bluuebunny/crossref_metadata_2025 huggingface dataset:
680-P: Residual ß-Cell Function in Long-Term Type 1 Diabetes Is Associated with a Fivefold Greater Mobilization of Endothelial Progenitor Cells after Exercise
Authors: TAYLOR GUY S. , SMITH KIERAN , SCRAGG JADINE , BASHIR AYAT , FLATT ANNELIESE , STEVENSON EMMA J. , MCDONALD TIMOTHY J. , ORAM RICHARD A. , SHAW JAMES A. , ROSS MARK D. , WEST DANIEL J.
Published: June 2020

Aims: β-cells can function for years after diagnosis in people with type 1 diabetes (T1D). It is unknown how C-peptide secretion impacts upon rare blood vessel protecting Endothelial and Hematopoietic Progenitor Cells (EPCs and HPCs), particularly in response to cardiovascular stress, such as exercise. We compared EPC and HPC counts at rest and after acute exercise in clinically diagnosed people with T1D with undetectable and high C-peptide.

Methods: After quantification of stimulated C-peptide, 11 participants with undetectable C-peptide (Cpepund <3 pmol/L) and 10 with high C-peptide (Cpephigh >200 pmol/L) were recruited, with no differences in age, fitness or HbA1c, while the Cpephigh group had shorter diabetes duration (27±13 vs. 11±3 years, p=0.01). After a maximal exercise test, participants attended a third visit to complete 45mins of walking at 60%VO2peak. Blood samples were taken at rest, immediately and 1 hour post exercise. Two HPC and five EPC phenotypes were enumerated by flow cytometry. Data (mean±SD) were analysed by two-way ANOVA and t-test with significance accepted at p≤0.05.

Results: The Cpephigh group displayed higher rest values of HPCs than the Cpepund group, and increased rest to post exercise mobilization (p<0.05). While resting counts were similar, exercise mobilized all EPC phenotypes in the Cpephigh group with no significant changes in the Cpepund group. CD34+CD45dimVEGFR2+ EPCs did not differ at rest (Cpephigh 28±13 vs. Cpeplow 22±7 cells/ml, p=0.22), while Cpephigh increased from rest to post exercise by 25±22 vs. 5±15 cells/ml in the Cpepund group (p=0.02).

Conclusion: People with T1D who maintained a high residual β-cell function had increased counts of HPCs and EPCs, and sustained a >5 fold exercise mobilization of EPCs compared to people with no C-peptide. Future research needs to understand if these differences are due to clinical characteristics or the potential direct impact of C-peptide upon vasculature.

Disclosure

K. Smith: None. J. Scragg: None. A. Bashir: None. A. Flatt: None. E.J. Stevenson: None. T.J. McDonald: None. R.A. Oram: None. J.A. Shaw: Advisory Panel; Self; Medtronic. Speaker’s Bureau; Self; Novo Nordisk A/S. M.D. Ross: None. D.J. West: None.

Funding

Diabetes Research & Wellness Foundation (to D.J.W.)
695-P: Grand-Maternal Exercise Improves Glucose Tolerance in Second Generation Offspring
Authors: WAGNER ANA B.A. , KUSUYAMA JOJI , NIGRO PASQUALE , MAKAREWICZ NATHAN S. , HIRSHMAN MICHAEL F. , GOODYEAR LAURIE J.
Published: June 2020

