bluuebunny/crossref_metadata_2025_split huggingface dataset:
2008-P: Roux-en-Y Gastric Bypass Surgery Can Modulate ER Stress and Inflammation on Subcutaneous Adipose Tissue in Nondiabetic Patients with Obesity
Authors: FERRAZ-BANNITZ RAFAEL , WELENDORF CAROLINE R. , COELHO PRISCILA O. , SALGADO WILSON , NONINO CARLA B. , BERALDO REBECA A. , FOSS-FREITAS MARIA CRISTINA 
Published: June 2020

Roux-en-Y gastric bypass (RYGB) is the most effective and durable treatment option for reducing adiposity and control abnormalities of metabolic syndrome in patient with severe obesity. Some studies have shown that the initial effect of RYGB on improving metabolic parameters is due to caloric restriction. However, the impact of RYGB on adipose tissue is still under debate. We evaluated 13 obese, nondiabetic patients (mean age 37 years, 100% women, BMI 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. Changes in anthropometric, biochemical e gene expression were evaluated with ANOVA and Pearson’s correlation analysis. BMI, fat mass and blood pressure decreased after 3M and 6M (P≤0.05 for all) compared with baseline. Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3M and 6M Post-RYGB showed that interleukins (IL6, TNF-α, and MCP1) and endoplasmic reticulum stress (ERS) genes (EIF2AK3 and CALR) decreased during the follow-up (P≤0.01 for all). Nonetheless, genes involved in energy homeostasis (ADIPOQ and AMPK), cellular response to oxidative stress (SIRT1, SIRT3, and NRF2), regulation of adipogenesis (PPARγ), mitochondrial biogenesis (PGC1α) and amino acid metabolism (GCN2) increased from baseline to all other time points evaluated (P≤0.01 for all). We also observed a strong positive correlation between PGC1α, SIRT1, and AMPK with BMI at 3M (P≤0.01 for all) and ADIPOQ and SIRT1 with BMI at 6M (P≤0.01 for all). Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process, in a gene expression level, during the caloric restriction and weight loss period after RYGB in patients without diabetes.

Disclosure
R. Ferraz-Bannitz: None. C.R. Welendorf: None. P.O. Coelho: None. W. Salgado Jr.: None. C.B. Nonino: None. R.A. Beraldo: None. M. Foss-Freitas: None.

Funding
Ribeirao Preto Clinical Hospital-FAEPA
2009-P: Improvement in Renal Function Associated with Endobarrier (EB)–Induced Weight Loss
Authors: RYDER ROBERT E.J. , YADAGIRI MAHENDER , IRWIN SUSAN P. , BURBRIDGE WYN , ALLDEN RACHAEL , BASHIR TAHIRA , BLEASDALE JOHN , FOGDEN EDWARD , ANDERSON MARK , GUPTA PIYA SEN , COCKWELL PAUL 
Published: June 2020

EB, a 60 cm proximal intestinal liner, endoscopically-implanted for up to 1 year, reduces weight and HbA1c. As the risk of progressive kidney-disease is increased by high BMI, we assessed the impact of EB on renal function. In 89 consecutive patients (aged 51.2 ± 8.0 years, 48.3% male, 55.1% europid, diabetes duration 10.8 (7.0-16.7) years, BMI 41.3 ± 6.9 kg/m2), mean ± SD HbA1c fell by 1.9 ± 1.8 %, from 9.4 ± 1.9 to 7.5 ± 1.2 % (p&lt;0.001), weight fell by 15.0 ± 8.3 kg from 119.1 ± 26.3 to 104.1 ± 27.0 kg (p&lt;0.001), systolic blood pressure (BP) from 138.4 ± 15.5 to 126.3 ± 16.9 mmHg (p&lt;0.001) (Table 1a). With regard to renal function, mean ± SD serum creatinine improved by 5.0 ± 15.5 μmol/L from 88.9 ± 41.8 to 83.9 ± 42.1 μmol/L (p=0.003) and estimated-Glomerular-Filtration-Rate (eGFR - abbreviated MDRD equation) improved by 6.5 ±10.7 ml/min/1.73m2 from 83.6 ± 23.4 to 90.1 ± 25.7 ml/min/1.73m2 (p&lt;0.001) (Table 1b). Eight patients had raised serum creatinine (&gt;133μmol/L) prior to EB; after implantation in 6 of these, creatinine reduced and in 3 creatinine normalised. It was noteworthy, that the 6 patients with renal impairment who sustained improvement had large weight loss (mean 17.3 kg), whereas the patients without improvement had lower weight loss (mean 6 kg). As well as previously documented improvements, in weight, HbA1c and BP, EB was associated with improvements in renal function. These observational findings warrant further investigation.

