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PREVENT: A Randomized, Placebo-controlled Crossover Trial of Avexitide for Treatment of Postbariatric Hypoglycemia.
Craig, CM, Lawler, HM, Lee, CJE, Tan, M, Davis, DB, Tong, J, Glodowski, M, Rogowitz, E, Karaman, R, McLaughlin, TL, et al
The Journal of clinical endocrinology and metabolism. 2021;(8):e3235-e3248
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Abstract
CONTEXT Postbariatric hypoglycemia (PBH), characterized by enteroinsular axis overstimulation and hyperinsulinemic hypoglycemia, is a complication of bariatric surgery for which there is no approved therapy. OBJECTIVE To evaluate efficacy and safety of avexitide [exendin (9-39)], a glucagon-like peptide-1 antagonist, for treatment of PBH. METHODS A multicenter, Phase 2, randomized, placebo-controlled crossover study (PREVENT). Eighteen female patients with PBH were given placebo for 14 days followed by avexitide 30 mg twice daily and 60 mg once daily, each for 14 days in random order. The main outcome measures were glucose nadir and insulin peak during mixed-meal tolerance testing (MMTT) and hypoglycemic events captured by self-monitoring of blood glucose (SMBG), electronic diary, and blinded continuous glucose monitoring (CGM). RESULTS Compared with placebo, avexitide 30 mg twice daily and 60 mg once daily raised the glucose nadir by 21% (P = .001) and 26% (P = .0002) and lowered the insulin peak by 23% (P = .029) and 21% (P = .042), corresponding to 50% and 75% fewer participants requiring rescue during MMTT, respectively. Significant reductions in rates of Levels 1 to 3 hypoglycemia were observed, defined, respectively, as SMBG <70 mg/dL, SMBG <54 mg/dL, and a severe event characterized by altered mental and/or physical function requiring assistance. CGM demonstrated reductions in hypoglycemia without induction of clinically relevant hyperglycemia. Avexitide was well tolerated, with no increase in adverse events. CONCLUSION Avexitide administered for 28 days was well tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters, reinforcing the targeted therapeutic approach and demonstrating durability of effect. Avexitide may represent a first promising treatment for patients with severe PBH.
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The use of Ursolit for gallstone prophylaxis following bariatric surgery: a randomized-controlled trial.
Sakran, N, Dar, R, Assalia, A, Neeman, Z, Farraj, M, Sherf-Dagan, S, Gralnek, IM, Hazzan, R, Mokary, SE, Nevo-Aboody, H, et al
Updates in surgery. 2020;(4):1125-1133
Abstract
BACKGROUND Although bariatric surgery (BS) predisposes patients to development of gallstone formation, a preventive strategy is still in debate. AIM: To compare the incidence of gallstone formation between patients treated with ursodeoxycholic acid (UDCA) vs. placebo for a duration of 6 months following BS. METHODS This multicenter randomized, double-blind controlled trial entails treatment with UDCA vs. an identical-looking placebo. The primary outcome was gallstone formation, as measured by abdominal ultrasound. RESULTS The data of 209 subjects were enrolled in the study, and 92 subjects completed the study and were analyzed (n = 46 for each study group). The high dropout rate was mainly due to difficulties in adding more medications and swallowing the pill. Among the subjects who completed the study, 77.2% were women, and their mean age and pre-surgery BMI were 42.2 ± 10.2 years and 44.4 ± 6.1 kg/m2, respectively. Gallstone formation was recorded in 45.7% (n = 21) vs. 23.9% (n = 11) of subjects among placebo vs. UDCA groups, respectively, p = 0.029. Subgroup-analysis, according to surgery type, found that the results were significant only for SG subjects (p = 0.041), although the same trend was observed for OAGB/RYGB. Excess Weight Loss percent (%EWL) at 6 months post-surgery was 66.0 ± 17.1% vs. 71.8 ± 19.5% for the placebo and UDCA groups, respectively; p = 0.136. A trend towards a reduction in prescribed comorbidity medications was noted within-groups during the follow-up period, as compared to baseline, with no between-group differences (p ≥ 0.246). Moreover, no between-group differences were found for blood test results (p ≥ 0.063 for all). CONCLUSION Administration of UDCA significantly decreased gallstone formation at 6 months at following BS. CLINICALTRIALS. GOV NUMBER NCT02319629.
