bluuebunny/crossref_metadata_2025_split huggingface dataset:
1100-P: A Four-Humanitarian Agency Survey of Diabetes Care in 83 Humanitarian Settings
Authors: KEHLENBRINK SYLVIA , MAHBOOB OMAR , AL-ZUBI SARA A. , BOULLE PHILIPPA , PERONE SIGIRIYA AEBISCHER , KIAPI LILIAN , ALANI AHMAD H. , HERING HEIKO , WOODMAN MICHAEL , KAYDEN STEPHANIE , DONELAN KAREN , PORNEALA BIANCA , MEIGS JAMES B. 
Published: June 2021

Background: We are currently facing unprecedented humanitarian crises. With diabetes at record-high levels and projected increases in humanitarian crises globally, data on the burden and management of DM in humanitarian crises is needed to stop unnecessary disability and death.
Methods: We surveyed data on diabetes care provision in humanitarian medical services in 2018 across 4 humanitarian agencies (Doctors Without Borders, International Committee of the Red Cross, International Rescue Committee, United Nations High Commissioner for Refugees) with 83 randomly selected sites across 27 countries in 5 global regions. Of 83 sites, 65 (78%) reported collecting DM care data and were used for cross-sectional analysis of rates and proportions.
Results: Of 65 sites, most were in the Eastern Mediterranean (n=29, 45%) and Africa (35%), with 20% elsewhere; 34% were refugee camps, 34% rural non-camp sites, 21% urban non-camp sites, 11% internally displaced persons (IDP) camps. Populations were mostly a mix of refugees, IDPs and the general population (n=46/65, 71%), with refugees only at 23% and IDPs only at 6% of sites. Of 65 sites, 58 were affected by conflict (89%), 5% epidemics, 1% natural disasters and 5% multiple crisis types. Most sites (n=49) were in protracted crises (75%), with 23% in recovery stages and 2% in acute crisis. Of 65 sites, 46 (71%) reported providing clinical DM management. However, only 66% had insulin available, 71% had capillary glucose testing, 55% urine dipstick glucose, 19% hemoglobin A1c testing, 22% home glucose monitoring, 35% community outreach, 58% patient education, 32% training of staff and 52% continuity of care systems.
Conclusions: DM services were mostly provided in protracted humanitarian settings. Services were widespread but often rudimentary and delivered to the general population as well as refugees and IDPs. Improving DM care for crisis-affected populations is urgently needed.

Disclosure
S. Kehlenbrink: None. S. Kayden: None. K. Donelan: None. B. Porneala: None. J. B. Meigs: Consultant; Self; Quest Diagnostics. O. Mahboob: None. S. A. Al-zubi: None. P. Boulle: None. S. Aebischer perone: None. L. Kiapi: None. A. H. Alani: None. H. Hering: None. M. Woodman: None.
1107-P: Trends of First-Line Antidiabetic Treatment among 2007-2017 Medicare Beneficiaries Newly Diagnosed with Type 2 Diabetes (T2D) and Their Determinants
Authors: LI YUJIA , HERNANDEZ INMACULADA , GABRIEL NICO , KANE-GILL SANDRA L. , ESSIEN UTIBE , TOLEDO FREDERICO , GUO JINGCHUAN 
Published: June 2021

