Proteome-wide associations with short- and long-term weight loss and regain after Roux-en-Y gastric bypass surgery.

OBJECTIVE: Gastric bypass surgery results in long-term weight loss. Small studies have examined protein changes during rapid weight loss (up to 1 or 2 years post surgery). This study tested whether short-term changes were maintained after 12 years. METHODS: A 12-year follow-up, protein-wide association study of 1,297 SomaLogic aptamer-based plasma proteins compared short- (2-year) and long-term (12-year) protein changes in 234 individuals who had gastric bypass surgery with 144 nonintervened individuals with severe obesity. RESULTS: There were 51 replicated 12-year protein changes that differed between the surgery and nonsurgery groups. Adjusting for change in BMI, only 12 proteins remained significant, suggesting that BMI change was the primary reason for most protein changes and not non-BMI-related surgical effects. Protein changes were related to BMI changes during both weight-loss and weight-regain periods. The significant proteins were associated primarily with lipid, uric acid, or resting energy expenditure clinical variables and metabolic pathways. Eight protein changes were associated with 12-year diabetes remission, including apolipoprotein M, sex hormone binding globulin, and adiponectin (p < 3.5 × 10-5 ). CONCLUSIONS: This study showed that most short-term postsurgical changes in proteins were maintained at 12 years. Systemic protection pathways, including inflammation, complement, lipid, and adipocyte pathways, were related to the long-term benefits of gastric bypass surgery.

Effects of Post-operative Nutritional Disorders Following Bariatric Surgery on Health Care Cost and Use.

PURPOSE: Risk of nutritional disorders (NDs) in bariatric surgical patients has led to guideline recommendations for pre- and post-operative nutrient deficiency screening. The aim of this study was to identify baseline factors associated with incident NDs and, in addition, to explore possible differences in health care spending and use between patients with and without incident NDs following bariatric surgery. MATERIALS AND METHODS: Using data linked with a state-wide bariatric surgical registry and a state-wide claims database, subjects who underwent bariatric surgery between July 1, 2013, and December 31, 2015, were identified. Incident NDs and health care cost and use outcomes following 1 year from surgery were extracted from the claims data. Logistic regression was used to identify baseline factors associated with incident NDs. Zero-inflated negative binomial regression and generalized linear regression were used to estimate health care cost and use outcomes. RESULTS: A total of 3535 patients who underwent bariatric surgery were identified. Of these patients, those without continuous health insurance enrollment (n=1880), having prevalent (pre-surgery) NDs (n=461), and missing baseline BMI (n=41) were excluded. Of patients analyzed (n=1153), about 30% had incident NDs, with a mean (SD) age and BMI at surgery of 46 (12) years and 48 (9.2) kg/m2, respectively. Patients with one incident ND had higher total health care spending (coefficient=$41118, p-value<0.01) and ED visits (IRR=1.86, p-value<0.01). CONCLUSION: Those without pre-operative NDs may have a higher chance of having NDs post-operatively. Taking multivitamins and continues monitoring are necessary to prevent any negative outcomes related to post-operative NDs.

Associations of Visceral, Subcutaneous, Epicardial, and Liver Fat with Metabolic Disorders up to 14 Years After Weight Loss Surgery.

Background: Bariatric surgery leads to long-term remission and reduced incidence of diabetes, hypertension, and dyslipidemia. Short-term studies suggest reduction in specific fat depots may be more predictive of health improvement than reduced body mass index (BMI). Visceral, subcutaneous, epicardial, and liver fat, measured 11 years after bariatric surgery, were associated with long-term remission and incidence of diabetes, dyslipidemia, and hypertension. Methods: Fat depots an average of 11 (maximum 14) years after surgery were quantified by noncontrast computed tomography in subjects who did (N = 261; 86% gastric bypass) or did not (N = 243) have bariatric surgery. Multiple regression related fat depots to disease endpoints with and without adjustment for change in BMI and surgical status. Results: Visceral fat was 42% lower, subcutaneous fat 20% lower, epicardial fat 30% lower, and liver-to-spleen density ratio 9% higher at follow-up in the bariatric surgery group compared with the nonsurgery group (all P < 0.01). Higher visceral fat at follow-up exam was significantly associated with reduced remission and increased incidence of diabetes, hypertension, and dyslipidemia. Subcutaneous fat was not associated with disease. The liver-to-spleen ratio was associated with the remission and incidence of hypertriglyceridemia and not with other fat depots. Epicardial fat was related to incidence of elevated low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol. Conclusions: Whether or not a patient shows greater long-term diabetes, dyslipidemia, or hypertension remission or incidence after bariatric surgery appears dependent on the amount of fat within specific fat depots measured at follow-up. Furthermore, associations of the three disease endpoints with different fat depots suggest varied fat depot pathology.

