bluuebunny/crossref_metadata_2025_split huggingface dataset:
2192-P: Extracellular Vesicles as Novel Mediators of Proinflammatory Cytokine-Induced ß-Cell Dysfunction
Authors: JAVEED NAUREEN , HER TRACY K. , VANDERBOOM PATRICK M. , LANZA IAN R. , MATVEYENKO ALEKSEY 
Published: June 2019

The presence of a proinflammatory islet microenviroment and consequent dysregulation of glucose-stimulated insulin secretion (GSIS) is a hallmark feature of both type 1 and type 2 diabetes. Recent evidence has implicated islet cell-derived extracellular vesicles (EVs) as novel mediators of cytokine-derived inflammatory stress in diabetes, however the mechanisms governing this process remain largely unknown. Therefore, we set out to test the hypothesis that cytokine-mediated β-cell dysfunction is mediated in part through β-cell autocrine release of proinflammatory EVs which promote inflammation and inhibit GSIS. Particle size analysis of EVs from conditioned media of cytokine treated (IL-1β, TNF-α, and IFNγ) Min6 β-cells (CytoEV) showed an overall increase in β-cell EV secretion (∼2 fold increase, P&lt;0.05) and a decrease in the average size of secreted EVs (P&lt;0.05) implicating a shift towards a more exosomal EV profile. Subsequently, functional assessment of isolated mouse islets treated (48h) with CytoEVs resulted in a significant suppression of GSIS (∼80%, P&lt;0.05 vs. control). Moreover, acute exposure to CytoEVs also recapitulated the transcriptional signature of β-cell failure in diabetes characterized by increased expression of key proinflammatory genes (e.g., Cxcl10, Tlr1, Tlr4), and a decrease in Insulin and Pdx-1 expression (∼40%, P&lt;0.05 for CytoEVs vs. control). Finally, proteomics analysis of CytoEVs from Min6 and INS-1 832/13 lines (compared to control EVs from each line) revealed a distinct proinflammatory profile consisting of proteins implicated in type 1 diabetes and dendritic cell maturation pathways (e.g., HLA-A, STAT1, INS, CPE etc., P&lt;0.05). Taken together, this work provides a novel mechanism of β-cell dysfunction in diabetes mediated by the autocrine exchange of proinflammatory EVs which has implications for the detection and treatment of β-cell failure in diabetes.

Disclosure
N. Javeed: None. T.K. Her: None. P.M. Vanderboom: None. I.R. Lanza: None. A. Matveyenko: None.
220-LB: Early-Life Famine Exposure and Hyperuricemia in Adulthood
Authors: WANG YUYING , ZHANG WEN , WAN HENG , CHEN CHI , CHEN YI , XIA FANGZHEN , HAN BING , LI QIN , GUO YUYU , WANG NINGJIAN , LU YINGLI 
Published: June 2019

Background and Aims: Hyperuricemia is a pathological condition associated with hypertension, metabolic dysfunctions, renal, and cardiovascular diseases. Epidemiologic studies indicated that early life famine exposure influences later risk of chronic disorders. But evidence in the association between famine exposure and hyperuricemia were limited. We aimed to investigate whether the association existed between famine exposure in early life and hyperuricemia in adulthood.
Methods: 12666 participants were enrolled in China based on SPECT-China study (ChiCTR-ECS-14005052, www.chictr.org.cn). Hyperuricemia was defined as UA &gt;420 μmol/L for men and &gt;360 μmol/L for women. The associations of famine exposure with hyperuricemia were assessed via logistic regression.
Results: For famine exposed women, fetal famine exposure was significantly associated with hyperuricemia (1.63 (95% CI 1.04-2.54), P=0.031). Early life famine exposure was only associated with hyperuricemia in lean women (fetal exposed: 1.9 (95% CI 1.11-3.24); childhood exposed: 1.91 (95% CI 1.05-3.47), P&lt;0.05), but not in obese subjects. Moreover, the insulin resistant female had a marginal significance of the association between fetal famine exposure and hyperuricemia (1.85 (95% CI 0.92-3.72), P=0.082). Significant association between fetal and childhood famine exposure and hyperuricemia was observed in lean and insulin resistant female (fetal exposed: 3.32 (95% CI 1.13-9.76); childhood exposed: 3.57 (95% CI 1.06-12.01), P&lt;0.05). However, no association was observed in male subjects.
Conclusions: Exposure to famine in early life period may lead to hyperuricemia in female, which indicates malnutrition in early life period may offer a modifiable factor for hyperuricemia development.

