Interferon-gamma released from omental adipose tissue of insulin-resistant humans alters adipocyte phenotype and impairs response to insulin and adiponectin release.

BACKGROUND: Inflammatory factors derived from adipose tissue have been implicated in mediating insulin resistance in obesity. We sought to identify these using explanted human adipose tissue exposed to innate and adaptive immune stimuli. METHODS: Subcutaneous and omental adipose tissue from obese, insulin-resistant donors was cultured in the presence of macrophage and T-cell stimuli, and the conditioned medium tested for its ability to inhibit insulin-stimulated glucose uptake into human Simpson-Golabi-Behmel Syndrome (SGBS) adipocytes. The nature of the inhibitory factor in conditioned medium was characterized physicochemically, inferred by gene microarray analysis and confirmed by antibody neutralization. RESULTS: Conditioned medium from omental adipose tissue exposed to a combination of macrophage- and T-cell stimuli inhibited insulin action and adiponectin secretion in SGBS adipocytes. This effect was associated with a pronounced change in adipocyte morphology, characterized by a decreased number of lipid droplets of increased size. The bioactivity of conditioned medium was abolished by trypsin treatment and had a molecular weight of 46 kDa by gel filtration. SGBS adipocytes exposed to a bioactive medium expressed multiple gene transcripts regulated by interferon-gamma (IFN-γ). Recombinant human IFN-γ recapitulated the effects of the bioactive medium and neutralizing antibody against IFN-γ but not other candidate factors abrogated medium bioactivity. CONCLUSIONS: IFN-γ released from inflamed omental adipose tissue may contribute to the metabolic abnormalities seen in human obesity.

Weight loss after laparoscopic adjustable gastric band and resolution of the metabolic syndrome and its components.

BACKGROUND: Substantial weight loss in the setting of obesity has considerable metabolic benefits. Yet some studies have shown improvements in obesity-related metabolic comorbidities with more modest weight loss. By closely monitoring patients undergoing bariatric surgery, we aimed to determine the effects of weight loss on the metabolic syndrome and its components and determine the weight loss required for their resolution. METHODS: We performed a prospective observational study of obese participants with metabolic syndrome (Adult Treatment Panel III criteria) who underwent laparoscopic adjustable gastric banding. Participants were assessed for all criteria of the metabolic syndrome monthly for the first 9 months, then 3-monthly until 24 months. RESULTS: There were 89 participants with adequate longitudinal data. Baseline body mass index was 42.4±6.2 kg m-2 with an average age was 48.2±10.7 years. There were 56 (63%) women. Resolution of the metabolic syndrome occurred in 60 of the 89 participants (67%) at 12 months and 60 of the 75 participants (80%) at 24 months. The mean weight loss when metabolic syndrome resolved was 10.9±7.7% total body weight loss (TBWL). The median weight loss at which prevalence of disease halved was 7.0% TBWL (17.5% excess weight loss (EWL)) for hypertriglyceridaemia; 11% TBWL (26.1-28% EWL) for high-density lipoprotein cholesterol and hyperglycaemia; 20% TBWL (59.5% EWL) for hypertension and 29% TBWL (73.3% EWL) for waist circumference. The odds ratio for resolution of the metabolic syndrome with 10-12.5% TBWL was 2.09 (P=0.025), with increasing probability of resolution with more substantial weight loss. CONCLUSIONS: In obese participants with metabolic syndrome, a weight loss target of 10-12.5% TBWL (25-30% EWL) is a reasonable initial goal associated with significant odds of having metabolic benefits. If minimal improvements are seen with this initial target, additional weight loss substantially increases the probability of resolution.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women.

AIMS: The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. METHODS: Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed. RESULTS: In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. INTERPRETATION: The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.

Controversies in bariatric surgery.

