Search

Background: Bariatric surgery leads to long-term remission and reduced incidence of diabetes, hypertension, and dyslipidemia. Short-term studies suggest reduction in specific fat depots may be more predictive of health improvement than reduced body mass index (BMI). Visceral, subcutaneous, epicardial, and liver fat, measured 11 years after bariatric surgery, were associated with long-term remission and incidence of diabetes, dyslipidemia, and hypertension. Methods: Fat depots an average of 11 (maximum 14) years after surgery were quantified by noncontrast computed tomography in subjects who did (N = 261; 86% gastric bypass) or did not (N = 243) have bariatric surgery. Multiple regression related fat depots to disease endpoints with and without adjustment for change in BMI and surgical status. Results: Visceral fat was 42% lower, subcutaneous fat 20% lower, epicardial fat 30% lower, and liver-to-spleen density ratio 9% higher at follow-up in the bariatric surgery group compared with the nonsurgery group (all P

OBJECTIVE Gastric bypass surgery results in long-term weight loss. Small studies have examined protein changes during rapid weight loss (up to 1 or 2 years post surgery). This study tested whether short-term changes were maintained after 12 years. METHODS A 12-year follow-up, protein-wide association study of 1,297 SomaLogic aptamer-based plasma proteins compared short- (2-year) and long-term (12-year) protein changes in 234 individuals who had gastric bypass surgery with 144 nonintervened individuals with severe obesity. RESULTS There were 51 replicated 12-year protein changes that differed between the surgery and nonsurgery groups. Adjusting for change in BMI, only 12 proteins remained significant, suggesting that BMI change was the primary reason for most protein changes and not non-BMI-related surgical effects. Protein changes were related to BMI changes during both weight-loss and weight-regain periods. The significant proteins were associated primarily with lipid, uric acid, or resting energy expenditure clinical variables and metabolic pathways. Eight protein changes were associated with 12-year diabetes remission, including apolipoprotein M, sex hormone binding globulin, and adiponectin (p < 3.5 × 10-5 ). CONCLUSIONS This study showed that most short-term postsurgical changes in proteins were maintained at 12 years. Systemic protection pathways, including inflammation, complement, lipid, and adipocyte pathways, were related to the long-term benefits of gastric bypass surgery.

Gastric bypass surgery results in long-term weight loss due to re-routing of the gastro-intestinal anatomy and dietary intake alterations. Studies have examined protein change during rapid weight loss (up to 1 year post-surgery), but whether protein changes are maintained long-term after weight stabilization is unknown. To identify proteins and pathways involved with the long-term beneficial effects of weight loss, abundances of 1297 blood-circulating proteins were measured at baseline, 2 and 12 years after Roux-en-Y gastric bypass surgery. Protein changes were compared between 234 surgery and 144 non-surgery subjects with severe obesity, with discovery and replication subgroups. Seventy-one protein changes were associated with 12-year BMI changes and 58 (7 unique) with surgical status. Protein changes, including ApoM, were most strongly associated with long-term changes in lipids (HDL-C and triglycerides). Inflammation, adipogenesis, cellular signaling, and complement pathways were implicated. Short-term improvements in protein levels were maintained long-term, even after some weight regain.

Background Progressive cardiac remodeling and worsening myocardial function over time have been proposed as potential mediators of heart failure in obesity. Methods and Results We serially assessed cardiac structure and function in 254 subjects participating in a longitudinal study of obesity. Demographic, clinical, laboratory, and echocardiographic features were determined at baseline and 2‐, 6‐, and 11‐year follow‐up. We measured body mass index ( BMI ) exposure as the area under the curve of the BMI at each of the 4 visits. At enrollment, mean age of the subjects was 47 years, 79% were women, mean BMI was 44 kg/m 2 , 26% had diabetes mellitus, 48% had hypertension, and 53% had hyperlipidemia. Between baseline and 11 years, BMI increased by 1.1 and 0.3 kg/m 2 in men and women, respectively. There were modest increases in left ventricular ( LV ) end‐diastolic volume, LV mass, and left atrial volume, and significant decreases in early/late mitral diastolic flow velocity ratio and E wave deceleration time. However, there were no significant changes in LV ejection fraction or ratio of early mitral diastolic flow velocity/early mitral annular velocity, whereas right ventricular fractional area change increased. Significant predictors of the change in LV mass were male sex, baseline BMI , BMI area under the curve, and change in LV stroke volume, but not smoking, hypertension, or diabetes mellitus. Conclusions In long‐standing, persistent severe obesity, there was evidence of cardiac remodeling over a period of 11 years, but no clear worsening of systolic or diastolic function. Measures of remodeling were most strongly related to BMI . The observed changes might predispose to heart failure with preserved ejection fraction, but are not classic for an evolving dilated cardiomyopathy.