Longitudinal Changes in Cardiac Structure and Function in Severe Obesity: 11-Year Follow-Up in the Utah Obesity Study.

Background Progressive cardiac remodeling and worsening myocardial function over time have been proposed as potential mediators of heart failure in obesity. Methods and Results We serially assessed cardiac structure and function in 254 subjects participating in a longitudinal study of obesity. Demographic, clinical, laboratory, and echocardiographic features were determined at baseline and 2-, 6-, and 11-year follow-up. We measured body mass index (BMI) exposure as the area under the curve of the BMI at each of the 4 visits. At enrollment, mean age of the subjects was 47 years, 79% were women, mean BMI was 44 kg/m2, 26% had diabetes mellitus, 48% had hypertension, and 53% had hyperlipidemia. Between baseline and 11 years, BMI increased by 1.1 and 0.3 kg/m2 in men and women, respectively. There were modest increases in left ventricular (LV) end-diastolic volume, LV mass, and left atrial volume, and significant decreases in early/late mitral diastolic flow velocity ratio and E wave deceleration time. However, there were no significant changes in LV ejection fraction or ratio of early mitral diastolic flow velocity/early mitral annular velocity, whereas right ventricular fractional area change increased. Significant predictors of the change in LV mass were male sex, baseline BMI, BMI area under the curve, and change in LV stroke volume, but not smoking, hypertension, or diabetes mellitus. Conclusions In long-standing, persistent severe obesity, there was evidence of cardiac remodeling over a period of 11 years, but no clear worsening of systolic or diastolic function. Measures of remodeling were most strongly related to BMI. The observed changes might predispose to heart failure with preserved ejection fraction, but are not classic for an evolving dilated cardiomyopathy.

Healthcare cost and utilization of bariatric surgical patients with and without preoperative mental health diagnoses.

BACKGROUND: Postoperative healthcare cost and use among patients with and without preoperative mental health illness are not well known. OBJECTIVE: This study compared total healthcare spending and use (emergency department [ED] visits and inpatient admissions) after 1 year post operation of those with and without preoperative mental health disorders. SETTING: United States. METHODS: Mental illness disorders were identified using International Classification of Disease-9/10 diagnosis codes in a statewide bariatric surgery registry and in claims databases that were linked to identify the study cohort. Generalized linear regression and zero-inflated negative binomial regression were used for the healthcare cost and use outcomes. RESULTS: Among 3580 registry patients with private insurance, 1610 patients with continuous enrollment and without missing body mass index data were included. Among patients, 56.8% (n = 915) had diagnosed mental health disorders before surgery. Those with mental illness spent more in total cost than those without mental illness (unstandardized coefficient = $18,513, P value < .01) in the first year after surgery. Those with mental illness had a 73% higher rate in ED visits (P value < .01), 83% higher rate in preventable ED use (P value < .01), and a 101% higher rate in hospital admissions (P value < .01) than those without mental illness. CONCLUSIONS: Patients with mental health diagnoses before having bariatric surgery appear to have significant positive association with surgical outcomes relating to postsurgical healthcare cost and utilization. Greater postsurgical surveillance may be warranted for bariatric surgery patients with preoperative mental illness to reduce postoperative ED visits and inpatient admissions.

Changes in Blood microRNA Expression and Early Metabolic Responsiveness 21 Days Following Bariatric Surgery.