Disclosure
Y. Wang: None. W. Zhang: None. H. Wan: None. C. Chen: None. Y. Chen: None. F. Xia: None. B. Han: None. Q. Li: None. N. Wang: None. Y. Lu: None.

Funding
National Natural Science Foundation of China (91857117, 81570726, 81600609, 81600614, 81800694]; Science and Technology Commission of Shanghai Municipality (18410722300, 16411971200, 16410723200); Commission of Health and Family Planning of Pudong District (PWZxq2017-17, PW2015D-5); Shanghai Municipal Commission of Health and Family Planning (15GWZK0202, 20164Y0079); Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ053); Clinical Research Plan of SHDC (16CR3076B)
2205-PUB: Temporal Patterns of Inpatient Hypoglycemia and Predictors of Recurrent Hypoglycemia in a Singapore Tertiary Medical Center
Authors: LIM PAIK SHIA , GOH SU-YEN , BEE YONG MONG , XIN XIAOHUI , ANG LI CHANG , SALLEHA NUR A. , TEH MING M. 
Published: June 2019

Background: Inpatients hypoglycemia has adverse impacts on patient outcomes and healthcare resources use. While recurrent hypoglycemia is largely preventable, limited studies were done within the Asia-Pacific context. We sought to determine whether temporal distributions of hypoglycemia exist between insulin and/or sulfonylureas (SU) treated patients and identify predictors of recurrent hypoglycemia at a tertiary medical center in Singapore.
Methods: We analyzed data of 420 hypoglycemic episodes (capillary blood glucose (CBG) ≤ 70mg/dL) in 207 diabetes patients at general medical wards over a 2-month period from 1st May 2017. This was analyzed by 4 time frames coincided with blood glucose monitoring times. Time periods associated with hypoglycemia were compared using the Chi-square test. Multivariate logistic regression estimated risk factors of recurrent hypoglycemia.
Results: Most frequent hypoglycemia episodes occurred between 04:00 and 09:59 (41.7%). Greater frequency was seen in insulin- and SU-treated than insulin-treated patients between 04:00 to 09:59 (58.3% vs.37.9% of readings for respective treatments, p&lt;0.05). It was also more frequent in insulin-treated than SU-treated patients between 10:00 to 15:59 (19.2% vs. 10.9%, p&lt;0.05). Nearly a third of patients had recurrent hypoglycemia (32.9%). Longer length of stay, treated with premixed insulin, age &lt; 65 years, HbA1C &gt; 7% and repeated CBG checking &gt; 30 minutes interval emerged as predictors of recurrent hypoglycemia with odds ratio of 1.07 (95% CI 1.03-1.11), 8.07 (95% CI 2.82-23.08), 3.71 (95% CI 1.59-8.65), 3.12 (95% CI 1.26-7.74) and 3.54 (95% CI 1.59-7.91), respectively.
Conclusions: Hypoglycemic episodes were more frequent in the early hours of the day in insulin and SU-treated inpatients. This may have implications for the continuing use of SU at inpatients. Recurrent hypoglycemia can be prevented by developing strategies targeting the modifiable iatrogenic risk factors.

