bluuebunny/crossref_metadata_2025 huggingface dataset:
551-P: Results from a National Multicenter Study: Health Professionals Report High Feasibility, Acceptability, and Utility of a New Pro Dialogue Tool in Routine Multisectorial Diabetes Care
Authors: SKOVLUND SOREN E. , GLÜMER CHARLOTTE , NIELSEN SIGNE H. , BERTHELSEN DORTHE B. , PERRILD HANS , BALK-MØLLER NINA C. , NØRGAARD LISE MELLERGAARD , TROELSEN LISE , PIETRASZEK ANNA , HESSLER DANIELLE M. , KAPLAN SHERRIE H. , EJSKJAER NIELS
Published: June 2021

Aim: To assess health care professionals’ (HCP) perceptions of feasibility, acceptability, and impacts of a new digital patient-reported outcome (PRO) dialogue tool in routine diabetes care.

Methods: A single-arm implementation study (MPRODIA) evaluating use of a PRO tool by 33 HCP in routine multi-sector diabetes care. Intervention: Persons with diabetes (PWD) filled out a digital questionnaire about health, well-being and self-care 1-8 days prior to the visit and their HCP used a PRO dialogue dashboard in the visit to facilitate a collaborative, person-centered dialogue. Primary outcome in this sub study was HCP responses to a clinical end-of-study Likert-Scale and Free-Text evaluation survey. Quantitative and explanatory qualitative data analyses were done with SPSS 25.0/Nvivo 12.

Results: 33 HCP at 7 unique sites used PRO in 474 diabetes visits and completed the end-of-study survey. 80% were diabetes specialized, 67% saw>10 PWD/week, 33% had <10 years of care experience. HCP confidence in use of PRO improved in pre-post analysis (3,8 (SD=.9) to 4,4 (SD=.7), range 1-5, p<0.05). 97% were confident in their ability to use PRO well (interpret and use PRO insights). 52% became more positive (3% more negative) towards the PRO tool overall over time. 85% reported improved work satisfaction (due to better preparation and dialogue), 0% worse satisfaction. 33% felt visits were less stressful, 21% felt it was somewhat more stressful with PRO (due to time constraints). All HCP indicated the desire to continue PRO use (9,0(SD=1,2), range 1-10) and recommend it to others (9,0(SD=1,4), range 1-10). 64% found it essential that HCP are trained in use of PRO prior to implementation.

Conclusions: HCP in both municipality and hospital settings found a new digital PRO diabetes tool to be highly acceptable and value-adding by improving the active participation of PWD and the delivery of quality person-centered care.

Disclosure

S. E. Skovlund: None. D. M. Hessler: Consultant; Self; Eli Lilly and Company. S. H. Kaplan: None. N. Ejskjaer: None. C. Glümer: None. S. H. Nielsen: None. D. B. Berthelsen: None. H. Perrild: n/a. N. C. Balk-møller: None. L. Nørgaard: None. L. Troelsen: None. A. Pietraszek: None.

Funding

Danish Health Data Authority
564-P: Long-Term Follow-up of Glycemic Excursion Minimization (GEM) Compared with Weight Loss in Management of Type 2 Diabetes (T2D)
Authors: COX DANIEL , MONCRIEF MATTHEW A. , MCCALL ANTHONY L.
Published: June 2021

In a recent randomized clinical trial, we compared 6 hours of conventional weight loss (WL) training to an equivalent amount of Glycemic Excursion Minimization (GEM) that is a paradigm-shift in lifestyle management for adults with T2D. GEM focuses on diminishing post-nutrient BG excursions by: 1) minimizing BG upsurge by reducing net carbohydrate ingestion, and 2) hastening BG recovery by increasing routine and post-meal physical activity.1 We now present the 13-month follow-up data, with no further training or contact, to evaluate the relative durability of these interventions. All of the WL and 97% of GEM participants who completed 3-month post-assessment also completed 13-month follow-up. At 13 months, WL participants sustained the improvement in BMI they showed at 3 months, while GEM participants continued to significantly benefit from lower HbA1c (p<.001), diabetes medication usage, cardiovascular risk, BMI, HDL, and improved psychological function regarding empowerment and diabetes distress (p’s <.01). Fifty-two percent of GEM participants were classified as Responders (mean HbA1c reduction of -1.5%). Being a GEM Responder at 13 months was unrelated to demographic or disease severity variables. Regression analyses indicated being a GEM long-term Responder was preceded by short-term post-treatment reduction of HbA1c, BMI and diabetes medication, correctly classifying 76% of eventual Responders and Non-responders. WL Responders could not be identified. Our data suggest GEM is a sustainable treatment option in the management of T2D.

1BMJ Open Diabetes Research & Care, 8:e001795. doi: 10.1136/bmjdrc-2020-001795.

Disclosure

D. Cox: Research Support; Self; Abbott Diabetes, Dexcom, Inc. M. A. Moncrief: Research Support; Self; Abbott Diabetes, Dexcom, Inc. A. L. Mccall: None.

Funding

National Institutes of Health (DK108957)
565-P: Loop Automated Insulin Delivery System: Reasons for Discontinued Use
Authors: WONG JESSIE J. , SUTTIRATANA SAKINAH , LANNING MONICA S. , DUNLAP ADRIENNE , HANES SARAH , HOOD KOREY K. , LAL RAYHAN , NARANJO DIANA
Published: June 2021

Background: Loop is an open-source do-it-yourself (DIY) automated insulin delivery system that allows users unrivaled control over physiologic settings that effect future glucose prediction. Over 9,000 individuals have adopted Loop, but little is known about those who discontinue.

Methods: Twenty Loop users (14 adults and 6 caregivers; 60% female, 85% white, 75% household income >$100k/year, and HbA1c 6.7±1.0%) participated in semi-structured interviews about their experiences with Loop following discontinuation. Qualitative data were transcribed, coded, and analyzed.