Background: Guidelines recommend initiating metformin at the time of T2D diagnosis in the absence of contraindications for asymptomatic patients. However, the evidence is scarce regarding real-world patterns and factors associated with antidiabetic treatment initiation in patients with newly diagnosed T2D.
Methods: We used a 5% random sample of Medicare beneficiaries newly diagnosed with T2D in 2007-2017 and followed them for one year. The outcome was time to initiation of an antidiabetic agent within the first year of diagnosis. We examined trends in the proportion of outcome and the therapeutic class initiated by year. We constructed Cox Proportional Hazard models to identify factors associated with treatment initiation.
Results: Of 231,408 patients newly diagnosed with T2D, the mean age was 71.7, and 62.2% were female. Only 13.7% initiated an antidiabetic agent within the first year of diagnosis. Although the proportion of initiation within one year of T2D diagnosis was relatively constant over time (12.7% in 2007 to 15.4% in 2017), the mean time to initiation decreased from 74.1 days in 2007 to 21.7 days in 2017 (p&lt;0.05). Of those who initiated treatment, 54.2% and 21.5% initiated metformin and sulfonylurea in 2007, while 84.4% and 6.0% initiated metformin and sulfonylurea in 2017, respectively. In the adjusted model, age (HR 0.92, 95%CI 0.91-0.93 for 10-year increase), female sex (HR 0.89, 95%CI 0.87-0.91), number of comorbidities (HR 0.86, 95%CI 0.86-0.87 for one additional) and residence in urban areas (HR 0.78, 95%CI 0.76-0.80) were associated with decreased hazards of antidiabetic initiation.
Conclusion: We found unexpectedly low rates of initiation of first-line treatment among Medicare beneficiaries with newly diagnosed T2D. The changes in the proportion of different drug classes reflect the change in guideline recommendations. Further investigation is needed to understand the causes underlying the low initiation.

Disclosure
Y. Li: None. I. Hernandez: Consultant; Self; Bristol-Myers Squibb Company, Pfizer Inc. N. Gabriel: None. S. L. Kane-gill: None. U. Essien: None. F. Toledo: Consultant; Self; AstraZeneca. J. Guo: None.
1111-P: Integrating Longitudinal Clinical and Baseline Multiomics Data for Predicting C-Peptide Progression in Newly Diagnosed Type 1 Diabetes
Authors: BRORSSON CAROLINE , ARMENTEROS JOSE JUAN ALMAGRO , MAZZONI GIANLUCA , KAUR SIMRANJEET , SCHULTE ANKE M. , MATHIEU CHANTAL , BRUNAK SØREN ,   ON BEHALF OF THE INNODIA CONSORTIUM
Published: June 2021

Background: Development of disease-modifying therapy for type 1 diabetes (T1D) is hampered by the limited understanding of pathogenesis, heterogeneity, lack of disease biomarkers and stratifiers. Using the INNODIA consortium pan-European infrastructure to collect prospective clinical data from newly diagnosed subjects combined with multi-omics data, we mined integrated datasets using deep learning to identify novel relationships that could transform the disease monitoring landscape.
Method: Samples collected &lt;6 weeks from diagnosis from 100 islet autoantibody positive participants were prioritised for omics analysis and the data integrated with clinical parameters and C-peptide (CP) from mixed meal tolerance tests (at 3, 6 and 12 months). SNP array data, plasma metabolomics, lipidomics and miRNAs, serum proteomics, whole blood RNA-sequencing and multiFACS immunomics from PBMCs were collected. We applied a variational autoencoder (VAE) to simultaneously integrate the data and learn CP progression over 12 months. The latent (lower dimensional) representation of the VAE integrated data was clustered to identify clinically meaningful subgroups.
Results: Clustering identified five age-independent subgroups with significantly different progression patterns (p&lt;0.05). Cluster 1 and 3 associated with lower fasted and stimulated CP. Cluster 2 and 5 associated with higher fasted CP, while cluster 4 most strongly associated with higher stimulated CP. Cluster 1 had the lowest stimulated CP at baseline, cluster 5 the lowest fasted CP and cluster 4 the highest fasted and stimulated CP at baseline. Investigation of the most predictive signals from the omics data is ongoing.
Discussion: The preliminary results suggest that the VAE can learn meaningful progression patterns from integrated clinical and multi-omics data, which holds great promise to uncover important data structures not readily discovered when analyzing single data types.