Maternal obesity and diet are critical risk factors for development of obesity and diabetes in both first (F1) and second (F2) generation offspring. Maternal exercise in mice improves F1 metabolic health and prevents the detrimental effects of maternal high-fat-diet (HFD) on F1 offspring. Whether the beneficial effects of maternal exercise can be transmitted to the F2 generation is unknown. Here, C57BL/6 females were fed a chow or HFD and subdivided into cages with (Exercise) or without (Sedentary) running wheels for 2wks before breeding and during ∼3wks gestation. Male F1 offspring were sedentary and chow-fed, and at 8 wks of age were bred with age-matched females from untreated parents. F2 offspring were studied based on grand-maternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained (n= ∼10 litters/group; 348 total mice). F2 offspring were sedentary and chow-fed and studied up to 52 wks of age. For F2 males, grand-maternal exercise significantly improved glucose tolerance at 24, 36 and 52 wks and decreased insulin concentrations at 52 wks. Grand-maternal exercise also resulted in F2 males with lower body weights, decreased fat mass and increased lean mass at 52wks. Grand-maternal HFD decreased glucose uptake in skeletal muscles and adipose tissue in F2 males, but there was no effect of grand-maternal exercise, suggesting that the mechanism for improved glucose tolerance in F2 males does not involve glucose uptake in these tissues. For female F2, grand-maternal exercise had no effect on insulin concentrations, body weights or tissue glucose uptake. However, grand-maternal exercise significantly improved glucose tolerance in female F2 at 36 and 52 wks, and decreased fat mass and increased lean mass. Maternal exercise has beneficial effects on the metabolic health of adult F2 male and female offspring. These novel findings suggest that maternal exercise can prevent obesity and diabetes in multiple generations and may help reduce the incidence of these diseases worldwide.

Disclosure

A.B.A. Wagner: None. J. Kusuyama: None. P. Nigro: None. N.S. Makarewicz: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. L.J. Goodyear: None.

Funding

American Diabetes Association (1-17-PMF-009 to A.B.A.W.); National Institutes of Health (R01DK101043)
696-P: Vasodilatory Response of the Muscular Artery Was Improved to Sheer Stress, but Paradoxically Decreased to Endothelium-Dependent Vasodilator in Diet and Aerobic Exercise in Type 2 Diabetes
Authors: HAN KYUNG AH , YANG BOYEON , MIN KYUNGWAN
Published: June 2020

The aims of this study were to investigate whether the stiffness of large elastic artery such as aorta and the muscular artery such as brachial artery improves through lifestyle modifications in type 2 diabetes. Total 82 overweight women with type 2 diabetes (age 55.0±7.6 years) were randomly assigned to control (C), diet (D), aerobic exercise (AE) and resistance exercise (RE) and completed the weight loss program for 12 weeks. We assessed BMI, augmentation index (AI) of aorta and also the flow-mediated dilation (FMD), the right brachial artery blood flow responses to an endothelium-independent vasodilator(ED), acetylcholine,, and an endothelium-dependent vasodilator(EID), isosorbide dinitrate, adiponectin/leptin ratio(ALR), free fatty acid(FFA), hsCRP, and insulin sensitivity (KITT) at baseline, and 12 week. There was no change in AI despite significant decreases in BMI in all intervention groups. FMD increased only in D and AE, but ED decreased in all 3 groups. EID increased only in D. The vascular function to sheer stress improved in muscular artery, not in large elastic artery with lifestyle changes. The response to isosorbide dinitrate was not consistent with FMD.

Disclosure

K. Han: None. B. Yang: None. K. Min: None.
707-P: Physical Exercise Decreases Notch1 Activation and Reduces the Gluconeogenesis in Liver of Obese Mice
Authors: GASPAR RAFAEL C. , MUÑOZ VITOR , NAKANDAKARI SUSANA C. , CRISOL BARBARA M. , VIEIRA RENAN F.L. , CONCEIÇÃO LUCIANA R. , SILVA ADELINO , CINTRA DENNYS E. , MOURA LEANDRO P. , ROPELLE EDUARDO R. , PAULI JOSÉ R.
Published: June 2020

Notch1 protein has an important role in the hepatic metabolism. In this way, it has been observed in obese individuals that Notch1 is correlated with insulin resistance in the liver, which makes it an interesting research target. On the other hand, the physical exercise are associated with the prevention and treatment of insulin resistance and type 2 diabetes. Thus, the present study aims to verify the role of physical exercise in the Notch1 protein modulation in the hepatic tissue of obese mice and its contribution in the control of gluconeogenesis. For this, we used obese mice induced by high fat diet and ob/ob animals. The trained animals group performed treadmill-running protocol, with intensity corresponding to 70% of the maximum running speed, for a period of four weeks. At the end of the exercise protocol (24 hours later), we analyzed the physiological parameters, mRNA levels, and protein content of key molecules in the control of gluconeogenesis and Notch1 signaling. We found that exercise reversed the physiological damage generated by obesity. In addition, trained animals showed a reduction in protein content and Notch1 activity when compared to the sedentary obese group. Furthermore, we observed reduction in pyruvate intolerance in exercised animals and a decrease in gluconeogenesis enzymes. Such findings were also observed in ob/ob mice submitted to physical exercise. Thus, we verified the physical exercise mice reduce Nocth1 activation and decrease PEPCK protein content. Finally, we found that inhibition of Notch1 activity decreases pyruvate intolerance as well as reduces the protein content of gluconeogenesis enzymes. Therefore, we concluded that physical exercise is able to modulate the Notch1 pathway in the liver and contribute to the gluconeogenesis control in obese mice.

