Improvement in coronary circulatory function in morbidly obese individuals after gastric bypass-induced weight loss: relation to alterations in endocannabinoids and adipocytokines.

AIMS: To investigate the effect of surgical gastric bypass-induced weight loss and related alterations in endocannabinoids (ECs) and adipocytokine plasma levels on coronary circulatory dysfunction in morbidly obese (MOB) individuals. METHODS AND RESULTS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) from rest (ΔMBF) and during pharmacologically induced hyperaemia were measured with &supl;³N-ammonia PET/CT in 18 MOB individuals with a body mass index (BMI) > 40 kg/m² at baseline and after a median follow-up period of 22 months. Gastric bypass intervention decreased BMI from a median of 44.8 (inter-quartile range: 43.3, 48.2) to 30.8 (27.3, 34.7) kg/m² (P < 0.0001). This decrease in BMI was accompanied by a marked improvement in endothelium-related ΔMBF to CPT and hyperaemic MBFs, respectively [0.34 (0.18, 0.41) from 0.03 (-0.08, 0.15) mL/g/min, P = 0.002; and 2.51 (2.17, 2.64) from 1.53 (1.39, 2.18) mL/g/min, P < 0.001]. There was an inverse correlation between decreases in plasma concentrations of the EC anandamide and improvement in ΔMBF to CPT (r = -0.59, P = 0.009), while increases in adiponectin plasma levels correlated positively with hyperaemic MBFs (r = 0.60, P = 0.050). Conversely, decreases in leptin plasma concentrations were not observed to correlate with the improvement in coronary circulatory function (r = 0.22, P = 0.400, and r = -0.31, P = 0.250). CONCLUSIONS: Gastric bypass-related reduction of BMI in MOB individuals beneficially affects coronary circulatory dysfunction. The dysbalance between ECs and adipocytokines appears to be an important determinant of coronary circulatory function in obesity.

Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammation via N-oleoylethanolamide (OEA)-mediated pathways.

Paradoxically, morbid obesity was suggested to protect from cardiovascular co-morbidities as compared to overweight/obese patients. We hypothesise that this paradox could be inferred to modulation of the "endocannabinoid" system on systemic and subcutaneous adipose tissue (SAT) inflammation. We designed a translational project including clinical and in vitro studies at Geneva University Hospital. Morbid obese subjects (n=11) were submitted to gastric bypass surgery (GBS) and followed up for one year (post-GBS). Insulin resistance and circulating and SAT levels of endocannabinoids, adipocytokines and CC chemokines were assessed pre- and post-GBS and compared to a control group of normal and overweight subjects (CTL) (n=20). In vitro cultures with 3T3-L1 adipocytes were used to validate findings from clinical results. Morbid obese subjects had baseline lower insulin sensitivity and higher hs-CRP, leptin, CCL5 and anandamide (AEA) levels as compared to CTL. GBS induced a massive weight and fat mass loss, improved insulin sensitivity and lipid profile, decreased C-reactive protein, leptin, and CCL2 levels. In SAT, increased expression of resistin, CCL2, CCL5 and tumour necrosis factor and reduced MGLL were shown in morbid obese patients pre-GBS when compared to CTL. GBS increased all endocannabinoids and reduced adipocytokines and CC chemokines. In morbid obese SAT, inverse correlations independent of body mass index were shown between palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA) levels and inflammatory molecules. In vitro, OEA inhibited CCL2 secretion from adipocytes via ERK1/2 activation. In conclusion, GBS was associated with relevant clinical, metabolic and inflammatory improvements, increasing endocannabinoid levels in SAT. OEA directly reduced CCL2 secretion via ERK1/2 activation in adipocytes.

Unstable shoes increase energy expenditure of obese patients.

BACKGROUND: Ergonomic unstable shoes, which are widely available to the general population, could increase daily non-exercise activity thermogenesis as the result of increased muscular involvement. We compared the energy expenditure of obese patients during standing and walking with conventional flat-bottomed shoes versus unstable shoes.¦METHODS: Twenty-nine obese patients were asked to stand quietly and to walk at their preferred walking speed while wearing unstable or conventional shoes. The main outcome measures were metabolic rate of standing and gross and net energy cost of walking, as assessed with indirect calorimetry.¦RESULTS: Metabolic rate of standing was higher while wearing unstable shoes compared with conventional shoes (1.11±0.20 W/kg(-1)vs 1.06±0.23 W/kg(-1), P=.0098). Gross and net energy cost of walking were higher while wearing unstable shoes compared with conventional shoes (gross: 4.20±0.42 J/kg(-1)/m(-1)vs 4.01±0.39 J/kg(-1)/m(-1), P=.0035; net: 3.37±0.41 J/kg(-1)/m(-1)vs 3.21±0.37 J/kg(-1)/m(-1); P=.032).¦CONCLUSION: In obese patients, it is possible to increase energy expenditure of standing and walking by means of ergonomic unstable footwear. Long-term use of unstable shoes may eventually prevent a positive energy balance.

