Current teaching about obesity in Australian universities, specialist medical colleges and through continuing medical education.
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Australia↗
Biomedical subjects
Paul E O'Brien
Publications and source records attributed to Paul E O'Brien.
The suppressor of cytokine signaling 3 inhibits leptin activation of AMP-kinase in cultured skeletal muscle of obese humans.
CONTEXT: Leptin is thought to regulate whole-body adiposity and insulin sensitivity, at least in part, by stimulating fatty acid metabolism via activation of AMP-kinase (AMPK) in skeletal muscle. Human obesity is associated with leptin resistance, and recent studies have demonstrated that hypothalamic expression of the suppressors of cytokine signaling 3 (SOCS3) regulates leptin sensitivity in rodents. OBJECTIVE: The objective of the study was to investigate the effects of leptin on fatty acid oxidation and AMPK signaling in primary myotubes derived from lean and obese skeletal muscle and evaluate the contribution of SOCS3 to leptin resistance and AMPK signaling in obese humans. RESULTS: We demonstrate that leptin stimulates AMPK activity and increases AMPK Thr172 and acetyl-CoA carboxylase-beta Ser222 phosphorylation and fatty acid oxidation in lean myotubes but that in obese subjects leptin-dependent AMPK signaling and fatty acid oxidation are suppressed. Reduced activation of AMPK was associated with elevated expression of IL-6 ( approximately 3.5-fold) and SOCS3 mRNA ( approximately 2.5-fold) in myotubes of obese subjects. Overexpression of SOCS3 via adenovirus-mediated infection in lean myotubes to a similar degree as observed in obese myotubes prevented leptin but not AICAR (5-amino-imidazole-4-carboxamide-1-beta-d-ribofuranoside) activation of AMPK signaling. CONCLUSIONS: These data demonstrate that SOCS3 inhibits leptin activation of AMPK. These data suggest that this impairment of leptin signaling in skeletal muscle may contribute to the aberrant regulation of fatty acid metabolism observed in obesity and that pharmacological activation of AMPK may be an effective therapy to bypass SOCS3-mediated skeletal muscle leptin resistance for the treatment of obesity-related disorders.
Adenylate Kinase↗
Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial.
BACKGROUND: Obesity is a major, growing health problem. Observational studies suggest that bariatric surgery is more effective than nonsurgical therapy, but no randomized, controlled trials have confirmed this. OBJECTIVE: To ascertain whether surgical therapy for obesity achieves better weight loss, health, and quality of life than nonsurgical therapy. DESIGN: Randomized, controlled trial. SETTING: University departments of medicine and surgery and an affiliated private hospital. PATIENTS: 80 adults with mild to moderate obesity (body mass index, 30 kg/m2 to 35 kg/m2) from the general community. INTERVENTIONS: Patients were assigned to a program of very-low-calorie diets, pharmacotherapy, and lifestyle change for 24 months (nonsurgical group) or to placement of a laparoscopic adjustable gastric band (LAP-BAND System, INAMED Health, Santa Barbara, California) (surgical group). MEASUREMENTS: Outcome measures were weight change, presence of the metabolic syndrome, and change in quality of life at 2 years. RESULTS: At 2 years, the surgical group had greater weight loss, with a mean of 21.6% (95% CI, 19.3% to 23.9%) of initial weight lost and 87.2% (CI, 77.7% to 96.6%) of excess weight lost, while the nonsurgical group had a loss of 5.5% (CI, 3.2% to 7.9%) of initial weight and 21.8% (CI, 11.9% to 31.6%) of excess weight (P < 0.001). The metabolic syndrome was initially present in 15 (38%) patients in each group and was present in 8 (24%) nonsurgical patients and 1 (3%) surgical patient at the completion of the study (P < 0.002). Quality of life improved statistically significantly more in the surgical group (8 of 8 subscores of Short Form-36) than in the nonsurgical group (3 of 8 subscores). LIMITATIONS: The study included mildly and moderately obese participants, was not powered for comparison of adverse events, and examined outcomes only for 24 months. CONCLUSIONS: Surgical treatment using laparoscopic adjustable gastric banding was statistically significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program.
Adult↗
Differential regulation of adiponectin receptor gene expression by adiponectin and leptin in myotubes derived from obese and diabetic individuals.
OBJECTIVE: This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin. RESEARCH METHODS AND PROCEDURES: Four distinct primary cell culture groups were established [Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 microg/mL) or leptin (2.5 microg/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real-time polymerase chain reaction analysis. RESULTS: AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8-fold and 2.5-fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups. DISCUSSION: Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese-prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.