BACKGROUND: There are many controversies related to bariatric surgery. This review explores selected areas. METHODS: A combination of randomized clinical trials (RCTs), systematic reviews and expert opinion have been brought together to highlight areas of importance or conflict. RESULTS AND CONCLUSION: Metabolic surgery is an increasingly preferred term rather than bariatric or obesity surgery. Reporting should be standardized to include appropriate weight measures, valid disease measures and data on loss to follow-up. There are many putative mechanisms of effect of key bariatric procedures, but satiety and early satiation appear central. Weight loss must be durable. Long-term outcome studies (more than 10-year follow-up) show that biliopancreatic diversion is most effective, with 72 per cent excess weight loss (EWL). Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding (LAGB) are equally effective, with 54 per cent EWL. There are no long-term data on vertical sleeve gastrectomy. Type II diabetes is a common and serious disease, usually associated with increased weight. Multiple RCTs have shown that bariatric surgery provides clear benefits over continuing with non-surgical therapies. The earlier the treatment, the more likely and durable will be the remission. Bariatric surgery should be available to all who are obese (body mass index over 30 kg/m(2) ). LAGB, a safe, effective, reversible outpatient procedure, is the author's preferred primary option.

Increased pyruvate dehydrogenase kinase expression in cultured myotubes from obese and diabetic individuals.

PURPOSE: To investigate the mechanisms of impairments in oxidative metabolism in obese and diabetic (T2DM) skeletal muscle, this study analysed the adaptive expression of genes involved in fatty acid (FA) oxidation and mitochondrial biogenesis in primary myotubes treated with elevated FAs. METHODS: Muscle samples from obese or obese T2DM donors were stored or processed into human primary skeletal muscle myotubes, which were treated for 6 h with a saturated (palmitic acid) or a monounsaturated (oleic acid) FA with or without a polyunsaturated FA (eicosapentaenoic acid: EPA). Real-time PCR analysis was used to determine mRNA expression. RESULTS: Basal pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in whole muscle samples from obese and T2DM subjects was increased compared to lean (P < 0.05; n = 13-20/group). In obese- and T2DM-derived myotubes, oleic acid treatment alone and in combination with EPA increased PDK4 mRNA expression compared to control (P < 0.05; n = 7/group), whereas palmitic acid alone and in combination with EPA only increased PDK4 mRNA in T2DM-derived myotubes compared to control (P < 0.05; n = 7/group). EPA alone did not alter mRNA expression of PDK4. CONCLUSIONS: These findings show that FAs induce the expression of PDK4 mRNA, which was increased in myotubes cultured from obese and T2DM donors. This persistent difference in PDK4 expression, present after culturing, suggests a fundamental alteration in the FA-mediated gene expression. This may in turn translate to differences in the regulation of oxidative substrate flux to impact on insulin sensitivity.

Axis I disorders in adjustable gastric band patients: the relationship between psychopathology and weight loss.

BACKGROUND: Bariatric surgery candidates have higher rates of co-morbid psychological illnesses than those in the general population. The effect of weight loss on these illnesses is unclear. METHODS: This prospective observational study explored psychiatric co-morbidities and weight loss outcomes in 204 gastric banding surgery candidates. Psychiatric co-morbidities were assessed prior to surgery and 2 years post-surgery. One hundred and fifty patients (74%) completed assessments at both time points. RESULTS: At baseline, 39.7% of the patients met the criteria for a current axis I disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Mood disorders were the most frequent (26.5%), followed by anxiety disorders (15.2%) and binge eating disorder (13.2%). Preoperative psychopathology predicted clinical psychopathology at 2 years. No preoperative or post-operative axis I disorder was significantly related to weight loss at 2 years. The frequency of current axis I disorders decreased significantly from 39.7% preoperatively to 20% 2 years post-surgery. CONCLUSIONS: The point prevalence of psychopathology in this sample of Australian bariatric candidates is high. Psychopathology, preoperatively and at 2 years of follow-up, was not associated with weight loss at 2 years.

GPR119 regulates genetic markers of fatty acid oxidation in cultured skeletal muscle myotubes.

Gene knockout and agonist studies indicate that activation of the G protein-coupled receptor, GPR119, protects against diet-induced obesity and insulin resistance. It is not known if GPR119 activation in skeletal muscle mediates these effects. To address this uncertainty, we measured GPR119 expression in skeletal muscle and determined the effects of PSN632408, a GPR119 agonist, on the expression of genes and proteins required for fatty acid and glucose oxidation in cultured myotubes. GPR119 expression was readily detected in rat skeletal muscle and mRNAs were induced by 12 weeks of high-fat feeding. Treatment of cultured mouse C2C12 myotubes with 5 µM PSN632408 or 0.5 mM palmitate reduced expression of mRNAs encoding fatty acid oxidation genes to similar extents. More so, treatment with PSN632408 decreased AMPKα (Thr172 phosphorylation) activity in the absence of palmitate and ACC (Ser79 phosphorylation) activity in the presence of palmitate. In human primary myotubes PSN632408 decreased expression of PDK4 and AMPKα2 mRNA in myotubes derived from obese donors. These data suggest GPR119 activation in skeletal muscle may impair fatty acid and glucose oxidation.

