bluuebunny/crossref_metadata_2025_split huggingface dataset:
584-P: Diabetes Distress, Depressive Symptoms, and Gender Disparities in Glycemic Control among African Americans with Type 2 Diabetes
Authors: HAWKINS JACLYNN M. , KOSCIELNIAK NIKOLAS J. , NWANKWO ROBIN , FUNNELL MARTHA M. , KLOSS KATHERINE A. , HALL DIANA , PIATT GRETCHEN 
Published: June 2021

Despite advances in diabetes self-management education and support (DSMES), disparities persist in clinical, behavioral, and psychosocial outcomes. Evidence suggests that, in addition to racial/ethnic disparities in diabetes self-management, gender disparities in glycemic control (A1c) exist in patients with type 2 diabetes (T2D). However, there is a knowledge gap in determining if gender differences in A1c are mediated by Diabetes Distress (DD) and/or Depressive Symptoms (DS), or if gender moderates this relationship. Therefore, we aimed to investigate the relationship between gender, DD, DS, and A1c in 94 African American adults with T2D from 9 churches in metro-Detroit, MI. All churches participated in a 15-month, cluster randomized controlled trial focused on DSMS efforts to maintain T2D outcomes following DSME. DD was defined as DD Scale score &gt;=3. DS was measured with the PHQ-9. PHQ-9 was categorized into no DS (PHQ-9 score &lt; 5), minimal DS (PHQ-9 score &gt;=5&lt;10), and depression (PHQ-9 scores &gt;=10). Participants were 44% male, had a mean age of 65.0±10.46 years, and 32% were prescribed insulin. Mean baseline A1c was 7.1±1.7 (males: 7.4±2.0; females: 6.9±1.5, p=0.78). 34.4% of participants reported having DD. More females (35%) reported DD compared to males (31.2%) p=0.72. Approximately 63% of participants reported no DS, 21% reported minimal DS, and 16% reported having DS. There were no differences in PHQ-9 scores when stratified by gender (p=0.17). Mixed effects logistic regression revealed that gender did not moderate the relationship between DD or DS and A1c. However, DD mediated gender differences in A1c (β=-1.7, p=0.02) but DS did not (β=-0.25, p=0.76). Gender differences in a1c for patients with T2D may be attributable to DD, but not DS. As females traditionally report higher DD levels than males and a1c is often worse in males than females, increased attention to these gender differences is warranted, particularly among African Americans.

Disclosure
J. M. Hawkins: None. N. J. Koscielniak: None. R. Nwankwo: None. M. M. Funnell: Other Relationship; Self; American Diabetes Association. K. A. Kloss: None. D. Hall: None. G. Piatt: None.

Funding
National Institutes of Health (5R01DK10473305)
592-P: Patient Perception of RT-CGM for Lifestyle Change Six Months after Two Sessions of RT-CGM
Authors: PORTER MICHAEL W. , NEEDLEMAN LEOR , RAMHMDANI SEBA , EHRHARDT NICOLE M. 
Published: June 2021

Background: Real-time continuous glucose monitoring (RT-CGM) provides glucose readings to patients with diabetes, potentially supporting self-care. Preliminary data suggests efficacy of these devices influencing behavior change but data are limited on the sustainability of this change following short term use.
Methods: Following completion of a 14 week intervention involving use of RT-CGM as a behavior modification tool, a 6 month follow up survey was conducted. The survey included ten questions evaluating the impact of the subject's participation in the study on their continued lifestyle and health. The final question of the survey inquired if the subject had a significant other available to answer questions regarding their awareness of the subject's participation and impact on their own lifestyle choices.
Results: Twenty-two participants with diabetes participated in the initial intervention, of which sixteen responded to the survey. In the six months since their participation, 100% of respondents reported that CGM continues to contribute to a healthier lifestyle. 75% reported that they have excluded or limited certain foods as a result of participating and participation has motivated them to increase activity level. If available, 88% reported that they would you like to wear a CGM device on a regular basis. 68.8 % reported subjective weight loss since participating in the study with 7 (63.7%) of those participants reporting a weight loss of 10lbs or greater. Of the 16 participants, 3 subjects had a significant other that lived with the subject throughout the study and was able to be contacted. Of these three, 1 reported feeling healthier and changing their food choices as a result of their partner wearing a CGM.
Conclusion: In patients with diabetes, RT-CGM creates a sustainable lifestyle impact 6 months following use and is a desired tool for self care. However, longer prospective studies need to be completed. Further evaluation of RT-CGM contribution to the “health” of the household is also needed.

