Subsequent Weight Loss Research Articles

Bidirectional Relationships Between Weight Change and Sleep Apnea in a Behavioral Weight Loss Intervention

ObjectiveTo examine the bidirectional relationship between weight change and obstructive sleep apnea (OSA) in the context of a behavioral weight loss intervention. Patients and MethodsAdults who were overweight or obese (N=114) participated in a 12-month behavioral weight loss intervention from April 17, 2012, through February 9, 2015. The apnea-hypopnea index (AHI), a marker of the presence and severity of OSA, was assessed at baseline, 6 months, and 12 months. Linear mixed models evaluated the effect of weight change on the AHI and the effect of OSA (AHI ≥5) on subsequent weight loss. Secondary analyses evaluated the effect of OSA on intervention attendance, meeting daily calorie goals, and accelerometer-measured physical activity. ResultsAt baseline, 51.8% of the sample (n=59) had OSA. Adults who achieved at least 5% weight loss had an AHI reduction that was 2.1±0.9 (adjusted mean ± SE) events/h greater than those with less than 5% weight loss (P<.05). Adults with OSA lost a mean ± SE of 2.2%±0.9% less weight during the subsequent 6-month interval compared with those without OSA (P=.02). Those with OSA were less adherent to daily calorie goals (mean ± SE: 25.2%±3.3% vs 34.8%±3.4% of days; P=.006) and had a smaller increase in daily activity (mean ± SE: 378.3±353.7 vs 1060.1±377.8 steps/d; P<.05) over 12 months than those without OSA. ConclusionBehaviorally induced weight loss in overweight/obese adults was associated with significant AHI reduction. However, the presence of OSA was associated with blunted weight loss, potentially via reduced adherence to behaviors supporting weight loss. These results suggest that OSA screening before attempting weight loss may be helpful to identify who may benefit from additional behavioral counseling.

Initial Beta-Hydroxybutyrate Elevation in Relation to Subsequent Weight Loss in Type 2 Diabetes via the SGLT2 Inhibitor Tofogliflozin

The elevation of ketones is clinically concerned in the use of SGLT2 inhibitor (SGLT2i), however little is known about the association between that elevation and subsequent clinical process. We aimed to clarify the association of the initial beta-hydroxybutyrate (BHB) elevation via the SGLT2i, tofogliflozin with subsequent weight loss in type 2 diabetes participants. Analyzed were 774 type 2 diabetes participants who received tofogliflozin in two phase 3 studies. The participants were divided into four groups according to the quartiles for their change in BHB after 4 weeks of tofogliflozin therapy. The adjusted assessments of variables were analyzed using an analysis of covariance model with the quartiles, their baseline values, age, sex, and eGFR as covariates. BHB levels significantly increased (mean: +107.1 µmol/L) from baseline to week 4. Those changes in the first (Q1), second (Q2), third (Q3), and fourth (Q4) quartiles, respectively, were -33.7, +31.4, +98.0, and +331.1 µmol/L. Glycemic control at baseline was poorer, while CPI was lower within the higher quartiles. The difference of BHB changes among the quartiles was maintained during tofogliflozin therapy. At week 52, the increase of BHB levels from baseline was significant (+142.7 µmol/L) in Q4, but not changed in Q1. The weight loss at week 52 in Q4 (least square mean: -3.6 kg) was greater than in Q1 (-2.4 kg) although the improvement of hyperglycemia was identical. Furthermore, the reduction in waist circumference and increase in adiponectin were greater in Q4. And the increase in fasting free fatty acid was also greater in Q4, but not changed in Q1. The distinct response of BHB elevation was observed early after the SGLT2i, tofogliflozin therapy. The higher initial BHB elevation resulted in the greater reduction in body weight, especially fat mass via lipolysis. The progressive weight loss might be clinically associated with one of the signs of the higher ketone elevation. Disclosure Y. Sato: None. K. Nunoi: None. K. Kaku: Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation, MSD K.K.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Ono Pharmaceutical Co., Ltd.. Advisory Panel; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Speaker's Bureau; Self; Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceuticals, Japan Inc., Kowa Pharmaceuticals, Japan Inc.. Advisory Panel; Self; Astellas, Japan Inc. A. Yoshida: Employee; Self; Kowa Pharmaceutical Co. Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd..

