Nicholas Finer

Differential Effects of Laparoscopic Sleeve Gastrectomy and Laparoscopic Gastric Bypass on Appetite, Circulating Acyl-ghrelin, Peptide YY3-36 and Active GLP-1 Levels in Non-diabetic Humans

Laparoscopic Roux-en-Y gastric bypass (LRYGBP) reduces appetite and induces significant and sustainable weight loss. Circulating gut hormones changes engendered by LRYGBP are implicated in mediating these beneficial effects. Laparoscopic sleeve gastrectomy (LSG) is advocated as an alternative to LRYGBP, with comparable short-term weight loss and metabolic outcomes. LRYGBP and LSG are anatomically distinct procedures causing differential entero-endocrine cell nutrient exposure and thus potentially different gut hormone changes. Studies reporting the comparative effects of LRYGBP and LSG on appetite and circulating gut hormones are controversial, with no data to date on the effects of LSG on circulating peptide YY3-36 (PYY3-36) levels, the specific PYY anorectic isoform. In this study, we prospectively investigated appetite and gut hormone changes in response to LRYGBP and LSG in adiposity-matched non-diabetic patients. Anthropometric indices, leptin, fasted and nutrient-stimulated acyl-ghrelin, active glucagon-like peptide-1 (GLP-1), PYY3-36 levels and appetite were determined pre-operatively and at 6 and 12xa0weeks post-operatively in obese, non-diabetic females, with ten undergoing LRYGBP and eight adiposity-matched females undergoing LSG. LRYGBP and LSG comparably reduced adiposity. LSG decreased fasting and post-prandial plasma acyl-ghrelin compared to pre-surgery and to LRYGBP. Nutrient-stimulated PYY3-36 and active GLP-1 concentrations increased post-operatively in both groups. However, LRYGBP induced greater, more sustained PYY3-36 and active GLP-1 increments compared to LSG. LRYGBP suppressed fasting hunger compared to LSG. A similar increase in post-prandial fullness was observed post-surgery following both procedures. LRYGBP and LSG produced comparable enhanced satiety and weight loss. However, LSG and LRYGBP differentially altered gut hormone profiles.

Adiposity and cardiovascular risk factors in a large contemporary population of pre-pubertal children

AIMSnto examine the associations of several markers of adiposity and a wide range of cardiovascular risk factors and biomarkers in pre-pubertal children.nnnMETHODS AND RESULTSnfour measures of adiposity,body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry (DXA)-determined fat mass, and leptin concentration, were available in up to 7589 children aged 8.8-11.7 (9.9 mean) years from the Avon Longitudinal Study of Parents and Children (ALSPAC). Thirteen per cent of boys and 18.8% of girls were overweight, and 5.3% of boys and 5% of girls were obese. Body mass index was highly correlated with waist circumference (r = 0.91), DXA fat mass (r = 0.87), and leptin concentration (r = 0.75), and all had similar associations with cardiovascular risk factors. A 1 kg/m(2) greater BMI was associated with 1.4 mmHg (95% CI 1.25-1.44) higher systolic blood pressure (BP). In 5002 children, a 1 kg/m(2) greater BMI was associated with a 0.05 mmol/L (95% CI 0.036-0.055) higher non-high-density lipoprotein (HDL) cholesterol and 0.03 mmol/L (95% CI -0.034 to -0.025) lower HDL cholesterol. There were also graded associations with apolipoproteins A1 and B, interleukin-6, and C-reactive protein. Comparing children who were obese with those who were normal weight, the odds ratio for hypertension was 10.7 (95% CI 7.2-15.9) for boys and 13.5 (95% CI 9.4-19.5) for girls.nnnCONCLUSIONnin pre-pubertal UK children, overweight/obesity is common and has broadly similar associations with BP, HDL cholesterol, and non-HDL cholesterol to those observed in adults. Future research should evaluate whether effective interventions to maintain healthy weight in childhood could have important benefits for adult cardiovascular risk.

Childhood Obesity and Vascular Phenotypes A Population Study

OBJECTIVESnThis study sought to assess the associations of childhood adiposity with vascular phenotype in pre-pubertal children.nnnBACKGROUNDnThe early-life metabolic consequences have consistently been demonstrated in obese children, but the time course and development of any vascular changes remain largely unexplored.nnnMETHODSnA total of 6,576 children age 10 to 11 years from the ALSPAC (Avon Longitudinal Study of Parents and Children) were studied. Childhood overweight and obesity were based on body mass index contemporary to vascular measures and supported by other adiposity measures, including fat mass and waist circumference on dual-energy x-ray absorptiometry. Heart rate, blood pressure, flow-mediated dilation in the brachial artery, and carotid to radial pulse wave velocity were measured in all children.nnnRESULTSnOverweight and obese children had higher heart rates (mean 72.4 ± 11 beats/min and 74.6 ± 12.2 beats/min vs. 71.7 ± 11 beats/min) and systolic blood pressures (mean 106.3 ± 9.1 mm Hg and 108 ± 10.2 mm Hg vs. 103.6 ± 9 mm Hg) compared with normal-weight peers. However, obese children had greater brachial diameters and resting and hyperemic blood flow, marginally increased endothelial function (higher flow-mediated dilation: mean 8.2 ± 3.2% vs. 8.1 ± 3.3%), and lower arterial stiffness (pulse wave velocity: mean 6.99 ± 1.0 m/s vs. 7.05 ± 1.23 m/s) compared with normal-weight children. These findings were not explained by metabolic differences.nnnCONCLUSIONSnGreater childhood adiposity is associated with adverse cardiometabolic risk factors, but with no evidence of vascular damage at age 9 to 11 years. This could represent physiological adaptation to the hyperemic state of adiposity in childhood.