Results: Prominent themes reflected the perception that the stress, effort and/or time required to set up Loop and achieve management goals exceeded potential benefits. Two quotes: “I couldn’t spend any more time trying to work on my settings and trying to make it better,” and “I know I could get an improvement with it, but the problem was the cost of it⋯I couldn’t concentrate anymore at work⋯it felt like fog in my brain.” Technical issues with component devices, connectivity issues, lack of technical support, cost (time, energy, supplies), fear of provider disapproval, concerns related to pregnancy, exercise, hypoglycemia and managing low insulin doses, and desire to try other new technologies were among other reasons for ending use. Participants indicated that improved technical assistance and expert guidance might lead to them to use Loop again in the future.

Conclusions: For those who manage to set up Loop there are additional challenges, even among individuals with adequate glycemic control and access to various financial, social, and personal resources. Technical support and education specific to setting calculations could expand Loop benefits, alleviate burden, and support sustained use among new Loop users.

Disclosure

J. J. Wong: None. S. Suttiratana: Employee; Spouse/Partner; CVS Health. M. S. Lanning: None. A. Dunlap: None. S. Hanes: None. K. K. Hood: Consultant; Self; Cecelia Health, Cercacor, LifeScan Diabetes Institute. R. Lal: Consultant; Self; Abbott Diabetes, Biolinq, Capillary Biomedical, Inc., Morgan Stanley, Tidepool. D. Naranjo: None.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust
590-P: Disparities in the Utilization of Bariatric Surgery among Obese Patients with or without Type 2 Diabetes: Evidence from the OneFlorida Clinical Research Consortium
Authors: CHEN GUANMING , DONAHOO WILLIAM T. , CARDEL MICHELLE , HOLGERSON ALLISON , AYZENGART ALEXANDER L. , GURKA MATTHEW J.
Published: June 2021

Background: Contemporary data characterizing the utilization of metabolic and bariatric surgery (MBS) by type 2 diabetes mellitus (T2DM) status are limited.

Methods: In this study, we analyzed data from patients 18-88 years of age eligible for MBS seen in the OneFlorida (https://onefloridaconsortium.org/) between 1/1/ 2012 to 12/31/2018. MBS eligibility was defined by any of the following criteria: (1) an encounter with a body mass index (BMI) ≥ 40 kg/m2; or (2) BMI ≥ 35 kg/m2 with at least one obesity-related comorbidity, including T2DM, hypertension, or hyperlipidemia. We compared patients’ characteristics stratified by T2DM status and whether they underwent common bariatric procedures including Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (AGB). We performed multivariable logistic regression to identify factors independently associated with receipt of MBS among diabetic patients.

Results: Among 190,606 patients with T2DM, 4103 (2.2%) of them underwent BS. Patients with diabetes were more likely to receive RYGB than those without T2DM (47.6% vs. 37.7%). We also observed that patients without diabetes aged between 18-44 years had a higher rate of MBS utilization than patients in that age range with diabetes (58.7% vs. 37.4%). The logistic regression results showed that female, higher pre-surgical BMI, had pre-surgical hypertension were strong indicators associated with bariatric treatment among patients with diabetes.

Conclusion: In this study, we observed that patients with obesity and T2DM still had relatively low rates of MBS. The observed differences in rates of MBS among different demographic subgroups could inform interventions that target reductions in these disparities.

Disclosure

G. Chen: None. W. T. Donahoo: None. M. Cardel: Consultant; Spouse/Partner; Weight Watchers International, Inc. A. Holgerson: None. A. L. Ayzengart: None. M. J. Gurka: None.
60-LB: Dendritic Cells Engineered with Tailored Multiepitopes-Encoding mRNA as Precision Medicine for Immunotherapy of Type 1 Diabetes
Authors: FITE REBUMA FIRDESSA , CREUSOT REMI J.
Published: June 2021

Type 1 diabetes (T1D) is a complex autoimmune disease characterized by heterogeneity in genetic risk factors and immune profiles of patients and for which a cure or approved treatment is not yet available. Antigen-specific immunotherapy (ASIT) offers a targeted treatment of T1D that selectively inhibits autoreactive T cells. So far, ASIT trials showed limited efficacy, as only a subset of patients is responsive. Thus, approaches that consider the genetic and immunological heterogeneity of T1D patients to provide more tailored treatments are needed. Using mRNA encoding multiple epitopes tailored to the NOD mouse (model of T1D), we engineered bone marrow-derived dendritic cells (DCs) by mRNA electroporation (mRNA-DCs). The mRNA is designed to enable optimal presentation of epitopes to both CD4 and CD8 T cells. Antigen presentation persisted at least three days in vivo. Markers of anergy as well as IL-10 expression were found to be upregulated in antigen-specific CD4 and CD8 T cells after treating NOD mice with mRNA-DCs. T1D development was significantly suppressed with 3 biweekly treatments with 106 DCs containing 2 µg of antigen mRNA. Moreover, efficacy of the mRNA-DCs was enhanced when mRNAs encoding antigens and IL-27 were co-delivered into DCs by electroporation or when DCs were treated with rapamycin during differentiation. Endogenous expression of antigens may enable post-translational modifications and more prolonged presentation. Thus, we developed a promising and customizable ASIT platform to deliver multiple epitopes to exogenous tolerogenic DCs (or to endogenous APCs using a nanoparticle-based platform not covered here) that will consider the patient’s immune profile for a precision medicine treatment of T1D.

Disclosure

R. Fite: None. R. J. Creusot: None.

Funding

American Diabetes Association (1-19-PMF-022 to R.F.F.)
60-OR: Patient Engagement in Diabetes Self-Management Education and Support (DSME/S) Using Immersive Virtual World Technology
Authors: MITCHELL SUZANNE , BRAGG ALEXA , WINTER MICHAEL , GARDINER PAULA , HOWARD JESSICA M. , LAIRD LANCE D.
Published: June 2021

Introduction: Immersive online technologies, such as virtual world (VW) platforms, can increase patient engagement in DSME/S. The Women in Control 2.0 (WIC2) trial compared DSME/S delivered in a VW vs. in-person for minority women with uncontrolled type 2 diabetes (HbA1c ≥8.0). We hypothesize the sense of presence afforded by a VW platform fosters patient engagement. Presence in a virtual reality setting is defined as a feeling of being immersed in an environment despite its artificiality.