Effect of laparoscopic sleeve gastrectomy on metabolic and nutritional changes at King Abdulaziz University Hospital, Saudi Arabia

Introduction: Bariatric surgery has been shown to be the most effective way to treat obesity. The outcome of weight-loss surgeries primarily focuses on reducing weight, and improving comorbidities and quality of life of patients. Postoperative nutritional deficiencies are well known complications of sleeve gastrectomy. Deficiencies of protein, iron, and vitamins B12 and D are often reported and may occur despite supplementation. Aim: The aim of this study was to assess the effect of laparoscopic sleeve gastrectomy on metabolic and nutritional changes among obese patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. Methods and Subjects: This is a retrospective review of patients who underwent sleeve gastrectomy surgery between January 2013 and January 2016 at KAUH, Jeddah, Saudi Arabia. Perioperative characteristics, biochemical profile [glycated hemoglobin (HbA1c), calcium, parathyroid (PTH), albumin, B12, lipid, and iron profile], and details on subsequent weight loss in terms of body mass index (BMI) and weight loss (kg) of the patients were obtained. Results: Sixty-six patients were included in the study. Forty-two (63.4%) were female with a mean age of 35.1 ± 10.3 years. Our results demonstrated a significant statistical reduction in weight and BMI with improvement in HbA1c, high-density lipoprotein, triglycerides, and low-density lipoprotein, and decrease in cholesterol level. On the contrary, other metabolic elements such as ferritin and vitamin B12 showed a significant decrease, whereas calcium, PTH hormone, and albumin showed no change. Conclusion: This study showed that sleeve gastrectomy had significant improvements of some biochemical markers in addition to reduction in weight and BMI.

Effect of body thickness on helical and direct treatment delivery modes: a phantom study.

Objective: Chemoradiation therapy is among the standard treatments for cancer, which often causes a decrease in appetite and subsequent weight loss. When weight loss occurs during treatment, the external body contour changes from that indicated during initial planning, causing changes in dose distribution to the target tumor regions and organs at risk (OARs). This study aimed to examine the dose changes to both the target regions and OARs, based on the dose-volume histogram (DVH).Methods: We established a 60 mm-diameter planning target volume (PTV) and a 30 mm-diameter rectum region of interest (OAR), using a phantom; this was followed by a 50 Gy/25 fraction irradiation to the target region that was measured using a two-dimensional-array ion chamber device. The measurement was conducted by varying the bolus thickness from 0 to −25 mm, in 5 mm decrements. In addition, the maximum dose for both PTV and OAR were evaluated based on the DVH, created using the Adaptive software.Results: The gamma analysis showed that the pass rate was less than 95% when the bolus thickness was altered by −25 mm for the helical delivery mode and by −10 mm for the direct delivery mode, resulting in a dose error greater than 3%. Results of the DVH evaluation revealed that the maximum dose of PTV increased by 5.18% when the bolus thickness was −25 mm for helical delivery, whereas a 9.95% increase was noted for the direct delivery mode compared with the dose at the reference level of 0 mm bolus thickness.Discussion: Our results suggest that it is necessary to formulate a new treatment plan owing to increased dose error, if the body thickness decreases by more than 20 mm and 10 mm for the helical and direct delivery modes, respectively. The results also demonstrate that helical delivery is less affected by changes in body thickness than direct delivery.

New Treatment Option for Autoimmune Enteropathy: A Rare Case of Intractable Diarrhea Treated with Vedolizumab

Autoimmune enteropathy is an uncommon cause of chronic diarrhea rarely seen in adults. The disease is secondary to an autoimmune process in the gut that leads to villous blunting and subsequent watery diarrhea, abdominal pain, and severe weight loss. The disease has only been described in 37 adults prior to our case, and variable treatment success has been documented with steroids, immunomodulators, and TNF-a inhibitors. This case is the first to show success in treating autoimmune enteropathy with vedolizumab and provides physicians with an additional therapeutic option when limited by a patient's comorbidities and side effects of other drugs.

