bluuebunny/crossref_metadata_2025_split huggingface dataset:
798-P: New Insights into Diabetes Burnout
Authors: ABDOLI SAMEREH , HESSLER DANIELLE M. , MILLER-BAINS KATE , VORA AMIT C. , SMITHER BETSEY , BURR ERIN M. , STUCKEY HEATHER L. 
Published: June 2020

Significance: Individuals with type 1 diabetes (T1D) frequently report experiencing diabetes burnout, a feeling of exhaustion, and frustration that may lead to ignoring self-care behaviors. Though the construct was identified in the early 1980s as a primary barrier to optimal diabetes care, scientific understanding of the concept is lacking. Prior literature has conflated diabetes burnout with the other psychosocial concepts of diabetes distress and depression. In an attempt to address the gap, our qualitative findings highlighted that diabetes burnout includes: (1) feelings of mental, emotional, and physical exhaustion, (2) detachment from illness identity, support systems, and self-care, and (3) a sense of powerlessness to re-take the ownership of self-care.
Aim: To examine the relationship between the three hypothesized dimensions of diabetes burnout and to determine if the data would be able to identify a relationship between diabetes burnout, distress, depression, and short-term outcomes.
Methods: We conducted a cross-sectional study on a sample of 111 adults with T1D who completed an online survey developed by existing valid and reliable measures.
Results: All dimensions of diabetes burnout were significantly correlated between .60 and .85 (p&lt;.001). We found that diabetes burnout was significantly associated with both depression (es=0.67; p&lt;.001) and diabetes distress (es=0.83; p&lt;.001). Although overall burnout score explained more of the variation in key diabetes outcomes such as last reported HbA1C or missed appointments than diabetes distress or depression, and those relationships persist and strengthen even after controlling for these other related constructs.
Conclusion: A single cross-sectional study is insufficient for any strong claims; however, this study challenges current knowledge on diabetes care by suggesting diabetes burnout as a distinct but interrelated concept with distress or depressions. These findings need to be replicated, ideally with larger and more diverse samples and with longitudinal studies.

Disclosure
S. Abdoli: None. D.M. Hessler: Consultant; Self; Eli Lilly and Company. K. Miller-Bains: None. A.C. Vora: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Novo Nordisk Inc. B. Smither: None. E.M. Burr: None. H.L. Stuckey: None.

Funding
Oak Ridge Associated Universities
799-P: Gender Differences in Diabetes Distress Comparing Dapagliflozin plus Saxagliptin to Glimepiride When Added to Metformin in Poorly Controlled Type 2 Diabetes
Authors: TESTA MARCIA A. , SIMONSON DONALD C. 
Published: June 2020

Distress due to diabetes symptoms and medication side effects is distinct from psychological disorders and can interfere with A1C control and quality of life (QOL). We analyzed patient-reported outcomes (PRO) during a double-blind, 156-wk randomized clinical trial to evaluate effects of gender and treatment on diabetes distress in T2D patients (A1C, 7.5-10.5%) receiving stable metformin (M) ≥1500 mg/d and assigned to either dual add-on therapy with dapagliflozin (D) 10 mg/d + saxagliptin (S) 5 mg/d (n = 227) or single add-on glimepiride (G) titrated 1-6 mg/d (n = 216). A1C, weight and PRO (353 items) were assessed at baseline and wks 12, 28, 52, 104 and 156, and analyzed using linear mixed-effects models. At wk 52, D+S+M resulted in greater reductions in A1C (-1.4±0.1 vs. -1.0±0.1%) and weight (-3.1±0.3 vs. 1.0±0.3 kg) vs. G+M (p&lt;0.001) that remained lower through wk 156. Men had lower A1C at each visit vs. women (all p&lt;0.05). Distress scores (0-100) due to weight gain for D+S+M vs. G+M (83.0±0.8 vs. 75.4±0.9), weight concern (59.9±1.3 vs. 52.5±1.4) and being overweight (40.6±1.2 vs. 44.8±1.2) all favored D+S+M (p&lt;0.01). Model interactions showed that women vs. men experienced greater distress (p = 0.01) that interfered with work, role and daily activities (p&lt;0.001) on G+M compared to D+S+M. Mental health (p = 0.11) and health perceptions (p = 0.59) did not show treatment differences. QOL ratings for women favored D+S+M (p&lt;0.01). Overall satisfaction (78.4±0.3 vs. 76.7±0.3, p&lt;0.001) favored D+S+M, as did subscales of work/role, effectiveness, side effects, burden, preference, net benefit, and regimen acceptance (all p&lt;0.05). Women showed greater improvements in treatment satisfaction compared to men. While addressing diabetes distress to improve a patient’s well-being is important, ameliorating diabetes distress related to medication side effects such as weight gain may also lead to improved adherence, self-care and glycemic control.