Disclosure
M. W. Porter: None. L. Needleman: None. S. Ramhmdani: None. N. M. Ehrhardt: Advisory Panel; Self; Novo Nordisk, Research Support; Self; Dexcom, Inc., Merck & Co., Inc., Novo Nordisk.
593-P: Effectiveness of Digital Therapeutics to Improve Clinical Outcomes in Patients with Type 2 Diabetes Mellitus on Insulin Therapy
Authors: ADHIKARY RISHI R. , KOLWANKAR SIDDDHESH , VERMA RITIKA , BHATT JITESH , PAKHALE KETAN L. , SAHAY RAKESH 
Published: June 2021

Background: Diabetes self-management education and support (DSMES) is integral towards maintaining continuity of care between physician visits especially for patients on insulin therapy to facilitate healthy coping. The present study explores the usage patterns and real-world effectiveness of the Wellthy CARE™ digital therapeutic (WDTx) platform in achieving glycemic control among patients with type 2 diabetes mellitus (T2DM) on insulin therapy.
Methods: The WDTx platform consists of a smartphone application with a 52-week program to provide DSMES through self-monitoring of blood glucose, access to evidence-based content regarding insulin usage and remote guidance by a health coach to enable lifestyle modifications and healthy coping. All app interactions were analyzed at baseline and during the program to determine factors driving patient engagement and clinical outcomes.
Results: Study participants (n=106) had a mean age of 51.4 years (SD 14.0 years) and consisted of 39 females (36.8%). Overall, a significant mean decrease in average blood sugar (ABS) by 29.9 mg/dl (95%CI 16.6-43.3 mg/dl, P&lt;0.001) was observed with a 31.9% reduction in proportion of hypoglycemia logs and an average of 6.1 app interactions per patient per week on the platform thus proving continuity of care provided through WDTx. Users in the highest tertile for early app interactions (within week 1) demonstrated a significant mean decrease in ABS by 30.8 mg/dl (95%CI 7.5-54.0 mg/dl, P&lt;0.01) while no significant change was seen in the corresponding lowest tertile. Over the entire program, users in the tertile with highest app engagement showed a significant mean decrease in ABS of 27.4 mg/dl (95%CI 8.8-46.1 mg/dl, P&lt;0.01) as compared to no significant change in the lowest tertile.
Conclusion: This study thus demonstrates the effectiveness of the WDTx platform to impart critical DSMES, maintain continuity of care and improve clinical outcomes in patients with T2DM on insulin therapy.

Disclosure
R. R. Adhikary: Employee; Self; Wellthy Therapeutics Pvt Ltd. S. Kolwankar: Employee; Self; Wellthy Therapeutics Pvt Ltd. R. Verma: Consultant; Self; Wellthy Therapeutics Pvt Ltd. J. Bhatt: Employee; Self; Wellthy Therapeutics Pvt Ltd. K. L. Pakhale: None. R. Sahay: Advisory Panel; Self; Cipla Inc., USV Private Limited, Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Pharma Ltd.
596-P: Machine Learning Prediction of Blood Glucose in Hospitalized Patients
Authors: ZALE ANDREW D. , ABUSAMAAN MOHAMMED S. , MATHIOUDAKIS NESTORAS 
Published: June 2021

