Long-Term effects of physical activity on weight loss, metabolic parameters and blood pressure in subjects undergoing bariatric surgery: A 5-year follow-up study.

BACKGROUND: bariatric surgery stands as an effective intervention for weight loss and improved metabolic control in obesity, although over time there is a proportion of weight regain and type-2-diabetes (T2D) relapse. AIMS: to explore the role of physical activity (PA) after surgery and its impact on metabolic parameters during a 5-year follow-up. METHODS: 148 individuals who underwent bariatric surgery completed scheduled examinations over 5-years. Physical assessments and laboratory tests were conducted pre-surgery and annually thereafter. PA levels were evaluated using the International Physical Activity Questionnaire. RESULTS: participants were split into the PA group, who engaged in regular physical activity, and No-PA group, who remained sedentary throughout. In T2D individuals before surgery, PA group showed significant reductions in blood pressure and a lower T2D recurrence (6.7 â€‹% vs 36 â€‹%) compared to No-PA group. In normoglycemic individuals, the PA group led to sustained BMI reduction and improved blood pressure control (p â€‹< â€‹0.001) compared to No-PA group, for the entire duration of follow-up. CONCLUSIONS: regular PA demonstrated cardio-metabolic benefits post-bariatric surgery. Integrating PA into post-bariatric care could enhance long-term outcomes.

Trends and safety of bariatric revisional surgery in Italy: multicenter, prospective, observational study.

BACKGROUND: Revisional bariatric surgery (RBS) represents a further solution for patients who experience inadequate weight loss (IWL) following primary bariatric surgery (BS) or significant weight regain (WR) following initial satisfactory response. RBS guidelines are lacking; however, an increased trend in further BS offerings has been reported recently. OBJECTIVE: Analyze trend, mortality, complication, readmission, and reoperation rates for any reason at 30 days after RBS in Italy. SETTING: Ten Italian high-volume BS centers (university hospitals and private centers). METHODS: Prospective, observational, multicenter study enrolling patients undergoing RBS between October 1, 2021, and March 31, 2022, registering reasons for RBS, technique, mortality, intraoperative and perioperative complications, readmissions, and reinterventions for any reason. Patients undergoing RBS during the same calendar interval in 2016-2020 were considered control patients. RESULTS: A total of 220 patients were enrolled and compared with 560 control-group patients. Mortality was .45% versus .35% (n.s), with an overall mortality of .25%, while open surgery or conversion to open surgery was registered in 1%. No difference was found for mortality, morbidity, complications, readmission (1.3%), and reoperation rates (2.2%). IWL/WR was the most frequent cause, followed by gastroesophageal reflux disease; Roux-en-Y gastric bypass was the most used revisional procedure (56%). Sleeve gastrectomy was the most revised procedure in the study group, while gastric banding was the most revised in the control group. RBS represents up to 9% of the total BS in the Italian participating centers. CONCLUSIONS: Laparoscopy represents the standard approach for RBS, which appears safe. Current Italian trends show a shift toward sleeve gastrectomy being the most revised procedure and Roux-en-Y gastric bypass being the most frequent revisional procedure.

Decreased Weight Loss Following Bariatric Surgery in Patients with Type 2 Diabetes.

