bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of efficiency of rare earth elements recovery from lignite coal combustion ash via five-stage extraction
Authors: Milicic Ljiljana , Terzic Anja , Pezo Lato , Mijatovic Nevenka , Brceski Ilija , Vukelic Nikola
Published: June 2021

Rare earth elements (REE) are frequently referred to as ingredients for
enhancements in modern industry, as they are extensively applied in many
industrial branches due to their accented electro-magnetic and optical
properties. REE have end-utilizations as catalysts, magnets, and as dopants
for ceramic materials. Rare earth minerals are scarce therefore the
unconventional REE-containing resources such as waste materials and
industrial byproducts are continuously being investigated. Coal combustion
products comprise REE concentrations varying between 200 ppm and 1500 ppm.
This quantity can be isolated though the extraction procedure. In this
study, the five stages extraction was conducted on the coal combustion ash
from the selected landfill site. The extractions of 32 elements (As, Ga, Ce,
Be, Ge, Nd, Cr, Zr, Eu, Cu, Nb, Gd, Co, Mo, Dy, Li, Ag, W, Mn, Cd, Au, Ni,
In, Hg, Pb, Sn, Tl, V, Sb, Th, Zn, and La) were conveyed. Chemical analyses
were conducted via XRF, ICP-OES, ICP-MS, and AAS techniques. The complexity
of the obtained data was examined by Principal component analysis and
Cluster analysis in order to derive interconnections between quantity of
elements and landfill characteristics, as well as mutual relationships among
the elements of interest, and to assess the accomplishment of REE recovery
from the coal ash.
Heidegger on beauty
Authors: Popovic Una
Published: June 2021

This paper is about Heidegger?s understanding of beauty, with regard to his
specific critique and reevaluation of traditional philosophical aesthetics,
known as overcoming of aesthetics. Namely, since the notion of beauty is not
the most prominent one in Heidegger?s understanding of aesthetics, my aim in
this paper is to point out to its role and function in the project of
overcoming of aesthetics and metaphysics, and consequently, in the
development of Heidegger?s later philosophy in general. I will focus my
analyses on two Heidegger?s lectures dating from 1935-1936, The Origin of
the Work of Art and The Introduction to Metaphysics. Both of these, in my
view, represent key texts for the analysis of the notion of beauty in
Heidegger. Firstly, I will analyze the relationship between beauty and art,
and thus show that Heidegger?s approach to beauty implies ontological
connotations (with regard to the question of Being), as well as a critique
of traditional relationship between beauty and art (art as production of
beauty). Secondly, I will stress the relation between beauty, truth and
light (shine), and thus indicate Heidegger?s positive approach to the
matter. Resulting from these analyses, Heidegger?s notion of beauty is shown
as a vital part of his overcoming of aesthetics and metaphysics, but also as
a specific aspect of various questions and problems of his later philosophy.
Additionally, the results of these analyses can become a starting point for
further interpretation of the relationship between beauty and form, and
between light (shine) and Being in Heidegger?s philosophy.
Gregorii Palamae Contra beccum. Antepigraphai of Gregory Palamas in Serbian Church-Slavonic translation
Authors: Knezevic Mikonja , Stefanovic-Banovic Milesa
Published: June 2021

This paper analyzes the basic theological foundations of John XI Bekkos, a
Unionist Patriarch from the XIII century. Particular attention is paid to
flori?legium known as Epigraphai, wherein Bekkos endeavoured to find
patristic support for his views and show that Eastern and Western Christian
traditions are actually compatible. Bekkos? theses presented in this work -
including his apology of filioque, which he relates to the doctrine of the
Eastern Church on procession of the Holy Spirit ?through Son? - were
criticized by Gregory Palamas in his work Antepigraphai. After exposition of
the key features of this work and (final) determination of its chronology,
we bring an editio princeps of its Serbian Church-Slavonic translation from
the XIV century. A Chilandar transcript from the end of the XIV century is
taken as a source text, but it is compared with other six known transcripts
of this translation.
1002-P: HbA1c Level in Severe COVID-19 Patients Is Not Only a Marker of Glycemic Status but Also of Acute Erythrocyte Damage
Authors: SHESTAKOVA MARINA V. , KONONENKO IRINA , KALMYKOVA ZILYA , ZHELEZNYAKOVA ANNA , MOKRYSHEVA NATALIA
Published: June 2021

Introduction: COVID-19 can trigger either transient stress-induced state, or newly onset diabetes mellitus (DM). It is well known that HbA1c serves as an indicator of glycemic status 12 weeks before the acute disease.

Aim: To examine glycemic status at admission and 6 weeks after hospital discharge in patients with confirmed COVID-19 but no previous DM-history.

Methods: Of 155 patients hospitalized with COVID-19 and pneumonia 111 persons had no previous DM-history. The levels of HbA1с, fasting and admission plasma glucose (FPG and APG) were measured at admission and 6 weeks after the discharge. The severity of COVID-19 was confirmed by CT scan, SpO2, serum IL-6, CRP, D-dimer.

Results: All 111 patients had normal FPG and APG values. According to HbA1c level all the patients were divided into two groups: A) HbA1c≤6.0% (n=64, median 5,8%) and B) HbA1c>6,0% (n=47, median 6,4%). Our particular interest was focused on the group B due to the discrepancy of high HbA1c level and normal FPG and APG. Group B patients were retested for glycemic status in 6±1 week after the discharge. Surprisingly the median HbA1c level dropped down from 6,4% to 5,7% in such a short period of time with no antidiabetic drugs. COVID-19 severity markers were significantly higher in the group B.

