Effective Therapy For Obesity Research Articles

A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety.

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. We designed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill, an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release and yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, P < 0.0001) and minimized the weight gain rate (P < 0.05) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

Pharmacological methods for weight reduction and their connection with the human gut microbiota

In the beginning of the twenty-first century, obesity has become a concerning world-wide issue due to its high prevalence in modern society. It is a metabolic disorder, caused by excessive accumulation of adipose tissue in the human organism – the main reason for which is increased caloric intake and decreased caloric expenditure in combination with dysregulation of hunger. It is a chronic systematic disease that leads to the development of a large number of health complications, the most common of which are: diabetes mellitus type 2, arterial hypertension, atherosclerosis, sleep apnea, different types of cancer and more. During the last decade, significant advancements have been made in regard to treatment of many endocrine and metabolic conditions, using pharmacological means, and some of these novel medications have proven to be an effective therapy for obesity. There is emerging evidence that such drugs can exhibit an effect over the human gut microbiota – the complex system of commensal bacteria located in the gastrointestinal tract, which could affect appetite, mucosal integrity, nutrient absorption, and that interaction can be the key to understanding the pathogenesis of obesity and its treatment.

Impact of Ursodeoxycholic Acid on Gall Stone Formation Post Bariatric Surgery

Introduction: Bariatric surgery is identified as highly effective therapy for obesity and help to loss wight that is become important public health priority because it increases the risk of condition including diabetes, cardiovascular disease, and several types of cancer whether by accomplishing mini-gastric bypass, Gastric bypass (Roux-en-Y) and sleeve gastrectomy [1] rapid weight loss increased incidence risk of gall stone formation [2]. Ursodeoxycholic acid is a bile acid which affect a reduction in cholesterol in biliary fluid primary by dispersing the cholesterol and forming a liquid-crystal phase [2], it’s can play a significant role in preventing of gall stone formation. Objective: Study potential effect of Ursodeoxycholic acid (UDCA) on gall stone formation after bariatric surgery. Methods: This study Cross-sectional Trials, review of all patient underwent bariatric surgery November 2021-Jun 2022, Taif Military Hospital in the department of surgery, the sample of study will be around 143 participants or more, data collection all patient underwent bariatric surgery. Results: A Total of 160 patients underwent bariatric surgery in Taif Armed Forces Hospitals from 2015 to 2021. Of these, 53 were male (33.1%) and 107 were female (66.9%). only 33 patients (20.6%) received Ursodeoxycholic acid, and 127 patients (79.4%) weren’t proscribed for them. However, 40 patients (25%) develop gall stone and underwent cholecystectomy, three of them were on Ursodeoxycholic acid (9%) and 37 patients weren’t on Ursodeoxycholic acid (29%). which shows that Ursodeoxycholic acid remarkable reduce the risk of gall stone formation post wight reduction surgery. Conclusion: In conclusion, bariatric procedures come with the risk of leading to the formation of gallstones. This is especially in the stage when a patient experiences rapid loss of weight. This is why a preventive measure is necessary and UDCA have been considered for this purpose. This study has shown that patients who use UDCA are less bound to have gallstone formations.

Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism.

Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes, and intestinal adaptation is a proposed mechanism for these effects. It was hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. This was a prospective, longitudinal, first-in-human study of gene expression (GE) in the "Roux limb" (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across six postoperative months, including at an early postoperative (1month ± 15 days) time point. RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid use. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibited GE changes characterized by anabolic growth and shift in metabolic substrate use. Paradoxically, anabolic growth in RL appeared to contribute to the catabolic state elicited by RYGB. These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without type 2 diabetes.