BACKGROUND: Bariatric surgery represents the most effective treatment for achieving significant and sustained weight loss. We aimed to assess whether presence of type 2 diabetes (T2D) at baseline, and T2D remission following bariatric surgery affect the weight loss outcome. METHODS: Data of 312 consecutive morbidly obese subjects who underwent bariatric surgery were analysed. Patients underwent either RYGB (77%), or sleeve gastrectomy (23%), and their body weight was followed-up for 1, 2, 3, 4, and 5 years at regular ambulatory visits (N = 269, 312, 210, 151, 105, at each year, respectively). T2D remission was assessed according to the ADA criteria. RESULTS: In the whole dataset, 92 patients were affected by T2D. Patients with T2D were older than patients without T2D (52 ± 9 vs 45 ± 11 years, p < 0.0001), but there were no differences in baseline BMI, sex, and type of intervention received. We found that presence of T2D at baseline was associated with smaller weight loss at 1, 2, 3, 4, and 5 years following bariatric surgery (δ BMI at 2 years: - 13.7 [7.7] vs - 16.4 [7.3] kg/m2; at 5 years - 12.9 [8.8] vs - 16.3 [8.7] kg/m2 in patients with T2D vs patients without T2D respectively, all p < 0.05). When dividing the patients with T2D in remitters and non-remitters, non-remitters had significantly smaller weight loss compared to remitters (δ BMI at 2 years: - 11.8 [6.3] vs - 15.4 [7.8] kg/m2; at 5 years: - 8.0 [7.1] vs - 15.0 [7.2] kg/m2, non-remitters vs remitters respectively, all p < 0.05). CONCLUSIONS: T2D is independently associated to smaller weight loss following bariatric surgery, especially in subjects not achieving diabetes remission. • Patients with T2D achieve smaller weight loss following bariatric surgery • When dividing the T2D patients in remitters and non-remitters, non-remitters achieve significantly smaller weight loss compared to remitters.

Laparoscopic bariatric surgery is safe during phase 2-3 of COVID-19 pandemic in Italy: A multicenter, prospective, observational study.

BACKGROUND: Sars-Cov-2 epidemic in Italy caused one of the greatest 2020 European outbreaks, with suspension of elective bariatric/metabolic surgery (BMS). From May 2020 a significant decline of the epidemic has been observed (phase 2); National Health Service protocols permitted elective BMS' resumption. A new, more severe COVID-19 surge, the "second wave", started on October 2020 (phase 3). AIM: The primary end point was to analyze the outcomes of any Sars-Cov-2 infection and related morbidity/mortality within 30 POD after laparoscopic BMS during phase 2-3; secondary end points were readmission and reoperation rates. METHODS: Study design prospective, multicenter, observational. SETTING: Eight Italian high-volume bariatric centers. All patients undergoing BMS from July 2020 through January 2021 were enrolled according to the following criteria: no Sars-Cov-2 infection; primary procedures; no concomitant procedure; age > 18 < 60 years; compensated comorbidities; informed consent including COVID-19 addendum; adherence to specific admission, in-hospital and follow-up protocols. Data were collected in a prospective database. Patients undergone BMS during July-December 2019 were considered a control group. RESULTS: 1258 patients were enrolled and compared with 1451 operated on in 2019, with no differences for demographics, complications, readmission, and reintervention rates. Eight patients (0·6%) tested positive for Sars-Cov-2 infection after discharge, as well as and 15 healthcare professionals, with no related complications or mortality. CONCLUSIONS: Introduction of strict COVID-19 protocols concerning the protection of patients and health-care professionals guaranteed a safe resumption of elective BMS in Italy. The safety profile was, also, maintained during the second wave of outbreak, thus allowing access to a cure for the obese population.

Bariatric and metabolic surgery during COVID-19 outbreak phase 2 in Italy: why, when and how to restart.

In Italy elective bariatric and metabolic surgery was cancelled on February 21,2020 at the beginning of the so-called phase 1 of the SARS-CoV-2 outbreak. Gradually it was restarted on May 4,2020 at the beginning of the so-called phase 2, when epidemiological data showed containment of the infection. Before the outbreak in eight high-volume bariatric centers 840 patients were surgically treated developing a Covid-19 infection, during phase 1, in only 5 cases (0.6%) without mortality. The post-operative complication rate was similar when compared to the 836 subjects submitted to bariatric surgery the year before. Since the high prevalence of infection in subjects with BMI > 30, it was argued that early intervention on obesity during phase 2 could help to minimize the effects of the disease in the event of a possible reversion to a SARS-CoV-2 outbreak phase 1. At the same time a prospective observational study from July 1 till the WHO declaration of the end of the pandemic has started in the eight high volume centers to monitor the post-operative outcome and its effect on SARS-CoV-2 infection.

Impact of Postprandial Hypoglycemia on Weight Loss After Bariatric Surgery.