Disclosure
R.E.J. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. M. Yadagiri: None. S.P. Irwin: None. W. Burbridge: None. R. Allden: None. T. Bashir: None. J. Bleasdale: None. E. Fogden: None. M. Anderson: None. P. Sen Gupta: None. P. Cockwell: Speaker’s Bureau; Self; Napp Pharmaceuticals.
2013-P: Lifestyle Intervention, Metformin, and Acarbose Treatments Differentially Impact Liver Fat Content, Serum Lipids, and Hormone Profiles in Obese Polycystic Ovary Syndrome Patients with Impaired Glucose Tolerance
Authors: LI SHENGXIAN , WANG YUYING , CAI JIE , LIU WEI , YIN HUIYONG , TAO TAO 
Published: June 2020

Introduction: Polycystic ovary syndrome (PCOS) is often associated with obesity, insulin resistance, abnormal glucose tolerance, lipid metabolic disorders, and fatty liver. It remains unknown how current therapies impact these different components of PCOS.
Objective: We aim to evaluate the effects of lifestyle intervention (low calorie diet, LCD), metformin and acarbose treatment on fat mass, insulin sensitivity, hormone profiles, liver fat content and lipids profile in obese PCOS patients with impaired glucose tolerance (IGT).
Methods: In a 12-week, randomized, open tag prospective clinical trial, we recruited thirty obese PCOS patients, and randomly divided them into three groups: LCD, metformin, and acarbose group. Body weight, adipose tissue distribution, and serum sex hormone levels were measured before and after treatment. MRI was used to measure the liver fat content (LFC) and abdominal fat mass (AFM); Insulin sensitivity and beta-cell function were evaluated by OGTT and two-step hyperglycemic clamp; Serum free fatty acids (FFAs) were measured by GC-MS.
Results: In all three groups, AFM and insulin secretion were significantly decreased as measured by MRI, OGTT and glucose clamp, respectively. LCD significantly improved the insulin sensitivity as determined by HOMA-IR, disposition index, and matsuda index. Metformin significantly improved hyperandrogenism. Interestingly, we found only acarbose significantly decreased triglyceride, FFAs, and LFC.
Conclusion: All treatment modalities were effective in the treatment of PCOS women with obesity and IGT, only acarbose significantly decreased the triglyceride and FFAs, and ameliorated the LFC, suggesting that acarbose is an effective agent that could be used in PCOS patients with IGT and fatty liver.

Disclosure
S. Li: None. Y. Wang: None. J. Cai: None. W. Liu: None. H. Yin: None. T. Tao: None.
2016-P: Bariatric Surgery May Improve Glucose Control among Patients with Type 1 Diabetes
Authors: VENDRAME FRANCESCO , CASU ANNA , PRATLEY RICHARD E. , CALHOUN PETER 
Published: June 2020

