bluuebunny/crossref_metadata_2025_split huggingface dataset:
2025-P: Protective Effects of Orlistat against High-Fat Diet-Induced Metabolic Disorders in Mice
Authors: KE JING , AN YAXIN , CAO BIN , ZHAO DONG 
Published: June 2019

Background: Accumulating evidence indicates that alterations of gut microbiota and metabolites have been involved in obesity and diabetes. Orlistat, a reversible inhibitor of pancreatic and gastric lipase, has beneficial effects on metabolism. However, the mechanism of its action is less understood.
Methods: Metabolic indices, including weight, glucose tolerance and plasma lipids were determined in WT (C57BL/6J mice), HFD and HFD + ORL group. The effects of orlistat on gut microbiota and circulating metabolites in mice were assessed by 16S rRNA gene sequencing from fecal samples and LC-MS/MS from plasma samples.
Results: Compared to HFD group, HFD + ORL group showed improvements in glucose tolerance and plasma cholesterol, and a distinct microbiota composition with a dominance of Rhodococcus and Pseudomonas on genus level, positively associated with ether lipid metabolism, fatty acid metabolism, α-linolenic acid metabolism and GnRH signaling pathway etc. Furthermore, metabolic perturbations caused by HFD were improved in the HFD + ORL group and were presented in PLS-DA analysis. The discrepant metabolites were involved in several metabolic pathways, such as alanine, aspartate and glutamate metabolism, as well as histidine metabolism etc. Intriguingly, fecal microbiome and metabolome results share two common metabolic pathways, linoleic acid metabolism and arachidonic acid metabolism.
Conclusion: Our study suggests that orlistat may exert protective effects against metabolic disorders through modulating gut microbiota, which was involved in some common metabolic pathways with metabolome.

Disclosure
J. Ke: None. Y. An: None. B. Cao: None. D. Zhao: None.
2026-P: Myeloid Sirtuin 6 Is a Molecular Switch of White Adipose Tissue Browning
Authors: LEE YOUNGYI 
Published: June 2019

Emerging evidence reveals that cold exposure enhances alternative activation of macrophages. We recently reported that myeloid sirtuin 6 (Sirt6) drives macrophage phenotypes into M2 type. However, its role in adaptive thermogenesis has not been explored. In this study, we demonstrate that myeloid Sirt6 ablation attenuates thermogenic responses in subcutaneous adipose tissue (scWAT) during cold exposure. Compared with wild type mice, myeloid Sirt6 KO (mS6KO) mice displayed a lower core body temperature and were glucose intolerant in response to cold exposure. Accordingly, expression levels of thermogenic proteins and number of multilocular lipid droplets were decreased in scWAT of mS6KO mice. Mechanistically, the infiltration of M2 macrophages in scWAT was impaired in mS6KO mice, which contributed to the suppression of lipolysis in adipocytes. Together, these results establish myeloid Sirt6 as a critical determinant of beige cell formation in scWAT.

Disclosure
Y. Lee: None.
2032-P: The Effects of Liraglutide on Ameliorating Diabetic Kidney Disease Is via SIRT1/TXNIP Pathway
Authors: LIANG RIYING , WANG MEIJUN , FU CHANG , XU FEN , CAI MENGYIN 
Published: June 2019

GLP-1 receptor agonist is one of the most effective drugs to treat type 2 diabetes. LEADER Clinical Trials revealed that liraglutide exerted its renoprotective effect by reducing microalbumin-urine and slowing down the decline of eGFR. However, the underlying mechanism remains elusive. High glucose exposure upregulates the expression of TXNIP, a pro-oxidative stress and pro-apoptotic protein, by regulating histone acetylation. SIRT1, a deacetylase, also plays an important role in protecting renal function. We investigated the role of SIRT1/TXNIP pathway in the beneficial effect of liraglutide on improving renal function. In our study, eight-week old male C57BL/6 mice were subjected to a chow diet or a high fat diet (HFD) for 12 weeks. Then, mice were divided into groups as follows: NC, HFD, HFD+ Liraglutide (HL) group for 8 weeks. The results revealed that the body weight, fasting blood glucose, glucose tolerance and insulin sensitivity were statistically improved in HL group when compared with HFD group. Significant reduction of kidney lipid deposition and Bowman’s capsule space were observed in HL group based on the histology results. Besides, urine albumin-to-creatinine ratio and apoptosis in the kidney were ameliorated in the HL group. Western blotting results revealed the expression of genes involved in apoptosis was notably downregulated after liraglutide treatment. In addition, the protein expression of SIRT1 was upregulated, whereas TXNIP was downregulated in the HL group. Collectively, the data indicated that the effect of liraglutide on renoprotection is via SIRT1/TXNIP pathway.