Background: Inpatient glucose management can be challenging due to various evolving factors that influence a patient's blood glucose (BG). Providers could benefit from a clinical decision support tool that predicts the trajectory of a patient's BG reading. The purpose of our study was to predict the category of a patient's next BG reading based on electronic medical record (EMR) data.
Methods: EMR data from 184,361 admissions, containing 4,538,418 BG readings from five hospitals in the Johns Hopkins Health System were collected over a 4.5 year period. The outcome was category of next BG reading: hypoglycemic (BG &lt;=70 mg/dl), controlled (BG 71-180 mg/dl), or hyperglycemic (BG &gt;180 mg/dl). A LogitBoost machine learning algorithm that included a broad range of clinical predictors was used to predict the outcome and validated internally (within one hospital) and externally (between different hospitals).
Results: Our machine learning model achieved 86.2% (95% CI: 86.1%-86.2%) accuracy on internal validation and 80.4%-83.2% on external validation. On internal validation, the positive likelihood ratio (+LR) for a prediction of controlled, hyperglycemic, and hypoglycemic were 2.4, 12.3, and 47.4 respectively; the negative likelihood ratio (-LR) for a prediction of controlled, hyperglycemic, and hypoglycemic were 0.09, 0.38, and 0.99 on internal validation. From a safety standpoint, only 0.23% of hyperglycemic observations were predicted to be hypoglycemic on internal validation. On external validation, the +LR for prediction of controlled, hyperglycemic, and hypoglycemic were 2.2-2.8, 6.3-8.5, and 23.1-62.7; the -LR for a prediction of controlled, hyperglycemic, and hypoglycemic were 0.13-0.16, 0.32-0.42, and 0.98-0.99.
Conclusions: A machine learning algorithm accurately predicts the category of a patient's next BG reading. Further studies should determine the success of implementing this model into the EMR to decrease the rates of hypoglycemia and hyperglycemia in hospitalized patients.

Disclosure
A. D. Zale: None. M. S. Abusamaan: None. N. Mathioudakis: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK111986)
612-P: Impact of Digital Intervention Tools on Engagement and Glycemic Outcomes
Authors: HERSHCOVITZ YIFAT , DAR SHARON , MANEJWALA OMAR , BACHER DROR 
Published: June 2021

Introduction: Digital therapeutic platforms in diabetes aim to improve condition self-management and clinical outcomes. Engagement actions are well evaluated by digital monitoring or by logging iterations, and clinical outcomes by target range measurements. A new product modification in the Dario application included development of in-App educational interactions about healthy eating habits. In addition, user experience feature that help users understand the context of their blood glucose measurement was developed. This study evaluated the effect of the digital product modification.
Method: A retrospective data evaluation study was performed on DarioTM members during the time before and after product modification. Digital engagement and clinical outcomes were measured on first to six months per each period to examine if habit formation was achieved.
Results: A group of total 9794 users who had enrolled in a membership for 6 months or longer was evaluated. The ratio of measurements logged with context (fasting, pre-meal, post-meal, bedtime) was increased significantly by 56% in the first month following product modification on average (51.3%. vs. 32.8%) (P&lt;0.001). Differences in the level of digital engagement remained stable over a 6 months period. The average number of days between measurements, i.e., “recency” decreased by 21% on average (2.71 vs. 3.45). Average ratios of high readings (180-400 mg/dL) were reduced by 12% on average over six months.
Conclusion: The present study demonstrates that product updates to digital platforms that guide on healthy eating and help users understand their glucose readings in context may assist users in improving the management of their diabetes.

