Remission and Relapse of Dyslipidemia After Vertical Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass in a Racially and Ethnically Diverse Population.

Importance: The comparative effectiveness of the most common operations in the long-term management of dyslipidemia is not clear. Objective: To compare 4-year outcomes associated with vertical sleeve gastrectomy (VSG) vs Roux-en-Y gastric bypass (RYGB) for remission and relapse of dyslipidemia. Design, Setting, and Participants: This retrospective comparative effectiveness study was conducted from January 1, 2009, to December 31, 2016, with follow-up until December 31, 2018. Participants included patients with dyslipidemia at the time of surgery who underwent VSG (4142 patients) or RYGB (2853 patients). Patients were part of a large integrated health care system in Southern California. Analysis was conducted from January 1, 2018, to December 31, 2021. Exposures: RYGB and VSG. Main Outcomes and Measures: Dyslipidemia remission and relapse were assessed in each year of follow-up for as long as 4 years after surgery. Results: A total of 8265 patients were included, with a mean (SD) age of 46 (11) years; 6591 (79.8%) were women, 3545 (42.9%) were Hispanic, 1468 (17.8%) were non-Hispanic Black, 2985 (36.1%) were non-Hispanic White, 267 (3.2%) were of other non-Hispanic race, and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 44 (7) at the time of surgery. Dyslipidemia outcomes at 4 years were ascertained for 2168 patients (75.9%) undergoing RYGB and 3999 (73.9%) undergoing VSG. Remission was significantly higher for those who underwent RYGB (824 [38.0%]) compared with VSG (1120 [28.0%]) (difference in the probability of remission, 0.10; 95% CI, 0.01-0.19), with no differences in relapse (455 [21.0%] vs 960 [24.0%]). Without accounting for relapse, remission of dyslipidemia after 4 years was 58.9% (1279) for those who underwent RYGB and 51.9% (2079) for those who underwent VSG. Four-year differences between operations were most pronounced for patients 65 years or older (0.39; 95% CI, 0.27-0.51), those with cardiovascular disease (0.43; 95% CI, 0.24-0.62), or non-Hispanic Black patients (0.13; 95% CI, 0.01-0.25) and White patients (0.13; 95% CI, 0.03-0.22). Conclusions and Relevance: In this large, racially and ethnically diverse cohort of patients who underwent bariatric and metabolic surgery in clinical practices, RYGB was associated with higher rates of dyslipidemia remission after 4 years compared with VSG. However, almost one-quarter of all patients experienced relapse, suggesting that patients should be monitored closely throughout their postoperative course to maximize the benefits of these operations for treatment of dyslipidemia.

Comparative effectiveness of gastric bypass and sleeve gastrectomy on predicted 10-year risk of cardiovascular disease 5 years after surgery.

BACKGROUND: Comparative evidence is needed when deciding which bariatric operation to undergo for long-term cardiovascular risk reduction. OBJECTIVES: The Effectiveness of Gastric Bypass vs. Gastric Sleeve for Cardiovascular Disease (ENGAGE CVD) study compared the effectiveness of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations for reduction of the American College of Cardiology and the American Heart Association-predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk 5 years after surgery. SETTING: Data for this study came from a large integrated healthcare system in the Southern California region of the United States. This is one of the most ethnically diverse (64% non-White) bariatric populations in the literature. METHODS: The ENGAGE CVD cohort consisted of 22,095 patients who underwent VSG or RYGB from 2009-2016. The VSG and RYGB were compared using a local instrumental variable approach to address observed and unobserved confounding, as well as to conduct heterogeneity of treatment effects for patients of different age groups, baseline-predicted 10-year CVD risk using the ASCVD risk score, and those who had type 2 diabetes (T2D) at the time of surgery. RESULTS: Patients (2771 RYGB and 6256 VVSG) were primarily women (80.6%), Hispanic or non-Hispanic Black (63.7%), and 46 ± 10 years of age, with a body mass index of 43.40 ± 6.5 kg/m2. The predicted 10-year ASCVD risk at surgery was 4.1% for VSG and 5.1% for RYGB, decreasing to 2.6% for VSG and 2.8% for RYGB 1 year postoperatively. By 5 years after surgery, patients remained with relatively low risk levels (3.0% for VSG and 3.3% for RYGB) and there were no significant differences in predicted 10-year ASCVD risk between VSG and RYGB at any time. CONCLUSION: Predicted 10-year ASCVD risk was low in this population and remained low up to 5 years for those with diabetes, Black and Hispanic patients, and older adults. Literature reporting significant differences between VSG and RYGB in 10-year ASCVD risk may be a result of residual confounding.

Minimum Threshold of Bariatric Surgical Weight Loss for Initial Diabetes Remission.

