bluuebunny/crossref_metadata_2025_split huggingface dataset:
49-LB: Reported Utility of Automated Blood Glucose Forecasts
Authors: GOLDNER DANIEL R. , HEYMAN MARK , HIRSCH ASHLEY , OSBORN CHANDRA Y. , LUBLING OZ , HUDDLESTON BRIAN , VLAHA RICHARD L. , PRENGER KAI , MURTHY RAGHU , STARKE JEFFREY , BRICENO JHONATHAN , LEDVINA DINAH , DACHIS JEFF 
Published: June 2019

Background: A growing number of people use apps to track diabetes data and identify retrospective patterns that can inform management behavior. In September 2018, One Drop launched Automated Decision Support, which predicts blood glucose 8 hours in the future for non-insulin-dependent users with type 2 diabetes (T2D). Predictions help inform diabetes decision-making prospectively, but only if users find them useful.
Objective: To understand how predictive insights facilitate behavior change in people with T2D, One Drop collected feedback from users and trained a machine learning model to predict when forecasts would be perceived as useful. This model was used to select timing and content of future forecasts and accompanying support messages. We then measured changes in feedback to assess forecast utility.
Methodology: An initial sample of 23,876 forecasts were sent via in-app notifications to 4679 users with T2D. Forecasts consisted of BG trend, duration, and level (“rising, but not too high, over the next 3 hours”) and, when appropriate, a support message relevant to forecast and user history. Forecast delivery was random, triggered with 50% probability when information was logged, no more than once/day/user.
Forecasts could be rated “Useful” or “Not Useful.” A machine learning model, trained on the initial sample, predicted the probability of each type of feedback. A second sample of 28838 forecasts were sent to 5506 users, with probability of usefulness determined by the model.
Results: In the 1st sample, 42.8% of forecasts received feedback from 69.6% of users; 87.1% was “Useful.” In the 2nd sample, 63.7% of forecasts received feedback from 67.1% of users; 92.4% was “Useful.”
Discussion: A new machine learning model tailored forecast delivery, reducing the “Not Useful” rate by 41.1% (from 12.9% of feedback to 7.6%). Correlations between useful forecasts and behavior change will be explored in future work.

Disclosure
D.R. Goldner: Employee; Self; One Drop. Stock/Shareholder; Self; One Drop. M. Heyman: Consultant; Self; Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Tandem Diabetes Care. Employee; Self; One Drop. A. Hirsch: Employee; Self; Informed Data Systems Inc. Research Support; Self; Fitbit, Inc., MannKind Corporation. Stock/Shareholder; Self; Informed Data Systems Inc. C.Y. Osborn: Employee; Self; One Drop. O. Lubling: Employee; Self; One Drop. B. Huddleston: Employee; Self; One Drop. R.L. Vlaha: Employee; Self; One Drop. K. Prenger: Employee; Self; One Drop. R. Murthy: Employee; Self; One Drop. J. Starke: Employee; Self; One Drop. J. Briceno: Employee; Self; One Drop. D. Ledvina: Employee; Self; One Drop. J. Dachis: Stock/Shareholder; Self; Informed Data Systems Inc.
493-P: Synchrotron Radiation Micro-CT Reveals Glomerular Loss without Glomerular or Renal Hypertrophy in Streptozotocin-Induced Type 1 Diabetic Mice
Authors: TAKIYAMA YUMI , SERA TOSHIHIRO , NAKAMURA MASANORI , BESSHO RYOICHI , TAKIYAMA TAKAO , OTA TSUGUHITO , HANEDA MASAKAZU 
Published: June 2019

