Bariatric Surgery-induced Weight Loss Research Articles

Tissue-specific inflammation and insulin sensitivity in subjects with obesity

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship.The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements.Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health.

Abstract 17000: Adipokines and Subclinical Myocardial Injury Following Bariatric Surgery

Background: Bariatric surgery results in marked weight loss and has many cardiometabolic benefits. Adipokines, proteins secreted by adipose tissue with diverse metabolic effects, are affected by bariatric surgery. Whether favorable changes in adipokines after bariatric surgery are associated with improvements in cardiac biomarkers is unknown. Methods: We studied 294 bariatric surgery patients and 294 controls matched on age, sex, BMI, and diabetes in the Geisinger Obesity Registry. We measured serum markers of subclinical cardiac injury (high-sensitivity cardiac troponin I [hs-cTnI]), cardiac fibrosis (galectin-3), and adipokines (adiponectin, leptin, resistin, visfatin) prior to surgery and 6-18 months post-surgery in bariatric surgery patients and at similar intervals in controls. We used linear regression to evaluate the associations of changes in log-transformed adipokines with changes in log-transformed hs-cTnI and galectin-3. Results: Participants (mean age 45; 83% female; 97% White; mean BMI 47 kg/m 2 ) undergoing bariatric surgery lost 38.5 kg and matched controls gained 0.4 kg on average. Leptin, resistin, visfatin, hs-cTnI and galectin-3 decreased while adiponectin increased in bariatric surgery participants. There were no significant changes in any biomarkers in control participants. Increasing adiponectin and decreasing leptin were associated with decreases in hs-cTnI, but these associations were attenuated by adjustment for weight loss ( Table ). Decreasing resistin was linked to decreasing hs-cTnI and galectin-3, and decreasing visfatin with decreasing galectin-3, independent of weight loss. Conclusion: Bariatric surgery induced weight loss results in favorable changes in adipokines, which are associated with reversal of subclinical myocardial injury, and to a lesser degree, with decreasing myocardial fibrosis. Associations for some adipokines were weight loss-dependent, while others were independent of weight loss.

Abstract 15895: Bariatric Surgery and Subclinical Myocardial Injury

Background: Obesity is linked with subclinical myocardial injury, even in those with metabolically healthy obesity (MHO). There is limited data on the impact of weight loss via bariatric surgery on myocardial injury, particularly at different levels of metabolic health. Methods: We prospectively evaluated 294 Geisinger Obesity Institute Registry participants undergoing bariatric surgery and 294 controls matched on age, sex, body mass index (BMI;± 5kg/m 2 ) and diabetes status. High-sensitivity cardiac troponin I (hs-cTnI) was measured pre-operatively and at 6-18 months post-operatively in bariatric surgery patients, and at similar intervals in controls. Using linear regression, we examined the association of bariatric surgery with change in log transformed hs-cTnI (ln-hs-cTnI), stratified by metabolic health status: MHO (metabolic syndrome absent), metabolically unhealthy obesity (MUO; metabolic syndrome present), and MUO with diabetes. We used logistic regression to characterize the association of weight change (modeled as a restricted cubic spline) with the OR of transitioning from detectable to undetectable hs-cTnI (limit of detection 1.2ng/L). Results: The mean age was 45 years with 83% female, 97% White, and mean BMI of 47 kg/m 2 . Baseline characteristics of bariatric surgery patients and controls were similar. Bariatric surgery was associated with significant reduction in ln-hs-cTnI compared with controls in each stratum of metabolic health (P for interaction = 0.63; Panel A). Bariatric surgery was associated with an OR of 9.02 (95% CI 3.52-23.10) for transitioning from detectable to undetectable hs-cTnI, with a dose response association between weight loss and higher odds of developing undetectable hs-cTnI (Panel B). Conclusion: Bariatric surgery induced weight loss mitigates subclinical myocardial injury in graded fashion and across metabolic health strata, which may reflect one mechanism for the cardioprotective benefits of weight loss.

A Comparative Analysis of Safety and Efficacy of Bariatric Surgery During the COVID-19 Pandemic and Pre-Pandemic Period: Insights from the Tehran Obesity Treatment Study.