Adiponectin↗
Preoperative weight loss with a very-low-energy diet: quantitation of changes in liver and abdominal fat by serial imaging.
BACKGROUND: A very-low-energy diet (VLED) can result in substantial, rapid weight loss and is increasingly prescribed before obesity surgery to minimize risk and difficulty by reducing liver size and abdominal adiposity. Despite its growing popularity, a VLED in this setting has received little attention. OBJECTIVE: The aim of this study was to investigate the efficacy and acceptability of a preoperative VLED. DESIGN: In a prospective observational study, 32 subjects (n = 19 men and 13 women) with a mean (+/-SD) age of 47.5 +/- 8.3 y and a body mass index (in kg/m(2)) of 47.3 +/- 5.3 consumed a VLED for 12 wk. Primary outcomes included changes in liver volume (LV) and in visceral and subcutaneous adipose tissue (VAT/SAT). Changes in body weight, anthropometric measures, and biochemical variables were also recorded, and compliance with, acceptability of, and side effects of treatment were assessed. Changes in LV and VAT/SAT area were measured by computed tomography and magnetic resonance imaging at baseline and weeks 2, 4, 8, and 12. RESULTS: Mean (+/-SD) LV, VAT/SAT, and body weight decreased significantly (P < 0.001 for all). The degree of LV reduction was directly related to the reduction in relative body weight (r = 0.54, P = 0.001) and initial LV (r = 0.43, P = 0.015). Eighty percent of the reduction in LV occurred between weeks 0 and 2 (P < 0.001). Reductions in body weight and VAT were uniform over the 12-wk period. Attrition was 14%. Acceptability was adequate but waned over time, and mild transitory side effects occurred. CONCLUSIONS: Given the observed early reduction in LV and the progressive reduction in VAT, we suggest that the minimum duration for a preoperative VLED be 2 wk. Ideally, the duration should be 6 wk to achieve maximal LV reduction and significant reductions in VAT and body weight without compromising compliance and acceptability.
Abdominal Fat↗
Obesity and the white blood cell count: changes with sustained weight loss.
BACKGROUND: Obesity is a chronic inflammatory condition, and elevated white blood cell counts (WBC) have widely recognized associations with inflammatory conditions. The authors explored the relationship between the WBC and degree of obesity, basic anthropometry, and clinical and biochemical markers of the metabolic syndrome at baseline, and with weight loss following Lap-Band surgery. METHODS: 477 patients with complete biochemical and clinical data at baseline and at 2 years were selected for analysis. Paired analysis assessed the change in WBC at 2 years, and stepwise linear regression assessed factors independently associated with baseline counts and any change at 2 years. RESULTS: Mean +/- SD weight loss at 2 years was 29.3 +/- 16.2 kg. There were significant decreases in total WBC (-12.2%), and major components, neutrophils (11.7%) and lymphocytes (6.9%), at 2 years (P<0.001 for all). Baseline WBC, neutrophils and lymphocyte counts increased with increasing BMI and decreased with age. Insulin levels were independently positively associated with higher neutrophil counts and triglycerides with higher lymphocyte counts. Age, gender, BMI and components of the metabolic syndrome when modeled together accounted for <10% of the variance of baseline counts. Higher BMI predicted a greater fall in the neutrophil counts at 2 years. Change in BMI at 2 years was the only independent predictor of the change in both neutrophils and lymphocytes, but accounted for <10% of the variance of change. CONCLUSION: BMI contributes to both baseline and weight loss WBC. However, crude WBC counts are influenced in minor ways by obesity markers and have limited value as clinical markers.
Adult↗
Systematic review of medium-term weight loss after bariatric operations.