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Food Addiction Is Associated with Binge Eating and Psychiatric Distress among Post-Operative Bariatric Surgery Patients and May Improve in Response to Cognitive Behavioural Therapy.
Cassin, S, Leung, S, Hawa, R, Wnuk, S, Jackson, T, Sockalingam, S
Nutrients. 2020;(10)
Abstract
The current study examined clinical correlates of food addiction among post-operative bariatric surgery patients, compared the clinical characteristics of patients with versus without food addiction, and examined whether a brief telephone-based cognitive behavioural therapy (Tele-CBT) intervention improves food addiction symptomatology among those with food addiction. Participants (N = 100) completed measures of food addiction, binge eating, depression, and anxiety 1 year following bariatric surgery, were randomized to receive either Tele-CBT or standard bariatric post-operative care, and then, repeated the measure of food addiction at 1.25 and 1.5 years following surgery. Thirteen percent of patients exceeded the cut-off for food addiction at 1 year post-surgery, and this subgroup of patients reported greater binge eating characteristics and psychiatric distress compared to patients without food addiction. Among those with food addiction, Tele-CBT was found to improve food addiction symptomatology immediately following the intervention. These preliminary findings suggest that Tele-CBT may be helpful, at least in the short term, in improving food addiction symptomatology among some patients who do not experience remission of food addiction following bariatric surgery; however, these findings require replication in a larger sample.
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Efficacy and Safety of the Duodeno-Jejunal Bypass Liner in Patients With Metabolic Syndrome: A Multicenter Randomized Controlled Trial (ENDOMETAB).
Caiazzo, R, Branche, J, Raverdy, V, Czernichow, S, Carette, C, Robert, M, Disse, E, Barthet, M, Cariou, B, Msika, S, et al
Annals of surgery. 2020;(5):696-702
Abstract
OBJECTIVE The aim of this study was to compare the efficacy and safety of 12-month implantation of a duodeno-jejunal bypass liner (DJBL) with conventional medical care in patients with metabolic syndrome (MS). SUMMARY BACKGROUND DATA DJBL is an endoscopic device for treating obesity and related disorders. The persistence of favorable results after 6 months has not been tested in a controlled study. METHODS We conducted a multicenter randomized controlled trial, stratified by center and diabetes status. The primary endpoint was the remission of MS at 12 months. The secondary endpoints included body mass index (BMI), glucose control, blood pressure, and lipids, assessed at 12 months after implantation, and again, at 12 months after the removal of the DJBL. Up to 174 subjects were planned to be randomized into either the DJBL or the control arm at a 2:1 ratio, respectively. Study enrollment was discontinued by the Scientific Monitoring Committee due to the early termination of the ENDO trial (NCT01728116) by the US Food and Drug Administration. The study was terminated after withdrawal of the device's European Conformity marking by the European Medicines Agency, and an interim analysis was performed. RESULTS A total of 82 patients were enrolled (67.5% female, 48.8% with diabetes). At 12 months after randomization, the primary endpoint was met in 6 (12%) DJBL patients and 3 (10%) controls (P = 0.72). Patients in the DJBL group experienced greater BMI loss [mean adjusted difference (95% confidence interval, CI) -3.1 kg/m (-4.4 to -1.9) kg/m, P < 0.001] and HbA1c change [mean adjusted difference -0.5% (95% CI -0.9 to -0.2); P < 0.001] than those in the control group. No difference remained statistically significant at 12 months after the removal of the DJBL. In the DJBL group, 39% of patients experienced at least one device-related serious adverse event, which was classified as Grade III Dindo-Clavien in 22%, and required premature device explantation in 16%. CONCLUSIONS The present study showed a transient clinical benefit of DJBL, which was only apparent at 1 year, when the device was still in situ, and was obtained at the risk of serious device-related adverse events in 39% of patients. These results do not support the routine use of DJBL for weight loss and glucose control in patients with MS.
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Comparative Effects of Medical Versus Surgical Weight Loss on Body Composition: a Pilot Randomized Trial.