1431-P: Development of a New Index Based on Preoperative Serum Lipocalin 2 to Predict Post-LSG Weight Reduction

Background: Bariatric surgery is the most effective therapy for obesity, but targeted weight reduction is not always achieved. Serum lipocalin-2 (LCN2) is closely associated with obesity, but its impact on weight loss after surgery is unknown. We aimed to access the reliability of LCN2 levels and other parameters as effective predictors of excellent weight loss (≥75% excess weight loss [EWL]) 1 year after bariatric surgery. Methods: This retrospective study evaluated 450 patients (aged 18-65 years) with obesity at 3 months and 1 year after laparoscopic sleeve gastrectomy (LSG) surgery. Seventy-four patients who underwent LSG surgery and met the inclusion and exclusion criteria were included in this study. Serum LCN2, thyroid function, and metabolic and anthropometric parameters were assessed. Weight reduction was expressed as %EWL and percent total weight loss (%TWL) at 3 months and 1 year post surgery. Multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate predictors of ≥75%EWL. Results: In our cohort, %EWL and %TWL were both strongly associated with preoperative serum LCN2 levels. The binary logistic regression analysis showed that preoperative LCN2, waist circumference, and glycated hemoglobin were independent predictors of excellent weight loss. Conclusions: Based on these results, we determined a new P index with better predictive value for excellent weight reduction (≥75%EWL) 1 year after LSG surgery. Disclosure N.Li: None. L.Su: None. S.Qu: n/a. X.Cheng: n/a. L.Bu: None. B.Xu: None. J.Zeng: None. S.Lei: None. L.Gu: None. L.Feng: None. B.Zhu: None. Y.Huang: n/a. L.Wang: None. Funding The Tranditional Medicine Project of Shanghai Municipal Health Commission (grant number 2020JP013) ; Shanghai Natural Science Foundation (grant number 21ZR1449400) ; Shanghai Pujiang Talent Plan (grant number 18PJD038)

1404-P: High Cardiorespiratory Fitness Exerts Metabolic Protection in Obese Rats Regardless of Caloric Restriction or Short-Term Exercise

Caloric restriction (CR) and exercise (EX) attenuate metabolic impairment in obesity. High cardiorespiratory fitness (CRF) also protects against metabolic syndrome. However, the interplay between CRF, obesity, CR, and EX on metabolic health remains unclear. Male rats were fed with either a normal diet (ND; n=6) or a high-fat diet (HFD; n=30) for 12 weeks. Baseline CRF was measured. Then, ND-fed rats received a ND for 16 more weeks. HFD-fed rats were divided into 5 groups (n=6/group) to receive either a HFD for 16 weeks (OB) , 40% CR for 6 weeks followed by an ad lib ND for weeks (CR-S) , 40% CR for 16 weeks (CR-L) , a HFD + an EX for 6 weeks followed by a ND without EX for weeks (EX-S) , or a HFD + an EX for 16 weeks (EX-L) . Then, anthropometry and blood metabolic parameters were evaluated. We found that CR and EX decreased insulin resistance and dyslipidemia in obesity. High baseline CRF was correlated with favorable anthropometry and metabolic profiles at follow-up in the ND, OB, CR-S, CR-L, and EX-S rats. However, these correlations were not shown in the EX-L rats (Figure) . Our findings suggested that high CRF also protects against metabolic impairment in obesity, regardless of CR or short-term EX. Hence, an enhancement of CRF may provide the better effective therapy for obesity. Otherwise, low-CRF people may get the greatest benefit on a protection against metabolic syndrome by long-term EX. Disclosure P. Pantiya: None. S.C. Chattipakorn: None. N. Chattipakorn: None.

Obesity and breast cancer: Preventive and therapeutic possibilities for bariatric surgery.

Breast cancer is the most common and second deadliest malignancy in women. With rising obesity rates and building evidence for a strong association with obesity, the incidence of breast cancer can be expected to increase. Weight loss reduces breast cancer risk, the mechanisms of which are still poorly understood. As an effective therapy for obesity, bariatric surgery may be a powerful tool in breast cancer prevention and treatment. This review details the potential physiologic mechanisms that may underlie this association, as well as recently published studies that reinforce the link between bariatric surgery and a reduction in incident breast cancer. The use of bariatric surgery as an adjunct therapy in endometrial cancer also raises the potential for similar use in select breast cancer patients. Despite the expanding potential applications of bariatric surgery in this field, publications to date have been strictly observational, highlighting a need for future clinical trials.