BACKGROUND: Although bariatric surgery is known to be effective in the short term, the durability of that effect has not been convincingly demonstrated over the medium term (> 3 years) and the long term (> 10 years). The authors studied the durability of weight loss after bariatric surgery based on a systematic review of the published literature. METHODS: All reports published up to September, 2005 were included if they were full papers in refereed journals published in English, of outcomes after Roux-en-Y gastric bypass (RYGBP), and its hybrid procedures of banded bypass (Banded RYGBP) and longlimb bypass (LL-RYGBP), biliopancreatic diversion with or without duodenal switch (BPD+/-DS) or laparoscopic adjustable gastric banding (LAGB). All reports that had at least 100 patients at commencement, and provided > or = 3 years of follow-up data were included. RESULTS: From a total of 1,703 reports extracted, 43 reports fulfilled the entry criteria (18 RYGBP; 18 LAGB; 7 BPD). Pooled data from all the bariatric operations showed effective and durable weight loss to 10 years. Mean %EWL for standard RYGBP was higher than for LAGB at years 1 and 2 (67 vs 42; 67 vs 53) but not different at 3, 4, 5, 6 or 7 years (62 vs 55; 58 vs 55; 58 vs 55; 53 vs 50; and 55 vs 51). There was 59 %EWL for LAGB at 8 years, and 52 %EWL for RYGBP at 10 years. Both the BPD+/-DS and the Banded RYGBP appeared to show better weight loss than standard RYGBP and LAGB, but with statistically significant differences present at year 5 alone. The LL-RYGBP was not associated with improved %EWL. Important limitations include lack of data on loss to follow-up, failure to identify numbers of patients measured at each data point and lack of data beyond 10 years. CONCLUSIONS: All current bariatric operations lead to major weight loss in the medium term. BPD and Banded RYGBP appear to be more effective than both RYGBP and LAGB which are equal in the medium term.
Bariatric Surgery↗
Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement.
BACKGROUND: The ability for aminotransferase levels to track histological features of non-alcoholic fatty liver disease (NAFLD) with weight loss has not been examined. METHODS: We examined the effect of weight loss following laparoscopic adjustable gastric banding surgery on the histological features of NAFLD and plasma aminotransferase concentrations (AST, ALT and GGT) in 60 (12M, 48F) selected severely obese patients. All 120 paired biopsies were de-identified and scored for lobular steatosis, fibrosis, inflammation, Mallory bodies and NASH. RESULTS: 30 patients (50%) had baseline histological features of non-alcoholic steatohepatitis (NASH). Repeat biopsies were taken at 29.5+/-10 months after baseline. Mean weight loss was 31.5+/-18 kg. There were improvements in AST, ALT, GGT, lobular steatosis, inflammation and fibrosis between baseline and follow-up (P<0.001 for all). Only 6 (10%) of repeat biopsies showed NASH. No change in aminotransferase concentrations predicted the change in steatosis, but changes in AST and GGT predicted improved scores for inflammation, fibrosis, Mallory bodies and NASH. The lowering of GGT best predicted the improvements in inflammation, fibrosis and NASH. CONCLUSION: With weight loss, falls in GGT and, to a lesser extent, in AST, are predictive of improved lobular inflammation and fibrosis, key prognostic features of NAFLD.
Adult↗
Obesity, weight loss and bariatric surgery.
Obesity is shaping up to be the major health care problem and one of the most frequent causes of preventable death in Western countries in the 21st century. Bariatric surgery is the only current treatment that has been shown to achieve major and durable weight loss. Major weight loss in the severely obese leads to total or partial control of a wide range of common and serious diseases, such as diabetes, heart disease and hypertension. Laparoscopic adjustable gastric banding is the most common type of obesity surgery performed in Australia. It is effective, relatively safe and minimally invasive. The blocks to broader application of bariatric surgery should be identified and resolved.
Anastomosis, Roux-en-Y↗
Inequalities in the provision of bariatric surgery for morbid obesity in Australia.
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Australia↗
Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study.
BACKGROUND: Class III obese patients have altered respiratory mechanics, which are further impaired in the supine position. The authors explored the hypothesis that preoxygenation in the 25 degrees head-up position allows a greater safety margin for induction of anesthesia than the supine position. METHODS: A randomized controlled trial measured oxygen saturation and the desaturation safety period after 3 min of preoxygenation in 42 consecutive (male:female 13:29) severely obese (body mass index > 40 kg/m) patients who were undergoing laparoscopic adjustable gastric band surgery and were randomly assigned to the supine position or the 25 degrees head-up position. Serial arterial blood gases were taken before and after preoxygenation and 90 s after induction. After induction, ventilation was delayed until blood oxygen saturation reached 92%, and this desaturation safety period was recorded. RESULTS: The mean body mass indexes for the supine and 25 degrees head-up groups were 47.3 and 44.9 kg/m, respectively (P = 0.18). The group randomly assigned to the 25 degrees head-up position achieved higher preinduction oxygen tensions (442 +/- 104 vs. 360 +/- 99 mmHg; P = 0.012) and took longer to reach an oxygen saturation of 92% (201 +/- 55 vs. 155 +/- 69 s; P = 0.023). There was a strong positive correlation between the induction oxygen tension achieved and the time to reach an oxygen saturation of 92% (r = 0.51, P = 0.001). There were no adverse events associated with the study. CONCLUSION: Preoxygenation in the 25 degrees head-up position achieves 23% higher oxygen tensions, allowing a clinically significant increase in the desaturation safety period--greater time for intubation and airway control. Induction in the 25 degrees head-up position may provide a greater safety margin for airway control.
