bluuebunny/crossref_metadata_2025_split huggingface dataset:
2087-P: Association between L-FABP with Lipid Metabolism and Alteration after Laparoscopic Sleeve Gastrectomy in Chinese Obese Subjects
Authors: YOU HUI , LIN ZIWEI , ZHU CUILING , WEN XIN , ZHANG MANNA , QU SHEN 
Published: June 2019

Liver fatty acid-binding protein (FABP1) is associated with intracellular transportation of fatty acids. However, only few studies indicated the relationship between serum FABP1 and metabolism. This study aimed to investigate the association of FABP1 levels and metabolism factors, and its change with laparoscopic sleeve gastrectomy (LSG) in Chinese. The cross-sectional analysis included a total of 187 subjects, of which 65 were with normal weight (BMI 18-24 kg/m2), 59 with over weight (BMI25-27 kg/m2), and 64 with obesity (BMI≥28 kg/m2). We found FABP1 levels in obese (303±235pg/ml, p&lt;0.05) and over-weight (189±187pg/ml, p&lt;0.07) subjects were significantly higher than those in normal-weight subjects (142±93pg/ml), and higher in NAFLD (225±220pg/ml, p&lt; 0.01) than in those without (129±74pg/ml) as well. In order to further investigated the correlation between FABP1 and metabolic factors, we performed a linear-regression analysis. We found FABP1 was positively correlated with BMI (R2=0.201, p&lt;0.001), ALT(R2=0.324, p&lt;0.001), AST(R2=0.387, p&lt;0.001), m-AST(R2=0.160, p&lt;0.001),[[γ]]-GT(R2=0.106, p&lt;0.001), DBIL(R2=0.078, p= 0.001), UA(R2 =0.111, p&lt;0.001), FBG(R2=0.066, p&lt;0.001), LDL(R2 =0.042, p=0.005) and negatively correlated with HDL(R2 =0.051, p= 0.002). Moreover, we also enrolled 25 severely obese patients who underwent LSG to observe its effects on FABP1. We found with the decline of BMI after surgery, FABP1(294±211pg/ml) were also gradient decreased at 3-month (230±227pg/ml, p=0.463), 6-month (144±154pg/ml, p=0.09) and 12-month (115±32pg/ml, p=0.045).
In conclusion, serum FABP1 were correlated with obesity and NAFLD, and it might be an important mediator participating in metabolism disorders.

Disclosure
H. You: None. Z. Lin: None. C. Zhu: None. X. Wen: None. M. Zhang: None. S. Qu: None.

Funding
National Key Research and Development Program of China (2018YFC1314101); National Natural Science Foundation of China (81700752, 81500687)
2094-P: Decreased Human Adipose Tissue-Resident Eosinophils in Obese Subjects Is Associated with Increased Insulin Resistance
Authors: HERNANDEZ JAMES D. , LI TING , RAU CASSANDRA , MASUDA MIA Y. , MADURA JAMES A. , JACOBSEN ELIZABETH A. , DEFILIPPIS ELEANNA 
Published: June 2019

