bluuebunny/crossref_metadata_2025 huggingface dataset:
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<.01), married parents (p<.01), and non-Hispanic White race/ethnicity (p<.01). YC were more likely to use pumps at 6 months if parents were non-Hispanic White (p<.05) and had private insurance (p<.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 >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<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), > 0.86 ≤ 0.93 (who forgot to take on one or more days in two weeks and less than one day per week), and > 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 > 0.93 (P = 0.02). The patients were divided into good (MAV > 0.86) and poor (MAV ≤ 0.86) adherence groups. On multivariate analysis of patient characteristics with P < 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.
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<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<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 (>8) by 28% and low (<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 (>8) and 18% reported very little relevance (<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<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 <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.)
844-P: Effects of Dapagliflozin, Metformin, or Exercise on Plasma Glucagon Concentrations in Individuals with Prediabetes: The PRE-D Trial
Authors: CLEMMENSEN KIM K.B. , BLOND MARTIN B. , AMADID HANAN , NIELSEN LEA B. , VISTISEN DORTE , KARSTOFT KRISTIAN , PERSSON FREDERIK , RIED-LARSEN MATHIAS , HOLST JENS J. , WEWER ALBRECHTSEN NICOLAI J. , TOREKOV SIGNE S. , QUIST JONAS S. , JØRGENSEN MARIT E. , FÆRCH KRISTINE
Published: June 2020

Introduction: Glucagon plays a role in the pathogenesis of type 2 diabetes. Yet, little is known about the effect of interventions aimed at preventing progression from prediabetes to diabetes on glucagon concentrations. We examined the effects of dapagliflozin, metformin or exercise on plasma glucagon concentration in individuals with HbA1c-defined prediabetes.

Methods: 120 individuals were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (interval training 30 min 5 days/week) or control (habitual living). A 75 g oral glucose tolerance test (OGTT; 0, 30, 60 and 120 min) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed-effects models were used to assess effects on fasting concentration, early (0-30 min) area under the curve relative to the fasting level (rAUC0-30 min) and full rAUC0-120 min for glucagon.

Results: At baseline, the median (Q1;Q3) age was 62 (54;68) years, HbA1c 5.9% (5.7;6.1%), fasting glucagon 11 (7;15) pmol/L, and 56% were men. No differences in the glucagon measures between groups from baseline to 13 or 26 weeks were observed (Table 1).

Conclusions: 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations in individuals with prediabetes.

Disclosure

K.K.B. Clemmensen: Research Support; Self; AstraZeneca, Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. M.B. Blond: None. H. Amadid: None. L.B. Nielsen: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K. Karstoft: Employee; Spouse/Partner; Novo Nordisk A/S. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; Amgen, AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S. M. Ried-Larsen: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. S.S. Torekov: Research Support; Self; Novo Nordisk Inc. J.S. Quist: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. K. Færch: None.

Funding

Novo Nordisk Foundation; AstraZeneca; University of Copenhagen; Innovation Foundation
847-P: Effect of Simple Multipronged Strategies in a Real-World Situation in Prevention of Diabetes in a Developing Country: Interim Report from South India
Authors: VISWANATHAN VIJAY , PARVEEN RIZWANA , MURUGAN PREMALATHA , KUMPATLA SATYAVANI
Published: June 2020

Aim: Implementation of newer intervention strategies in Prediabetes (PDM) may delay the onset of DM. Aim was to see the effect of simple multi pronged approach in a real world situation to prevent progression to DM.

Methods: PDM subjects (n=220) were assigned into 2 groups(Gp) from Aug 2017 in a diabetes centre in Chennai, India. OGTT was done and diagnosis was by WHO criteria. PDM subjects; IFG, IGT, Elevated 1h PG, were assigned to control and intervention groups; (n=110 in each). Gp1 received standard care, Gp2 intensive counseling on physical activity (PA) and diet (reducing calories, carbohydrates, fat, increasing fibre). PA included walking for 150min/week and customized advice based on profession. Working subjects to avoid prolonged sitting at work place, using stairs in work areas, walking instead of hiring vehicles for short distances; Business professionals advised to walk in corridors during stay in hotels for business purpose; Housewives to do simple walks in balconies and terrace, to avoid electronic appliances. Subjects were followed up(FU) once in 6 months and repeated OGTT. Calls, mails and SMS used for FU. Those came for FU(n=91;47vs41) till Sep 2019 were included for interim analysis.