Disclosure
R. Liang: None. M. Wang: None. C. Fu: None. F. Xu: None. M. Cai: None.
2047-P: UK First National Health Service (NHS) Endobarrier (EB) Service: Maintenance of Improvement One Year after Device Removal
Authors: RYDER ROBERT E.J. , GUPTA PIYA SEN , YADAGIRI MAHENDER , IRWIN SUSAN P. , BURBRIDGE WYN , BASHIR TAHIRA , WYRES MELANIE C. , ALLDEN RACHAEL , BLEASDALE JOHN , FOGDEN EDWARD , ANDERSON MARK 
Published: June 2019

EB, a 60cm endoscopically inserted proximal intestinal liner, reduces weight and HbA1c over 1-year. In the 1st NHS EB service, we provided EB to patients with sub optimally controlled diabesity and monitored outcomes in a registry. 32/46 (70%) completing 1-year post EB removal (age 51.1±7.5 years, 56% male, diabetes duration 14 (8-21) years, BMI 41.7±7.8 kg/m2) attended follow-up. During EB treatment, mean ± SD HbA1c fell by 2.1±1.9%, from 9.5±1.9 to 7.4±1.1% (p&lt;0.001), weight by 17.0±8.9 kg from 121.1 ± 28.4 to 104.1±29.1 kg (&lt;0.001), systolic BP from 140.0±15.3 to 126.4±15.9 mmHg (&lt;0.001), serum alanine aminotransferase (marker of liver fat) from 29.1±17.7 to 18.2±9.7 U/L (p&lt;0.001). Median (IQR) total daily insulin dose reduced from 104 (60-140) to 20 (0-59) units (n=21, p&lt;0.001); 7/21 (33%) insulin treated patients discontinued insulin. 1-year post EB removal 13/32 (41%) demonstrated sustained improvement with 12/32 (37%) partially sustaining improvement and 7/32 (22%) reverting to baseline (Figure). Of those deteriorating, 6/7 (86%) had depression and/or bereavement. 41/46 (89%) achieved the planned full year of EB treatment but 5/46 (11%) had early EB removal (4 GI bleed, 1 liver abscess) with all 5 fully recovering after removal. Our data demonstrates EB as highly effective in patients with refractory diabesity, with maintenance of significant improvement 1-year after removal in 78%.

Disclosure
R.E.J. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. P. Sen Gupta: None. M. Yadagiri: None. S.P. Irwin: Speaker's Bureau; Self; AstraZeneca. W. Burbridge: None. T. Bashir: None. M.C. Wyres: None. R. Allden: None. J. Bleasdale: None. E. Fogden: None. M. Anderson: None.
2050-P: A Multifactorial Telemedical Care Model for Long-Term Treatment of Obesity—A Randomized Controlled Trial
Authors: MARTIN RÖHLING , MARTIN KATHARINA , ELLINGER SABINE , MARTIN STEPHAN , KEMPF KERSTIN 
Published: June 2019