Conclusions: We suggest two explanations for this faster than expected HbA1c decrease: 1) patients with HbA1c>6,0% will progress to DM later, and, therefore, a longer follow-up is needed; 2) SARS-CoV-2 virus has extensively glycosylated spike(S)-protein that may bind to erythrocytes. High-pressure liquid chromatography (the standard method for HbA1c) probably fails to separate the glycated 1-β-chain of hemoglobin from glycated viral spikes. In this case, abnormally high HbA1c in COVID-19 patients with no DM-history may serve as a marker of severe viral erythrocyte damage rather than a marker for the glucose control. This hypothesis is confirmed by the prompt (in 6 weeks) normalization of HbA1c level following the virus elimination.

Disclosure

M. V. Shestakova: None. I. Kononenko: None. Z. Kalmykova: None. A. Zheleznyakova: None. N. Mokrysheva: None.

Funding

Ministry of Science and Higher Education of the Russian Federation (075-15-2020-899)
1005-P: Patients with Overweight and Obesity at High-Risk for Type 2 Diabetes: A Predictive Model
Authors: TURCHIN ALEXANDER , MORRISON FRITHA J. , SHUBINA MARIA , SHINDE SHRADDHA , AHMAD NADIA , KAN HONG
Published: June 2021

Obesity is the most common chronic disease in the U.S. Patients with obesity are at high risk for type 2 diabetes mellitus (T2DM); however, many of their risk factors for T2DM are modifiable. It is important to identify patients with obesity at high risk for T2DM to appropriately direct treatment and resources.

We conducted an observational study of EMR data of 399,711 adults with BMI ≥ 25 kg/m2 and without baseline T2DM between 2000 and 2019. We first identified a literature-based pool of risk factors for T2DM onset and conducted variable selection by applying LASSO penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset.

Over a mean of 7.4 years of follow-up, 38,898 (9.8%) study patients developed T2DM. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of T2DM was associated with gestational diabetes (HR 2.53; 95% CI 2.12-3.01), Asian and Hispanic race/ethnicity (HRs 2.38 and 1.94; 95% CIs 2.24-2.53 and 1.86-2.02, respectively), family history of DM (HR 2.00; 95% CI 1.95-2.04) and PCOS (HR 1.84; 95% CI 1.63-2.07). Female sex (HR 0.77; 95% CI 0.75-0.79), having a partner (HR 0.90; 95% CI 0.88-0.92) or commercial insurance (HR 0.86; 95% CI 0.84-0.88) were associated with a lower risk of T2DM. Characteristics found in >5% of patients that carried additional risk included proteinuria (5.0% of patients; HR 1.53; 95% CI 1.47-1.59), hypertension (23.9%; HR 1.21; 95% CI 1.18-1.25), high cholesterol (11.9%; HR 1.19; 95% CI 1.15-1.23), and history of smoking (40.5%; HR 1.18; 95% CI 1.15-1.21). Each standard deviation increase in BMI (5.2 kg/m2) was associated with a 1.51-fold (95% CI 1.49-1.52) increase in T2DM onset.

It is feasible to use predictive modeling to identify patients with overweight and obesity at high risk of T2DM. This approach could be utilized to guide population management and clinical treatment decisions.

Disclosure

A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc.

Funding

Eli Lilly and Company
1006-P: Progression to Type 2 Diabetes Despite a Baseline Fasting Plasma Glucose ≤ 80 mg/dl in a Population-Based Cohort
Authors: EGAN AOIFE M. , WOOD-WENTZ CHRISTINA , BAILEY KENT R. , VELLA ADRIAN
Published: June 2021

Fasting plasma glucose (FPG) concentration is a major predictor of a person’s risk of developing diabetes mellitus (DM). However, we sought to examine characteristics of individuals who develop DM despite a baseline FPG of ≤ 80mg/dL. The Rochester Epidemiology Project (REP) links the medical records of virtually all persons who have resided in Olmsted County, MN, USA between 1966 and present. Electronic laboratory data are available from 2005. Using REP, we identified individuals with ≥ 2 FPG tests from 2005-17, after excluding people who met criteria for DM on/before their first FPG. Those who developed DM (FPG > 125mg/dL) were assigned an event date as the date of their first diagnostic value. Subjects who did not develop DM were censored at their last FPG value on/before Dec 31, 2017. The entire cohort consisted of 44,815 individuals, of whom 3689 (8.2%) developed DM. Although higher baseline FPG was strongly related to development of DM, 2315 had a baseline FPG of ≤ 80mg/dL with 130 (5.6%) developing DM. Within this subset, those who progressed were older at baseline (40 ± 11 vs. 36 ± 12 years, p<0.02) and were more likely to be male (38 vs. 22%, p<0.001). Those who progressed had no difference between BMI at baseline and time of diagnosis (28 ± 8 vs. 29 ± 8 kg/m2, p=0.07). Medical record review suggested that individuals who progressed had high medical complexity. Specifically, 28 (22%) were repeatedly exposed to high dose glucocorticoids during follow up, including 10 (8%) who received a solid organ transplant. Fifteen (12%) had a substance abuse disorder. Nineteen (15%) were treated with insulin at one year following diagnosis, four of whom were diagnosed with type 1 DM. Twenty nine (22%) had a first degree relative with DM. Additional longitudinal follow up revealed that 20 (15%) were deceased at a median time of 2.5 years following the DM diagnosis. While progression to DM in the context of a baseline FPG of ≤ 80mg/dL is uncommon, it typically occurs in the setting of significant medical comorbidity.