Background: Early metabolic responses following bariatric surgery appear greater than expected given the initial weight loss and coincide with improvement in diabetes. We hypothesized that small non-coding microRNA changes might contribute to regulating mechanisms for metabolic changes and weight loss in patients with severe obesity and diabetes. Methods: Twenty-nine type 2 patients with severe obesity (mean BMI 46.2 kg/m2) and diabetes underwent Roux-en-Y gastric bypass (RYGB) surgery. Clinical measurements and fasting blood samples were taken preoperatively and at day 21 postoperatively. Normalization of fasting glucose and HbA1c following bariatric surgery (short-term diabetes remission) was defined as withdrawal of anti-diabetic medication and fasting glucose < 100 mg/dL (5.6 mmol/L) or HbA1c < 6.0%. MicroRNA expression was determined by quantitative polymerase chain reaction and tested for significant changes after surgery. Results: BMI decreased by 3.8 kg/m2 21 days postoperatively. Eighteen of 29 RYGB (62%) had short-term diabetes remission. Changes from pre- to post-surgery in 32 of 175 microRNAs were nominally significant (p < 0.05). Following multiple comparison adjustment, changes in seven microRNAs remained significant: miR-7-5p, let-7f-5p, miR-15b-5p, let-7i-5p, miR-320c, miR-205-5p, and miR-335-5p. Four pathways were over-represented by these seven microRNAs, including diabetes and insulin resistance pathways. Conclusion: Seven microRNAs showed significant changes 21 days after bariatric surgery. Functional pathways of the altered microRNAs were associated with diabetes-, pituitary-, and liver-related disease, with expression in natural killer cells, and pivotal intestinal pathology suggesting possible mechanistic roles in early diabetes responses following bariatric surgery.

Weight and Metabolic Outcomes 12 Years after Gastric Bypass.

BACKGROUND: Few long-term or controlled studies of bariatric surgery have been conducted to date. We report the 12-year follow-up results of an observational, prospective study of Roux-en-Y gastric bypass that was conducted in the United States. METHODS: A total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux-en-Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (nonsurgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia. RESULTS: The follow-up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was -45.0 kg (95% confidence interval [CI], -47.2 to -42.9; mean percent change, -35.0) at 2 years, -36.3 kg (95% CI, -39.0 to -33.5; mean percent change, -28.0) at 6 years, and -35.0 kg (95% CI, -38.4 to -31.7; mean percent change, -26.9) at 12 years; the mean change at 12 years in nonsurgery group 1 was -2.9 kg (95% CI, -6.9 to 1.0; mean percent change, -2.0), and the mean change at 12 years in nonsurgery group 2 was 0 kg (95% CI, -3.5 to 3.5; mean percent change, -0.9). Among the patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. The odds ratio for the incidence of type 2 diabetes at 12 years was 0.08 (95% CI, 0.03 to 0.24) for the surgery group versus nonsurgery group 1 and 0.09 (95% CI, 0.03 to 0.29) for the surgery group versus nonsurgery group 2 (P<0.001 for both comparisons). The surgery group had higher remission rates and lower incidence rates of hypertension and dyslipidemia than did nonsurgery group 1 (P<0.05 for all comparisons). CONCLUSIONS: This study showed long-term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux-en-Y gastric bypass. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Association of Patient Age at Gastric Bypass Surgery With Long-term All-Cause and Cause-Specific Mortality.

IMPORTANCE: Bariatric surgery is effective in reducing all-cause and cause-specific long-term mortality. Whether the long-term mortality benefit of surgery applies to all ages at which surgery is performed is not known. OBJECTIVE: To examine whether gastric bypass surgery is equally effective in reducing mortality in groups undergoing surgery at different ages. DESIGN, SETTING, AND PARTICIPANTS: All-cause and cause-specific mortality rates and hazard ratios (HRs) were estimated from a retrospective cohort within 4 categories defined by age at surgery: younger than 35 years, 35 through 44 years, 45 through 54 years, and 55 through 74 years. Mean follow-up was 7.2 years. Patients undergoing gastric bypass surgery seen at a private surgical practice from January 1, 1984, through December 31, 2002, were studied. Data analysis was performed from June 12, 2013, to September 6, 2015. A cohort of 7925 patients undergoing gastric bypass surgery and 7925 group-matched, severely obese individuals who did not undergo surgery were identified through driver license records. Matching criteria included year of surgery to year of driver license application, sex, 5-year age groups, and 3 body mass index categories. INTERVENTION: Roux-en-Y gastric bypass surgery. MAIN OUTCOMES AND MEASURES: All-cause and cause-specific mortality compared between those undergoing and not undergoing gastric bypass surgery using HRs. RESULTS: Among the 7925 patients who underwent gastric bypass surgery, the mean (SD) age at surgery was 39.5 (10.5) years, and the mean (SD) presurgical body mass index was 45.3 (7.4). Compared with 7925 matched individuals not undergoing surgery, adjusted all-cause mortality after gastric bypass surgery was significantly lower for patients 35 through 44 years old (HR, 0.54; 95% CI, 0.38-0.77), 45 through 54 years old (HR, 0.43; 95% CI, 0.30-0.62), and 55 through 74 years old (HR, 0.50; 95% CI, 0.31-0.79; P < .003 for all) but was not lower for those younger than 35 years (HR, 1.22; 95% CI, 0.82-1.81; P = .34). The lack of mortality benefit in those undergoing gastric bypass surgery at ages younger than 35 years primarily derived from a significantly higher number of externally caused deaths (HR, 2.53; 95% CI, 1.27-5.07; P = .009), particularly among women (HR, 3.08; 95% CI, 1.4-6.7; P = .005). Patients undergoing gastric bypass surgery had a significantly lower age-related increase in mortality than severely obese individuals not undergoing surgery (P = .001). CONCLUSIONS AND RELEVANCE: Gastric bypass surgery was associated with improved long-term survival for all patients undergoing surgery at ages older than 35 years, with externally caused deaths only elevated in younger women. Gastric bypass surgery is protective against mortality even for older patients and also reduces the age-related increase in mortality observed in severely obese individuals not undergoing surgery.

