespiratory fitness tended to be associated with better physical and weight-specific HRQOL. Adjustment for differences in gender, age, and BMI attenuated the significance of associations between fitness and physical measures from the SF-36, whereas adjustment eliminated significance of associations between fitness and weight-specific HRQOL in most cases. Results suggest that CRF confers some HRQOL benefits in severely obese adults, though these benefits may largely be explained by differences in age, gender, and BMI.

Health outcomes of gastric bypass patients compared to nonsurgical, nonintervened severely obese.

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight-loss intervention. Three groups of severely obese subjects (N = 1,156, BMI >or= 35 kg/m(2)) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population-based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes-related variables, resting metabolic rate (RMR), sleep apnea, and health-related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF-36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux-en-Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight-loss intervention was highly effective for weight loss, improved health-related quality of life, and resolution of major obesity-associated complications measured at 2 years.

Two-year changes in health-related quality of life in gastric bypass patients compared with severely obese controls.

BACKGROUND: Few weight loss surgery trials have evaluated the changes in health-related quality of life (HRQOL) relative to obese individuals not participating in weight loss interventions. In a prospective study at a bariatric surgery practice, we evaluated the 2-year changes in HRQOL in gastric bypass patients compared with 2 severely obese groups who did not undergo surgical weight loss. METHODS: A total of 308 gastric bypass patients were compared with 253 individuals who sought but did not undergo gastric bypass and 272 population-based obese individuals using the weight-related (Impact of Weight on Quality of Life-Lite) and general (Medical Outcomes Study 36-item Short-Form Health Survey) HRQOL questionnaires at baseline and 2 years of follow-up. RESULTS: The percentage of weight loss was 34.2% for the gastric bypass and 1.4% for the no gastric bypass groups, with a .5% gain for population-based obese group. Both measures of HRQOL showed greater improvements for the gastric bypass group, even after controlling for baseline differences. Effect sizes for changes in physical and weight-related HRQOL were very large for gastric bypass, but small to medium for the 2 comparison groups. Effect sizes for changes in the psychosocial aspects of HRQOL were moderate to very large for gastric bypass, but small for the 2 comparison groups. Of the gastric bypass patients, 97% had meaningful improvements in the Impact of Weight on Quality of Life-Lite total score compared with 43% of the no gastric bypass group and 30% of the population-based obese group. CONCLUSION: Dramatic improvements had occurred in weight-related and physical HRQOL for gastric bypass patients at 2 years after surgery compared with 2 severely obese groups who had not undergone surgery. These results support the effectiveness of gastric bypass surgery in improving patients' HRQOL.

Cancer incidence and mortality after gastric bypass surgery.

Despite weight loss recommendations to prevent cancer, cancer outcome studies after intentional weight loss are limited. Recently, reduced cancer mortality following bariatric surgery has been reported. This study tested whether reduced cancer mortality following gastric bypass was due to decreased incidence. Cancer incidence and mortality data through 2007 from the Utah Cancer Registry (UCR) were compared between 6,596 Utah patients who had gastric bypass (1984-2002) and 9,442 severely obese persons who had applied for Utah Driver's Licenses (1984-2002). Study outcomes included incidence, case-fatality, and mortality for cancer by site and stage at diagnosis of all gastric bypass patients, compared to nonoperated severely obese controls. Follow-up was over a 24-year period (mean 12.5 years). Total cancer incidence was significantly lower in the surgical group compared to controls (hazard ratio (HR) = 0.76; confidence interval (CI) 95%, 0.65-0.89; P = 0.0006). Lower incidence in surgery patients vs. controls was primarily due to decreased incidence of cancer diagnosed at regional or distant stages. Cancer mortality was 46% lower in the surgery group compared to controls (HR = 0.54; CI 95%, 0.37-0.78; P = 0.001). Although the apparent protective effect of surgery on risk of developing cancer was limited to cancers likely known to be obesity related, the inverse association for mortality was seen for all cancers. Significant reduction in total cancer mortality in gastric bypass patients compared with severely obese controls was associated with decreased incidence, primarily among subjects with advanced cancers. These findings suggest gastric bypass results in lower cancer risk, presumably related to weight loss, supporting recommendations for reducing weight to lower cancer risk.

Serum bilirubin levels, UGT1A1 polymorphisms and risk for coronary artery disease.