Disclosure

A. M. Egan: None. C. Wood-wentz: None. K. R. Bailey: None. A. Vella: Research Support; Self; Novo Nordisk.

Funding

National Institutes of Health (DK78646, DK116231, DK126206, K12HD065987)
1011-P: Major Depressive Disorder Is Associated with Higher Risk of Readmission following DKA
Authors: RAMIREZ MARCELO , MURTHI MUKUNTHAN , SHARMA BHAROSA , ATLURI RAMTEJ , SHAKA HAFEEZ , VELAZQUEZ GENARO
Published: June 2021

Introduction: Diabetic ketoacidosis (DKA) is a medical emergency associated with significant patient mortality and morbidity. Studies have shown that the presence of Major Depressive Disorder (MDD) is associated with an increased incidence of DKA. We aimed to assess whether MDD was associated with increased risk of readmission following DKA.

Methods: We utilized the National Readmission Database for 2016 to identify hospitalized adult patients with a principal diagnosis of DKA and a secondary diagnosis of MDD from January 1 to November 30, 2016. We excluded patients with elective and traumatic admissions. We utilized a multivariate cox regression model to identify independent predictors of readmission.

Results: Of 15,981 patients with MDD and DKA who were discharged, 23.2%(n=3710) were readmitted within 30-days. The most common reason for readmission was DKA (63.9%, n=2371). In the multivariate cox regression model, MDD was associated with higher risk of readmission (HR: 1.17, 95% CI: 1.1 - 1.26, p=0.04) when adjusted for comorbidities and hospital characteristics. Of those MDD patients with DKA who were readmitted, type 1 DM (HR: 1.14, 95% CI: 1 - 1.3, p=0.04), CHF (HR: 1.40, 95% CI: 1.1 - 1.78, p=0.006), and CKD (HR: 1.44, 95% CI: 1.17 - 1.79, p=0.001) were associated with higher risk of readmission. Obesity (HR: 0.75, 95% CI: 0.59 - 0.97, p=0.025), private insurance (HR: 0.64, 95% CI: 0.53 - 0.79, p<0.001), median patient household income between $54,000-$70,999 (HR: 0.73, 95% CI: 0.63 - 0.85, p<0.001) and $71,000 or more (HR: 0.74, 95% CI: 0.62- 0.89, p=0.002) were associated with lower risk of readmission.

Conclusion: In this study, we found that patients with MDD admitted for DKA had a 17% increased risk of readmission within 30 days of discharge in comparison to those without MDD. This could be explained by their propensity for poor adherence to diet, exercise, and recommended pharmacological therapy. Further studies need to be done to assess and target the exact precipitants of readmission.

Disclosure

M. Ramirez: None. M. Murthi: None. B. Sharma: None. R. Atluri: None. H. Shaka: None. G. Velazquez: None.
103-LB: Real-World Persistence, Adherence, Health Care Resource Utilization, and Costs in People with Type 2 Diabetes (T2D) Switching from Basal Insulin (BI) to Second-Generation BI (Insulin Glargine 300 U/mL [Gla-300]) vs. First-Generation BI (Insulin Glargine 1
Authors: WRIGHT EUGENE , GILL JASVINDER , HUSE SAMUEL , LI XUAN , REID TIMOTHY , ZHOU FANG L.
Published: June 2021

This retrospective observational study using the Optum Clinformatics claims database included data from adults (≥18 y) with T2D who had received prior basal insulin (BI) (NPH, Gla-100, IDet) in the 6-month baseline period, and switched to either the second-generation (2nd-gen) BI, Gla-300 or a first-generation (1st-gen) BI (Gla-100, IDet) (treatment switch=index date) between April 1, 2015 and August 31, 2019. Participants were followed from index date for 12 months or plan disenrollment or death. Cohorts were propensity score matched (PSM) on baseline demographic/clinical characteristics. Outcomes were persistence (days on treatment without discontinuation), adherence (proportion days covered), healthcare resource utilization and costs. After PSM (n=3077/cohort; mean age 68 y, 52% female), cohorts were well balanced except for 1 variable (hospitalization) with standardized difference >0.1, which was adjusted in models as a covariate. During the 12-month follow-up period, higher proportions of participants who received Gla-300 vs. 1st-gen BI were persistent (45.5 vs. 42.1%; adjusted p=.0001) and adherent (42.8 vs. 38.2%; adjusted p=.0006). All-cause healthcare resource utilization was lower for Gla-300 vs. 1st-gen BI (emergency room visits 111.9 vs. 148.8 events per 100 patient-years [PY]; inpatient hospitalizations 45.3 vs. 65.9 events per 100 PY; adjusted p<.0001). Total healthcare costs were numerically lower for Gla-300 vs. 1st-gen BI ($41,255 vs. $45,316 per PY). Switching to Gla-300 was associated with significantly better persistence, adherence, and—despite these associated costs—lower all-cause healthcare resource utilization vs. switching to a 1st-gen BI, in people with T2D previously treated with BI therapy. This is the first study to assess these outcomes in tandem.

Disclosure

E. Wright: Advisory Panel; Self; Abbott Diabetes, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Sanofi, Consultant; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; American Diabetes Association, Speaker’s Bureau; Self; Bayer Healthcare Pharmaceuticals Inc., Sanofi. J. Gill: Employee; Self; Sanofi US, Other Relationship; Self; American Diabetes Association, Stock/Shareholder; Self; Sanofi US. S. Huse: Consultant; Self; Sanofi US. X. Li: Employee; Self; Sanofi US. T. Reid: Other Relationship; Self; Sanofi US. F. L. Zhou: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi.