INTRODUCTION: Postprandial hypoglycemia (PPHG) is a well-known complication after bariatric surgery (BS). However, it is not known whether PPHG affects weight loss after BS. AIMS: To assess the impact of PPHG on weight loss after BS in subjects without and with type 2 diabetes mellitus (T2D). METHODS: Data from 338 subjects who had undergone gastric bypass (RYGB) or sleeve gastrectomy (LSG) and were followed up for at least 2 years were analyzed. At each follow-up visit, the patient's anthropometric and biochemical characteristics were recorded and the Edinburgh Questionnaire was performed to evaluate the presence of PPHG symptoms. RESULTS: Before surgery: younger age and lower BMI predicted PPHG after BS (p = 0.02 and p = 0.0008, respectively). Also, the baseline OGTT indicated that subjects who developed PPHG had an earlier glucose peak and more often had low glucose levels at 2 h compared with the no-PPHG group (p = 0.03 and p = 0.004, respectively). After surgery: Mild-to-moderate PPHG occurred equally after RYGB and LSG (38% vs 25%, p = ns when accounting for confounders), and in T2D who achieved remission and those who did not (29.5% vs 28.6%, ns). At the 2-year follow-up, occurrence of PPHG was independently associated with smaller weight loss (p = 0.0006). CONCLUSIONS: Mild-to-moderate PPHG is a frequent complication after bariatric surgery and results in smaller weight loss after 2 years. Age, baseline BMI, and an earlier glucose peak during OGTT predict PPHG after bariatric surgery.

Using Skin Bioengineering to Highlight How Weight and Diabetes Mellitus Modify the Skin in the Lower Limbs of Super-Obese Patients.

AIM: To evaluate the distinct contribution of obesity and diabetes (DM) to the skin modification in metabolic diseases. METHODS: We analysed all patients admitted for bariatric surgery in our hospital with BMI between 38 and 47 kg/m2, with (Group 1) or without (Group 2) DM and compared them with a group of nonobese diabetic patients (Group 3) and healthy volunteers (Group 4). The following features were evaluated: hardness, temperature, hydration and thickness alongside with anthropometric measures of foot and leg. RESULTS: For the general characteristics, patients differed in age and body mass index. As predictable all circumferences (dorsal foot, sovramalleolar and under the knee) were significantly higher in obese with no differences depending on DM (all parameters: p<0.01 in Group 1 and Group 2 vs Group 3 and Group 4). Skin temperature was significantly higher in all obese, irrespectively from the presence of DM (1st metatarsal head: p=0.02 Group 1 and Group 2 vs Group 3 and Group 4; 5th metatarsal head: p<0.01 in Group 1 and Group 2 vs Group 3 and Group 4). Skin hydration score showed increased anhydrosis in both diabetics and severe obesity (p<0.01 in Group 1 and Group 3 vs Group 2 and Group 4). Increase in thickness of skin and subcutaneous tissues was observed (at heel: p<0.01 in Group 1 and Group 2 vs Group 3 and Group 4 and under the scaphoid p=0.03 Group 1 and Group 2 vs Group 3 and Group 4) and plantar fascia (in both regions p=0.02 Group 1 and Group 2 vs Group 3 and Group 4) in all obese patients, with or without DM. CONCLUSION: Severe obesity significantly affects both shape and structure of the foot, possibly exposing these patients to a higher risk of biomechanical stress. On such a background DM, modifying skin hydration and protective mechanisms exerts a synergistic role further increasing the risk of trauma and ulcers.

Differential Impact of Weight Loss and Glycemic Control on Inflammasome Signaling.