Methods: We used a triangulation mixed-methods design embedded within the WIC2 clinical trial. For the 145 participants randomized to the VW study arm, we measured participant experience of physical, self and social “presence” in the VW using the validated Multimodal Presence Scale (MPS) and 63 participated in qualitative interviews. We analyzed participant experiences in the VW with qualitative data collected via direct observation, focus group, and key informant interviews. We calculated the MPS scores and conducted a qualitative thematic analysis of transcripts. Qualitative and quantitative data were collected independently and integrated using a conceptual mapping process to correlate participants’ experience of DSME/S in the VW.

Results: Half of participants were over 56yo and had a mean baseline HbA1c of 9.9% (SD=1.75). Two-thirds of the VW participants reported a sense of social (63.7%) and physical (63.1%) presence, while half-experienced self (49.0%) presence in the VW. Data integration led to three themes related to “presence” in a VW: (1) Self-presence fosters user identification with the personalized avatar (2) Physical presence fosters a growth mindset through imaginative play and visualization, and (3) social presence fosters peer social support.

Conclusion: Patient engagement in DSME/S is enhanced by the sense of physical, social and self- presence experienced by learners when using immersive technology software in a peer group context.

Disclosure

S. Mitchell: Other Relationship; Self; See Yourself Health LLC, Speaker's Bureau; Self; Merck Sharp & Dohme Corp. A. Bragg: None. M. Winter: None. P. Gardiner: None. J. M. Howard: None. L. D. Laird: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK10653)
62-OR: Fostering Sustainability through Diabetes Self-Management Support in African-American Churches: Results of the Praise Diabetes Project
Authors: PIATT GRETCHEN , PROVENZANO ANTHONY M. , NWANKWO ROBIN , HALL DIANA , KLOSS KATHERINE A. , HAWKINS JACLYNN M. , FUNNELL MARTHA M.
Published: June 2021

A gap exists between diabetes self-management education (DSME), DSMS practices, and the infrastructure needed to foster sustainability of improved outcomes, particularly in low-resource communities. We determined the relative effectiveness of 3 parallel DSMS approaches in improving A1c and diabetes distress (DD). Moderate DD was 2.0-2.9 and high DD was ≥ 3.0. 370 individuals [mean age: 64.6 years, 74% female, 100% African American (AA), mean A1c: 7.7%±1.9, 22.8% with moderate DD] from 21 AA churches in southeast Michigan and northwestern Ohio, took part in a cluster randomized trial from 2016-2020. Data were collected at baseline, 6, 9, 21, and 33 months. Churches were randomized to one of three DSMS approaches [Parish Nurse (PN) + Peer Leader (PL) DSMS (n=123), PL DSMS (n=127), or PN DSMS (n=109)]. Twenty-one PNs and 28 PLs were trained to facilitate DSMS at each church. Sustained reduction in A1c was observed in all groups (PNPL: -0.2%, p=0.68; PN: -0.2%, p=0.13). PL had borderline statistically significant reductions (-0.3%, p=0.08). The proportion of participants with A1c < 7% also improved over time in each group (PNPL: 57.3 vs. 60.7%, p=0.21; PL: 57.3 vs. 62.7%, p=0.44; PN: 40.9 vs. 44.1%, p=0.66), but not significantly. Of those who achieved A1c < 7% following DSME (9-month follow-up), 81.3% of participants, across all groups, sustained the goal at 33 months. PN had the most participants with sustained glycemic control (PNPL: 81.6%, PL: 76.7%, PN: 86.9%). Significant improvements in mean DD scores were observed from baseline to 33 months in all groups (PNPL: 2.1 vs. 1.8, p=0.05; PL: 2.0 vs. 1.7, p=0.004). Moreover, there was a 50% reduction in the proportion of participants with moderate DD in PL (31.7% vs. 12.2%) and PN (27.5% vs. 15%) and severe DD in PN (10% vs. 5%). Varied approaches to DSMS within the context of existing community infrastructures (AA churches) fostered the sustainability of improvements in diabetes-related outcomes.

Disclosure

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

Funding

National Institutes of Health (R01DK103733)
631-P: Reliability of the Freestyle Libre Continuous Monitoring System in the Inpatient Setting: Implications for the COVID-19 Surge
Authors: MURRAY-BACHMANN RENEE , ZISKOVICH KARINA , SARBANES MULUGETA , LEUNG TUNG MING , MYERS ALYSON , MURTHI SWETHA , PORETSKY LEONID
Published: June 2021

Introduction: Standard point of care capillary blood glucose testing (POCT) is commonly used in hospitalized patients to monitor their glucose levels. This technique is associated with increased staff/patient contact and patient discomfort. We examined the correlation of the capillary blood glucose results obtained by the POCT device (Accuchek Inform II) with the serum glucose values obtained by the hospital laboratory and with the glucose readings obtained by the FDA-waived for in-patient use (because of COVID-19 pandemic) Freestyle Libre continuous glucose monitoring system (CGMS).

Methods: For this prospective cohort study fifty-two adult participants who were diagnosed with diabetes mellitus and admitted to non-critical units were recruited. Among them, 41 (79%) were male, 50 (96%) had type 2 diabetes mellitus. CGMS sensors were placed on patients’ arms, POCT and serum glucose measurements were taken as ordered. Descriptive statistics were calculated and linear mixed models were used to determine correlation.

Results: There were a total of 467 Accuchek-Libre pairs with a highly statistically significant association between pairs, p<0.0001. There were also 44 serum glucose -Libre pairs, with a highly statistically significant association, p<0.0001. On average, for each unit increase in Libre glucose level, there was a 0.92 unit increase in Accuchek glucose level as well as a 1.05 unit increase in serum glucose level.

