bluuebunny/crossref_metadata_2025_split huggingface dataset:
810-P: The Diminishing Cost-Effectiveness of the Newer Glucose-Lowering Drugs in the United States, 2010-2018
Authors: LI PIAOPIAO , PATEL RAHUL S. , VOURI SCOTT M. , SHI LIZHENG , FONSECA VIVIAN , SHAO HUI 
Published: June 2021

Background: The difference between the costs of the newer and older glucose-lowering drugs has been steadily increasing since 2010. In 2018, newer drugs cost 8-12 times more than older drugs (except for insulin). This study aimed to understand how this change in drug cost influenced the cost-effectiveness (CE) of newer drugs compared with older drugs.
Methods: We conducted a systematic literature review to identify US-based CE studies comparing newer (i.e., dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide 1 receptor agonists (GLP1-RA), and sodium-glucose transport protein 2 inhibitors) with older glucose-lowering drugs. The identified 12 studies all reported the CE of newer drugs based on drug costs estimated before 2010. We have updated the corresponding CE of each study by replacing the old cost estimates with 2018 estimates from the 2018 IBM® MarketScan® Commercial Claims Databases. The time window and willingness to pay threshold were consistent with each original study.
Results: Only 8% of the original studies suggested that the older drugs were cost-effective. However, 58% of studies were in favor of the older drugs after the cost update. Among the 4 studies comparing newer drugs with thiazolidinediones, all studies suggested thiazolidinedione to be cost-effective in the updated analysis, while the original results all favored newer drugs. For the 4 studies comparing newer drugs with sulfonylureas, 2 studies suggested the sulfonylureas to be cost-effective after the cost update. All 4 studies suggested newer drugs to be cost-effective when compared with insulin in the original study. Only 1 flipped its conclusion when 2018 costs were used. Our sensitivity analysis shows that our results are robust up to a 30% rebate.
Conclusion: Significant changes in the cost of glucose-lowering drugs have impacted the economic value of different glucose-lowering agents substantially. More CE analyses are warranted to support the drug choice in T2DM management.

Disclosure
P. Li: None. R. S. Patel: None. S. M. Vouri: None. L. Shi: Research Support; Self; AstraZeneca, Sanofi. V. Fonseca: Consultant; Self; Abbott Diabetes, Asahi Kasei Corporation, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Intarcia Therapeutics, Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Stock/Shareholder; Self; Amgen Inc., Bravo4health, Mellitus Health. H. Shao: Research Support; Self; Sanofi.
830-P: The Development of a New Computer Adaptive Test of Illness Burden for Use in People with Type 2 Diabetes Mellitus (T2DM)
Authors: MITCHELL SUZANNE , KALLEN MICHAEL A. , BRAGG ALEXA , MOLDOVAN IOANA , HOWARD JESSICA M. , JACK BRIAN W. , MINER JENNIFER A. , GRAVES CHRISTOPHER M. , CARLOZZI NOELLE 
Published: June 2021

In recent years, a growing body of research has established that social determinants of health influence the health outcomes of patients, especially those with T2DM. We developed a new patient-reported outcome (PRO) measure of an important social determinant of behavior that is specific to persons with T2DM: illness burden. Qualitative and quantitative methods informed the development of this new PRO. A literature review and semi-structured key informant interviews guided the establishment of an initial item pool. Expert and patient review, reading level assessment (to ensure no item had &gt;5th grade reading-level language), and a translatability review were all used to refine the original item pool to 47 items. The refined item pool was then tested in 225 patients with T2DM. No items had sparse response option cells or problems with monotonicity; two items were deleted due to low item-rest correlations. Factor analyses (exploratory and confirmatory) supported the retention of 29 items. With those 29 remaining items, a constrained (common slope) graded response model (GRM) fit assessment indicated that two items had misfit and were excluded. No items displayed differential item functioning by age, sex, education, or socio-economic status. Thus, the final item bank is comprised of 27 items. Psychometric considerations (based on item information values) were used, in conjunction with expert content review, to select a 6-item static short form. IRT-based item parameters were employed to make this new measure available as a computer adaptive test. Internal consistency of the new PRO was excellent (α ≥ .90 for all administration formats). The new Illness Burden item bank captures patients’ perceptions of the impact that having T2DM has on their daily lives. It can be used in conjunction with the broader measurement system, the Re-Engineered Discharge for Diabetes Computer Adaptive Test, to evaluate important social determinants of behavior in persons with T2DM.