The glomerular number and size are major factors in predicting outcomes in renal disease. We have recently established synchrotron radiation microcomputed tomography (SRµCT) imaging of the glomeruli in perfused kidneys, and reported the glomerular and renal hypertrophy, but not glomerular loss in obese type 2 diabetic db/db mice. To visualize pathophysiological basis of diabetic kidney of type 1 diabetes, we here explored SRµCT imaging of the glomeruli in streptozotocin-induced type 1 diabetic male mice (STZ mice) and of control male C57BL/6J mice (control mice). STZ mice at the age of 22 weeks significantly showed hyperglycemia and elevated urinary albumin excretion, but not hypertension or body weight changes compared to control mice. There was approximately 22% loss of the total glomerular number (Nglom) of STZ mice compared to that of control mice (p&lt;0.001). STZ mice had fewer glomerular number in all renal cortical zone of the whole kidney than control mice (p=0.003). However, type 1 diabetes had no impact on the mean glomerular volume (Vglom), coefficient of variation (CV; SD/mean) of glomerular volume, and renal volume (Vkidney) (Vglom, p=0.149; CV, p=0.591; Vkidney, p=0.093 vs. control mice, respectively). Nglom was significantly correlated with body weight (r=0.458, p=0.032), blood glucose levels (r=-0.623, p=0.002) or HbA1c (r=-0.530, p=0.011). Vglom was correlated with Vkidney (r=0.622, p=0.002) by each other. Multivariate regression analysis with the stepwise forward method identified blood glucose (β=-0.665, p&lt;0.001) and systolic blood pressure (β=-0.499, p=0.001) as significant independent determinants of Nglom. Our study, for the first time, demonstrated a significant reduction of the total glomerular number in STZ mice, without affecting the glomerular volume or renal volume. These results indicate the glomerular pathology markedly differs between type 1 and type 2 diabetes.

Disclosure
Y. Takiyama: None. T. Sera: None. M. Nakamura: None. R. Bessho: None. T. Takiyama: None. T. Ota: None. M. Haneda: None.
5-OR: Cardioprotective Effect of Luseogliflozin in Patients with Type 2 Diabetes and Established Cardiovascular Disease
Authors: INA YUJIRO , KISHI TAKUYA , SEKIGUCHI NAOTAKA , SAKANE NAOKI 
Published: June 2019

Recent published CV outcome trials have revealed that sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduced the combined CV endpoint and incidences of heart failure-associated hospitalizations in patients with type 2 diabetes mellitus (T2DM) and CV disease (CVD). However, detailed mechanisms of the benefits by SGLT2i still remain unknown. Especially, nobody can show the consensus opinion in the mechanistic effects of SGLT2i on the left ventricular (LV) diastolic dysfunction associated with T2DM. We focused the spectral tissue Doppler-derived E/e' ratio, which has been validated in simple and reproducible noninvasive assessment of LV diastolic pressures independent of rhythm, and evaluated whether or not the treatment of SGLT2i, luseogliflozin, used for 6 months could affect cardiac function in 25 patients with T2DM and CVD. Luseogliflozin used for 6 months significantly reduced HbA1c levels (8.2 ± 1.2% to 7.4 ± 0.6%, p &lt; 0.01) and systolic blood pressure (SBP)(125.6 ± 18.1 mmHg to 119.3 ± 16.8 mmHg, p = 0.04) compared to baseline levels. Moreover, luseogliflozin also significant reduced left atrial (LA) (42.2 ± 5.7 mm to 39.9 ± 6.8 mm, p = 0.01) and LV diameters (diastolic, 49.5 ± 6.9 mm to 47.6 ± 7.6 mm, p = 0.01; systolic, 35.8 ± 9.1 mm to 33.9 ± 9.8 mm, p &lt; 0.01). Remarkably, early annular tissue Doppler (e’) velocity and peak early diastolic velocity/basal septal diastolic velocity (E/e’) ratio were significantly improved, and these benefits were augmented in the group of e’&lt; 6.0cm/sec of baseline (e’ velocity, 4.8 ± 0.6 cm/sec to 5.8 ± 0.9 cm/sec, p &lt; 0.01; E/e’ ratio, 13.0 ± 4.9 to 10.9 ± 3.4, p = 0.03, respectively). There was a significant negative correlation between the changes in E/e’ ratio and baseline of E/e.’ These results indicated that lusegliflozin improved hemodynamics associated with LV diastolic function in the patients with T2DM and CVD, and support the cardio-protective effects of SGLT2i of T2DM with CVD.