Brown adipocyte progenitor population is modified in obese and diabetic skeletal muscle.

Brown adipose tissue mitochondria express the unique thermogenic uncoupling protein-1. Recently, brown adipocyte progenitors have been identified in the CD34+ cell population of human skeletal muscle. The aims of this study were firstly to determine if obesity and diabetes have altered amounts of muscle brown adipocyte progenitors and, secondly, to establish if the latter are correlated with clinical parameters of obesity and diabetes. Body mass index (BMI), plasma glucose, insulin, cholesterol and triglycerides as well as homeostasis model assessment were measured in lean (n=10), obese (n=18) and obese-diabetic (n=15) subjects and muscle biopsies were taken from the rectus abdominus. CD34 being also expressed on endothelial cells, we measured CD31, another endothelial marker, and expressed the brown adipocyte progenitors, as the CD34/CD31 mRNA ratio. The latter was significantly reduced in the obese vs lean subjects suggesting a smaller pool of brown adipocyte progenitors. More strikingly, for lean and obese subjects negative correlations were observed between the CD34/CD31 mRNA ratios and BMI, fasting insulin levels and homeostasis model assessment. These correlations highlight the potential physiological relevance of the muscle CD34/CD31 mRNA ratio.

Night eating syndrome and nocturnal snacking: association with obesity, binge eating and psychological distress.

OBJECTIVE: Night eating syndrome (NES) is characterized by a time-delayed pattern of eating relative to sleep, where most food is consumed in the evening and night. This study aimed to investigate the clinical significance of NES and nocturnal snacking by exploring the relationship between NES and (1) obesity, (2) binge eating disorder (BED) and (3) psychological distress. SUBJECTS: One hundred and eighty bariatric surgery candidates, 93 members of a non-surgical weight loss support group and 158 general community respondents (81 males/350 females, mean age: 45.8+/-13.3 years, mean body mass index (BMI): 34.8+/-10.8 and BMI range: 17.7-66.7). METHODS: NES diagnosis required within the previous 3 months: (1) no appetite for breakfast, (2) consumption of > or =50% of daily energy after 1900 hours and (3) sleep difficulties > or =3 nights/week. Nocturnal snacking (awakening to eat) was recorded. Validated questionnaires assessed BED, symptoms of depression, appearance dissatisfaction (AD) and mental health-related quality of life (MHQoL). NES and binge eating (BE) (> or =1 episode/week) were confirmed by interview. RESULTS: NES criteria were met by 11.1% of the total cohort. Across all groups, BE (P=0.001), BMI (P=0.003) and male gender (P=0.013) explained 10% of NES variance. Individuals with co-morbid NES and BE reported similarly elevated psychological distress as other binge eaters. NES alone was not associated with psychological distress. Those with NES who consumed nocturnal snacks reported poorer MHQoL (P=0.007) and greater depressive symptoms (P=0.039) and hunger (P=0.013) than others with NES. Low MHQoL (P=0.007) and male gender (P=0.022) explained 27% of the variance in the nocturnal snacking group. DISCUSSION: In this study, NES was positively associated with BMI, BE and male gender. Elevated psychological distress was only apparent in those who consumed nocturnal snacks. Further characterization and understanding of the clinical significance of NES and nocturnal snacking is required.

Leptin stimulation of COXIV is impaired in obese skeletal muscle myotubes.