Funding

Sanofi US
1034-P: Association between Estimated Glomerular Filtration Rate (eGFR) and Proteinuria (UP) to Predict Risk of Start of Dialysis in People with and without Diabetes (DM)
Authors: OSAWA TAEKO , FUJIHARA KAZUYA , YAMADA MAYUKO H. , YAGUCHI YUTA , SATO TAKAAKI , KITAZAWA MASARU , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , SONE HIROHITO
Published: June 2021

Although UP is a very important feature of diabetic nephropathy, decreased eGFR without UP has become phenotypic of renal complications of DM in the new definition of DKD. Although both UP and reduced eGFR are strong predictors of kidney disease, only a few studies have examined the association between these two variables and risk of dialysis in the same cohort that included people with and without DM. We analyzed data from a nationwide claims database involving 335,778 participants (DM 20,223, non-DM 315,555) during 2008-16. Multivariate Cox regression model identified risks of starting dialysis. HRs were compared among 8 groups of combinations of DM+/-, UP (-, ≥+) and eGFR (<60, ≥60). Compared with eGFR ≥60, HRs for starting dialysis in those with eGFR <60 in DM- and DM+ were 14.5 (10.3-20.6) and 15.7 (10.8-22.9), respectively. In comparison with UP (-), HRs for starting dialysis with UP (≥+) in DM- and DM+ were 8.00 (5.85-11.0) and 8.01 (5.45-11.8), respectively. In DM-, compared with UP(-)eGFR ≥60, the HRs for UP(≥+)eGFR ≥60, UP(-)eGFR <60 and UP(≥+)eGFR <60 were 1.19 (0.55-2.60), 4.21 (2.47-7.17) and 113.4 (77.9-165.0), respectively. In DM+, those values were 3.83 (2.15-6.83), 6.47 (3.33-12.6) and 94.4 (58.5-152.4), respectively. In comparison with DM(-)UP(-)eGFR ≥60, risks of starting dialysis for DM(+)UP(≥+)eGFR ≥60, DM(+)UP(-)eGFR <60 and DM(+)UP(≥+)eGFR <60 significantly increased 17.7 (10.6-29.7), 25.5 (13.8-47.1) and 358.1 times (239.1-536.5), respectively.

In summary, both eGFR<60 and UP(≥+) were independent predictors for starting dialysis regardless of DM and they exhibited a synergistic risk of dialysis. Both eGFR<60 and UP(+) present an extremely high risk for dialysis especially in DM. These results may be helpful in considering the relationship between the need for strict therapeutic interventions for eGFR and UP and the risk of dialysis, according to the presence or absence of DM.

Disclosure

T. Osawa: None. K. Fujihara: None. M. H. Yamada: None. Y. Yaguchi: None. T. Sato: None. M. Kitazawa: None. Y. Matsubayashi: None. T. Yamada: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Funding

Japan Society for the Promotion of Science (18K17897)
104-OR: Novel GIP/GLP-1/Glucagon Receptor Agonist LY3437943: A First-in-Human Dose Study in Healthy Subjects
Authors: URVA SHWETA , DU YU , THOMAS MELISSA K. , MILICEVIC ZVONKO , COSKUN TAMER , BENSON CHARLES , LOGHIN CORINA
Published: June 2021

Multifunctional incretins are in clinical development for several metabolic conditions. Novel LY3437943 has potent agonist activity on glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon receptors. The primary objective of this randomized, double-blind, placebo (PBO)-controlled, Phase 1, first in human study was to assess safety and tolerability of single-ascending doses of LY3437943. Forty-five healthy subjects were randomized (6:2) to subcutaneous LY3437943 (6 rising dose levels) or PBO. Vital signs, ECGs, laboratory data and adverse events (AEs) were monitored to assess safety and tolerability. LY3437943 pharmacokinetics (PK) as well as change from baseline (BL) in fasting insulin, C-peptide and weight were measured. Appetite was assessed using a visual analog scale (VAS). The most common treatment-emergent AEs were gastrointestinal, including vomiting (with higher doses), abdominal distention and nausea, which were dose-dependent, mostly mild in severity, occurred within 4 days of dosing and resolved within a week of onset. Dose-dependent increases in heart rate and decreases in systolic blood pressure were observed, which returned to near BL by Day 29. Mean terminal half-life of LY3437943 ranged from 134-165 h (∼7 days) across the 6 doses, supporting once-weekly dosing. Dose-dependent increases in mean fasting insulin and C-peptide, with maximum levels observed at 24 and 48 h, returned to near BL by Day 15. Dose-dependent weight loss was statistically significant with the 3 highest doses vs. PBO (up to 3.5 kg at the highest dose). Weight loss was maintained up to Day 43 following single administration of the two highest doses. Overall VAS score significantly increased with higher doses vs. PBO, reflecting decreased appetite. Triple-agonist peptide LY3437943 had a safety and tolerability profile similar to other incretins in Phase 1 trials with PK and pharmacodynamic outcomes that support further clinical evaluation.

Disclosure

S. Urva: Employee; Self; Eli Lilly and Company. Y. Du: None. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. Z. Milicevic: Employee; Self; Eli Lilly and Company. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. C. Benson: Employee; Self; Eli Lilly and Company. C. Loghin: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1046-P: Automated Early Flagging of Undiagnosed CKD Using Real-World Data
Authors: MALAGARRIGA DANIEL , CHITTAJALLU SIVA , GALLEY PAUL J. , SINGH INDERJIT , ODEGARD JOHN T.
Published: June 2021

Aims: Early diagnosis and treatment of chronic kidney disease (CKD) may delay disease progression since 45% of patients are not diagnosed until stage 3. We examine the Kidney Disease Improving Global Outcomes (KDIGO) clinical guidelines that define rules based on the longitudinal progression of urine albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) for flagging CKD in people with type 2 diabetes (T2-PwD).

Methods: EHR data from over 400,000 T2-PwDs in the Indiana Network for Patient Care (INPC) database were used for this analysis. The KDIGO clinical practice guidelines defines CKD as persistently elevated urine albumin excretion (>=30 mg/g), or persistently reduced eGFR (< 60 ml/min per 1.73m2), or both, for more than 3 months. Our automated system scanned each patient’s longitudinal record and identified those patients with abnormal UACR and eGFR values in the cases where sufficient values were available. A flag associated with either UACR or eGFR or both and the date of flagging is indicated by the system if abnormal marker values persist for more than 3 months. CKD is indicated if one or both flags are triggered.