Conclusion: These findings indicate excellent correlation between the standard POCT and the CGMS as well as between serum glucose and the CGMS values. Because of the advantages of the CGMS glucose readings over blood capillary glucose testing (reduced patient discomfort and reduced staff exposure to patients during the pandemic) hospitals should consider replacing capillary blood glucose testing with CGMS.

Disclosure

R. Murray-bachmann: None. K. Ziskovich: None. M. Sarbanes: None. T. Leung: None. A. Myers: None. S. Murthi: None. L. Poretsky: None.
632-P: Flash Glucose Monitoring in Hypoglycemia Monitor in Type 1 Diabetes
Authors: LI JUNXIAN , LIU FANG
Published: June 2021

Aims: Hypoglycemia is an acute complication of patients with type 1 diabetes. This study investigated flash glucose monitoring in hypoglycemia monitor in patients with type 1 diabetes.

Methods: A total of 120 patients with type 1 diabetes were recruited and randomly divided to implement FreeStyle LibreTM as flash glucose monitoring group (n=60) and retrospective continuous glucose monitoring system (CGMS) as control group (n=60). Both groups carried out CGMS at least two times a year and filled three questionnaires including Diabetes Monitoring and Treatment Satisfaction Questionnaire (DMTSQ), Diabetes Specific Quality of Life (DQoL) and Chinese Version Hypoglycemia Fear Survey II (CFH II). Clinical Data, CGM metrics and Questionnaire scores were collected at first visit and one year follow up.

Results: The result showed that the time below range (TBR) and the glucose coefficient of variation (CV) were significantly higher in flash glucose monitoring group than control group (all P <0.05). TBR was prolonged with the increase of CV (P <0.05) and low blood glucose index (LBGI) (P <0.05) in both two groups. After multiple stepwise linear regression, CV and LBGI were independent risk factors for TBR (Standardized Coefficients β=0.665, β=0.762, respectively, All P<0.001 ). After one year followed up, the scores of DQoL and DMTSQ had no significant difference, but number of hypoglycemia times per month and scores of behavior part of CFH II significantly decreased in flash glucose monitoring group compared with a year ago (all P<0.05).

Conclusions: Glucose CV and LBGI were independent risk factors for TBR. And Flash glucose monitoring decreased number of hypoglycemia times per month and fear behavior of hypoglycemia in patients with type 1 diabetes after one year.

Disclosure

J. Li: None. F. Liu: None.

Funding

National Key Research and Development Program of China (2017YFC1309601)
646-P: Efficacy and Safety of Evogliptin plus Metformin Added to Insulin Therapy in Elderly Indian Patients with Type 2 Diabetes
Authors: GUHA SHAIBAL , RANJAN RAJEEV , GAURAV AMIT , RANJAN PRAKASH
Published: June 2021

Objective: The combination of evogliptin plus metformin and insulin has known to be effective for the treatment of type 2 diabetes (T2D). However, longitudinal efficacy and safety for elderly patients have not been established. Here, we evaluated whether Evogliptin plus metformin added to insulin therapy safely improved glycemic control for T2D patients older than 65 years of age.

Method: Thirty two T2D patients (male/female 20/12; age 76.2± 6.3 years, HbA1c 8.4±0.8%, DOD 6.9±2.1 years) who were administrated insulin were recruited and Evogliptin (5 mg) plus Metformin (500 mg) was added to their treatment regimen. Before and 6 months after adding Lira, we assessed metabolic parameters and the data from CGM.

Result: Six months after adding evogliptin plus metformin, HbA1c ( from 8.4±0.8% to 7.2±1.2%; P=0.003) and body weight ( from 62.8±8.3 kg to 61.2±4.6 kg, P=0.006) were significantly improved despite the daily dose ( from 58.5±11.2 IU/day to 45.63±14.4 IU/day, P=0.005) and number of insulin injections per day being reduced. CGM analysis revealed that SD and ≥180 mg/dL AUC were significantly decreased and hypoglycemic events were not increased. Furthermore, 22% of patients with suboptimal glycemic control (A1C>7%) achieved a composite outcome consisting of improvement in A1C, weight loss and insulin dose reduction.

Conclusion: These results suggest that the administration of evogliptin plus metformin could safely improve glycemic control and reduce body weight in elderly patients with T2DM undergoing insulin therapy. The reduction of glucose fluctuation and number of insulin injections may improve the quality of life of elderly T2D patients, especially those who require social support.

Disclosure

S. Guha: None. R. Ranjan: None. A. Gaurav: None. P. Ranjan: None.
671-P: Liraglutide Possibly Prevents Progression of Dementia in Patients with Type 2 Diabetes
Authors: YOSHIDA MAMI , YOSHIDA AI , OH ERIKO , YAMAMOTO NAOMUNE , SASAKI EUN , YOSHIDA SHIGERU , OHSAWA NAKAAKI , SUGINO MASAKAZU , KOYAMA IKUO
Published: June 2021

Purpose: The purpose of this study is to assess the usefulness of liraglutide in elderly patients with type 2 diabetes to prevent progression of dementia.

Methods: We retrospectively reviewed 31 outpatients with 65 years of age or older, who have been treated with liraglutide for 6 years (Group G; 12 males/19 females, 73.1 ± 8.6 years-old, HbA1c 7.5 ± 0.4%, 9 patients with cerebrovascular diseases, 8 patients with cardiovascular diseases, 16 patients with insulin therapy). Daily dose of liraglutide was 0.9 mg except 2 patients (0.6 mg). We examined Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on MRI, max-IMT measured by carotid artery ultrasonography, visceral fat area, concentrations of HbA1c and FPG, serum levels of CRP, HDL/LDL cholesterol, and TG, both before and after the treatment. Age, HbA1c, and VSRAD values-matched 16 patients who were treated with linagliptin were analyzed as a control (Group D).