Disclosure
S. Mitchell: Other Relationship; Self; See Yourself Health LLC, Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. M. A. Kallen: None. A. Bragg: None. I. Moldovan: None. J. M. Howard: None. B. W. Jack: None. J. A. Miner: None. C. M. Graves: None. N. Carlozzi: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R21DK121092)
855-P: Health Care Delivery for Young Adults (YAs) with Type 1 Diabetes (T1D) during the Pandemic
Authors: SHAPIRA AMIT , TINSLEY LIANE J. , FREINER EMILY , LAFFEL LORI M. , TOSCHI ELENA 
Published: June 2021

Background: YAs, aged 18-30 years, with T1D have high risk of worsening glycemic control and loss to follow-up. In March 2020, the COVID-19 pandemic required a sudden change in healthcare delivery from in-person to telehealth visits. We aimed to evaluate use of telehealth by YAs with T1D during this time and assess characteristics associated with telehealth usage.
Method: Frequency of telehealth visits from 3/16/2020 to 9/30/2020 was compared with in-person visits during the same calendar period before COVID-19 (3/16/2019 to 9/30/2020) in a sample of YAs with T1D seen by pediatric and adult diabetes clinicians. The Electronic Health Record provided demographic and clinical data for YAs aged 18-30 with a pre-pandemic A1c. Descriptive statistics and t-tests compared data before and during COVID-19.
Results: Pre-COVID-19, there were 1177 YAs (50% male) with mean±SD age 24.4±3.4 years, T1D duration 12.8±5.9 years, and A1c 8.1±1.6%; 46% were pump-treated, 55% used CGM, and 91% had private insurance. In 2019, there were 2961 visits; in 2020, there were 2701 visits. For the two 6-month periods, the mean number of visits per YA declined significantly, from 2.5±2.5 in 2019 to 2.3±3.1 in 2020 (p=.02). Further, 20% (n=240) of YAs had no visits during the pandemic period. YAs with an A1c &lt;7% pre-pandemic (21%, n=247) had fewer visits during the pandemic than before the pandemic (1.6±2.7 vs. 2.2±2.7, p=.001). YA males (p=.01), those using CGM (p=.02), and those on injection based therapy (p=.0002) had fewer visits during COVID-19.
Conclusions: The majority of YAs (80%) maintained follow-up T1D care during the initial six months of telehealth implementation due to COVID-19, especially those with less favorable characteristics (e.g., A1c ≥7%, no CGM use). Maintaining telehealth options can become an effective means to improve future health outcomes for at-risk groups, such as YAs with T1D.

Disclosure
A. Shapira: None. L. J. Tinsley: None. E. Freiner: None. L. M. Laffel: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompe, Insulogic LLC, Janssen Pharmaceuticals, Inc., Laxmi Therapeutic Devices, LifeScan, Lilly Diabetes, Medtronic, Provention Bio, Inc. E. Toschi: Consultant; Self; Medtronic.