New Treatment Option for Autoimmune Enteropathy: A Rare Case of Intractable Diarrhea Treated with Vedolizumab

Autoimmune enteropathy is an uncommon cause of chronic diarrhea rarely seen in adults. The disease is secondary to an autoimmune process in the gut that leads to villous blunting and subsequent watery diarrhea, abdominal pain, and severe weight loss. The disease has only been described in 37 adults prior to our case, and variable treatment success has been documented with steroids, immunomodulators, and TNF-a inhibitors. This case is the first to show success in treating autoimmune enteropathy with vedolizumab and provides physicians with an additional therapeutic option when limited by a patient's comorbidities and side effects of other drugs.

"Memory bias" for recall of experiences during initial weight loss is affected by subsequent weight loss outcome.

Research has suggested that memories of mood, emotions, and behaviors are not purely unbiased retrieval, but more similar to reconstructions based on current opinions, positive or negative experiences associated with the memory, and how a person believes they would have felt, thought, or acted. We investigated this memory bias in 66 adult participants with overweight/obesity who rated their mood, emotions, and behaviors during a 12-week, Internet-based behavioral weight loss program and later recalled these ratings at Month 3 (immediate post-test) and Month 12 (follow-up). At Month 3, participants recalled the intervention more positively than reported previously, p=.010, but reported remembering the intervention more negatively at the Month 12 follow-up, p=.004. Memory bias was associated with initial weight loss and regain, ps<.05, such that participants who lost more weight at Month 3 remembered their mood, emotions, and behaviors during intervention more positively, and those who regained more weight at Month 12, more negatively. Future research should investigate whether this bias is associated with willingness to re-engage with intervention.

Difficult to Swallow: A Case of Dysphagia Lusoria

The term Dysphagia Lusoria, which stands for “freak of nature,” was coined by Bayford in 1794, which he used to describe dysphagia in an elderly woman who died of esophageal obstruction and subsequent weight loss as a result of the aberrant right subclavian retro-esophageal artery. CASE REPORT: A 65-year-old male presented to the ED with a nonproductive cough for one month and difficulty swallowing solids for one week. The patient stated the cough was initially intermittent and dry in nature and progressed in persistency with a noticeable dysphagia to solid foods. He said that he had lost about 10 pounds since the onset of solid food dysphagia. He denied progression of dysphagia to liquid. His past medical history was significant for asbestos exposure and he had a 5 pack year smoking history with continued episodic alcohol intake of 12 beers per week. The patient was subsequently admitted to the hospital and an esophagram was performed which revealed an aberrant right subclavian artery impression in the posterior wall of esophagus. General surgery was consulted and an EGD was performed that showed gastritis and duodenitis and the patient was started on a PPI and sucralfate. Vascular surgery was also consulted for the suspected aberrant right subclavian and recommended a CTA chest which was consistent with aberrant right subclavian artery, as well as calcified pleural plaques. No surgical intervention was recommended. The patient was counseled on smoking and alcohol abuse and educated about his condition causing dysphagia. DISCUSSION: In the majority of cases, dysphagia lusoria is asymptomatic or presents with mild dysphagia. A small minority of adult patients, however, have a severe symptoms leading to an inability to swallow and subsequent malnutrition. Hence, the coined name dysphagia lusoria. In children, it can present as stridor and repeated chest infections due to tracheal softening, whereas in adults, it presents mainly with difficulty in swallowing and in severe cases, failure to thrive. Due to nonspecificity of the symptoms and nondiagnostic endoscopy in most of the cases, the diagnosis of dysphagia lusoria can be challenging. For mild to moderate symptomology, lifestyle modifications including changes in diet and reassurance are recommended. More severe cases require surgical ntervention. Dysphagia lusoria, although a rare cause of symptomatic dysphagia, is a diagnosis that should be considered due to its difficulty of confirmation.Figure: Barium swallow showing impression in the posterior wall of upper thoracic esophagus at cervicothoracic junction area correlating with vascular impression from the aberrant right subclavian artery.Figure: Sagittal view of CTA scan showing aberrant subclavian artery compressing the esophagus.Figure: Axial view of CTA scan showing aberrant subclavian artery compressing the esophagus.

