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Polygenic risk score for predicting weight loss after bariatric surgery.

ABSTRACT: BACKGROUND:The extent of weight loss among patients undergoing bariatric surgery is highly variable. Herein, we tested the contribution of genetic background to such interindividual variability after biliopancreatic diversion with duodenal switch. METHODS:Percentage of excess body weight loss (%EBWL) was monitored in 865 patients over a period of 48 months after bariatric surgery, and two polygenic risk scores were constructed with 186 and 11 (PRS186 and PRS11) single nucleotide polymorphisms previously associated with body mass index (BMI). RESULTS:The accuracy of the %EBWL logistic prediction model - including initial BMI, age, sex, and surgery modality, and assessed as the area under the receiver operating characteristics (ROC) curve adjusted for optimism (AUCadj = 0.867) - significantly increased after the inclusion of PRS186 (?AUCadj = 0.021; 95% CI of the difference [95% CIdiff] = 0.005-0.038) but not PRS11 (?AUCadj= 0.008; 95% CIdiff= -0.003-0.019). The overall fit of the longitudinal linear mixed model for %EBWL showed a significant increase after addition of PRS186 (-2 log-likelihood = 12.3; P = 0.002) and PRS11 (-2 log-likelihood = 9.9; P = 0.007). A significant interaction with postsurgery time was found for PRS186 (? = -0.003; P = 0.008) and PRS11 (? = -0.008; P = 0.03). The inclusion of PRS186 and PRS11 in the model improved the cost-effectiveness of bariatric surgery by reducing the percentage of false negatives from 20.4% to 10.9% and 10.2%, respectively. CONCLUSION:These results revealed that genetic background has a significant impact on weight loss after biliopancreatic diversion with duodenal switch. Likewise, the improvement in weight loss prediction after addition of polygenic risk scores is cost-effective, suggesting that genetic testing could potentially be used in the presurgical assessment of patients with severe obesity. FUNDING:Heart and Stroke Foundation of Canada (G-17-0016627) and Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health (no. 950-231-580).

SUBMITTER: de Toro-Martin J

PROVIDER: S-EPMC6171810 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Polygenic risk score for predicting weight loss after bariatric surgery.

de Toro-Martín Juan J Guénard Frédéric F Tchernof André A Pérusse Louis L Marceau Simon S Vohl Marie-Claude MC

JCI insight 20180906 17

<h4>Background</h4>The extent of weight loss among patients undergoing bariatric surgery is highly variable. Herein, we tested the contribution of genetic background to such interindividual variability after biliopancreatic diversion with duodenal switch.<h4>Methods</h4>Percentage of excess body weight loss (%EBWL) was monitored in 865 patients over a period of 48 months after bariatric surgery, and two polygenic risk scores were constructed with 186 and 11 (PRS186 and PRS11) single nucleotide p ...[more]

PMID: 30185664

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Project description:Importance:Perception of weight loss requirements before bariatric surgery varies among patients, physicians, and health insurance payers. Current clinical guidelines do not require preoperative weight loss because of a lack of scientific support regarding its benefits. Objective:To examine the association of preoperative body mass index (BMI) and weight loss with 30-day mortality after bariatric surgery. Design, Setting, and Participants:This cohort study used data from 480 075 patients who underwent bariatric surgery from 2015 to 2017 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program, which covers more than 90% of all bariatric surgery programs in the United States and Canada. Clinical and demographic data were collected at all participating institutions using a standardized protocol. Data analysis was performed from December 2018 to November 2019. Exposures:Preoperative BMI and weight loss. Main Outcomes and Measures:30-day mortality after bariatric surgery. Results:Of the 480 075 patients (mean [SD] age 45.1 [12.0] years; 383 265 [79.8%] women), 511 deaths (0.1%) occurred within 30 days of bariatric surgery. Compared with patients with a preoperative BMI of 35.0 to 39.9, the multivariable-adjusted odds ratios for 30-day mortality for patients with preoperative BMI of 40.0 to 44.9, 45.0 to 49.9, 50.0 to 54.9, and 55.0 and greater were 1.37 (95% CI, 1.02-1.83), 2.19 (95% CI, 1.64-2.92), 2.61 (95% CI, 1.90-3.58), and 5.03 (95% CI, 3.78-6.68), respectively (P for trend < .001). Moreover, compared with no preoperative weight loss, the multivariable-adjusted odds ratios for 30-day mortality for patients with weight loss of more than 0% to less than 5.0%, 5.0% to 9.9%, and 10.0% and greater were 0.76 (95% CI, 0.60-0.96), 0.69 (95% CI, 0.53-0.90), and 0.58 (95% CI, 0.41-0.82), respectively (P for trend = .003). Conclusions and Relevance:In this study, even moderate weight loss (ie, >0% to <5%) before bariatric surgery was associated with a lower risk of 30-day mortality. These findings may help inform future updates of clinical guidelines regarding bariatric surgery.