OBJECTIVE: Interleukin (IL)-1ß is involved in obesity-associated inflammation and in the pathogenesis of type 2 diabetes (T2D) mellitus. Our aim was to correlate serum IL-1ß and caspase-1 levels with weight loss, glucose metabolism, and insulin resistance (IR) after bariatric surgery. METHODS: A total of 32 patients with morbid obesity and T2D (Ob-T2D) and 29 patients with morbid obesity and normal glucose tolerance (Ob-NGT), treated by Roux-en-Y gastric bypass, were studied before and 1 year after surgery. Sixteen healthy individuals served as a control (HC) group. IR was assessed by the oral glucose insulin sensitivity method. Plasma IL-1ß levels and caspase-1 were measured. RESULTS: Presurgery BMI was similar in Ob-NGT and Ob-T2D. IR was progressively impaired in Ob-NGT and Ob-T2D (P < 0.0001). Fasting plasma IL-1ß and caspase-1 levels were lower in HCs than in patients with Ob-NGT or Ob-T2D (P < 0.02; P = 0.05), and both were inversely correlated with IR (P = 0.01; P = 0.02). After surgery, BMI decreased and IR improved to a similar extent in Ob-NGT and Ob-T2D (P < 0.0001). Plasma caspase-1 concentrations normalized in both groups (P < 0.0001), whereas plasma IL-1ß levels normalized only in Ob-NGT. CONCLUSIONS: Plasma IL-1ß and caspase-1 levels were inversely correlated with IR. Caspase-1 levels normalized after weight loss, whereas IL-1ß normalized only in people without T2D, suggesting the persistence of a systemic inflammatory condition in people with T2D.

Abdominal pain and internal hernias after Roux-en-Y Gastric Bypass: are we dealing with the tip of an iceberg?

BACKGROUND: Abdominal pain is the most frequent cause of hospital admission after Roux-en-y gastric bypass (RYGB). Among numerous possible underlying causes, internal hernias represent one of the most peculiar and insidious conditions, setting challenging diagnostic and therapeutic problems for the surgeon. The aim of this study is to analyze aspecific abdominal pain incidence and characteristics after RYGB, discriminating peculiar aspects suggestive of internal hernias. METHODS: 13 patients submitted to internal hernia repair after laparoscopic antecolic RYGB and a group of 49 controls (non-complicated RYGB) have been assessed using a specific questionnaire. Overall aspecific abdominal pain incidence and characteristics have been analysed. Typical pain traits and predisposing conditions for internal hernias have been investigated. RESULTS: 33% of controls reported aspecific abdominal pain after RYGB, mainly early postprandial, deep, remittent, colicky, located in the upper left abdomen. 77% of the case patients reported prodromal episodes of pain similar to the controls. The only significant differences between prodromal and acute episodes were pain intensity and quality (continuous). Excess weight lost at 3 months significantly correlated with internal hernia occurrence (p: 0.002). CONCLUSIONS: Based on abdominal pain characteristics, we can reasonably postulate the presence of remittent bowel torsions (remittent internal hernia) in many patients after antecolic RYGB, only occasionally complicating. Therapeutic management of these cases remains controversial, being laparoscopic exploration a reasonable option when symptomatology is suggestive.

Postprandial hypoglycaemia after Roux-en-Y gastric bypass in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB. METHODS: A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery. PPHG was defined as a plasma glucose level of ≤3.3 mmol/l when not taking glucose-lowering agents. Insulin sensitivity was assessed by oral glucose insulin sensitivity index and beta-cell function by mathematical modelling of the plasma glucose, insulin and C-peptide concentrations. RESULTS: After surgery, PPHG occurred in 11 of 35 individuals who underwent RYGB. Before surgery, BMI was lower, glycaemic control less good and time of glucose peak earlier in the PPHG vs No PPHG group, and the duration of diabetes was shorter with PPHG (all p ≤ 0.05). In addition, insulin sensitivity was greater in the PPHG than No PPHG group (p = 0.03). After surgery, BMI and fasting glucose and insulin levels decreased similarly in the two groups; insulin secretion during the first hour of the OGTT increased more in the PPHG than No PPHG group (p = 0.04). Beta-cell glucose sensitivity increased more in individuals with PPHG than those without (p = 0.002). Over the same time interval, the glucagon-like peptide 1 (GLP-1) response was lower in individuals with PPHG before surgery (p = 0.05), and increased more after surgery. At 2 h after glucose ingestion in the OGTT, postsurgery plasma glucagon level was significantly lower in the PPHG than No PPHG group. CONCLUSIONS/INTERPRETATION: In morbidly obese individuals with type 2 diabetes, spontaneous PPHG may occur after bariatric surgery independently of a remission of diabetes. Before surgery, individuals had a shorter duration and were more insulin sensitive. Two years after surgery, these individuals developed greater beta-cell glucose sensitivity, and showed greater insulin and GLP-1 release early in the OGTT.

