bluuebunny/crossref_metadata_2025_split huggingface dataset:
816-P: Perception of Risk for Developing Diabetes in Employees, Dependents, and Retirees of a Large Self-Insured Employer
Authors: JOINER KEVIN , MCEWEN LAURA N. , HERMAN WILLIAM H. 
Published: June 2020

According to the Health Belief Model, adults with prediabetes (pDM) who perceive higher personal risk for developing diabetes (DM) may be more enthusiastic about engaging in the Diabetes Prevention Program (DPP) than those who perceive lower personal risk. Between 2015 and 2019, the University of Michigan, a self-insured employer, offered to cover the DPP at no out-of-pocket cost for individuals with pDM among all its employees, dependents, and retirees. We surveyed 720 people with pDM who engaged in the DPP and a random sample of 2379 people with pDM who did not engage in the DPP. Perception of risk for developing DM was assessed using the item: “What do you think your risk is for getting diabetes over the next 5 years?”, and defined as a continuous variable (1-“almost no chance” to 4-“high chance”). Engagement in the DPP was defined as a dichotomous variable (yes-no). Linear regression was used to test associations between perceived risk for developing DM and engagement in the DPP. A cohort of 533 people who engaged in the DPP and 1023 people who did not engage in the DPP responded to the survey, response rates of 74% and 43%, respectively. Among the people with data on perceived DM risk (N=1547), the mean age was 55±11 years, 62% were women, 73% were non-Hispanic white, 64% had a level of education of 4-year college graduate or more, 60% had a family income ≥$75,000/year, the mean BMI was 31±7 kg/m2, 48% were aware of their pDM, 51% had a family history of DM, and 9% of the women had a history of gestational diabetes (GDM). In bivariate analyses, perceived personal DM risk differed by age, sex, education, BMI, awareness of pDM, family history of DM, and history of GDM (women only) (all at P&lt;0.05). People who engaged in the DPP had a higher mean risk perception 2.52±0.04 vs. 2.40±0.03 (P=0.0044) than those who did not engage in the DPP. These findings suggest that for adults with pDM, perceived personal risk for developing DM may motivate engagement in risk-reducing programs such as the DPP.

Disclosure
K. Joiner: None. L.N. McEwen: None. W.H. Herman: Consultant; Spouse/Partner; Nestlé. Other Relationship; Self; Merck Sharp & Dohme Corp.

Funding
National Institutes of Health (R01DK109995)
819-P: How Does Diabetes Impact Everyday Life and What Are the Diabetes Support Needs in People with Diabetes and Severe Mental Illness?
Authors: KNUDSEN LENETTE , ANDERSEN GREGERS S. , JOENSEN LENE E. , WIBAEK RASMUS , JØRGENSEN MARIT E. , HANSEN DORTE L. 
Published: June 2020

Background: People with diabetes and severe mental illness (SMI) are less likely to receive appropriate diabetes treatment and experience greater barriers in diabetes management compared to people without SMI. Research is needed in diabetes related patient reported outcomes to improve the diabetes support in this population.
Aim: To explore overall wellbeing, levels of diabetes distress and diabetes support needs in people with diabetes and SMI.
Methods: People with diabetes and SMI treated in psychiatric out-patient clinics in the Capital Region of Denmark (n=87, mean age 52, 59% men) completed a questionnaire on psychosocial health (self-rated health, WHO-5, PAID-5), diabetes’ impact on everyday life (1=no impact to 10=high impact), relevance of diabetes support from psychiatric nurses (1=not relevant to 10=very relevant) and level of diabetes support from health care providers (“no support”, “some support”, “high support”). Participants could also indicate if they did not have contact with the health care providers (not included in analyses).
Results: Self-reported health was reported to be poor or fairly poor by 64 % and 70 % reported low well-being (WHO-5&lt;50). Compared to people with diabetes without SMI more participants reported high diabetes distress, PAID≥ 8 (51% vs. 26%). Diabetes’ impact on everyday life was reported high (&gt;8) by 28% and low (&lt;3) by 30%. Of the participants, 68% (n=21), 59% (n=40) and 26%(n=18) reported psychologists, psychiatrists and psychiatric nurses provided no diabetes support. One third (33%) reported it was highly relevant to receive diabetes support from the psychiatric nurses (&gt;8) and 18% reported very little relevance (&lt;3).
Conclusion: Low quality of life and high diabetes distress is common in people with diabetes and SMI and many do not receive diabetes support as part of psychiatric care. Enhancing diabetes support from psychiatric nurses may be relevant to improve diabetes support in people with diabetes and SMI.