Disclosure
P. Lim: None. S. Goh: None. Y. Bee: None. X. Xin: None. L. Ang: None. N.A. Salleha: None. M.M. Teh: None.
2208-PUB: Prevalence of Type 2 Diabetes Is Higher in Patients with Heart Failure than in Patients with Stable Coronary Artery Disease
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN-PURIN DANIELA , LARCHER BARBARA , MADER ARTHUR , STERNBAUER SIMON , SAID ABDURAHMAN , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ 
Published: June 2019

High prevalence rates of type 2 diabetes (T2DM) have been reported both in stable coronary artery disease (CAD) and in heart failure (HF) patients, but data directly comparing T2DM prevalence between these patient populations are not available. Here, we therefore aimed at comparing the prevalence of T2DM and of prediabetes in 195 patients with angiographically proven stable CAD who had no history, signs or symptoms of heart failure, and in 183 patients with a diagnosis of HF according to current European Society of Cardiology criteria. Using ADA criteria for the diagnosis of diabetes, T2DM prevalence was significantly higher in HF than in CAD patients (48.6% vs. 22.6%; p&lt;0.001). Also, the proportion of patients reporting a history of diabetes was significantly higher in HF than in CAD patients (37.7% vs. 16.9%; p&lt;0.001). HF remained associated with a higher prevalence of T2DM after multivariate adjustment (OR 2.89 [1.77-4.72]; p&lt;0.001). In contrast, among the patients who did not have diabetes, the prevalence of prediabetes (FPG 100-125 mg/dl or HbA1c 5.7-6.5%) was similar in HF as in CAD patients (66.0 vs. 62.3% =0.558). We conclude that the prevalence of T2DM is even higher in patients with HF than in patients with stable CAD.

Disclosure
C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. B. Larcher: None. A. Mader: None. S. Sternbauer: None. A. Said: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
2222-PUB: Type 2 Diabetes as a Predictor of Cardiovascular Events in Peripheral Artery Disease vs. Coronary Artery Disease
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN-PURIN DANIELA , LARCHER BARBARA , MADER ARTHUR , SCHINDEWOLF MARC , BAUMGARTNER IRIS , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ 
Published: June 2019

Patients with established cardiovascular disease (CVD) are at a very high risk of cardiovascular events, and cardiovascular risk is considered extremely high in those with the combination of CVD and diabetes. However, the impact of type 2 diabetes (T2DM) on cardiovascular event risk may differ between different manifestations of CVD. To address this issue, we prospectively recorded cardiovascular events over 10 years in 1472 patients with angiographically proven stable coronary artery disease (CAD), of whom 454 had T2DM as well as in 465 patients with sonographically proven peripheral artery disease (PAD), of whom 204 had T2DM. Both among CAD and among PAD patients, those with T2DM were at a significantly higher risk of cardiovascular events than those who did not have diabetes (56.0% vs. 44.5%; p&lt;0.001 and 68.5% vs. 50.6%; p&lt;0.001, respectively). Cardiovascular risk was significantly higher in PAD than in CAD patients, both among those with T2DM (68.0% vs. 56.0%; p=0.003) and among those who did not have diabetes (50.6% vs. 44.5%; p=0.047). In multivariate analyses, T2DM (HR 1.48 [1.13-1.70); p&lt;0.001) and presence of PAD versus that of CAD (HR 1.93 [1.64-2.28];p&lt;0.001) were mutually independent predictors of cardiovascular events. An interaction term T2DM by PAD vs. CAD was non-significant (p=0.146), indicating that the relative risk increase conferred by T2DM did not differ significantly between PAD and CAD patients. We conclude that T2DM increases cardiovascular event risk among patients with PAD as well as among those with CAD and that PAD confers a higher risk of cardiovascular events than stable CAD irrespective of the presence of T2DM.