Development of a New Index Based on Preoperative Serum Lipocalin 2 to Predict Post-LSG Weight Reduction

BackgroundBariatric surgery is the most effective therapy for obesity, but targeted weight reduction is not always achieved. Serum lipocalin-2 (LCN2) is closely associated with obesity, but its impact on weight loss after surgery is unknown. We aimed to access the reliability of LCN2 levels and other parameters as effective predictors of excellent weight loss (≥ 75% excess weight loss (EWL)) 1 year after bariatric surgery.MethodsThis retrospective study evaluated 450 patients (aged 18–65 years) with obesity at 3 months and 1 year after laparoscopic sleeve gastrectomy (LSG) surgery. Seventy-four patients who underwent LSG surgery and met the inclusion and exclusion criteria were included in this study. Serum LCN2, thyroid function, and metabolic and anthropometric parameters were assessed. Weight reduction was expressed as %EWL and percent total weight loss (%TWL) at 3 months and 1 year post surgery. Multivariable logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to evaluate predictors of ≥ 75%EWL.ResultsIn our cohort, %EWL and %TWL were both strongly associated with preoperative serum LCN2 levels. The binary logistic regression analysis showed that preoperative LCN2, waist circumference, and glycated hemoglobin were independent predictors of excellent weight loss.ConclusionsBased on these results, we determined a new P index with better predictive value for excellent weight reduction (≥ 75%EWL) 1 year after LSG surgery.Graphical abstract

Effects of Tele-Exercise on Body Weight, Body Mass Index, and Fat Mass of Obese Employees

Purpose: Obesity is a growing health problem in Indonesia caused by physical inactivity. Meanwhile, employees are a group that is susceptible to obesity as they often have limited time while working sedentarily in front of a desk or computer, especially during the COVID-19 pandemic. This causes risks of many cardiovascular diseases, obesity and can indirectly cause death. Tele-exercise, a live online video exercise, may be the solution to this problem. Therefore, the purpose of this study is to analyse the effects of tele-exercise on body weight, BMI, and fat mass percentage as indicators of obesity. Methods: The research was conducted from July 2020 to January 2021 according to the policy regarding the pandemic. Also, it used a pre-post quasy experimental design. A total of 39 subjects were given tele-exercise involving 2 strength training and 1 cardio training per week for 3 months. Findings: Subsequently, the results showed that exercise had a significant effect (p&lt;0.05) on BMI and body weight, while fat mass percentage only decreased significantly (p&lt;0.05) from the second to third assessment. Originality: To our knowledge, this is the first study analysing the effects of tele-exercise on obese employee’s body weight, body mass index and fat mass. Conclusion: This proves that tele-Exercise is an effective therapy for obesity that does not require a large space, and has beneficial online aspects, especially during the pandemic. The timing of measurement and hydration status should be considered to assess the body composition.

Glucagon-like Peptide-1 Receptor Analogues for the Treatment of Obesity.

There is an increasing prevalence of obesity worldwide, associated with significant morbidity and mortality, which frequently reduces quality of life and life expectancy. Consequently, there is a substantial and growing personal and economic burden necessitating the development of more effective therapies for obesity. Glucagon-like peptide-1 receptor analogues (GLP-1RAs) are licensed for the treatment of type 2 diabetes (T2D), and there is substantial evidence that these drugs not only improve cardiovascular outcomes but also promote weight loss. More recent evidence supports the use of the GLP-1RAs liraglutide and semaglutide in people with obesity without T2D. This article discusses the results of the major cardiovascular outcome trials for GLP-1RAs in people with T2D, the SCALE Obesity and Prediabetes study (Effect of liraglutide on body weight in non-diabetic obese subjects or overweight subjects with co-morbidities: SCALE™ - Obesity and Pre-diabetes; ClinicalTrials.gov identifier: NCT01272219; investigating liraglutide) and the STEP studies (Semaglutide treatment effect in people with obesity; assorted studies; investigating subcutaneous semaglutide). We also highlight the importance of a cost-effective approach to obesity pharmacotherapy. Clinicians should consider the use of GLP-1RAs in people with obesity, especially those with T2D or other obesity-related diseases, such as hypertension and dyslipidaemia. Ongoing trials, as well as clinical and cost-effectiveness appraisals, are anticipated over the next 12 months, and their findings may change the current landscape of obesity pharmacotherapy.

Combination gut hormones: prospects and questions for the future of obesity and diabetes therapy.