Aging Modulates the Influence of Arginase on Endothelial Dysfunction in Obesity.

Objective- Arginase can reduce NO availability. In this study, we explored arginase as a determinant of endothelial dysfunction in small arteries from obese patients and its relationship with aging and microvascular remodeling. Approach and Results- Small arteries were dissected after subcutaneous fat biopsies and evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation was assessed by acetylcholine, repeated under L-NAME ( N G-nitro-L-arginine-methyl ester), N(ω)-hydroxy-nor-l-arginine (arginase inhibitor) and gp91ds-tat (NADPH [nicotinamide adenine dinucleotide phosphate oxidase] oxidase inhibitor) in vessels from young (age <30 years) control and obese and old (>30 years) control and obese subjects. Media-lumen ratio and amount of vascular wall fibrosis were used as markers of vascular remodeling. Amount of vascular superoxide anions and NO production were determined with immunofluorescence, whereas arginase expression was quantified using Western blot and quantitative polymerase chain reaction. Obese and older age groups had lower vascular NO, as well as higher media-lumen ratio, wall fibrosis, intravascular superoxide, and blunted inhibitory effect of L-NAME on acetylcholine versus controls and younger age groups. N(ω)-hydroxy-nor-l-arginine restored the acetylcholine-induced vasodilation in young and, to a lesser extent, in old obese subjects. This effect was abolished by addition of L-NAME. Gp91ds-tat increased the vasodilatory response to N(ω)-hydroxy-nor-l-arginine in old obese. Superoxide anions and arginase I/II levels were higher in the vascular wall of obese versus controls. Conclusions- Arginase contributes to microvascular endothelial dysfunction in obesity. Its impact is reduced by aging because of higher levels of vascular oxidative stress. Obesity is accompanied by accelerated microvascular remodeling, the extent of which is related to the amount of arginase in the vascular wall.

Publisher Correction: Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Estimation of Urinary Creatinine Excretion and Prediction of Renal Function in Morbidly Obese Patients: New Tools from Body Composition Analysis.

BACKGROUND/AIMS: In obese subjects the accuracy of prediction of renal function is quite low. The aim of this study was to obtain a more accurate estimate of urinary creatinine excretion (UCr), creatinine clearance (CCr), and GFR from body cell mass (BCM). METHODS: Seventy-three adult morbidly obese patients (BMI 35.2-64.5 kg/m2) were examined. BCM was calculated from body impedance analysis. CCr was measured (mCCr) and was predicted from BCM and antropometric data (MR-BCMCCr), with Cockcroft and Gault (C&GCCr) and Salazar and Corcoran (S&CCCr) formulas. GFR was predicted from BCM (BCM GFR) and with MDRD and CKD-EPI formulas. RESULTS: Multiple regression (MR) indicated a strict linear correlation between UCr, BCM and anthropometric data. UCr predicted from MR equation (MR-BCMUCr) was very similar to measured UCr. MR-BCMCCr (168±46 mL/min) and mCCr (167±51 mL/min) were also similar, while significant differences were found between mCCr, C&GCCr and S&CCCr. The correlation and the agreement between MR-BCMCCr and mCCr were closer and prediction error was lower than the other formulas. BCM GFR (125±32 mL/min) had close correlations and agreements with MDRD GFR and CKD EPI formulas. CONCLUSIONS: In morbidly obese patients the measurement of BCM meliorates the prediction of UCr and CCr, and allows the prediction of GFR.

Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery.