Funding
Thomas J. Beatson, Jr. Foundation; National Institutes of Health (T32DK007260, P30DK036836)
862-P: Impact of COVID-19 on Pediatric Endocrinology Practice and Diabetes Care in Children: A Survey
Authors: CHAMBERS MELISSA , SINHA MADHUMITA 
Published: June 2021

Objective: As the global pandemic caused by the SARS-CoV-2 virus continues unabated, healthcare delivery has been altered significantly impacting patients and providers. We examined the impact of COVID-19 on pediatric endocrinology practice and the challenges faced in pediatric diabetes care.
Methods: A 27-item electronic survey was designed, pilot-tested, and deployed to pediatric endocrinology providers using the e-mail discussion lists of the American Academy of Pediatrics, Section on Endocrinology, and the Pediatric Endocrinology Clinical Case Mailing List (May and June 2020). The survey had questions regarding changes in practice, telemedicine use, and observed changes in diabetes disease manifestation.
Results: 114 unique responses were analyzed, 79.3% were female respondents. Most (95.6%) providers surveyed were practicing in the United States, and 87.7% reported a decline in their patient volume. Telemedicine use was common [97% (95% CI: 92.4% - 99.4%)] and recent [83.3% (95% CI: 75.2% - 89.7%)] with 98% utilizing remote glycemia monitoring tools. Children with diabetes in underserved and remote locations faced significant barriers to telemedicine use such as lack of connectivity (61%), and devices (59%). Negative consequences on health due to the pandemic included, delay in diabetes diagnosis (33.3%), lack of follow-up (22.0%) and higher diabetic ketoacidosis cases (22.0%). Increased anxiety was commonly reported (66%).
Conclusion: The COVID-19 pandemic has led to decline in patient volumes, with rapid adaptation to telemedicine use. Providers noted negative effects due to the pandemic on diabetes care including mental health. Benefits from telemedicine use were observed with a digital divide in underserved populations.

Disclosure
M. Chambers: None. M. Sinha: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
875-P: Breathe Diabetes Management Program: A Personalized App to Assist Type 2 Diabetics in India to Achieve Healthy Outcomes
Authors: GOYAL PAWAN K. , VERMA ROHAN , KAICKER ADITYA , DEKA SAURAV , PALUKURI SRIVANI , CHANDOLIA BETINA 
Published: June 2021

Introduction: Use of Digital therapeutics can act as a valuable tool enabling more personalized care among diabetics. The Breathe Diabetes Management Program (BDMP) delivers personalized interventions encouraging them to track their blood glucose level, weight, and physical activity.
Objective: To assess BDMP app in type 2 diabetics in achieving healthy outcomes in Indian population.
Methodology: The group of participants (N=181, A1C &gt;6.5%) was divided into 3 groups - (1) patients treated with the BDMP plus Doctor-prescribed medication (n=60), (2) patients treated with the BDMP plus Doctor-prescribed medication plus Stress Reduction module (n=61) and (3) patients only taking the Doctor-prescribed medication (control group with n=60).
Results: At the end of the 16 weeks, patients from Group 1 showed 81.6% program completion rate, 46.01% program adherence, an average of 5.64% of baseline body weight loss, an average of 0.68% reduction in A1C and Penn State Worry Questionnaire (PSWQ) score average change from 56.3 to 44.5 (score ranges 16-80, higher score indicates higher worry). Patients from Group 2 showed 88.5% program completion rate, 51.95% program adherence, an average of 6.02% of baseline body weight loss, average of 0.74% reduction in A1C and a PSWQ score average change from 58.6 to 40.8. Patients from Group 3 showed an average of 0.38% of baseline body weight loss, average of 0.28% reduction in A1C and a PSWQ score average change from 56.2 to 55.5. The difference between all the groups was found to be statistically significant (p&lt;0.05).
Conclusion: The BDMP helped the patients of Group 1 in significant weight loss, reduction in A1C, and improved stress levels. BDMP along with the Stress Reduction module in Group 2 produced even better outcomes. The results suggest that Digital Therapeutics is a scalable and sustainable solution to the growing problem of type 2 diabetes, and that mental well-being should be considered a part of the solution.