Varma, S, Lee, CJ, Brown, TT, Maruthur, NM, Schweitzer, M, Magnuson, T, Kamel, I, Clark, JM
Obesity surgery. 2019;(8):2503-2510
Abstract
OBJECTIVE Bariatric surgery leads to more rapid and greater weight loss (WL) compared to medical weight loss (MWL), but the differences in body composition (BC) changes for these modalities remain unclear. Due to the known health risks associated with central adiposity, we compared the changes in regional distribution of fat mass (FM) and lean mass (LM) after surgical versus MWL. METHODS In this 1:1:1 randomized trial among 15 persons with type 2 diabetes and body mass index (BMI) 30-39.9 kg/m2, we compared changes in BC, by dual-energy X-ray absorptiometry and abdominal computerized tomography, at time of 10%WL or 9 months after intervention (whichever came first). Participants underwent MWL, adjustable gastric banding (AGB), or Roux-en-Y gastric bypass (RYGB). Non-parametric tests evaluated BC differences (FM, LM, and visceral adipose tissue [VAT]) within and across all three arms and between pair-wise comparisons. RESULTS Twelve female participants (75% African American) completed the study. Patient age, BMI, and baseline anthropometric characteristics were similar across study arms. AGB lost more LM (MWL - 5.2%, AGB - 10.3%, p = 0.021) and VAT (MWL + 10.9%, AGB - 28.0%, p = 0.049) than MWL. RYGB tended to lose more VAT (MWL +10.9%, RYGB - 20.2%, p = 0.077) than MWL. AGB tended to lose more LM than RYGB (AGB - 12.38%, RYGB - 7.29%, p = 0.15). CONCLUSIONS At similar WL, AGB lost more LM and VAT than MWL; RYGB similarly lost more VAT. Given the metabolic benefits of reducing VAT and retaining LM, larger studies should confirm the changes in BC after surgical versus medical WL. CLINICAL TRIAL REGISTRATION NCTDK089557 - ClinicalTrials.gov.
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Sera of Obese Type 2 Diabetic Patients Undergoing Metabolic Surgery Instead of Conventional Treatment Exert Beneficial Effects on Beta Cell Survival and Function: Results of a Randomized Clinical Study.
Constantin, A, Dumitrescu, M, Nemecz, M, Picu, A, Smeu, B, Guja, C, Alexandru, N, Georgescu, A, Tanko, G
Obesity surgery. 2019;(5):1485-1497
Abstract
BACKGROUND Pancreatic beta cells are highly sensitive to oxidative and endoplasmic reticulum (ER) stress, commonly occurring in type 2 diabetes (T2D) and obesity. OBJECTIVE We aimed at investigating cellular responses of human beta cells exposed to sera from obese T2D patients treated differently, namely by conventional therapy or laparoscopic sleeve gastrectomy (LSG). METHODS Serum samples from obese T2D men randomized to conventional treatment or LSG were taken at baseline and 6 months later. After exposing 1.1B4 cells to study patients' sera, the following were assessed: cellular viability and proliferation (by MTT and xCELLigence assays), reactive oxygen species (ROS) production (with DCFH-DA), and expression of ER stress markers, oxidative- or autophagy-related proteins and insulin (by real-time PCR and Western blot). RESULTS At 6-month follow-up, patients undergoing LSG achieved an adequate glycemic control, whereas conventionally treated patients did not. As compared to 1.1B4 cells incubated with baseline sera (control), cells exposed to sera from LSG-treated participants exhibited (i) increased viability and proliferation (p < 0.05); (ii) diminished levels of ROS and p53 (p < 0.05); (iii) enhanced protein expression of autophagy-related SIRT1 and p62/SQSTM1 (p < 0.05); (iv) significantly decreased transcript levels of ER stress markers (p < 0.05); and (v) augmented insulin expression (p < 0.05). Conversely, the 6-month conventional therapy appeared not to impact on circulating redox status. Moreover, 1.1B4 cells exposed to sera from conventionally treated patients experienced mild ER stress. CONCLUSION Circulating factors in patients with improved diabetes after metabolic surgery exerted favorable effects on beta cell function and survival.
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Effects of Cognitive Behavioral Therapy on Eating Behaviors, Affective Symptoms, and Weight Loss After Bariatric Surgery: a Randomized Clinical Trial.