The prevalence of obesity in patients with type 1 diabetes (T1D) is increasing. Obesity and metabolic syndrome are risk factors which contribute to the development and progression of micro- and macrovascular complications. Several studies have shown the beneficial and durable effect of bariatric surgery in patients with type 2 diabetes, but data in patients with T1D are scarce. We evaluated the impact of bariatric surgery in adult T1D patients enrolled in the T1D Exchange Registry. Clinical characteristics, comorbidities, socioeconomic factors and laboratory data were obtained within 5 years before or after bariatric surgery. A linear mixed model was used to compare glycemic and clinical outcomes before and after surgery controlling for patient characteristics. Overall, data were available for 38 patients of which 34 were female, 31 were white non-Hispanic (2 missing race); age and T1D duration at time of surgery was 43±9 yrs and 22 ± 13 yrs. After bariatric surgery, patients had lower HbA1c (8.7±1.4 before vs. 8.1±1.3% after), BMI (37.3±10.2 vs. 33.0±7.2 kg/m2), and LDL level (88±27 vs. 79±19 mg/dL), but only BMI reached statistical significance (Table). Although limitations include a small number of subjects and lack of information on type of surgery, this is to date the largest sample size. Our results suggest evidence T1D bariatric surgery is associated with improvement in diabetes control, although more research is needed.

Disclosure
F. Vendrame: None. A. Casu: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Janssen Scientific Affairs, LLC., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (G-2016PG-T1D053)
2019-P: Gender Influence on Body Habitus for an Underserved Population with Type 2 Diabetes and Food Insecurity
Authors: BEVIER WENDY C. , GLANTZ NAMINO M. , LAREZ ARIANNA J. , KUJAN MARY A. , CONNEELY CASEY , CASTORINO KRISTIN N. , KERR DAVID 
Published: June 2020

In the United States, type 2 diabetes (T2D) has a disproportionate impact on underserved populations, and this appears to be related to excess weight. Although reasons are likely multifactorial, it is unclear if there are gender-related influences on obesity risk for these populations. We compared body habitus by gender for 218 adults [84% Mexican-American, 152 females, mean (SD) age 56.2 (10.7) years, HbA1c 8.1 (2.0) %, BMI 31.2 (6.7) kg/m2, 45% uninsured, 42% food insecure (U.S. Household Food Security Survey)] with T2D participating in 2 clinical trials (NCT03830840 and NCT03940300). Comparisons were made for BMI, waist circumference (WC), relative fat mass (RFM), systolic blood pressure (SBP), HbA1c, and food security by gender (Table). Results expressed as mean (SD), unless specified. Significant associations (Spearman’s Rho) were found between WC and BMI (rs= 0.82) and WC and RFM (rs=0.66, both p&lt;0.001) for all participants and when stratified by gender (p&lt;0.001). There were no significant associations between HbA1c and RFM or BMI, except for BMI and HbA1c in males (rs=-0.31, p=0.02). Food insecure adults had higher HbA1c (%) levels than those who were food secure (median [IQR] 7.65 [6.98-9.35] versus 7.30 [6.40-8.63], p=0.02).
In conclusion, gender may be an important influence on body habitus for underserved populations with T2D. Food insecurity is also common and can impact glycemic control.

Disclosure
W.C. Bevier: None. N.M. Glantz: Research Support; Self; Abbott, Eli Lilly and Company. A.J. Larez: Research Support; Self; Eli Lilly and Company. M.A. Kujan: None. C. Conneely: None. K.N. Castorino: Research Support; Self; Abbott, Dexcom, Inc., Medtronic, Mylan, Novo Nordisk Inc. D. Kerr: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; Glooko, Inc.

Funding
Eli Lilly and Company; U.S. Department of Agriculture (2018-01793)
2020-P: ß3-Adrenergic Receptors Regulate Lipolysis and Thermogenesis in Human Brown/Beige Adipocytes
Authors: CERO CHERYL , LEA HANNAH J. , ZHU KENNETH Y. , CYPESS AARON M. 
Published: June 2020