Variability in Weight Change Early in Behavioral Weight Loss Treatment: Theoretical and Clinical Implications.

ObjectiveResponse early in weight loss treatment predicts long-term weight change. Weight variability, independent of absolute early weight change, may also relate to long-term outcomes. This study examined whether weight variability early in treatment predicted later weight loss and maintenance.MethodsParticipants were 183 completers of a yearlong behavioral weight loss program (M age = 51, 81% female, 69% white, M body mass index = 35 kg/m2). Weight variability was calculated using weights from the first 6 and 12 weekly treatment sessions. Multiple linear regressions examined whether weight variability predicted subsequent weight change 6, 12, and 24 months later.ResultsWeight variability over 6 and 12 weeks predicted less subsequent weight loss at 12 (6-week: β = 0.18, p = 0.02; 12-week: β = 0.33, p < 0.01) and 24 (6-week: β = 0.17, p = 0.03; 12-week: β = 0.15, p = 0.05) months. Relationships held adjusting for covariates. Weight variability was more strongly associated with 6-month weight change in men than women (β = 0.27, p = 0.01).ConclusionsElevated weight variability early in a weight loss program predicted poor long-term outcomes, possibly reflecting inconsistent weight control behaviors. Tracking weight variability could prove useful for improving treatment outcome.

Longitudinal impact of weight misperception and intent to change weight on body mass index of adolescents and young adults with overweight or obesity

ObjectiveAccurate perception of one's weight status is believed to be necessary to motivate weight loss intention and subsequent weight loss among those with overweight/obesity. This proposed pathway, however, is understudied in longitudinal research. This study examined the indirect effect of weight change intention on the relationship between weight status perception and BMI change among adolescents with overweight/obesity. MethodsParticipants included 2664 adolescents with overweight/obesity (52% female) from the National Longitudinal Study of Adolescent Health. Longitudinal associations between Wave II weight status perception (accurate versus misperception) and intent to change weight (i.e., gain, lose, stay the same) on BMI change (Wave II–Wave IV) were examined using multiple linear regression. Indirect effects of weight change intention were investigated using the Monte Carlo method. Analyses were stratified by gender. ResultsAccurate perceivers (81.0% female; 60.1% male) were more likely than misperceivers (i.e., perception of “about the right weight”) to report weight loss intention (p<0.001). Among females, weight status misperception and weight loss intention individually were associated with smaller (β=−1.37, 95% CI [−2.64, −0.10]) and greater (β=1.18, 95% CI [0.11, 2.25]) BMI gains, respectively. Among males, fully adjusted models suggested that weight status misperception was associated with significantly smaller gains in BMI over time (β=−1.51, 95% CI [−2.38, −0.63]). Weight change intention did not emerge as an indirect effect for either gender. ConclusionsAlthough weight status misperception was protective against weight gain, weight change intention did not provide an explanation for this relationship.

Hypoxia-Related Hormonal Appetite Modulation in Humans during Rest and Exercise: Mini Review.