Results: Out of 422,089 patients 35,573 (8%) were identified as diagnosed with CKD. Only 3% of these patients had at least 2 UACR readings and, therefore, the automated system considered primarily eGFR as the marker for flagging CKD. Out of 35,573 patients with CKD diagnosis, 16,342 (46%) had an eGFR warning flag that predated the CKD diagnosis date. The system flagged a potential identification as much as 599 days (median value) in advance of the diagnosis of CKD in the dataset.

Conclusion: Our results show that earlier identification of CKD onset can be automated to flag patients wherein a positive diagnosis of CKD is likely. This flag can then prompt a confirmatory diagnosis of CKD, allowing better treatment interventions and management of CKD, reducing the burden of disease, and potentially decreasing costs associated with treatments in later CKD stages.

Disclosure

D. Malagarriga: None. S. Chittajallu: Employee; Self; Roche Diabetes Care. P. J. Galley: Employee; Self; Roche Diabetes Care. I. Singh: Employee; Self; Roche Diabetes Care. J. T. Odegard: Employee; Self; Roche Diabetes Care.
1049-P: Finding Equity: Utilizing Artificial Intelligence to Identify Social and Infrastructural Predictors of Diabetes Mortality in Florida
Authors: CISTOLA ANDREW
Published: June 2021

DM outcomes represent one of the largest avoidable cost burdens with opportunity for improvement in the U.S. health care system. Improving health equity in the context of DM will require targeted community improvements, infrastructure investments, and policy interventions that are designed to maximize the impact of resource allocation through the use of available data and computational resources. By using an Artificial Intelligence approach to evaluate over 2000 socio-economic and infrastructural predictors of DM mortality, this study used a specific series of modeling techniques to identify significant predictors without human selection and compare their predictive ability with all possible factors when passed through artificial neural networks. The final regression model using zip code and county level predictors had an R2 of 0.863. Significant predictors included: Population % White, Population % Householders, Population % Spanish spoken at home, Population % Divorced males, Population % With public health insurance coverage, Population % Employed with private health insurance coverage, Manufacturing-Dependent Designation, Low Education Designation, Population % Medicare Part A and B Female Beneficiaries, Number of Short Term General Hospitals with 50-99 Beds. Using a multi-layered perceptron to predict zip codes at risk the C-statistic for all 2000+ predictors was 0.7938 while the 13 selected predictors was 0.8232. This indicates that these factors are highly relevant for DM mortality in Florida. This process was completed without the need of human variable selection and indicates how AI can be used for informative precision public health analyses for targeted population health management efforts.

Disclosure

A. Cistola: None.
1052-P: Clinical Characteristics of Osteoporosis in Postmenopausal Women with Type 2 Diabetes Mellitus
Authors: WANG YAN , LINA ZHANG , GUO LIXIN
Published: June 2021

Objective: To investigate clinical characteristics and risk factors of osteoporosis in postmenopausal women with type 2 diabetes mellitus.

Method: A total of 410 postmenopausal women with type 2 diabetes of natural menopause with no history of fracture were collected from outpatients of Beijing Hospital (Oct 2017 - Nov 2019). Bone mineral density (BMD) at lumbar spine L1-L4 and hip was measured using dual-energy X-ray absorptiometry. Biochemical markers of bone and glucose metabolism were evaluated. Patients were divided into three groups based on BMD: A (osteoporosis): T ≤-2.5 SD; B (osteopenia) -2.5 < T ≤ -1 SD; C (normal bone mineral density) T > -1 SD. Statistical differences of age, menopausal age, diabetes age, BMI and biochemical indexes were compared between groups.

Result: 1. Case number based on lumbar spine BMD: 189 in A (46.1%), 147 in B (35.9%), and 74 in C (18.0%). ANOVA analysis showed group A patients had the highest age (F 5.698, p 0.004), age of diabetes onset (F 7.596, p 0.001), ALP (F 3.231, p 0.041) and menopausal duration (F 7.596, p 0.001), but the lowest BMI (F 11.456, p 0.000). Logistic multivariate regression showed body mass index is an independent risk factor for osteoporosis in postmenopausal women with type 2 diabetes [A vs. C: OR1.224 (95% CI 1.106-1.355, p 0.000); A vs. B: OR1.172 (95% CI 1.079-1.274, p 0.000].2. Case number based on femoral neck BMD: 159 in A (38.8%), 188 in B (45.9%), 63 in C (15.3%). ANOVA analysis showed group A patients had the highest age (F 21.484, p 0.000), age of diabetes onset (F 10.125, p 0.000) and PTH (F3.691, 0.026), but the lowest BMI (F 11.456, p 0.000). Logistic multivariate regression showed body mass index is an independent risk factor for osteoporosis in postmenopausal women with type 2 diabetes [A vs. C: OR1.267 (95% CI 1.120-1.433, p 0.000); A vs. B: OR1.195 (95% CI1.099-1.301, p 0.000)].

Conclusion: Osteoporosis in postmenopausal women with type 2 diabetes is associated with older age, longer menopause duration, older age of diabetes onset and lower BMI.

Disclosure

Y. Wang: None. Z. Lina: None. L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China.
1059-P: Unmet Social Needs and Diabetes-Related Emergency Department Visits and Hospitalization: A Nationally Representative Study of U.S. Safety-Net Health Center Patients
Authors: YAN ALICE , SHI ZUMIN , OZIEH MUKOSO N. , WILLIAMS JONI S.
Published: June 2021

Introduction: Evidence shows that social determinants of health (SDOH) account for more variation in health outcomes than medical care. This study examined the association between unmet social needs and diabetes-related emergency department (ER) visits and hospitalizations.