Low levels of the antioxidative serum bilirubin are associated with vascular aging and an increased risk for coronary artery disease (CAD). UGT1A1 is the major gene influencing bilirubin concentrations. Therefore, we investigated an association of bilirubin levels and two polymorphisms in the promoter of UGT1A1 (-53(TA-repeat) polymorphism and T-3279G) in 477 patients with premature, familial CAD and 619 age- and sex-matched controls. Bilirubin concentrations were significantly lower in cases than in controls (0.62+/-0.36 vs. 0.76+/-0.41 mg/dl for men, p=1.2 x 10(-10); and 0.42+/-0.29 vs. 0.55+/-0.23 mg/dl, p=1.9 x 10(-9) for women). Both polymorphisms showed a strong association with bilirubin levels with higher levels for homozygote carriers of the minor allele. These associations were most pronounced in male controls and patients (p=5.9 x 10(-26) and p=3.4 x 10(-16), respectively, for the -53(TA-repeat) polymorphism). Logistic regression analysis revealed low bilirubin levels but not the UGT1A1 polymorphisms to be significantly associated with CAD: OR (95% CI) 0.90 (0.86-0.94), p=2.6 x 10(-6) for men and 0.77 (0.68-0.87), p=3.2 x 10(-5) for women, respectively for each 0.1mg/dl increase of bilirubin. These results indicate that it is rather decreased bilirubin levels in general than the changes in the genetic variation of this gene that increase the risk for CAD.

Health and health-related quality of life: differences between men and women who seek gastric bypass surgery.

BACKGROUND: The aim of this study was to examine the differences between male and female bariatric surgery candidates with respect to health-related quality of life (HRQOL), health, sociodemographic variables, and interactions among these variables in a bariatric surgery practice in the United States. Women seek bariatric surgery 5 times more often than men. Research on gender differences in HRQOL is limited, and the results are conflicting. METHODS: A total of 794 surgery candidates (mean age 42.2 y; body mass index 46.9 kg/m2; 84.8% women) completed both a weight-related (Impact of Weight on Quality of Life-Lite questionnaire) and a generic (Medical Outcomes Study Short-Form-36) measure of HRQOL. Health was evaluated by questionnaire and clinical interviews. RESULTS: Compared to men, women reported reduced HRQOL on 3 of the 5 scales assessing obesity-specific HRQOL and also the physical aspects of general HRQOL. Women also had double the rate of depression (48.5% versus 22.5%), and men had double the rate of sleep apnea (80.3% versus 40.2%). Women were younger, less obese, and were less likely to be married. No gender differences were found in the association between HRQOL and co-morbidities. However, an increasing number of co-morbidities was associated with decreasing physical and mental HRQOL. Additionally, depression was associated with decreased mental HRQOL, and coronary heart disease was associated with decreased physical HRQOL. CONCLUSION: Women's reduced HRQOL, particularly in self-esteem, sexual life, and physical functioning, and their greater rates of depression, might play a role in their decision to seek bariatric surgery. Although we could not determine causality, this study is a first step toward understanding why women seek surgery 5 times more often than men.

Long-term mortality after gastric bypass surgery.

BACKGROUND: Although gastric bypass surgery accounts for 80% of bariatric surgery in the United States, only limited long-term data are available on mortality among patients who have undergone this procedure as compared with severely obese persons from a general population. METHODS: In this retrospective cohort study, we determined the long-term mortality (from 1984 to 2002) among 9949 patients who had undergone gastric bypass surgery and 9628 severely obese persons who applied for driver's licenses. From these subjects, 7925 surgical patients and 7925 severely obese control subjects were matched for age, sex, and body-mass index. We determined the rates of death from any cause and from specific causes with the use of the National Death Index. RESULTS: During a mean follow-up of 7.1 years, adjusted long-term mortality from any cause in the surgery group decreased by 40%, as compared with that in the control group (37.6 vs. 57.1 deaths per 10,000 person-years, P<0.001); cause-specific mortality in the surgery group decreased by 56% for coronary artery disease (2.6 vs. 5.9 per 10,000 person-years, P=0.006), by 92% for diabetes (0.4 vs. 3.4 per 10,000 person-years, P=0.005), and by 60% for cancer (5.5 vs. 13.3 per 10,000 person-years, P<0.001). However, rates of death not caused by disease, such as accidents and suicide, were 58% higher in the surgery group than in the control group (11.1 vs. 6.4 per 10,000 person-years, P=0.04). CONCLUSIONS: Long-term total mortality after gastric bypass surgery was significantly reduced, particularly deaths from diabetes, heart disease, and cancer. However, the rate of death from causes other than disease was higher in the surgery group than in the control group.