Disclosure
Y. Ina: None. T. Kishi: None. N. Sekiguchi: None. N. Sakane: Board Member; Spouse/Partner; Kao Corporation.
503-P: Inhibition of Glucose Transporter 9 Increases Serum Uric Acid Level but Attenuates Renal Albumin Excretion in Streptozotocin-Induced Diabetic Rats: A Role of Hepatic Uric Acid Metabolism
Authors: CHEN CHUPING , RAN JIANMIN , ZHANG RUYI , CHEN GUANGSHU , ZHU PING , QIU JINGXIAN , TAN RONGSHAO , LIU YAN 
Published: June 2019

Background: In previous studies, we confirmed that endogenous uric acid (UA) formation increases in the streptozotocin (STZ)-induced diabetic rats with renal injury. Yet changes of renal UA reabsorption and hepatic UA metabolism remain unclear in this model.
Methods: STZ-induced diabetic rats and control rats were treated with benzbromarone (BZ), a glucose transporter 9 (GLUT9) inhibitor for 8 weeks. At baseline, 4 and 8 weeks after BZ treatment, blood samples were collected for fasting blood glucose (FBG), serum uric acid (SUA), serum creatinine (SCr), and blood urea nitrogen (BUN). Simultaneous urinary samples were tested and daily urinary amount of albumin (UAE), uric acid (UUA), creatinine (UCR), urea nitrogen (UUN) were calculated. Gene expressions of GLUT9, xanthine oxidase (XO), urate transporter 1 (URAT1) in the kidney and GLUT9, XO as well as uricase in the liver were detected by RT-PCR.
Results: 1) Compared with normal rats, FBG, BUN, UUN, UAE and UUA were significantly increased, while SUA was significantly decreased in diabetic rats, while SCr and UCR levels were compared. Treatment with BZ did not change FBG in both rats. BZ significantly decreased SCr, BUN and UAE levels but increased SUA in diabetic rats. 2) In the kidney, expression of GLUT9 and XO was increased, while URAT1 was not altered in diabetic rats if compared with control rats. BZ treatment exerted no any effects on gene expression of GLUT9 and XO. 3) In the liver, gene expression of XO and uricase was compared between diabetic and normal rats, while GLUT9 was significantly upregulated in diabetic rats. BZ treatment remarkably inhibited GLUT9 expression but left XO and uricase unchanged in diabetic rats.
Conclusions: 1) Inhibition of hepatic GLUT9 in STZ-induced diabetic rats increased SUA indicates that GLUT9 pathway for UA metabolism is critical in this model. 2) BZ treatment attenuates urinary albumin excretion in diabetes.

Disclosure
C. Chen: None. J. Ran: None. R. Zhang: None. G. Chen: None. P. Zhu: None. J. Qiu: None. R. Tan: None. Y. Liu: None.
504-P: TGF-ß1 and VCAM-1 as Early Diagnostic Biomarkers of Diabetic Kidney Disease Progression
Authors: DARIA CHUB , PERTSEVA NATALIIA 
Published: June 2019

Aim: To evaluate the significance of using transforming growth factor beta 1 (TGF-β1) and vascular adhesion molecule -1 (VCAM-1) as early prognostic markers of diabetic kidney disease (DKD) progression in patients with DM type 1 and 2.
Materials and Methods: The study included 66 patients with T1DM, 58 with T2DM and 20 healthy volunteers. Diabetic patients were divided into three groups depending on the estimated glomerular filtration rate. All patients were equal for age and sex. The endothelial function was determined by TGF-β1 and VCAM-1 levels. Recognitive Operating Characteristic - was used to assess the discrimination ability (diagnostic test value) to be a predictor of DKD progression.
Results: Patients of all study groups had significantly higher (p˂0,05) levels of TGF-b1 and VCAM-1 versus control group. That’s present endothelial dysfunction in DM patients. The diagnostic value of TGF-b1 and VCAM-1 was compared with diagnostic value of AU. The highest test’s sensitivity and specificity has TGF-b1, its predictive ability concerning DKD progression can be assessed as “excellent” for both types of DM (Se = 100.0; Sr = 100.0; AUC = 1.000; p &lt; 0.001). VCAM-1 has “excellent” operating characteristics for predicting DKD progression in T2DM (Se = 100,0; SP = 88,89; AUC = 0,923; p &lt;0.001) and “very good” in T1DM (Se = 86,36; Sp = 90.48; AUC = 0.866; p &lt;0.001). AU has “good” operating characteristics concerning DKD progression: Se = 57,50; Sd = 97.44; AUC = 0.785; p &lt;0,001 for type1 and 2 DM. That’s shows us evaluation of AU in DM has a high specificity, but low sensitivity of the prognosis DKD progression for both types of DM.
Conclusion: We provide evidences that TGF-β1 and VCAM-1 can be used for prediction of DKD progression in patients with type 1 and type 2 DM. Diagnostic capabilities of VCAM-1 and TGF-β1 significantly exceed the diagnostic capabilities of AU, which determines them as early markers.

