Current teaching about obesity in Australian universities, specialist medical colleges and through continuing medical education.
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Biomedical subjects
Publications and source records attributed to John B Dixon.
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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.
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.
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.
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.
BACKGROUND: The reducing opposed multilobed (ROM) flap involves a series of transpositions effected cephalic and caudal to the primary defect, sequentially mobilized toward and then into the primary defect. OBJECTIVE: To compare the ROM flap with other techniques to close defects below the knee after excision of skin tumor. METHOD: This retrospective study compares 140 defects closed with a ROM flap with 85 defects closed with traditional techniques. RESULTS: A total of 225 defects between 11 and 44 mm in diameter were excised over 3 years from July 1, 2002. There were 140 defects closed by ROM flap and 85 non-ROM closures including 29 "O-to-Z" flaps and 12 bilateral transposition flaps. A total of 111 squamous cell carcinomas, 64 basal cell carcinomas, and 11 melanoma were excised. ROM flap closures developed 20 complications (14.3%): 13 infections, 5 partial dehiscence, and 2 partial end flap necrosis. Non-ROM closures developed 27 complications (31.8%): 13 infections, 6 partial end flap necrosis, 4 partial dehiscence, 2 wound depression, 1 hemorrhage, and 1 persisting pain. Three ROM and 7 non-ROM cases suffered two complications. The total complication rate was significantly lower with ROM flaps (p=.003), including lower end flap necrosis incidence (p=.027). CONCLUSION: The ROM flap results in fewer complications than traditional techniques when closing defects 11 to 45 mm in size on the leg and foot. In particular, end flap necrosis incidence is lower with ROM flap closure.
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.
Individuals with night eating syndrome (NES) display a time-delayed pattern of food intake, outside the natural circadian rhythm. High prevalence estimates have been reported among bariatric surgery candidates, and some evidence suggests that NES is positively associated with obesity, negatively associated with weight loss efficacy, and follows a chronic course. In order to evaluate current NES theory, and the association between NES and bariatric surgery, literature searches were conducted to identify relevant literature published in English up to 2005. Because of inconsistencies in NES characterization, and significant heterogeneity in study design and methods, a qualitative assessment of NES and its relation to bariatric surgery was then undertaken. Within the literature, variable NES definitions highlight the distinct lack of clarity as to which behavioral features constitute a clinically meaningful entity. Prevalence estimates appear high among persons seeking bariatric surgery; however, no consistent pre- or postoperative demographic, clinical, or psychological factors reliably differentiate NES from non-NES. Further examination of the clinical significance, correlates, and course of NES in general and surgical samples is important, given the link with obesity. The ways in which NES departs from "normal" eating behavior must be clarified. Behavioral and psychological traits of NES need elucidation, and the establishment of agreed diagnostic criteria is essential for research to move forward. Therapy options should focus on aspects of the syndrome that cause greatest impairment, distress, or health risk.
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.
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.
BACKGROUND: Obesity is a chronic disease requiring a similar long term approach to management as that of other chronic conditions. OBJECTIVE: This article discusses the role of medications in the overall management of obesity. DISCUSSION: Management needs to be multifaceted, aiming to alter the patient and family micro-environment to one favouring better weight control through sustainable behavioural changes to physical activity and diet. Weight loss medications may provide additional benefit. Currently we have only two medications suitable for long term therapy--orlistat and sibutramine. Sibutramine, which acts centrally to suppress appetite, has shown efficacy for up to 2 years. Orlistat, a lipase inhibitor, reduces fat absorption and has been shown to reduce and maintain weight for up to 4 years. The effect of these medications is modest, generally providing less than 5 kg weight loss when compared with placebo. Patients need to have realistic expectations and understand the benefits of sustained modest weight loss. It is important that weight loss medications are prescribed in combination with lifestyle modification.
BACKGROUND: Obesity is rapidly becoming Australia's biggest health care issue. OBJECTIVE: This article discusses the role of surgery, in particular laparascopic adjustable gastric banding, in the management of obesity. DISCUSSION: The acceptability and uptake of surgery as a solution to obesity has, in the past, been low. This is largely due to the risks of bypass and stapling procedures, as well as the lack of long term efficacy. Laparoscopic adjustable gastric banding has, over the past 13 years, proven not only to be safe, but effective both in terms of weight loss and control of the comorbidities associated with obesity. It is currently the most effective solution we have available for patients who suffer from obesity.
Obesity is a chronic relapsing disease requiring a similar long term approach to management as that of other chronic conditions. Management needs to be multifaceted aiming to achieve sustainable behavioural changes to physical activity and diet to alter the patient and family microenvironment to one favouring better weight control. A range of therapies including specific diets, calorie counting, meal replacements, very low calorie diets, pharmacotherapy, intragastric balloons and surgery can provide very useful additional benefit. Use of these should be guided by the extent of weight loss required to reduce BMI to an acceptable level with regard to the patient's ethnicity, risk and comorbid conditions. Patients need to set goals that are optimistic, but realistic, and understand the benefits of sustained modest weight loss and the likelihood of weight regain requiring repeat episodes of weight loss. Practitioners need to be informed about the efficacy of current therapies and their combinations to enhance choice of suitable methods for achieving the optimal weight loss required by the patient. They will also need to anticipate trigger points for renewed periods of weight loss in the event of weight regain, as relapse is likely but not a reason for abandoning the battle.
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.
Adiponectin is an adipocyte-derived hormone associated with antidiabetic actions. In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2. In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects. Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052). In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside. In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation. In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected. Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1. These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.
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.
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.
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.