Background: The prevalence of metabolic syndrome (MetS) generally rises with increasing adiposity, but tends to plateau at the highest levels of body mass index (BMI) with some individuals, even with severe obesity, expressing few or no components of MetS. We examined factors associated with the expression of MetS in severely obese women participating in a large observational study. Methods: Anthropometrics, including Heath equation-adjusted bioimpedance-determined fat-free mass (FFM) and fat mass (FM), lipids and related laboratory measurements, resting energy expenditure (REE), and respiratory quotient (RQ), were studied in 949 women with severe obesity. Results: Even though the mean BMI was 45.7 kg/m2 and all participants met MetS criteria for increased waist circumference, 30% of subjects did not have MetS. Unadjusted FM (P = 0.0011), FFM (P

Background Few studies have assessed differences in the gut microbiota composition after bariatric surgery in the long term or whether differences are correlated with remission of type 2 diabetes. Objectives This observational study assessed differences in the gut microbiota between individuals at up to 13 years after surgery and a comparison group of individuals with severe obesity. The relationship between type 2 diabetes remission and the gut microbiota was also assessed. Setting University. Methods Stool samples were collected from individuals completing bariatric surgery (surgery group; n = 16) and individuals with severe obesity that did not receive surgery (nonsurgery group; n = 19) as part of the 12-year follow-up in the Utah Obesity Study. Metabolic health data were collected at baseline and the follow-up examination. The gut microbiota was quantified by sequencing the V4 region of the 16 S rRNA gene. Significant differences in microbiota composition with surgery and other covariates were determined by Unifrac distance analysis and permutational multivariate analysis of variance. Significant differences in the relative abundance of individual bacterial taxa were assessed using analysis of composition of microbiomes software. Results The surgery group had higher relative abundances of Verrucomicrobiaceae (5.7 ± 1.3% versus 1.1 ± .3%) and Streptococcaceae (6.3 ± 1.0% versus 3.2 ± .8%), but lower relative abundances of Bacteroidaceae (8.8 ± 1.8% versus 18.6 ± 2.3%) 10.6 years after surgery. In a small subset of 8 individuals, a higher relative abundance of Akkermansia muciniphila was correlated with type 2 diabetes remission. Conclusions Differences in the gut microbiota are evident a decade after bariatric surgery compared with individuals with severe obesity that did not undergo surgery. The observed long-term differences are consistent with previous findings.

Understanding of the long-term clinical outcomes associated with bariatric surgery has recently been advanced. Research related to the sequelae of diabetes—in particular, long-term microvascular and macrovascular complications—in patients who undergo weight-loss surgery is imperative to this pursuit. While numerous randomized control trials have assessed glucose control with bariatric surgery compared with intensive medical therapy, bariatric surgery outcome data relating to microvascular and macrovascular complications have been limited to observational studies and nonrandomized clinical trials. As a result, whether bariatric surgery is associated with a long-term reduction in microvascular and macrovascular complications when compared with current intensive glycemic control therapy cannot be determined because the evidence is insufficient. However, the consistent salutary effects of bariatric surgery on diabetes remission and glycemic improvement support the opportunity (and need) to conduct high-quality studies of bariatric surgery versus intensive glucose control. This review provides relevant background information related to the treatment of diabetes, hyperglycemia, and long-term complications; reports clinical findings (to date) with bariatric surgery; and identifies ongoing research focusing on long-term vascular outcomes associated with bariatric surgery.

Obesity and low cardiorespiratory fitness are both established predictors of cardiovascular disease morbidity and mortality. Whether the protective effects of fitness outweigh the deleterious effects of obesity, however, remains a topic of debate. To extend knowledge of the relative influence of fitness and fatness on cardiovascular disease outcomes, however, attention must be paid to measurement quality. Eliminating inherent bias of self-report and including the highest quality assessments of cardiorespiratory fitness and fatness simultaneously are imperative for head-to-head comparisons. Studies must move beyond body mass index and total body fat percentage to differentiate the heterogenous effects of various adipose tissue depots on cardiovascular risk. Imaging techniques that measure visceral adiposity and other risk-laden ectopic adipose depots while also quantifying cardioprotective adipose depots such as lower body subcutaneous fat and even non-adipose tissues such as skeletal muscle may further illuminate the influence of body composition on cardiovascular health. This review underscores key studies within a large body of literature that provide the foundation for the fit-vs.-fat debate in the context of cardiovascular disease risk, and identifies important considerations for future research.