Disclosure
C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. B. Larcher: None. A. Mader: None. M. Schindewolf: None. I. Baumgartner: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
2242-PUB: Retinal Biomarkers Indicative of Diabetic Peripheral Neuropathy
Authors: NEMETH SHEILA C. , BURGE MARK R. , WIGDAHL JEFFREY , CARMICHAEL JUSTIN C. , GUO XIAOSHAN , JOSHI VINAYAK , SOLIZ PETER 
Published: June 2019

The purpose of this study was to identify biomarkers that are indicative of diabetic peripheral neuropathy (DPN). From a cohort of 21 DPN and 18 controls, optic disc- and macula-centered images were taken. Sixty vascular parameters were measured using computer-assisted software. Statistically significant differences in vascular parameters between subjects with DPN and controls showed that DPN subjects could be differentiated from controls using retinal biomarkers. Statistical significance (p &lt; 0.05) was obtained for 13 retinal features, including fractal dimension, vein width, number of 1st branching vessels, and vessel tortuosity. The reduced fractal dimensions in DPN patients indicate a deterioration of the retinal vascular architecture. The reduced total number of vessels, as well as the total number of venules, contribute to the lower fractals in the DPN patients and supports the findings of a sparser retinal vascular network for DPN subjects. A difference in standard deviation for vessel width may suggest a greater loss of vascular tone and regulation in DPN subjects. A difference in the number of 1st branching vessels in venules was observed, which may indicate that the DPN subjects had fewer numbers of these first bifurcations. This feature would also contribute to the lower fractal dimension as well as a sparser retinal vascular network. Similarly, the statistical difference in the angle of the first daughter vessel suggests that the retinal vascular architecture has deviated from its optimal flow and/or function due to the disease process. The increased difference in curvature tortuosity in the arterioles in DPN correlates with chronic hypertensive retinopathy. We found statistically significant differences in 13 out of 60 retinal vascular features (22%) between control and DPN subjects. As such, the retina reflects the widespread vascular structural abnormalities occurring in diabetic patients with DPN.

Disclosure
S.C. Nemeth: None. M.R. Burge: None. J. Wigdahl: None. J.C. Carmichael: None. X. Guo: None. V. Joshi: None. P. Soliz: Stock/Shareholder; Self; VisionQuest Biomedical LLC.

Funding
National Institutes of Health (R43DK104578-01)
2243-PUB: Impact of Sudomotor Impairment on Physical Fatigue after 16 Weeks of Aerobic Exercise
Authors: GRAY COREY M. , YAHYA ABDALGHANI , ALENAZI AQEEL M. , ALSHEHRI MOHAMMED , RUCKER JASON L. , PASNOOR MAMATHA , KLUDING PATRICIA 
Published: June 2019

Introduction: Sudomotor impairment (SI) is common in people with diabetic peripheral neuropathy (DPN) and could potentially influence the effects of exercise. Exercise is known to improve outcomes such as physical fatigue (PF); however, the impact of SI on PF is not clear. Thus, our objective was to examine the impact of sudomotor function on PF change after 16-weeks of moderate intensity aerobic exercise (AEx).
Methods: People with DPN (n=17) who participated in 16-weeks of AEx were included in this secondary analysis. Sudomotor function was evaluated at baseline via a quantitative sudomotor axon reflex test and classified as normal (n=6), mild (n=6), moderate (n=3), or severe (n=2). Self-reported PF was assessed at baseline and post-intervention via a fatigue questionnaire. A Kruskal-Wallis test evaluated the impact of baseline sudomotor function on change in PF after exercise. Dunn’s tests were used to evaluate multiple comparisons. Association between sudomotor function and PF change was evaluated via a Spearman’s correlation. Alpha was set at 0.05.
Results: Changes in PF are reported as negative (↓in PF) and positive (↑in PF) values. Median PF changes of -29%, -30%, 0%, and 14% were observed for normal, mild, moderate, and severe groups, respectively with a significant between-group difference (p=0.039). Pairwise comparisons revealed significant differences between normal and moderate (p=0.025), normal and severe (p=0.047), and mild and moderate (p=0.04) groups. A moderate correlation between SI and PF change (r=0.630, p=0.007) was observed.
Conclusions: Our results indicate that change in PF following 16-weeks of AEx may be influenced by SI. SI can limit the body’s ability to dissipate heat during exercise, potentially exacerbating PF through disruptions in the thermoregulatory negative feedback loop. This could influence response to exercise, and future research should examine the effects of underlying mechanisms of SI on PF in this population.