Disclosure
C. Brorsson: Employee; Spouse/Partner; Novo Nordisk A/S. J. Almagro armenteros: None. G. Mazzoni: Employee; Self; Novo Nordisk A/S. S. Kaur: None. A. M. Schulte: None. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis. S. Brunak: Board Member; Self; Intomics A/S, Proscion A/S, Stock/Shareholder; Self; Hoba Therapeutics Aps, Novo Nordisk A/S. On behalf of the innodia consortium: n/a.

Funding
INNODIA (115797)
1129-P: The Genetic Architecture of Cardiovascular Disease in Individuals with Type 2 Diabetes
Authors: RICHARD ERIN L. , CAO STEVEN , SHADYAB ALADDIN , SALEM RANY 
Published: June 2021

Background: Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease including coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD). However, the genetic underpinnings of cardiovascular disease in those with T2DM is not well understood.
Methods: Using 15 studies from dbGaP and the UK Biobank, we conducted the largest to date genome-wide association studies (GWAS) for CHD, stroke and PVD in up to 61,880 individuals with T2DM including 47,140 of European, 8,891 of African, 2,622 of Hispanic, 2,120 of South Asian and 1,107 of East Asian ancestry. GWAS were combined via ancestry-specific and transethnic meta-analyses with fixed-effects. Additional transethnic analysis with MR-MEGA was conducted to account for heterogeneity in allelic effects correlated with ancestry.
Results: We replicated previously reported CHD associated loci at genome-wide significance (GW, p≤5×10-8) including 9p21, LPA, and PSRC1. Combining our results with those of prior CHD GWAS in T2DM revealed additional GW significant signals in known CHD loci: PHACTR1, ADAMTS7, HHIPL1, and LPL. European ancestry specific analysis confirmed prior GW significant associations between LPA and PHACTR1 loci and PVD. MR-MEGA analysis of PVD identified novel GW significant loci in CNST and AVPI1. We found a significant genetic correlation of 0.74 (SE= .27) between CHD and PVD. Transethnic analysis of stroke GWAS yielded no GW significant loci. However, African ancestry specific analysis yielded two novel GW signals in the NKAIN2 and BRF1 loci. A significant association between interleukin-6 signaling and stroke was identified using pathway analysis.
Conclusions: Ancestry-specific and transethnic analysis of cardiovascular disease in T2DM confirmed prior CHD GWAS findings and revealed novel associations with PVD and stroke that warrant further investigation.

Disclosure
E. L. Richard: None. S. Cao: None. A. Shadyab: None. R. Salem: None.

Funding
National Institutes of Health
1138-P: Diabetes Induced by Immunotherapy
Authors: VY DUCHDA 
Published: June 2021

Introduction: Immunotherapy in the field of oncology consists of administering substances that stimulate the immune system involved in its recognition and destruction of the tumor, on the other hand it gives side effects including diabetes.
Observation: After 29 injections of Pembrolizumab to treat his pulmonary adenocarcinoma, a 62-years old man was hospitalized with inaugural diabetic ketoacidosis with plasma glucose 5.47g and pH 7.07 in blood gas. The dosage of the C peptide is low, the antibodies specific for autoimmune diabetes were negatives at the time of diagnosis. HLA DR3/DQ2 study reveals a predisposition to autoimmune type 1 diabetes. Basal-bolus insulin therapy was started with a correct balance of diabetes.
Discussion: Diabetes induced by anti-PD1 immunotherapy is more common in patients older than 50 years and shown between one month and nineteen months after starting treatment. The reason for hospitalization is always diabetic ketoacidosis with very high plasma blood glucose levels and deep insulinopenia. The HLA studying of patients shown a predisposition to autoimmune diabetes.
Conclusion: The management of diabetes induced by immunotherapy requires consultation between the endocrinologist and the oncologist. Patient education with the initial assessment diabetes are essential before and during treatment with immunotherapy. An initial assessment (the fasting blood glucose, HbA1c) routinely before starting anti-PD1 therapy and determination of fasting blood glucose before each course of treatment, once a month during the first three months then every three months or urgently if clinical signs are present suggestive of diabetes. In addition, insulin therapy should start immediately in case of diagnosis is made.