Adipose and Height Growth Through Childhood and Blood Pressure Status in a Large Prospective Cohort Study

Raised blood pressure (BP) is the worlds leading mortality risk factor. Childhood BP substantially predicts adult levels, and although both prenatal and postnatal growth influence it, their relative importance is debated. In a longitudinal study (Avon Longitudinal Study of Parents and Children) of 12 962 healthy children, we aimed to assess the relative contribution of different growth periods and of standardized measures of height versus weight-for-height (an adiposity marker) to BP at age 10 years. Conditional growth modeling was used in the 3230 boys and 3346 girls with BP measurements. Systolic BP was inversely associated with birth weight and weight-for-height but not length (−0.33, −0.27, and −0.12 mm Hg · SD−1; P=0.003, 0.035, and 0.35, respectively). In infancy, weight, weight-for-height, and height gains were all positively associated with systolic BP (0.90, 0.41, and 0.82 mm Hg · SD−1, respectively; all P<0.001). After infancy, all of the growth modalities were positively associated with systolic BP (weight, 1.91; weight-for-height, 1.56; height, 1.20 mm Hg · SD−1; all P<0.001). Similar but weaker associations were found with diastolic BP. Although BP at 10 years was associated with both prenatal and early postnatal growth, their influence was small compared with that of later growth. Because BP ranking relative to the population is substantially determined in the first decade of life, a focus on strategies to reduce the development of adiposity from infancy onward, rather than an emphasis on the nutrition and weight of mothers and infants, should bring greater reductions in population BP.

Pharmacotherapy for obesity: novel agents and paradigms.

Public health initiatives focused on obesity prevention and lifestyle intervention programmes for patients with obesity have struggled to contain the obesity epidemic to date. In recent years, antiobesity drug therapies have had a limited role in clinical treatment algorithms for patients with obesity. Indeed, a number of high-profile antiobesity drug suspensions have markedly impacted upon the landscape of obesity pharmacotherapy. In this review, we discuss the advent of an increasing array of pharmacotherapeutic agents, which are effective both in inducing weight loss and in maintaining weight loss achieved by lifestyle measures. The development of these drugs as antiobesity agents has followed varying paths, ranging from lorcaserin, a selective serotonin agent, exploiting the beneficial central actions of fenfluramine but without the associated systemic side effects, to liraglutide, a gut hormone already used as a glucose-lowering drug but with appetite-suppressant properties, or the novel drug combination of phentermine/topiramate, two ‘old’ drugs used in lower doses than with previous therapeutic uses, resulting in an additive effect on weight loss and fewer side effects. We summarize the key findings from recent randomized controlled trials of these three drugs. Although these agents lead to clinically important weight loss when used as monotherapy, the use of antiobesity drugs as adjunctive therapy post intensive lifestyle intervention could prove to be the most successful strategy. Moreover, a progressive approach to obesity pharmacotherapy perhaps offers the best opportunity to finally address the obesity crisis on a mass scale.

The impact of a health professional recommendation on weight loss attempts in overweight and obese British adults: a cross-sectional analysis

Objectives To examine the effect that health professional (HP) advice to lose weight has on overweight and obese adults’ motivation to lose weight and attempts to lose weight. Design Cross-sectional survey. Setting Great Britain. Participants 810 overweight or obese (body mass index ≥25u2005kg/m2) adults. Main outcome measures Participants were asked if they had ever received HP advice to lose weight and reported their desire to weigh less (ideal weight ≤95% of current weight) and whether they were attempting to lose weight. Results Only 17% of overweight and 42% of obese respondents recalled ever having received HP advice to lose weight. HP advice was associated with wanting to weigh less (89% vs 61% among those not receiving advice) and attempting to lose weight (68% vs 37%). In multivariable analyses, HP advice to lose weight was associated with increased odds of wanting to weigh less (OR=3.71, 95% CI 2.10 to 6.55) and attempting to lose weight (OR=3.53, 95% CI 2.44 to 5.10) independent of demographic characteristics and weight status. Conclusions HP advice to lose weight appears to increase motivation to lose weight and weight loss behaviour, but only a minority of overweight or obese adults receive such advice. Better training for HPs in delivering brief weight counselling could offer an opportunity to improve obese patients’ motivation to lose weight.

Early weight loss while on lorcaserin, diet and exercise as a predictor of week 52 weight-loss outcomes.

To identify an early treatment milestone that optimizes sensitivity and specificity for predicting ≥5% weight loss at Week (W) 52 in patients with and without type 2 diabetes on lorcaserin or placebo.