Left ventricular hypertrophy in severe obesity: interactions among blood pressure, nocturnal hypoxemia, and body mass.

Obese subjects have a high prevalence of left ventricular (LV) hypertrophy. It is unclear to what extent LV hypertrophy results directly from obesity or from associated conditions, such as hypertension, impaired glucose homeostasis, or obstructive sleep apnea. We tested the hypothesis that LV hypertrophy in severe obesity is associated with additive effects from each of the major comorbidities. Echocardiography and laboratory testing were performed in 455 severely obese subjects with body mass index 35 to 92 kg/m(2) and 59 nonobese reference subjects. LV hypertrophy, defined by allometrically corrected (LV mass/height(2.7)), gender-specific criteria, was present in 78% of the obese subjects. Multivariable regression analyses showed that average nocturnal oxygen saturation <85% was the strongest independent predictor of LV hypertrophy (P<0.001), followed by systolic blood pressure (P<0.015) and then body mass index (P<0.05). With regard to LV mass, there were synergistic effects between hypertension and body mass index (P interaction <0.001) and between hypertension and reduced nocturnal oxygen saturation. Severely obese subjects had normal LV endocardial fractional shortening (35+/-6% versus 35+/-6%) but mildly decreased midwall fractional shortening (15+/-2% versus 17+/-2%; P<0.001), indicating subtle myocardial dysfunction. In conclusion, more severe nocturnal hypoxemia, increasing systolic blood pressure, and body mass index are all independently associated with increased LV mass. The effects of increased blood pressure seem to amplify those of sleep apnea and more severe obesity.

TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition.

The molecular etiology of obesity predisposition is largely unknown. Here, we present evidence that genetic variation in TBC1D1 confers risk for severe obesity in females. We identified a coding variant (R125W) in TBC1D1 that segregated with the disease in 4p15-14-linked obesity pedigrees. In cases derived from pedigrees with the strongest linkage evidence, the variant was significantly associated with obesity (P=0.000007) and chromosomes carrying R125W accounted for the majority of the evidence that originally linked 4p15-14 with the disease. In addition, by selecting families that segregated R125W with obesity, we were able to generate highly significant linkage evidence for an obesity predisposition locus at 4q34-35. This result provides additional and confirming evidence that R125W affects obesity susceptibility, delimits the location of an obesity gene at 4q34-35 and identifies a gene/gene interaction that influences the risk for obesity predisposition. Finally, although the function of TBC1D1 is unknown, the protein is structurally similar to a known regulator of insulin-mediated Glut4 translocation.

Obesity and sexual quality of life.

OBJECTIVES: Reduced sexual quality of life is a frequently reported yet rarely studied consequence of obesity. The objectives of this study were to 1) examine the prevalence of sexual quality-of-life difficulties in obese individuals and 2) investigate the association between sexual quality of life and BMI class, sex, and obesity treatment-seeking status. RESEARCH METHODS AND PROCEDURES: Subjects consisted of 1) 500 participants in an intensive residential program for weight loss and lifestyle modification (BMI = 41.3 kg/m2), 2) 372 patients evaluated for gastric bypass surgery (BMI = 47.1 kg/m2), and 3) 286 obese control subjects not seeking weight loss treatment (BMI = 43.6 kg/m2). Participants completed the Impact of Weight on Quality of Life-Lite, a measure of weight-related quality of life. Responses to the four Sexual Life items (assessing enjoyment, desire, performance, and avoidance) were analyzed by BMI, sex, and group. RESULTS: Higher BMI was associated with greater impairments in sexual quality of life. Obese women reported more impairment in sexual quality of life than obese men for three of four items. Gastric bypass surgery candidates reported more impairment in sexual quality of life than residential patients and controls for most items. In general, residential patients reported levels of impairment greater than or equal to controls. DISCUSSION: Obesity is associated with lack of enjoyment of sexual activity, lack of sexual desire, difficulties with sexual performance, and avoidance of sexual encounters. Sexual quality of life is most impaired for women, individuals with Class III obesity, and patients seeking gastric bypass surgery.

Design and rationale of the Utah obesity study. A study to assess morbidity following gastric bypass surgery.

