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"Ikramuddin, S"
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Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery
2018
Background:Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined.Materials and Methods:Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation.Results:Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery.Conclusions:These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.
Journal Article
The learning curve for laparoscopic Roux-en-Y gastric bypass is 100 cases
by
Ikramuddin, S.
,
Schauer, P.
,
Hamad, G.
in
Adult
,
Anastomosis, Roux-en-Y - education
,
Anastomosis, Roux-en-Y - statistics & numerical data
2003
The purpose of this study was to determine the effect of operative experience on perioperative outcomes for laparoscopic Roux-en-Y gastric bypass (LGB).
Between July 1997 and September 2001, 750 patients underwent LGB for the treatment of morbid obesity at our center. We evaluated the perioperative outcomes of the first 150 consecutive patients to determine if a learning curve effect could be demonstrated. The patients were divided into three groups (1, 2, and 3) of 50 consecutive patients, and outcomes for each group were compared.
The patients in group 3 had a larger body mass index (BMI), were more likely to have had prior abdominal surgery, and were more likely to have secondary operations at the time of LGB. Operating time decreased from a mean of 311 min in group 11 to 237 min in group 3, and technical complications were reduced by 50% after an experience of 100 cases.
Operative time and technically related complications decreased with operative experience even though heavier patients and higher-risk patients were more predominant in the latter part of our experience. LGB is a technically challenging operation with a long learning curve. To minimize morbidity related to the learning curve, strategies for developing training programs must address these challenges.
Journal Article
Correction to: Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery
2019
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Journal Article
Symptomatic improvement in gastroesophageal reflux disease (GERD) following laparoscopic Roux-en-Y gastric bypass
by
Rakitt, T.
,
Gourash, W.
,
Schauer, P. R.
in
Anastomosis, Roux-en-Y - methods
,
Biological and medical sciences
,
Female
2002
The purpose of this study was to determine the effect of laparoscopic Roux-en-Y gastric bypass (LRYGBP) on symptomatic control of gastroesophageal reflux disease (GERD).
Morbidly obese patients (n = 435) who underwent LRYGBP for morbid obesity were assessed for changes in GERD symptoms, quality of life, and patient satisfaction after surgery.
A total of 238 patients (55%) had evidence of chronic GERD, and 152 patients (64%) voluntarily participated in the study. The mean body mass index (BMI) was 48 kg/m2. The mean excess weight loss was 68.8% at 12 months. There was a significant decrease in GERD-related symptoms, including heartburn (from 87% to 22%, p<0.001); water brash (from 18% to 7%, p<0.05); wheezing (from 40% to 5%, p<0.001) laryngitis (from 17% to 7%, p<0.05); and aspiration (from 14% to 2%, p<0.01) following LRYGBP. Postoperatively, the use of medication decreased significantly both for proton pump inhibitors (from 44% to 9%, p<0.001) and for the H2 blockers (from 60% to 10%, p<0.01). SF-36 physical function scores and the mental component summary scores improved after the operation (87 vs 71; p<0.05 and 83 vs 66; p<0.05, respectively). Overall patient satisfaction was 97%.
LRYGBP results in very good control of GERD in morbidly obese patients with follow-up as late as 3 years. Morbidly obese patients who require surgery for GERD may be better served by LRYGBP than fundoplication because of the additional benefit of significant weight loss.
Journal Article
Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for the Treatment of Obesity in the ReCharge Trial
by
Shah, Sajani N.
,
Tweden, Katherine S.
,
Shikora, Scott A.
in
Adult
,
Autonomic Nerve Block - adverse effects
,
Autonomic Nerve Block - instrumentation
2017
Background
The ReCharge Trial demonstrated that a vagal blocking device (vBloc) is a safe and effective treatment for moderate to severe obesity. This report summarizes 24-month outcomes.
Methods
Participants with body mass index (BMI) 40 to 45 kg/m
2
, or 35 to 40 kg/m
2
with at least one comorbid condition were randomized to either vBloc therapy or sham intervention for 12 months. After 12 months, participants randomized to vBloc continued open-label vBloc therapy and are the focus of this report. Weight loss, adverse events, comorbid risk factors, and quality of life (QOL) will be assessed for 5 years.
Results
At 24 months, 123 (76 %) vBloc participants remained in the trial. Participants who presented at 24 months (
n
= 103) had a mean excess weight loss (EWL) of 21 % (8 % total weight loss [TWL]); 58 % of participants had ≥5 % TWL and 34 % had ≥10 % TWL. Among the subset of participants with abnormal preoperative values, significant improvements were observed in mean LDL (−16 mg/dL) and HDL cholesterol (+4 mg/dL), triglycerides (−46 mg/dL), HbA1c (−0.3 %), and systolic (−11 mmHg) and diastolic blood pressures (−10 mmHg). QOL measures were significantly improved. Heartburn/dyspepsia and implant site pain were the most frequently reported adverse events. The primary related serious adverse event rate was 4.3 %.
Conclusions
vBloc therapy continues to result in medically meaningful weight loss with a favorable safety profile through 2 years.
Trial Registration
https://clinicaltrials.gov/ct2/show/NCT01327976
Journal Article
FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes
by
Connett, John
,
Billington, Charles
,
Sachdev, Saachi
in
Adult
,
Bile
,
Bile Acids and Salts - blood
2016
Background
This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment.
Methods
Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (
n
= 15) or RYGB (
n
= 15).