Methods: Cross-sectional data on adults (aged≥18 years) with self-reported diabetes from the 2014 Health Center Patient Survey (HCPS) was analyzed. Outcome (binary) was diabetes-related ER visits or hospitalizations in prior 12 months. The independent variables were 17 SDOH unmet social factors clustered into three domains: (1) basic needs; (2) health-related social needs; and (3) adverse income or assets factors. Responses were coded as binary (unmet or met). Logistic regression models tested the association between adverse SDOH and outcome, adjusting for sociodemographic covariates.

Results: Among 5592 participants (63.0% female and 22.8% Blacks), 1282 had diabetes (weighted prevalence=22.5%). Of the diabetic participants, 50.9% were unstably housed and 51.3% were food stamp recipients and their top 3 unmet needs were related to service from the health center (home visit, counseling, and health education). In the univariable model, no interpreting service and not receiving help from the health center were statistically inversely associated with, and unstable housing and receiving food stamps were positively associated with the outcome. In the fully adjusted model, those who received food stamps were 3.57 times more likely to have diabetes-related ER visits or hospitalization (95%CI: 1.08 - 11.82). Age was (45-54 vs. 18-44 yrs) (OR= 0.31 95%CI: 0.13-0.78) also significantly associated with ER visits or hospitalizations.

Conclusions: Findings suggest that receiving food stamps was the strongest predictor for diabetes ER visit. Diabetes interventions that target food stamp/SNAP recipients may improve their health outcomes.

Disclosure

A. Yan: None. Z. Shi: None. M. N. Ozieh: None. J. S. Williams: None.
106-OR: A First-in-Human Single Ascending Dose Study of Oxyntomodulin Analog LY3305677 in Healthy Subjects
Authors: THAM LAI-SAN , THOMAS MELISSA K. , BENSON CHARLES , BRAY ROSS , TANG CHENG CAI , LOGHIN CORINA
Published: June 2021

LY3305677 (LY) is an acylated single chain peptide analog of mammalian oxyntomodulin designed for once weekly dosing. It has dual pharmacology of GLP-1 and glucagon and has therapeutic potential for T2D, obesity and NASH. This randomized, double blind, placebo-controlled phase 1 study assessed safety and tolerability of single ascending doses of LY. Healthy subjects (N=48) were randomized (6:2) and 47 received subcutaneous LY (6 doses: 0.03 mg to 5.0 mg) or placebo. Safety biomarkers, LY pharmacokinetics (PK), and key exploratory pharmacodynamic (PD) biomarkers were assessed including fasting insulin, glucagon, triglyceride levels, and body weight. Most common LY-related AEs were gastrointestinal events. Dose-dependent increase in nausea, decreased appetite, and vomiting were seen. Most of the events were mild and transient. Increase in heart rate was noted, which returned to baseline for most groups at follow-up visit. No injection site reactions were seen. Median time to maximum LY concentration ranged from 18.2 to 72.1 h, and geometric mean half-life ranged from 7.5 to 9.8 days. Generally, mean fasting insulin level increased within 24 h and lasted over 8 days. At Day 8, LY 2.5 mg and 5.0 mg reduced mean fasting glucagon levels by 2.33 pmol/L and 2.67 pmol/L, respectively as compared with placebo. At Day 5, mean fasting triglyceride levels reduced from baseline by 0.5 mmol/L with LY 5.0 mg as compared to 0.1 mmol/L with placebo. Change from baseline in body weight reached a maximum -2.4 kg with the 5 mg dose, versus -0.5 kg for placebo at Day 8 and this effect was sustained through Day 29 at 5 mg.

LY3305677 PK properties are suitable for once-weekly dosing with a safety and tolerability profile similar to other incretins in Phase 1 trials, supporting future clinical evaluation.

Disclosure

L. Tham: Employee; Self; Eli Lilly and Company. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. C. Benson: Employee; Self; Eli Lilly and Company. R. Bray: None. C. Tang: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Novartis AG. C. Loghin: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1062-P: Attainment of Glycemic Targets among Adults with Diabetes in Canada: A Cross-Sectional National Diabetes Repository Study
Authors: WEISMAN ALANNA , PERKINS BRUCE A.
Published: June 2021

Objective: International societies and clinical practice guidelines recommend a Hemoglobin A1c target of ≤7.0% for the majority of adults with type 1 (T1D) and type 2 diabetes (T2D). However, the proportion meeting this target and its predictors have not been comprehensively described outside of the USA or in population-based data sources.

Methods: Adults with diabetes were identified in the National Diabetes Repository, a primary care electronic medical record (EMR) database from 5 Canadian provinces, from January 2015 to June 2019. Individuals were categorized as T1D (using a previously validated algorithm), T2D not prescribed insulin, or T2D prescribed insulin. Using the most recent HbA1c, proportions of individuals with HbA1c ≤7.0% were determined and compared using Chi-square tests. Multivariable logistic regression models were used to assess the association between predictors and meeting the HbA1c target.

Results: Of 83,273 eligible adults in the National Diabetes Repository, 1484 had T1D, 10,473 had T2D prescribed insulin and 71,316 had T2D not prescribed insulin. Proportions meeting the HbA1c target of ≤7.0% were 23.9%, 24.9%, and 62.4%, respectively (p=0.4 for T1D vs. T2D prescribed insulin, p<0.0001 for other comparisons). In multivariable logistic regression models, depression was associated with reduced likelihood of meeting the HbA1c target for T1D (OR 0.74, 95% CI 0.55-0.98). Male sex, lower income quintile, and insulin use were associated with reduced likelihood of meeting the HbA1c target for T2D (0.85(0.83-0.88); 0.83(0.79-0.88); 0.23(0.22-0.24)).