The COVID-19 pandemic has raised global health concerns and posed challenges for postoperative follow-up care for patients undergoing bariatric surgery due to social distancing rules. This was a cohort study on patients with morbid obesity who underwent bariatric surgery and had been enrolled in Tehran Obesity Treatment Study. Patients who had surgery between March 2020 and March 2021 were classified as those undergoing the procedure amid the COVID-19 pandemic, while those who had surgery between March 2017 and March 2018 were categorized as the pre-pandemic group. The study included 982 patients in the pre-COVID-19 pandemic group and 602 patients in the COVID-19 pandemic group, with mean ages of 39.61 and 39.51 years, respectively. After adjusting for preoperative body mass index (BMI) and surgery type, the patients who underwent surgery during the COVID-19 pandemic demonstrated comparable results to the pre-COVID-19 group in terms of total weight loss %, excess weight loss %, BMI reduction, and fat mass reduction during the 12-month postoperative period. Additionally, the rate of complications with a grade≥III based on the Clavien-Dindo classification was significantly lower in patients who underwent surgery during the COVID-19 pandemic. Notably, there were no deaths reported in either group. Despite social isolation and unfavorable lifestyle modifications, bariatric surgery-induced weight loss after one year was the same in patients undergoing the procedure either before or after the implementation of social distancing measures. More research is needed to analyze the influence of the COVID-19 pandemic on the long-term outcomes of bariatric surgery.

Factors Associated With Cognitive Improvement After Bariatric Surgery Among Patients With Severe Obesity in the Netherlands

Bariatric surgery-induced weight loss is often associated with improved cognitive function. However, improvement in cognitive function is not always exhibited by all patients, and the mechanisms behind cognitive improvement remain unknown. To investigate the association of changes in adipokines, inflammatory factors, mood, and physical activity with alterations in cognitive function after bariatric surgery among patients with severe obesity. This cohort study included 156 patients with severe obesity (body mass index [calculated as weight in kilograms divided by height in meters squared], >35) eligible for Roux-en-Y gastric bypass, aged between 35 and 55 years, who were enrolled in the BARICO (Bariatric Surgery Rijnstate and Radboudumc Neuroimaging and Cognition in Obesity) study between September 1, 2018, and December 31, 2020. Follow-up was completed July 31, 2021; 146 participants completed the 6-month follow-up and were included in the analysis. Roux-en-Y gastric bypass. Overall cognitive performance (based on a 20% change index of the compound z score), inflammatory factors (eg, C-reactive protein and interleukin 6 levels), adipokines (eg, leptin and adiponectin levels), mood (assessed via the Beck Depression Inventory), and physical activity (assessed with the Baecke questionnaire). A total of 146 patients (mean [SD] age, 46.1 [5.7] years; 124 women [84.9%]) completed the 6-month follow-up and were included. After bariatric surgery, all plasma levels of inflammatory markers, including C-reactive protein (median change, -0.32 mg/dL [IQR, -0.57 to -0.16 mg/dL]; P < .001) and leptin (median change, -51.5 pg/mL [IQR, -68.0 to -38.4 pg/mL]; P < .001), were lower, whereas adiponectin levels were higher (median change, 0.15 μg/mL [IQR, -0.20 to 0.62 µg/mL]; P < .001), depressive symptoms were (partly) resolved (median change in Beck Depression Inventory score, -3 [IQR, -6 to 0]; P < .001), and physical activity level was higher (mean [SD] change in Baecke score, 0.7 [1.1]; P < .001). Cognitive improvement was observed in 43.8% (57 of 130) of the participants overall. This group had lower C-reactive protein (0.11 vs 0.24 mg/dL; P = .04) and leptin levels (11.8 vs 14.5 pg/mL; P = .04) and fewer depressive symptoms at 6 months (4 vs 5; P = .045) compared with the group of participants who did not show cognitive improvement. This study suggests that lower C-reactive protein and leptin levels, as well as fewer depressive symptoms, might partly explain the mechanisms behind cognitive improvement after bariatric surgery.

Limited Bariatric Surgery-induced Weight Loss in Subjects With Type 2 Diabetes: Predictor Variables in Adipose Tissue.