Disclosure
P. K. Goyal: None. R. Verma: None. A. Kaicker: None. S. Deka: None. S. Palukuri: None. B. Chandolia: None.
885-P: C-Reactive Protein Predicts COVID-19 Infection Severity and Length of Hospitalization
Authors: KREIT HELEN , CHERUKURI SUNDAR V. , MANDANIA ROSHNI A. , DEOKER ABHIZITH , GUPTE AKSHAY A. , MOSSAYEBI ALI , CONCHA JEANNIE B. , JUNG HYEJIN , WAGLER AMY E. , BAJPEYI SUDIP 
Published: June 2021

Chronic stress can lead to many systemic complications and low-grade systemic inflammation including increased levels of inflammatory cytokines, such as C-reactive protein (CRP). CRP is a marker of systemic inflammation and is associated with depression and perceived stress. Elevations can result in weakened immune responses, thereby increasing the risk of complications and mortality from infections. Recent evidence suggests that uncontrolled inflammatory responses associated with COVID-19 are a major determinant of disease severity.
Purpose: The purpose of the study was to determine the effects of chronic stress, measured by CRP, on the severity and the length of hospitalization in COVID-19 patients.
Methods: This retrospective study used medical records from patients admitted to the University Medical Center, El Paso, TX with COVID-19 (n=436 (272M/164F); age 57.3 ± 0.8 years; BMI 29.42 ± 0.3 Kg/m2). Chronic stress was measured by blood CRP level. Severity of COVID-19 infection was determined by the peripheral oxygen saturation (SpO2) measured during the time of hospitalization. Length of hospitalization was determined by the number of days spent in the hospital. Patients were categorized into low CRP (&lt; 3mg/L) vs. high CRP (&gt; 3mg/L) groups and were compared using unpaired t-test.
Results: Patients with high CRP level had greater COVID-19 severity, measured by SpO2 (Low CRP: 94.2% ± 0.4 vs. high CRP: 91.9% ± 0.4; p&lt;0.01), and greater length of hospital stay (low CRP: 6.5 ± 1.3 days vs. high CRP 8.8 ±0.5 days; p&lt;0.05). CRP level was also negatively associated with SpO2 (r= -0.16, p&lt;0.001) and positively associated with the length of hospitalization (r= 0.23, p&lt;0.0001).
Conclusion: Higher levels of CRP are associated with worsened severity and increased length of hospitalization in COVID-19 patients. CRP levels should be considered in laboratory workup for COVID-19 patients and treatment should focus on reducing inflammatory damage.

Disclosure
H. Kreit: None. S. Bajpeyi: None. S. V. Cherukuri: None. R. A. Mandania: None. A. Deoker: None. A. A. Gupte: None. A. Mossayebi: None. J. B. Concha: None. H. Jung: None. A. E. Wagler: None.
890-P: CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Promotes Adipocyte Proliferation through Transcriptional Activation of NEK8 in T2DM and Obesity
Authors: CHEN YAN 
Published: June 2021

Background: Adipogenesis is a complex biological process and the main cause of obesity. CDK5 Regulatory Subunit-Associated Protein 1-like 1 (CDKAL1) serves as a susceptibility gene for obesity and type 2 diabetes (T2DM). However, whether CDKAL1 plays any functional role in adipocyte proliferation had not been well investigated.
Methods: CDKAL1 expression was manipulated using a specific shRNA or the CDKAL1-full length expressing recombinant plasmids. MTT assay was performed to determine 3T3-L1 cell growth with either overexpression or downregulation of CDKAL1. Interaction between CDKAL1 and never-in-mitosis A-related kinase 8 (NEK8) in HEK293T and 3T3-L1 cells was examined using Co-immunoprecipitation (Co-IP) and Confocal immunofluorescence staining. Western blot assay was performed to determine the protein expression of NEK8 and CDKAL1. Dual-luciferase reporter assay was used to detect the transcriptional regulation of CDKAL1 on NEK8. The in vivo role of CDKAL1 and NEK8 was explored in an in vivo mouse model of T2DM.
Results: In the present study, we found that overexpression of CDKAL1 promoted adipocyte proliferation of 3T3-L1 cells, whereas knockdown of CDKAL1 delayed 3T3-L1 proliferation. Mechanically, CDKAL1 interacted with NEK8 and transcriptionally activated its expression in adipocytes. Moreover, elevated levels of CDKAL1 and NEK8 were observed in patients with T2DM compared to the healthy subjects. Implantation of 3T3-L1 cells with CDKAL1 overexpression increased blood glucose in dietetic mice.
Conclusions: Collectively, these findings suggest that CDKAL1 functions as a positive regulator of adipocyte proliferation, providing novel experimental evidences into the link between CDKAL1 and T2DM and obesity.