Disclosure
D. Vy: None.
114-OR: Overexpression of Alpha-1 Antitrypsin in MSCs Delays Onset of Type 1 Diabetes in the NOD Mice by Increasing Their Antiinflammatory and Protection Functions
Authors: WEI HUA , GOU WENYU , STRANGE CHARLIE , WANG HONGJUN 
Published: June 2021

We have shown that overexpression of human alpha-1 antitrypsin (hAAT) in mesenchymal stromal cells (hAAT-MSCs) improves mobility and function of MSCs. In this study we further characterized hAAT MSCs and control MSCs and compared their therapeutic effects in the prevention of type 1 diabetes in the spontaneous non-obese diabetic (NOD) mice. Bone marrow specimens from three individual donors were purchased from StemExpress. Cells were grown to passage 3-4 and infected with hAAT-containing virus for hAAT-overexpression. Single Cell RNAseq was performed by the 10X Genomic System. Proteomic Analysis of exosomes was performed at the MUSC Proteomic Core. MSCs and hAAT-MSCs from one donor were injected into the NOD mice at 8 weeks of age. Mice blood glucose levels were measured twice per week. Cell infiltration into islets was analyzed by H&E staining of pancreatic tissues. Single cell RNAseq analysis showed that hAAT-MSCs and control MSCs have different gene expression signatures, in which hAAT-MSCs showed increased expressions of chemokine (C-X-C motif) ligands (CXCL1, 3, 8), HES5 and others. Exosome proteomic analysis indicates that exosomes from these two types of cells have distinct protein patterns. In hAAT-MSCs cells, platelet degranulation proteins were upregulated and proteins involved in cell-cell adhesion, and cell division were been downregulated. In the NOD mice, a single dose of hAAT-MSCs led to delayed onset of T1D, associated with reduced cell infiltration into the islets. hAAT-MSC therapy showed more profound protection compared to control MSCs. It is likely that overexpression of hAAT enhanced the anti-inflammatory function (via regulating chemokines) promoting the Notch signaling pathway (via regulating HES5) and lead to improved protection in the NOD mice.

Disclosure
H. Wei: None. W. Gou: None. C. Strange: None. H. Wang: None.

Funding
National Institutes of Health (1R01DK105183, DK120394, DK118529); U.S. Department of Veterans Affairs (I01BX004536)
1143-P: ZnT8 Autoantibody Positivity Does Not Predict Pediatric Diabetes Presentation or Subsequent Clinical Course
Authors: DAHL AMANDA R. , JENKINS SARAH , ZBACNIK JADE , FOSTER JESICA , PITTOCK SIOBHAN 
Published: June 2021

Introduction: Type 1 diabetes specific autoantibodies are glutamic acid decarboxylase (GAD65), protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence of ZnT8 antibodies(Ab) was predictive of clinical presentation at diagnosis or subsequent disease course.
Methods: Between January 2003 and May 2019, 105 patients aged ≤ 21 years with a clinical diagnosis of T1DM had at least 1 diabetes autoantibody measured. For subjects who had less than 4 autoantibodies analyzed initially, residual serum sample was retrieved, and remaining autoantibodies were analyzed. Retrospective chart review was completed. At diagnosis, we evaluated BMI z-score, HbA1c, and the presence and severity of DKA. Complications recorded post diagnosis included episodes of DKA, diagnosis of autoimmune (AI) disease, and the presence of vascular complications.
Results: Of the 105 patients, 71 were ZnT8(+) (68%). When comparing ZnT8Ab(+) to (-) patients at diagnosis, there was no difference in age (p=0.94), BMI z-score (p=0.83) or presence of DKA (p=0.26). There was no difference in duration of follow up between ZnT8 Ab (+) and (-) groups (p=0.54). Over follow-up, (0.05-15.7 years), there was no difference in rates of DKA episodes (p=0.71). There were no macrovascular complications recorded and no difference in microvascular complications between the 2 groups (p=0.14). There were more AI conditions in the ZnT8Ab(+) group, 77% compared to 23% in ZnT8Ab(-), but this did not reach statistical significance (p=0.12).
Conclusions: Our study, unlike others, suggests that the presence of ZnT8 Ab does not result in a difference in disease course at presentation. This study adds to the literature as it has follow up on patients. Over up to 15 years of follow-up, there is no difference in complications between those with and without ZnT8 Ab’s. This study should be validated with larger numbers and longer follow up.