Hjelmesæth, J, Rosenvinge, JH, Gade, H, Friborg, O
Obesity surgery. 2019;(1):61-69
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BACKGROUND The long-term effects of presurgical psychological interventions on weight loss, eating behaviors, affective symptoms, and health-related quality of life remain uncertain. This study aimed to assess the 4-year effects of cognitive behavioral therapy (CBT) before bariatric surgery on these outcomes. METHODS Single-center randomized controlled parallel-group trial. Patients were assessed after CBT before bariatric surgery (n = 98) and 1 year (n = 80) and 4 years (n = 61) after surgery. The intervention group received a 10-week preoperative individual CBT focusing on self-monitoring to identify triggers of dysfunctional eating behaviors in order to improve regulation of eating as well as the breaking of the interrelationship between eating behaviors, negative mood, and dysfunctional cognitions. RESULTS The 61 patients (70% women) had a mean (SD) age of 42.4 (10.1) years and BMI 43.5 (4.4) kg/m2. Preoperative CBT was not associated with 1- and 4-year reduction of dysfunctional eating behaviors, affective symptoms and body weight, or improved health-related quality of life. Patients with minor or considerable symptoms of depression receiving CBT had lower mean BMI than controls, both before surgery, - 1.1 kg/m2, and - 1.5 kg/m2, and 4-years after surgery, - 2.9 kg/m2 and - 7.5 kg/m2, respectively. CONCLUSION Presurgical CBT was not associated with better long-term outcomes. However, in patients with minor or considerable symptoms of depression, CBT was associated with lower body weight before and 4 years after surgery. Additional studies are required to verify whether patients with symptoms of depression should be offered CBT before and/or after bariatric surgery, and which clinical aspects the CBT should address. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT01403558.
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The feasibility of a behavioral group intervention after weight-loss surgery: A randomized pilot trial.
Lent, MR, Campbell, LK, Kelly, MC, Lawson, JL, Murakami, JM, Gorrell, S, Wood, GC, Yohn, MM, Ranck, S, Petrick, AT, et al
PloS one. 2019;(10):e0223885
Abstract
BACKGROUND Formal psychosocial support programs after weight-loss surgery are limited in scope and availability. OBJECTIVE This randomized pilot study evaluated the feasibility of a postoperative behavioral intervention program. MATERIALS AND METHODS Postoperative weight-loss surgery patients (N = 50) were recruited from February 2017-July 2017 and randomized to a four-month behavioral program or usual care wait-list. Outcomes evaluated in addition to feasibility included health-related quality of life (Short Form -36), psychosocial functioning and adherence. Secondary outcomes included within-group changes for each outcome. RESULTS Out of eight possible sessions, intervention participants attended a mean of 4.2 sessions. Intervention group participants experienced greater improvements in the social functioning domain of health-related quality of life compared to usual care. Self-reported dietary adherence in the intervention group remained stable, while usual care group dietary adherence declined. Within the intervention group, participants also reported gains in the physical function, pain and general health aspects of quality life from baseline to post-treatment. No differences in weight, mood or other eating behaviors (e.g., loss of control, emotional eating) were evident between groups. CONCLUSION Though participation in a postoperative behavioral intervention varied, the program helped participants to maintain aspects of quality of life and self-reported adherence to dietary recommendations. TRIAL REGISTRATION ClinicalTrials.gov NCT03092479.
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Preoperative liver shrinking diet for bariatric surgery may impact wound healing: a randomized controlled trial.
Chakravartty, S, Vivian, G, Mullholland, N, Shaikh, H, McGrath, J, Sidhu, PS, Jaffer, O, Patel, AG
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2019;(1):117-125
Abstract
BACKGROUND In bariatric surgery, preoperative very low-calorie diets (VLCD) may better meet the technical demands of surgery by shrinking the liver. However, diets may affect tissue healing and influence bowel anastomosis in an as-yet-undefined manner. OBJECTIVE This randomized controlled trial aimed to examine the effect on collagen deposition in wounds in patients on a 4-week VLCD before laparoscopic gastric bypass. SETTING University hospital. METHODS The trial was undertaken in patients undergoing laparoscopic Roux-en-Y gastric bypass, with a control group (n = 10) on normal diet and an intervention group (n = 10) on VLCD (800 kcal) for 4 weeks. The primary outcome measured was expression of collagen I and III in skin wounds, with biopsies taken before and after the diet and 7 days postoperatively as a surrogate of anastomotic healing. Secondary outcome measures included liver volume and fibrosis score, body composition, operating time, blood loss, hospital stay, and complications. RESULTS Patients in both groups were similar in age, sex, body mass index (53.4 versus 52.8 kg/m2), co-morbidities, liver volume, and body composition. Expression of mature collagen type I was significantly decreased in diet patients compared with controls after 4 weeks of diet and 7 days after surgery. This was significant decrease in liver volume (23% versus 2%, P = .03) but no difference in operating times (129 versus 139 min, P = .16), blood loss, length of stay, or incidence of complications. CONCLUSIONS Preoperative diets shrink liver volume and decrease expression of mature collagen in wounds after surgery. Whether the latter has a detrimental effect on clinical outcomes requires further evaluation.