Traitement de l'hypertension artérielle chez le sujet obèse [Treatment of hypertension in obese patients].

Prevalence of obesity and hypertension has increased these last decades. Around 60 to 70% of the incidence of hypertension is related to obesity. The relationship between obesity and hypertension is now well established. The sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system are activated in obese patients, mostly by insulin, and predispose the kidney to reabsorb sodium and water. In obese patients with hypertension, it is recommended to target a blood pressure < 140/90 mmHg. Lifestyle changes (weight loss, physical activity, low-salt diets) are useful to decrease blood pressure but are difficult to maintain in the long-term. When drugs are necessary, drugs that are metabolically neutral should be used, and often need to be combined to other drug classes in order to achieve blood pressure target.

Measurement of glomerular filtration rate in obese patients: pitfalls and potential consequences on drug therapy.

Epidemiological studies have shown that obesity is associated with chronic kidney disease and end stage renal disease. These studies have used creatinine derived equations to estimate glomerular filtration rate (GFR) and have indexed GFR to body surface area (BSA). However, the use of equations using creatinine as a surrogate marker of glomerular filtration and the indexation of GFR for BSA can be questioned in the obese population. First, these equations lack precision when they are compared to gold standard GFR measurements such as inulin clearances; secondly, the indexation of GFR for 1.73 m(2) of BSA leads to a systematic underestimation of GFR compared to absolute GFR in obese patients who have BSA that usually exceed 1.73 m(2). Obesity is also associated with pathophysiological changes that can affect the pharmacokinetics of drugs. The effect of obesity on both renal function and drug pharmacokinetics raises the issue of correct drug dosage in obese individuals. This may be particularly relevant for drugs known to have a narrow therapeutic range or excreted by the kidney.

Energy expenditure before and during energy restriction in obese patients.

Twenty-four hour energy expenditure (24 EE), resting metabolic rate (RMR), spontaneous physical activity and body composition were determined in 7 obese patients (5 females, 2 males, 174 +/- 9% IBW, 38 +/- 2% fat mass) on 2 different occasions: before weight reduction, and after 10 to 16 weeks on a hypocaloric diet as outpatients, the recommended energy intake varying from 3500 to 4700 kJ/day depending on the subject. Mean body weight loss was 12.6 +/- 1.9 kg, ie 13% of initial body weight, 72% being fat. Twenty-four hour energy expenditure (24 EE) was measured in a respiration chamber with all the subjects receiving 10418 kJ/d before weight reduction and an average of 3360 +/- 205 kJ/d while on the diet. When expressed in absolute values, both 24 EE and RMR decreased during the hypocaloric diet from 9819 +/- 442 to 8229 +/- 444 and from 7262 +/- 583 to 6591 +/- 547 kJ/d respectively. On the basis of fat-free-mass (FFM), 24 EE decreased from 168 +/- 6 to 148 +/- 5 kJ/kg FFM/d whereas RMR was unchanged (approximately 120 kJ/kg FFM/d). Approximately one half of the 24 EE reduction (1590 kJ/d) was accounted for by a decrease in RMR, the latter being mainly accounted for by a reduction in FFM. Most of the remaining decline in 24 EE can be explained by a decreased thermic effect of food, and by the reduced cost of physical activity mainly due to a lower body weight. Therefore, there seems little reason to evoke additional mechanisms to explain the decline in energy expenditure during dieting.

Unstable shoes increase energy expenditure of obese patients.