Results: After 6 years, VSRAD was significantly deteriorated in Group D (1.06±0.98→1.39±1.05 (p<0.01)) but not in Group G (1.28±0.80→1.39±1.1 (NS)). Max IMT and visceral fat are was significantly improved in Group G (2.41±1.50→2.09±0.84 (p<0.05), 141.1±57.2→127.2±52.9 (p<0.01)), but not in group D (2.04±1.01→1.99±0.68 (NS), 102.4±66.5→106.6±62.7cm2 (NS)). CRP was decreased in Group G (0.12±0.11→0.09±0.12mg/dl (p<0.01)). HbA1c (7.5±0.4 → 7.0±0.5 vs. 7.3±0.3 → 6.8±0.4%), FPG (137±19 → 121±11 vs. 129±12→110±15mg/dl), were significantly improved in both groups (p<0.01). No hypoglycemia requiring medical intervention was observed. Only TG in Group G (167±53→147±34mg/dl (p <0.01)) was improved in lipid parameters. During the 6 years, antidementia drugs were prescribed for 2 patients in both groups. A stroke event was found in a patient of Group D.

Conclusion: Liraglutide possibly prevent progression of dementia. The reduction of visceral obesity may contribute to this beneficial effect through anti-arteriosclerosis.

Disclosure

M. Yoshida: None. A. Yoshida: None. E. Oh: None. N. Yamamoto: None. E. Sasaki: None. S. Yoshida: None. N. Ohsawa: None. M. Sugino: None. I. Koyama: None.
687-P: ß-Cell Function and Glycemic Response to Dulaglutide in Patients with Type 2 Diabetes
Authors: HASEBE MASASHI , YOSHIJI SATOSHI , IWASAKI YORIHIRO , KIMURA SADAHITO , SENO YOHEI , KEIDAI YAMATO , HARAGUCHI TAKUYA , IWASAKI KANAKO , WADA YOSHIHARU , HONJO SACHIKO , FUJIKAWA JUN , HAMASAKI AKIHIRO
Published: June 2021

Aims: The effect of β-cell function on glycemic response to dulaglutide (DU) is not fully understood in clinical settings. We explored a suitable clinical marker of β-cell function to predict glycemic response to DU in patients with type 2 diabetes (T2D).

Methods: We retrospectively analyzed 141 patients who commenced once-weekly DU 0.75 mg after undergoing a meal tolerance test (MTT) with a standardized meal from September 2015 to December 2019 at our hospital. β-cell function was assessed by fasting and 2h postprandial serum C-peptide immunoreactivity (CPR) as well as increment of CPR (dCPR) in the MTT. We analyzed the suitability of each measurement as a marker for β-cell function and its association with glycemic response to DU using linear and logistic regression with adjustment for baseline HbA1c.

Results: In 141 patients, 2h postprandial CPR (PCPR) and dCPR showed significant inverse correlation with baseline HbA1c (r = -0.25 and -0.33, respectively; P < 0.01 for both), while fasting CPR (FCPR) did not (r = 0.02; P = 0.853). Given the association of high baseline HbA1c and impairment of meal-stimulated insulin secretion measured with PCPR and dCPR, we adopted FCPR as a marker for β-cell function with less influence from baseline HbA1c in the following analysis. Of the 141 patients, 59 patients continued DU without initiating any additional glucose-lowering agents for more than 6 months. The baseline mean ± SD HbA1c, fasting plasma glucose, and FCPR of the 59 patients were 8.9 ± 1.2%, 9.2 ± 2.3 mmol/L, 0.50 ± 0.29 nmol/L, respectively. The mean ± SE change in HbA1c 0-6 months was -1.2 ± 0.2%. FCPR was significantly associated with a reduction in HbA1c (P = 0.031). Furthermore, FCPR was a significant predictor for achieving a reduction in HbA1c ≥ 1% over 6 months (OR, 1.40; 95% CI, 1.14-1.71; P = 0.039) with the area under the receiver operating characteristics curve of 0.83.

Conclusions: FCPR is less affected by baseline HbA1c than PCPR and dCPR, and can be a useful marker for predicting glycemic response to DU.

Disclosure

M. Hasebe: None. S. Honjo: None. J. Fujikawa: None. A. Hamasaki: None. S. Yoshiji: None. Y. Iwasaki: None. S. Kimura: None. Y. Seno: None. Y. Keidai: None. T. Haraguchi: None. K. Iwasaki: None. Y. Wada: None.
689-P: Association of Preoperative Glycemic Response to GLP-1 Receptor Agonists (GLP-1RA) and Outcomes of Bariatric Surgery
Authors: AMUSIN DANIEL , KUCHTA KRISTINE , EWING TATUM , TUCKER LYNN , CAMPBELL MICHELLE , UJIKI MICHAEL , BILLINGS LIANA K.
Published: June 2021

Background: GLP1RAs are an increasingly common treatment in the setting of type 2 diabetes mellitus (T2DM). One hypothesized mechanism by which bariatric surgery contributes to T2DM remission is by increasing intestinal GLP-1 secretion. We aimed to evaluate the association of the response to GLP1RA pre-operatively on hemoglobin A1c (HbA1c) level and weight loss after bariatric surgery.

Methods: The NorthShore bariatric surgery database was retrospectively queried for patients with T2DM who had taken a GLP1RA prior to Roux-en-Y gastric bypass (N=38) or gastric sleeve surgery (N=9). GLP1RA response was measured by change in HbA1c from initiation of therapy to 6mo. Outcomes included HbA1c level and percent total body weight loss (TBWL) at 6mo, 1 and 2yr post-op. The association between GLP1RA response and post-operative outcomes was evaluated with partial correlation coefficients adjusted for baseline HbA1c with/without baseline weight.

Results: The average HbA1c at initiation of therapy was 8.3±1.4% and decreased by 1.1±1.5% on GLP1RA treatment with liraglutide being most commonly prescribed (44.7%). A greater decrease in HbA1c from GLP1RA was correlated with a lower HbA1c at 6mo (r=0.38, p=0.02), and 2yr (r=0.43, p=0.03), but not 1yr (r=0.35, p=0.06) or TBWL. After adjustment for baseline weight, the association remained at 6mo (r=0.37, p=0.02). Stratification by procedure noted a strong association between GLP1RA response and reduced post-operative HbA1c at 6mo (r=0.99, p<0.01) and TBWL at 1yr (r=0.82, p=0.02) and 2yrs (r=0.99, p=0.01) for patients who had undergone gastric sleeve, but not gastric bypass.