Results
Mean HbA1c decreased from 9.7 to 6.4 % after RYGB and from 9.1 to 6.1 % in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB, FGF19 increased in the fasted (93 ± 15 to 152 ± 19 pg/ml;
P
= 0.008) and postprandial states (area under the curve (AUC), 10.8 ± 1.9 to 23.4 ± 4.1 pg × h/ml × 10
3
;
P
= 0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC ×10
3
, 6.63 ± 1.3 to 15.16 ± 2.56 μM × h;
P
= 0.003) and decreased after IMM (AUC ×10
3
, 8.22 ± 1.24 to 5.70 ± 0.70;
P
= 0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (
r
= 0.54,
P
= 0.04) and trended negatively with HbA1c (
r
= −0.44;
P
= 0.09); these associations were not observed after IMM.
Conclusions
BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.
Journal Article
Laparoscopic conversion of vertical banded gastroplasty to a Roux-en-Y gastric bypass
by
Ikramuddin, S.
,
Leslie, D. B.
,
Kellogg, T. A.
in
Biological and medical sciences
,
Digestive system. Abdomen
,
Endoscopy
2007
The vertical banded gastroplasty was the mainstay of bariatric surgery for over a decade. Though this procedure is now rarely performed many of these patients will present with failure or maladaptive eating and its sequelae. Some of these patients who demonstrate the motivation for lifestyle modification as well as many of these with complications will be candidates for revisional surgery. This article reviews the technical challenges in performing these revisions using minimally invasive techniques. In addition it reviews outcomes of laparoscopic conversion and tips for patient selection and success.
Journal Article
Outcomes of laparoscopic Toupet compared to laparoscopic Nissen fundoplication
by
Ikramuddin, S.
,
Fernando, H. C.
,
Luketich, J. D.
in
Adult
,
Aged
,
Biological and medical sciences
2002
Recent reports suggest that partial fundoplications such as the laparoscopic Toupet (LT) ultimately suffer from a higher recurrence rate compared to complete wraps such as the laparoscopic Nissen fundoplication (LNF). This article summarizes our experience with LT and LNF.
Over a 45-month period (February 1995 to November 1998), 206 patients underwent laparoscopic antireflux operations. The LNF group included 163 patients and the LT group included 43 patients. Global quality of life was measured using the Medical outcomes short form 36 (SF36).
There were no differences in disease severity, except that the LT group had a higher incidence of esophageal dysmotility (37.2% 8.6%, p < 0.05). Early outcomes were similar, with no perioperative deaths and morbidity occurring in 15 (9.2%) LNF and 5 (11.6%) LT patients (p = not significant). Long-term follow-up was available in 142 patients at a mean of 19.7 months. A greater number of LT patients required proton pump inhibitors (38 vs 20%) and were dissatisfied (21 vs 7%) with their surgery (p < 0.05). SF36 physical function scores were better in the LNF group (85 vs 74; p < 0.05). Significantly more (p < 0.05) of the LT patients complained of dysphagia (34.5 vs 15%) on follow-up. There were no differences in the incidence of symptoms related to the gas-bloat syndrome. The observed differences between the LT and LNF groups did not appear to be related to differences in esophageal motility.
Short-term results were similar for LT and LNF, but with longer follow-up, better results were seen with LNF. Even in the setting of moderate decreases of esophageal motility, complete fundoplication yields superior results.
Journal Article
The EMPOWER Study: Randomized, Prospective, Double-Blind, Multicenter Trial of Vagal Blockade to Induce Weight Loss in Morbid Obesity
by
Brancatisano, Anthony
,
Takata, Mark
,
Kow, Lilian
in
Appetite
,
Australia - epidemiology
,
Autonomic Nerve Block - methods
2012
Background
Intermittent, reversible intraabdominal vagal blockade (VBLOC® Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia.
Methods
Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (
n
= 192) or control (
n
= 102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12 months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM.
Results
Study subjects consisted of 90 % females, body mass index of 41 ± 1 kg/m
2
, and age of 46 ± 1 years. Device-related complications occurred in 3 % of subjects. There was no mortality. 12-month percent EWL was 17 ± 2 % for the treated and 16 ± 2 % for the control group. Weight loss was related linearly to hours of device use; treated and controls with ≥12 h/day use achieved 30 ± 4 and 22 ± 8 % EWL, respectively.
Conclusions
VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.
Journal Article
Sustained Weight Loss with Vagal Nerve Blockade but Not with Sham: 18-Month Results of the ReCharge Trial
by
David B. Sarwer
,
Mehran Anvari
,
Charles J. Billington
in
Abdominal Pain - etiology
,
Body Mass Index
,
Care and treatment
2015
Background/Objectives. Vagal block therapy (vBloc) is effective for moderate to severe obesity at one year. Subjects/Methods. The ReCharge trial is a double-blind, randomized controlled clinical trial of 239 participants with body mass index (BMI) of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions. Interventions were implantation of either vBloc or Sham devices and weight management counseling. Mixed models assessed percent excess weight loss (%EWL) and total weight loss (%TWL) in intent-to-treat analyses. At 18 months, 142 (88%) vBloc and 64 (83%) Sham patients remained enrolled in the study. Results. 18-month weight loss was 23% EWL (8.8% TWL) for vBloc and 10% EWL (3.8% TWL) for Sham (P<0.0001). vBloc patients largely maintained 12-month weight loss of 26% EWL (9.7% TWL). Sham regained over 40% of the 17% EWL (6.4% TWL) by 18 months. Most weight regain preceded unblinding. Common adverse events of vBloc through 18 months were heartburn/dyspepsia and abdominal pain; 98% of events were reported as mild or moderate and 79% had resolved. Conclusions. Weight loss with vBloc was sustained through 18 months, while Sham regained weight between 12 and 18 months. vBloc is effective with a low rate of serious complications.
Journal Article