Disclosure

R.C. Gaspar: None. V. Muñoz: None. S.C. Nakandakari: None. B.M. Crisol: None. R.F.L. Vieira: None. L.R. Conceição: None. A. Silva: None. D.E. Cintra: None. L.P. Moura: None. E.R. Ropelle: None. J.R. Pauli: None.

Funding

São Paulo Research Foundation (2019/11338-9, 2017/20542-3)
750-P: Characterizing Diabetes Distress in Adolescents with Type 1 Diabetes
Authors: CAO VIENA T. , ESHTEHARDI SAHAR S. , ANDERSON BARBARA , HILLIARD MARISA E.
Published: June 2020

Objective: Adolescents are often expected to take on more autonomy in their T1D management, which can increase diabetes distress. Elevated distress has been linked to suboptimal glycemic outcomes. Characterizing the aspects of diabetes distress that teens report as most difficult may help care teams address the most relevant psychosocial concerns during this challenging developmental stage.

Methods: We analyzed baseline data from two behavioral trials, totaling 135 adolescents (age 12-17) with T1D (M age=15.1±1.6, 57% female, 59% non-Hispanic White, M HbA1c=8.7±1.9). Youth completed the Problem Areas in Diabetes Teen scale, a measure of diabetes distress where teens rate how much each of 26 items is a problem for them (6-point scale, 5-6 represent a “serious problem”). We extracted HbA1c from the electronic medical record.

Results: The Table presents the frequency with which teens rated each item as “serious problem” and significant correlations with HbA1c.

Conclusion: A wide range of issues (20 of 26 items) were endorsed by ≥10% of teens as very distressing. At least 20% identified social issues and concerns about possible complications as problems causing serious distress. Items significantly linked to HbA1c were not necessarily those that teens found most distressing. Addressing teens’ most pressing concerns may help them feel understood, reduce self-management barriers, and ultimately improve quality of life and health.

Disclosure

V.T. Cao: None. S.S. Eshtehardi: None. B. Anderson: None. M.E. Hilliard: None.

Funding

National Institutes of Health (1R21DK107951); Texas Children’s Hospital; Caroline Weiss Law Fund for Research in Molecular Medicine
792-P: Understanding Barriers to Diabetic Foot Care in an Urban Low-Income Hospital: A Focus Group Qualitative Assessment
Authors: FAYFMAN MAYA , SCHECHTER MARCOS , AMOBI CHIMORA N. , WILLIAMS REBEKAH N. , HILLMAN JOANNA L. , RAJANI RAVI , ZIEMER DAVID C. , ALAM MUHAMMAD M. , KEMPKER RUSSELL , UMPIERREZ GUILLERMO E.
Published: June 2020