Few long-term or controlled studies of bariatric surgery have been conducted to date. We report the 12-year follow-up results of an observational, prospective study of Roux-en-Y gastric bypass that was conducted in the United States.A total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux-en-Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (nonsurgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia.The follow-up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was -45.0 kg (95% confidence interval [CI], -47.2 to -42.9; mean percent change, -35.0) at 2 years, -36.3 kg (95% CI, -39.0 to -33.5; mean percent change, -28.0) at 6 years, and -35.0 kg (95% CI, -38.4 to -31.7; mean percent change, -26.9) at 12 years; the mean change at 12 years in nonsurgery group 1 was -2.9 kg (95% CI, -6.9 to 1.0; mean percent change, -2.0), and the mean change at 12 years in nonsurgery group 2 was 0 kg (95% CI, -3.5 to 3.5; mean percent change, -0.9). Among the patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. The odds ratio for the incidence of type 2 diabetes at 12 years was 0.08 (95% CI, 0.03 to 0.24) for the surgery group versus nonsurgery group 1 and 0.09 (95% CI, 0.03 to 0.29) for the surgery group versus nonsurgery group 2 (P0.001 for both comparisons). The surgery group had higher remission rates and lower incidence rates of hypertension and dyslipidemia than did nonsurgery group 1 (P0.05 for all comparisons).This study showed long-term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux-en-Y gastric bypass. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Large case-control studies using genome-wide association markers have been published identifying genes related to obesity (1). At least 17 genetic regions have been suggested by such studies. The best replicated of these genes are the FTO and MC4R genes (2–8). There is a long history of candidate gene studies relating common genetic variants to various measures of obesity (9). The gene with the most frequent prevalence of multiple mutations or polymorphisms related to obesity is the MC4R gene (10). Because obesity is an appetite-related condition, the genes related to appetite control have been studied in various populations, particularly the NPY and NPY receptor genes. Generally, there has been poor replication of variants in NPY, PYY, NPY1R and NPY5R being associated with obesity, while more positive studies have implicated NPY2R, a well-known candidate gene for obesity development and control of food intake (11–20). However, even the NPY2R studies have not been compelling because of their marginal significance levels and findings that occur most often in men rather than women (12–14). In addition, most of these studies have genotyped SNPs in the 5’ region of the NPY2R gene or one of the three synonymous change variants in exon 2 of the gene. The NPY2R gene has two exons, but the start codons for transcription occur at exon 2, not exon 1. Intron 1 is a region with low linkage disequilibrium (LD) that is not well tagged by the 5’ SNPs, which are located in one LD block, or the downstream end of intron 1 and exon 2 SNPs, which are in a second LD block. Therefore, we typed multiple markers in intron 1, along with some previously studied 5’ and exon 2 SNPs. The independence of the NPY2R association with BMI was assessed by also typing one or more SNPs in the NPY, NPY1R, NPFFR2 (a G-protein receptor that binds neuropeptides), PPARGC1A (a PPAR-γ coactivator of gene transcription including UCP1), OR7D4 (an olfactory receptor gene), and MC4R genes (14, 21–24). Four SNPs were genotyped in the NPFFR2 gene that formed a haplotype previously shown to be associated with leanness (25). The SNP rs9939609 in the FTO gene was previously genotyped in these subjects and was significantly associated with BMI (5). In addition to testing the independence of each of the above genes on BMI, the ability of haplotypes to improve the associations with BMI was assessed.

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 t...

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.

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.

Background Several studies have reported that carriers of the 103I allele of the melanocortin-4 receptor (MC4R) gene had lower body weight than did persons with the wild-type genotype. A recent study found an association of the MC4R 103I variant with carbohydrate intake, which may mediate some of the association of this variant with leanness. Objective The purpose of the study was to investigate the association between the MC4R V103I polymorphism and the dietary intake of persons with severe obesity, which was derived by using the Willett food-frequency questionnaire. Design The MC4R V103I polymorphism was genotyped in a group of 1029 severely obese white subjects with an average body mass index (BMI; in kg/m(2)) of 46.0 (range: 33-92). Results Carriers of the 103I allele had significantly higher daily energy (364 kcal/d or 19%; P = 0.03) and carbohydrate (57 g/d or 27%; P = 0.01) intakes than did noncarriers, but there was no relation with BMI. No notable association of this polymorphism with lipid and glucose variables of the metabolic syndrome was observed. Conclusions The higher dietary intake of carbohydrates in severely obese persons with the MC4R 103I variant is in line with previous findings. It may indicate a differential effect on body size measures in extremely obese subjects as compared with the general population.

OBJECTIVE—High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity. RESEARCH DESIGN AND METHODS—Four single nucleotide polymorphisms within SLC2A9 (rs6855911, rs7442295, rs6449213, and rs12510549) were genotyped in the population-based prospective Bruneck Study (n = 800) and in a case-control study from Utah including 1,038 subjects recruited for severe obesity and 831 control subjects. RESULTS—We observed highly significant associations between all four polymorphisms and uric acid levels in all study groups. Each copy of the minor allele decreased age- and sex-adjusted uric acid levels by 0.30–0.35 mg/dl on average, which translates to a relative decrease of 5–6% with P values ranging from 10−9 to 10−11 in the combined analysis. An extended adjustment for BMI, creatinine, gout medication, and alcohol intake improved P values to a range of 10−14 to 10−20. The association was more pronounced in women and the population-based Bruneck Study and was significantly modified by BMI, with stronger effect sizes in individuals with high BMI. CONCLUSIONS—Genetic variants within SLC2A9 have significant effects on uric acid levels and are modified by sex and BMI.