Lifestyle interventions are indicated as first-line therapy to fight obesity focusing on various aspects of a healthy lifestyle. However, as most of these lifestyle programs only include single components, we designed a multifactorial, telemedical and group-based seminar program to improve weight loss in overweight individuals.
Overweight volunteers (BMI ≥25 kg/m2) were randomized into a starting intervention group (SI, n=15) or a waiting list control group (WL, n=15). The multicomponent intervention consisted of a (1) group-based seminar program addressing low-carbohydrate nutrition, physical activity, and the carbohydrate-blood glucose-insulin relationship. Further components used were (2) low-carbohydrate formula diet, (3) flash-glucose-monitoring devices and (4) telemedical supervision. Both groups received telemedical devices at baseline. After the 12-weeks intervention phase of SI, WL started with the same intervention. Participants received monthly calls by coaches until week 26. Data were recorded before and after 12, 26 and 52 weeks of follow-up.
After 12 weeks of intervention, SI demonstrated a stronger reduction in weight compared to WL (-7.8 kg vs. -1.5 kg; P&lt;0.001). The estimated treatment difference between both groups was -6.3 kg with 95% confidence interval (95% CI) [-7.4; -4.5] (P&lt;0.001). Compared to WL, fat mass and eating behavior improved in SI as well (all P&lt;0.01). Furthermore, SI improved fasting blood glucose, HbA1c, quality of life (all P&lt;0.05), fasting insulin, blood pressure (both P&lt;0.01), and eating behavior (P&lt;0.001) in the within-group analysis, while WL did not show any changes. After 26 and 52 weeks of follow-up, weight reduction could be maintained in the SI-group by -9.7 kg [95% CI: -16.1; -3.2] (P&lt;0.001) and -7.8 kg [95% CI: -15.4; -0.9] (P&lt;0.05), respectively.
A multifactorial program leads to long-term clinically relevant weight reductions and improvements in cardiovascular risk factors in overweight individuals.

Disclosure
M. Röhling: None. K. Martin: None. S. Ellinger: None. S. Martin: Consultant; Self; Almased Wellness GmbH, AstraZeneca, Lilly Diabetes. K. Kempf: Speaker's Bureau; Self; cognomed, Kirchheim Verlag.
2061-P: Inflammation Status Is Independent Risk Factor for the Development of Metabolic Syndrome in Both Metabolically Healthy Obese and Nonobese Adults
Authors: HUR KYU YEON , CHOI MIN SUN , PARK SUNG WOON , LEE SEUNG-EUN , AHN JIYEON , PARK JUN , PARK HYUNJU , KIM GYURI , JIN SANG-MAN , KIM JAE HYEON , LEE MOON-KYU 
Published: June 2019

Objectives: The fact that metabolic syndrome is accompanied by a low-grade inflammation suggests inflammation may play an important role in the etiology. The aim of our study was to assess the association between heterogeneity of inflammation status and the incidence of metabolic syndrome (MetS) in the metabolically healthy persons who are either obese or nonobese.
Methods: This longitudinal study included all metabolically healthy persons who underwent four or more follow-up comprehensive health examinations either annually or biennially from August 2006 through August 2013 at the Health Promotion Center at Samsung Medical Center, Seoul, Republic of Korea. Metabolic health was defined as absence of any component of the MetS except obesity. We defined obesity using the BMI, which is classified into categories of normal (18.0-22.9 kg/m2), overweight (23-24.9 kg/m2), and obesity (25 kg/m2). Hematological indices such as WBC count or its subtypes (neutrophils, lymphocytes, monocytes) and hsCRP were measured. The outcome was the 7-year cumulative incidence of MetS.
Results: The person-years follow-up were 17,786 in normal weight, 10,376 in overweight, and 7,391 in obesity group. Baseline age, sex, physical activity, smoking, exercise, fasting plasma glucose, HbA1c, blood pressure, lipid profile, hematologic parameters, hsCRP were adjusted. Cox regression multivariate analysis resulted in neutrophil count (&gt; 2,750/mm3) was associated with increased incidence of MetS in normal weight (HR 1.7; CI 1.29-2.35; p &lt;0.001), overweight (HR 1.59; CI 1.29-1.95; p &lt;0.001), and obesity (HR 1.26; CI 1.10-1.45; p&lt;0.001).
Conclusion: This longitudinal analysis showed the neutrophil count is associated with the incidence of MetS in the metabolically heathy persons who are either obese or nonobese. Therefore, inflammatory status could be an independent risk factor for the development of metabolic syndrome irrespective of obesity.