Disclosure
Y. Chen: None.

Funding
Chinese Postdoctoral Science Foundation (2019M651218); Natural Science Foundation of Jilin Province (20190201031JC)
893-P: Triglyceride-Rich Remnant Lipoproteins, Insulin Resistance, and Subclinical Inflammation in Youth with Type 2 Diabetes
Authors: VILLALOBOS-PEREZ ALFREDO , ZENNO ANNA , CRAVALHO CELESTE K. , MATTA SAMANTHA , COURVILLE AMBER B. , MABUNDO LILIAN , SHARMA VANDHNA R. , DAWSON JOSHUA M. , HAYMOND MOREY W. , CHUNG STEPHANIE T. 
Published: June 2021

Youth with type 2 diabetes (T2D-Y) have severe insulin resistance (IR) and increased risk for atherosclerotic cardiovascular disease (ASCVD). High levels of remnant triglyceride-rich lipoproteins (TRLp), the sum of small very low-density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) particles, may mediate this additional risk. Yet, the relationship of remnant TRLp with IR and inflammation in at-risk youth is unknown. We compared lipoprotein particles in 48 youth: 33 T2D-Y and 15 age/BMI matched peers without diabetes (age 15.5 ± 2.6 y, Tanner Stage IV-V, BMI 38.6 ± 7.4 kg/m2) and determined the relationship of remnant TRLp with IR and GlycA, a composite marker of inflammation. Fasting lipoprotein particle size and number, apolipoprotein B (apoB) and GlycA were derived from the NMR LipoProfile®. Insulin sensitivity was determined by the Matsuda index during a multi-sample 75g OGTT. T2D-Y had higher A1c (7.0 ± 1.2 vs. 5.6 ± 0.3%, P&lt;0.01), lower Matsuda index (1.3 ± 1.0 vs. 2.5 ± 1.3, P&lt;0.01) and higher GlycA (431 ± 73 vs. 390 ± 50 μmol/L, P=0.05). Triglyceride and low density (LDL) particles were higher in T2D-Y (ApoB: 74 ± 16 vs. 56 ± 12 mg/dL; total LDL particles: 1314 ± 298 vs. 983 ± 224 nmol/L; small LDL particles: 881 ± 348 vs. 492 ± 235 nmol/L; total TRLps: 111 ± 52 vs. 71 ± 30 nmol/L, and remnant TRLps: 97 ± 45 vs. 63 ± 29 nmol/L, all P&lt;0.01). HDL particles were not different between groups. Matsuda index inversely correlated with GlycA (r=-0.4, P=0.01), total and remnant TRLps (both r=-0.5, P&lt;0.01) and small LDL particles (r=-0.4, P=0.03), but not with total LDL or HDL particles. GlycA was associated with small LDLp (r=0.3, P=0.07 and remnant TRLp (all r=0.2, P=0.1) but this was not statistically significant. The high-risk profile marked by high remnant TRLps and small LDL particles in T2D-Y was associated with IR and an inflammatory marker, supporting the need for longitudinal studies to determine whether reducing TRLps and inflammation will reduce ASCVD risk.

