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Relevant Weight Reduction and Reversed Metabolic Co-morbidities Can Be Achieved by Duodenojejunal Bypass Liner in Adolescents with Morbid Obesity.
Homan, M, Kovač, J, Orel, R, Battelino, T, Kotnik, P
Obesity surgery. 2020;(3):1001-1010
Abstract
BACKGROUND Duodenojejunal bypass liner (DJBL) is an endoscopic, reversible bariatric procedure resulting in weight loss and metabolic co-morbidities improvements in the adults. OBJECTIVES To determine safety and effectiveness of 12-month treatment with DJBL in adolescents with severe obesity (BMI > 35 kg/m2) and co-morbidities. METHODS Post-pubertal subjects were treated with DJBL in an open-label, prospective clinical trial (NTC0218393). They were examined at 3 monthly intervals during the 12 months of DJBL treatment and 12 months of follow-up. RESULTS DJBL was successfully placed in 19/22 adolescents (13 females, mean age (95%CI); 17.3 (16.7-17.9) years, BMI-SDS 3.7 (3.6-3.9)). There were no serious device-related adverse effects. Clinically relevant percent total weight loss (%TWL) (mean (95%CI)) 11.4 (7.4-15.3) % and BMI decrease - 4.9 (- 2.4 to - 7.4) kg/m2 was observed at DJBL removal (n = 19). At 12 months after device removal, %TWL was 4.1 (- 2.6-10.8) % and BMI decrease - 2.6 (0.2 to - 5.4) kg/m2 when compared with values at baseline (n = 13). HOMA-IR (- 2.1 (- 3 to - 1.3), WBISI 1.15 (0.23 to 2.07), total cholesterol, LDL-c, and triglycerides levels also improved during DJBL treatment and relapsed similarly to weight at 12-month follow-up. A decrease in iron stores, Zn, and Se levels was determined during DJBL treatment and spontaneously improved at follow-up. CONCLUSIONS Twelve months of DJBL treatment was safe and effective in adolescents with morbid obesity. Weight regain following device removal and relapse of metabolic complications should be expected.
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Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β.
Hepprich, M, Wiedemann, SJ, Schelker, BL, Trinh, B, Stärkle, A, Geigges, M, Löliger, J, Böni-Schnetzler, M, Rudofsky, G, Donath, MY
Cell metabolism. 2020;(4):699-709.e5
Abstract
Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra (clinicaltrials.govNCT03200782; n = 12). Both drugs reduced postprandial insulin release and prevented hypoglycemia (symptomatic events requiring rescue glucose: placebo = 7/12, empagliflozin = 2/12, and anakinra = 2/12, pvallikelihood ratio test (LRT) = 0.013; nadir blood glucose for placebo = 2.4 mmol/L, 95% CI 2.18-2.62, empagliflozin = 2.69 mmol/L, 95% CI 2.31-3.08, and anakinra = 2.99 mmol/L, 95% CI 2.43-3.55, pvalLRT = 0.048). Moreover, analysis of monocytes ex vivo revealed a hyper-reactive inflammatory state that has features of an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.
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Laparoscopic Roux-en-Y gastric bypass surgery influenced pharmacokinetics of several drugs given as a cocktail with the highest impact observed for CYP1A2, CYP2C8 and CYP2E1 substrates.
Puris, E, Pasanen, M, Ranta, VP, Gynther, M, Petsalo, A, Käkelä, P, Männistö, V, Pihlajamäki, J
Basic & clinical pharmacology & toxicology. 2019;(2):123-132
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There is a lack of information about the changes in drug pharmacokinetics and cytochrome P450 (CYP) metabolism after bariatric surgery. Here, we investigated the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery on pharmacokinetics of nine drugs given simultaneously which may reveal changes in the activities of the main CYPs. Eight obese subjects undergoing LRYGB received an oral cocktail containing nine drugs, substrates of various CYPs: melatonin (CYP1A2), nicotine (CYP2A6), bupropion (CYP2B6), repaglinide (CYP2C8), losartan (CYP2C9), omeprazole (CYP2C19/CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A). The 6-hours pharmacokinetic profiles in serum and urine of each drug or corresponding metabolite as well as their metabolic ratios were compared before surgery with those at a median 1 year later. LRYGB exerted variable effects on the pharmacokinetics of these drugs. The geometric mean AUC0-6 (90% confidence interval) of melatonin, bupropion, repaglinide, chlorzoxazone and midazolam after LRYGB was 27 (19%-41%), 54 (43%-67%), 44 (29%-66%), 160 (129%-197%) and 74 (62%-90%) of the pre-surgery values, respectively. The pharmacokinetics of losartan, omeprazole and dextromethorphan did not change in response to surgery. Nicotine was not detected in serum, while geometric mean of AUC0-6 of its metabolite, cotinine, increased by 1.7 times after surgery. There were 3.6- and 1.3-fold increases in the AUC ratios of 6-hydroxymelatonin/melatonin and hydroxybupropion/bupropion, respectively. The cocktail revealed multiple pharmacokinetic changes occurring after LRYGB with the greatest effects observed for CYP1A2, CYP2C8 and CYP2E1 substrates. Future studies should be focused on CYP1A2, CYP2A6, CYP2C8 and CYP2B6 to clarify the changes in activities of these enzymes after LRYGB.