Project description:Obesity is a global health challenge that warrants effective treatments to avoid its multiple comorbidities. Bariatric surgery, a cornerstone treatment to control bodyweight excess and relieve the health-related burdens of obesity, can promote accelerated bone loss and affect skeletal strength, particularly after malabsorptive and mixed surgical procedures, and probably after restrictive surgeries. The increase in bone resorption markers occurs early and persist for up to 12 months or longer after bariatric surgery, while bone formation markers increase but to a lesser extent, suggesting a potential uncoupling process between resorption and formation. The skeletal response to bariatric surgery, as investigated by dual-energy X-ray absorptiometry (DXA), has shown significant loss in bone mineral density (BMD) at the hip with less consistent results for the lumbar spine. Supporting DXA studies, analyses by high-resolution peripheral quantitative computed tomography (HR-pQCT) showed lower cortical density and thickness, higher cortical porosity, and lower trabecular density and number for up to 5 years after bariatric surgery. These alterations translate into an increased risk of fall injury, which contributes to increase the fracture risk in patients who have been subjected to bariatric surgery procedures. As bone deterioration continues for years following bariatric surgery, the fracture risk does not seem to be dependent on acute weight loss but, rather, is a chronic condition with an increasing impact over time. Among the post-bariatric surgery mechanisms that have been claimed to act globally on bone health, there is evidence that micro- and macro-nutrient malabsorptive factors, mechanical unloading and changes in molecules partaking in the crosstalk between adipose tissue, bone and muscle may play a determining role. Given these circumstances, it is conceivable that bone health should be adequately investigated in candidates to bariatric surgery through bone-specific work-up and dedicated postsurgical follow-up. Specific protocols of nutrients supplementation, motor activity, structured rehabilitative programs and, when needed, targeted therapeutic strategies should be deemed as an integral part of post-bariatric surgery clinical support.