Health benefits of gastric bypass surgery after 6 years.

CONTEXT: Extreme obesity is associated with health and cardiovascular disease risks. Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term, long-term outcomes are uncertain. OBJECTIVE: To examine the association of Roux-en-Y gastric bypass (RYGB) surgery with weight loss, diabetes mellitus, and other health risks 6 years after surgery. DESIGN, SETTING, AND PARTICIPANTS: A prospective Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese (body mass index [BMI] ≥ 35) participants aged 18 to 72 years (82% women; mean BMI, 45.9; 95% CI, 31.2-60.6) who sought and received RYGB surgery (n = 418), sought but did not have surgery (n = 417; control group 1), or who were randomly selected from a population-based sample not seeking weight loss surgery (n = 321; control group 2). MAIN OUTCOME MEASURES: Weight loss, diabetes, hypertension, dyslipidemia, and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment. RESULTS: Six years after surgery, patients who received RYGB surgery (with 92.6% follow-up) lost 27.7% (95% CI, 26.6%-28.9%) of their initial body weight compared with 0.2% (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, -1.2% to 1.2%) in control group 2. Weight loss maintenance was superior in patients who received RYGB surgery, with 94% (95% CI, 92%-96%) and 76% (95% CI, 72%-81%) of patients receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after surgery, respectively. Diabetes remission rates 6 years after surgery were 62% (95% CI, 49%-75%) in the RYGB surgery group, 8% (95% CI, 0%-16%) in control group 1, and 6% (95% CI, 0%-13%) in control group 2, with remission odds ratios (ORs) of 16.5 (95% CI, 4.7-57.6; P < .001) vs control group 1 and 21.5 (95% CI, 5.4-85.6; P < .001) vs control group 2. The incidence of diabetes throughout the course of the study was reduced after RYGB surgery (2%; 95% CI, 0%-4%; vs 17%; 95% CI, 10%-24%; OR, 0.11; 95% CI, 0.04-0.34 compared with control group 1 and 15%; 95% CI, 9%-21%; OR, 0.21; 95% CI, 0.06-0.67 compared with control group 2; both P < .001). The numbers of participants with bariatric surgery-related hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for the RYGB surgery group and 2 control groups, respectively. CONCLUSION: Among severely obese patients, compared with nonsurgical control patients, the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years.

Laparoscopic reversal of gastric bypass with sleeve gastrectomy for treatment of recurrent retrograde intussusception and Roux stasis syndrome.

BACKGROUND: We reported on our experience of 23 patients with retrograde intussusception (RINT) in 2007. That series has increased to 54 patients. Surgical resection of the jejunojejunostomy appears to be the most effective treatment. We treated 8 patients with documented or suspected recurrent RINT despite resection, by reversing their gastric bypass with sleeve gastrectomy to avoid weight regain. METHODS: The medical records of 8 patients who had undergone treatment of suspected recurrent RINT with reversal of their gastric bypass followed by sleeve gastrectomy were reviewed to evaluate the outcomes, complications, weight loss, and relief of symptoms. RESULTS: All 8 patients were women, aged 29-56 years. The mean body mass index at reversal was 22.3-36.5 kg/m(2) (mean 30). The follow-up period was 1-28 months (mean 20.8). The body mass index at the last visit was 21.3-33 kg/m(2) (mean 26). Complications occurred in 5 patients. Patient 1 developed delayed splenic bleeding that required splenectomy on the second postoperative day. Patient 2 developed a gastric fistula 6 weeks after surgery after dilation. Patient 4 developed a superior mesenteric vein thrombosis at 2 weeks postoperatively. Patient 7 developed a proximal small bowel obstruction. Also, 4 patients required dilation of the gastrogastrostomy. At the last follow-up visit, the patients did not have symptoms of recurrent RINT and had not regained their weight. CONCLUSION: Laparoscopic reversal of gastric bypass with sleeve gastrectomy for recurrent RINT or RINT-like symptoms (Roux stasis symptoms) resulted in a significant risk of complications in this small group of patients but appears to be effective for relieving the symptoms of RINT with minimal risk of weight regain, at least in the medium term.