Disclosure
K. Hur: None. M. Choi: None. S. Park: None. S. Lee: None. J. Ahn: None. J. Park: None. H. Park: None. G. Kim: None. S. Jin: None. J. Kim: None. M. Lee: None.
2066-P: Improvement of Hepatic Steatosis Index in Patients with Type 1 Diabetes and Obesity after Intensive Lifestyle Intervention: A One-Year Matched-Cohort Observational Study
Authors: TOMAH SHAHEEN , TASABEHJI MHD WAEL , GHAZI FAYEZ , SALAH TAREQ , ZHANG HONGXIA , ASHRAFZADEH SAHAR , HAMDY OSAMA 
Published: June 2019

Prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing among patients with type 1 diabetes (T1D). Little is known about the impact of weight reduction on NAFLD in this population. We utilized the Hepatic Steatosis Index (HSI), a noninvasive surrogate predictor of NAFLD, to evaluate the effect of intensive lifestyle intervention (ILI) on hepatic steatosis in patients with T1D and obesity after one year.
We evaluated 88 adult patients with T1D and obesity who participated in a 12-week ILI program in real-world clinical practice within the past 13 years. We excluded 11 patients per the International Associations for Diagnosis of NAFLD guidelines. A total of 77 patients were included in the analysis (mean age 43±12 years, 65% female, diabetes duration 22±12 years, HSI 46.2±6.1, A1C 8.2±1%, body weight 102.5±17 kg, BMI 35.7±5 kg/m2). We matched them in 1:1 ratio with a cohort of similar T1D patients who received standard diabetes care at the same practice during the same period (mean age 43±12 years, 65% female, diabetes duration 22±9 years, HSI 45±5.7, A1C 8.2±0.9%, body weight 100±17 kg, BMI 35.3±5 kg/m2). HSI was calculated as 8*ALT/AST+BMI (+2 if female). There were no differences in HSI between the 2 cohorts at baseline.
At 1 year, the ILI group lost an average of 5.6±2.7 kg (5.8%, p&lt;0.05) and the control group maintained their baseline body weight (p&lt;0.001 between groups). HSI decreased significantly from baseline in the ILI group (-2.7±1.05, p=0.01) but did not change in the control group (0.6±0.9, p=0.53, p&lt;0.001 between groups). A greater proportion of patients in the ILI group achieved HSI &lt;36 (NAFLD cut-off) (11.7% compared to 1.3% in the control group, p&lt;0.01).
We conclude that an ILI program in real-world clinical practice may improve HSI in patients with T1D and obesity compared to standard care after 1 year. A greater proportion of patients enrolled in ILI achieved HSI indicative of lower likelihood of NAFLD diagnosis.

Disclosure
S. Tomah: Stock/Shareholder; Self; Amarin Corporation. M. Tasabehji: None. F. Ghazi: None. T. Salah: None. H. Zhang: None. S. Ashrafzadeh: None. O. Hamdy: Advisory Panel; Self; AstraZeneca, Sanofi-Aventis. Consultant; Self; Abbott, Merck & Co., Inc. Research Support; Self; National Dairy Council. Stock/Shareholder; Self; Healthimation, LLC.
2069-P: Energy Expenditure during Sleep Is an Independent Marker of Prediabetes—A Cross-Sectional Study of Overweight/Obese Subjects
Authors: TUCCINARDI DARIO , ROSSINI GIOVANNI , MADDALONI ERNESTO , MAGGI DARIA , MONTE LAVINIA , FIORITI ELVIRA , KYANVASH SHADI , POZZILLI PAOLO , MANFRINI SILVIA 
Published: June 2019