OBJECTIVE: There are few studies testing the amount of weight loss necessary to achieve initial remission of type 2 diabetes mellitus (T2DM) following bariatric surgery and no published studies with use of weight loss to predict initial T2DM remission in sleeve gastrectomy (SG) patients. RESEARCH DESIGN AND METHODS: With Cox proportional hazards models we examined the relationship between initial T2DM remission and percent total weight loss (%TWL) after bariatric surgery. Categories of %TWL were included in the model as time-varying covariates. RESULTS: Of patients (N = 5,928), 73% were female; mean age was 49.8 ± 10.3 years and BMI 43.8 ± 6.92 kg/m2, and 57% had Roux-en-Y gastric bypass (RYGB). Over an average follow-up of 5.9 years, 71% of patients experienced initial remission of T2DM (mean time to remission 1.0 year). With 0-5% TWL used as the reference group in Cox proportional hazards models, patients were more likely to remit with each 5% increase in TWL until 20% TWL (hazard ratio range 1.97-2.92). When categories >25% TWL were examined, all patients had a likelihood of initial remission similar to that of 20-25% TWL. Patients who achieved >20% TWL were more likely to achieve initial T2DM remission than patients with 0-5% TWL, even if they were using insulin at the time of surgery. CONCLUSIONS: Weight loss after bariatric surgery is strongly associated with initial T2DM remission; however, above a threshold of 20% TWL, rates of initial T2DM remission did not increase substantially. Achieving this threshold is also associated with initial remission even in patients who traditionally experience lower rates of remission, such as patients taking insulin.

Comparative Effectiveness of Gastric Bypass and Vertical Sleeve Gastrectomy for Hypertension Remission and Relapse: The ENGAGE CVD Study.

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Best practices in policy and access (coding and reimbursement) for weight loss surgery.

To update evidence-based best practice guidelines for coding and reimbursement and establish policy and access standards for weight loss surgery (WLS). Systematic search of English-language literature on WLS and health-care policy, access, insurance reimbursement, coding, private payers, public policy, and mandated benefits published between April 2004 and May 2007 in MEDLINE, EMBASE, and the Cochrane Library. Use of key words to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. We identified 51 publications in our literature search; the 20 most relevant were examined in detail. These included reviews, cost-benefit analyses, and trend and cost studies from administrative databases. Literature on policy issues surrounding WLS are very sparse and largely focused on economic analyses. Reports on policy initiatives in the public and private arenas are primarily limited to narrative reviews of nonsurgical efforts to fight obesity. A substantial body of work shows that WLS improves or reverses most obesity-related comorbidities. Mounting evidence also indicates that WLS confers a significant survival advantage for those who undergo it. WLS is a viable and cost-effective treatment for an increasingly common disease, and policy decisions are more frequently being linked to incentives for national health-care goals. However, access to WLS often varies by payer and region. Currently, there are no uniform criteria for determining patient appropriateness for surgery.

Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism.

The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2 thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We performed cross-sectional analysis of fasting serum bile acid composition and both fasting and post-meal metabolic variables, in three subject groups: (i) post-GB surgery (n = 9), (ii) without GB matched to preoperative BMI of the index cohort (n = 5), and (iii) without GB matched to current BMI of the index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 +/- 4.84 micromol/l) than in both overweight (3.59 +/- 1.95, P = 0.005, Ov) and severely obese (3.86 +/- 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids were all significantly higher in GB compared to Ov (P < 0.05). Total bile acids were inversely correlated with 2-h post-meal glucose (r = -0.59, P < 0.003) and fasting triglycerides (r = -0.40, P = 0.05), and positively correlated with adiponectin (r = -0.48, P < 0.02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P < 0.003). Total bile acids strongly correlated inversely with thyrotropic hormone (TSH) (r = -0.57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB.

Peptide YY levels are elevated after gastric bypass surgery.

OBJECTIVE: Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux-en-Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut-derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose. RESEARCH METHODS AND PROCEDURES: PYY and ghrelin levels after a 75-gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls. RESULTS: After substantial body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased approximately 10-fold after a 75-gram glucose load to a peak of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time-points. In contrast, PYY levels in obese and lean controls increased to a peak of approximately 2-fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY. DISCUSSION: Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY(3-36) replacement could represent an effective therapy for obesity.

Therapy insight: weight-loss surgery and major cardiovascular risk factors.

Weight-loss surgery is an effective treatment for severe, medically complicated and refractory obesity. It reverses, eliminates or significantly ameliorates major cardiovascular risk factors related to obesity. In a large proportion of patients, the therapy produces significant weight loss, reduces the risk of disability and premature death, and improves quality of life. Surgical treatment by gastric-restrictive and malabsorptive procedures started several decades ago in the US. Since the 1970s, accrued clinical experience and advances in technology, particularly in minimally invasive surgical approaches, have changed this therapy. Some procedures have evolved, whereas others have become obsolete. Today's weight-loss operations are safe, effective and potentially life-saving options for severely obese cardiology patients. This review describes weight-loss surgery procedures and their effects on cardiovascular risk factors.

Coding and reimbursement for weight loss surgery: best practice recommendations.