Project description:ImportanceBariatric surgery induces significant weight loss for severely obese patients, but there is limited evidence of the durability of weight loss compared with nonsurgical matches and across bariatric procedures.ObjectivesTo examine 10-year weight change in a large, multisite, clinical cohort of veterans who underwent Roux-en-Y gastric bypass (RYGB) compared with nonsurgical matches and the 4-year weight change in veterans who underwent RYGB, adjustable gastric banding (AGB), or sleeve gastrectomy (SG).Design, setting, and participantsIn this cohort study, differences in weight change up to 10 years after surgery were estimated in retrospective cohorts of 1787 veterans who underwent RYGB from January 1, 2000, through September 30, 2011 (573 of 700 eligible [81.9%] with 10-year follow-up), and 5305 nonsurgical matches (1274 of 1889 eligible [67.4%] with 10-year follow-up) in mixed-effects models. Differences in weight change up to 4 years were compared among veterans undergoing RYGB (n = 1785), SG (n = 379), and AGB (n = 246). Data analysis was performed from September 9, 2014, to February 12, 2016.ExposuresBariatric surgical procedures and usual care.Main outcomes and measuresWeight change up to 10 years after surgery through December 31, 2014.ResultsThe 1787 patients undergoing RYGB had a mean (SD) age of 52.1 (8.5) years and 5305 nonsurgical matches had a mean (SD) age of 52.2 (8.4) years. Patients undergoing RYGB and nonsurgical matches had a mean body mass index of 47.7 and 47.1, respectively, and were predominantly male (1306 [73.1%] and 3911 [73.7%], respectively). Patients undergoing RYGB lost 21% (95% CI, 11%-31%) more of their baseline weight at 10 years than nonsurgical matches. A total of 405 of 564 patients undergoing RYGB (71.8%) had more than 20% estimated weight loss, and 224 of 564 (39.7%) had more than 30% estimated weight loss at 10 years compared with 134 of 1247 (10.8%) and 48 of 1247 (3.9%), respectively, of nonsurgical matches. Only 19 of 564 patients undergoing RYGB (3.4%) regained weight back to within an estimated 5% of their baseline weight by 10 years. At 4 years, patients undergoing RYGB lost 27.5% (95% CI, 23.8%-31.2%) of their baseline weight, patients undergoing AGB lost 10.6% (95% CI, 0.6%-20.6%), and patients undergoing SG lost 17.8% (95% CI, 9.7%-25.9%). Patients undergoing RYGB lost 16.9% (95% CI, 6.2%-27.6%) more of their baseline weight than patients undergoing AGB and 9.7% (95% CI, 0.8%-18.6%) more than patients undergoing SG.Conclusions and relevancePatients in the Veterans Administration health care system lost substantially more weight than nonsurgical matches and sustained most of this weight loss in the long term. Roux-en-Y gastric bypass induced significantly greater weight loss among veterans than SG or AGB at 4 years. These results provide further evidence of the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations.

Project description:BACKGROUND/OBJECTIVES:Despite the effectiveness of bariatric surgery, there is still substantial variability in long-term weight outcomes and few factors with predictive power to explain this variability. Neuroimaging may provide a novel biomarker with utility beyond other commonly used variables in bariatric surgery trials to improve prediction of long-term weight-loss outcomes. The purpose of this study was to evaluate the effects of sleeve gastrectomy (SG) on reward and cognitive control circuitry postsurgery and determine the extent to which baseline brain activity predicts weight loss at 12-month postsurgery. SUBJECTS/METHODS:Using a longitudinal design, behavioral, hormone and neuroimaging data (during a desire for palatable food regulation paradigm) were collected from 18 patients undergoing SG at baseline (<1 month prior) and 12-month post-SG. RESULTS:SG patients lost an average of 29.0% of their weight (percentage of total weight loss (%TWL)) at 12-month post-SG, with significant variability (range: 16.0-43.5%). Maladaptive eating behaviors (uncontrolled, emotional and externally cued eating) improved (P<0.01), in parallel with reductions in fasting hormones (acyl ghrelin, leptin, glucose, insulin; P<0.05). Brain activity in the nucleus accumbens (NAcc), caudate, pallidum and amygdala during desire for palatable food enhancement vs regulation decreased from baseline to 12 months (P (family-wise error (FWE))<0.05). Dorsolateral and dorsomedial prefrontal cortex activity during desire for palatable food regulation (vs enhancement) increased from baseline to 12 months (P(FWE)<0.05). Baseline activity in the NAcc and hypothalamus during desire for palatable food enhancement was significantly predictive of %TWL at 12 months (P (FWE)<0.05), superior to behavioral and hormone predictors, which did not significantly predict %TWL (P>0.10). Using stepwise linear regression, left NAcc activity accounted for 54% of the explained variance in %TWL at 12 months. CONCLUSIONS:Consistent with previous obesity studies, reward-related neural circuit activity may serve as an objective, relatively robust predictor of postsurgery weight loss. Replication in larger studies is necessary to determine true effect sizes for outcome prediction.

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Polygenic risk score for predicting weight loss after bariatric surgery.

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Polygenic risk score for predicting weight loss after bariatric surgery.

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