The impact of type 2 diabetes mellitus (T2D) at baseline on limited weight loss (WL) after bariatric surgery (BS) remains controversial, and the potential underlying mechanisms incompletely understood. We aimed at gaining further insight on this relationship and identifying novel associations between adipose tissue (AT) parameters and short-term WL outcomes in subjects with or without T2D undergoing BS. Mid-term WL trajectories after BS have been evaluated in a cohort of 1659 subjects (cohort 1) with (n = 543) and without T2D (n = 1116). Paired subcutaneous and visceral AT samples were obtained from a cohort of 48 pairs of subjects with and without T2D matched for age, sex, BMI, and type of BS (cohort 2). Differences in AT parameters between groups were evaluated and potential associations with WL response explored. T2D was independently associated with a 5% lesser mid-term WL in cohort 1, while HbA1c, insulin treatment, and number of T2D medications prior to BS were only related to short-term WL outcomes. In cohort 2, a number of differentially expressed genes in AT were identified between groups, while fat cell size and fibrosis were comparable. Subcutaneous ATG7 expression was found as an independent predictor of limited WL 1 year after surgery (β: -12.21 ± 4.41, P = .008) and its addition to a clinical model significantly improved the amount of WL variability explained (R2 = 0.131 vs R2 = 0.248, F change P = .009). Our results highlight the importance of T2D as determinant of limited WL following BS and suggest that dysregulated macroautophagy in subcutaneous AT may contribute to this association.

Individuals with type 2 diabetes have higher density of small intestinal neurotensin-expressing cells

Neurotensin (NT) is a gastro-intestinal hormone involved in several pathways that regulate energy and glucose homeostasis. NT was hypothesized to act in synergy with incretin hormones to potentiate its anti-diabetic effects. Additionally, circulating NT levels were shown to rise after bariatric surgery-induced weight loss. Knowledge of NT-secreting cells distribution along the small intestine and its variation according to diabetes status could provide insights on NT role in mediating type 2 diabetes (T2D) improvement after bariatric surgery. So, our aims were to characterize NT-expressing cell distribution along the human small intestine and to compare the relative density of NT-expressing cells in the small intestine of individuals with and without T2D undergoing bariatric surgery for obesity treatment. Autopsy-derived small intestine fragments (n = 30) were obtained at every 20 cm along the entire intestinal length. Additionally, jejunum biopsies (n = 29) were obtained during elective gastric bypass interventions from patients with (n = 10) or without T2D (n = 18). NT-expressing cells were identified by immunohistochemistry and quantified via computerized morphometric analysis. NT-expressing cell density increased along the human small intestine. NT-expressing cell density was significantly higher from 200 cm distal to the duodenojejunal flexure onward, as well as in subjects with T2D when compared to those without T2D. NT-expressing cell density increases along the human small gut, and a higher density is found in individuals with T2D. This finding suggests a potential role for NT in the mechanisms of disease and T2D improvement observed after bariatric surgery.

Abstract P117: Weight Loss is Associated With Increases in Mitochondrial DNA Copy Number

Background: Mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function that is independently associated with increased cardiovascular disease risk. Individuals with obesity and cardiometabolic risk factors have lower mtDNA-CN levels. However, the modifiability of mtDNA-CN following a weight loss intervention has remained largely unexplored. Hypothesis: Bariatric surgery-induced weight loss is associated with longitudinal increases in circulating mtDNA-CN levels. Methods: In the BARI-Heart prospective cohort of bariatric surgery patients, we quantified mtDNA-CN from whole blood samples collected at three visits: 3 to 6 months prior to surgery, 2-4 weeks prior to surgery, and 6 months post-surgery. We used linear mixed models with random effects to assess changes in mtDNA-CN after bariatric surgery, with the pre-surgery visits while awaiting bariatric surgery serving as the control period. We used multivariable linear regression to evaluate the dose-response association between weight loss and change in mtDNA-CN. Results: We included 71 participants (mean age 45 years, 74% female, 88% White). While mtDNA-CN levels did not change significantly during the pre-surgery period (V1 to V2), mtDNA-CN significantly increased after bariatric surgery (V2 to V3) (Figure). In linear mixed models adjusting for age, sex, and smoking, mtDNA-CN was higher after bariatric surgery than immediately prior to bariatric surgery (Table: ß=0.141, p &lt; 0.001). This increase in mtDNA-CN remained significant following further adjustment for changes in cardiometabolic risk factors (ß=0.116, p &lt; 0.01). In linear regression, each 10% greater weight loss was associated with a 1.6% increase in mtDNA-CN. Conclusions: Weight loss via bariatric surgery is associated with significant increases in mtDNA-CN, independent of cardiometabolic risk factors. Improvements in mitochondrial function may mediate some of the cardiovascular benefits of significant weight loss.

Cognition and brain oxygen metabolism improves after bariatric surgery-induced weight loss: A pilot study.