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Biliopancreatic Diversion Induces Greater Metabolic Improvement Than Roux-en-Y Gastric Bypass.
Harris, LA, Kayser, BD, Cefalo, C, Marini, L, Watrous, JD, Ding, J, Jain, M, McDonald, JG, Thompson, BM, Fabbrini, E, et al
Cell metabolism. 2019;(5):855-864.e3
Abstract
Diabetes remission is greater after biliopancreatic diversion (BPD) than Roux-en-Y gastric bypass (RYGB) surgery. We used a mixed-meal test with ingested and infused glucose tracers and the hyperinsulinemic-euglycemic clamp procedure with glucose tracer infusion to assess the effect of 20% weight loss induced by either RYGB or BPD on glucoregulation in people with obesity (ClinicalTrials.gov number: NCT03111953). The rate of appearance of ingested glucose into the circulation was much slower, and the postprandial increases in plasma glucose and insulin concentrations were markedly blunted after BPD compared to after RYGB. Insulin sensitivity, assessed as glucose disposal rate during insulin infusion, was ∼45% greater after BPD than RYGB, whereas β cell function was not different between groups. These results demonstrate that compared with matched-percentage weight loss induced by RYGB, BPD has unique beneficial effects on glycemic control, manifested by slower postprandial glucose absorption, blunted postprandial plasma glucose and insulin excursions, and greater improvement in insulin sensitivity.
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Sleeve gastrectomy surgery: when 2 alcoholic drinks are converted to 4.
Acevedo, MB, Eagon, JC, Bartholow, BD, Klein, S, Bucholz, KK, Pepino, MY
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018;(3):277-283
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BACKGROUND While it is well established that Roux-en-Y gastric bypass (RYGB) causes a rapid and heightened peak blood alcohol concentration (BAC), results from previous studies on the effects of sleeve gastrectomy (SG) on alcohol pharmacokinetics are conflicting. Data from 2 studies found SG did not affect BAC, whereas another study found SG caused a heightened peak BAC after alcohol ingestion. Moreover, these 3 studies estimated BAC from breathalyzers, which might not reliably estimate peak BAC. OBJECTIVES The aims of this study were to evaluate (1) the effect of SG, relative to RYGB and a presurgery group, on alcohol pharmacokinetics and subjective effects, and (2) whether breathalyzers are reliable in this population. SETTING Single-center prospective nonrandomized trial. METHODS We performed alcohol challenge tests in 11 women who had SG surgery 1.9 ± .1 years ago (body mass index = 35.1 ± 6.6 kg/m2), 8 women who had RYGB surgery 2.2 ± .4 years ago (body mass index = 30.0 ± 5.2 kg/m2), and 9 women who were scheduled for bariatric surgery (body mass index = 44.1 ± 4.0 kg/m2). BACs were estimated from breath samples and measured by gas chromatography at various times after consuming approximately 2 standard drinks. RESULTS BAC increased faster, peak BAC was approximately 2-fold higher, and feelings of drunkenness were heightened in both SG and RYGB groups relative to the presurgery group (P values<.001). BAC estimated from breath samples underestimated BAC by 27% (standard deviation = 13%) and missed peak BACs postsurgery. CONCLUSIONS SG, similar to RYGB, causes marked alterations in the response to alcohol ingestion manifested by a faster and higher peak BAC. The breathalyzer is invalid to assess effects of gastric surgeries on pharmacokinetics of ingested alcohol.
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GLP-1 and GLP-2 Levels are Correlated with Satiety Regulation After Roux-en-Y Gastric Bypass: Results of an Exploratory Prospective Study.