Disclosure
C.M. Gray: None. A. Yahya: None. A.M. Alenazi: None. M. Alshehri: None. J.L. Rucker: None. M. Pasnoor: Advisory Panel; Self; Alexion Pharmaceuticals, Inc., Terumo BCT. Consultant; Self; Momenta Pharmaceuticals. P. Kluding: None.

Funding
National Center for Advancing Translation Sciences (UL1TR000001); Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD057850)
225-LB: Demographic and Clinical Comparisons of South Asians with Type 2 Diabetes vs. Caucasians and African Americans in an Urban Clinical Setting
Authors: AHMED AMIYA , RAHMAN WEDAD , MUNIR KASHIF M. 
Published: June 2019

Background: The incidence of type 2 diabetes (T2D) is rising worldwide. South Asians are at higher risk, nearly 2-4 times greater than white Europeans, and tend to develop T2D at an earlier age and lower BMI. Prior studies have shown a potential advantage of incretin-based therapies in South Asians. The purpose of this study is to compare baseline characteristics of South Asians with T2D with those of other ethnic groups and to determine whether South Asians have a better glycemic response to incretin-based therapies in an urban United States diabetes center.
Methods: Retrospective chart review of patients with T2D at the University of Maryland Center for Diabetes and Endocrinology from 2010-16 was performed. Adult patients (ages 18-85) with T2DM were included. A total of 43 South Asians (India, Bangladesh, Pakistan, Sri Lanka) and 182 non-South Asians (further subclassified into black or Non-Hispanic white) were enrolled. Data on age of T2DM diagnosis, family history, BMI, diabetic medications, exercise, blood pressure, and presence of micro- or macrovascular complications were collected. Baseline characteristics were compared and tested for statistical significance by Chi-square test and student t-tests.
Results: South Asians were diagnosed with T2D at a lower BMI (29 vs. 34; p&lt;0.0001) compared to their non-south Asian counterparts. In the South Asian group, there was a trend towards lower age at diagnosis, higher incidence of CAD and nephropathy compared to non- South Asians. No differences in hemoglobin A1c between South Asians vs. non-South Asians were noted at 3-month follow-up after initiation of incretin-based therapy.
Conclusion: South Asians are more likely to have T2D at a lower BMI than black or Non-Hispanic white patients in an urban United States setting. No significant difference in T2DM complications was noted among ethnic groups, and incretin-based therapies did not have a significant effect on in South Asians vs. non-South Asians.

Disclosure
A. Ahmed: None. W. Rahman: None. K.M. Munir: None.
2251-PUB: Relationship between Type 2 Diabetes and Dyslipidemia in Adult Residents of Minhang District, Shanghai: A Multistage, Stratified Cluster Sampling Survey
Authors: LIANG TONGTONG , XU DONGLI , YAO BAODONG 
Published: June 2019