Disclosure
C. Daria: None. N. Pertseva: None.
508-P: Gemigliptin Ameliorates Renal Fibrosis by Attenuating NLRP3-Mediated Inflammation in a Murine Model
Authors: JUNG GWONSOO , CHOI YEON-KYUNG , SEO JUNG BEOM , PARK SUNG DON , KIM NAYOUNG , KIM MIN-JI , KIM JUNG-GUK , LEE IN-KYU , PARK KEUN-GYU 
Published: June 2019

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although activation of NOD-like receptor protein 3 (NLRP3) inflammasome has been reported to play an important role in the progression of renal fibrosis, the relevance of DDP-4 inhibitor to NLRP3 inflammation on its ameliorating effect on renal fibrosis has not been fully studied. The aim of this study was to investigate the association of renoprotective effect of gemigliptin with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.
Methods: We evaluated the effects of gemigliptin on renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. We quantitated levels of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment through immunohistochemical and western blot analysis. In human kidney tubular epithelial HK-2 cells, we defined the effect of gemigliptin on TGF-β-stimulated production of profibrotic proteins.
Results: We observed that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, caspase-1, ASC, and IL-1β, which had all been clearly increased by UUO. Furthermore, TGF-β markedly increased NLRP3 inflammasome markers, which were attenuated by gemigliptin.
treatment. Additionally, gemigliptin treatment attenuated phosphorylated NF-κB levels, which had been increased in the UUO kidney as well as in TGF-β-treated cultured renal cells.
Conclusion: The present study demonstrated that the renoprotective effect of gemigliptin is associated with amelioration of NLRP3 inflammasome.

Disclosure
G. Jung: None. Y. Choi: None. J. Seo: None. S. Park: None. N. Kim: None. M. Kim: None. J. Kim: None. I. Lee: Board Member; Self; NovMetapharm Co, Inc. K. Park: None.

Funding
National Research Foundation of Korea
509-P: Utility of Serum Cystatin C in Early Kidney Dysfunction in Prediabetics
Authors: BRANDA JULIA I.F. , ALMEIDA BIANCA , VIVOLO SANDRA R.G. 
Published: June 2019