Conclusion: To our knowledge, this is the first study examining the association of GLP1RA response on glycemic and weight outcomes post-bariatric surgery in people with T2DM. Despite a number of limitations, results from this small cohort suggest the need for further evaluation of this relationship as a potentially useful predictor of surgical outcomes.

Disclosure

D. Amusin: None. K. Kuchta: None. T. Ewing: None. L. Tucker: None. M. Campbell: None. M. Ujiki: Advisory Panel; Self; Boston Scientific Corporation, Consultant; Self; Cook Medical, Speaker’s Bureau; Self; Medtronic. L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi.
70-LB: Continuous Glucose Monitoring Data Sharing in Older Adults with Type 1 Diabetes and Their Care Partners
Authors: ALLEN NANCY A. , LITCHMAN MICHELLE L. , CHAMBERLAIN JAMES , GRIGORIAN ERNEST , IACOB ELI , BERG CYNTHIA
Published: June 2021

Background: Family members of older adults with type 1 diabetes (T1D) regularly become part of the diabetes care team yet often lack knowledge about how to become involved to prevent hypo- and hyperglycemia. Real-time continuous glucose monitoring (RT-CGM) with data sharing could facilitate diabetes management among older adults with T1D and their family members.

Methods: Older adults with T1D (n=20) and their care partners (n=20) received a RT-CGM data sharing intervention called SHARE. SHARE included dyadic communication strategies, problem-solving strategies, and action planning. People with diabetes (PWD) wore the RT-CGM for 12 weeks while sharing their glucose data with a care partner. Feasibility data were obtained on intervention dose, implementation processes, satisfaction, and diabetes-related quality of life using RT-CGM. Descriptive statistics were used to examine feasibility, satisfaction, and demographic data.

Results: The SHARE intervention was feasible, had high self-reported satisfaction for PWD and their care partner, and high adherence (96±6.8%) with wearing the RT-CGM. We found broad improvements in diabetes-related quality of life using RT-CGM in PWD and their care partners. Although the majority of PWD were willing to share hyperglycemia data (55%), several chose not to. The majority of PWD were willing to talk about glucose numbers with a care partner (n=70%). For this feasibility study, the SHARE intervention was not targeted at improving glucose levels but rather on communication and problem-solving strategies. There were no significant trends in the RT-CGM data (e.g., time in range) between baseline and 12 weeks.

Conclusion: Older adults with T1D diabetes and their care partners identified the positives of RT-CGM with SHARE as having someone else aware of glucose levels and working together with a partner on diabetes self-management. SHARE may improve dyadic communication and problem-solving around glucose management in older adults.

Disclosure

N. A. Allen: Research Support; Self; Dexcom, Inc. M. L. Litchman: Research Support; Self; Abbott Diabetes. J. Chamberlain: Speaker’s Bureau; Self; Abbott Diabetes, Dexcom, Inc. E. Grigorian: None. E. Iacob: None. C. Berg: None.

Funding

University of Utah Center on Aging; University of Utah One U Caregiving Initiative; Dexcom, Inc.
725-P: Low Fasting Glucose and Insulin Deficiency Were Related with Superiority of Insulin Degludec/Aspart Compared with Basal Insulin in Patients with Type 2 Diabetes
Authors: JANG HAN NA , YANG YE SEUL , OH TAE JUNG , KOO BO KYUNG , LEE SEONGOK , JUNG HYE SEUNG
Published: June 2021

Objective: In spite of expected benefit of insulin degludec/aspart (IDegAsp), efficacy of once-daily IDegAsp compared to basal insulin has not been established. We searched for clinical factors associated with efficacy of once-daily IDegAsp.

Methods: We collected medical records of adults with type 2 diabetes under basal insulin of 3 hospitals. From the basal insulin cohort, patients were enrolled who switched to once-daily IDegAsp and continued over 6 months. Those who maintained basal insulin were selected as a control group, by Propensity-score matching with HbA1c, insulin doses, etc.

Results: The basal insulin cohort was comprised of 324 patients, and the IDegAsp group and the control were 87 patients, respectively. Baseline clinical variables and HbA1c were comparable between two groups (8.7±0.9 vs. 8.6±0.9%). After 6 months with comparable changes in insulin doses, HbA1c in the IDegAsp group was lower than that in the control (8.1±1.0 vs. 8.4±1.1%, p=0.029). With the comparable HbA1c, baseline FPG was lower in the IDegAsp (124±38 vs. 148±51 mg/dL, p<0.001). A regression analysis between FPG and HbA1c in the basal insulin cohort revealed that most participants in the IDegAsp group had lower FPG than predicted from their HbA1c. Then subgroup analysis was done according to the difference (ΔFPG) between measured FPG and predicted FPG. When compared to each control group further matched for baseline FPG, the favorable effects of IDegAsp on the reduction of HbA1c changes was significant only in the subgroup where measured FPG was severely lower than predicted FPG (98±19 vs. 140±11 mg/dL). ΔFPG was significantly correlated with fasting C-peptide (r=0.19) and glucose increment at postprandial 2 hours (r=-0.514).

Conclusion: Once-daily IDegAsp was effective than basal insulin on reduction of HbA1c in patients with lower FPG than predicted from their HbA1c, which suggested severe insulin deficiency and marked postprandial hyperglycemia.