Disclosure
L. Knudsen: None. G.S. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S. L.E. Joensen: None. R. Wibaek: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. D.L. Hansen: None.

Funding
Jascha Foundation (6994)
82-OR: Exosomes from Human ß-Cells Incorporate Stress Granule Components and May Serve as Biomarkers of ß-Cell Stress in Type 1 Diabetes
Authors: SYED FAROOQ , MAIER BERNHARD F. , ANDERSON-BAUCUM EMILY , MASTRACCI TERESA L. , EVANS-MOLINA CARMELLA , MIRMIRA RAGHAVENDRA 
Published: June 2020

In early T1D, β cells are subjected to stresses such as inflammation, putative viral infections and increased ER protein load. Under these conditions, β cells activate the integrated stress response, which is highlighted by a block in the translation of mRNAs. These translationally-inhibited mRNAs are compartmentalized into non-membranous inclusions known as stress granules (SGs). During chronic stress, SGs may be sequestered into endosomes and released as components of extracellular vesicles (EVs) into circulation. We hypothesized, the RNA content of EVs may serve as a reflection of ongoing β cell stress. To test this possibility, we measured EV-associated preproinsulin (PPI) mRNA from supernatant of a cultured human β cell line and human islets treated with and without cytokines (IL-1β and IFN-γ) to mimic T1D conditions. Cytokine treatment resulted in a block in mRNA translation initiation, decreased protein synthesis, and increased formation of SGs. Studies using single molecule FISH confirmed that in stressed human β cells there is significant colocalization of PPI mRNA with G3BP1, a marker of SGs. Moreover, stressed human β cells expressing G3BP1-RFP and CD63-GFP (a marker of EVs) exhibited co-localization of SGs with EVs, suggesting that SG contents incorporate into EVs. PPI mRNA was recoverable almost exclusively in EVs isolated from supernatants of stressed human islet cultures. Pharmacological inhibition of EV release decreased PPI mRNA content in the culture media, implying that PPI mRNA is released from β cells within EVs. Droplet digital PCR analysis demonstrated significantly higher levels of PPI mRNA in circulation of new-onset T1D subjects compared to healthy, age-matched controls. Taken together, our data demonstrate that PPI mRNA is released from stressed β cells as a consequence of translational blockade, SG formation, and EV release, and indicate that circulating PPI mRNA might serve as a biomarker reflective of β cell stress.

Disclosure
F. Syed: None. B.F. Maier: None. E. Anderson-Baucum: None. T.L. Mastracci: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb. R. Mirmira: Advisory Panel; Self; Hibercell, Sigilon Therapeutics, Veralox Therapeutics. Employee; Spouse/Partner; Eli Lilly and Company.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK104166 to R.M., C.E-M.), (R01DK60581 to R.M.), (R01DK093954 to C.E-M.); U.S. Department of Veterans Affairs (I01BX001733 to C.E-M.); JDRF (3-SRA-2014-41-Q-R to C.E-M, R.M.), (3-PDF-2016-199-A-N to F.S.); Sigma Beta Sorority; Ball Brothers Foundation; George and Frances Ball Foundation; Holiday Management Foundation (to C.E-M., R.M.)
821-P: Highs and Lows and Type 1 Diabetes Mellitus: The Lived Experience of Young Adults with T1DM
Authors: OTTIGNON MADELEINE , OCONNOR MELISSA , WHITEHOUSE CHRISTINA 
Published: June 2020

Background: Type 1 diabetes (T1DM) is a chronic autoimmune disease that affects the body’s production of the hormone insulin. T1DM is diagnosed during childhood and adolescence and may have significant impacts on mental health. Understanding the impact of T1DM on mental health during adolescence may increase our understanding of the mental health needs of young adults with T1DM.
Purpose: To describe the lived experiences of young adults with T1DM and how it relates to their mental health status during adolescence.
Methods: A qualitative explorative study using semi-structured interviews. A purposive sample of young adults with T1DM were recruited through social media and through an announcement in the monthly, national newsletter of the College Diabetes Network. Participants were interviewed individually via Apple Facetime and Google Hangouts. Self-reported demographic and clinical information was also collected. Professionally transcribed data were analyzed using thematic analysis.
Results: The sample was comprised of 18 young adults, the mean age was 20.4 years ± 1.21. Average age of diagnosis was 9.7 years ± 3.76. The interviews generated 4 major themes: (1) isolation, (2) maturity, (3) social support, and (4) challenges experienced by participants.
Conclusions/Implications: The young adults in this study report many positive and negative influences on mental health during adolescence. Many participants agreed that while they had support through family and friends, they felt they would best be reached by other people with T1DM. Participants also identified a lack of resources for managing T1DM in adolescence and negative judgement from healthcare providers regarding lifestyle/food choices. This research provides information about the importance of addressing mental health needs of young adults with T1DM during adolescence. Continued education for educators and health care providers regarding the importance of using person-centered non-judgement language is essential.