PURPOSE: This paper details the design and baseline characteristics of a study on the morbidity associated with Roux-en-Y gastric bypass surgery (GBP) in severely obese adults. This study is designed to assess the effectiveness of GBP in reducing morbidity and maintaining weight loss. A wide array of clinical tests and psycho-behavioral questionnaires are included as part of the study. METHODS: Three groups (n=1156 severely obese) have been recruited for this study: cases who were approved for and participated in surgery (n=415), a control group of GBP seeking individuals who were denied surgery (n=420) and a control group that was randomly chosen from a population of severely obese participants who were not seeking GBP (n=321). Clinical measures include: a physician interview and detailed medical history, resting electro- and echocardiograms, a submaximal exercise treadmill test and electrocardiogram, pulmonary function, limited polysomnography, resting metabolic rate, anthropometrics, resting and exercise blood pressure, comprehensive blood chemistry and urinalysis and dietary, quality of life and physical activity questionnaires. Most participants (76%) were tested following an overnight stay in a clinical research center. Remaining participants underwent less extensive testing in an outpatient clinic. RESULTS: Baseline characteristics of the 1156 participants are available for selected measures. Mean+/-S.D. for BMI was 46+/-7.5 kg/m(2) (range=33 to 92) and for age was 44+/-11.4 years (range=18 to 72). The prevalence of diabetes and hypertension was 19% and 35%, respectively. Of the participants who had an echocardiogram or polysomnogram, 92% had left-ventricular hypertrophy and 85% had mild to severe sleep apnea. The two control groups were similar to the surgical group. At approximately 24 months, all participants will have a second clinical examination. Statistical comparisons of changes in morbidity variables will be made between the surgical and control groups. CONCLUSIONS: This study design facilitates assessment of risks and benefits of GBP to perform recommendations on whether or not to perform surgery on the severely obese patient. Baseline and 2-year exams provide valuable data for comparison to future long-term follow-up data that can be collected at 5 and 10 years.

Health-related quality of life in patients seeking gastric bypass surgery vs non-treatment-seeking controls.

BACKGROUND: Previous research has found that health-related quality of life (HRQOL) differs among obese individuals depending on treatment-seeking status, with greater impairments found in obese individuals seeking treatments of greatest intensity. The goals of this study were to determine: 1) if there are differences in obesity-specific HRQOL between seekers of gastric bypass surgery and non-treatment-seeking controls; and, 2) if the presence and number of co-morbid conditions impacts on HRQOL. METHODS: Participants were 339 surgical cases (mean age 42.9, mean BMI 47.7, 85.5% women) and 87 controls (mean age 48.8, mean BMI 43.5, 71.3% women). Obesity-specific HRQOL was assessed using the Impact of Weight on Quality of Life-Lite (IWQOL-Lite). Subjects were given a detailed medical history to determine the presence of co-morbid conditions. RESULTS: After controlling for BMI, age, and gender, obesity-specific HRQOL was significantly more impaired (P<.001) in the surgery-seeking group than in the control group on all 5 scales and total score of the IWQOL-Lite. For total score, physical function and sexual life, there was increasing impairment with increasing number of co-morbid conditions. Treatment-seeking status, BMI, gender, and the presence of depression accounted for most of the variance in IWQOL-Lite total score. CONCLUSIONS: Persons seeking gastric bypass expe rience poorer HRQOL than non-treatment-seeking individuals after controlling for BMI, age, and gender. The presence of co-morbid conditions contributes to some aspects of HRQOL impairment.

A major predisposition locus for severe obesity, at 4p15-p14.

Although the predisposition to morbid obesity is heritable, the identities of the disease-causing genes are largely unknown. Therefore, we have conducted a genomewide search with 628 markers, using multigenerational Utah pedigrees to identify genes involved in predisposition to obesity. In the genomewide search, we identified a highly significant linkage to high body-mass index in female patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.1 and a nonparametric linkage (NPL) score of 5.3. To further delineate the linkage, we increased both the marker density around D4S2632 and the size of our pedigree data set. As a result, the linkage evidence increased to a multipoint HLOD score of 9.2 (at D4S3350) and an NPL score of 11.3. Evidence from almost half of the families in this analysis support this linkage, and therefore the gene in this region might account for a significant percentage of the genetic predisposition to severe obesity in females. However, further studies are necessary to clarify the effect that this gene has in males and in the general population.