Disclosure

H. Jang: None. Y. Yang: None. T. Oh: None. B. Koo: None. S. Lee: None. H. Jung: Research Support; Self; Novo Nordisk.

Funding

National Research Foundation of Korea (2019R1A2C1007397); Korean Diabetes Association (2019F-10)
751-P: First-in-Human, Single and Repeated Dose Study of SCO-267, a GPR40 Full Agonist, in Healthy Adults and Subjects with Glucose Intolerance
Authors: NISHIZAKI HARUNOBU , MATSUOKA OSAMU , ACHIRA MEGURU , KAGAWA TOMOYA , WATANABE MASANORI , MORITOH YUSUKE
Published: June 2021

The clinical potential of SCO-267, an orally available allosteric full agonist against GPR40 that regulates islet and gut hormone secretion, is largely unknown. Here, we present the first clinical study using the GPR40 full agonist. A randomized, single-center, double-blind, placebo-controlled, phase 1 study was conducted to investigate safety, tolerability, and pharmacokinetics as primary endpoints and pharmacodynamics as secondary endpoints of single (5-320 mg) and repeated doses (80 and 160 mg, Q.D.) of SCO-267 in healthy adults and subjects with glucose intolerance (HbA1c range 6.6-8.8%). SCO-267 was generally safe and well tolerated at all doses up to 4 days. The plasma SCO-267 concentration increased generally dose-dependently and its pharmacokinetic profiles suggests the potential for once-daily oral dosing in a clinical setting. The pharmacokinetic profiles of SCO-267 was similar between Japanese and Caucasian subjects, and healthy subjects and those with glucose intolerance. Pharmacokinetic profiles of SCO-267 in healthy adults were unaltered with repeated doses. SCO-267 was hardly detected in urine, suggesting that it is eliminated by non-renal mechanisms. SCO-267 single dose (40 and 80 mg) stimulated secretion of insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY), and normalized glucose intolerance during an oral glucose tolerance test in subjects with glucose intolerance. SCO-267 repeated dose (80 and 160 mg) stimulated secretion of insulin, glucagon, GLP-1, GIP, and PYY in healthy adults.

In conclusion, SCO-267 was safe, well tolerated, and pharmacokinetic profiles support a once-daily dosing regimen. SCO-267 further stimulated islet and gut hormone secretion and normalized glucose tolerance in humans. These findings support the further development of SCO-267 for diabetes, obesity, and nonalcoholic steatohepatitis.

Disclosure

H. Nishizaki: Employee; Self; Scohia Pharma Inc. O. Matsuoka: None. M. Achira: Employee; Self; PRA Health Sciences KK. T. Kagawa: Employee; Self; Scohia Pharma Inc. M. Watanabe: Employee; Self; Scohia Pharma Inc. Y. Moritoh: Employee; Self; Scohia Pharma Inc.
763-P: Dorzagliatin Add-On to Metformin Achieved Sustained Efficacy and Good Safety Profiles in T2D Patients in a 52-Week Phase 3 Trial (DAWN)
Authors: CHEN LI , ZHANG YI , YANG WENYING
Published: June 2021

Metformin, as recommended in various guidelines, is the currently preferred first-line treatment for T2D and often used in combination with other antidiabetic agents. Despite advances in diabetes therapeutics, there was still a lack of improvement in reaching clinical targets. Previous results on dorzagliatin from a monotherapy trial (SEED) have shown sustained efficacy and safety profiles in drug-naive T2D patients over 52 weeks. In this randomized, double-blind, placebo-controlled trial, the efficacy and safety of dorzagliatin add-on to metformin in T2D patients were evaluated. Patients were treated with metformin at 1500 mg/day as basic therapy throughout the 52-week treatment period. A total of 767 eligible Chinese patients were randomized to 75 mg dorzagliatin or placebo (1:1) BID groups for 24 weeks, followed by another 28 weeks with dorzagliatin (75 mg BID) in both groups. The primary endpoint was the change of the HbA1c from baseline at week 24. The HbA1c from baseline was reduced by 1.02% at week 24 in the dorzagliatin group, superior to the placebo (P<0.0001), with effects sustained till the end of the 52-week treatment. The target response rate (HbA1c <7.0%) at week 24, was 44.4% in the dorzagliatin group compared to 10.7% in the placebo group (P<0.0001). At week 24, the 2h-PPG was reduced from baseline by 5.45 mmol/L with dorzagliatin, significantly lower than placebo (P<0.0001). Dorzagliatin significantly improved β-cell function at week 24, as measured by HOMA2-β and HOMA2-IR (P<0.05). No drug-related serious adverse events, and severe hypoglycemia were reported. There was less than 1% hypoglycemia (blood glucose <3.0 mmol/L) during the 52 weeks. With a novel mechanism of action, dorzagliatin add-on to metformin has shown sustained glycemic control and good safety profiles over 52 weeks, offering a new solution to T2D patients with insufficiently controlled blood glucose on metformin.

Disclosure

L. Chen: None. Y. Zhang: Employee; Self; Hua Medicine. W. Yang: None.
764-P: Preventive Effect of Cranberry Extract for SGLT2i-Associated Urinary Tract Infection: A Case Control Study
Authors: GAUTAM ASHISH , AGRAWAL PRABHAT K. , PURSNANI NIKHIL , MAHESHWARI PRADEEP K. , RANI RUCHI
Published: June 2021

Introduction: Glycosuric effect of SGLT2i is often complicated by Genito-urinary tract infection (GUTI). Despite all measures (hydration, hygiene, and healthy toilet habits) the risk is still 4-9%. Withdrawing SGLT2i from treatment deprives patient of its multiple benefits. On the contrary, frequent antibiotics and antifungal use emerges risk of drug resistance. Cranberry contain fungistatic benzoic acid and proanthocyanidins which inhibit the adherence of p-fimbriae of E.Coli.

Aim and Objective: This study was designed to observe the preventive effect of cranberry extract for recurrent GUTI due to SGLT2i use in T2DM.

Methods: One hundred and three subjects having T2DM, using SGLT2i as OHA were selected as cases. Cases were prescribed cranberry extract 300mg BD for 6 months. Comparators were also 98, age and sex-matched subjects having T2DM and using SGLT2i. Comparators were not prescribed cranberry extract. Subjects with uncontrolled glycemic targets and other risk factors for recurrent GUTI were excluded. Both groups were followed for 6 months and periodically evaluated for symptomatic and/or pathologically proven UTI using standard definition.

