Faculty Bibliography

Cost-effective therapies to address the growing epidemic of obesity are a leading priority in modern medicine. Intragastric balloons (IGBs) are one such option, with increased effectiveness compared with pharmacotherapy and lifestyle and a lower rate of adverse events than bariatric surgery. IGBs are endoscopically placed or swallowed space-occupying devices in the stomach. Three IGB systems were approved in 2015 to 2016 by the Food and Drug Administration for use in the United States, with more devices nearing approval. This paper reviews the adverse events and efficacy of IGBs, and practice setup, management of common complications, and dietary advice for patients.

ObjectivesTherapies less invasive than surgery and more effective than lifestyle and pharmacotherapy are needed to contend with the obesity epidemic. Intragastric balloons (IGBs) are a minimally invasive endoscopic weight loss method recently approved for use in the US. The purpose of the study is to assess the effect of IGBs on metabolic outcomes associated with obesity.MethodsMEDLINE, Embase, and Cochrane Database were searched through July 2016. Dual extraction and quality assessment of studies using Cochrane risk of bias tool were performed independently by two authors. Primary outcomes included the change from baseline in metabolic parameters. Secondary outcomes included resolution and/or improvement in metabolic co-morbidities and association with baseline parameters.Results10 randomized controlled trials (RCT) and 30 observational studies including 5,668 subjects were analyzed. There was moderate-quality evidence for improvement in most metabolic parameters in subjects assigned to IGB therapy as compared to conventional non-surgical therapy in RCTs: mean difference (MD) in fasting glucose change: -12.7 mg/dl (95% confidence interval (CI) -21.5, -4); MD in triglycerides: -19 mg/dl (95% CI -42, 3.5); MD in waist circumference: -4.1 cm (95% CI -6.9, -1.4); MD in diastolic blood pressure: -2.9 mm Hg (95% CI -4.1, -1.8). The odds ratio for diabetes resolution after IGB therapy was 1.4 (95% CI 1.3, 1.6). The rate of serious adverse events was 1.3%.ConclusionsIGBs are more effective than diet in improving obesity-related metabolic risk factors with a low rate of adverse effects, however the strength of the evidence is limited given the small number of participants and lack of long-term follow-up.Am J Gastroenterol advance online publication, 24 January 2017; doi:10.1038/ajg.2016.530.

BACKGROUND: Intragastric balloons (IGBs) are safe and effective in inducing weight loss in obese patients. The objective of this study was to review and analyze the available data of the effect of IGB on markers of nonalcoholic fatty liver disease (NAFLD) and liver enzymes. METHODS: Searches were performed of MEDLINE and Embase databases from inception through January 2016. Study inclusion criteria were the following: >/=5 overweight or obese adult patients undergoing intragastric balloon placement, with liver tests [alanine aminotransferase (ALT) or gamma-glutamyl transpeptidase (GGT)] or markers of NAFLD (e.g., imaging, biopsy) reported before balloon insertion and after balloon removal at 6 months. RESULTS: Nine observational studies and one randomized trial were identified. ALT decreased by -10.02 U/l (95 % CI, -13.2, -6.8), GGT decreased by -9.82 U/l (95 % CI, -12.9, -6.8), and BMI decreased by -4.98 kg/m2 (-5.6, -4.4) with IGB therapy. Hepatic steatosis improved from baseline after 6 months of balloon therapy by magnetic resonance imaging (fat fraction, 16.7 +/- 10.9-7.6 +/- 9.8, p = 0.003), ultrasound (severe liver steatosis, 52-4 %, p < 0.0001). Histological NAFLD activity score was lower after 6 months of IGB versus control with sham endoscopy and diet (2 +/- 0.75 vs. 4 +/- 2.25, p = 0.03). CONCLUSION: The use of intragastric balloon decreases liver enzymes and is potentially an effective short-term treatment for NAFLD as part of a multidisciplinary approach. Larger, more rigorous trials are needed to confirm the effect of IGBs on NAFLD.

Although mutations in the Wnt/beta-catenin signaling pathway are linked with the metabolic syndrome and type 2 diabetes in humans, the mechanism is unclear. High-fat-fed male C57BL/6 mice were treated for 4 wk with a 2'-O-methoxyethyl chimeric antisense oligonucleotide (ASO) to decrease hepatic and adipose expression of beta-catenin. beta-Catenin mRNA decreased by approximately 80% in the liver and by 70% in white adipose tissue relative to control ASO-treated mice. beta-Catenin ASO improved hepatic insulin sensitivity and increased insulin-stimulated whole body glucose metabolism, as assessed during hyperinsulinemic-euglycemic clamp in awake mice. beta-Catenin ASO altered hepatic lipid composition in high-fat-fed mice. There were reductions in hepatic triglyceride (44%, P < 0.05) and diacylglycerol content (60%, P < 0.01) but a 30% increase in ceramide content (P < 0.001). The altered lipid content was attributed to decreased expression of sn-1,2 diacylglycerol acyltransferase and mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase and an increase in serine palmitoyl transferase. The decrease in cellular diacyglycerol was associated with a 33% decrease in PKCepsilon activation (P < 0.05) and 64% increase in Akt2 phosphorylation (P < 0.05). In summary, Reducing beta-catenin expression decreases expression of enzymes involved in hepatic fatty acid esterification, ameliorates hepatic steatosis and lipid-induced insulin resistance.-Popov, V. B., Jornayvaz, F. R., Akgul, E. O., Kanda, S., Jurczak, M. J., Zhang, D., Abudukadier, A., Majumdar, S. K., Guigni, B., Petersen, K. F., Manchem, V. P., Bhanot, S., Shulman, G. I., Samuel, V. T. Second-generation antisense oligonucleotides against beta-catenin protect mice against diet-induced hepatic steatosis and hepatic and peripheral insulin resistance.