OBJECTIVE: To investigate the effects of leptin on the mRNA abundance of key genes involved in fatty acid oxidation and mitochondrial biogenesis in cultured skeletal muscle myotubes derived from lean and obese individuals. RESEARCH METHODS AND PROCEDURES: Rectus abdominus muscle biopsies were obtained from surgical patients to establish primary skeletal muscle cell cultures. Two distinct primary cell culture groups were established (Lean and Obese) n = 7 in each group. Differentiated cultures were then exposed to leptin (2.5 µg/ml) for 6 h. mRNA expression was subsequently measured by real-time PCR analysis. RESULTS: Basal mRNA expression of ßHAD, COXIII, COXIV, PGC-1α and SOCS3 in the cultured human skeletal muscle myotubes were similar, however, PDK4 mRNA was elevated (P < 0.05) in the myotubes derived from obese individuals. The addition of leptin resulted in a 2.5-fold increase in COXIV mRNA expression in the myotubes derived from Lean individuals only (P < 0.05). There was also a tendency for leptin to increase COXIII, ßHAD and PDK4 mRNA expression in this same group. Leptin had no impact on the gene expression of all measured transcripts in myotubes derived from obese individuals. CONCLUSION: Short-term exposure of human skeletal muscle myotubes to leptin stimulated the expression of the mitochondrial enzyme COXIV in myotubes derived from lean individuals, an effect that was abrogated in myotubes derived from obese individuals. These data demonstrate a novel capacity for leptin to increase mitochondrial biogenesis and thus, a possible increased capacity for lipid oxidation and the persistence of a defect in leptin signalling in human myotubes cultured from obese individuals.

Changes in fat-free mass during significant weight loss: a systematic review.

OBJECTIVE: To identify the proportion of weight lost as fat-free mass (FFM) by various weight loss interventions. METHODS: Medline and Embase were systematically searched for reliable measurements of FFM before and after weight loss of >10 kg and eligible data were pooled. In a fixed effect model of % FFM loss/weight loss (%FFML), linear regression analysis was used to determine the influence of degree of caloric restriction, exercise, magnitude of weight loss, initial body mass index (BMI) and type of surgery. RESULTS: Data were included from 26 cohorts treated with dietary and behavioral interventions and 29 cohorts of bariatric surgery patients. The degree of caloric restriction was positively associated with %FFML (r (2)=0.31, P=0.006) and in three randomized controlled trials exercise was shown to decrease %FFML. Compared with laparoscopic adjustable gastric banding (LAGB), biliopancreatic diversion (BPD) and roux en Y gastric bypass (RYGB) caused greater log(e) (natural log) %FFML (r (2)=0.453, P<0.001). Differences in log(e) %FFML between surgical procedures were independent of initial BMI and magnitude of weight loss. CONCLUSIONS: The degree of caloric restriction, exercise and rate of weight loss influence the proportion of weight lost as FFM after non-surgical interventions. For surgical interventions, BPD and RYGB result in greater %FFML than LAGB.

Polysomnography before and after weight loss in obese patients with severe sleep apnea.

OBJECTIVE: While obstructive sleep apnea (OSA) is strongly related to obesity, few studies have examined polysomnographic (PSG) changes with major weight loss. We examined the effect of weight loss following laparoscopic adjustable gastric banding (LAGB) on the PSG changes in patients with severe OSA. In addition, we studied daytime sleepiness, the metabolic syndrome and quality of life (QOL). METHODS: A prospective study was conducted of 25 severely obese patients (17 men, eight women) with paired diagnostic PSG, biochemical and questionnaire studies, the first prior to LAGB and the second at least 1 y later. Subjects with a baseline apnea-hypopnea index (AHI) >25/h were included. RESULTS: Subject baseline age was 44.7 y, weight 154 kg and body mass index 52.7 kg/m(2). The second PSG study was conducted 17.7+/-10 (range 12-42) months after surgery and mean percentage of excess loss and weight loss were 50.1+/-15% (range 24-80%) and 44.9+/-22 kg (range 18-103 kg), respectively. There was a significant fall in AHI from 61.6+/-34 to 13.4+/-13, improved sleep architecture with increased REM and stage III and IV sleep, daytime sleepiness, as measured by Epworth Sleepiness Scale, of 13+/-7.0 to 3.8+/-3.0, and fewer patients requiring nasal continuous positive airways pressure (CPAP). There were also major improvements in the metabolic syndrome, QOL, body image and fewer symptoms of depression (P<0.05 for all). CONCLUSION: Weight loss provides major improvement or resolution of OSA and CPAP requirements. It also reduces daytime sleepiness, and improves the metabolic syndrome and QOL. LAGB placement should be considered a broadly effective therapy for sleep apnea in the severely obese patient.

Body composition changes following laparoscopic gastric banding for morbid obesity.