The primary objectives of this pilot study were to assess cognition and cerebral metabolic rate of oxygen (CMRO2) consumption in people with severe obesity before (baseline), and again, 2- and 14-weeks after sleeve gastrectomy bariatric surgery. Six people with severe/class 3 obesity (52 ± 10 years, five females, body mass index (BMI) = 41.9 ± 3.9 kg/m2), and 10 normal weight sex- and age-matched healthy controls (HC) (48 ± 6 years, eight females, 22.8 ± 1.9 kg/m2). Global CMRO2 was measured non-invasively using MRI and cognition using the Integneuro testing battery. Following a sleeve gastrectomy induced weight loss of 6.4 ± 2.5kg (% total-body-weight-lost = 5.4) over two-weeks, cognition total scores improved by 0.8 ± 0.5 T-scores (p=0.03, 15.8% improvement from baseline). Weight loss over 14-weeks post-surgery was 15.4 ± 3.6kg (% total-body-weight-lost = 13.0%) and cognition improved by 1.1 ± 0.4 (p=0.003, 20.6% improvement from baseline). At 14-weeks, cognition was 6.4 ± 0.7, comparable to 6.0 ± 0.6 observed in the HC group. Baseline CMRO2 was significantly higher compared to the HC (230.4 ± 32.9 vs. 177.9 ± 33.9 µmol O2/100 g/min, p=0.02). Compared to baseline, CMRO2 was 234.3 ± 16.2 µmol O2/100 g/min at 2-weeks after surgery (p=0.8, 1.7% higher) and 217.3 ± 50.4 at 14-weeks (p=0.5, 5.7% lower) after surgery. 14-weeks following surgery, CMRO2 was similar to HC (p=0.17). Sleeve gastrectomy induced weight loss was associated with an increase in cognition and a decrease in CMRO2 observed 14-weeks after surgery. The association between weight loss, improved cognition and CMRO2 decrease should be evaluated in larger future studies.

Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals

BackgroundObesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery.ResultsOur analysis revealed 41 significant (Bonferroni p < 0.05) and 1169 (false discovery rate p < 0.05) suggestive differentially methylated positions (DMPs) associated with weight loss due to bariatric surgery. Among the 41 significant DMPs, 5 CpGs were replicated in an independent cohort of BMI-discordant monozygotic twins (the heavier twin underwent diet-induced weight loss). The effect sizes of these 5 CpGs were consistent across discovery and replication sets (p < 0.05). We also identified 192 differentially methylated regions (DMRs) among which SMAD6 and PFKFB3 genes were the top hypermethylated and hypomethylated regions, respectively. Pathway enrichment analysis of the DMR-associated genes showed that functional pathways related to immune function and type 1 diabetes were significant. Weight loss due to bariatric surgery also significantly decelerated epigenetic age 12 months after the intervention (mean = − 4.29; p = 0.02).ConclusionsWe identified weight loss-associated DNA-methylation alterations targeting immune and inflammatory gene pathways in blood samples from bariatric-surgery patients. The top hits were replicated in samples from an independent cohort of BMI-discordant monozygotic twins following a hypocaloric diet. Energy restriction and bariatric surgery thus share CpGs that may represent early indicators of response to the metabolic effects of weight loss. The analysis of bariatric surgery-associated DMRs suggests that epigenetic regulation of genes involved in endothelial and adipose tissue function is key in the pathophysiology of obesity.

The antigen CD300e drives T cell inflammation in adipose tissue and elicits an antibody response predictive of the insulin sensitivity recovery in obese patients

Obesity and insulin resistance (IR), the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation. Bariatric surgery leads to a considerable reduction in the adipose tissue mass and systemic inflammation along with a reduction of IR, with a whole-body metabolic improvement. However, a sizable portion of people experience an IR relapse within few years of remission.Numerous studies have attempted to explore the best clinical predictors of the improvement of insulin sensitivity and the maintenance of glucose homeostasis after bariatric surgery, but no simple fasting blood test has been found to be effective in predicting the short and long-term beneficial effects on glycaemia.With the present study, we investigated T-cell and antibody responses against CD300e, an antigen highly expressed in the adipose tissue of patients with obesity before the bariatric surgery-induced weight loss. We found both in fat tissue and in peripheral blood anti-CD300e-specific T helper 1 responses. Moreover, we evidenced in the sera of individuals with obesity an antibody response towards CD300e and revealed the existence of a significant correlation between the level of antibodies before surgery and the maintenance of glucose control after the intervention.

Response to immune checkpoint blockade improved in pre-clinical model of breast cancer after bariatric surgery.