Disclosure
Y. Hershcovitz: Employee; Self; DarioHealth. S. Dar: Employee; Self; DarioHealth. O. Manejwala: Employee; Self; DarioHealth, Stock/Shareholder; Self; DarioHealth. D. Bacher: Employee; Self; DarioHealth.
63-LB: Achieving Both Target Time-in-Range and Coefficient of Variation
Authors: TAKEISHI SOICHI , INOUE TATSUO 
Published: June 2021

We studied how to achieve both the target time in range (70-180 mg/dL) [TIR] and target coefficient of variation (CV). In a cross-sectional study, we analyzed 24-h glucose levels measured using CGM (iPro2) for 150 patients with type 2 diabetes. We calculated the “mean of all absolute differences between glucose levels and the ‘reference glucose levels (R)’” (M1, in mg/dL), corresponding to 21 R (110, 111⋯130 mg/dL), as a metric to achieve the target TIR. We also calculated the “percentage of the mean absolute deviation to mean glucose levels” (M2, in %) as a metric to achieve the target CV. The R values for which M1 most correlated to TIR were 117 and 118 mg/dL (r = -0.95, p &lt; 0.001). M2 correlated to CV (r = 0.99, p &lt; 0.001; M2 = 0.85 × CV - 0.43). The optimal cutoff value (OC) for TIR &gt; 70% in “M1 for R of 117.5 mg/dL” (M1, 117.5) was 44.6 mg/dL (sensitivity, 96%; specificity, 96%; AUC, 0.99; p &lt; 0.001). The OC for CV &lt; 36% in M2 was 31.5% (sensitivity, 100%; specificity, 100%; AUC, 1). The OC for “both TIR &gt; 70% and CV &lt; 36%” in “M1, 117.5 × M2,” was 842.0 (sensitivity, 90%; specificity, 89%; AUC, 0.96; p &lt; 0.001). Putting all glucose levels close to 117.5 mg/dL may be the most efficient method to increase the TIR as much as possible. Based on our results, the simple target values are as follows: “M1, 117.5 of 42.5 mg/dL” (75-160) [if all glucose levels are within 75-160 mg/dL, M1, 117.5 is sure to be &lt; 42.5 mg/dL] × M2 of 20% = 850 (≈ 842)” (T1); “M1, 117.5 of 27.5 mg/dL (90-145) × M2 of 30% = 825 (≈ 842)” (T2). For T1, if the range that satisfies both 75-160 mg/dL and “‘24 h mean glucose levels on the day before’ ± ‘20 % of the mean glucose levels’” (mean ± 20%) is used as an alarm threshold in a personal CGM, keeping all glucose levels within the range as much as possible may achieve both TIR &gt; 70% and CV &lt; 36%. For T2, if the range that satisfies both 90-145 mg/dL and mean ± 30% is used as an alarm threshold, keeping all glucose levels within the range as much as possible may achieve both TIR &gt; 70% and CV &lt; 36%.

Disclosure
S. Takeishi: None. T. Inoue: None.
63-OR: Focused Educational Screening Improves Knowledge of Diabetes as a Leading Risk Factor for Chronic Kidney Disease
Authors: VO LISA , PARIS MELANIE , ALAWODE MOLLY , SPIGLER MICHAEL 
Published: June 2021

Background: Diabetes is the leading cause of chronic kidney disease (CKD) and a major risk factor in the progression of kidney failure or end-stage kidney disease. An estimated 34.2 million Americans have diabetes, and 1 in 3 adults with diabetes may have CKD, many of whom do not know they have it. Interventions to increase CKD awareness and its complications may help promote early testing and identification among adults with diabetes. The American Kidney Fund (AKF) developed a 5-minute CKD education session and focused this intervention in the District of Columbia-Maryland-Virginia (DMV) metropolitan area.
Methods­: In 2020, AKF administered a 5-item questionnaire at two AKF kidney disease screening events to assess CKD knowledge before and after 5-minute CKD education sessions. Individuals demonstrating CKD risk factors, including self-reported history of diabetes or elevated blood sugar level results, attended the education sessions. We compared responses from 129 participants and performed a paired samples t-test to determine the education sessions’ effectiveness in improving CKD knowledge.
Results: The average pre-post scores increased from 57% to 89% (t(128)=10.65, p&lt;0.001), with the largest gains in understanding the definition of CKD (11% to 86%, t(128)=17.62, p&lt;0.001). There was a significant difference in pre-post scores for identifying diabetes and high blood pressure as the top risk factors for CKD (49% to 86%, t(128)=6.62, p&lt;0.001). For the best ways to prevent CKD, keeping a healthy blood sugar level and healthy blood pressure level was also significant (65% to 89%, t(128)=4.91, p&lt;0.001).
Conclusion: Our study demonstrated low awareness of CKD risk factors. Educational sessions are effective for improving CKD knowledge and increasing awareness about diabetes as a major risk factor. Our study supports the expansion of CKD-related educational programs for populations at high risk for CKD.