BACKGROUND: Ergonomic unstable shoes, which are widely available to the general population, could increase daily non-exercise activity thermogenesis as the result of increased muscular involvement. We compared the energy expenditure of obese patients during standing and walking with conventional flat-bottomed shoes versus unstable shoes. METHODS: Twenty-nine obese patients were asked to stand quietly and to walk at their preferred walking speed while wearing unstable or conventional shoes. The main outcome measures were metabolic rate of standing and gross and net energy cost of walking, as assessed with indirect calorimetry. RESULTS: Metabolic rate of standing was higher while wearing unstable shoes compared with conventional shoes (1.11 ± 0.20 W/kg(-1) vs 1.06 ± 0.23 W/kg(-1), P=.0098). Gross and net energy cost of walking were higher while wearing unstable shoes compared with conventional shoes (gross: 4.20 ± 0.42 J/kg(-1)/m(-1)vs 4.01 ± 0.39 J/kg(-1)/m(-1), P=.0035; net: 3.37 ± 0.41 J/kg(-1)/m(-1) vs 3.21 ± 0.37 J/kg(-1)/m(-1); P=.032). CONCLUSION: In obese patients, it is possible to increase energy expenditure of standing and walking by means of ergonomic unstable footwear. Long-term use of unstable shoes may eventually prevent a positive energy balance.

Roux-en-Y gastric bypass vs gastric banding for morbid obesity: a case-matched study of 442 patients.

HYPOTHESIS: Gastric banding (GB) and Roux-en-Y gastric bypass (RYGBP) are used in the treatment of morbidly obese patients. We hypothesized that RYGBP provides superior results. DESIGN: Matched-pair study in patients with a body mass index (BMI) less than 50. SETTING: University hospital and regional community hospital with a common bariatric surgeon. PATIENTS: Four hundred forty-two patients were matched according to sex, age, and BMI. INTERVENTIONS: Laparoscopic GB or RYGBP. MAIN OUTCOME MEASURES: Operative morbidity, weight loss, residual BMI, quality of life, food tolerance, lipid profile, and long-term morbidity. RESULTS: Follow-up was 92.3% at the end of the study period (6 years postoperatively). Early morbidity was higher after RYGBP than after GB (17.2% vs 5.4%; P<.001), but major morbidity was similar. Weight loss was quicker, maximal weight loss was greater, and weight loss remained significantly better after RYGBP until the sixth postoperative year. At 6 years, there were more failures (BMI>35 or reversal of the procedure/conversion) after GB (48.3% vs 12.3%; P<.001). There were more long-term complications (41.6% vs 19%; P.001) and more reoperations (26.7% vs 12.7%; P<.001) after GB. Comorbidities improved more after RYGBP. CONCLUSIONS: Roux-en-Y gastric bypass is associated with better weight loss, resulting in a better correction of some comorbidities than GB, at the price of a higher early complication rate. This difference, however, is largely compensated by the much higher long-term complication and reoperation rates seen after GB.

Impact de la chirurgie bariatrique sur la santé et la qualité de vie du patient obèse [Impact of bariatric surgery on health and quality life of obese patients]

The important weight loss due to bariatric surgery allows to improve and even correct, a great part of the comorbidities induced by obesity, as well as quality of life, and to reduce the coming out of cardiovascular and metabolic diseases in operated patients. The impact of surgical treatment on the patient's health and quality of life also allows to reduce direct and indirect costs of morbid obesity. However, its effects on mortality have not yet been clearly proved. The preoperative evaluation and the long term follow-up by a skilled team are essential to reduce potential complications, especially on the nutritional field and the risks of recovered weight linked to binge eating disorders.

Brachial or wrist blood pressure in obese patients: which is the best?

OBJECTIVE: Blood pressure (BP) measured in obese patients with a large arm circumference using a cuff of standard width may be overestimated. METHODS: We compared in this study the BP readings obtained with oscillometric devices at the left arm (OMRON HEM 705-CP) and the left wrist (OMRON R6) (Omron Medizintechnik, Mannheim, Germany) in lean (n=15) and obese (n=11) patients. RESULTS: No difference was found in diastolic BP between the two groups, nor between the arm and the wrist. Systolic BP measured at the arm was, however, significantly lower in obese (99+/-9 mmHg, mean+/-SD) than in lean (107+/-14 mmHg; P<0.001) patients, whereas systolic BP determined at the wrist averaged 106 mmHg in both groups. CONCLUSION: The use of validated wrist BP measuring devices appears therefore particularly appealing in obese individuals with a large arm circumference

Counselling overweight and obese patients in primary care: a prospective cohort study.