Bariatric surgery is a sustainable weight loss approach, including vertical sleeve gastrectomy (VSG). Obesity exacerbates tumor growth, while diet-induced weight loss impairs progression. It remains unknown how bariatric surgery-induced weight loss impacts cancer progression or alters response to therapy. Using a pre-clinical model of obesity followed by VSG or diet-induced weight loss, breast cancer progression and immune checkpoint blockade therapy were investigated. Weight loss by VSG or weight-matched dietary intervention before tumor engraftment protected against obesity-exacerbated tumor progression. However, VSG was not as effective as diet in reducing tumor burden despite achieving similar weight and adiposity loss. Leptin did not associate with changes in tumor burden; however, circulating IL-6 was elevated in VSG mice. Uniquely, VSG tumors displayed elevated inflammation and immune checkpoint ligand PD-L1+ myeloid and non-immune cells. VSG tumors also had reduced T lymphocytes and markers of cytolysis, suggesting an ineffective anti-tumor microenvironment which prompted investigation of immune checkpoint blockade. While obese mice were resistant to immune checkpoint blockade, anti-PD-L1 potently impaired tumor progression after VSG through improved anti-tumor immunity. Thus, in formerly obese mice, surgical weight loss followed by immunotherapy reduced breast cancer burden. Finally, we compared transcriptomic changes in adipose tissue after bariatric surgery from patients and mouse models. A conserved bariatric surgery-associated weight loss signature (BSAS) was identified which significantly associated with decreased tumor volume. Findings demonstrate conserved impacts of obesity and bariatric surgery-induced weight loss pathways associated with breast cancer progression.

Impact of weight loss on brain age: Improved brain health following bariatric surgery

Individuals living with obesity tend to have increased brain age, reflecting poorer brain health likely due to grey and white matter atrophy related to obesity. However, it is unclear if older brain age associated with obesity can be reversed following weight loss and cardiometabolic health improvement. The aim of this study was to assess the impact of weight loss and cardiometabolic improvement following bariatric surgery on brain health, as measured by change in brain age estimated based on voxel-based morphometry (VBM) measurements. We used three distinct datasets to perform this study: 1) CamCAN dataset to train the brain age prediction model, 2) Human Connectome Project (HCP) dataset to investigate whether individuals with obesity have greater brain age than individuals with normal weight, and 3) pre-surgery, as well as 4, 12, and 24 month post-surgery data from participants (n = 87, age: 44.0 ± 9.2 years, BMI: 43.9 ± 4.2 kg/m2) who underwent a bariatric surgery to investigate whether weight loss and cardiometabolic improvement as a result of bariatric surgery lowers the brain age. As expected, our results from the HCP dataset showed a higher brain age for individuals with obesity compared to individuals with normal weight (T-value = 7.08, p-value < 0.0001). We also found significant improvement in brain health, indicated by a decrease of 2.9 and 5.6 years in adjusted delta age at 12 and 24 months following bariatric surgery compared to baseline (p-value < 0.0005 for both). While the overall effect seemed to be driven by a global change across all brain regions and not from a specific region, our exploratory analysis showed lower delta age in certain brain regions (mainly in somatomotor, visual, and ventral attention networks) at 24 months. This reduced age was also associated with post-surgery improvements in BMI, systolic/diastolic blood pressure, and HOMA-IR (T-valueBMI=4.29, T-valueSBP=4.67, T-valueDBP=4.12, T-valueHOMA-IR=3.16, all p-values < 0.05). In conclusion, these results suggest that obesity-related brain health abnormalities (as measured by delta age) might be reversed by bariatric surgery-induced weight loss and widespread improvements in cardiometabolic alterations.

Impact of Bariatric Surgery-Induced Weight Loss on Anterior Eye Health in Patients with Obesity.

The aim of the present research was to assess the effect of bariatric surgery-induced weight loss on the tear film and ocular surface of patients with obesity. A total of 29 participants with obesity (aged 47.2 ± 10.1 years, 8 male) were measured at baseline and followed up one year after Roux-en-Y gastric bypass (RYGB) surgery. General anthropometric data, as well as serum lipid markers of cholesterol, were assessed in all individuals. Bilateral anterior eye measurements of tear meniscus height (TMH), non-invasive tear breakup time, bulbar and limbal redness and infrared meibography were captured using the Keratograph K5M (Oculus) and ocular surface damage was evaluated using fluorescein sodium and lissamine green staining. Bariatric surgery resulted in significant loss of weight (body mass index p < 0.001) and an improvement in the blood lipid profile (p < 0.01) in all participants. However, there were no statistically significant differences between the baseline and one-year follow-up for any of the measured clinical ocular surface and tear film variables (all p > 0.05). Although there were trends for a reduced TMH and a decrease in meibomian gland dropout after bariatric surgery, these differences were also insignificant (p > 0.05). In conclusion, weight reduction through bariatric surgery did not have an effect on the tear film or ocular surface in unselected patients with obesity.