Eosinophils (EOS) have been shown to play a major role in animal adipose tissue (AT) metabolism by promoting insulin sensitivity (IS) through an increase in alternatively activated macrophages (M2). Additionally, AT EOS are known to be decreased in obese mice. Currently, translational evidence is lacking for the role of EOS in human AT metabolism and IS. We investigated whether human AT-resident EOS numbers, as in animal models, are decreased in obese subjects and correlate with their degree of insulin resistance (IR). To date, we have studied 16 lean subjects (F15/M1, age 43 +2 years old; BMI 22.5+0.4kg/m2; HOMA-IR: 0.99 +0.38) and 22 obese, IR subjects (17F/5M, age 42 +1.3 years old; BMI: 38.9 +1.0kg/m2; HOMA-IR:5.0 +1.6) undergoing elective laparoscopic surgery. During surgical procedure, subcutaneous (SC) and omental (OM) fat was harvested. Stromal vascular fraction (SVF) was isolated after collagenase digestion of the fat samples. SVF was subjected to FACS analysis using BD Biosciences FACSAria III Cell Sorter with EOS count normalized as percent of CD45+ cells. Viable EOS were isolated and cytospin preparation was stained with a Diff-Quik. EOS isolated from SC AT of lean(L) subjects were found to significantly outnumber those obtained from obese (Ob) subjects by a 2.1:1 ratio (SC L:2.34 +0.29 vs. SC Ob: 1.11 +0.21, P&lt;0.03). A similar, but non-significant, trend was observed in OM. Furthermore, the number of SC AT-EOS was significantly inversely correlated with BMI, % fat and QUICKI index. qPCR analysis of SC AT mRNA revealed significantly increased classically activated macrophage markers (M1) (IL-1, IL-6, TNFα) in Ob vs. L, respectively while M2 markers (ARG-1, CCL24, CCL26) were significantly decreased in Ob vs. L. Based on these results we propose that, as in animal models, AT-resident EOS mediate AT metabolism and potentially IS by preserving an anti-inflammatory milieu within lean AT. Further studies are needed to elucidate the mechanism(s) involved.

Disclosure
J.D. Hernandez: None. T. Li: None. C. Rau: None. M.Y. Masuda: None. J.A. Madura: None. E.A. Jacobsen: None. E. DeFilippis: None.

Funding
Arizona Department of Health Services (14-00003606); Arizona Biomedical Research Commission; Kathryn H. and Roger Penske Career Development Award
2100-P: The Association between Blood Glucose and Different Anthropometrics and Body Composition Measures in the Chinese Population: Results from the Pinggu Metabolic Disease Study
Authors: ZHANG FANG , LI YUFENG , ZHAO YINGXI , ZHOU XIANGHAI , JI LINONG 
Published: June 2019

Introduction: Empirical cohort have evidenced that central adiposity is the strongest modifiable risk factor for T2DM, however most studies neglect the absolute measures including visceral fat area (VFA) and subcutaneous fat (SFA). This study aims to analyze the strength of association between FPG, 2hPPG, HbA1c and nine anthropometrics measures, to explore the best indicator for hyperglycemic risks.
Methods: Analyses were based on the data from the Pinggu Metabolic Disease study in 2013-2014. Excluded participants with self-reported DM, dyslipidemia and hyperuricemia, 2940 were included. Anthropometrics, VFA and SFA were measured. Logistic regression was used to find the association between per standard increase and risk for high FPG (≥7.0 mmol/L), 2hPPG (≥11.1 mmol/L), HbA1c (≥6.5%).
Results: Higher VFA and SFA were associated with higher FPG, 2hPPG and HbA1c after adjusting for other covariates. The strongest association was waist to hip ratio (WHR) for FPG and 2hPPG, and waist circumference (WC) for HbA1c. The strength of association between SFA, VFA and FPG, 2hPPG and HbA1c was less than WHR and WC. VSR showed a comparably weak strength of association. See Figure for detail result.
Conclusion: WHR and WC remains the best indicators of high risk factor for hyperglycemia among healthy Chinese population.

Disclosure
F. Zhang: None. Y. Li: None. Y. Zhao: None. X. Zhou: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.
2103-P: Sex Differences in Human Adipose Tissue: Comprehensive Transcriptome Profiling
Authors: BOGU GIREESH , SNYDER MICHAEL , MCLAUGHLIN TRACEY 
Published: June 2019

The sexual dimorphism of adipose tissue is incompletely understood. Differences in total and regional adiposity have been described, but the molecular basis for these differences is unclear. We have conducted the first comprehensive transcriptome analysis in adipose tissue from healthy age and BMI-matched women and men. Results demonstrate upregulation of lipid and carbohydrate metabolism in pre and postmenopausal women vs. men. In men few genes were upregulated: the majority of these were related to inflammation vs. upregulation of inflammatory genes in men. Measurement of regional and intrahepatic fat, adipose cell size, and systemic insulin resistance complement RNAseq (n=39) and rtPCR (n=54) results.