Most reports of outcome following obesity surgery report weight and co-morbidity changes only. We studied body composition changes in 17 adult patients (15 F, 2 M, age 43+/-2 years, range 28-58 years), with morbid obesity (initial BMI 40.4+/-4.9 kg/m(2), range 34.7-48.8) who were managed surgically by laparoscopically inserting an adjustable gastric band. Body composition was studied before and after surgery (mean interval of 909+/-51 days, range 441-1155 days) using anthropometry (abdominal circumference, AC, sum of four skinfold thicknesses, SFSUM), whole-body potassium counting (TBK), in vivo neutron activation analysis total body nitrogen (TBProtein) and whole-body dual-energy ray absorptiometry (total body percent fat TBF%, and total body bone mineral density TBBMD). Weight loss over the study period was 23.4+/-2.5 kg. ( p<0.0003) with an AC reduction of 20.0+/-4.5 cm ( p<0.008). Both SFSUM and TBF% were significantly reduced ( p<0.02 and p<0.0005 respectively). Both TBK and TBProtein after normalization for sex and height, were significantly ( p<0.0054 and p<0.001 respectively) reduced, but the ratio of loss of fat mass to fat-free mass, at 4.4:1 was usual for weight loss, and there was no significant changes in the ratio of potassium to protein. TBBMD, after normalization relative to a young same sex adult, was not significantly changed. In this group of patients, most of the substantial weight loss over a 2- to 3-year period was due to loss of fat mass, with relatively less reduction in the components of fat-free mass. Adjustable laparoscopic gastric banding induces fat loss without significant other deleterious effects on body composition.

Improvements in insulin sensitivity and beta-cell function (HOMA) with weight loss in the severely obese. Homeostatic model assessment.

AIMS: To examine the effect of weight loss on insulin sensitivity and beta-cell function in severely obese subjects of varying glycaemic control. PATIENTS AND METHODS: Subjects were 254 (F:M 209:45) patients having adjustable gastric banding for severe obesity, with paired biochemical data from before operation and at 1-year follow up. The homeostatic model assessment method was used to calculate insulin sensitivity (HOMA%S) and beta-cell function (HOMA%B). Subjects were grouped by diabetic status and by pre-weight loss HbA1c. RESULTS: Initial mean (sd) weight and body mass index were 128 (26) kg and 46.2 (7.7) kg/m2, respectively, and at 1-year were 101 (22) kg and 36.4 (6.7) kg/m2. The percentage of excess weight lost (%EWL) was 44.3 (14)%. HOMA%S improved from 37.5 (16)% presurgery to 62 (25)% (P < 0.001). %EWL was the only predictor of HOMA%S improvement (r = 0.28, P < 0.001). Subjects with normal fasting glucose, impaired fasting glucose and Type 2 diabetes had a fall, no change and increase in HOMA%B, respectively. The improvement in HOMA%B in subjects with diabetes (n = 39) was inversely related to the time with diabetes (r = -0.36, P = 0.02). In non-diabetic subjects the HOMA%S-HOMA%B relationship was favourably altered with weight loss, so that for any given HOMA%S there was an increase in HOMA%B (f = 11.8, P = 0.001). This improvement in HOMA%B was positively related to %EWL (r = 0.25, P = 0.019). DISCUSSION: There are beneficial changes in both insulin sensitivity and beta-cell function with weight loss. Modern laparoscopic obesity surgery may have an important early role in the management of Type 2 diabetes in obese subjects.

Reduced plasma homocysteine in obese red wine consumers: a potential contributor to reduced cardiovascular risk status.