Obesity is characterized by insulin-resistance (IR), enhanced lipolysis, and ectopic, inflamed fat. We related the histology of subcutaneous (SAT), visceral fat (VAT), and skeletal muscle to the metabolic abnormalities, and tested their mutual changes after bariatric surgery in type 2 diabetic (T2D) and weight-matched non-diabetic (ND) patients. We measured IR (insulin clamp), lipolysis (2H5-glycerol infusion), ß-cell glucose-sensitivity (ß-GS, mathematical modeling), and VAT, SAT, and rectus abdominis histology (light and electron microscopy). Presurgery, SAT and VAT showed signs of fibrosis/necrosis, small mitochondria, free interstitial lipids, thickened capillary basement membrane. Compared to ND, T2D had impaired ß-GS, intracapillary neutrophils and higher intramyocellular fat, adipocyte area in VAT, crown-like structures (CLS) in VAT and SAT with rare structures (cyst-like) ~10-fold larger than CLS. Fat expansion was associated with enhanced lipolysis and IR. VAT histology and intramyocellular fat were related to impaired ß-GS. Postsurgery, IR and lipolysis improved in all, ß-GS improved in T2D. Muscle fat infiltration was reduced, adipocytes were smaller and richer in mitochondria, and CLS density in SAT was reduced. In conclusion, IR improves proportionally to weight loss but remains subnormal, whilst SAT and muscle changes disappear. In T2D postsurgery, some VAT pathology persists and beta-cell dysfunction improves but is not normalized.

Sleeve Gastrectomy: Correlation of Long-Term Results with Remnant Morphology and Eating Disorders.

BACKGROUND: Remnant dimension is considered one of the crucial elements determining the success of sleeve gastrectomy (SG), and dilation of the gastric fundus is often believed to be the main cause of failure. OBJECTIVES: The main outcome of this study is to find correlations between remnant morphology in the immediate post-operative stage, its dilation in years, and the long-term results. The second purpose aims to correlate preoperative eating disorders, taste alteration, hunger perception, and early satiety with post-SG results. MATERIALS AND METHODS: Remnant morphology was evaluated, in the immediate post-operative stage and over the years (≥2 years), through X-ray of the oesophagus-stomach-duodenum calculating the surface in anteroposterior (AP) and right anterior oblique projection (RAO). Presurgery diagnosis of eating disorders and their evaluation through "Eating Disorder Inventory-3" (EDI3) during follow-up were performed. Change in taste perception, sense of appetite, and early satiety were evaluated. Patients were divided into two groups: "failed SGs (EWL<50%) and "efficient SGs" (EWL >50%). RESULTS: There were a total of 50 patients (37 F, 13 M), with mean age 52 years, preoperative weight 131 ± 21.8 kg, and BMI 47.4 ± 6.8 kg/m2. Post-operative remnant mean dimensions overlapped between the two groups. On a long-term basis, an increase of 57.2 and 48.4% was documented in the AP and RAO areas respectively. In "failed" SGs, dilation was significantly superior to "efficient" SGs (AP area 70.2 vs 46.1%; RAO area 59.3 vs 39%; body width 102% vs 41.7%). Preoperative eating disorders were more present in efficient SGs than in failed SGs with the exception of sweet eating. There were no significant changes to taste perception during follow-up. Fifty-two percent of efficient SGs vs 26% of failed SGs reported a persistent lack of sense of hunger; similarly, 92.5 vs 78% declared the persistence of a sense of early satiety. The two groups did not statistically differ as far as all the variables of the EDI3 are concerned. CONCLUSION: On a long-term basis, the remnant mean dilation is around 50% compared to the immediate post-operative stage but failed SGs showed larger remnant dilation than efficient SGs and, in percentage, the more dilated portion is the body of the stomach. As far as all the EDI3 variables obtained are concerned, the two groups did not statistically differ. Of all eating disorders, sweet eating seems to be weakly connected to SG failure.

Risk Factors for Spontaneously Self-Reported Postprandial Hypoglycemia After Bariatric Surgery.