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Intravenous iron sucrose versus oral iron administration for the postoperative treatment of post-bariatric abdominoplasty anaemia: an open-label, randomised, superiority trial in Brazil.
Montano-Pedroso, JC, Bueno Garcia, E, Alcântara Rodrigues de Moraes, M, Francescato Veiga, D, Masako Ferreira, L
The Lancet. Haematology. 2018;(7):e310-e320
Abstract
BACKGROUND Anaemia and iron deficiency are common after post-bariatric abdominoplasty, which can involve removal of large areas of skin with associated blood loss. Because the oral absorbability of iron is reduced after bariatric surgery (through reduced intake, reduction of gastric acid secretion for conjugation of iron, and separation of the iron-absorptive areas of the duodenum and jejunum), it has been hypothesised that postoperative intravenous iron supplementation might be used to treat anaemia and iron deficiency in patients submitted to post-bariatric plastic surgeries. We aimed to assess whether intravenous iron administered postoperatively in post-bariatric abdominoplasty could result in increased blood haemoglobin concentrations compared with oral iron supplementation. METHODS In this open-label, randomised, superiority trial, we recruited women aged 18-55 years undergoing post-bariatric abdominoplasty at two public tertiary referral hospitals in São Paulo, Brazil. Eligible women had been treated for previous obesity with bariatric surgery using the vertical banded gastroplasty technique with Roux-en-Y gastric bypass by laparotomy; had grade III contour deformity via the Pittsburgh rating scale; and had a post-bariatric body-mass index (BMI) lower than 32 kg/m2, with stabilised weight loss for at least 6 months. Women were randomly assigned (1:1) to receive postoperative iron supplementation with two intravenous infusions of 200 mg of iron sucrose (intravenous group) or 100 mg of iron polymaltose complex orally twice a day for 8 weeks (oral group). The primary outcome in both groups was blood haemoglobin concentration at postoperative day 56 after abdominoplasty, with a minimum clinically relevant difference of 1·5 g/dL. Analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01857011, and the Brazilian Clinical Trials Registry, number RBR-2JGRKQ. The trial is completed. FINDINGS From April 7, 2014, to June 27, 2016, 102 post-bariatric patients were assessed for eligibility. 56 patients were eligible and were randomly assigned, with 28 allocated to each group. Mean baseline haemoglobin concentration was slightly higher in the oral group than in the intravenous group (12·71 g/dL [SD 1·06] vs 12·24 g/L [1·09]), and by post-operative day 56 was 12·54 g/dL (SD 1·18) and 12·80 g/dL (0·81), respectively (mean difference of 0·26 g/dL, 95% CI -0·28 to 0·80; p=0·009 in favour of the intravenous group). The minimum clinically relevant difference in concentrations was not reached. No adverse events were recorded in the intravenous group, whereas in the oral group, constipation was recorded in five (18%) patients, diarrhoea in three (11%), and nausea in one (4%) patient. INTERPRETATION Postoperative intravenous administration of iron increased haemoglobin concentrations at 56 days post-operatively and reduced iron deficiency, without adverse events. Although superiority of intravenous iron was not shown, intravenous administration might be useful in post-bariatric patients, especially in those who have body-contouring treatment involving a second surgery within a short period of time. Larger trials, and trials using higher intravenous doses of iron, are needed to further assess the potential efficacy and safety of intravenous iron administration after post-bariatric plastic surgery. FUNDING The São Paulo Research Foundation (FAPESP).