Conclusions: In a Canadian population-based primary-care EMR database, less than one-fourth of adults with T1D and T2D prescribed insulin, whereas two-thirds of adults with T2D not prescribed insulin, attain the recommended HbA1c target of ≤7.0%. Further research and implementation approaches are required to optimize outcomes in diabetes, particularly for those requiring insulin.

Disclosure

A. Weisman: None. B. A. Perkins: Advisory Panel; Self; Abbott Diabetes, Boehringer Ingelheim International GmbH, Insulet Corporation, Novo Nordisk Canada Inc., Other Relationship; Self; Abbott Diabetes, Medtronic, Novo Nordisk Canada Inc.

Funding

Diabetes Action Canada
1068-P: Diabetes and Comorbidities Risk Assessment in Hospitalization and Fatalities from the Mexican COVID-19 Surveillance System
Authors: GALLARDO-RINCÓN HECTOR , MONTOYA ALEJANDRA , MARTINEZ-JUAREZ LUIS ALBERTO , LOMELIN-GASCON JULIETA , SAUCEDO-MARTINEZ EDUARDO R. , MUJICA-ROSALES RICARDO , TAPIA-CONYER ROBERTO
Published: June 2021

The SARS-CoV-2 outbreak poses a challenge to the Mexican health care system due to its high complication and lethality rates in patients with diabetes and comorbidities. Here, we evaluate the association among diabetes and main comorbidities [obesity, hypertension and chronic kidney disease (CKD)] on COVID-19 outcomes (prevalence, hospitalization, lethality and hospital fatality) in Mexican population. We used available public data released by the Mexican COVID-19 surveillance system (MC-19SS) from January 1st to December 31st of 2020. All 3,401,172 records of SARS-CoV-2 suspected population over or equal to 20 years old were included, out of whom 1,384,470 tested positive. Multiple logistic regression models were fitted to assess the risk over several outcomes (hospitalization and fatality), with self-reported diabetes and comorbidities in confirmed cases, adjusting for age, sex, smoking status and marginalization of the place of residence. Overall population tested, 399,953 (11.8%) subjects had diabetes. Of them, 47.8% also had hypertension, 9.0% obesity and 7.0% CKD. Patients who tested positive to COVID-19 had a higher proportion of diabetes (14.7%). From the 203,310 COVID-19 positive patients with diabetes, 95,225(46.8%) were hospitalized and of those 45,128(47.4%) died; also 4,701 died without had been hospitalized. People with diabetes had significant (p<.005) higher odds of hospitalization OR:2.2, hospital 1.27 and non-hospital 1.98 fatality. Nevertheless, subjects with diabetes and other chronic disease experience higher rates of several outcomes. Diabetes and CKD had the highest odds of hospitalization 7.3 died in hospital (2.14) or out of hospital (6.5) compared with cases without diabetes. This analysis points out that diabetes contributes to the risk of infection and worse outcomes for those infected by SARS-CoV-2. More must be done to combat and prevent diabetes and comorbidities to reduce the burden of COVID-19.

Disclosure

H. Gallardo-rincón: None. A. Montoya: None. L. Martinez-juarez: Research Support; Self; Lilly Global Health Partnership. J. Lomelin-gascon: None. E. R. Saucedo-martinez: None. R. Mujica-rosales: None. R. Tapia-conyer: None.
1069-P: How Does Exposure to Overnutrition In Utero Lead to Childhood Adiposity? A Longitudinal Study in the Exploring Perinatal Outcomes among Children (EPOCH) Cohort
Authors: PERNG WEI , KELSEY MEGAN M. , SAUDER KATHERINE A. , DABELEA DANA
Published: June 2021

We explored the longitudinal sequence of metabolic changes linking overnutrition in utero to development of adiposity among initially normal weight children in the EPOCH cohort. This study includes 312 normal weight youth (body mass index [BMI] z <1 SD per the World Health Organization growth reference) that were exposed (n=144) or unexposed (n=168) to overnutrition in utero (maternal BMI ≥25 kg/m2 or gestational diabetes). Fasting insulin, glucose and adiposity were obtained at research visits during childhood (age 10 y) and adolescence (age 16 y). We examined associations of overnutrition in utero with natural log transformed fasting insulin at baseline, followed by associations of baseline fasting insulin with adiposity (BMI z, subcutaneous [SAT] and visceral fat depots [VAT]), insulin resistance (HOMA-IR), and fasting glucose during follow-up using linear mixed models that accounted for child age, sex, and race/ethnicity; maternal education and prenatal smoking. Baseline BMI z, fasting glucose, HOMA-IR, and adiposity markers (except for slightly higher SAT in exposed youth [+10 mm2]) were not different by exposure status. Overnutrition in utero corresponded with 14% (1%, 29%) higher baseline fasting insulin, even after controlling for child VAT, SAT, or VAT:SAT. Higher baseline fasting insulin was, in turn, associated with greater adiposity (0.41 [0.26, 0.55] SD BMI z; 13.9 [2.4, 25.4] mm2 SAT; 2.0 [0.1, 3.8] mm2 VAT) and HOMA-IR (0.88 [0.69, 1.07]) across follow-up, but not with fasting glucose. These results suggest that overnutrition in utero may result in hyperinsulinemia during childhood and precede accrual of adiposity. However, since our study started at age 10 y, studies in normal weight youth starting earlier, and with repeated assessments of insulin sensitivity, β cell function and glycemia, are needed to clarify the sequence of metabolic changes resulting from early exposures.