156-OR: Central Neural Processing of Sweet Taste Is Altered following Bariatric Surgery

Bariatric surgery causes marked changes in eating behavior, including reduced preference for highly sweet foods. No studies have addressed the brain response to receipt of this primary taste modality following weight loss surgery. Eighteen women (BMI 47.5±7.6 kg/m2, age 43.1±10.2 y) rated perceived intensity and liking of sucrose solutions (0, 0.1, 0.4, 0.86 &amp; 1.M) in a three-block randomized design, and underwent functional magnetic resonance imaging (fMRI) to assess brain responses to 0.40 M and 0.M sucrose sprayed onto the tongue relative to water (14 sucrose and 34 water trials in two 5:52 min long scans) , before and after bariatric surgery-induced weight loss. Eight women underwent Roux-en-Y and had sleeve gastrectomy. The post-surgery visit occurred 4.7 months (range 3-9) following the pre-surgery assessment. BMI was significantly reduced to 38.0±7.8 kg/m2. There was no effect of weight loss on rated sucrose solution intensity. However, post-surgical “preferred sweetness” of the test solutions was significantly lower (0.53±0.12 vs. 0.22±0.M; p&amp;lt;0.008) . Across the whole sample (pre- and post-surgery) , both sucrose concentrations relative to water activated bilateral insula and lateral frontal/orbitofrontal areas (p&amp;lt;0.001, k=5) . However, only 0.4M sucrose elicited the left nucleus accumbens (NAc) response (pFW E=0.005, k=17, family wise error-corrected within a bilateral NAc mask) . Pre-surgery activations included the anterior cingulate cortex (ACC) and bilateral insula as well as NAc (left: p=0.001, k=33; right p=0.009, k=17) . Post-surgery activations were present only in the ACC and bilateral insula. NAc responses were significantly greater pre-surgery relative to post-surgery (pFWE =0.026, k=6) . These data strongly suggest that bariatric surgery significantly affects central neural processing of sweet taste. While salience-assigning ACC and insula responses did not differ, nucleus accumbens region coding reward responded less post-surgically. Disclosure J.Alessi: None. K.Sawin: None. G.D.Chittum: None. S.E.Oswalt: None. M.Dzemidzic: None. D.A.Kareken: None. R.V.Considine: Other Relationship; Lilly. Funding American Diabetes Association (1-18-ICTS-036)

Circulating neurofilament is linked with morbid obesity, renal function, and brain density

Neurofilament light chain (NfL) is a novel biomarker reflecting neuroaxonal damage and associates with brain atrophy, and glial fibrillary acidic protein (GFAP) is a marker of astrocytic activation, associated with several neurodegenerative diseases. Since obesity is associated with increased risk for several neurodegenerative disorders, we hypothesized that circulating NfL and GFAP levels could reflect neuronal damage in obese patients. 28 morbidly obese and 18 lean subjects were studied with voxel based morphometry (VBM) MRI to assess gray and white matter densities. Serum NfL and GFAP levels were determined with single-molecule array. Obese subjects were re-studied 6 months after bariatric surgery. Morbidly obese subjects had lower absolute concentrations of circulating NfL and GFAP compared to lean individuals. Following bariatric surgery-induced weight loss, both these levels increased. Both at baseline and after weight loss, circulating NfL and GFAP values correlated inversely with eGFR. Cross-sectionally, circulating NfL levels correlated inversely with gray matter (GM) density, and this association remained significant also when accounting for age and total eGFR. GFAP values did not correlate with GM density. Our data suggest that when determining circulating NfL and GFAP levels, eGFR should also be measured since renal function can affect these measurements. Despite the potential confounding effect of renal function on NfL measurement, NfL correlated inversely with gray matter density in this group of subjects with no identified neurological disorders, suggesting that circulating NfL level may be a feasible biomarker of cerebral function even in apparently neurologically healthy subjects.