Disclosure
L. Vo: None. M. Paris: None. M. Alawode: None. M. Spigler: None.
637-P: Effectiveness of Fixed Ratio Combination of IGlarLixi in People with Type 2 Diabetes Mellitus: Experience from Routine Clinical Practice
Authors: KIS JANOS T. , NAGY GABOR , STELLA PETER 
Published: June 2021

Background: Currently no data are available on the real-world effectiveness of the fixed ratio combination of insulin glargine 100 U/ml and lixisenatide (iGlarLixi). This non-interventional study (it was conducted in Hungary) aimed to evaluate its effects on glycaemic control and hypoglycaemia in real-world practice.
Methods: The single-arm, 6-month (with follow-up visits at 3 and 6 months) study included uncontrolled adults with type 2 diabetes (HbA1c&gt;7,5%) treated by oral antidiabetics (OAD) +/- basal insulin. iGlarLixi treatment was started at the time of inclusion.
Results: Of the included 442 participants, 353 were involved in the efficacy analyses. 282 (79.9%) subjects were treated with OADs, while the remaining 71 (20.1%) with basal insulin and OAD(s) before inclusion. The proportion of participants achieving at least 1.0% HbA1c reduction during the observation period was 60.9% (primary endpoint). All glycaemic variables (mean±SD) improved significantly (p&lt;0,001) during follow-up (HbA1c from 8.9±1.3% to 7.4 ±1.0%, fasting blood glucose from 9.0±2.2 mmol/L to 6.9±1.2 mmol/L, and postprandial blood glucose from 11.3±2.3 mmol/L to 8.5±1.5 mmol/L). All changes were clinically and statistically significant. Body weight was also decreased from 90.5±18.0 kg to 88.2±17.8 kg. Only 37 subjects (10.5%) self-reported at least one symptomatic hypoglycaemic episode during the study. There was no severe hypoglycaemic episode being reported. Frequency of gastrointestinal adverse events was low (5 patients, 1.4%).
Conclusion: The first prospective, non-interventional study confirmed several results from the LIXILAN programme in a real-life setting. iGlarLixi significantly improved glycaemic control with low frequency of hypoglycaemia and gastrointestinal adverse events in a heterogenous population of people with type 2 diabetes. Results confirm similar efficacy and safety in routine clinical care than in randomized controlled trials.

Disclosure
J. T. Kis: None. G. Nagy: Employee; Self; Sanofi-Aventis. P. Stella: Employee; Self; Sanofi-Aventis.

Funding
Sanofi
641-P: Novel Microsphere Formulation Developments of Long-Acting GLP-1 RA Including Exenatide, Liraglutide, and Semaglutide
Authors: JUNG JIN G. 
Published: June 2021