Cazzo, E, Pareja, JC, Chaim, EA, Geloneze, B, Barreto, MR, Magro, DO
Obesity surgery. 2017;(3):703-708
Abstract
BACKGROUND Changes in satiety regulation are known to play a pivotal role in the weight loss effects of Roux-en-Y gastric bypass (RYGB) and the mechanisms by which these changes occur are not entirely known. There are previous reports of the influence of GLP-1 to cause enhancement of satiation, but in regard to GLP-2, it remains unclear. This study aimed to determine whether there is a correlation between the levels of GLP-1 and GLP-2 and satiety regulation following RYGB. MATERIALS AND METHODS An exploratory prospective cohort study was made which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 levels were determined before and after surgery and correlated with visual analogue scale scores for satiety. RESULTS GLP-2 AUC after standard meal tolerance test (MTT) was significantly higher following surgery (945.3 ± 449.1 versus 1787.9 ± 602.7; p = 0.0037). Postoperatively, GLP-1 AUC presented a significant negative correlation with the mean score obtained in the first question of the visual analogue scale ("how hungry do you feel?") (p = 0.008); GLP-2 AUC presented a significant positive correlation with the mean score of the third ("how full do you feel?") question, and a significant positive correlation with the mean score achieved in the fourth question ("how much do you think you can eat?"), (p = 0.005 and p = 0.042, respectively). CONCLUSION GLP-1 and GLP-2 were significantly correlated with satiety assessment within this sample. Further research is necessary to confirm these findings.
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Roux-en-Y Gastric Bypass Surgery Has Unique Effects on Postprandial FGF21 but Not FGF19 Secretion.
Harris, LLS, Smith, GI, Mittendorfer, B, Eagon, JC, Okunade, AL, Patterson, BW, Klein, S
The Journal of clinical endocrinology and metabolism. 2017;(10):3858-3864
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CONTEXT Fibroblast growth factor (FGF)19 and FGF21 are secreted by the intestine and liver in response to macronutrient intake. Intestinal resection and reconstruction via bariatric surgery may alter their regulation. OBJECTIVE We tested the hypothesis that weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery, but not matched weight loss induced by laparoscopic adjustable gastric banding (LAGB), increases postprandial plasma FGF19 and FGF21 concentrations. DESIGN Glucose kinetics and plasma FGF19 and FGF21 responses to mixed meal ingestion and to glucose-insulin infusion during a hyperinsulinemic-euglycemic clamp procedure, with stable isotope tracer methods, were evaluated in 28 adults with obesity before and after 20% weight loss induced by RYGB (n = 16) or LAGB (n = 12). RESULTS LAGB- and RYGB-induced weight loss increased postprandial plasma FGF19 concentrations (P < 0.05). However, weight loss after RYGB, but not LAGB, increased postprandial plasma FGF21 concentrations (1875 ± 330 to 2976 ± 682 vs 2150 ± 310 and 1572 ± 265 pg/mL × 6 hours, respectively). The increase in plasma FGF21 occurred ∼2 hours after the peak in delivery of ingested glucose into systemic circulation. Glucose-insulin infusion increased plasma FGF21, but not FGF19, concentrations. The increase in plasma FGF21 during glucose-insulin infusion was greater after than before weight loss in both surgery groups without a difference between groups, whereas plasma FGF19 was not affected by either procedure. CONCLUSIONS RYGB-induced weight loss has unique effects on postprandial FGF21 metabolism, presumably due to rapid delivery of ingested macronutrients to the small intestine and delivery of glucose to the liver.
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Surgery-related gastrointestinal symptoms in a prospective study of bariatric surgery patients: 3-year follow-up.
Kalarchian, MA, King, WC, Devlin, MJ, White, GE, Marcus, MD, Garcia, L, Yanovski, SZ, Mitchell, JE
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2017;(9):1562-1571
Abstract
BACKGROUND Having accurate information on bariatric surgery-related gastrointestinal (GI) symptoms is critical for patient care. OBJECTIVE To report on surgery-related GI symptoms over the first 3 years following Roux-en-Y gastric bypass and laparoscopic adjustable gastric band. SETTING Three academic medical centers in the United States. METHODS As a substudy of the Longitudinal Assessment of Bariatric Surgery Consortium, 183 participants (pre-surgery median body mass index = 45.1 kg/m2; median age = 46 yr; 83.1% female). completed the Eating Disorder Examination-Bariatric Surgery Version interview at≥1 annual assessment. Patients self-reported frequency of dysphagia, dumping syndrome, and spontaneous vomiting. RESULTS Prevalence of dysphagia at least once weekly decreased post-laparoscopic adjustable gastric band surgery from 43.9% (95% confidence interval [CI], 32.2-55.6) in year 1 to 27.5% (95% CI, 15.2-39.9) in year 3 (P = .02). Dysphagia and dumping at least once weekly also appeared to decrease in years 1-3 post-Roux-en-Y gastric bypass (i.e., from 16.7% [95% CI, 9.4-24.1] to 10.9% [95% CI, 4.0-17.8] and from 9.9% [95% CI, 4.3-15.5] to 6.3% [95% CI, 1.7-10.9], respectively), but power was limited to evaluate trends. Vomiting at least once weekly was rare (<6%) in years 1-3 following both procedures. Controlling for potential confounders and surgical procedure, loss of control eating at least once weekly was associated with higher risk of at least once weekly dysphagia (relative risk = 2.01, 95% CI, 1.36-2.99, P = .001). CONCLUSIONS The prevalence of bariatric surgery-related GI symptoms appears to decrease across follow-up. Symptoms were associated with loss of control eating, suggesting a target for clinical intervention.