Objective: A previous epidemiological study showed an association of the insulin-induced gene 2 (INSIG2) gene with BMI. Additionally, experimental investigations in animals and cell culture provided evidence that this gene might be involved in lipoprotein and free fatty acid (FFA) metabolism. Therefore, the aim of this study was to examine the association between the rs7566605 variant near the INSIG2 gene and BMI and to extend it to other quantitative measures of obesity, as well as parameters of lipoprotein and FFA metabolism. Methods and Procedures: We genotyped rs7566605 in a group of severely obese white patients (n = 1,026) with an average BMI of 46.0 kg/m2 and a control group (n = 818) from Utah, as well as in the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study from Austria, which is based on a healthy working population (n = 1,696). Results: We observed no difference in the genotype frequency of rs7566605 of INSIG2 between obese subjects and population-based controls from Utah. Furthermore, we did not find evidence of an association with measures of body composition (BMI, waist, waist-to-hip ratio, percentage body fat, amount of visceral and subcutaneous abdominal adipose fat) or lipoprotein metabolism (total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides, and FFAs) in the Utah study population or in the independent SAPHIR study. Discussion: Our results do not support an association of the INSIG2 gene with the regulation of body weight or parameters related to lipoprotein metabolism.

The question of whether or not nonsurgical intentional or voluntary weight loss results in reduced mortality has been equivocal, with long-term mortality following weight loss being reported as increased, decreased, and not changed. In part, inconsistent results have been attributed to the uncertainty of whether the intentionality of weight loss is accurately reported in large population studies and also that achieving significant and sustained voluntary weight loss in large intervention trials is extremely difficult. Bariatric surgery has generally been free of these conflicts. Patients voluntarily undergo surgery and the resulting weight is typically significant and sustained. These elements, combined with possible non-weight loss-related mechanisms, have resulted in improved comorbidities, which likely contribute to a reduction in long-term mortality. This paper reviews the association between bariatric surgery and long-term mortality. From these studies, the general consensus is that bariatric surgical patients have: 1) significantly reduced long-term all-cause mortality when compared to severely obese non-bariatric surgical control groups; 2) greater mortality when compared to the general population, with the exception of one study; 3) reduced cardiovascular-, stroke-, and cancer-caused mortality when compared to severely obese non-operated controls; and 4) increased risk for externally caused death such as suicide.

We identified eight candidate thinness predisposition variants from the Illumina HumanExome chip genotyped on members of pedigrees selected for either healthy thinness or severe obesity. For validation, we tested the candidates for association with healthy thinness in additional pedigree members while accounting for effects of obesity-associated genes: NPFFR2, NPY2R, FTO, and MC4R. Significance was obtained for the interaction of FTO rs9939609 with APOH missense variant rs52797880 (minor allele frequency 0.054). The thinness odds ratio was estimated as 2.15 (p < 0.05) for the combination of APOH heterozygote with the homozygote for the non-obesity FTO allele. Significance was not obtained for any other combination of a candidate variant with an obesity gene or for any of the eight candidates tested independently.

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.

The purpose of this study was to determine if the U.S. National Institutes of Health Diabetes Prevention Program (DPP) could be successfully implemented in a worksite setting. Thirty-seven adult employees of BD Medical Systems of Sandy, Utah were enrolled in a single-group time-series study using the DPP. Two-hour oral glucose tolerance tests (OGTT) and other outcomes were measured at baseline, 6 months, and 12 months. Weight, body mass index, waist circumference, 2-hour OGTT, very low density lipoproteins, triglycerides, and aerobic fitness were significantly improved at 6 and 12 months and showed overall significant improvement across time. Fasting blood insulin, total cholesterol, low density lipoproteins, and total cholesterol/high density lipoproteins ratio were significantly improved at 6 months, but not at 12 months. Eighteen of the program participants (51%) were no longer in the pre-diabetes and diabetes categories after 1 year. Existing worksite health promotion and occupational health professionals can successfully offer the DPP and help employees improve glucose tolerance.

Background/Objectives.To identify copy number variants (CNVs) which are associated with body mass index (BMI).Subjects/Methods.CNVs were identified using array comparative genomic hybridization (aCGH) on members of pedigrees ascertained through severely obese (BMI ≥ 35 kg/m2) sib pairs (86 pedigrees) and thin (BMI ≤ 23 kg/m2) probands (3 pedigrees). Association was inferred through pleiotropy of BMI with CNVlog⁡2intensity ratio.Results.A 77-kilobase CNV on chromosome 20q13.3, confirmed by real-time qPCR, exhibited deletions in the obese subjects and duplications in the thin subjects (P=2.2×10-6). Further support for the presence of a deletion derived from inference by likelihood analysis of null alleles for SNPs residing in the region.Conclusions.One or more of 7 genes residing in a chromosome 20q13.3 CNV region appears to influence BMI. The strongest candidate isARFRP1, which affects glucose metabolism in mice.