Obesity is associated with numerous chronic ailments and represents one of the major health and economic issues in the modernized societies. Accordingly, there is an obvious need for novel treatment approaches. Recently, based on the reports of reduced appetite and subsequent weight loss following high-altitude sojourns, exposure to hypoxia has been proposed as a viable weight-reduction strategy. While altitude-related appetite modulation is complex and not entirely clear, hypoxia-induced alterations in hormonal appetite modulation might be among the key underlying mechanisms. The present paper summarizes the up-to-date research on hypoxia/altitude-induced changes in the gut and adipose tissue derived peptides related to appetite regulation. Orexigenic hormone ghrelin and anorexigenic peptides leptin, glucagon-like peptide-1, peptide YY, and cholecystokinin have to-date been investigated as potential modulators of hypoxia-driven appetite alterations. Current evidence suggests that hypoxia can, especially acutely, lead to decreased appetite, most probably via reduction of acylated ghrelin concentration. Hypoxia-related short and long-term changes in other hormonal markers are more unclear although hypoxia seems to importantly modulate leptin levels, especially following prolonged hypoxic exposures. Limited evidence also suggests that different activity levels during exposures to hypoxia do not additively affect hormonal appetite markers. Although very few studies have been performed in obese/overweight individuals, the available data indicate that hypoxia/altitude exposures do not seem to differentially affect appetite regulation via hormonal pathways in this cohort. Given the lack of experimental data, future well-controlled acute and prolonged studies are warranted to expand our understanding of hypoxia-induced hormonal appetite modulation and its kinetics in health and disease.

Type 2 Diabetes Mellitus in Children and Adolescents: An update

Childhood type 2 Diabetes Mellitus (DM) has increasingly been reported worldwide. It is commonly associated with childhood obesity.It may be presented with classical manifestation of DM such as polyuria, polydipsia, weight lossor acute complications like Diabetic ketoacidosis (DKA), Hyperglycemic Hyperosmolar State (HHS) or features of insulin resistance syndrome. Many a cases it may remain asymptomatic and hence undiagnosed.So,overweight children and adolescents who met screening criteria such as family history of type 2 DM, signs of insulin resistance, and high risk ethnics should undergo screening. Emphasis should be given on early diagnosis and optimum management plan to avoid grave consequences of it in early part of life. Diagnosis of type 2 Diabetes Mellitus in children should be done on the basis of standard diagnostic criteria such as American Diabetic Association (ADA) criteria. Both non-pharmacological and drug management are important equally. Multidisciplinary team approach including self-management plan is mandatory for obtaining optimal therapeutic goals of type 2 DM in children and adolescents. Lifestyle modification, dietary intervention, weight reduction, patient education, psychological support, and oral anti diabetic drugs and insulin therapy should be included in comprehensive diabetic management plan. Complications of type 2 DM should be minimized by all means with strict glycemic control and management of co-morbidity if any. Emphasis should also be given on prevention of type 2 DM by adopting a healthy lifestyle characterized by healthy eating behavior, regular physical activity and subsequent modest weight loss that can prevent the progression of impaired glucose tolerance to clinical diabetes mellitus.J Bangladesh Coll Phys Surg 2017; 35(1): 24-30

Conventional influenza vaccines influence the efficacy of a candidate universal influenza vaccine in mice

Abstract Universal influenza vaccines are designed to protect against diverse strains of influenza virus. In a pandemic, universal vaccines could be life-saving. Candidate vaccines are usually tested in naïve animals, despite intended use in the human population that has a varied immune history, including responses to vaccination. To be more relevant to humans, we tested a candidate universal influenza vaccine in mice with a history of conventional vaccination. Female BALB/c mice were given two intramuscular doses of inactivated influenza vaccine (IIV) or diphtheria and tetanus toxoids vaccine (DT), one month apart. Another group had two intranasal (i.n.) doses of live attenuated influenza virus (LAIV). One month after the second dose, mice were given the universal vaccine, recombinant adenoviruses expressing influenza A NP and M2 (rAd-NP+M2, i.n.). Antibody responses to universal vaccine antigens NP and M2 were assessed by ELISA. T-cell responses to antigens were determined by IFN-γ ELISPOT. Mice were challenged with mouse-adapted A/FM/1/47 (H1N1) and subsequent weight loss determined rAd-NP+M2 efficacy. Efficacy was enhanced, inhibited or unaffected by prior history. Mice given Afluria IIV and LAIV lost less weight and had a greater antibody and T-cell response to NP than mice without prior vaccination, which are examples of enhanced rAd-NP+M2 efficacy. Inhibited vaccine efficacy was observed in mice that received Fluvirin IIV and mice had low IgG2a antibodies to NP and M2. Fluzone IIV and DT had no effect on rAd-NP+M2 efficacy. This study demonstrates that the protection by the universal influenza vaccine may be affected by a history of conventional vaccination, and suggests that performance in humans would be influenced by immune history.