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Energy restriction and Roux-en-Y gastric bypass reduce postprandial α-dicarbonyl stress in obese women with type 2 diabetes.
Maessen, DE, Hanssen, NM, Lips, MA, Scheijen, JL, Willems van Dijk, K, Pijl, H, Stehouwer, CD, Schalkwijk, CG
Diabetologia. 2016;(9):2013-7
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AIMS/HYPOTHESIS Dicarbonyl compounds are formed as byproducts of glycolysis and are key mediators of diabetic complications. However, evidence of postprandial α-dicarbonyl formation in humans is lacking, and interventions to reduce α-dicarbonyls have not yet been investigated. Therefore, we investigated postprandial α-dicarbonyl levels in obese women without and with type 2 diabetes. Furthermore, we evaluated whether a diet very low in energy (very low calorie diet [VLCD]) or Roux-en-Y gastric bypass (RYGB) reduces α-dicarbonyl stress in obese women with type 2 diabetes. METHODS In lean (n = 12) and obese women without (n = 27) or with type 2 diabetes (n = 27), we measured the α-dicarbonyls, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and glucose in fasting and postprandial plasma samples obtained during a mixed meal test. Obese women with type 2 diabetes underwent either a VLCD or RYGB. Three weeks after the intervention, individuals underwent a second mixed meal test. RESULTS Obese women with type 2 diabetes had higher fasting and particularly higher postprandial plasma α-dicarbonyl levels, compared with those without diabetes. After three weeks of a VLCD, postprandial α-dicarbonyl levels in diabetic women were significantly reduced (AUC MGO -14%, GO -16%, 3-DG -25%), mainly through reduction of fasting plasma α-dicarbonyls (MGO -13%, GO -13%, 3-DG -33%). Similar results were found after RYGB. CONCLUSIONS/INTERPRETATION This study shows that type 2 diabetes is characterised by increased fasting and postprandial plasma α-dicarbonyl stress, which can be reduced by improving glucose metabolism through a VLCD or RYGB. These data highlight the potential to reduce reactive α-dicarbonyls in obese individuals with type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov NCT01167959.
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Weight loss induced by very low calorie diet is associated with a more beneficial systemic inflammatory profile than by Roux-en-Y gastric bypass.
Lips, MA, van Klinken, JB, Pijl, H, Janssen, I, Willems van Dijk, K, Koning, F, van Harmelen, V
Metabolism: clinical and experimental. 2016;(11):1614-1620
Abstract
INTRODUCTION Weight loss interventions such as Roux-en-Y gastric bypass (RYGB) and very low calorie diets (VLCD) lead to improvement of glucose metabolism in obese individuals with type-2 diabetes. Weight loss can also positively influence the unfavorable inflammatory profile associated with obesity. However, a direct comparison of the effect of VLCD and RYGB on systemic inflammation is lacking. METHODS Systemic inflammation was investigated in age- and BMI-matched morbidly obese T2DM women by determining the number and activation- or memory status of peripheral blood leukocytes by flow cytometry, in addition to measuring circulating levels of cytokines and CRP. Systemic inflammation was assessed one month before and three months after RYGB (n=15) or VLCD (n=12). An age matched group of lean women (n=12) was studied as control group. RESULTS Three months after the intervention, CRP and leptin levels were reduced whereas adiponectin levels were increased both by RYGB and VLCD. TNF-α levels were increased by RYGB, but reduced by VLCD. IL-2 and IL-6 levels were reduced and IL-4 levels were increased by VLCD but not affected by RYGB. The number of activated peripheral cytotoxic T (CD8+CD25+) and B (CD19+CD38+) cells was significantly higher after RYGB than after VLCD. CONCLUSION In conclusion, RYGB and VLCD have differential effects on the activation status of peripheral leukocytes and levels of cytokines in obese women with T2DM, despite comparable weight loss three months after the intervention. VLCD seems to have more favorable effects on the inflammatory profile as compared to RYGB.