Normal sleep is characterized by increased glycogen stores and reduced glucose turnover by metabolically active tissues, thus it is a state of decreased metabolism. It has been reported that reduced sleep quality is associated with disrupted glucose metabolism. However, the relationship between Sleep Metabolic Rate (SMR) and prediabetes defined by the presence of IFG and/or IGT, during 75-g OGTT, has not been clarified.
The aim of this study was to investigate the role of SMR in the association between sleep quality and prediabetes.
A total of 226 individuals [women 72.1%; mean (DS) age 50.46 (±13.1) years; BMI 33.4 (±8.41) Kg/m2] undergoing the OGTT, were also asked to wear a metabolic holter (Armband) for 3-days, to assess their daily energy expenditure (DEE). The Armband was also capable of measuring the SMR, the Total Sleep Time (TST) and Sleep Efficiency (SE). The SMR has been adjusted for Free Fat Mass (FFM) to reduce the overweight/obesity influence on energy expenditure (SMR/FFM).
A total of 78 subjects were identified as prediabetic. No difference in TST, SE, and DEE was observed between NGT and prediabetics. The SMR/FFM was significantly higher in patients with prediabetes (p&lt;.004). Using multivariate logistic regression, with prediabetes status as dependent variable and sleep efficiency, age, fat mass, gender and SMR/FFM as independent variables, the latter resulted an independent marker of prediabetes (OR 1.52, 95% CI 1.03-2.24) p .034, Nagelkerke’s r2: 0.12.
The SMR/FFM increase in prediabetic overweight/obese subjects may be explained through several mechanisms such as the increased nocturnal gluconeogenesis and the possible shift towards other substrates utilization (e.g., cori and glucose-alanine cycle).

Disclosure
D. Tuccinardi: None. G. Rossini: None. E. Maddaloni: Speaker's Bureau; Self; Merck & Co., Inc., Pikdare. D. Maggi: None. L. Monte: None. E. Fioriti: None. S. Kyanvash: None. P. Pozzilli: None. S. Manfrini: None.
2074-P: Significant Reduction of Visceral Adiposity in Type 2 Diabetics with Doctor-Supervised Weight Loss Program
Authors: DEMBROWSKI GERALD , BARNES JESSICA 
Published: June 2019

Metabolic syndrome (MS), which affects ∼23% of the U.S. population, dramatically increases the risk of cardiovascular disease (CVD) and type 2 diabetes. While pharmacotherapies are available to treat diabetes (DIA), few strategies exist that target visceral adiposity (VA) as a means to reduce risk of current and future morbidity and mortality. Commercial weight loss programs target body weight but provide minimal effect on actual components of MS including VA. The 20Lighter Program (T20LP), employs change in VA as a primary outcome measure and clinical indicator of CVD and metabolic disease risk reduction. A retrospective review, via an IRB-approved protocol, of the first 2200 participants completing T20LP found 270 reported taking at least one prescription DIA medication (oral and/or injectable) at the time of enrollment. From baseline to 60 days, each group (diabetes, DIA; and nondiabetes, non-DIA) showed statistically significant and clinically meaningful reductions in body weight (13.8±1.1%; 14.0±0.32%), Body Mass Index (BMI) (13.2±0.14%; 13.4±0.06%), body fat (15.4±0.30%; 15.5±0.15%), and VA (25.2±0.18%; 25.8±0.09%). When the two groups were compared, a small numerical divergence in mean change was found in some outcomes favoring the DIA group, but none held statistical significance. Data reported as: (DIA; non-DIA) and shown as mean±SEM. Our data show participants on prescription medications for DIA attain significant and clinically relevant reductions in body weight, BMI, body fat, and VA. Diabetics participating in T20LP are capable of achieving body composition and metabolic improvements on par with nondiabetics, and nondiabetics showed no advantage in any physiologic or metabolic outcome in our study. T20LP is a comprehensive lifestyle program complementing existing strategies to provide overweight and obese adults and teens diagnosed with and at risk of MS with safe and effective weight loss and VA reduction.