Disclosure
G. Bogu: None. M. Snyder: Advisory Panel; Self; Jungla. Consultant; Self; Merck & Co., Inc. Other Relationship; Self; 10x Genomics, Akna, Filtricine, Illumina, Inc., January, Personalis, Qbio, SensOmics. T. McLaughlin: Advisory Panel; Self; January. Stock/Shareholder; Self; Eiger BioPharmaceuticals.

Funding
American Diabetes Association (1-11-CT-35 to T.M.); National Institute of Diabetes and Digestive and Kidney Diseases
211-OR: Analysis of Longitudinal Autoantibody Profiles and the Progression Rates to Type 1 Diabetes
Authors: GHALWASH MOHAMED , ANAND VIBHA , LIU BIN , KOSKI EILEEN , NG KENNEY , DUNNE JESSICA L. , LUNDGREN MARKUS , REWERS MARIAN , VEIJOLA RIITTA ,   FOR T1DI STUDY GROUP
Published: June 2019

Clinical type 1 diabetes (T1D) is preceded by asymptomatic islet-autoimmunity (IA) with presence of islet autoantibodies (AAb). However, both AAb profiles (clusters) during IA phase and progression rate to T1D are heterogeneous. It is unclear if AAb profiles affect the progression to T1D similarly in different countries. We analyzed data from 3 prospective birth cohorts, DAISY (U.S.), DiPiS (Sweden), and DIPP (Finland), to address this question. We developed a similarity algorithm that considers subject-level temporal IA profiles (based on 4 AAbs - IAA, GADA, IA2A, and ZnT8A positivity or negativity), age at which AAb developed, and imbalance in AAb positivity by weighting positive AAb matches higher than negative ones. Using this subject-level similarity measure, we performed hierarchical clustering of AAb positive subjects having at least 3 visits. We used a log-rank test to identify the number of clusters in 1125 DIPP subjects (329 T1D cases), 309 DAISY subjects (70 cases), and 226 DiPiS subjects (33 cases). Each dataset was individually clustered. We identified three clusters in each dataset associated with different rate of progression from seroconversion to T1D - slow progressors (SP), moderate progressors (MP) and fast progressors (FP). These were distributed as follows: DIPP (654 SP with 3% 10-year T1D risk, 356 MP with 60% risk, 115 FP with 96% risk); DAISY (215 SP with 6% 10-year risk, 92 MP with 62% risk, 2 FP with 100% risk); and DiPiS (160 SP with 3% 10-year risk, 62 MP with 58% risk, 4 FP with 100% risk). Finally, we tested the generalizability of the clusters by 1) learning a clustering from one data set “learned clusters,” 2) classifying subjects from another (independent) data set with the “learned clusters,” and 3) measuring how often the subjects were assigned to the same cluster (SP, MP, FP) as the “internal” clustering. The average accuracy of cluster transfer was high (mean = 87.9%, sd = 1.1%) suggesting that the IA profile predicts progression rate to T1D independently of the population.

Disclosure
M. Ghalwash: None. V. Anand: None. B. Liu: None. E. Koski: None. K. Ng: None. J.L. Dunne: None. M. Lundgren: None. M. Rewers: None. R. Veijola: None.

Funding
JDRF
2114-P: Use of Visceral Fat Area Measurement for Evaluating Obesity in Elderly Patients with Type 2 Diabetes
Authors: MINAMIZUKA TAKUYA , MAEDA YUKARI , KOSHIZAKA MASAYA , ISHIKAWA TAKAHIRO , MAEZAWA YOSHIRO , YOKOTE KOUTARO 
Published: June 2019