Disclosure
M. Ottignon: None. M. OConnor: None. C. Whitehouse: None.
83-OR: Pancreatic Exocrine to Endocrine Cell Cross Talk Mediates Endoplasmic Reticulum Stress and Beta-Cell Dysfunction in MODY8
Authors: KAHRAMAN SEVIM , DIEGISSER DANIELLE , JOHANSSON BENTE B. , MOLVEN ANDERS , KULKARNI ROHIT 
Published: June 2020

MODY8 (maturity onset diabetes of the young, type 8) is a dominantly inherited monogenic form of diabetes. This disease is associated with frameshift mutations in the carboxyl ester lipase (CEL) gene expressed by pancreatic acinar tissue. Patients with the mutation develop childhood-onset exocrine pancreas dysfunction followed by diabetes during adulthood. However, it is unclear how CEL mutations cause diabetes in MODY8 patients. In this study, we investigated the potential crosstalk between exocrine acinar cells and endocrine beta cells in vitro. Co-culture of beta cells (EndoC-bH1 beta cells) with donor cells (HEK293 embryonic kidney cells or 266-6 acinar cells) overexpressing mutant or wild type CEL gene in an in vitro transwell system demonstrated transfer of mutant protein from donor cells to beta cells. While both the wild type and mutant CEL proteins were observed to be taken up by the beta cells there was a significantly higher amount of the mutant (11.4±2.3% cells) compared to the wild type protein (1.8±0.7% cells) (n=3, p&lt;0.01 mutant vs. wild type). The mutant protein formed intracellular aggregates represented as punctuate structures within the cytoplasm of beta cells. Culturing beta cells in mutant donor cell-conditioned media for 12 days activated the unfolded protein response, and increased endoplasmic reticulum stress by promoting the gene expression of BiP, spliced XBP1, and caused beta cell secretory dysfunction (insulin stimulation index 16.7 mM/3.3 mM: 1.3±0.1 (mutant) vs. 2.1±0.3 fold (wild type), n=8, p=0.05). Our data indicate a unique crosstalk between pancreatic acinar and beta cells, which adversely affects the latter by increasing ER stress and impairing insulin secretion. This study provides one possible explanation of how a mutant gene expressed specifically in acinar cells causes endocrine cell dysfunction and diabetes in MODY8 patients.

Disclosure
S. Kahraman: None. D. Diegisser: None. B.B. Johansson: None. A. Molven: None. R. Kulkarni: None.

Funding
National Institutes of Health (R01DK67536)
833-P: Standardized Assessment of Diabetes Distress in Routine Type 1 Diabetes Care
Authors: KOMPALA TEJASWI , FU POLLY , FOLICK ANDREW K. , BABEY MURIEL , KOH EILEEN , MEHTA PARAS , FISHER LAWRENCE , MASHARANI UMESH , NEINSTEIN AARON B. 
Published: June 2020

Background: Diabetes distress (DD) refers to the feelings of stress, worry, and fear related to living with diabetes, and is a commonly unrecognized experience. Although greater DD is modestly associated with higher hemoglobin A1c, DD is common even among patients with A1c at goal. Despite its prevalence, regular assessment for DD in clinical care is not standard. This study evaluates the implementation of standardized DD assessment into a routine clinic visit.
Methods: As part of a quality improvement initiative within an academic diabetes clinic, a multi-disciplinary team of endocrinologists, psychologist, and clinic administrators introduced a validated diabetes distress scale for adults with type 1 diabetes (T1-DDS) into the clinic check-in process. Patients were coached by medical assistants to complete the T1-DDS. DD scores were calculated and provided to patient and provider. Clinicians were trained to discuss DD and deliver focused counseling interventions to patients within the scheduled visit. Implementation outcomes were assessed by interview and querying the electronic health record.
Results: Surveyed providers had positive perceptions of conducting the assessment (acceptability). Clinic staff and providers believed it was feasible to incorporate DD assessment and counseling into a preexisting scheduled visit. Since inception of this program, 95% of eligible patients seen in clinic were assessed for diabetes distress. Of those assessed, 100% discussed the results with the provider. Prevalence of clinically significant DD in all patients screened was 90.4%. Even in patients with A1c less than 7.0%, 88% reported high DD. Of those with DD, 52.6% scored highest in the subcategory of powerlessness.
Conclusions: Implementation of DD assessment into routine clinical care is feasible and acceptable by providers. Even in patients with optimal glycemic control, DD is highly prevalent. Screening for DD should be incorporated into standard comprehensive diabetes care.