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.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.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).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.

Background: The concept of a cardiomyopathy due to obesity is based mainly on relatively small cross sectional studies that are hampered by referral bias. Methods: We analyzed 254 severely obese subjects (BMI ≥ 35 kg/m2) participating in a longitudinal study of obesity and CV disease. All of the

Interaction between maternal obesity, intrauterine environment and adverse clinical outcomes of newborns has been described. Using statewide birth certificate data, this retrospective, matched-control cohort study compared paired birth weights and complications of infants born to women before and after Roux-en-Y gastric bypass surgery (RYGB) and to matched obese non-operated women in several different groups. Women who had given birth to a child before and after RYGB (group 1; n=295 matches) and women with pregnancies after RYGB (group 2; n=764 matches) were matched to non-operated women based on age, body mass index (BMI) prior to both pregnancy and RYGB, mother’s race, year of mother/s birth, date of infant births and birth order. In addition, birth weights of 13 143 live births before and/or after RYGB of their mothers (n=5819) were compared (group 3). Odds ratios (ORs) for having a large-for-gestational-age (LGA) neonate were significantly less after RYGB than for non-surgical mothers: ORs for groups 1 and 2 were 0.19 (0.08–0.38) and 0.33 (0.21–0.51), respectively. In contrast, ORs in all three groups for risk of having a small for gestational age (SGA) neonate were greater for RYGB mothers compared to non-surgical mothers (ORs were 2.16 (1.00–5.04); 2.16 (1.43–3.32); and 2.25 (1.89–2.69), respectively). Neonatal complications were not different for group 1 RYGB and non-surgical women for the first pregnancy following RYGB. Pregnancy-induced hypertension and gestational diabetes were significantly lower for the first pregnancy of mothers following RYGB compared to matched pregnancies of non-surgical mothers. Women who had undergone RYGB not only had lower risk for having an LGA neonate compared to BMI-matched mothers, but also had significantly higher risk for delivering an SGA neonate following RYGB. RYGB women were less likely than non-operated women to have pregnancy-related hypertension and diabetes.

Background —Cardiorespiratory fitness is favorably associated with most modifiable coronary heart disease (CHD) risk factors. Findings are limited, however, by few data for women, persons with existing CHD, and low-risk populations. In the present study, we described cross-sectional associations between cardiorespiratory fitness and CHD risk factors in a large cohort of middle-aged men and women, of whom the majority were LDS Church members (Mormons), with and without existing CHD. Methods and Results —Comprehensive health examinations were performed on 3232 men (age 45.9±10.8 years) and 1128 women (age 43.8±12.8 years) between 1975 and 1997. Maximal treadmill exercise testing was used to categorize those with (12% of the men and 10% of the women) and those without CHD into age- and sex-specific cardiorespiratory fitness quintiles. After adjustments for age, body fat, smoking status, and family history of CHD, favorable associations were observed between fitness and most CHD risk factors among men and women, regardless of CHD status. Conclusions —These data indicate that enhanced levels of cardiorespiratory fitness may confer resistance to elevations in CHD risk factors even in a low-risk sample of middle-aged men and women. Furthermore, these findings reinforce current public health recommendations that advocate increased national levels of physical activity and cardiorespiratory fitness for primary and secondary CHD prevention.

The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE- TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues.

A Utah family with morbid obesity was extended to include 122 persons in four generations for the purpose of characterizing anthropometric and biochemical variables in family members with and without morbid obesity. Seventy-seven subjects had blood drawn for biochemical analyses. Of the 77 subjects, 12 were morbidly obese (≥44.5 kg or 100 pounds overweight), 20 were between 22.5–45.4 kg (50 and 99 pounds) overweight and 45 were less than 22.5 kg (50 pounds) overweight Sixty-two randomly-ascertained controls were used for comparisons of age- and gender-adjusted study variables. Morbidly obese subjects had mean body mass indices (BMI) of 41.0 kg/m2 (62 kg over ideal weight) compared to 25.3 kg/m2 (10 kg overweight) in the