Early postoperative weight loss predicts maximal weight loss after sleeve gastrectomy and Roux-en-Y gastric bypass

BackgroundPrevious studies show that ‘poor responders’ to Roux-en-Y gastric bypass (RYGBP) may be identified on the basis of early postoperative weight loss. Early identification of poor responders could allow earlier provision of postoperative behavioural and/or intensive lifestyle interventions and enhance their maximal weight loss. Our aim was to investigate whether early postoperative weight loss predicts the maximal weight loss response after RYGBP and sleeve gastrectomy (SG).MethodsWe undertook a retrospective cross-sectional study of 1,456 adults who underwent either RYGBP (nxa0=xa0918) or SG (nxa0=xa0538) as a primary procedure in one of two European centres. Postoperative weight loss was expressed as weight loss velocity (WLV) and percentage weight loss. Linear regression analyses were performed to determine the association of early postoperative weight loss with maximal %WL, including adjustment for baseline variables.ResultsThere was marked variability in maximal %WL following both RYGBP (mean 32.9xa0%, range 4.1–60.9xa0%) and SG (mean 26.2xa0%, range 1.1–58.3xa0%). WLV 3–6xa0months postoperatively was more strongly associated with maximal %WL (r2xa0=xa00.32 for RYGBP and r2xa0=xa00.26 for SG, Pxa0<xa00.001 for both) than either WLV 0–6xa0weeks or 6xa0weeks to 3xa0months postoperatively (r2xa0=xa00.14 and 0.10 for RYGBP, respectively; r2xa0=xa00.18 and 0.21 for SG, respectively; Pxa0<xa00.001 for all). Multiple linear regression analysis, including baseline variables of age, sex, preoperative BMI, type 2 diabetes, ethnicity, and bariatric centre, revealed that 3–6xa0month WLV was an independent predictor of maximal %WL in both SG and RYGBP groups (standardised β-coefficients 0.51 and 0.52, respectively; Pxa0<xa00.001 for both).ConclusionsThere is a marked variability in weight loss response following RYGBP and SG. Early postoperative weight loss can be used to identify patients whose predicted weight loss trajectories are suboptimal. Early targeting of poor responders with more intensive postoperative lifestyle and behavioural support could potentially enhance their weight loss response.

New medications for treatment of obesity: metabolic and cardiovascular effects.

The management of obesity remains a major challenge. Dietary therapy often fails, whereas bariatric surgery, although successful, is demanding and applicable to a limited number of patients. Drug therapy has had many setbacks over the past 20 years because of serious adverse effects; however, several new drugs for the treatment of obesity are either licensed in some parts of the world, submitted for registration, or completing phase III trials. These include combinations (at low dose) of existing drugs, e.g., bupropion + naltrexone (Contrave), phentermine + topiramate (Qsymia), higher doses of existing drugs licensed for other indications (liraglutide, 3 mg), and new entities (lorcaserin). We discuss the challenges and opportunities for obesity pharmacotherapy and review in detail the efficacy of the new drugs regarding weight loss and both desirable and potential undesirable cardiovascular (CV) and metabolic risk factors. Substantial barriers remain, even if the drugs are approved, in successfully integrating these agents into weight management practice, largely related to cost, patient acceptability, and clinician willingness to be engaged in obesity treatment. Although hard clinical outcome benefit (at least for CV outcomes) has yet to be established, obesity pharmacotherapy may soon address many of the challenges in the clinical management of obesity, although newer and better drug combinations and more evidence of benefit from appropriately designed outcome trials is needed.

Selenium supplementation and exercise: effect on oxidant stress in overweight adults

Both obesity and acute high‐intensity exercise increase oxidant stress levels. This study investigates whether selenium (Se) supplementation could be a potential effective therapy to reduce obesity‐associated oxidant stress and exercise‐induced oxidant stress. Ten normal‐weight (NW) (22.80 ± 0.41 kg/m2) and ten overweight (OW) healthy subjects (28.00 ± 0.81 kg/m2) were assessed during a randomized double‐blind Se supplementation study (200 µg sodium selenite/day for 3 weeks) with a 3‐week placebo control and inversion of treatment periods. Blood levels of lipid hydroperoxide (LH), superoxide dismutase (SOD), erythrocyte glutathione (GSH), and total antioxidant status (TAS), were measured at rest, pre‐, and postexercise (30 min 70% VO2 max before and after treatment (pretreatment (week 0 and 12) and post‐treatment (week 3 or 15)). At rest, compared to placebo, Se supplementation had no significant effect on LH, SOD, GSH, and TAS levels. However, Se supplementation decreased LH levels in the OW group, immediately postexercise (−0.25 ± 0.12 µmol/l, P = 0.05) compared to placebo treatment. Postexercise, with or without Se supplementation, no changes in TAS, SOD, and GSH levels were observed in both the NW and OW group. This study has highlighted a potential benefit of Se in reducing LH levels postexercise in OW individuals. Given that oxidant stress is a predictor of coronary events, it is imperative to better understand oxidant stress‐related responses to lifestyle factors (in particular “high‐risk” population groups) and potential antioxidant therapy.