Abstract MP089: Sleep Apnea is Reduced Following a Behavioral Weight Loss Intervention but Impedes Weight Loss Outcomes

Introduction: Several trials have documented that behavioral weight loss interventions reduce obstructive sleep apnea (OSA) severity. However, despite the known bidirectional association between body weight and OSA severity, few studies have addressed whether the presence of OSA impedes weight loss outcomes in a lifestyle intervention. Hypothesis: We hypothesized that a behavioral weight loss intervention would significantly reduce OSA severity, but that the presence of OSA would lead to poorer weight loss outcomes. Methods: Overweight and obese adults (N = 101; 50.6 ± 10.3 y, body mass index: 34.1 ± 4.6; 91.1% female, 80.2% white) who participated in a 12-mo behavioral weight loss intervention study and had OSA assessed were included in these secondary analyses. Participants wore a limited-channel home sleep testing device (ResMed ApneaLink Plus) for one night at baseline, 6 and 12 mo. Measures of OSA severity included the apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and snoring index (i.e., number of snoring events divided by flow recording time). Weight change at 6 and 12 mo was expressed as percentage change from baseline. Linear mixed models were used to evaluate the effect of the intervention on OSA measures, and ANCOVA models examined the effect of weight change on OSA and the effect of OSA on subsequent weight loss. All analyses were adjusted for age, sex, and race. Results: Baseline AHI, ODI, and snoring index were 6.6 ± 7.1, 8.7 ± 8.3, and 109.9 ± 122.0, respectively; 50.5% of the sample had a baseline AHI ≥ 5. AHI and ODI, but not the snoring index, were significantly reduced by the end of the intervention (12-mo changes: -1.3 [P &lt; .05], -2.3 [P &lt; .01], -2.8 [P = .82], respectively). Weight loss at 6 and 12 mo were 9.0 ± 6.0% and 9.1 ± 8.3%, respectively. Participants with ≥ 5% weight loss at 6 mo had significant reductions in AHI (P = .02), ODI (P &lt; .05), and the snoring index (P &lt; .001) at 6 mo; adults with ≥ 5% weight loss at 12 mo had a significant reduction in the snoring index at 12 mo (P &lt; .01), but not AHI (P = .29) or ODI (P = .39), relative to baseline. Participants with a baseline AHI ≥ 5 lost significantly less weight at 6 mo compared to those without OSA at baseline (-8.4% vs. -11.4%; P &lt; .01), and those with an AHI ≥ 5 at 6 mo lost significantly less weight at 12 mo compared to those without OSA at 6 mo (-7.1% vs. -10.9%; P = .04). Conclusion: Behavioral weight loss interventions in overweight and obese adults lead to significant improvement in OSA severity. However, the presence of at least mild OSA is associated with less favorable weight loss in this population. Future work should explore the mechanisms underlying the blunted weight loss in overweight and obese adults with OSA.

Abstract P4-13-03: Changes in the gut microbiome of post-menopausal women 2 weeks after initiating a structured weight loss intervention