Importance Bariatric surgery is effective in reducing all-cause and cause-specific long-term mortality. Whether the long-term mortality benefit of surgery applies to all ages at which surgery is performed is not known. Objective To examine whether gastric bypass surgery is equally effective in reducing mortality in groups undergoing surgery at different ages. Design, Setting, and Participants All-cause and cause-specific mortality rates and hazard ratios (HRs) were estimated from a retrospective cohort within 4 categories defined by age at surgery: younger than 35 years, 35 through 44 years, 45 through 54 years, and 55 through 74 years. Mean follow-up was 7.2 years. Patients undergoing gastric bypass surgery seen at a private surgical practice from January 1, 1984, through December 31, 2002, were studied. Data analysis was performed from June 12, 2013, to September 6, 2015. A cohort of 7925 patients undergoing gastric bypass surgery and 7925 group-matched, severely obese individuals who did not undergo surgery were identified through driver license records. Matching criteria included year of surgery to year of driver license application, sex, 5-year age groups, and 3 body mass index categories. Intervention Roux-en-Y gastric bypass surgery. Main Outcomes and Measures All-cause and cause-specific mortality compared between those undergoing and not undergoing gastric bypass surgery using HRs. Results Among the 7925 patients who underwent gastric bypass surgery, the mean (SD) age at surgery was 39.5 (10.5) years, and the mean (SD) presurgical body mass index was 45.3 (7.4). Compared with 7925 matched individuals not undergoing surgery, adjusted all-cause mortality after gastric bypass surgery was significantly lower for patients 35 through 44 years old (HR, 0.54; 95% CI, 0.38-0.77), 45 through 54 years old (HR, 0.43; 95% CI, 0.30-0.62), and 55 through 74 years old (HR, 0.50; 95% CI, 0.31-0.79; P P = .34). The lack of mortality benefit in those undergoing gastric bypass surgery at ages younger than 35 years primarily derived from a significantly higher number of externally caused deaths (HR, 2.53; 95% CI, 1.27-5.07; P = .009), particularly among women (HR, 3.08; 95% CI, 1.4-6.7; P = .005). Patients undergoing gastric bypass surgery had a significantly lower age-related increase in mortality than severely obese individuals not undergoing surgery ( P = .001). Conclusions and Relevance Gastric bypass surgery was associated with improved long-term survival for all patients undergoing surgery at ages older than 35 years, with externally caused deaths only elevated in younger women. Gastric bypass surgery is protective against mortality even for older patients and also reduces the age-related increase in mortality observed in severely obese individuals not undergoing surgery.

Iron overload is associated with increased diabetes risk. We therefore investigated the effect of iron on adiponectin, an insulin-sensitizing adipokine that is decreased in diabetic patients. In humans, normal-range serum ferritin levels were inversely associated with adiponectin, independent of inflammation. Ferritin was increased and adiponectin was decreased in type 2 diabetic and in obese diabetic subjects compared with those in equally obese individuals without metabolic syndrome. Mice fed a high-iron diet and cultured adipocytes treated with iron exhibited decreased adiponectin mRNA and protein. We found that iron negatively regulated adiponectin transcription via FOXO1-mediated repression. Further, loss of the adipocyte iron export channel, ferroportin, in mice resulted in adipocyte iron loading, decreased adiponectin, and insulin resistance. Conversely, organismal iron overload and increased adipocyte ferroportin expression because of hemochromatosis are associated with decreased adipocyte iron, increased adiponectin, improved glucose tolerance, and increased insulin sensitivity. Phlebotomy of humans with impaired glucose tolerance and ferritin values in the highest quartile of normal increased adiponectin and improved glucose tolerance. These findings demonstrate a causal role for iron as a risk factor for metabolic syndrome and a role for adipocytes in modulating metabolism through adiponectin in response to iron stores.

Background Few studies have evaluated the long-term outcomes of bariatric surgery patients in relation to obese individuals not participating in weight loss interventions. Our objective was to evaluate the 6-year changes in health-related quality of life (HRQOL) in gastric bypass (GB) patients versus 2 obese groups not undergoing surgical weight loss. The study setting was a bariatric surgery practice. Methods A total of 323 GB patients were compared with 257 individuals who sought but did not undergo gastric bypass and 272 population-based obese individuals using weight-specific (Impact of Weight on Quality of Life-Lite) and general (Medical Outcomes Study Short-Form 36 Health Survey) HRQOL questionnaires at baseline and 2 and 6 years later. Results At 6 years, compared with the controls, the GB group exhibited significant improvements in all domains of weight-specific and most domains of general HRQOL (i.e., all physical and some mental/psychosocial). The 6-year percentage of excess weight loss correlated significantly with improvements in both weight-specific and physical HRQOL. The HRQOL scores were fairly stable from 2 to 6 years for the GB group, with small decreases in HRQOL corresponding to some weight regain. Conclusions GB patients demonstrated significant improvements in most aspects of HRQOL at 6 years compared with 2 nonsurgical obese groups. Despite some weight regain and small decreases in HRQOL from 2 to 6 years postoperatively, the HRQOL was relatively stable. These results support the effectiveness of weight loss achieved with gastric bypass surgery for improving and maintaining long-term HRQOL.