Adult↗
Birth outcomes in obese women after laparoscopic adjustable gastric banding.
OBJECTIVE: This prospective study sought to examine the outcomes of 79 consecutive first pregnancies (> 20 weeks of gestation) in women following laparoscopic adjustable gastric banding (LAGB) for severe obesity. METHODS: The 79 women are from a cohort of 1,382 consecutive patients. The prospectively collected data from 79 first pregnancies has been compared with these patients' previous penultimate pregnancies (n= 40), obstetric histories from matched severely obese subjects (n = 79), and community outcomes. RESULTS: The mean maternal weight gain was 9.6 +/- 9.0 kg, compared with 14.4 +/- 9.7 kg for the 40 penultimate pregnancies of women in this group (P < .001). There was no difference in birth weights: 3,397 g compared with 3,350 g for preband pregnancies, and these were consistent with normal community birth weights. The incidence of pregnancy-induced hypertension (10%) and gestational diabetes (6.3%) were comparable with community levels (12% and 5.5%) and lower than the obese cohort (38% and 19%) and these patients' penultimate pregnancies (45% and 15%). Monitoring and, if necessary, band adjustments during pregnancy provided more favorable maternal weight outcomes (P = .027). Neonatal outcomes, including stillbirths, preterm deliveries, low birth weight, and high birth weight, were consistent with community values. One woman developed anemia during pregnancy. CONCLUSION: Pregnancy outcomes after LAGB are consistent with general community outcomes rather than outcomes from severely obese women. The adjustability of the LAGB assists in achieving these outcomes. Adjustability is appealing because it allows adaptation to the altered requirements of pregnancy. LEVEL OF EVIDENCE: II-2.
Adult↗
Permeability of the silicone membrane in laparoscopic adjustable gastric bands has important clinical implications.
BACKGROUND: The single most important attribute of the laparoscopic adjustable gastric band (LAGB) is its adjustability. Having the correct volume of fluid within the band is crucial for optimal performance. We observe a small reduction of the satiety-promoting effect with time. The characteristics and clinical relevance of volume change have not been adequately investigated. METHOD: One observer measured the saline volume within the 10-cm Lap-Band in 118 consecutive patients who fulfilled the entry criteria. The same observer had performed and recorded the previous adjustment. Initial volume, final volume and time between observations provide the data for analysis. In addition, a range of adjustable gastric bands currently available were bench-tested to assess broad applicability of findings. RESULTS: The difference between observations varied from 0.0 ml to -1.0 ml, median of -0.1 interquartile range (IQR) 0.0-0.2 ml. Two factors were associated with volume change: time in days between the observations (r = -0.55, P<0.001) and the initial volume within the band system (r = -0.50, P<0.001). These two independent factors accounted for a significant proportion of the variance observed (Cox and Snell R2 = 0.45, P<0.001). Replacement of any discrepancy appears to maintain effectiveness. All six bands showed similar saline loss when bench-tested. CONCLUSION: Adjustable gastric bands are semipermeable, leading to a small reduction in saline volume with time. Patients should be informed of this effect, attend for regular follow-up visits and seek help if the band's effectiveness appears reduced. We recommend that the volume present should be checked and readjusted at least every 6 months.
Equipment Failure Analysis↗
Minimal reporting requirements for weight loss: current methods not ideal.
BACKGROUND: There is variety in the reporting of weight loss outcomes within the bariatric literature. Our aim is to compare methods of reporting weight loss in surgical and medical studies, and in addition look for a minimal reporting requirement that allows meaningful comparison. METHOD: A review of methods of reporting weight loss in studies published during 2004 was conducted. Bariatric surgical studies included all reports from MEDLINE-listed journals, and medical studies included reports of non-surgical weight loss from 9 leading journals. RESULTS: 65 surgical and 36 non-surgical reports were retrieved. There were 3 common (>20% of reports) methods of reporting in the surgical literature; mean weight, percentage of excess weight loss (%EWL) and body mass index (BMI), and 4 in the medical literature; mean weight loss, weight, percentage weight loss and BMI. %EWL was reported in 2/3 of surgical reports and in none of the non-surgical. The origin of ideal weight for %EWL calculations was reported in 10 (23%) of these studies and included 5 differing definitions. All methods of reporting other than those using "ideal weight" can be calculated from mean weight and BMI at all time-points. CONCLUSION: There is complexity and confusion in the reporting of bariatric surgery weight outcomes when calculations are based on ideal weight. Providing weight (kg) and BMI (kg/m2) at all time-points allows the reader to interpret and compare the results in the context of the population of interest. These two measures should be provided as a minimum by all journals reporting on intentional weight loss.