Disclosure
M.A. Testa: Stock/Shareholder; Spouse/Partner; GI Windows. Stock/Shareholder; Self; Phase V Technologies, Inc. D.C. Simonson: Stock/Shareholder; Self; GI Windows. Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc.
805-P: The Joint Association of Diabetes Distress and Depressive Symptoms with All-Cause Mortality in Japanese Patients with Type 2 Diabetes: A Prospective Cohort Study
Authors: HAYASHINO YASUAKI , OKAMURA SHINTARO 
Published: June 2020

Aims/Hypothesis: The independent association of depressive symptoms and diabetes distress (DD) with the mortality risk in patients with diabetes has not been evaluated. We examined the temporal joint association of DD and depression at baseline and the subsequent risk of all-cause mortality.
Methods: The longitudinal data of 3118 patients with type 2 diabetes were obtained from a large Japanese diabetes registry. To assess the joint association of DD and depression at baseline with the subsequent risk of all-cause mortality, the Cox proportional hazards model was used with adjustment for potential confounders.
Results: The mean age, body mass index, and HbA1c level were 64.7 years, 24.6 kg/m2, and 58.6 mmol/mol (7.5%), respectively, and 38.1% of the participants were women. We observed 238 of any death cases during the median follow-up of 7.1 years (incidence ratio = 12.3 per 1000 person-years). In the multivariable-adjusted models evaluating the DD and depression separately, the hazard ratios (HRs) of all-cause mortality were 1.67 (95% confidence interval [CI], 1.14-2.43; p = 0.008) and 1.40 (95%CI, 1.05-1.85; p = 0.020), respectively. In such models evaluating the joint association of DD and depression, compared with DD (−)/depression (−), the HRs of all-cause mortality for DD (−)/depression (+), DD (+)/depression (−), and DD (+)/depression (+) were 1.34 (95%CI, 0.99-1.86; p = 0.056), 1.96 (95%CI, 1.10-3.50; p = 0.023), and 1.71 (95%CI, 1.06-2.77; p = 0.029), respectively. In the stratified analysis by gender, the aforementioned significant association was observed only in men.
Conclusions: We observed a significant independent association of DD and depression with all-cause mortality in male patients with type 2 diabetes, and this finding was only observed in men, not in women. Further research is needed to determine the mechanism of the association between DD or depression and mortality.

Disclosure
Y. Hayashino: None. S. Okamura: None.

Funding
Manpei Suzuki Diabetes Foundation; Japan Society for the Promotion of Science (25460641)
806-P: Weight Loss vs. Postprandial Glucose Reduction in Adults with Type 2 Diabetes: A Randomized Clinical Trial
Authors: COX DANIEL , BANTON TOM , MONCRIEF MATTHEW A. , DIAMOND ANNE , HOLMES VIOLA , WOLF ANNE , FANG KUN , MCCALL ANTHONY L. 
Published: June 2020

Background: Weight loss (WL) is the initial treatment of choice for adults with t2d, but it is inappropriate for lean patients, unwanted/unsuccessful for some obese individuals, and unsustainable for others. An alternative is needed.
Aim: Because post-prandial glucose (PPG) contributes strongly to A1c, we tested if a treatment focused on reducing PPG by reducing carbohydrate intake and increasing physical activity (Glycemic Excursion Minimization - GEM) would be equal or superior to WL for improving A1c and secondary benefits. We also hypothesized GEM would be enhanced by the quality and quantity of blood glucose (BG) feedback.
Methods: Generally healthy adults (t2d ≤ 10 years, not on insulin, A1c ≥ 6.8) were randomized to WL (n = 36) or one of 3 GEM subgroups: 1) Didactic (GEMD, n = 35) taught participants how to choose low glycemic load foods, reduce sedentary time and increase moderate routine physical activity, 2) Didactic + systematic BG monitoring (GEMS, n =48) before and after meals and physical activity to educate, activate and motivate food and activity choices, or 3) Didactic + continuous glucose monitoring (GEMC, n = 43). WL treatment was led by diabetes nutritionists and followed the CDC Prevent T2 weight loss manual. GEM treatment was led by a diabetes nurse educator. All subjects received 6 hours of training, BG meters and wore activity monitors. A1c, weight, UKPDS, DDS, DES and PHQ-9 were assessed pre and 3 months post treatment.
Results: The GEM subgroups did not differ, so they were combined. Both WL and GEM significantly reduced weight and diabetes distress (regimen). Only GEM significantly improved A1c (8.3 to 7.3, p &lt;.001), cardiovascular risk (p &lt;.001), empowerment (p &lt;.001), and diabetes distress (emotional, p &lt;.02).
Discussion: Lifestyle interventions focused on minimizing PPG by reducing carbohydrates and increasing routine physical activity are effective alternatives to WL. Adding BG monitoring did not significantly enhance GEM’s effectiveness.