The effect of sleep apnea on the reproductive function of obese men is not entirely elucidated. The objective of this study was to define the effect of sleep apnea on the reproductive hormones and sexual function in obese men. This study included 89 severely obese men with BMI ≥35 kg/m2 considering gastric bypass surgery. Anthropometrics (weight, and BMI), reproductive hormones, and sleep studies were measured. The sexual quality of life was assessed using the Impact of Weight on Quality of Life-Lite questionnaire (IWQOL-Lite). The mean age of our patients was 46.9 ± 11.0 years, the mean BMI was 47.8 ± 8.7 kg/m2 and the mean weight was 337.7 ± 62.4 lb. After correction for age and BMI, means of free testosterone per severity group of sleep apnea were as follows: no or mild sleep apnea 74.4 ± 3.8 pg/ml, moderate sleep apnea 68.6 ± 4.2 pg/ml, and severe sleep apnea 60.2 ± 2.92 pg/ml, P = 0.014. All other parameters of sleep apnea including hypopnea index, percent time below a SpO2 of 90%, and percent time below a SpO2 of 80% were also negatively correlated with testosterone levels after correction for age and BMI. BMI and presence of coronary artery disease decreased the sexual quality of life. Sleep apnea was associated with reduced sexual quality of life. In summary, sleep apnea negatively affects testosterone levels independent of BMI. Severely obese men had decreased sexual quality of life.

Recent studies have shown major gene effects for obesity in randomly ascertained families. To investigate the familial aggregation of a specific subset of obesity, which is particularly prone to medical complications, families with morbid obesity were studied. This condition occurs in 1%-2% of the population and is defined as 45.5 kg (100 pounds) or more over ideal weight. First-degree relatives of 221 morbidly obese probands (1560 adults) were identified, and height and weight (current and greatest) were obtained from each family member. Morbid obesity occurred in the family members of the probands 8 times more often than in the general population. Of the morbidly obese probands, 48% had one or more first-degree relatives who were also morbidly obese compared to a 6% population estimate. By the ages of 20-24, 12% of the morbidly obese probands were already 45.5 kg or more overweight, and 45% were 22.7 kg (50 pounds) or more overweight. There was little difference in the prevalence of familial morbid obesity by the gender of the probands: 47% of the male probands and 48% of the female probands had another morbidly obese relative, while 67% and 53% of the early onset (before age 25) male and female probands, respectively, had one or more first-degree relatives who were also morbidly obese. In addition to the extreme degree of familial aggregation, the prevalence of morbid obesity in parent-offspring sets was calculated within the morbidly obese families. Morbidly obese families who have one or two morbidly obese parents have a 2.6 times increased risk (p

The objective of this study was to test the hypothesis that gastric bypass surgery (GBS) would favorably impact cardiac remodeling and function.GBS is increasingly used to treat severe obesity, but there are limited outcome data.We prospectively studied 423 severely obese patients undergoing GBS and a reference group of severely obese subjects that did not have surgery (n = 733).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); p0.0001), 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.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.

Obesity is associated with significantly increased cardiovascular mortality that has been attributed, in part, to sympathetic activation. Gastric bypass surgery (GBS) appears to increase long-term survival in the severely obese, but the mechanisms responsible for this increase are still being sought. Heart rate (HR) recovery after exercise reflects the balance of cardiac autonomic input from the sympathetic and parasympathetic systems. Blunted HR recovery is a very powerful predictor of increased mortality, whereas enhanced HR recovery portends a good prognosis.The purpose of this study was to evaluate the effect of marked weight loss achieved via GBS on HR recovery.Severely obese patients underwent submaximal exercise testing (80% predicted maximum HR) at baseline and 2 years after GBS (n = 153) or nonsurgical treatment (n = 188).Patients in the GBS group lost an average of 100 ± 37 lb compared to 3 ± 22 lb in the nonsurgical group (P.001, GBS vs nonsurgical). Resting HR decreased from 73 bpm to 60 bpm in the GBS group and from 74 bpm to 68 bpm in nonsurgical patients (P.001). HR recovery improved by 13 bpm in the GBS group but did not change in the nonsurgical group (P.001 GBS vs nonsurgical). In multivariable analysis, the independent correlates of HR recovery at the 2-year time point were resting HR, treadmill time, age, body mass index, and HOMA-IR (an index of insulin resistance).Marked weight loss 2 years after GBS resulted in a significant decrease in resting HR and an enhancement in HR recovery after exercise. These changes likely are attributable to improvement in insulin sensitivity and cardiac autonomic balance. Whether and to what extent this contributes to a reduction in cardiovascular mortality with GBS remains to be determined.

Objective To describe the influence of the TTTA aromatase polymorphism (TTTAn) on the relation between obesity and plasma estradiol (E 2 ) in obese men. Design A 2-year cohort study. Setting Clinical research center. Patient(s) Severely obese men (31 who had had gastric bypass surgery and 118 controls). Intervention(s) Men were genotyped for the TTTAn CYP19A1 polymorphism. Anthropomorphic measures, plasma E 2 , and other hormonal levels were determined at baseline and 2-year follow-up. Main Outcomes Measure(s) Relationships between weight and changes in weight and plasma E 2 were examined in relation to the TTTAn polymorphism. Result(s) The mean age was 46.5 ± 10.82 years, and mean body mass index was 47.1 ± 8.46 kg/m 2 . The most common repeats were 7 and 11. TTTAn number did not correlate with plasma E 2 in the univariate analysis. When patients were stratified per weight group, the correlation between plasma E 2 and weight was seen only among men with a higher TTTA repeat at baseline and 2 years. Similarly, only men with higher TTTA exhibited reduced E 2 levels after weight loss. Conclusion(s) A higher TTTA repeat is associated with a strengthened relationship between obesity and E 2 . The well-established effect of increased weight on plasma E 2 appears to be absent in men with low TTTA numbers.