Result: Nine out of 103 cases and, 6 out of 98 comparators were excluded from observation either due to loss to follow-up, poor compliance, or getting complicated UTI leading to permanent drug withdrawal. Average incidence of GUTI among 94 cases (M=1.9, SD=1.4) matched to 92 comparators (M=2.6, SD=1.8), demonstrated significantly lesser frequency, z=-2.21, u=3510.5 and p=.027. No demonstratable or significant side effect due to cranberry extract was reported during the observation period. Average HbA1c reduction after observation period among cases (M=-0.3) compared with comparators (M=0.2) didn’t demonstrated significant difference (z=-1.84, p=.06). Cranberry extract didn’t show any effect over glycemic values.

Conclusion: Cranberry extract when used as an add-on to SGLT2i demonstrated a significant reduction in the incidence of GUTI.

Disclosure

A. Gautam: None. P. K. Agrawal: None. N. Pursnani: None. P. K. Maheshwari: None. R. Rani: None.
766-P: DA-1241, a Novel GPR119 Agonist: Data on Safety, Tolerability, and Pharmacokinetics (PK) from Part 1 of a Phase 1b Multiple Ascending Dose (MAD) Study in Healthy Volunteers (HV)
Authors: KIM MI-KYUNG , LEE DAE YOUNG , JEONG JIYOON , GRIMM MICHAEL , FRANEY BRIDGETTE B. , HOMPESCH MARCUS
Published: June 2021

Background and Aim: DA-1241 is a novel small molecule selective GPR119 agonist. In preclinical studies DA-1241 enhanced insulin and GLP-1 secretion, reduced glucose excursions, lowered blood glucose and improved dyslipidaemia. The primary objective of Part 1 of this study was to assess the safety and tolerability of multiple once daily oral doses of DA-1241 compared to placebo in HV. Secondary objective was to estimate the plasma PK characteristics.

Methods: Part 1 was a double blind placebo-controlled, single-center study of DA-1241 in HV. Three sequential cohorts of HV (n=8/cohort) were blinded and randomized (3:1) to receive DA-1241: 50, 100 or 200 mg (n=6/cohort) or placebo (n=2/cohort), as single daily oral doses for 28 days. Safety data reviews and dose escalation decisions between cohorts took place after all subjects of an ongoing cohort had completed procedures through day 14.

Results: Overall 24 male subjects participated in Part 1 (Age 38.4 ± 10.7, BMI 26.0 ± 2.7). All doses tested were safe and well tolerated. There were no SAEs and no discontinuations due to AE. All TEAE’s were mild with no obvious dose relation and resolved spontaneously. The day 28 Cmax and AUC0-tau PK parameters showed dose proportional characteristics across the tested dose range, with Cmax (50mg: 464.9 ± 284.1; 100mg: 569.3 ± 173.2; 200mg: 1653.2 ± 615.4 ng/mL) and AUC0-tau (50mg: 5168.4 ± 1651.2; 100mg: 7620.0 ± 1837.7; 200mg: 19167 ± 9088.8 h*ng/mL). Tmax was reached at 2.9 ± 1.8; 2.3 ± 1.2 and 1.9 ± 0.6 hours respectively with a t1/2 of 590 ± 370; 368 ± 355 and 537 ± 395 hours, values for 50, 100, and 200 mg doses respectively.

Conclusion: Data from this phase 1b study in HV confirmed a favorable safety, tolerability and PK profile of DA-1241, and supported a progression of the clinical development program into patients.

Disclosure

M. Kim: Employee; Self; Dong-A ST Co. Ltd. D. Lee: Employee; Self; Dong-A ST Co. Ltd. J. Jeong: Employee; Self; Dong-A ST Co. Ltd. M. Grimm: None. B. B. Franey: None. M. Hompesch: Other Relationship; Self; Wiley, Stock/Shareholder; Self; ProSciento, Inc.
77-LB: A Retrospective Analysis of the Association between HbA1c and Continuous Glucose Monitor Use for U.S. Patients with Type 2 Diabetes
Authors: NORMAN GREGORY J. , PAUDEL MISTI L. , BANCROFT TIM , LYNCH PETER M.
Published: June 2021

Background: Use of real-time continuous glucose monitoring (rtCGM) reduces HbA1c in individuals with type 2 diabetes (T2D) treated with intensive insulin regimens in randomized clinical trials. However, the effects of CGM use on glycemia in T2D patients in real world settings, particularly those treated with less intensive therapies, has not been well studied.

Materials and Methods: This large retrospective, observational analysis utilized data from the Optum Research Database (ORD) to assess the glycemic effects of CGM use (any CGM or real-time CGM [rtCGM]) compared with self-monitoring of blood glucoses (SMBG) within a large T2D population treated with intensive insulin therapy (IIT) and non-intensive therapies (NIT), including basal insulin only, and non-insulin medications. Outcomes were changes from baseline in HbA1c up to 6 months post index date in all patients and by treatment regimen. The percentage of patients who achieved ≥1.0 HbA1c reductions was also assessed.

Results: Data from 82,983 eligible patients were assessed (Any CGM, n=1,406; rtCGM, n=148; SMBG, n=81,575). Significant HbA1c reductions were observed with Any CGM (-0.46) and rtCGM (-0.72) vs. SMBG (-0.09), ps < 0.001. HbA1c reductions were significant in CGM vs. SMBG users in the ITT (Any CGM, -0.38%; rtCGM, -0.68%, ps<0.001) and NIT groups (Any CGM, -0.67%, p<0.001, and rtCGM, -0.87, p=0.008). Significantly higher percentages of Any CGM and rtCGM vs. SMBG users achieved ≥1.0 HbA1c reductions in the IIT and NIT groups. Effects of Any CGM and rtCGM were attenuated but remained statistically significant in multivariate adjusted models for the overall T2D cohort.

Conclusions: Use of CGM (Any CGM or rtCGM) confers notable benefits in improving glycemic control regardless of therapy regimen. These findings support expanding CGM access to the broader T2D population.

Disclosure

G. J. Norman: Employee; Self; Dexcom, Inc. M. L. Paudel: None. T. Bancroft: None. P. M. Lynch: Employee; Self; Dexcom, Inc.