Background: Serum cystatin C (sCys C) has been proposed as a marker of kidney function with advantages compared to creatinine. It is unclear whether renal damage begin in prediabetes (PDM), when sCys C could be a promisor marker of early kidney dysfunction. We investigated whether sCys C differed between normoglycemic (NG) and PDM subjects and contributed to the detection of kidney dysfunction.
Methods: A cross-sectional analysis of 947 nondiabetic participants (mean age 45.7 years) from the Brazilian Longitudinal Study of Adult Health was performed. sCys C (determined by ELISA) and CKD-EPI eGFR were compared between NG and PDM (fasting plasma glucose: 100-125 mg/dL or 2-hour post-load: 140-199 mg/dL or A1c: 5.7-6.4%). PDM were stratified in 4 groups according to altered sCys C and albumin excretion rate (AER): normal sCys C and AER (G1), abnormal sCys C and normal AER (G2), normal sCys C and abnormal AER (G3) and abnormal sCys C and AER (G4) were compared using ANOVA.
Results: PDM subjects (n = 671) had anthropometric and biochemical data higher than NG (n=276), higher sCys C levels [0.67 (0.41-0.95) vs. 0.48 (0.31-0.81), p&lt;0.001] and lower eGFR (96.3±17.4 vs. 100.6±17.1 mL/min/1.73m2, p&lt;0.001). In eGFR categories (60-&lt;90, 90-&lt;125 and ≥125 mL/min/1.73m2), sCys C were always higher in PDM subjects than in NG. Comparing NG individuals, hyperfiltrants had lower sCys C than normofiltrants (p=0.03) but not than mildly reduced eGFR individuals (p=0.12). Considering the PDM groups, eGFR gradually dropped from G1 to G4 (96.8±17.4 vs. 96.2±16.9 vs. 94.0±17.2 vs. 77.2±25.4 mL/min/1.73m2, p-trend = 0.06) and, as expected, mean eGFR in G4 was lower than in G1 (p=0.017).
Conclusion: Our data confirmed that sCys C is increased in PDM. Reduced sCys C only in NG hyperfiltrant subjects could suggest an inability of hyperfiltrant PDM to excrete Cys C. No statistical evidence that sCys C could be an early marker of kidney dysfunction in prediabetes was found; prospective studies should address its utility to detect dysfunction before AER elevation.

Disclosure
J.I.F. Branda: None. B. Almeida: None. S.R.G. Vivolo: None.
51-LB: The Impact of Digital Health Coaching on the Diabetes Distress Scale (DDS)
Authors: ALLISON MATTHEW , SRIVASTAVA UMA , BURTON STEPHEN BILLY , RASULNIA MAZI , PATEL DHIREN 
Published: June 2019

The ADA’s recent release of the Standards of Medical Care in Diabetes recommends including technology-based methods for the delivery of effective diabetes self-management education and support. Self-management of diabetes involves meal planning, taking medications, blood glucose monitoring, physical activity, coordinating care, and others. The program developed by Pack Health addresses all of the tasks above and more through a structured 12-week program, evidence-based tools, and a non-prescriptive Health Advisor. The program has over 60 proactive outbound touchpoints that originate from the Health Advisor (via text messages, emails, and/or phone calls). The Pack Health program collects and utilizes patient-reported outcomes (PROs) along with clinical measures, self-reported by patients. All data is used for coaching sessions and evaluation purposes.
This study examines the impact of Digital Health Coaching on a national diabetes population (n=198) and an African American sub-population (n=57) enrolled in the South (AL, GA, FL, MS) upon completion of the initial 12-weeks of engagement. The DDS is a 17-item scale that captures four critical dimensions of distress: emotional burden, regimen distress, interpersonal distress and physical distress. DDS score benchmarks are established at little to no diabetes distress (&lt;2.0), moderate diabetes distress (2.0-2.9), high diabetes distress (≥3.0). Health coaching demonstrates the following impact:
National Diabetes Population:
Baseline: 3.0; Post: 2.2; Improvement: 0.8
African Americans in the South:
Baseline: 3.0; Post: 2.1; Improvement: 0.9
The data above emphasizes that digital coaching program can have a significant impact on Diabetes Distress for a general population and African American population in the South.

Disclosure
M. Allison: None. U. Srivastava: None. S.B. Burton: None. M. Rasulnia: None. D. Patel: None.
51-OR: Medios—A Smartphone-Based Artificial Intelligence Algorithm in Screening for Diabetic Retinopathy
Authors: SOSALE BHAVANA , SOSALE ARAVIND R. , MURTHY HEMANTH , NARAYANA SRIKANTH , SHARMA USHA , GOWDA SAHANA G.V. , NAVEENAM MURALIDHAR 
Published: June 2019