Retrograde (reverse) jejunal intussusception might not be such a rare problem: a single group's experience of 23 cases.

BACKGROUND: Retrograde (reverse) intussusception of the jejunum is thought to be a very rare occurrence, having been reported approximately 15 times (21 patients) in medical studies. A review of our own experience of >15,000 Roux-en-Y gastric bypass patients found 23 cases treated since 1996. This is the largest single-center report to date. METHODS: A chart review dating back to 1996 revealed 23 patients with retrograde intussusception involving the jejunum. Their charts were reviewed. A variety of data was reviewed to identify the risk factors for developing intussusception, as well as the presentation, findings, and treatment. RESULTS: We identified 23 patients with retrograde intussusception involving the jejunum. Of these 23 patients, 22 had undergone Roux-en-Y gastric bypass. One patient had undergone Roux-en-Y choledochojejunostomy. Of the 23 patients, 1 (4%) had a gastrojejunal intussusception and 22 (96%) jejunojejunal intussusceptions. All patients were women, with a median age of 32 years (range 20-50). The mean body mass index at gastric bypass was 45.2 kg/m2 (range 39.4-55). Of the 23 patients, 19 (83%) had undergone open and 4 (17%) laparoscopic gastric bypass. The median duration from gastric bypass to the diagnosis of intussusception was 51 months (range 6-288). Of the 23 patients, 8 (35%) presented with gangrene, perforation, or nonreducable obstruction, 9 (39%) had a spontaneous reduction, and in 6 (26%), the obstruction was successfully reduced at surgery. The treatment was surgical resection in 16 (70%) with 2 recurrences (12.5%), simple reduction in 2 (9%) with 100% recurrence, and plication in 5 patients (22%) with 2 recurrences (40%). CONCLUSION: Retrograde intussusception of the jejunum after gastric bypass is probably more common than previously believed. Although resection and revision of the area of intussusception appears to be effective, more information is needed about the treatment and possible prevention of this disorder.

Laparoscopic ventral incisional hernia repair: a more effective alternative to conventional repair of recurrent incisional hernia.

Conventional repair of recurrent ventral incisional hernia is associated with a higher recurrence rate (30%-50%) than repair of primary incisional hernia (11%-20%). Laparoscopic incisional hernia repair (LIHR) can significantly reduce the recurrence rate of primary hernia to less than 5%. In this study, we evaluate the efficacy of repairing recurrent incisional hernia laparoscopically. One-hundred and seventy consecutive patients undergoing LIHR between January 1995 and December 2002 were prospectively reviewed. Patients with recurrent incisional hernia (n=69) were compared to patients with primary incisional hernia (n=101). Patient demographics and perioperative and postoperative data were recorded prospectively. Follow-up was obtained from office visits and telephone interviews. Statistical analysis was performed using the Student t test and the chi(2) test. Results are expressed as means +/- standard deviation. The patients with recurrent incisional hernia had a mean of 1.9 +/- 1.3 previous repairs, higher body mass index (BMI) (34 +/- 6 kg/m(2) vs. 33 +/- 8 kg/m(2), P=0.46), larger defect size (123 +/- 115 cm(2) vs. 101 +/- 108 cm(2), P=0.06), and longer operative time (119 +/- 61 minutes vs. 109 +/- 44 minutes, P=0.11). The complication rate was higher in the recurrent group (28% vs. 11%, P=0.01), but the recurrence rate was not different (7% vs. 5%, P=0.53). The mean time to recurrence was significantly shorter in the recurrent group (3 +/- 2 months vs. 14 +/- 7 months, P < 0.0001). The mean follow-up interval was 19 +/- 18 months in the recurrent group and 27 +/- 20 months in the primary group. Although laparoscopic repair of recurrent incisional hernia resulted in a higher recurrence and complication rate than laparoscopic repair of primary incisional hernia, the rates were lower than those reported for conventional repair of recurrent incisional hernia. Laparoscopic repair of recurrent incisional hernia is an effective alternative to conventional repair.