Disclosure
G. Dembrowski: Stock/Shareholder; Self; 20Lighter Program. Stock/Shareholder; Spouse/Partner; 20Lighter Program. J. Barnes: Stock/Shareholder; Self; 20Lighter Program. Stock/Shareholder; Spouse/Partner; 20Lighter Program.
2078-P: Association of Dietary Intake of Phosphorus with Obesity in Japanese Patients with Type 2 Diabetes Mellitus (T2DM)
Authors: HATTA MARIKO , FUJIHARA KAZUYA , MATSUBAYASHI YASUHIRO , TAKEDA YASUNAGA , NEDACHI RINA , ISHII DAI , HORIKAWA CHIKA , KATO MITSUTOSHI , MAEGAWA HIROSHI , SONE HIROHITO , STUDY GROUP JDDM 
Published: June 2019

Although serum phosphate concentrations have been consistently reported to have a negative correlation with BMI, there have been some conflicting reports of the relationship of dietary intake of phosphorus with BMI. Thus, we investigated the association between phosphorus intake and obesity in Japanese patients with diabetes mellitus. Analyzed were 1891 patients with T2DM (mean age, 62 y; men, 62%) in our nationwide registry who had completed a food frequency questionnaire. Obesity was defined according to BMI &gt;25. The association between phosphorus intake and obesity was determined by multivariate regression as well as quintile analyses. Mean daily intake of phosphorus was 996 mg in men and 977 mg in women, values that were quite close to those of the general population in Japan. Intake of phosphorus was significantly associated with decreased risk of obesity with an odds ratio (OR) of 0.90 (0.87-0.94) per 50 mg increase in phosphorus intake. Quintile analysis revealed potent negative correlations in both men and women (Table). Food groups strongly associated with phosphorus among our patients were fish (0.58), dairy products (0.54) and beans (0.52). These results imply the clinical relevance of controlling phosphorus intake as part of medical nutrition therapy for patients with T2DM.

Disclosure
M. Hatta: None. K. Fujihara: None. Y. Matsubayashi: None. Y. Takeda: None. R. Nedachi: None. D. Ishii: None. C. Horikawa: None. M. Kato: None. H. Maegawa: Research Support; Self; Antares Pharma, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.
2079-P: Association of Serum FAM19A5 with Metabolic and Vascular Risk Factors in Human Subjects With or Without Type 2 Diabetes
Authors: LEE YOU-BIN , KIM JUNG A. , ROH EUN , HONG SO-HYEON , CHOI KYUNG MOOK , BAIK SEI HYUN , YOO HYE JIN 
Published: June 2019

Introduction: A recent in-vitro and in-vivo experimental study has revealed that family with sequence similarity 19 [chemokine (C-C motif)-like] member A5 (FAM19A5), a novel secreted adipokine has inhibitory effects on proliferation and migration of vascular smooth muscle cells, and neointima formation of injured arteries. However, the relationship between serum FAM19A5 level and cardio-metabolic risks has not been evaluated in humans. For the first time, we investigated the association between serum FAM19A5 concentration with various metabolic and vascular risk factors in human subjects with or without type 2 diabetes.
Methods: Circulating FAM19A5 concentration was measured in 223 individuals (45 without diabetes and 178 with type 2 diabetes), and the association of FAM19A5 level with cardio-metabolic risk factors including body composition, plasma glucose, glycated hemoglobin (HbA1c), and atherosclerosis was explored.
Results: Serum FAM19A5 (pg/ml) was higher in patients with type 2 diabetes [172.70 (116.19, 286.42)] compared with that in individuals without diabetes [92.09 (70.32, 147.24)] (p&lt;0.001). Advance in serum FAM19A5 tertile was associated with a trend of increase in waist hip ratio (WHR), fasting plasma glucose (FPG), and mean brachial-ankle pulse wave velocity (baPWV) values. Serum FAM19A5 was positively correlated with waist circumference, WHR, alanine aminotransferase, FPG, HbA1c, and mean baPWV values. Multiple stepwise regression analysis identified WHR, low density lipoprotein cholesterol, and baPWV as determining factors for log-transformed serum FAM19A5 concentration (R2=0.0689).
Discussion: A novel adipokine FAM19A5 was closely related to various metabolic and vascular risk factors in human subjects, suggesting its potential as a biomarker of cardio-metabolic disease in humans.

Disclosure
Y. Lee: None. J.A. Kim: None. E. Roh: None. S. Hong: None. K. Choi: None. S. Baik: None. H. Yoo: None.