Disclosure
A. Villalobos-perez: None. S. T. Chung: None. A. Zenno: None. C. K. Cravalho: None. S. Matta: None. A. B. Courville: None. L. Mabundo: None. V. R. Sharma: None. J. M. Dawson: None. M. W. Haymond: Advisory Panel; Self; Daiichi Sankyo, Zealand Pharma A/S, Other Relationship; Self; AstraZeneca, Stock/Shareholder; Self; Xeris Pharmaceuticals, Inc.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
906-P: Parents Experience Diabetes Distress Too: Parental Reports and Association with Quality of Life and Teen A1C
Authors: INVERSO HAILEY , MOORE HAILEY R. , MORROW TROY , JASER SARAH S. , STREISAND RANDI 
Published: June 2021

Background: Diabetes distress (DD) is a negative emotional response commonly associated with type 1 diabetes (T1D). Similar to youth, parents may experience their own DD resulting from the burdens associated with supporting their child with T1D. Parental DD can have a negative impact on quality of life (QoL), and disruptive factors, such as family conflict, may exacerbate parental DD. Clinical and psychosocial outcomes associated with DD have been previously examined in teens, yet less is known about the association among parental DD, QoL, and diabetes outcomes in parents of teens experiencing DD.
Methods: 60 parent-teen dyads have enrolled thus far in the ongoing THR1VE! study, a positive psychology texting-based intervention. Teens (M age 16.2 ± 1.5, 68% female, M T1D duration 7.7 ± 3.9) were eligible if they reported experiencing moderate or higher DD. Parents (83% female; 78% married/partnered; 78% white) completed the Parents - Problem Areas in Diabetes, Revised Diabetes-Related Family Conflict, and Type 1 Diabetes and Life questionnaires at baseline. A1c data were gathered at routine diabetes clinic appointments or through at-home A1c kits. Associations among parental reports of DD, diabetes-related family conflict, parental QoL, and A1c were examined.
Results: Higher parental DD was positively associated with higher parent-reported family conflict (r= 0.54), lower parental QoL (r=0.63), and higher teen A1c (r=0.31). Higher parent-reported family conflict was also associated with lower QoL (r=0.40) and higher A1c (r= 0.35), all p &lt;0.05.
Conclusion: Similar to prior findings for teens with DD, results suggest that for parents of distressed teens, parents’ own experience of DD is also related to psychosocial variables including family conflict and QoL. Importantly, parental DD is related to children’s glycemic control, suggesting that increased psychological support for parents with teens with DD is warranted.

Disclosure
H. Inverso: None. H. R. Moore: None. T. Morrow: None. S. S. Jaser: None. R. Streisand: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK121316)
91-OR: Visit-to-Visit Variability of Glycated Albumin Was Associated with the Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes
Authors: ZHOU JIAN , DAI DONGJUN , SHEN YUN , LU JINGYI , WANG YUFEI , ZHU WEI , BAO YUQIAN , HU GANG 
Published: June 2021

Background: The association between long-term glycemic variability and diabetic retinopathy (DR) among patients with type 2 diabetes has not been clarified yet.
Objective: The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of DR in patients with type 2 diabetes.
Design: A prospective cohort study of 315 patients (191 males and 124 females) with at least 3 measurements of HbA1c and GA prior to baseline was performed. Different GA and HbA1c variability markers were calculated, including coefficient of variation (CV), variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit HbA1c and GA variability and the risk of DR.
Results: During a mean follow-up period of 3.42 years, 81 participants developed incident DR. Multivariate-adjusted hazard ratios (HRs) of DR across tertiles of GA-CV values were 1.00, 1.42, and 2.12 (P for trend=0.027), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of DR were found. Multivariable-adjusted HRs of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of DR after multivariate adjustment.
Conclusion: The visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.

Disclosure
J. Zhou: None. D. Dai: None. Y. Shen: None. J. Lu: None. Y. Wang: None. W. Zhu: None. Y. Bao: None. G. Hu: None.

Funding
National Key Research and Development Project of China (2018YFC2000802); Shanghai Municipal Education Commission (20161430); Shanghai Municipal Key Clinical Specialty