Disclosure
D. Cox: Research Support; Self; Dexcom, Inc. T. Banton: Research Support; Self; Dexcom, Inc. M.A. Moncrief: Research Support; Self; Dexcom, Inc. A. Diamond: Research Support; Self; Dexcom, Inc. V. Holmes: None. A. Wolf: None. K. Fang: None. A.L. McCall: None.

Funding
Dexcom, Inc. (IIS-2017-047); National Institutes of Health (R01DK108957)
808-P: Parent Characteristics Associated with Diabetes Device Use in Young Children Newly Diagnosed with Type 1 Diabetes (T1D)
Authors: SINISTERRA MANUELA , JACANGELO JULIANA , WANG CHRISTINE H. , TULLY CARRIE , MONAGHAN MAUREEN , HILLIARD MARISA E. , STREISAND RANDI 
Published: June 2020

Introduction: Diabetes devices may improve glycemic control in young children (YC) with T1D. However, little is known about which families are most likely to start using diabetes devices soon after diagnosis. This study examined relationships among demographics, parent mood and anxiety, and continuous glucose monitor (CGM) and insulin pump use in YC in approximately the first 6 months post-diagnosis.
Methods: Participants were 157 parent-child dyads, newly diagnosed with T1D (child age M=4.5 years, 90% mothers, 61% White, 75% married), enrolled in a RCT. Parents completed the Center for Epidemiological Studies-Depression Scale (CES-D) and PROMIS-A (parental anxiety) to assess mood and anxiety. Diabetes device use was assessed by parent-report. About six months after diagnosis, parents again completed the CES-D and provided updates on diabetes device use. χ2 tests were used to compare device use based on parent mood/anxiety and demographics.
Results: At baseline, 20% of YC used CGM (M days post-diagnosis =27.4±15) and 2.5% used insulin pumps. At first check-in (M days post-diagnosis= 163.4±51.3), 57% used CGM and 14% used pumps. CGM use at 6 months was not related to anxiety at baseline or depression at either timepoint, but was significantly related to higher income (p&lt;.01), married parents (p&lt;.01), and non-Hispanic White race/ethnicity (p&lt;.01). YC were more likely to use pumps at 6 months if parents were non-Hispanic White (p&lt;.05) and had private insurance (p&lt;.05).
Discussion: Parent mood and anxiety were not related to early device use, but non-Hispanic White families with married parents and higher SES were more likely to adopt devices soon after diagnosis. Future studies should explore the directionality of these relationships to draw more definitive conclusions about the disparities associated with early device use in YC. Further research exploring characteristics of families who maintain or stop using devices over time may inform clinical care.

Disclosure
M. Sinisterra: None. J. Jacangelo: None. C.H. Wang: None. C. Tully: None. M. Monaghan: Research Support; Self; American Diabetes Association. M.E. Hilliard: None. R. Streisand: None.