Obesity represents an important public health challenge for the twenty-first century: globalised, highly prevalent and increasingly common with time, this condition is likely to reverse some of the hard-won gains in mortality accomplished in previous centuries. In the search for safe and effective therapies for obesity and its companion, type 2 diabetes mellitus (T2D), the gut hormone glucagon-like peptide-1 (GLP-1) has emerged as a forerunner and analogues thereof are now widely used in treatment of obesity and T2D, bringing proven benefits in improving glycaemia and weight loss and, notably, cardiovascular outcomes. However, GLP-1 alone is subject to limitations in terms of efficacy, and as a result, investigators are evaluating other gut hormones such as glucose-dependent insulinotropic peptide (GIP), glucagon and peptide YY (PYY) as possible partner hormones that may complement and enhance GLP-1's therapeutic effects. Such combination gut hormone therapies are in pharmaceutical development at present and are likely to make it to market within the next few years. This review examines the physiological basis for combination gut hormone therapy and presents the latest clinical results that underpin the excitement around these treatments. We also pose, however, some hard questions for the field which need to be answered before the full benefit of such treatments can be realised.

Bariatric surgery for the treatment of chronic kidney disease in obesity and type 2 diabetes mellitus.

Bariatric surgery is an effective therapy for obesity, hypertension and type 2 diabetes mellitus that is refractory to maximal medical therapy. Results of long-term cohort studies and emerging evidence from randomized clinical trials have revealed that, in addition to its beneficial effects on weight reduction, blood pressure and metabolic control, bariatric surgery might reduce the incidence and long-term progression of chronic kidney disease (CKD). Preclinical studies have provided experimental verification that bariatric surgery improves key parameters of kidney injury at the functional, structural and ultrastructural levels, and effects a programme of transcriptomic change in the kidney that is coherent with injury resolution. Multiple mechanisms explain these observations, ranging from predictable aspects of risk-factor reduction to some novel and unforeseen renoprotective benefits of surgery. Current evidence therefore supportsthe judicious use of bariatric surgery to treat patients with obesity, diabetes and CKD. Optimizing the benefits of surgery requires careful patient selection and consideration of how to identify and mitigate some of the challenges associated with these surgical procedures.

A rodent model of partial intestinal diversion: a novel metabolic operation.

Metabolic surgery is safe and the most effective therapy for obesity and its co-morbidities. New procedures may allow for better tailoring of metabolic surgery to the individual patient. To evaluate the impact, comparative effectiveness, and mechanisms of the partial intestinal diversion (PID), vertical sleeve gastrectomy (VSG), and the combination of PID and VSG on weight and glucose regulation. University research facility, United States. Three cohorts of high-fat diet-induced obese male rats were randomized to distal PID (DPID), proximal PID (PPID), VSG, VSG and DPID (VSG/DPID), or sham operation (Sham). Animals were followed for 11 (cohort 1) or 10 (cohorts 2 and 3) weeks. Outcomes included weight and composition, food intake, glucose metabolism, lipids, bile acids, and energy balance. Statistical comparisons were performed using Tukey's multiple comparison test applied to analysis of variance. DPID and not PPID resulted in significant weight and body fat reductions relative to Sham. Improved glucose tolerance was seen in all surgical groups though this reached statistical significance for only DPID and VSG compared with Sham. Improvements in baseline glucose and insulin, corresponding insulin resistance, and plasma lipids were noted in DPID compared with Sham. Though the magnitude of weight and body composition changes and metabolic benefit tended to be larger for VSG relative to DPID, it only reached statistical significance for lipids. VSG and VSG/DPID resulted in similar outcomes. Markedly reduced food intake occurred after VSG and more modestly after DPID. Stool caloric content was higher in DPID relative to all groups. DPID is an effective metabolic operation resulting in notable weight and fat loss and metabolic improvement relative to sham-operated rodents. Interestingly, combining VSG with DPID added little additional benefit to the effects of VSG.