Disclosure
A. R. Dahl: None. S. Jenkins: None. J. Zbacnik: None. J. Foster: None. S. Pittock: None.
1148-P: Liver Androgen Receptor Knockout Delays the Onset of Diet-Induced Metabolic Dysfunction in Female Mice Compared with Male Mice
Authors: OLIVER TRINITEE R. , OSEI-NTANSAH ADJOA , ANDRISSE STANLEY , LOFTON TAYLOR , FALZARANO CLAIRE 
Published: June 2021

Polycystic ovarian syndrome (PCOS) is a hormonal disorder with insulin resistance (IR) and hyperandrogenism (HA) as drivers of the condition. PCOS women have an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Our lab explores NAFLD in PCOS through a mouse model with a liver androgen receptor (AR) knockout (LivARKO). The role of AR in high-fat diet (HFD) induced metabolic disease is not fully understood. We hypothesized that LivARKO would cause dysglycemia in males but protect from dysglycemia in females.
To test the hypothesis, we collected data from mice fed a HFD or a caloric adjusted control diet (CD) over the course of two months. We performed glucose tolerance (GTT), insulin tolerance (ITT), and pyruvate tolerance (PTT) tests.
At 1-month, HFD female LivARKO mice displayed no difference in glucose tolerance compared to CD LivARKO female mice, suggesting that at one month LivARKO is protecting female mice from HFD-induced metabolic dysfunction. HFD male LivARKO mice displayed impaired glucose tolerance (IGT) compared to CD LivARKO mice. Thus, LivARKO was not protective against HFD-induced glucose metabolic dysfunction in male mice. At 2-months, HFD showed IGT compared to Control diet in male and female LivARKO mice, suggesting that LivARKO slowed the progression to metabolic disease in female mice but did not fully stop it. HFD male and female LivARKO mice did not display significant changes in insulin tolerance at 1-month compared to CD mice. HFD male and female LivARKO mice showed impaired pyruvate tolerance starting at 1-month and continuing at 2-months compared to CD LivARKO mice. The impairment was significantly greater in male mice.
In conclusion, we found that it took LivARKO female mice longer to show dysglycemia from HFD than male LivARKO mice. Thus, in females, LivARKO slowed the progression to metabolic disease, but did not fully stop it. The impaired PTT suggests the effects of HFD may alter hepatic gluconeogenic regulation.

Disclosure
T. R. Oliver: None. A. Osei-ntansah: None. S. Andrisse: None. T. Lofton: None. C. Falzarano: None.

Funding
National Science Foundation (HRD-1931045)
1153-P: Sodium-Glucose Cotransporter-2 Inhibitors Increase Food Intake via a Mechanism That Acts on the Central Nervous System Involving Phosphorylation of Adenosine Monophosphate-Activated Protein Kinase in the Lateral Hypothalamus
Authors: TAKEDA KENJI , ONO HIRAKU , OHNO TOMOHIRO , YOKOTE KOUTARO 
Published: June 2021