DF21-0668 Bariatric Surgery Induced Weight Loss Relation to Peripheral Neuropathy by Sudoscan: Clinical Study

Background: Obesity is a risk factor for peripheral neuropathy (PN). PN is found in subjects with diabetes, pre-diabetes and metabolic syndrome. Bariatric surgery (BS) – most successful obesity treatment results in stable weight loss. Though, BS impact on PN is unknown. Aim: To investigate impact of weight loss on PN in type 2 diabetes (T2DM) post-BS by Sudoscan. Method: A male (51yrs), T2DM diagnosed 8yrs ago; pre-operative examination results: weight-145 kg, BMI-42kg/m2, HbA1c-10.2%, T/A -150/90mmHg (on ACE/Amlodipine); vitamins D/B12 - within the normal range. Patient was on intensive insulin therapy (sol. Glulisine, short-acting insulin/SAI+ sol. Glargine, long-acting insulin/LAI): LAI - 24 IU/at bedtime; SAI-12x12x12 IU / before main meals. Neuropathy tests/BNT (monofilament, tip-term, vibration tests) were moderately positive; Sudoscan revealed moderate PN (scores 50 feet/48 hands). Diagnosis: T2DM, diabetic neuropathy, obesity class III, AH II. Treatment: BS (sleeve-gastrectomy) was performed; dietary therapy, multivitamins, calcium citrate, iron, vitamins D/ B12 were initiated post-operatively. Results: Post-operatively weight loss and glycemic profile improved, insulin doses gradually reduced, finally insulin and antihypertensive therapy were stopped. Post-operative examination results (month 3): HbA1c-6.7%, BMI-33.2kg/m2, T/A -130/80 mmHg; no symptoms of high ABP and/or hyperglycemia. Neuropathic complains and test scores improved: BNT - weak positive; by Sudoscan - moderate neuropathy (scores 55 feet/50 hands). Vitamins D/B12 and ionized calcium levels - within normal range. Patient was physically active. Dietary therapy/physical activity continued. Examination results (month 6): HbA1c-5.9%, BMI-28.9kg/m2, T/A - 120/70 mmHg. BNT results - weak positive; by Sudoscan - moderate neuropathy (scores 68 feet/56 hands). Treatment: dietary therapy, physical activity, calcium citrate, vitamins D/B12, multivitamins. Examination results (month 12): HbA1c-5.4%, BMI-26.5kg/m2, T/A -125/70 mmHg; general condition - satisfactory, mood/motivation – high; no PN symptoms; weight loss continued. BNT were near normal; no neuropathy by Sudoscan (scores 75 feet/68 hands). Discussion: The case study shows positive impact of weight loss on glycemia control, ABP and PN. Data of some research indicate positive effect weight loss on diabetic/non-diabetic PN. Further studies are necessary to approve these findings.

Macrophage activation marker sCD163 is associated with liver injury and hepatic insulin resistance in obese patients before and after Roux-en-Y gastric bypass.

BackgroundMacrophages are associated with metabolic complications to obesity including fatty liver disease and impaired hepatic and muscle insulin sensitivity (IS). Bariatric surgery induces weight loss and improves IS. We investigated associations between the macrophage activation marker soluble (s)CD163, alanine‐aminotransferase (ALT), and IS before and after Roux‐en‐Y Gastric Bypass (RYGB).MethodsWe analyzed sCD163 from 10 type 2 diabetes (T2D) and 10 obese patients with normal glucose tolerance (NGT) undergoing RYGB for associations with hepatic, adipose tissue, and muscle IS and ALT after 1‐week, 3, and 12 months postoperatively. IS was evaluated by hyperinsulinemic‐euglycemic clamp in combination with glucose tracer technique.ResultsPreoperative sCD163 correlated with ALT (r = 0.58, p = 0.007) and tended to associate inversely with hepatic (r = −0.39, p = 0.1) and adipose tissue (r = −0.39, p = 0.09), but not muscle IS. Following RYGB, sCD163 decreased significantly in all patients. The decrease in sCD163 during the first 3 months correlated inversely with the improvement of hepatic IS (r = −0.65, p = 0.01) and tended to be associated with changes in muscle IS (r = −0.45, p = 0.09). After 3 months sCD163 remained associated with ALT (r = 0.75, p < 0.001) and inversely with hepatic IS (r = −0.39, p = 0.1), but not muscle or adipose tissue IS. One year after RYGB, sCD163 correlated with ALT (r = 0.61, p = 0.007), but not with hepatic, adipose tissue, or muscle IS.ConclusionMacrophage activation is associated with liver injury and hepatic IS in obese patients. Improvements in these measures correlate during the first 3 months following RYGB, supporting a link between macrophages and hepatic IS in severe obesity and diabetes.