Antioxidant-upregulated mesenchymal stem cells reduce inflammation and improve fatty liver disease in diet-induced obesity

BackgroundThe incidence of obesity and diabetes is increasing rapidly. Optimal management is still elusive. Obesity associated with type 2 diabetes is known to cause adipose tissue inflammation, increase oxidative stress, and cause white fat hyperplasia and mitochondrial dysfunction. In this study, we investigated whether mitochondrial and cytosolic antioxidant-upregulated mesenchymal stem cell (MSC) delivery reduces oxidative stress and subsequently improves glucose tolerance, reduce systemic inflammation, and improves fatty liver disease in diet-induced obese (DIO) mouse models.MethodsAntioxidant genes Sod2 (mitochondrial) and catalase (cytosolic) or null (control) were upregulated in human adipose tissue-derived MSCs using adenoviral constructs. Modified MSCs were then delivered intraperitoneally into mice that were fed a 45% or 60% high-fat diet (HFD), and animals were followed for 4 weeks.ResultsOver 4 weeks, body weight remained stable; however, we noted a significant reduction in liver fat content by histological analysis and liver triglyceride assay. Triglyceride assay (p < 0.01) confirmed reduced liver fat accumulation in animals that received either Sod2- or Cat-MSCs. There was a lower plasma level of inflammatory marker TNFα, measured in mice that were fed either 45% or 60% HFD and received Sod2- or Cat-MSCs, indicating reduced systemic inflammation. Ucp1 mRNA was upregulated approximately 100–1000-fold for omental fat and 10–100-fold for pericardial fat compared to the Null-MSC-receiving group. Pcgc1a and Prdm16 mRNA upregulation was also noted particularly for pericardial fat. Glucose tolerance showed a positive improvement trend with a lower area under the curve (AUC) values for both Sod2- and Cat-MSCs groups in comparison to control. For mice fed with 60% HFD and that received Sod2-MSCs, glucose levels were significantly lower than control (*p < 0.05) at a time point of 60 min in the glycemic curve during glucose tolerance test.ConclusionReduction of oxidative stress post-antioxidant-upregulated MSC delivery, intraperitoneally, reduces systemic inflammation and fat accumulation in the liver. There is evidence of an increase in browning of white adipose tissue depots with concomitant improvement of glucose tolerance in a weight-independent fashion. Antioxidant-upregulated MSC delivery may be a safe yet effective therapy for obesity and prediabetes and improves related complication such as non-alcoholic fatty liver disease.

Short-Term Outcomes of Inflammatory Bowel Disease after Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy

Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are the most effective therapies for obesity and may have beneficial effects on the immune system. Therefore, we compared RYGB vs SG outcomes in patients with inflammatory bowel disease (IBD). In this retrospective cohort study, we identified 54 patients with either Crohn's disease (CD; n= 31) or ulcerative colitis (UC; n= 23), diagnosed before bariatric surgery, between 2000 and 2017. Nineteen patients underwent RYGB and 35 patients underwent SG. Patients presenting for RYGB and SG were of similar age (46.2 ± 9.5 years vs 47.2 ± 12.3 years), preoperative BMI (48.5 ± 7.7 kg/m2 vs 44.9 ± 7.3 kg/m2) and IBD status, as measured by medications. Both operations led to significant weight loss at 1 year. After RYGB and SG, there were no significant differences in the proportion of patients with UC who had improved (27% vs 8%), unchanged (64% vs 92%), or worse (9% vs 0%) IBD medication requirements, respectively. Similar analysis in the patients with CD showed no significant differences in the proportion who had improved (37.5% vs 44%), or unchanged (25% vs 52%) IBD-medication requirements after RYGB and SG, respectively. However, there was a significant difference in the proportion of patients who had worsened CD after RYGB compared with SG (37.5% vs 4%; p= 0.016). There was a greater rate of surgical complications after RYGB compared to SG (26% vs. 3%; p= 0.02). A sizable proportion of patients experienced improvements in IBD post-bariatric surgery. However, in CD patients, RYGB was associated with a significantly greater number of patients with increased IBD-medication requirements. Sleeve gastrectomy led to less weight loss, but had a lower rate of severe complications compared with RYGB. In patients with IBD, and particularly CD, SG may be the safer surgery.

Is bromocriptine an effective therapy for obesity?

EVIDENCE-BASED ANSWER Probably not. Over about a week, bromocriptine does not decrease percent body fat or body weight compared with placebo (SOR: C, small placebo-controlled crossover study). Bromocriptine is associated with decreased percent body fat and body weight after 6 weeks, but no difference is found at 6 to 8 months (SOR: C, small case series).