Abstract Background Change in the relative composition of the gut microbiome at the phyla level, particularly decreases in Bacteroidetes and increases in Firmicutes species, has been associated with both obesity and increased risk for breast cancer. It is unclear how rapidly the microbiome changes in response to a reduced calorie and fat diet during a weight loss intervention. As a planned sub-study of a clinical trial with a structured behavioral weight loss intervention with randomization to high dose omega-3 fatty acids or placebo (NCT02101970; clinical trials.gov), we evaluated changes in the gut microbiome after 2 weeks of dietary intervention. Methods 46 post-menopausal women at increased risk for breast cancer with a BMI &amp;gt; 27 kg/m2 had a baseline 3 day food record, DXA, and blood and breast tissue sampling for biomarkers. They were then started on a reduced fat and calorie diet (~1200 kcal/day from 2 portion-controlled entrees, 3 low calorie high protein shakes, and 5 servings of fruits/vegetables daily), recommendation to exercise 225 minutes per week, and a weekly behavioral intervention. Fecal samples were collected at baseline, after 2 weeks of diet but prior to study agent, and after 6 months of weight loss intervention. Stool samples were stored at -20°C until brought to the clinic, and then at -80°C until DNA extraction. Bacterial taxonomic classification was performed using real-time PCR and 16S pyrosequencing using specific 16S rRNA primers. Baseline Healthy Eating Index (HEI) was calculated from the 3 day food record; fruit and vegetable servings were obtained from weekly food logs. Results 42 women completed the 6 month weight loss intervention. At baseline, median BMI was 31.0 kg/m2 and HEI was 58 (range 28-90) with 12 and 23 servings of fruits and vegetables per week. Median relative weight loss at 6 months was -11.9 % (0 to -22.7 %). When dichotomized to relative losses of &amp;lt;10% vs &amp;gt;10% (which we have previously shown to be associated with significant improvement in blood and breast tissue risk biomarkers [Fabian Cancer Prev Res 2013]), women with 6 month &amp;gt;10% loss had favorable change in the two major stool phyla at 2 weeks with a median 10% increase for Bacteroidetes and 8% decrease for Firmicutes. Conversely, women with &amp;lt;10% loss showed a decrease (median -11%) in Bacteroidetes and an increase (median 16%) for Firmicutes. Fruit and vegetable consumption also differed between the weight loss groups. The &amp;gt;10% loss group had higher baseline consumption of vegetables and continued this after starting the diet. The more adherent a woman was to dietary recommendations in the first weeks of dietary intervention, the more likely she was to lose &amp;gt;10% weight by 6 months. Conclusions Favorable modulation of the gut microbiome early in a weight loss intervention is associated with subsequent substantial weight loss. Microbiome assessment after 6 months of weight loss intervention is in progress. Supported by a grant from the Breast Cancer Research Foundation and pilot funds from National Cancer Institute Cancer Center Support Grant P30 CA168524. Citation Format: Fabian CJ, Kimler BF, Umar S, Ahmed I, Befort CA, Nydegger JL, Kreutzjans AL, Powers KR, Klemp JR, Spaeth KR, Sullivan DK. Changes in the gut microbiome of post-menopausal women 2 weeks after initiating a structured weight loss intervention [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-13-03.

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers. After return to the same body weight as chow fed control mice, the fasting insulin, glucose, and hepatic triglyceride levels were fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome.

Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.

Exosomes from obese adipose contain dysregulated microRNAs linked to insulin signaling, as compared with lean controls, providing a direct connection between adiposity and insulin resistance. This study tested the hypotheses that gastric bypass surgery and its subsequent weight loss would normalize adipocyte-derived exosomal microRNAs associated with insulin signaling and the associated metabolome related to glucose homeostasis. African American female subjects with obesity (N = 6; age: 38.5 ± 6.8 years; BMI: 51.2 ± 8.8 kg/m2 ) were tested before and 1 year after surgery. Insulin resistance (HOMA), serum metabolomics, and global microRNA profiles of circulating adipocyte-derived exosomes were evaluated via ANCOVA and correlational analyses. One year postsurgery, patients showed decreased BMI (-18.6 ± 5.1 kg/m2 ; P < 0.001), ameliorated insulin resistance (HOMA: 1.94 ± 0.6 presurgery, 0.49 ± 0.1 postsurgery; P < 0.001), and altered metabolites including branched chain amino acids (BCAA). Biological pathway analysis of predicted mRNA targets of 168 surgery-responsive microRNAs (P < 0.05) identified the insulin signaling pathway (P = 1.27E-10; 52/138 elements), among others, in the data set. The insulin signaling pathway was also a target of 10 microRNAs correlated to changes in HOMA (P < 0.05; r > 0.4), and 48 microRNAs correlated to changes in BCAA levels. These data indicate that circulating adipocyte-derived exosomes are modified following gastric bypass surgery and correlate to improved postsurgery insulin resistance.