Objective: In Japan, obesity is defined as a body mass index (BMI) ≥25 kg/m2. Sarcopenic obesity (low BMI with visceral fat accumulation) has high mortality and is common in elderly people. We evaluated the value of visceral fat area (VFA) measurement in elderly type 2 diabetes (T2D) patients for determining sarcopenic obesity.
Methods: We analyzed 124 T2D patients who were hospitalized for glycemic control. They were divided into elderly people (aged ≥65 years) (n=74) and non-elderly people (aged &lt;65 years) (n=50). They were further divided according to BMI (&lt;25 kg/m2 and ≥25 kg/m2) and VFA (&lt;100 cm2 and ≥100 cm2). We compared the number and percentages of significantly different metabolism related items by BMI or VFA grouping between the elderly and non-elderly groups. The correlation between BMI and VFA was also analyzed.
Results: We observed the following patient characteristics: the elderly group; 55 men (74.3%), average age 73.2 years, BMI 24.7 kg/m2, and VFA 137.7 cm2; and the non-elderly group; 25 men (50%), average age 49.8 years, BMI 31.8 kg/m2, and VFA 180.7 cm2. Only 6/43 (14.0%) metabolism related items differed significantly between patients with BMI ≥25 kg/m2 and those with BMI &lt;25 kg/m2 in the elderly group, whereas 18/43 (41.9%) items differed significantly between patients with BMI ≥25 kg/m2 and those with BMI &lt;25 kg/m2 in the non-elderly group. In the elderly group, 15/43 (34.9%) metabolism related items differed significantly between patients with VFA ≥100 cm2 and those with VFA &lt;100 cm2, whereas in the non-elderly group, 18/43 (41.9%) items differed significantly between patients with VFA ≥100 cm2 and those with VFA &lt;100 cm2. The correlation between BMI and VFA was stronger in the non-elderly group than in the elderly group.
Conclusion: Although BMI is a simple and useful index of obesity evaluation, sarcopenic obesity may be overlooked. In elderly patients who tend to have sarcopenic obesity, VFA measurement might be a more useful index of obesity.

Disclosure
T. Minamizuka: None. Y. Maeda: None. M. Koshizaka: Research Support; Self; Astellas Pharma Inc., Pfizer Health Research Foundation, Taisho Pharmaceutical Co., Ltd. T. Ishikawa: None. Y. Maezawa: None. K. Yokote: None.
2128-P: Exploring the Role of Autophagy in Pancreatic Alpha Cells
Authors: HIMURO MIWA , MIYATSUKA TAKESHI , SUZUKI LUKA , MIURA MASAKI , KATAHIRA TAKEHIRO , GOTO HIROMASA , NISHIDA YUYA , SASAKI SHUGO , FUJITANI YOSHIO , WATADA HIROTAKA 
Published: June 2019

Autophagy is known to play a pivotal role in intracellular quality control through the degradation of subcellular damaged organelles and components. Whereas autophagy is essential for maintaining β-cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting α cells. To analyze the role of autophagy in α cells, we generated a mutant mouse model lacking Atg7, a key molecule for autophagosome formation, specifically in α cells. Histological analysis demonstrated an increased number of glucagon-positive cells, with a multilayered structure, in the islets under Atg7 deficiency, although metabolic profiles, such as body weight, blood glucose and plasma glucagon levels, were comparable between Atg7-deficient mice and control littermates. Consistent with our previous findings that Atg7 deficiency suppressed β-cell proliferation, cellular proliferation was suppressed in Atg7-deficient α cells.
These findings suggest that α-cell autophagy plays a role in maintaining α-cell mass and normal islet architecture, but appears to be dispensable for metabolic homeostasis.

Disclosure
M. Himuro: None. T. Miyatsuka: None. L. Suzuki: None. M. Miura: None. T. Katahira: None. H. Goto: None. Y. Nishida: None. S. Sasaki: None. Y. Fujitani: Research Support; Self; Takeda Pharmaceutical Company Limited. H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited.