Disclosure

W. Perng: None. M. M. Kelsey: Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. K. A. Sauder: None. D. Dabelea: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068001); Colorado Clinical and Translational Sciences Institute (KL2-TR002534 to W.P.)
1078-P: Disparities in HbA1c Testing and Diabetes Outcomes: SEARCH for Diabetes in Youth
Authors: SAUDER KATHERINE A. , STAFFORD JEANETTE M. , EHRLICH SHELLEY R. , LIESE ANGELA D. , MARCOVINA SANTICA M. , MOTTL AMY K. , PIHOKER CATHERINE , SAYDAH SHARON , SHAH AMY S. , DAGOSTINO RALPH , DABELEA DANA
Published: June 2021

Hemoglobin A1c (HbA1c) monitoring over time is thought to facilitate care and support diabetes management goals, but only half of youth and young adults with diabetes report ≥3 HbA1c tests/year despite poor glycemic control. We explored disparities in HbA1c testing over time and association with HbA1c levels and microvascular complications (retinopathy, neuropathy, or nephropathy) in the SEARCH for Diabetes in Youth study. Individuals diagnosed with diabetes at <20 years (n=707 type 1, n=112 type 2) did research visits at 8 and 13 years diabetes duration (mean ages 18 and 23 years, respectively). We used one logistic regression model per diabetes type to identify correlates of reporting ≥3 HbA1c tests/year at both visits, and used one multiple linear and one logistic regression model per type to examine associations of reporting ≥3 HbA1c tests/year at both visits with HbA1c levels or microvascular complications, adjusting for HbA1c testing correlates. In type 1 diabetes, odds of reporting ≥3 HbA1c tests/year at both visits decreased with older age at diagnosis (OR 0.91 [95%CI 0.88-0.95]), longer duration of diabetes (OR 0.91 [0.84-0.999]), not having a personal doctor (0.43 [0.30-0.62]), and lapses in health insurance (OR 0.51 [0.28-0.93]). In turn, HbA1c testing ≥3 times/year at both visits was associated with lower HbA1c levels (-0.32% [-0.61 to -0.03]) but not microvascular complications (OR 0.74 [0.49-1.10]) at 13 years duration. In type 2 diabetes, odds of reporting ≥3 HbA1c tests/year at both visits was lower when not receiving care from endocrinologists (OR 0.15 [0.04-0.48]), but not associated with other sociodemographic or clinical factors, and not observed to be associated with HbA1c levels or microvascular complications at 13 years duration.

In conclusion, we report that mainly healthcare-related factors are associated with disparities in HbA1c testing frequency over time in youth-onset type 1 and type 2 diabetes, and these disparities are associated with HbA1c levels in type 1 diabetes.

Disclosure

K. A. Sauder: None. R. Dagostino: Consultant; Self; AstraZeneca, Biogen, Daiichi Sankyo. D. Dabelea: None. J. M. Stafford: None. S. R. Ehrlich: None. A. D. Liese: None. S. M. Marcovina: None. A. K. Mottl: Advisory Panel; Self; Bayer U. S. C. Pihoker: None. S. Saydah: None. A. S. Shah: None.

Funding

National Institutes of Health; Centers for Disease Control and Prevention
109-LB: Comparative Effectiveness of Insulin Glargine 300 U/mL (Gla-300) and Insulin Degludec 100 U/mL (iDeg-100) in Insulin-Naïve Type 2 Diabetes Adults: RESTORE-2 Real-World Study
Authors: FADINI GIAN PAOLO , BUZZETTI RAFFAELLA , NICOLUCCI ANTONIO , ROSSI MARIA CHIARA , LAROSA MONICA , CUCINOTTA DOMENICO ,   ON BEHALF OF RESTORE-2 STUDY GROUP
Published: June 2021

Second generation basal insulin (2BI) provide similar/improved efficacy with better safety compared to first generation BI. Real-world data on 2BI in patients with type 2 diabetes (T2D) are still limited.

The study aimed at comparing effectiveness of 2BI (Gla-300 vs. iDeg-100) in insulin-naïve T2D.

This was a retrospective, non-inferiority, multicenter study, from electronic medical records. All patients initiating Gla-300 or iDeg-100 in January 2017-2020 were 1:1 propensity score matched. Linear mixed models for repeated measures were applied to assess changes during 6 months in HbA1c, fasting blood glucose (FBG), body weight, and insulin doses. Incidence rates (IR) of hypoglycemic events were compared using Poisson regression models.

Overall, 19 centers provided data on 357 patients in each PSM cohort. Estimated mean baseline levels of HbA1c were 9.2%. Marked reductions in HbA1c after 6 months were documented: -1.70%; (95%CI -1.90; -1.50) in Gla-300 group and -1.69%; (95%CI -1.89; -1.49) in IDeg-100 group (between group mean difference: 0.01; 95%CI -0.29; 0.27), confirming non-inferiority of Gla-300 vs. IDeg-100. FBG was reduced by about 60 mg/dl in both groups; minor changes in body weight were documented. In both groups, the mean prescribed dose was about 12 U (0.15 U/Kg) and was slightly titrated during 6 months up to +4U (0.20 U/Kg).

IR (episodes per patient-months) of BG≤70 mg/dl was 0.13 (95%CI 0.07;0.26) in Gla-300 group and 0.14 (95%CI 0.07;0.27) in IDeg-100 group (p=0.87). IR of BG<54 mg/dL was 0.02 (95%CI 0.01;0.05) in Gla-300 group and 0.02 (95%CI 0.01;0.04) in IDeg-100 group (p=0.49). No severe hypoglycemic episodes were reported. In T2DM adults, initiation of Gla-300 or IDeg-100 was associated with similar improvements in glycemic control, no weight gain, low hypoglycemia rates, with no severe episodes. These data can contribute in overcoming clinical inertia in BI initiation and dose titration.

Disclosure

G. Fadini: Board Member; Self; Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Sanofi. R. Buzzetti: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi & Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi & Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. D. Cucinotta: None. On behalf of restore-2 study group: n/a.

Funding

Sanofi