Funding
National Institutes of Health (R01DK102561)
809-P: Parent Characteristics and Young Children’s Presentation at New Diagnosis of Type 1 Diabetes (T1D)
Authors: CLARY LAUREN , SINISTERRA MANUELA , LEVY WENDY , MARKS BRYNN E. , HILLIARD MARISA E. , STREISAND RANDI , TULLY CARRIE 
Published: June 2020

Introduction: New onset of T1D is stressful for patients and families and may be particularly so when the child is acutely ill at diagnosis. To characterize family experiences at new onset in young children, we examined associations among diabetic ketoacidosis (DKA) status, length of hospitalization, family demographics, and parent psychological outcomes. We hypothesized that parents of children in DKA or with longer hospitalizations would have more depressive symptoms, perceived stress, and anxiety.
Methods: We enrolled 157 parents (90% female, M age=34.9y ± 7, 61% White, 75% married) of children ages 1-6 years (M age=4.5) newly diagnosed with T1D. Parents self-reported on depressive symptoms (Center for Epidemiological Studies Depression Scale; CESD), anxiety (Patient Reported Outcomes Measurement Information Systems; PROMIS), and stress (Perceived Stress Scale; PSS), as well as family demographics and subjective social status at baseline (M days post diagnosis=27.4 ± 15) of a behavioral RCT. DKA status and length of hospitalization at diagnosis were obtained via medical chart review.
Results: Over 1/3 (37%, n=57) of the sample presented in DKA and 22.9% were hospitalized &gt;2 nights (M length = 1.92 nights), however neither were associated with parental psychological outcomes. Non-white parents, younger children, and lower subjective social status were associated with DKA at diagnosis (all p&lt;0.05).
Conclusions: Children’s illness severity at T1D diagnosis was not associated with parents’ self-reported stress, anxiety, or depressive symptoms. However, demographic differences of children in DKA at diagnosis suggest health disparities exist. Given that DKA is life-threatening and has neurocognitive effects, efforts to increase awareness and education about T1D onset symptoms in communities, schools, and pediatricians is warranted.

Disclosure
L. Clary: None. M. Sinisterra: None. W. Levy: None. B.E. Marks: None. M.E. Hilliard: None. R. Streisand: None. C. Tully: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102561)
81-LB: Daily Tracking of Hemoglobin A1C through Personalized Glycation Model
Authors: FABRIS CHIARA , BECK ROY , KOVATCHEV BORIS 
Published: June 2020

Glycated hemoglobin (A1c) is the gold-standard metric of average glycemia and quality of glycemic control, and a key predictor of long-term diabetes complications. We present a method for tracking A1c from continuous glucose monitoring (CGM)-derived time-in-range (TIR), which provides daily estimates of A1c (eA1c). The method uses a dynamical model of hemoglobin glycation/clearance and is calibrated with a single lab A1c value. CGM data collected by the DIAMOND study from 304 individuals with type 1 and type 2 diabetes (T1D/T2D) over 24 weeks were used in the analysis. Lab A1c samples were collected at weeks 12 and 24. Three population parameters were estimated by training the model on data from 50/50 randomly selected T1D/T2D subjects; the remaining 103/101 subjects were used for model validation. One individual glycation parameter was estimated from the week 12 lab A1c for each subject (model calibration), and was fixed thereafter. The week 24 lab A1c samples were used to test model performance (Table 1). The TIR-A1c relationship is mediated by glycation parameters, 3 population and 1 personal, the latter estimated using a single lab A1c value. Following this personalization, TIR provides accurate estimates of A1c in both T1D and T2D for (at least) 3 months post calibration. Thus, CGM-derived TIR can be a viable clinical alternative to A1c, allowing daily tracking of changes in average glycemia via a dynamical model of hemoglobin glycation.

Disclosure
C. Fabris: Consultant; Self; Abbott. R. Beck: None. B. Kovatchev: Advisory Panel; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc., Sanofi, Tandem Diabetes Care. Other Relationship; Self; Dexcom, Inc., Johnson & Johnson, Sanofi.

Funding
University of Virginia Strategic Investment in Diabetes (88); Dexcom, Inc.
81-OR: The Impact of Proinflammatory Cytokines on Human Pancreatic Islet Alternative Splicing Patterns
Authors: WU WENTING , SYED FAROOQ , SIMPSON EDWARD , LEE CHIH-CHUN , EIZIRIK DECIO L. , MIRMIRA RAGHAVENDRA , LIU YUNLONG , EVANS-MOLINA CARMELLA 
Published: June 2020