Funding
Japan Society for the Promotion of Science
213-OR: Lowering HbA1c during the First 2 Years Predicts a Lower Long-Term HbA1c on a Clinic Level
Authors: HANAS RAGNAR , HANBERGER LENA , SAMUELSSON ULF , ÅKESSON KARIN 
Published: June 2019

Background: Mean HbA1c in children and adolescents varies between countries, but there is a considerable variation also between clinics within the same country. It has been difficult to characterize factors that contribute to this difference. We aimed to compare early metabolic control with long-term mean HbA1c in clinics within Sweden.
Methods: The Swedish pediatric diabetes quality registry (SWEDIABKIDS) covers 98% of children and adolescents &lt; 18 years in Sweden. We captured overall mean HbA1c for 36/42 clinics (6 had less than 20 patients with &lt; 2 years’ duration) and compared with HbA1c over the first 2 years of diabetes. Values with &lt; 3 months’ duration were not included as these are affected by glucose levels before diagnosis.
Results: Mean overall HbA1c for all 42 clinics was 54.6 (95% CI 53.3-55.9) mmol/mol (7.1%, 95% CI 7.0-7.3) and over the first 2 years for the 36 clinics 50.1 (95% CI 48.0-52.2) mmol/mol (6.7%, 95% CI 6.5-6.9). The correlation for the 36 clinics was r=0.677 (p&lt;0.001). R2 was 0.458, i.e., 45.8% of the variation in overall HbA1c was explained by HbA1c during the first 2 years of diabetes.
Conclusions: An intensive education program at the onset of diabetes resulting in a low HbA1c early on is a good investment for the long-term metabolic control. Mean HbA1c during the first 2 years will be a good variable to measure the effectiveness and success on a clinic level of new implementations in diabetes treatments.

Disclosure
R. Hanas: Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; AstraZeneca. L. Hanberger: None. U. Samuelsson: None. K. Åkesson: Speaker's Bureau; Self; Novo Nordisk A/S.
2131-P: Dextran Sulfate and HGF Ameliorate Type 1 Diabetes
Authors: LU GEMING , ZHANG TUO , HOMANN DIRK , GARCIA-OCAÑA ADOLFO 
Published: June 2019

Type 1 diabetes (T1D) results from loss of immune tolerance and β-cells. Currently, research on T1D treatments focus on regeneration and preservation of β-cells and restoration of immune tolerance. The sulfated synthetic polysaccharide dextran sulfate (DS), a mild anticoagulant and blood volume expander used in clinic, inhibits dendritic cell maturation and activation. DS administration increases circulating hepatocyte growth factor (HGF) in rodents and humans. In this study, we tested the effects of DS on: T1D development in NOD mice; β-cell survival, function and mitochondrial activity in cytokine-treated islets; and, the profile of immune activation and tolerance markers. DS treatment reduced spontaneous T1D onset in female NOD mice from 70% to 20%. T1D prevention in the wake of DS treatment was associated with preserved plasma insulin and β-cell mass, and reduced β-cell death. DS synergized with HGF in protecting mitochondrial function of cytokine-treated islets in vitro, maintaining maximal respiration, ATP production and glucose-stimulated insulin secretion. Pancreas histology showed decreased immune cell infiltration in islets of DS-treated mice. Splenocytes and pancreatic lymph nodes of DS-treated mice displayed decreased IFNγ+ CD8+ and CD4+, and increased IL4+ CD4+ and FoxP3+ CD4+ cells. In vitro, DS+HGF increased both the inhibitory phenotype of bone marrow derived macrophages (BMDM) downregulating IL1β, TNFα, and iNOS and increasing IL10, and the number of FoxP3+ CD4+ treated with αCD3 and αCD28 in the absence of TGF β. DS+HGF enhanced mitochondrial mass, potential, oxidative phosphorylation and expression of OXPHOS complexes, metabolic features of inhibitory BMDMs and regulatory T cells. Collectively, these results indicate that DS and HGF ameliorate T1D in NOD mice by alleviating the metabolic impairment induced by inflammation in islets and by boosting mitochondrial function to preserve β-cell function and upregulate M2 macrophages and regulatory T cells. DS and HGF can be of great value for treating T1D.

Disclosure
G. Lu: None. T. Zhang: None. D. Homann: None. A. Garcia-Ocaña: None.