Disclosure
T. Kompala: None. P. Fu: None. A.K. Folick: None. M. Babey: None. E. Koh: None. P. Mehta: None. L. Fisher: None. U. Masharani: None. A.B. Neinstein: Consultant; Self; Steady Health.
835-P: Self-Reported Psychosocial and Behavioral Determinants of Hypoglycemia among Older Adults with Diabetes
Authors: FANG MICHAEL , ECHOUFFO TCHEUGUI JUSTIN B. , WINDHAM B. GWEN , SELVIN ELIZABETH 
Published: June 2020

Background: Few studies have examined the psychosocial and behavioral determinants of hypoglycemia in older adults with type 2 diabetes.
Methods: We conducted a cross-sectional analysis of the self-reported causes of hypoglycemia among participants in the Atherosclerosis Risk in Communities (ARIC) study (visit 6, 2016-2017) with diagnosed diabetes who self-reported experiencing at least one episode of hypoglycemia in the past 12 months. Information on hypoglycemia history and potential causes of low glucose were obtained through in-person interviews. Participants could select multiple hypoglycemia causes.
Results: Among the 818 ARIC participants with diabetes (mean age 79), 362 (44%) self-reported experiencing hypoglycemia in the past year. Overall, 68% of these individuals attributed experiencing low glucose to improper food timing (e.g., skipping a meal); 32% to eating the wrong type of food; 19% to increased physical activity; and 12% to wrong medication dosage. Eight to 20% also reported that mood change or illness contributed to prior hypoglycemic events (Figure).
Conclusion: Timing of meals in older adults with diabetes may be an important component in diabetic education to reduce hypoglycemia risk. Further research is needed to determine how emotions and illness relate to hypoglycemia.

Disclosure
M. Fang: None. J.B. Echouffo Tcheugui: None. B. Windham: None. E. Selvin: None.

Funding
National Heart, Lung, and Blood Institute (T32HL007024 to M.F.); National Institute of Diabetes and Digestive and Kidney Diseases (K24DK106414 to E.S.)
836-P: The Effect of Intensive Lifestyle Modification Compared with Metformin Interventions on Fasting Blood Glucose: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: KUCAB MICHAELA , BOATENG TERENCE , YOUNG IAN , GUCCIARDI ENZA 
Published: June 2020

Background: Type 2 diabetes mellitus (T2DM) is a prevalent disease and remains a substantial economic burden on society. Intensive lifestyle modification (ILM) and metformin are common interventions aimed at individuals with prediabetes to prevent the progression to T2DM.
Objective: To assess the effect of ILM and metformin interventions by evaluating fasting blood glucose (FBG).
Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Databases including MEDLINE, CINHAL, Nutrition and Food Sciences, and ProQuest were searched. Inclusion criteria were individuals with prediabetes, had separate ILM and metformin interventions, and assessed baseline and post-intervention FBG. Exclusion criteria were individuals outside the age of 13-65 years, had unrelated medical conditions, taking other diabetic medications, and &lt;12 weeks in duration. Statistical analysis was completed using the Comprehensive Meta-Analysis software (CMA).
Results: Of 257 studies, 5 RCTs with a total of 4,045 participants were included for analysis. ILM was significantly associated with a lower FBG level post-intervention compared to metformin (MD±SEM=-0.15±0.068; p=0.026) and placebo (MD±SEM= -0.37±0.12; p=0.003). Metformin was significantly associated with a lower FBG post-intervention compared to placebo (MD±SEM= -0.25±0.059; p=0.00).
Conclusion: ILM and metformin interventions are associated with an improvement in FBG compared to placebo. Although our analysis showed a statistical benefit of ILM compared to metformin, we conclude that the clinical significance in FBG is comparable for supporting both interventions. In addition, appropriate cost-effective interventions should be considered to reduce the economic burden on society. Prioritizing multidisciplinary teams is important for successful implementation and preventing T2DM in this population.