BACKGROUND: Moderate alcohol consumption is associated with improved vascular risk profile and decreased mortality in the middle aged. An elevated homocysteine concentration is an independent risk factor for cardiovascular disease. OBJECTIVE: To examine the relationship between alcohol consumption and homocysteine concentrations in severely obese patients (body mass index (BMI)>35). DESIGN: A careful alcohol history was obtained from 350 (male:female 1:5) consecutive patients as part of preoperative assessment for surgical treatment of obesity. Data were obtained concerning amount, frequency, timing and type of alcohol consumption. Fasting homocysteine, serum folate and vitamin B(12) concentrations were measured. Differences between groups were assessed using Student t-test, and ANOVA. Linear regression was used to assess factors influencing homocysteine concentration. RESULTS: There is a U-shaped relationship between alcohol consumption and homocysteine concentrations, with light to moderate consumption being associated with lower concentrations. Those consuming <100 g/week (n=165) of alcohol had geometric mean (95% CI of mean) serum homocysteine concentrations of 8.5 (8.2-8.9) micromol/l compared with 9.5 (9.1-9.9) micromol/l for non or rare consumers (n=153; P=0.001). The lower concentrations of homocysteine in regular consumers were associated with higher folate concentrations of 9.4 (8.6-10.2) ng/ml when compared with non-consumers 7.5 (7.1-7.8) ng/ml (P=0.001). Red wine consumers (n=42) had lower fasting concentrations of homocysteine 7.8 (7.5-8.1) micromol/l compared with 153 non-consumers 9.4 (9.0-9.8) micromol/l (P<0.001), 82 beer and spirit consumers 9.0 (8.4-9.7) micromol/l (P=0.005) and 73 white wine consumers 8.8 (8.2-9.4 micromol/l (P=0.013). Red wine consumption was an independent predictor for lower homocysteine concentrations. CONCLUSION: Mild to moderate alcohol consumption, especially red wine consumption, in obese subjects is associated with lower fasting homocysteine concentrations. This may reduce cardiovascular risk and help explain the 'French paradox'.

Inhibition of beta-catenin translocation in rodent colorectal tumors: a novel explanation for the protective effect of nonsteroidal antiinflammatory drugs in colorectal cancer.

In a rodent colorectal cancer model, nonsteroidal antiinflammatory drugs reduce tumor mass by increasing the rate of tumor cell apoptosis and decreasing proliferation. We have examined beta-catenin as a potential target for these agents in colorectal cancer. Carcinogen-treated rats were treated for 23 weeks with a range of nonsteroidal antiinflammatory drugs. Control animals received vehicle alone. Intracellular beta-catenin was examined using immunohistochemistry. In tumors from untreated animals, staining was seen in the cytoplasm and nucleus (median 24% of nuclei). The frequency of nuclear beta-catenin staining correlated directly with the volume of tumor and inversely with the rate of apoptosis. In tumors from treatment groups, the cytoplasmic staining for beta-catenin was unchanged; however, nuclear staining was absent except in the celecoxib group, where it was reduced to a median of 14%. Colorectal tumors from animals treated with NSAIDs show reduced levels of nuclear beta-catenin immunoreactivity.

Quality of life after lap-band placement: influence of time, weight loss, and comorbidities.

OBJECTIVE: To assess the quality of life (QOL) in severely obese subjects before and after Lap-Band gastric restrictive surgery and identify factors that may influence change. RESEARCH METHODS AND PROCEDURES: All patients, over a 3-year period, attending for preoperative assessment (n = 459) or annual review after surgery (n = 641) have completed the Short Form-36 (SF-36) health survey. Eight domain and physical component summary (PCS) and mental component summary (MCS) scores were calculated. Scores were analyzed in groups based on time after surgery and compared with community normal (CN) values. Paired preoperative and 1-year scores (n = 218) data were used to find predictors of QOL change. RESULTS: All preoperative mean scores (n = 459) were lower than CN values, with greater impairment in the PCS (36.8 +/- 9.5 vs. CN: 51.3 +/- 8.3, p < 0.001) than in the MCS (45.7 +/- 8.2 vs. CN: 48.8 +/- 9.5, p < 0.001) scores. After 1 year, scores were closer to CN scores (PCS: 52.4 +/- 8.2 and MCS: 48.4 +/- 7.7), and these remained closer for 4 years. Preoperative obesity comorbidity, especially physical disability, was the best predictor of poor preoperative SF-36 scores and of improvement in scores at 1 year. The percentage of excess weight loss at 1 year (46 +/- 16%) was of little predictive value of improved QOL. DISCUSSION: Severely obese subjects have poor health-related QOL as measured by the SF-36 health survey. Lap-Band surgery for this group has provided a dramatic and sustained improvement in all measures of the SF-36. Improvement is greater in those with greater preoperative disability, and the extent of weight loss is not a good predictor of improved QOL.

Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is common in severely obese subjects and can progress to cirrhosis and liver failure. Predicting advanced or progressive disease may help in selecting patients for liver biopsy and assist the development of therapeutic options. METHODS: Liver biopsies were taken at laparoscopic obesity surgery in 105 consecutive patients. The clinical and biochemical variables were analyzed for correlation with specific histologic features. RESULTS: Twenty-six patients (25%) were found to have nonalcoholic steatohepatitis (NASH), and 11 (42%) of these had advanced fibrosis. A raised index of insulin resistance (odds ratio [OR] 9.3, 95% confidence interval [CI] 3.4-26), systemic hypertension (OR 5.2, 95% CI 2.0-13.5), and raised alanine aminotransferase (OR 8.6, 95% CI 3.1-23.5) were independent predictors of NASH. A combination of 2 or 3 of these predictors allows a sensitivity of 0.8 and specificity of 0.89 for NASH. Alcohol consumption was associated with a reduction in NASH (OR 0.35, 95% CI 0.12-1.00) and diabetes (OR 0.18, 95% CI 0.047-0.67). CONCLUSION: Insulin resistance and systemic hypertension, features of the metabolic syndrome, are independently associated with advanced forms of NAFLD. Moderate alcohol consumption seems to reduce the risk of NAFLD in the severely obese, possibly by reducing insulin resistance.

Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.

OBJECTIVE: To investigate homocysteine levels and their relationship with serum folate and vitamin B12 concentrations with weight loss after the Lap-Band form of gastric restrictive surgery, with the view to minimizing risk. METHODS: We measured levels of fasting plasma homocysteine (tHcy), folate (serum and RBC) and vitamin B12 in two groups. The study group was 293 consecutive patients at 12 (n=192) or 24 (n=101) months review after surgery. The controls were 244 consecutive patients presenting for this surgery. RESULTS: The group losing weight had higher geometric mean tHcy levels: 10.4 (95% CI, 9.8-10.8) micromol/l compared with 9.2 (95% CI, 8.9-9.7) in controls (P<0.001). This occurred with higher folate levels and unchanged vitamin B12 levels. Levels of folate and B12 together explained 35% (r (2)) of the homocysteine variance in the weight loss group compared with only 9% (r (2)) in controls (P<0.001). Those taking regular multivitamin supplements had lower tHcy levels: 9.6 (9.1-10.0) micromol/l vs 12.3 (11.4-13.3) in those not taking supplements (P<0.001). A low normal plateau of tHcy levels occurred at levels of folate >15 ng/l and B12)600 ng/ml. A curvilinear relationship exists between these cofactors and tHcy levels, with the dose-response relationship shifted to the right in the weight loss group. CONCLUSION: This study shows elevated tHcy levels with weight loss, without lower serum folate or vitamin B(12) levels. There is an altered dose-response relationship with higher serum B(12) and folate levels required to maintain recommended tHcy levels. Patients losing weight have significant health benefits; however, they may be at greater risk of vascular events or fetal abnormality in association with raised tHcy levels. Multivitamin supplementation is effective in lowering tHcy levels.

Pregnancy after Lap-Band surgery: management of the band to achieve healthy weight outcomes.

BACKGROUND: Severely obese women have higher obstetric risks and poorer neonatal outcomes. Weight loss reduces obstetric risk. The introduction of a laparoscopically-placed adjustable gastric band, a safe and effective method of weight loss, has given us the ability and responsibility to adjust the band in relation to pregnancy. OBJECTIVE: Our aim was to devise a safe management plan to achieve healthy maternal weight gain (Institute of Medicine 1990) during pregnancy. METHODS: In a cohort group of 650 patients to have a Lap-Band placement for severe obesity, we have reviewed the management of the band and pregnancy outcomes of all women (n=20) to complete a pregnancy (n=22) with a band in-situ. RESULTS: All 22 pregnancies were singleton, with no primary caesarean sections (3 for recurring indications). The mean maternal weight gain was 8.3 kg compared with 15.2 kg for the 15 previous pregnancies of women in this group (p<0.05). There was no difference in birth weights. Obstetric complications were minimal, and there were no premature or low birth weight infants. 11 of 15 subjects with active management of the band achieved a maternal weight gain within the advised range compared with only 2 of 7 prior to this. CONCLUSION: The ability to adjust gastric restriction allows optimal control of maternal weight change in pregnancy and should help avoid the risks of excessive weight change.