Benefits of bariatric surgery before elective total joint arthroplasty: is there a role for weight loss optimization?

BackgroundThe association between obesity and osteoarthritis is well established, as is the increased risk of postoperative complications after total knee arthroplasty (TKA) and total hip arthroplasty (THA) among patients with obesity. ObjectiveTo evaluate the outcomes after TKA/THA based on whether the surgery was performed before or after bariatric surgery. SettingIntegrated, multispecialty, community teaching hospital. MethodsThe medical records of all patients who underwent bariatric surgery from 2001 to 2014 were reviewed. Statistical analysis included χ2 test and t tests. A P value<.05 was considered significant. ResultsOne-hundred and two patients were included; 36 had TKA/THA before their bariatric procedure, 66 underwent TKA/THA after their bariatric procedure. TKAs/THAs were performed at a mean of 4.9±3.2 years before and 4.3±3.3 years after bariatric surgery. Body mass index for those undergoing TKA/THA after bariatric surgery was lower than those with TKA/THA before bariatric surgery (37.6±7.4 versus 43.7±5.7 kg/m2; P<.001). Operative time and length of stay (LOS) were significantly decreased for TKA/THA performed after versus before bariatric surgery: 81.7±33.9 min versus 117±38.1 min; P<.001 and 2.9±0.7 versus 3.8±1.4 d; P<.001, respectively. Early complications and late reinterventions were similar. ConclusionsDecreased operative time and LOS were observed among patients who underwent TKA/THA after versus before their bariatric surgery. Patients who underwent TKA/THA after bariatric surgery had lower body mass index before and 1 year after TKA/THA. Postoperative complication rates were similar. Benefits of bariatric surgery and subsequent weight loss should be considered among patients with obesity requiring TKA/THA. Optimal timing of TKA/THA and bariatric surgery has yet to be established.

Development of high oxidation resistant coating of nanostructured MgO on carbon nanotubes via simple precipitation technique in Mg/CO gas system

The synthesis of oxide-coated carbon nanotubes (CNTs) by a simple precipitation reaction in Mg/CO gaseous system was studied. The results showed that nanostructured MgO could be uniformly coated on the surface of CNTs via inhomogeneous Mg(g) and CO(g) precipitation reaction. Furthermore, we have developed a mixing procedure based on simultaneous agitation and ultra-sonication in order to break CNT bundles and prepare highly dispersed starting materials. By applying such mixing procedure, dispersed and distinct nano-oxide coated CNTs were synthesized which can be efficiently utilized in different composite matrices. Oxidation resistance of samples was investigated by DSC/TG thermal analysis. The results showed that oxide-coated CNTs present superior resistance against oxidation even at rather elevated temperature of 1000°C and total weight loss of coated CNTs was measured to be less than 1wt% during heat treatment at such temperature. Finally, coating adhesion was evaluated employing ultrasonic waves (as mechanical force) and subsequent weight loss measurement at temperature of 1000°C.

A145 - The Benefits of Bariatric Surgery Prior to Elective Total Joint Arthroplasty: Is There a Role for Weight Loss Optimization?

The association between obesity and osteoarthritis is well-established, as is the increased risk of postoperative complications after total knee arthroplasty (TKA) and total hip arthroplasty (THA) among patients with obesity. The role of bariatric surgery among patients requiring TKA/THA is not well understood. It is possible that bariatric surgery and subsequent weight loss may result in fewer complications, including wound infections, reduced operative times, and improved physical functioning after TKA/THA. The objective of this study was to evaluate the outcomes after TKA/THA based on whether they were performed before or after bariatric surgery.