CONTEXT: Postprandial hypoglycemia (PPHG) is a recognized complication of Roux-en-Y gastric bypass (RYGB) surgery. Data on PPHG after laparoscopic sleeve gastrectomy (LSG) are scant. OBJECTIVE: The objective of the study was to identify preoperative predictors of PPHG in subjects spontaneously self-reporting PPHG after RYGB or LSG. Patients, Setting, and Intervention: Nondiabetic patients spontaneously self-reporting symptoms/signs of PPHG (PPHG group, 21 RYGB and 11 LSG) were compared in a case-control design with subjects who never experienced spontaneous or oral glucose tolerance test (OGTT)-induced hypoglycemia over 24 months after surgery (No-PPHG group, 13 RYGB and 40 LSG). Paired pre- and postoperative 3-hour OGTTs were analyzed in all participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the oral glucose insulin sensitivity index and ß-cell function by mathematical modeling of the C-peptide response to glucose. RESULTS: Before surgery, the body mass index was lower in PPHG than No-PPHG patients in the RYGB (P = .002) and trended similarly in the LSG group (P = .08). Fasting glycemia and the glucose-OGTT nadir were lower in the PPHG than the No-PPHG subjects in both surgery groups. Before surgery, insulin sensitivity was higher in PPHG than No-PPHG in the RYGB (393 ± 55 vs 325 ± 44 mL/min-1 · m-2, P = .001) and LSG groups (380 ± 48 vs 339 ± 60 mL/min-1 · m-2, P = .05) and improved to a similar extent in all groups after surgery. Before surgery, ß-cell glucose sensitivity was higher in PPHG than No-PPHG in both RYGB (118 ± 67 vs 65 ± 24 pmol/min-1 · m2 · mM-1) and LSG patients (114 ± 32 vs 86 ± 33) (both P = .02) and improved in all subjects after surgery. CONCLUSIONS: In subjects self-reporting PPHG after surgery, lower presurgery plasma glucose concentrations, higher insulin sensitivity, and better ß-cell glucose sensitivity are significant predictors of PPHG after both RYGB and LSG.

Decreased expression of hepatic glucokinase in type 2 diabetes.

BACKGROUND/OBJECTIVES: Increased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK). METHODS: We examined expression of these enzymes in liver biopsies from 12 nondiabetic and 28 diabetic individuals. Diabetic patients were further separated into those with HbA1c lower or higher than 7.0. RESULTS: In diabetic subjects with HbA1c > 7.0, we found that gluconeogenic enzymes were expressed normally, but GCK was suppressed more than 60%. Moreover, HbA1c and fasting glucose were negatively correlated with GCK, but showed no correlation with G6PC, PCK1, or PCK2. CONCLUSION: These findings suggest an underlying dysregulation of hepatic GCK expression during frank diabetes, which has implications for the therapeutic use of glucokinase activators in this population.

Early postoperative weight loss predicts maximal weight loss after sleeve gastrectomy and Roux-en-Y gastric bypass.

BACKGROUND: Previous studies show that 'poor responders' to Roux-en-Y gastric bypass (RYGBP) may be identified on the basis of early postoperative weight loss. Early identification of poor responders could allow earlier provision of postoperative behavioural and/or intensive lifestyle interventions and enhance their maximal weight loss. Our aim was to investigate whether early postoperative weight loss predicts the maximal weight loss response after RYGBP and sleeve gastrectomy (SG). METHODS: We undertook a retrospective cross-sectional study of 1,456 adults who underwent either RYGBP (n = 918) or SG (n = 538) as a primary procedure in one of two European centres. Postoperative weight loss was expressed as weight loss velocity (WLV) and percentage weight loss. Linear regression analyses were performed to determine the association of early postoperative weight loss with maximal %WL, including adjustment for baseline variables. RESULTS: There was marked variability in maximal %WL following both RYGBP (mean 32.9 %, range 4.1-60.9 %) and SG (mean 26.2 %, range 1.1-58.3 %). WLV 3-6 months postoperatively was more strongly associated with maximal %WL (r (2) = 0.32 for RYGBP and r (2) = 0.26 for SG, P < 0.001 for both) than either WLV 0-6 weeks or 6 weeks to 3 months postoperatively (r (2) = 0.14 and 0.10 for RYGBP, respectively; r (2) = 0.18 and 0.21 for SG, respectively; P < 0.001 for all). Multiple linear regression analysis, including baseline variables of age, sex, preoperative BMI, type 2 diabetes, ethnicity, and bariatric centre, revealed that 3-6 month WLV was an independent predictor of maximal %WL in both SG and RYGBP groups (standardised ß-coefficients 0.51 and 0.52, respectively; P < 0.001 for both). CONCLUSIONS: There is a marked variability in weight loss response following RYGBP and SG. Early postoperative weight loss can be used to identify patients whose predicted weight loss trajectories are suboptimal. Early targeting of poor responders with more intensive postoperative lifestyle and behavioural support could potentially enhance their weight loss response.