Activation of rodent brown adipose tissue (BAT) via pharmacological stimulation of β3-adrenergic receptors (β3-AR) leads to metabolic benefit, however in humans, the physiological relevance of BAT and β3-AR remain controversial. To investigate the role of the β3-AR in human brown adipocytes, first, we established a human primary supraclavicular adipocyte in vitro model that upon differentiation preserved the physiological properties brown adipose tissue with increased β-ARs, adipogenic, thermogenic and brown/beige markers. Next, we selective silenced β3-AR expression in differentiated primary brown/beige adipocytes using a lipofectamine-based non-viral transfection. 48h of transfection of siRNA targeting ADRB3 (siRNA-ADRB3) resulted in a 90% reduction in ADRB3 mRNA levels, relative to control siRNA-transfected cells (siRNA-Ctrl). siRNA-ADRB3 also reduced genes of fatty acid metabolism, thermogenesis (UCP1, 90% decrease), and mitochondrial mass. Functionally, lower cAMP levels, lipolysis, oxygen consumption rates and higher glycolysis were caused by silencing β3-AR receptor. Immortalized brown adipocyte (hBA’s), from a separate subject, displayed a similar decrease in lipolysis and cellular respiration. Mirabegron, the selective human β3-AR agonist, stimulated BAT lipolysis and thermogenesis, that were lost after knockdown ADRB3. Similarly, selective subtype human β-AR agonists dobutamine (β1-AR agonist) and terbutaline (β2-AR agonist) treatment also increased lipolysis and thermogenesis, that were also attenuated when β3-AR was silenced. Thus, the β3-AR maintains multiple components of the human brown/beige adipocyte lipolytic and thermogenic cellular machinery. These findings indicate that ADRB3 and β3-AR agonists could be used to achieve metabolic benefit in humans.

Disclosure
C. Cero: None. H.J. Lea: None. K.Y. Zhu: None. A.M. Cypess: None.
2022-P: Partial-Body Cryotherapy Acutely Augments Resting Metabolism in Obese Women
Authors: CODELLA ROBERTO , NARDI MASSIMO DE , DELBARBA SUNDEEP , FACHERIS CARLO , LUZI LIVIO 
Published: June 2020

Cryotherapy has been shown to reduce pro-inflammatory response, relieve pain and enhance muscles’ post-exercise recovery. Cryostimulation could be also proposed as an alternative strategy to trigger cold-induced thermogenesis in overweight/obese subjects. In this study, 16 obese (BMI: 32±4 kg/m2) women (43.4±4.8 years) underwent Partial-Body Cryotherapy (PBC) (-130°C x 150sec) for 5 days (1/day, h 07:00 AM). Resting energy metabolism (REE) was assessed by indirect calorimetry pre- and post-PBC on day 1 and day 5. Subjects were energy-controlled (physical activity and dietary intake). Before 5th-day PBC, REE was increased by 5.5% versus pre-1st-day PBC values (1755±265 vs. 1664±241 kcal/day; p=0.0005). With a similar design, in a larger sample of 80 subjects (F=61; M=19; 34.4±11.1 years; BMI: 24.4±4.8 kg/m2), REE augmented by 1.89% (p=0.02) after PBC of day 1. In a multivariate analysis, multiple regression output a positive relationship between cryostimulated REE and body weight (Spearman r=0.68; p&lt;0.0001, Figure). Altogether, these preliminary data suggest that cold-induced thermogenesis could be explored as an alternative therapy to combat weight gain and obesity. Longitudinal studies could test chronic effects of cryotherapy, estimating the extent of the metabolic adaptations that could be favorably preserved.

Disclosure
R. Codella: None. M. De Nardi: None. S. Delbarba: None. C. Facheris: None. L. Luzi: None.
2025-P: Relation between Serum Uric Acid and Autonomic Function, Blood Pressure, and Visceral Obesity in Prediabetes and Type 2 Diabetes with Short Duration
Authors: DIMOVA RUMYANA , CHAKAROVA NEVENA , GROZEVA-DAMYANOVA GRETA , TANKOVA TSVETALINA 
Published: June 2020