Two recent genome-wide association studies identified the liver expressed transmembrane protein adiponutrin to be associated with liver related phenotypes such as non-alcoholic fatty liver disease and liver function enzymes. These associations were not uniformly reported for various ethnicities. The aim of this study was to investigate a common non-synonymous variant within adiponutrin (rs738409, exon 3) with parameters of liver function in three independent West Eurasian study populations including a total of 4290 participants.The study was performed in (1) the population based Bruneck Study (n=783), (2) the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk Study from Austria based on a healthy working population (n=1705), and the Utah Obesity Case-Control Study including a group of 1019 severely obese individuals (average body mass index 46.0 kg/m(2)) and 783 controls from the same geographical region of Utah. Liver enzymes measured were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT).A strong recessive association of this polymorphism was found with age and gender adjusted ALT and AST concentrations: being homozygous for the minor allele resulted in a highly significant increase of ALT concentration of 3.53 U/l (p=1.86 x 10(-9)) and of AST concentration of 2.07 U/l (p=9.58 x 10(-6)), respectively. The associations were consistently found in all three study populations.The highly significant associations of this transversion polymorphism within the adiponutrin gene with increased ALT and AST concentrations support a role for adiponutrin as a susceptibility gene for hepatic dysfunction.

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 ≥ 35 kg/m2) 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.

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.

Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23 274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m(2)) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 x 10(-7)), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 x 10(-6)) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 x 10(-4)). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoproteins.

Coronary artery disease (CAD) is common and multifactorial. Members of the Church of Jesus Christ of Latter-day Saints (LDS, or Mormons) in Utah may have lower cardiac mortality than other Utahns and the US population. Although the LDS proscription of smoking likely contributes to lower cardiac risk, it is unknown whether other shared behaviors also contribute. This study evaluated potential CAD-associated effects of fasting. Patients (n(1) = 4,629) enrolled in the Intermountain Heart Collaborative Study registry (1994 to 2002) were evaluated for the association of religious preference with CAD diagnosis (> or = 70% coronary stenosis using angiography) or no CAD (normal coronaries

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/m 2 ; 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.

Three polymorphisms of the glutamate decarboxylase 2 gene, which encodes the glutamic acid decarboxylase enzyme, have been associated with severe obesity in a large French cohort. One of these polymorphisms was shown to have functional consequences on promoter expression. Another polymorphism was associated with insulin levels and secretion. These associations were examined in 855 severely obese Utah subjects (mean BMI = 48 kg/m(2)) and a normal-weight and normoglycemic subset (N = 130, mean BMI = 22 kg/m(2)) of a random sample of the Utah population (N = 462). Comparisons of the normal-weight random group with the severely obese group did not result in significant genotype or allele frequency differences for any of the three polymorphisms, C61450A, T83897A, or A-243G (all por = 0.18). Haplotypes were also not related to severe obesity (p = 0.10). None of the polymorphisms was significantly related to fasting glucose, insulin levels, or homeostasis model assessment insulin resistance or secretion indices. This study of normal-weight and severely obese subjects from Utah does not provide evidence for involvement of the three genotyped polymorphisms in the glutamate decarboxylase 2 gene with obesity or with insulin- and glucose-related measures associated with obesity.

KOLOTKIN, RONETTE L., MARTIN BINKS, ROSS D. CROSBY, TRULS OSTBYE, RICHARD E. GRESS, AND TED D. ADAMS. Obesity and sexual quality of life. Obesity. 2006;14:472–479. 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/m 2 ), 2) 372 patients evaluated for gastric bypass surgery (BMI 47.1 kg/m 2 ), and 3) 286 obese control subjects not seeking weight loss treatment (BMI 43.6 kg/m 2 ). 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.

Adipose triglyceride lipase (ATGL) was recently described to predominantly perform the initial step in triglyceride hydrolysis and therefore seems to play a pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the first study investigating genetic variations within the ATGL gene in humans, 12 polymorphisms identified via sequencing and database search were studied in 2,434 individuals of European ancestry from Utah. These polymorphisms and their haplotypes were analyzed in subjects not taking diabetes medication for association with plasma free fatty acids (FFAs) as primary analysis, as well as triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190, respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an outcome. FFA concentrations were significantly associated with several single nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003), consistent with additive inheritance. The pattern was similar when considering triglyceride concentrations. Furthermore, two SNPs showed associations with glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype analysis supported and extended the shown SNP association analyses. These results complement previous findings of functional studies in mammals and elucidate a potential role of ATGL in pathways involved in components of the metabolic syndrome.