Disclosure
M. Kucab: None. T. Boateng: None. I. Young: None. E. Gucciardi: None.
84-LB: HbA1c Reduction after Initiation of the FreeStyle Libre System in Type 2 Diabetes Patients on Long-Acting Insulin or Noninsulin Therapy
Authors: MILLER EDEN , BRANDNER LAURA , WRIGHT EUGENE 
Published: June 2020

Data for patients with type 2 diabetes (T2D) on long-acting insulin (LAI) or non-insulin therapy using continuous glucose monitors is limited. This study evaluates change in HbA1c from baseline to 6mo and baseline to 12mo after starting a FreeStyle Libre system for T2D patients on LAI and non-insulin (including GLP-1) therapy. A retrospective, observational analysis was performed by linking data from the LibreView® data management platform, DRG (a commercial medical and pharmacy claims database), and Quest lab HbA1c. Only deidentified data was used for analysis. Index was the first date of data in LibreView (Nov 2017-Sept 2019). Medication and diagnosis were from DRG. HbA1c tests were from Quest. Baseline A1c must be ≥ 6.5% within 6mo prior to index. HbA1c tests closest to +180 days (+150-210) used for 6mo; closest to +360 days (+330-390) used for 12mo. The 6mo T2D cohort (n=774) reduced HbA1c by -0.8%. The 12mo T2D cohort (n=207) reduced HbA1c by -0.6%. The greatest reduction in HbA1c was seen in the T2D non-insulin group at 6mo (-0.9%, n=497) and 12mo (-0.7% n=120). All groups saw clinically significant reduction in HbA1c (Table). Reduction in HbA1c post-FreeStyle Libre use supports the real-world effectiveness of the system in T2D patients using long-acting insulin or non-insulin therapies.

Disclosure
E. Miller: None. L. Brandner: Employee; Self; Abbott Laboratories. E. Wright: Advisory Panel; Self; Abbott, Sanofi. Consultant; Self; Abbott, AstraZeneca, Bayer U.S., Boehringer Ingelheim Pharmaceuticals, Inc., MannKind Corporation, Merck & Co., Inc., Voluntis France. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes.
843-P: Optimization of DNA Vaccine Platforms for Type 1 Diabetes
Authors: FERNANDEZ JORGE POSTIGO 
Published: June 2020

Immunotherapies are currently expanding to treat several autoimmune disorders with the goal to achieve antigen-specific tolerance. However, in type 1 diabetes (T1D), the success of such approaches remain elusive. Plasmid DNA (pDNA) platforms encoding critical antigens are easy to produce at low cost and offer prolonged antigen expression as well as design flexibility. Thus far, a limited fraction of diabetogenic T cells can be engaged using this platform due to the use of a single antigen produced in native form (i.e., pDNA encoding human proinsulin now in phase II clinical trial) despite ample evidence of epitope spreading and existence of neoepitopes. We previously demonstrated that a combination of major pDNA-encoded epitopes from multiple beta-cell antigens delivered in vivo significantly delay the onset of T1D, similar to proinsulin-pDNA, and is more suitable for precision therapy of T1D patients. Optimization is still needed to improve in vivo pDNA delivery and achieve long-lasting tolerance in T1D. Treatment was most effective when the encoded epitopes were targeted for secretion during an 8-week treatment. Antigen-specific CD4+ and CD8+ T cell responses were evident as late as 2 weeks after pDNA administration, indicating that it may be possible to reduce the frequency of treatment while preserving antigen presence in vivo. Although antigen expression and T cell responses were achieved by different routes of administration (intramuscular, intradermal or subcutaneous), the network of cells involved in presenting pDNA-encoded antigens likely differs and influences the outcome and amplitude of the immune response. Additionally, formulation of pDNAs into nanoparticles influences the draining of pDNA complexes to different lymphoid tissues, while having negligible effect on pDNA immunogenicity in vitro. Our work establishing optimal parameters of antigen targeting, expression duration and DNA delivery modalities will lead to better protocols to translate these DNA-based therapies into the clinic.

Disclosure
J. Postigo Fernandez: None.

Funding
American Diabetes Association (1-18-PDF-151 to J.P.F.)