Aim: The present study assesses the relation between uric acid and cardiovascular autonomic function (CAF), blood pressure (BR) and visceral obesity at early stages of glucose intolerance.
Material and Methods: A total of 100 subjects - 50 males, mean age 47.4±14.2years, mean BMI 32.2±7.5kg/m2, divided into 3 groups according to glucose tolerance: 30 subjects with normal glucose tolerance (NGT), 37 with prediabetes and 33 with type 2 diabetes (T2D) with duration ≤5 years were included. Glucose tolerance was assessed by OGTT according to WHO 2006 criteria. Anthropometric indices, BP, HbA1c and plasma glucose were measured. Body fat distribution was estimated by a bioimpedance method (InBody 720, BioSpace). CAF was assessed by ANX-3.0 using frequency-domain analysis during standard clinical tests.
Results: Uric acid levels were higher in prediabetes and T2D (p&lt;0.0001 and p=0.004, respectively) as compared to NGT. There was a decreased parasympathetic tone at rest (p=0.026 and p=0.001, respectively), deep breathing (p=0.025 and p=0.003, respectively), Valsalva maneuver (p=0.023 and p=0.003, respectively) and standing (p=0.012 and p=0.002, respectively) test in T2D in comparison to prediabetes and NGT. Sympathetic tone was diminished at rest (p=0.004), deep breathing (p=0.040) and standing (p=0.016) test in T2D as compared to NGT. Uric acid positively correlated with waist circumference (r=44, p&lt;0.0001), visceral fat area (r=24, p=0.022), diastolic BP (r=0.023) and HbA1c (r=22, p=0.030); and negatively with sympathetic activity at rest (r=-23, p=0.024), deep breathing (r=-26, p=0.010) and standing (r=-21, 0=0.039) test and with parasympathetic activity during deep breathing test (r=-21, p=0.033).
Conclusions: It seems to be an increase in uric acid levels and a decline in CAF in prediabetes and T2D with short duration. Uric acid is probably associated with CAF, visceral obesity and BP at early stages of dysglycaemia.

Disclosure
R. Dimova: Consultant; Self; Amgen, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Sanofi, Wörwag Pharma. N. Chakarova: None. G. Grozeva-Damyanova: None. T. Tankova: Board Member; Self; Amgen, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi, Servier.
2026-P: Efficacy of Internet-Based Intensive Weight Management or Exenatide Treatment on Weight Loss and Metabolism in Overweight/Obese PCOS
Authors: ZHENG SIYUAN , ZHANG YING , LI RENYUAN , XUE JIAO , SHEN HUANLING 
Published: June 2020

To evaluate efficacy of internet-based intensive weight management or exenatide treatment on weight loss and metabolism in overweight/obese patients with polycystic ovary syndrome(PCOS). The study recruited 50 overweight/obese patients with PCOS into intensive lifestyle intervention group(ILI) for internet-based intensive weight management, which characterized with strict-energy and low-carbohydrate diets(1100-1400 kcal of total energy and less than 50g of carbohydrates per day), nutritional meal-replacement diets for lunch and dinner, online reporting followed by nutrionists, exercises, behavioral intervention and medication(metformin, 500mg Tid), for 3 months. 50 BMI matched subjects assigned to 3 months of exenatide injection (10μg bid)in our previous study were recruited as control group (EXE group). Oral glucose tolerance test were performed to assess glucose tolerance and insulin sensitivity. Anthropometric, glycolipid metabolic markers, sex hormone level and inflammatory state were measured and compared between two intervention. After 3 months of intervention, decreases of weight(ILI group 10.02 ± 3.06 kg vs. EXE group 6.15 ± 2.28 kg), BMI (ILI group 3.98±1.26 kg/m2 vs. EXE group 2.54±1.05 kg/m2), HOMA-IR(2.60 ± 2.37 vs. 1.06 ± 2.04), WC, FBG, FINS, TG and UA in ILI group were more statistically significant than EXE group. There were no significant differences in decreases of 2hPBG, 2hINS, testosterone and hs-CRP between two groups(P&gt; 0.05). There were no statistically differences in improvements of total cholesterol, LDL-C, ALT, and AST in both groups (P&gt; 0.05). It is suggested that internet-based intensive weight management in overweight/obese PCOS can significantly reduce weight, improve central obesity and insulin resistance. These effects were significantly better than exenatide treatment. However there were no significant differences in improvements of testosterone level and inflammatory state.