BACKGROUND: Primary care physicians are well positioned to provide counselling for overweight and obese patients, but no prospective study has assessed the effectiveness of this counselling in primary care. We aimed to evaluate weight reduction counselling by primary care physicians, and its relationship with weight change and patients' behaviour to control weight. DESIGN: A prospective cohort study. METHODS: We enrolled 523 consecutive overweight and obese patients from two Swiss academic primary care clinics. Physicians and patients were blinded to the study aims. We assessed the use of 10 predefined counselling strategies for weight reduction, and weight change and behaviour to control weight after 1 year. RESULTS: Sixty-five per cent of patients received some form of weight reduction counselling whereas 35% received no counselling. A total of 407 patients completed the 1-year follow-up. Those who received counselling lost on average (SD) 1.0 (5.0) kg after 1 year, whereas those who were not advised gained 0.3 (5.0) kg (P = 0.02). In multivariate analysis, each additional counselling strategy was associated with a mean weight loss of 0.2 kg (95% confidence interval 0.03-0.4, P = 0.02). Patients counselled by their physician had more favourable behaviour to control weight than those not counselled, such as setting a target weight (56 versus 36%) or visiting a dietician (23 versus 10%, both P < 0.001). CONCLUSIONS: Weight reduction counselling by primary care physicians is associated with a modest weight loss and favourable behaviour to control weight. However, many obese and overweight patients receive no advice on weight loss during primary care visits.

Relationship between autonomic neuropathy and thermogenesis in non diabetic and diabetic obese patients.

Autonomic neuropathy is a well known complication of diabetes. Diabetes is often superimposed on obesity. A reduction in the variability of the heart rate in the resting state has been demonstrated in 16 obese diabetic subjects as well as in 34 obese non-diabetic subjects. The coefficient of variation (CV) of the heart rate during 30 minutes of resting was significantly decreased in both obese groups (3.9 +/- 0.2% for the diabetics; 5.2 +/- 0.2%, p less than 0.01 for the non diabetics) as compared to their own controls (4.5 +/- 0.6% and 6.5 +/- 0.4%, respectively). Age also contributes to decreased heart rate variability. Furthermore, this defect of autonomic function has been correlated with the blunted glucose-induced thermogenesis (GIT) seen in both obese groups (r = 0.52, p. less than 0.001): the increase in energy expenditure over basal values following a 100 g oral glucose load was only 4.8 +/- 0.8% for the diabetic obese group (p less than 0.001), and 8.5 +/- 0.7% for the non-diabetic obese group (p less than 0.001) as opposed to their own controls (12.4 +/- 1.3% and 13.3 +/- 0.6% respectively). Measurement of the variability of heart rate in obese individuals may be of predictive value in assessing blunted glucose-induced thermogenesis in non diabetic and diabetic obese patients.

Psychometric evaluation of the IWQOL-Lite (Spanish version) when applied to a sample of obese patients awaiting bariatric surgery

Background Obesity may have an impact on key aspects of health-related quality of life (HRQOL). In this context, the Impact of Weight Quality of Life (IWQOL) questionnaire was the first scale designed to assess HRQOL. The aim of the present study was twofold: to assess HRQOL in a sample of Spanish patients awaiting bariatric surgery and to determine the psychometric properties of the IWQOL-Lite and its sensitivity to detect differences in HRQOL across groups. Methods Participants were 109 obese adult patients (BMI¿ 35 kg/m2) from Barcelona, to whom the following measurement instruments were applied: IWQOL-Lite, Depression Anxiety Stress Scales, Brief Symptom Inventory, and self-perception items. Results Descriptive data regarding the IWQOL-Lite scores obtained by these patients are reported. Principal components analysis revealed a five-factor model accounting for 72.05% of the total variance, with factor loadings being adequate for all items. Corrected itemtotal correlations were acceptable for all items. Cronbach"s alpha coefficients were excellent both for the subscales (0.880.93) and the total scale (0.95). The relationship between the IWQOLLite and other variables supports the construct validity of the scale. Finally, sensitivity analysis revealed large effect sizes when comparing scores obtained by extreme BMI groups. Conclusions This is the first study to report the application of the IWQOL-Lite to a sample of Spanish patients awaiting bariatric surgery and to confirm that the Spanish version of the instrument has adequate psychometric properties.

Effect of orlistat in obese patients with binge eating disorder.

OBJECTIVE: Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder. RESEARCH METHODS AND PROCEDURES: Eighty-nine patients with clinically diagnosed binge eating disorder and a BMI > or = 30 kg/m2 were randomized in double-blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced-calorie diet. RESULTS: After 24 weeks, the mean weight loss from baseline for orlistat-treated patients was significantly greater than for patients receiving placebo (-7.4% vs. -2.3%; p = 0.0001) (intent-to-treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011). DISCUSSION: Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.