Objective: To investigate the relationship between type 2 diabetes and dyslipidemia in adult residents of Minhang District, Shanghai.
Methods: A multistage, stratified cluster sampling survey were conducted among 3099 adult residents aged 35 and above in Minhang District. The prevalence rate should be adjusted according to the population distribution of the Sixth National Population census data in this area. Logistic regression analysis was used for multivariate analysis.
Results: The adjusted prevalence rate of type 2 diabetes and dyslipidemia were 18.18% and 50.61%, respectively. The increased rates of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were 28.03%, 19.56% and 3.56%, respectively, and the decreased rate of high-density lipoprotein cholesterol (HDL-C) was 14.32%. TC, TG and LDL-C were positively correlated with fasting blood glucose (FBG) with linear correlation coefficients 0.068, 0.190 and 0.049, respectively. While HDL-C was negatively correlated with FBG with linear correlation coefficient -0.076. The relationship between the TC, TG, LDL-C and HDL-C and the 2-hours blood glucose (2hBG) after oral glucose tolerance test (OGTT) was the same as that between the TC, TG, LDL-C and HDL-C and the FBG and the linear correlation coefficients were 0.121, 0.166, 0.116 and -0.045, respectively. Dyslipidemia and higher TG were independent risk factors of type 2 diabetes (OR=1.69, 95% CI:1.32-2.17; OR=1.53, 95% CI:1.21-1.94), adjusting sex, age, education level, occupation, smoking, drinking, BMI and hypertension.
Conclusion: Dyslipidemia is closely associated with type 2 diabetes among adult residents in Minhang District. Comprehensive prevention and control measures for dyslipidemia and type 2 diabetes should be carried out.

Disclosure
T. Liang: None. D. Xu: None. B. Yao: None.
2256-PUB: Fixed-Ratio Insulin Degludec/Liraglutide (IDegLira) vs. Basal-Bolus Treatment in Type 2 Diabetic (T2DM) Patients with Diabetic Foot Ulcers (DFU) and Critical Limb Ischemia (CLI)
Authors: FALCETTA PIERPAOLO , INDOVINA FRANCESCO S. , GIANNARELLI ROSA , PIAGGESI ALBERTO , PENNO GIUSEPPE , MICCOLI ROBERTO , PRATO STEFANO DEL , COPPELLI ALBERTO 
Published: June 2019

We report results from the clinical use of IDegLira compared to basal-bolus (BB) insulin regimen in T2DM patients admitted to our department because of DFU and CLI. We retrospectively identified 44 consecutive T2DM patients admitted to our diabetes ward because of DFU (M/F: 24/20; age: 67.3±9.5 years; BMI: 30.6±5.2 Kg/m2; diabetes duration (DD): 23.5±9.9 years; HbA1c 71.7±24.5 mmol/mol). During hospitalization, 28 patients (Group A: M/F: 15/13; age: 65.7±8.9 years; BMI: 32.6±4.8 Kg/m2; DD: 21.1±9.9 years; HbA1c 76.1±25.2 mmol/mol) previously on BB (63.7±33.9 U/day), were started on IDegLira (IDeg 22.8±7.8 U/day, liraglutide 0.82±0.3 mg/day) while the remaining 16 (Group B; M/F: 9/7; age: 70.4±10.1 years; BMI: 30.3±2.2 Kg/m2; DD: 27±9.2 years; HbA1c 63.9±22.0 mmol/mol; all p=NS vs. Group A) continued BB (43±18 U/day), allowing comparison over a mean follow-up period of 3 months. Patients were comparable with respect to distal lesions, pain-relieving, antibiotic therapies, revascularization procedures and surgical treatments performed. In Group A, BMI, HbA1c and LDL-C improved significantly (26.4±10.1 Kg/m2; 54±11 mmol/mol; 61.5±32 mg/dl; p&lt;0.05 vs. baseline) during the follow-up period. No change occurred in Group B whereas Group A also had significant improvement of inflammatory markers (Fibrinogen: 635±178 vs. 437±121 mg/dl; ESR: 74±34 vs. 48±13 mm/h; CRP: 5.2±1.7 vs. 0.8±1.0 mg/dl; all p&lt;0.05 vs. baseline). Ulcer healing was achieved in 17 patients in Group A (61%), and in 3 patients (19%) in Group B (p&lt;0.05). These data suggest that treatment with IDegLira can have positive effects on metabolic and inflammatory parameters of complicated T2DM patients with DFU and CLI, probably contributing to greater ulcer healing observed in this category of patients.

Disclosure
P. Falcetta: None. F.S. Indovina: None. R. Giannarelli: None. A. Piaggesi: None. G. Penno: None. R. Miccoli: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. A. Coppelli: None.