Five-Year Glycemic and Metabolic Outcomes after Bariatric Surgery in an Asian Population with Type 2 Diabetes

Background: Metabolic-bariatric surgery (MBS) leads to durable weight loss and significant metabolic improvement in type 2 diabetes mellitus (T2DM) patients with obesity. However, data on durability of control is often lacking in Asia. Aim: We report 5-year glycemic and metabolic outcomes in a T2DM cohort who had MBS from 2008-2012 at a tertiary center in Singapore. Methodology: Patient demographics and biochemical parameters were retrieved from a web-based data repository. DM remission was defined as HbA1c ≤6% without DM medications. Results: There were 59 patients with a mean age of 43.0±9.5 years and 37.3% were males (Table 1). Most (76.3%) had gastric bypass while 23.7% had sleeve gastrectomy. Baseline mean weight and BMI were 114.4±27.4 kg and 42.5±10.5 kg/m2 respectively. Mean weight loss of 26% was achieved at 1 year and sustained over 5 years. Mean HbA1c decreased from 8.3% to 5.8% and 6.3% at 1 and 5 years respectively, with use of fewer DM, anti-hypertensive and lipid-lowering medications. At 5 years, 18 of 43 (41.9%) patients achieved sustained remission of diabetes with 6 (14.0%) having relapse of DM after initial remission at 1 year. Conclusion: MBS is effective therapy for obesity and DM with durable glycemic and metabolic control associated with lower medication use over 5 years in this Asian population.Table 1. Characteristics of subjects at baseline and over 5-year follow upPatient characteristicsPre-surgery (n=59)12 months (n=47)24 months (n=40)36 months (n=37)48 months (n=38)60 months (n=43)GenderMaleFemale22(37.3%)37(62.7%)NANANANANAAge (years)43.0 ± 9.5NANANANANAEthnicityChineseMalayIndianOther24 (40.7%)20 (33.9%)14 (23.7%)1 (1.7%)NANANANANADiabetes mellitus duration (months)92.1±96.3NANANANANATypes of surgerySleeve gastrectomyMini gastric bypassRoux-en-Y gastric bypass14(23.7%)16(27.1%)29(49.2%)NANANANANAWeight (kg)114.4±27.484.9±20.5*84.5±21.0*87.5±23.0*83.0±19.9*83.8±21.5*Body Mass Index (BMI) (%)42.5±10.531.9±8.3*31.3±7.4*32.5±8.2*31.3±8.06*32.0±8.67*Systolic blood pressure (mmHg)127.0±14.6125.6±17.3125.8±18.2130.2±17.7129.7±13.3135.4±19.2Diastolic blood pressure (mmHg)77.0±9.577.5±11.878.3±10.880.5±8.778.8±10.775.8±8.7Fasting blood glucose (mmol/L)8.51±3.125.51±1.93*5.99±2.11*6.59±2.57*6.72±2.51*6.73±2.55*HbA1c (%)8.32±1.385.82±0.82*6.09±1.09*6.51±1.31*6.53±1.11*6.32±1.02*Lipid panel (mmol/L)Total cholesterolLDLTriglycerideHDL4.56±0.882.75±0.811.69±0.741.05±0.264.77±0.942.83±0.611.19±0.56*1.32±0.29*4.81±0.77*2.84±0.731.30±0.51*1.46±0.54*4.79±0.86*2.78±0.701.42±0.68*1.37±0.32*4.54±0.912.52±0.801.41±0.76*1.38±0.28*4.17±0.522.28±0.451.30±0.70*1.30±0.28*Number of DM medications1.90±1.030.42±0.79*0.31±0.68*0.45±0.93*0.57±1.10*0.60±1.19*Antihypertensive medications1.64±1.210.42±0.70*0.39±0.72*0.37±0.79*0.40±0.83*0.45±0.95*Lipid-lowering medications0.81±0.570.17±0.38*0.25±0.44*0.31±0.50*0.27±0.49*0.33±0.51*Diabetes remission (n)NA2824121218Continuous data as mean ± SD; categorical data as n (%)* Presence of significant difference when compared to pre-surgery data (p&amp;lt;0.05) Disclosure Z. Liew: None. A. Maung: None. S. Ganguly: Advisory Panel; Self; Novo Nordisk Inc.. P. Lee: None. K. Tham: None.