Tumour necrosis factor-alpha participates on the endothelin-1/nitric oxide imbalance in small arteries from obese patients: role of perivascular adipose tissue.

AIMS: We assessed the impact of vascular and perivascular tumour necrosis factor-alpha (TNF-α) on the endothelin (ET)-1/nitric oxide (NO) system and the molecular pathways involved in small arteries from visceral fat of obese patients (Obese) and Controls. METHODS AND RESULTS: Isolated small arteries from 16 Obese and 14 Controls were evaluated on a pressurized micromyograph. Endogenous ET-1 activity was assessed by the ETA blocker BQ-123. TNF-α and NO were tested by anti-TNF-α infliximab (IFX) and N(ω)-nitro-l-arginine methylester (L-NAME). Gene and protein expression of TNF-α, ET-1, ETA, and ETB receptors were determined by RT-PCR and IHC on arterial wall and in isolated adipocytes. Obese showed a blunted L-NAME-induced vasoconstriction, which was potentiated by IFX, and an increased relaxation to BQ-123, unaffected by L-NAME but attenuated by IFX. Perivascular adipose tissue (PVAT) removal reversed these effects. Obese showed intravascular superoxide excess, which was decreased by apocynin (NAD(P)H oxidase inhibitor), L-NAME, and BQ-123 incubations, and abolished by IFX. An increased vascular expression of ET-1, ETA, and ETB receptors, and higher vascular/perivascular TNF-α and TNF-α receptor expression were also detected. The arterial expression and phosphorylation of c-Jun N-terminal kinase (JNK) were higher in Obese vs. Controls, and downregulated by IFX. CONCLUSIONS: In small arteries of Obese, PVAT-derived TNF-α excess, and an increased vascular expression of ET-1 and ETA receptor, contribute to the ET-1/NO system imbalance, by impairing tonic NO release. Reactive oxygen species excess, via NAD(P)H oxidase activation, induces the endothelial nitric oxide synthase uncoupling, which in turn generates superoxide and impairs NO production. The up-regulated JNK pathway represents a crucial molecular signalling involved in this process.

Comparative use of different techniques for leak and bleeding prevention during laparoscopic sleeve gastrectomy: a multicenter study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an approved primary procedure for morbid obesity, but it is associated with serious complications, such as staple line leaks and bleeding. The objective of this study was to assess the effectiveness of staple line reinforcement (SLR) in reducing leaks and bleeding after LSG. METHODS: A total of 1162 patients underwent LSG (305 males, 857 females). The mean age was 43.7 years and the mean body mass index was 48 kg/m(2). The patients were divided into 6 groups based on the type of SLR, including a no-SLR control group, with evaluation of leaking and bleeding risk and correlation of patients' characteristics with complications. RESULTS: A total of 189 patients underwent LSG without reinforcement. The SLR method was oversewing in 476 patients, bovine pericardium in 312, synthetic polyester in 76, glycolide/trimethylene copolymer in 63, and thrombin matrix in 46. The overall leak frequency was 2.8%; higher with synthetic polyester (7.8%), 4.8% with no reinforcement, and lower with bovine pericardium strips (.3%; P<.01). Postoperative hemorrhage occurred in 35 patients (3%), with a higher frequency being observed without SLR (13.7%; P = .02). Only diabetes was a risk-factor for a leak (P< .01). CONCLUSION: SLR with bovine pericardium strips significantly reduced the leak risk. Postoperative bleeding was significantly lower with all SLR-methods, although there was no significant difference among the various techniques. Patients with type II diabetes had a higher risk of staple line leak after LSG. Further randomized, controlled studies are needed to improve our understanding of the efficacy of SLR during LSG.