Disclosure
S. Zheng: None. Y. Zhang: None. R. Li: None. J. Xue: None. H. Shen: None.
203-LB: Redosing of Suboptimally Controlled Diabetic Mice with Human Neo-islets, 3D Aggregates of Mesenchymal Stromal and Pancreatic Islet Cells, Durably Restores Euglycemia: Relevance to the Treatment of Diabetic Humans
Authors: CHOWDHURY SABIHA S. , GOOCH ANNA , ZHANG PING , HU ZHUMA , WESTENFELDER CHRISTOF 
Published: June 2020

We reported that the i.p. administration of allogeneic Neo-Islets (NIs; 3D aggregates of allogeneic, culture-expanded Islet cells (ICs) with immune- and cyto-protective Mesenchymal Stromal Cells (MSCs)), durably restores normoglycemia in autoimmune type-1 diabetic NOD mice through omental engraftment. Similarly, our ongoing, FDA-guided pilot study in insulin dependent pet dogs (INAD 012-0776) demonstrates that allogeneic canine NI therapy significantly improves both glycemic control and insulin needs (&gt; 1.5 years), and this without eliciting an allo-immune response. The current study was undertaken in preparation of a Phase I Clinical Trial in order to determine whether NIs engineered from human cells (hNIs) could also reduce insulin need, and whether redosing of suboptimally controlled diabetic mice could fully restore euglycemia, as is frequently required in human recipients of islet transplants.
Hyperglycemia (blood glucose &gt; 350 mg/dL x 3 days) was induced with streptozotocin in adult NOD/SCID mice and blood glucose levels were controlled with insulin pellets (Linbits) until i.p. hNI (2x10e5 hNIs/kg bw) or vehicle administration (n=6/group). Blood glucose levels, weights, ip glucose tolerance tests [GTT) were closely monitored.
While no mice in the hNI treated group died (vs. 4 in the control group), hNI therapy partially reduced glucose levels . Therefore, on day 64 post initial treatment, mice were re-dosed with hNIs (2x10e5 hNIs/kg bw) and followed together with controls as above. This second dose of hNI completely and durably restored euglycemia and normalized ip GTTs.
We conclude that this minimally invasive, safe and highly effective therapy supports our current pursuit of an IND for the conduct of a pioneering Clinical Trial in subjects with T1DM.

Disclosure
S.S. Chowdhury: Employee; Self; SymbioCellTech. A. Gooch: Employee; Self; SymbioCellTech. P. Zhang: Employee; Self; SymbioCellTech. Z. Hu: Employee; Self; SymbioCellTech. C. Westenfelder: Consultant; Self; SymbioCellTech.
203-OR: ADA Presidents’ Select Abstract: Landscape of Liver Cell Heterogeneity and Reprogramming during NASH Pathogenesis Revealed by Single Cell RNA Sequencing
Authors: XIONG XUELIAN 
Published: June 2020

Nonalcoholic steatohepatitis (NASH) is rapidly emerging as a prevalent liver disease that is associated with metabolic syndrome. NASH increases the risk for end-stage liver diseases such as cirrhosis and liver cancer and currently has no effective treatments. Despite this, the pathophysiological mechanisms underlying NASH initiation and progression remain poorly understood. We and others have previously established a diet-induced NASH model in mice that recapitulates key aspects of human NASH pathologies, including hepatic steatosis, liver injury, inflammation, and liver fibrosis in the context of obesity and insulin resistance. Here we performed single-cell RNA sequencing (sc-RNAseq) analysis on liver cells isolated from healthy and diet-induced NASH mice to map the landscape of liver cell heterogeneity and reprogramming during NASH pathogenesis. Our analysis revealed a highly interconnected ligand-receptor signaling network among different liver cell types that is disrupted during NASH progression. Hepatic stellate cells are emerging as a hub of signaling in the liver by secreting “stellakines” and respond to vasoactive hormones. Finally, we identified TREM2-expressing macrophages as a unique disease-associated macrophage population that is linked to NASH severity in humans. This work reveals the transcriptomic landscape of liver cells at single-cell resolution and uncovers key aspects of NASH-associated reprogramming of liver non-parenchymal cells.

Disclosure
X. Xiong: None.