Potential beneficial effects of bariatric surgery on the prevalence of kidney cancer: a national database study.

The incidence of obesity has been steadily increasing, especially in developed countries. Also, obesity is considered one of the modifiable risk factors of kidney cancer. This study aims to determine the impact of bariatric surgery-induced weight loss on the prevention of kidney cancer. Academic Hospital, United States. The National (Nationwide) Inpatient Sample (NIS) was queried for the period 2010 to 2015 for first-time kidney cancer-related hospitalization, used as a proxy for cancer incidence, in patients with a history of bariatric surgery (cases) and patients with obesity but no history of bariatric surgery (controls). Patients with a previous diagnosis of cancer were excluded from the analysis. In order to identify comparable patients, all controls had to have a body mass index ≥35 kg/m2, as per the existing qualification criteria for bariatric surgery. The International Classification of Diseases-9 codes (ICD-9) was used to identify admissions for kidney cancer. A univariate analysis was conducted to compare demographics and co-morbidities between groups. A multivariate logistic regression model was performed to assess differences between surgical and control groups and adjust for independent variables such as smoking history and family history of malignancy. All percentages and means (with confidence intervals [CIs]) were weighted. A total of 2,300,845 were included in the analysis, of which 2,004,804 controls-subjects, with a mean age of 54.4 ± .05 years, and 296,041 treatment-subjects, with a mean age of 51.9 ± .05 years. Demographics and co-morbidities, such as tobacco use, diabetes, and hypertension, were also measured. Patients with a history of bariatric surgery were significantly less likely to experience renal cancer than patients without a history of bariatric surgery, with 5935 cases in the control group and 684 in the case group (P < .0001). After a multivariate logistic regression was performed, the OR was 1.10 (95% CI: 1.02-1.22, P < .0224). Our finding suggests that bariatric surgery-induced weight loss could significantly prevent first-time kidney cancer-related hospitalizations in patients with obesity. Prospective studies are needed to confirm our findings.

Concomitant Cholecystectomy for Asymptomatic Gallstones in Bariatric Surgery-Safety Profile and Feasibility in a Large Tertiary Referral Bariatric Center.

Obesity is a risk factor for gallstone formation, which can be exacerbated by bariatric surgery-induced rapid weight loss. Current guidelines do not recommend concomitant cholecystectomy (CC) for asymptomatic gallstones during the bariatric surgery procedure. However, long-term follow-up studies have shown that the incidence of post-bariatric surgery symptomatic gallstones necessitating therapeutic cholecystectomy increases to 40%. Therefore, some surgeons advocate simultaneous cholecystectomy during the bariatric surgery for asymptomatic individuals. This study aims to evaluate the safety of performing cholecystectomy for asymptomatic gallstones during the bariatric procedure. Data from a consecutive series of patients that underwent primary laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric bypass (LRYGB) or conversion of LSG to a LRYGB with or without concomitant cholecystectomy for asymptomatic gallstones between Jan 2010 and Dec 2017 were retrieved from the database. The primary endpoint was the complication rate. Secondary endpoints were the surgical operating room time (ORT) and the length of hospital stay (LOS). Out of the 2828 patients who were included, 120 patients underwent a concomitant cholecystectomy during their bariatric procedure (LSG or LRYGB) for asymptomatic gallbladder stones and were compared to the 2708 remaining patients who only had bariatric surgery. None of the concomitant cholecystectomy patients developed a gallbladder-related complication. There was no significant increase in the rate of minor or major complications between the CC groups and the non-CC groups (LSG: 6.7% vs. 3.2%, p=0.132; LRYGB: 0% vs. 2.3%, p =0.55; and conversion of LSG to LRYGB: 20% vs. 7.1%, p = 0.125, respectively). In addition, there was no significant increase in the length of hospital stay (1.85 ±4.19 days vs. 2.24 ±1.82, p=0.404) for LSG group and (1.75 ±2.0 vs. 2.3 ±2.1, p=0.179) for LRYGB group. Adding the cholecystectomy to the bariatric procedure only added an average of 23 min (min) (27 min when added to LSG and 18 min when added to LRYGB). As one of the largest series reviewing concomitant cholecystectomy in bariatric surgery, this study showed that in skilled laparoscopic bariatric surgical hands, concomitant cholecystectomy during bariatric surgery is safe and prevents potential future gallstone-related complications. Long-term large prospective randomized trials are needed to further clarify the recommendation of prophylactic concomitant cholecystectomy during bariatric surgery.