Results: Mean age of subjects was 44 years and duration of FU was 12.1 (range 4-28) months. There was a significant difference in conversion rate to DM. (Gp1 vs. 2;34 vs. 9.1%,p=0.004). The subjects who reverted back to normal was significantly higher in Gp 2 compared to Gp1 (31.8 vs. 10.6%;p =0.012). The survival curve showed mean survival time for Gp1 was 19.6 (95% CI 16.6-22.8) and Gp2 was 22.2 months (CI 19.9-24.4;p=0.014). In Gp2, there was a significant reduction in Wt, body fat (p=0.022), WHR(P=0.003), elevated 1 hr glucose (p=0.004) whereas in Gp1 reduction was observed only in glucose levels (p<0.001).

Conclusion: It was possible to prevent diabetes in subjects with prediabetes using multi-pronged intervention strategies in real world scenario.

Disclosure

V. Viswanathan: None. R. Parveen: None. P. Murugan: None. S. Kumpatla: None.
850-P: Continued Monitoring of the Foreign-Body Response to Improve Long-Term Success of Macroencapsulation Devices for Type 1 Diabetes: A Proof-of-Concept Study
Authors: BEATTY RACHEL M. , DOLAN EIMEAR B. , ROBINSON SCOTT T. , OCONNOR RAYMOND , WYLIE ROBERT , DUFFY GARRY P.
Published: June 2020

Over 463 million people are living with diabetes mellitus (DM). Type 1 DM results from an autoimmune destruction of pancreatic β-cells and accounts for 5-10% of cases. Macroencapsulation devices are a promising therapy for the treatment of T1DM as they improve insulin producing cell retention and viability. However they have had limited success due to a complex cascade of events, causing fibrous encapsulation and ultimately device failure (the foreign body response (FBR)). The FBR is a critical hurdle associated with the success of implantable devices. Here, we aim to develop a biosensing membrane that monitors the FBR in real time; ensuring steps can be taken to modulate the host’s response to the implant. A biosensing membrane was developed consisting of a conductive layer of nonmetallic, highly conductive acrylic adhesive sandwiched between two layers of 0.08 mm thermoplastic polyurethane (TPU). Thereafter the membrane was incorporated into a refillable macroencapsulation device with soft robotic capabilities. In vitro experiments were carried out using electrical impedance spectroscopy. Baseline impedance measurement were taken for porous and non-porous devices using a buffered saline (PBS). Various concentrations of Matrigel (30%, 40%, 50% and 60%) were left to solidify on the membrane, as it contains extracellular matrix proteins, making it analogous to fibrotic tissue components. A significant increase of impedance was seen across the Matrigel groups when compared to PBS alone (p<0.001). A significant difference was also evident between the varying concentrations of Matrigel along the spectra, an example of which is 30% vs. 50% Matrigel at 1.2649 Hz (p<0.001). We have developed a novel approach to measure the membrane permeability in vitro. Monitoring the FBR in vivo, will provide feedback on the functionality of implanted devices, to improve their longevity for the delivery of insulin producing cells.

Disclosure

R.M. Beatty: None. E.B. Dolan: None. S.T. Robinson: None. R. OConnor: None. R. Wylie: None. G.P. Duffy: None.
852-P: Is Real-Time CGM Superior to Flash Glucose Monitoring? Results of the Type 1 Diabetes CORRIDA Randomized Control Trial
Authors: SOUPAL JAN , HÁSKOVÁ ANETA , GRUNBERGER GEORGE , PETRUZELKOVA LENKA , PARKIN CHRISTOPHER , SKRHA JAN , RADOVNICKÁ LUCIE , HOROVA EVA , PRAZNY MARTIN
Published: June 2020

Background: The trial aim was to compare the efficacy of real-time and intermittently-scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control.