OBJECTIVE: To review the use and usefulness of billing codes for services related to weight loss surgery (WLS) and to examine third party reimbursement policies for these services. RESEARCH METHODS AND PROCEDURES: The Task Group carried out a systematic search of MEDLINE, the Internet, and the trade press for publications on WLS, coding, reimbursement, and coding and reimbursement policy. Twenty-eight articles were each reviewed and graded using a system based on established evidence-based models. The Massachusetts Dietetics Association provided reimbursement data for nutrition services. Three suppliers of laparoscopic WLS equipment provided summaries of coding and reimbursement information. WLS program directors were surveyed for information on use of procedure codes related to WLS. RESULTS: Recommendations focused on correcting or improving on the current lack of congruity among coding practices, reimbursement policies, and accepted clinical practice; lack of uniform coding and reimbursement data across institutions; inconsistent and/or inaccurate diagnostic and billing codes; inconsistent insurance reimbursement criteria; and inability to leverage reimbursement and coding data to track outcomes, identify best practices, and perform accurate risk-benefit analyses. DISCUSSION: Rapid changes in the prevalence of obesity, our understanding of its clinical impact, and the technologies for surgical treatment have yet to be adequately reflected in coding, coverage, and reimbursement policies. Issues identified as key to effective change include improved characterization of the risks, benefits, and costs of WLS; anticipation and monitoring of technological advances; encouragement of consistent patterns of insurance coverage; and promotion of billing codes for WLS procedures that facilitate accurate tracking of clinical use and outcomes.

Role of protein kinase C in intestinal ischemic preconditioning.

INTRODUCTION: Tissue protection by ischemic preconditioning (IPC) has been previously characterized in organs such as the heart and involves at least in part PKC activation. It is not yet clear whether such preconditioning against ischemia/reperfusion (I/R) injury operates in the intestine, and, if so, whether IPC involves protein kinase C (PKC). MATERIALS AND METHODS: IPC of the small intestine in male Sprague Dawley rats was induced by 10-min superior mesenteric artery (SMA) clamp followed by 120-min reperfusion. Sham-operated control or IPC rats were then rechallenged with 20-min SMA clamp. Histological injury to jejunal mucosa was assessed by microscopic examination and Parks' injury score (Grade 0-4; 0 = no damage). PKC activity was determined by immunoprecipitation of specific isoforms followed by in vitro kinase assay using mucosal scrapings of the harvested jejunum. Data were expressed as mean +/- SEM and analyzed by one-way ANOVA with multiple comparison tests. RESULTS: Ten-minute SMA clamp led to epithelial damage that was fully reversed by 120-min reperfusion. Activity of several PKC isoforms (PKCalpha, -delta, -epsilon) increased after 10-min ischemia. Epithelial injury associated with 20-min SMA clamp was attenuated by prior IPC. The protective effect of IPC on intestinal mucosa was prevented when animals were pretreated with the conventional (c) and novel (n) PKC inhibitor Go6850, but not with Go6976 (selective cPKC inhibitor), rottlerin (selective PKCdelta inhibitor), or saline control. CONCLUSIONS: Brief mesenteric ischemia induces a reversible epithelial injury in rats associated with activation of several PKC isoforms. Injury induced by mesenteric ischemia is reduced by brief ischemic preconditioning, an effect that is abolished by nonselective PKC inhibition but not by a selective inhibitor of cPKC or PKCdelta. The results suggest that activation of nPKC isoform(s), especially PKCepsilon during and following ischemic insults (IPC), may play an important role in protection against I/R injury in the intestine.

Effects of weight loss surgeries on liver disease.

Obesity is the single most significant risk factor for the development of nonalcoholic fatty liver disease (NAFLD) in children and adults. NALFD is estimated to occur in 30 to 100% of obese adults, and in approximately 53% of obese children. The majority of obese patients have ultrasonographic evidence of fatty liver; 30% have histologically documented nonalcoholic steatohepatitis (NASH). Up to 25% of patients with NASH may progress to cirrhosis. In the United States, an estimated 65% of adults are overweight and 31% are obese. Between 2001 and 2002, the number of people with severe obesity, who are more than 100 pounds overweight, rose to nearly 11 million. Since 1970, levels of childhood and teen overweight have climbed to approximately 16% in those aged 6 to 19 years. Recent findings indicate that key features of NAFLD and NASH improve or resolve dramatically with weight loss. This article discusses weight loss surgeries and their effects on liver disease.

Electrogenic ion transport in mammalian colon involves an ammonia-sensitive apical membrane K+ conductance.

It is remarkable that high ammonia concentrations can be present within the colonic lumen without compromising normal epithelial function. We investigated the impact of luminal ammonia on Cl- secretion in native tissue. Stripped human colonic mucosa and unstripped rat distal colon were used. Paired samples were mounted in modified Ussing chambers for electrophysiological studies. In rat distal colon, apical ammonia dose-dependently blocked forskolin-activated short-circuit current with an IC50 to approximately 5 mM. Basolateral NH4Cl was less effective. Luminal methylamine (50 mM), chromanol 293B (10-50 microM), and Ba2+ (5 mM) blocked cAMP-activated short-circuit current but apical clotrimazole (100 microM) was without effect. In stripped human colonic mucosa, luminal but not basolateral NH4Cl (10 mM) and luminal Ba2+ (5 mM) suppressed forskolin-activated short-circuit current. Ammonia may be an endogenous regulator of colonic water and salt secretion. Apical K+ channels may be involved in the regulation of cAMP-stimulated Cl- secretion in mammalian colon.