Bariatrics↗
Shoulder pain is a common problem following laparoscopic adjustable gastric band surgery.
BACKGROUND: Shoulder-tip pain is commonly reported following laparoscopic adjustable gastric band (LAGB) placement. The incidence, nature and factors that may increase the risk of pain have not been explored. METHODS: A prospective extensive collection of patient characteristics and operative details was obtained from consecutive patients having band placement for severe obesity. Postoperatively, the presence and characteristics of shoulder pain were obtained using a structured interview at discharge from hospital, and at 1 and 5 weeks after placement. RESULTS: 66% and 21% of patients at 1 and 5 weeks respectively following surgery reported pain predominantly in the left shoulder. At 5 weeks, only 7% found the pain of concern and 5% required analgesics. There were no factors found that predicted the presence and severity of pain at 1 week. Injury to the crus of the diaphragm (OR 4.2, 1.4-12.6, P=0.01) and a past history of any upper abdominal surgery (OR 4.2, 1.5-11.7, P=0.007) independently predicted an increased risk of pain at 5 weeks. CONCLUSION: Shoulder pain following LAGB surgery is common, usually affects the left shoulder, and can in some cases last 5 weeks or more. Avoiding injury to the crura during the procedure may prevent more prolonged pain.
Adult↗
Surgery as an effective early intervention for diabesity: why the reluctance?
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Bariatrics↗
Laparoscopic adjustable gastric banding induces prolonged satiety: a randomized blind crossover study.
The sustainability of surgically induced weight loss implies that energy homeostasis is favorably altered. We investigated the hypothesis that laparoscopic adjustable gastric banding (LAGB) induces prolonged satiety and that plasma ghrelin is involved. Seventeen weight-stable subjects who had achieved LAGB-induced weight loss attended blind crossover breakfast tests, one with optimal band restriction and one with reduced restriction. Standardized meals were consumed (0900 h) after 14-h fasting. Satiety visual analog scales were completed hourly (0700-1100 h) before and after feeding. Blood glucose, plasma insulin, ghrelin, and leptin levels were measured. Seventeen body mass index-matched controls were tested. Optimal restriction was associated with significantly greater fasting and postprandial satiety levels than reduced restriction (P < 0.01). Glucose, insulin, ghrelin, and leptin levels did not alter between optimal and reduced restriction. LAGB subjects displayed higher ghrelin (+12%, P = 0.13) and lower glucose (-17%, P = 0.018), insulin (-33%, P = 0.016), and leptin (-32%, P = 0.05) 4-h area under the curve levels than controls. Optimal LAGB restriction increased fasting and postprandial satiety levels. This supports the hypothesis that LAGB provides prolonged satiety, present even during fasting, favorably influencing energy homeostasis. Plasma insulin, leptin, and ghrelin appeared unrelated to the satiety effect and displayed orexigenic compensatory changes. Identifying the mechanisms underlying LAGB-induced satiety may assist the understanding of human energy homeostasis and obesity.
Adult↗
Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss.
The effect of significant weight loss on nonalcoholic fatty liver disease remains unclear. In this case series of 36 selected obese patients, we examined the effect of weight loss on nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. These 36 patients (11 males, 25 females) had paired liver biopsies, the first at the time of laparoscopic adjustable gastric band placement and the second after weight loss. Second biopsies were obtained from two groups: those requiring a subsequent laparoscopic procedure (n = 19) and those with index biopsy score of 2 or greater for zone 3-centric hepatic fibrosis (n = 17). All biopsies were scored, blinded to the patient's identity and clinical condition, for individual histological features and for NASH stage and grade. Initial biopsies demonstrated NASH in 23 patients and steatosis in 12 patients. Repeat biopsies were taken at 25.6 +/- 10 months (range, 9-51 months) after band placement. Mean weight loss was 34.0 +/- 17 kg, and percentage of excess weight loss was 52 +/- 17%. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis at the second biopsy (P <.001 for all). Portal abnormalities remained unchanged. Only four of the repeat biopsies fulfilled the criteria for NASH. There were 18 patients with an initial fibrosis score of 2 or more compared with 3 patients at follow-up (P <.001). Those with the metabolic syndrome (n = 23) had more extensive changes before surgery and greater improvement with weight loss. In conclusion, weight loss after surgery provides major improvement or resolution of obesity and metabolic syndrome-associated abnormal liver histological features in severely obese subjects.
Adult↗