Methods: In this randomized study, adults with T1D and normal hypoglycemia awareness (GOLD score <4) used rtCGM (Guardian Connect Mobile) or isCGM (Freestyle Libre) during 4 days of physical activity (sport period) and in the subsequent 4 weeks (home period). Main endpoints were time in hypoglycemia (<3.9 mmol/l [<70 mg/dl]) and time in range (3.9-10.0 mmol/l [70-180 mg/dl]). To check for bias between the different sensors used by the rtCGM and isCGM systems, the isCGM group wore an additional blinded Enlite sensor (iPro2) for 6 days.

Results: Sixty adults with T1D (age 38±13 years, HbA1c 7.8±1.1% [62±12 mmol/mol]) were randomized to rtCGM (n=30) or isCGM (n=30). All participants completed the study. Time in hypoglycemia (<3.9 mmol/l) was lower among rtCGM participants in the sport period (6.8±5.5% vs. 11.4±8.6%, respectively; p=0.018) and the home period (5.3±2.5% vs. 7.3±4.4%, respectively; p=0.035). Hypoglycemia differences were significant and most notable during the night. rtCGM participants spent more time in range than isCGM participants throughout both the sport (78.5±10.2% vs. 69.7±16%, respectively; p=0.0149) and home (75.6±9.7% vs. 67.4±17.8%, respectively; p=0.0339) periods. The results were robust to the insignificant bias between rtCGM and isCGM sensors that blinded CGM found in the isCGM arm.

Conclusion: rtCGM was superior to isCGM in preventing hypoglycemia and improving time in range in T1D adults with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management.

Disclosure

J. Soupal: Advisory Panel; Self; Abbott. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc. A. Hásková: None. G. Grunberger: Research Support; Self; Medtronic. L. Petruzelkova: None. C. Parkin: Consultant; Self; Abbott, CeQur Corporation, Dexcom, Inc., DreaMed Diabetes, Novo Nordisk Inc., Onduo, Roche Diabetes Care, Valeritas, Inc. J. Skrha: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. L. Radovnická: None. E. Horova: None. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd.

Funding

15-26705A (Program RVO-VFN00064165)
855-P: Utilization of Continuous Glucose Monitoring (CGM) and Its Impact on the Care of Veterans
Authors: BARSAMYAN GAYANE , SILVA ALEXIS DA , WHYTE LOREN , AMOLE MOROLAKE , GHAYEE HANS , LEEY JULIO A.
Published: June 2020

Background: Continuous Glucose Monitoring (CGM) is useful in the management of patients on insulin therapy. In late 2017 a diagnostic CGM clinic was implemented in our VA hospital to aid in the management of diabetes. Our aim is to measure the impact of CGM technology in the veteran population.

Methods: Retrospective chart review of all the patients who received a diagnostic CGM (Libre Pro) between January 2018 through October 2019. Patients underwent a diagnostic CGM (blind) if they were on insulin therapy or had an A1c > 7%. We evaluated: glycemic control and travel distance to the VA hospital. A total of 208 patients with diabetes were included in the study (males 91%). The most common diagnosis was T2D 86%, followed by T1D 14%. The mean A1c was 8.4% +/- 1.8. CGM data was examined by an endocrinologist and necessary medication adjustments were recommended.

Results: Patients wore the CGM on an average of 10.3 days +/- 4.6, the glucose average was 174.7 +/- 56. In 20 patients, the sensor did not recorded data. The time in range (70-180 mg/dL) was 45% +/- 26, the time above the range was 26 +/- 27. Hypoglycemia (<70 mg/dL) was seen more than 5% of the CGM wore in 32% of patients. In 65% of patient, the CGM prompted a change in treatment regimen. Because CGM results and physician recommendations were communicated via telephone, patients saved an average travel distance of 60 miles SD 38.5, or roughly 120 of roundtrip travel time. Of the patients whose insulin regimen changed after CGM placement, the average HbA1c decreased from 8.2% to 7.5% (p < 0.05). 100% of participants surveyed rated their satisfaction at highest and reported they would wear the CGM device again.

Conclusion: A diagnostic CGM clinic significantly improved glycemic control and reduced travel time in the studied veteran population. The diagnostic CGM was well accepted. A rational use of CGM technology may therefore lead to improved diabetes management.

Disclosure

G. Barsamyan: None. A. da Silva: None. L. Whyte: None. M. Amole: None. H. Ghayee: None. J.A. Leey: None.