Alternative splicing (AS) is a tightly regulated mechanism whereby pre-mRNA transcripts are processed to generate structurally distinct mRNA and protein isoforms. AS within the β cell has been proposed as a potential mechanism that may exacerbate autoimmunity and unmask novel immunogenic epitopes in type 1 diabetes (T1D). Here, we employed a computational strategy to catalog AS events in human islets treated with IL-1β + IFN-γ, as an ex vivo model of T1D. In total, 970 events were identified in cytokine-treated islets, with the majority (44.8%) involving a skipped exon. To identify potentially pathogenic AS events, we utilized ExonImpact, which is a validated machine learning based method, that derives 31 curated features of protein structure from RNA sequencing results. ExonImpact identified 129 AS events predicted to impact protein structure; differentially spliced mRNAs were enriched in gene ontology pathways that included “actin filament-based movement” and “post-Golgi vesicle-mediated transport.” Whereas variants in MHC Class II genes are strongly associated with T1D risk, expression of Class II genes in the β-cell has been controversial. Notably, we identified 98 AS events in MHC Class II genes. Targeted qPCR was used to validate reduced inclusion of Exon5 in HLA-DMB, which is a Class II gene involved in shaping the immunopeptidome. RNA-FISH demonstrated increased abundance of the splice variant in pancreatic sections from human T1D donors. Finally, a k-mer based approach was used to identify RNA binding proteins associated with skipped-exon events. Serine and Arginine Rich Splicing Factor 2 exhibited increased expression in response to IL-1β + IFN-γ and was implicated in 37.2% of potentially pathogenic events, including HLA-DMB Exon5 exclusion. Together, these findings suggest that stimulus specific isoform expression may control how β-cells respond to inflammatory signals in T1D and potentially contribute to amplification of the autoimmune attack against the β-cells.

Disclosure
W. Wu: None. F. Syed: None. E. Simpson: None. C. Lee: None. D.L. Eizirik: None. R. Mirmira: Advisory Panel; Self; Hibercell, Sigilon Therapeutics, Veralox Therapeutics. Employee; Spouse/Partner; Eli Lilly and Company. Y. Liu: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK093954, UC4-DK-104166); U.S. Department of Veterans Affairs (I01BX001733); Sigma Beta Sorority; Ball Brothers Foundation; George and Frances Ball Foundation; Indiana Diabetes Research Center (P30DK097512)
815-P: Medication Adherence by Pill Count Using Medical Reconciliation in Patients with Type 2 Diabetes
Authors: SHIOMI MEGUMI , TANAKA YOICHI , KUROBUCHI MOMOKA , TAKADA TESSHU , OTORI KATSUYA 
Published: June 2020

Background: For medication adherence, pill count is a reliable objective for evaluation. In Japan, at the time of hospitalization, all prescription medicines of patients are checked by medical reconciliation and a pill count is done. This study investigated factors affecting medical adherence by pill count using medical reconciliation.
Methods: This retrospective study included 76 patients (mean age 65.6±12.6 years, 60.5% of men) with type 2 diabetes mellitus who had been taking oral hypoglycemic agents (OHAs) for more than 48 weeks. Patients whose OHAs were managed by another person or those who were taking psychotropic drugs were excluded. To evaluate medication adherence, medication adherence value (MAV) was calculated: (total prescription days-prescription days of OHAs brought when admitted)/(days from start of OHAs to hospitalization). The relationship between MAV and patient characteristics was analyzed.
Results: Subjects were divided into MAV of ≤ 0.86 (those who forgot to take medicine on one or more days per week), &gt; 0.86 ≤ 0.93 (who forgot to take on one or more days in two weeks and less than one day per week), and &gt; 0.93 (who forgot less than one day in two weeks). HbA1c showed a significantly higher value in the group of ≤ 0.86 compared with the group of &gt; 0.93 (P = 0.02). The patients were divided into good (MAV &gt; 0.86) and poor (MAV ≤ 0.86) adherence groups. On multivariate analysis of patient characteristics with P &lt; 0.2 in the univariate analysis as explanatory variables, lower age and no insulin therapy were independent factors for poor adherence (P = 0.004; P = 0.02). Dosing period, Dosing time, number of doses, and types of OHAs were non-independent factors. However, in the poor adherence group, taking 3 doses a day was an independent factor (P = 0.03).
Conclusion: Our findings suggest that poor adherence was independently associated with lower age and no insulin therapy in type 2 diabetes patients. In poor adherence patients, taking 3 doses a day was a factor for reduced adherence.

Disclosure
M. Shiomi: None. Y. Tanaka: None. M. Kurobuchi: None. T. Takada: None. K. Otori: None.