Sodium glucose cotransporter-2 (SGLT2) inhibitors are widely used for diabetes treatment. Although SGLT2 inhibitors have been clinically observed to increase food intake, roles or even the presence of SGLT2 in the central nervous system (CNS) has not been established. We aimed to elucidate potential functions of SGLT2 in the CNS, and the effects of CNS-targeted SGLT2 inhibitors on food intake. We administered three kinds of SGLT2 inhibitors, tofogliflozin, dapagliflozin, and empagliflozin, into the lateral ventricle (LV) in rats and evaluated their effects on food intake. Bolus ICV SGLT2 inhibitor induced an increase in food intake. Tofogliflozin had the strongest effect among these drugs. No effect was observed when the same dose of tofogliflozin was administered intraperitoneally. We also evaluated the effects of tofogliflozin administration in the third (3V) and fourth ventricle (4V). Food intake was most markedly enhanced when tofogliflozin was infused into the LV. Fewer or no effects were observed with infusion into the 3V or 4V, respectively. Intraperitoneal administration of liraglutide, a GLP-1 receptor agonist known to suppress food intake, was combined with central tofogliflozin to elucidate whether GLP-1 signaling antagonizes the effect of central SGLT2 inhibitors on food intake. Systemic administration of liraglutide suppressed the effect of ICV tofogliflozin on food intake. To elucidate potential molecular mechanisms mediating changes in feeding, hypothalamic areas associated with food intake regulation were harvested and analyzed after intracerebroventricular administration (ICV) of tofogliflozin. ICV tofogliflozin increased phosphorylation of AMPK in the lateral hypothalamus.
In conclusion, SGLT2 activity in the CNS may regulate food intake through AMPK phosphorylation in the lateral hypothalamic area.

Disclosure
K. Takeda: None. H. Ono: None. T. Ohno: None. K. Yokote: None.

Funding
Japan Society for the Promotion of Science (15K09398, 18K08502, 20H00524); Japan Agency for Medical Research and Development (17GM5010002H0001, 18GM5010002H0002, 19GM5010002H0003, 20GM5010002H0004)
1154-P: Mediobasal Hypothalamic PACAP Is Essential for Energy Balance by Stimulating Energy Expenditure
Authors: JOHNSON DAVID Q. , BASU RASHMITA , FLAK JONATHAN 
Published: June 2021

Body energy homeostatic mechanisms dynamically balance energy expenditure with energy intake, and the brain plays a critical role in this process. While mediobasal hypothalamic (MBH) signaling is essential for natural elevations in energy expenditure, the downstream anatomical mechanisms are not clear at this point. The MBH contains several important nuclei for energy expenditure control, such as the Ventromedial Hypothalamus (VMN). Because VMN-specific expression of pituitary adenylate cyclase-activating polypeptide (PACAP) decreases with both under-nutrition and loss of leptin action, we tested the hypothesis that MBH PACAP controls energy expenditure. To test this hypothesis, we administered local AAVCre injections into Adcyap1flox (gene that encodes for PACAP) mice. While our approach ensured that peripheral PACAP expression was completely intact, AAV injections did spread into nearby hypothalamic regions, resulting in a MBH loss of function (PACAPMBHKO), rather than a purely VMN knockout. However, all mice exhibited a near complete bilateral ablation of PACAP mRNA in the VMN without interfering with PACAP mRNA in nearby populations that highly express PACAP (e.g., preoptic area (POA) and medial amygdala). In both male and female mice, PACAPMBHKO induced obesity and more than a two-fold increase in adipose mass. VO2, expressed as a function of lean mass, was decreased particularly in the first few hours of the dark cycle, when the mice consume food. Because MBH PACAP cells do not directly project to the spinal cord, PACAP must activate a circuit via a downstream site to stimulate energy expenditure. PAC1r cells primarily overlay with VMN, the primary MBH site containing PACAP, projections in the POA and to a lesser extent in the periaqueductal grey and bed nucleus of the stria terminalis. MBH PACAP, as well as associated signaling targets, are critical components to the control of energy balance by activating energy expenditure.

Disclosure
D. Q. Johnson: None. R. Basu: None. J. Flak: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-17-INI-15 to J.F.); Indiana University