Objective: Clinical applications of Glucagon-like peptide-1 receptor agonists (GLP1-RA) were greatly limited due to its short half-life. The current study aims at the formulation and characterization of sustained-release (SR)-GLP1-RAs to prolong the release profile with lag phase-free formulation technology.
Methods: The long-acting drugs of those GLP1-RAs were prepared by an ultrasonic spray drying process with biodegradable PLGA polymer. Once the PLGA polymer and each API were dissolved in acetic acid, those were applied to the ultrasonic spray dryer to produce the microspheres which encapsulate the API in PLGA polymer. The pharmacokinetic profiles of long-acting SR-Exenatide, SR-Liraglutide, and SR-Semaglutide were determined by using Sprague-Dawley rats after a single injection subcutaneously. APIs were used as controls.
Results: The optimized SR-Exenatide has demonstrated favorable physicochemical properties, such as mean particle size (20 ± 3 μm), percent of entrapment efficiency (90 ± 5 %), and the final drug loading (5 ± 0.5 %), with uniformly sized microspheres. Furthermore, the pharmacokinetic parameters appeared that its release profile extends up to 4 weeks without lag phase which showed 11.4 days of Tmax and 68% of relative bioavailability (BA) when 2mg/kg dose applied. Not only SR-Exenatide but also SR-Liraglutide and SR-Semaglutide showed the extended-release profile up to 1 week and 4 weeks in the rats, respectively.
Conclusion: Those results showed the potentials of lag phase-free, long-acting, high productivity, and mass production. Taken together with the lag phase-free formulation and long-acting ultrasonic spray drying technologies, it will provide the rationales for the clinical development of SR-GLP1-RAs for once-weekly or -monthly formulations. As we have a GMP facility to produce long-acting drugs, we will actively and clinically investigate those SR-GLP1-RAs for antidiabetic therapy.

Disclosure
J. G. Jung: None.
642-P: A Model-Based Evaluation of Nausea and Vomiting Events for Additional Doses of Dulaglutide in Existing and Dulaglutide-Naïve Patients with Type 2 Diabetes
Authors: THAM LAI-SAN , LIM JEAN S.K. , TANG CHENG CAI , JUNG HEIKE , KONIG MANIGE , LOO LI SHEN 
Published: June 2021

Dulaglutide (DU) 3 mg and 4.5 mg once weekly (QW) doses were recently approved for additional glycemic control in adult patients with type 2 diabetes. If needed, a dose-escalation scheme from 1.5 mg to 3 mg and then 4.5 mg can be applied after at least 4-weeks on each dose. For GLP-1 receptor agonists, such as DU, common gastrointestinal (GI) side effects include nausea (N) and vomiting (V). These GI effects are dose-dependent but attenuate over time with chronic dosing. To enhance prescriber understanding of GI effects following dose escalation in existing and DU-naïve patients, a Markov chain Monte Carlo pharmacokinetic/pharmacodynamic joint model was developed with Phase 3 AWARD-11 data (n=1842) which compared 3 mg and 4.5 mg DU to 1.5 mg, to evaluate probabilities of daily N and V events. The model was initiated with priors from a similar Phase 2 model (n=317). In this model, dose increment raised the probability of developing a GI event, and preceding N events enhanced the probability of V events. Development of GI tolerance to N and V was both time and DU concentration dependent. Model-predictions of the percentage of patients presenting with ≥1 N or V event per day for a given dosing scenario were generated via simulations of 100 trials with 300 patients per scenario from the AWARD-11 dataset and compared with the AWARD-11 dose-escalation scheme over a 52-week duration. Patients already on DU 1.5 mg QW for at least 4 weeks can escalate to 3 mg QW any time, and if needed increase to 4.5 mg QW after 4 weeks on 3 mg. Simulations showed ≤3% and ≤1% increase in N and V events, respectively compared to AWARD-11 dose escalation scheme. For DU-naïve patients starting at 0.75 mg QW, N and V events were reduced by ≤2% and ≤1%, respectively, after escalating to 1.5 mg QW and 3 mg after ≥4 weeks at each dose. Whether in DU-naïve patients or those already on 1.5mg, simulations showed no meaningful increase in N and V when dose escalation occurred at intervals of at least 4 weeks.

Disclosure
L. Tham: Employee; Self; Eli Lilly and Company. J. S. K. Lim: Employee; Self; Eli Lilly and Company. C. Tang: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Novartis AG. H. Jung: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Konig: Employee; Self; Eli Lilly and Company. L. Loo: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company.