Experience with FreeStyle Libre Flash glucose monitoring system in management of refractory dumping syndrome in pregnancy shortly after bariatric surgery.

Bariatric surgery is an effective therapy for obesity but is associated with long-term complications such as dumping syndromes and nutritional deficiencies. We report a case of a 26-year-old caucasian female, with history of morbid obesity and gestational diabetes (GDM), who became pregnant 4 months after Roux-en-Y bypass surgery. She developed GDM during subsequent pregnancy, which was initially managed with metformin and insulin. Nocturnal hypoglycaemia causing sleep disturbance and daytime somnolence occured at 19 weeks of pregnancy (19/40). Treatment with rapid-acting carbohydrates precipitated further hypoglycaemia. Laboratory investigations confirmed hypoglycaemia at 2.2 mmol/L with appropriately low insulin and C-peptide, intact HPA axis and negative IgG insulin antibodies. The patient was seen regularly by the bariatric dietetic team but concerns about compliance persisted. A FreeStyle Libre system was used from 21/40 enabling the patient a real-time feedback of changes in interstitial glucose following high or low GI index food intake. The patient declined a trial of acarbose but consented to an intraveneous dextrose infusion overnight resulting in improvement but not complete abolishment of nocturnal hypoglycaemia. Hypoglycaemias subsided at 34/40 and metformin and insulin had to be re-introduced due to high post-prandial blood glucose readings. An emergency C-section was indicated at 35 + 1/40 and a small-for-gestational-age female was delivered. There have been no further episodes of hypoglycaemia following delivery. This case illustrates challenges in the management of pregnancy following bariatric surgery. To our knowledge, this is the first use of FreeStyle Libre in dumping syndrome in pregnancy following bariatric surgery with troublesome nocturnal hypoglycaemia.Learning points:Bariatric surgery represents the most effective treatment modality in cases of severe obesity. With increasing prevalence of obesity, more people are likely to undergo bariatric procedures, many of which are women of childbearing age.Fertility generally improves after bariatric surgery due to weight reduction, but pregnancy is not recommended for at least 12–24 months after surgery. If pregnancy occurs, there are currently little evidence-based guidelines available on how to manage complications such as dumping syndromes or gestational diabetes (GDM) in women with history of bariatric surgery.Diagnosis of GDM relies on the use of a 75 g oral glucose tolerance test (OGTT). The use of this test in pregnant women is not recommended due to its potential to precipitate dumping syndrome. Capillary glucose monitoring profiles or continuous glucose monitoring (CGM) is being currently discussed as alternative testing modalities.As the CGM technology becomes more available, including the recently introduced FreeStyle Libre Flash glucose monitoring system, more pregnant women, including those after bariatric surgery, will have access to this technology. We suggest urgent development of guidelines regarding the use of CGM and flash glucose monitoring tools in these circumstances and in the interim recommend careful consideration of their use on a case-to-case basis.

Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system. Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities. Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).

Bariatric surgery and long-term nutritional issues.

Bariatric surgery is recognized as a highly effective therapy for obesity since it accomplishes sustained weight loss, reduction of obesity-related comorbidities and mortality, and improvement of quality of life. Overall, bariatric surgery is associated with a 42% reduction of the cardiovascular risk and 30% reduction of all-cause mortality. This review focuses on some nutritional consequences that can occur in bariatric patients that could potentially hinder the clinical benefits of this therapeutic option. All bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal tract; this alteration makes these patients more susceptible to developing nutritional complications, namely, deficiencies of macro- and micro-nutrients, which could lead to disabling diseases such as anemia, osteoporosis, protein malnutrition. Of note is the evidence that most obese patients present a number of nutritional deficits already prior to surgery, the most important being vitamin D and iron deficiencies. This finding prompts the need for a complete nutritional assessment and, eventually, an adequate correction of pre-existing deficits before surgery. Another critical issue that follows bariatric surgery is post-operative weight regain, which is commonly associated with the relapse of obesity-related co-morbidities. Nu-tritional complications associated with bariatric surgery can be prevented by life-long nutritional monitoring with the administration of multi-vitamins and mineral supplements according to the patient’s needs.