Background: Pupil dilatation, access to ophthalmologists, size and cost of fundus cameras, and network connectivity issues are barriers to diabetic retinopathy (DR) screening in primary care. This makes artificial intelligence a potential alternative in DR screening. This study aims to evaluate the performance of an offline AI algorithm - Medios in DR Screening using non mydriatic retinal images taken from the smartphone based Remidio Fundus on Phone (NM-FOP) retinal camera.
Methods: Non mydriatic retinal images from 900 patients with diabetes were captured prospectively with the Remidio NM FOP camera at Diacon Hospital, Bangalore, India. The images were graded by 5 ophthalmologists as per the International Diabetic Retinopathy Classification System and the majority diagnosis was considered as the ground truth. Two images [posterior pole (macula centered), nasal field] were captured per eye for each patient, and were analyzed offline on-device using the Medios AI. The diagnosis of Medios AI was compared to that of the ophthalmologist.
Results: DR was present in 252 patients. Performance of the AI for referable DR (Moderate NPDR or worse, or presence of DME) was - Sensitivity 93% (95% CI 91.3%-94.7%), Specificity: 92.5% (95% CI 90.8%-94.2%). Performance of the AI for all DR (Mild NPDR or worse, or presence of DME) was - Sensitivity: 83.3% (95% CI 80.9%-85.7%), Specificity: 95.5% (95% CI 94.1%-96.8%). Sensitivity for sight threatening DR (STDR) [severe NPDR, proliferative DR (PDR) or presence of DME] was 95.2% (95% CI 88.2%-98.6%). The 3 PDRs missed by the AI were post laser with no active changes visible. This is a common exclusion criteria in other studies, and when excluded, the sensitivity for STDR was found to be 98.7%.
Conclusion: This is one of the largest studies evaluating the performance of AI using non mydriatic retinal images offline. The Medios AI algorithm’s sensitivity and specificity exceeds the FDA mandated superiority end point and can be used for DR screening.

Disclosure
B. Sosale: None. A.R. Sosale: None. H. Murthy: None. S. Narayana: None. U. Sharma: None. S.G.V. Gowda: None. M. Naveenam: None.
518-P: Involvement of Low-Density Lipoprotein Receptor-Related Protein 5 in Chronic Kidney Diseases via Modulation of TGF-β-Smad2/3 Signaling
Authors: HE XUEMIN , CHENG RUI , HUANG CHAO , CHEN YANMING , MA JIAN-XING 
Published: June 2019

Aims: Low-density lipoprotein receptor-related protein 5 (LRP5) is known as a co-receptor of canonical Wnt signaling. This study aimed to investigate LRP5’s role in chronic kidney diseases including diabetic and obstructive nephropathies, and its new role in regulating TGF-β-Smad2/3 signaling in renal fibrogenesis.
Methods: The expression of LRP5 was examined in the kidneys of Akita mice, db/db mice and mice with obstructive nephropathy. The regulation of TGF-β signaling by LRP5 was determined in both obstructed kidneys and in human proximal tubule epithelial cells exposed to TGF-β1. Interaction of LRP5 with TGF-β receptors was evaluated by Co-IP assays, immunostainings and cell fractionation.
Results: We found that LRP5 levels were substantially up-regulated in the renal tubules of diabetic mice and mice with obstructive nephropathy. In the obstructed kidneys, Lrp5 knockout significantly ameliorated tubulointerstitial fibrosis and attenuated the increases of TGF-β1 and TGF-β receptors (TβRI and TβRII), without affecting canonical Wnt signaling. Utilizing SBE-Luc reporter mice and immunostaining assays, LRP5 depletion was demonstrated to attenuate the activation and nuclear translocation of Smad2/3, whereas LRP5 overexpression enhanced TGF-β-Smad2/3 signaling in tubule epithelial cells. Obstruction-induced LRP5 and TβRI were co-localized in the injured tubules, and furthermore, LRP5 was co-precipitated with TβRI and TβRII. The extracellular domain of LRP5 was essential for its association with TGF-β receptors and profibrotic activity. In addition, LRP5 stabilized TGF-β receptors, increased their membrane presentation in the absence of TGF-β1, and promoted the TGF-β1-induced formation of TβRI/TβRII heterodimers and internalization of these receptors.
Conclusion: These findings reveal a novel profibrotic activity of LRP5 by interacting with TGF-β receptors, independent of canonical Wnt signaling.

Disclosure
X. He: None. R. Cheng: None. C. Huang: None. Y. Chen: None. J. Ma: None.