Funding
National Institutes of Health (DK113079, DK020541, W81XWH-17-1-0363)
2142-P: Toll-Like Receptors 2 and 4 Act as Brakes to Regulate Adaptive ß-Cell Mass Expansion in Diet-Induced Obesity
Authors: JI YEWEI , SUN SHENGYI , QI LING 
Published: June 2019

Restoration of β cell mass via β cell regeneration is a promising approach for treatment of diabetes. However, β cell proliferative capacity declines after adolescence and remains extremely low during entire adulthood, posing a significant roadblock in β cell regeneration therapy. The mechanism that inhibits β cell replication in adult and obesity remains enigma. Toll-Like Receptors (TLRs) are membrane-spanning proteins that recognize microbes-derived structurally conserved molecules and play a key role in innate immune response. Serendipitously, our study demonstrated that Toll-like receptor (TLR) 2/TLR4 act as molecular “brakes” for diet-induced β cell replication in both mice and humans. The combined loss of TLR2/TLR4, but not individually, dramatically increases facultative β, not α, cell replication, leading to progressively enlarged β cell mass and hyperinsulinemia in diet-induced obesity. Mechanistically, loss of TLR2/TLR4 increases β cell proliferation and nuclear abundance of Cyclin D2 and cyclin-dependent kinase 4 (CDK4) in an extracellular signal-regulated kinase (ERK)-dependent manner. These data reveal a novel negative regulatory mechanism governing adaptive β cell mass expansion in diet-induced obesity and suggest that selective targeting of TLR2/TLR4 pathways may hold promise for reversing β cell failure in diabetic patients.

Disclosure
Y. Ji: None. S. Sun: None. L. Qi: None.

Funding
American Diabetes Association (1-12-CD-04, 1-19-IBS-235 to L.Q.); JDRF (47-2012-767, 1-SRA-2014-251-Q-R, 2-SRA-2018-539-A-B); American Heart Association (17SDG33670192); Michigan Nutrition Obesity Research Center (P30DK089503); Howard Hughes Medical Institute (59107338)
2144-P: Early Administration of Dapagliflozin Preserves Pancreatic Beta-Cell Mass through an Epigenetic Modification in a Mouse Model of Type 2 Diabetes
Authors: ASAHARA SHUN-ICHIRO , KANNO AYUMI , KIDO YOSHIAKI 
Published: June 2019

Aims: The preservation of pancreatic β-cell mass is an essential factor in the onset and development of type 2 diabetes mellitus. Recently, sodium-glucose co-transporter 2 inhibitors have been launched as anti-hyperglycemic agents, and their organ protective effects are attracting attention. They are also reported to have favorable effects on the preservation of pancreatic β-cell mass, but the appropriate timing for the administration of sodium-glucose co-transporter 2 inhibitors is obscure.
Materials and Methods: In this study, we administered a sodium-glucose co-transporter 2 inhibitor, dapagliflozin, to an animal model of type 2 diabetes mellitus, db/db mice, and investigated the adequate timing and duration for its administration. We also conducted microarray analysis and methylated DNA immunoprecipitation (MeDIP) using pancreatic islets from db/db mice.
Results: We found that dapagliflozin preserved pancreatic β-cell mass depending on the duration of administration, and markedly improved blood glucose levels. If the duration was the same, the earlier administration of dapagliflozin was more effective in preserving pancreatic β-cell mass, increasing serum insulin levels, and improving blood glucose levels. From the analysis of microarray, we discovered that the expression of Agr2, Tff2, and Gkn3 was significantly upregulated following the early administration of dapagliflozin. This upregulated gene expression might provide a legacy effect for the preservation of pancreatic β-cell mass. In addition, MeDIP analysis revealed that early administration of dapagliflozin affected DNA methylation in pancreatic islets of db/db mice.
Conclusions: We expect that the early administration of dapagliflozin would provide a long-lasting effect in preserving pancreatic β-cell mass.

Disclosure
S. Asahara: Research Support; Spouse/Partner; AstraZeneca. A. Kanno: None. Y. Kido: Research Support; Self; AstraZeneca.

Funding
AstraZeneca K.K.; Ono Pharmaceutical Co., Ltd.