Diabetes is a leading cause of lower limb loss in the United States that disproportionately affects minority groups of lower socioeconomic status. The reasons for these disparities are poorly characterized. We employed qualitative (focus group discussions, FGD) and quantitative (survey) methods among persons with diabetic foot disease. Participants were stratified into two groups: a diabetic foot ulcer (DFU) group and minor amputation (ankle or below) group. The FGDs addressed patient experience with a goal of understanding: (1) foot care knowledge, (2) barriers to care, and (3) preferred foot-related educational methods. 5 sessions were conducted with 6-12 people each. Participants were recruited from clinics at a safety-net hospital in Atlanta that provides care to an inner-city population with a high burden diabetic foot related complications. Forty participants (90% Black) were enrolled. Surveys revealed an adequate knowledge of proper diabetic foot care, with ≥70% of participants correctly answering questions relating to proper self-care. Several dominant themes emerged from the FGDs. Personal barriers to self-care included lack of motivation, difficulty accessing supplies due to cost and/or lack of insurance, and being unable to limit activity for proper offloading. Participants frequently reported systematic barriers, citing difficulty making timely appointments and reaching a provider to arrange care. Participants reported that foot-related knowledge and access to care improved with greater disease severity but that knowledge and interventions seemed to come too late in their disease course. They expressed interest in peer support groups to facilitate learning and sharing information about diabetic foot care. These findings indicate patients with DFU or minor amputations in our institution have adequate footcare-related knowledge, but barriers to care and lack of motivation limit appropriate foot care.

Disclosure

M. Fayfman: None. M. Schechter: None. C.N. Amobi: None. R.N. Williams: None. J.L. Hillman: None. R. Rajani: None. D.C. Ziemer: None. M.M. Alam: None. R. Kempker: None. G.E. Umpierrez: None.
830-P: Screening for Depressive Symptoms in Adolescent Type 2 Diabetes Point to a Need for Improvement in Clinical Processes and Resources
Authors: STONE JENINE Y. , MULVANEY SHELAGH A. , MARA CONSTANCE A. , KICHLER JESSICA C. , MAJIDI SHIDEH , DRISCOLL KIMBERLY A. , WESTEN SARAH C. , RAWLINSON ALANA , JACOBSEN LAURA M. , HOOD KOREY K. , MONAGHAN MAUREEN , ADAMS REBECCA N.
Published: June 2020

Objective: To document rates of elevated depressive symptoms endorsed during routine screening for adolescents and young adults (AYA) with type 2 diabetes (T2D), review clinical actions taken in response to screening results, and evaluate associations of depressive symptoms with AYA characteristics.

Research Design and Methods: The Patient Health Questionnaire (PHQ) was administered to 218 AYA with T2D using the PHQ-2 or PHQ-9 in routine pediatric diabetes care at 4 academic medical centers. Data from electronic health records were collected from the screening date and 12 months prior.

Results: The mean age was 16.77 (SD 2.10 years); 56% male; 74% non-Hispanic White; Mean T2D duration 3.48 (SD 2.51 years). On the PHQ, 21.6% of AYA with T2D endorsed elevated depressive symptoms (PHQ score≥10) and 15.2% endorsed thoughts of self-harm. Older age, shorter T2D duration, not on insulin, and more blood glucose checks per day were significantly associated with more depressive symptoms. Of those AYAs endorsing the harm-to-self item, 8.3% were in mental health treatment. For AYAs expressing harm-to-self who were not in treatment (91.7%),18.2% did not have a documented referral for mental health treatment in the medical record.

Conclusions: Screening for depressive symptoms identifies individuals in need of referral for mental health treatment; however, a focus on self-harm assessment, standardized methods for documentation of symptoms, mental health referrals and increased referral resources are needed.

Disclosure

J.Y. Stone: None. S.A. Mulvaney: None. C.A. Mara: None. J.C. Kichler: None. S. Majidi: Advisory Panel; Self; Companion Medical. K.A. Driscoll: None. S.C. Westen: None. A. Rawlinson: None. L.M. Jacobsen: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. M. Monaghan: Research Support; Self; American Diabetes Association. R.N. Adams: Employee; Self; Virta Health Corp.

Funding

National Center for Advancing Translational Sciences (UL1TR002243, UL1TR001427)
834-P: Understanding Risks for Depressive Symptoms among Caregivers of Young Children Newly Diagnosed with T1D: The Role of Social Support and Social Problem-Solving
Authors: WANG CHRISTINE H. , SINISTERRA MANUELA , HERRERA NICOLE , TULLY CARRIE , CLARY LAUREN , MONAGHAN MAUREEN , HILLIARD MARISA E. , STREISAND RANDI
Published: June 2020

Introduction: Elevated depressive symptoms are common in caregivers following their children’s T1D diagnoses. In the general population, strong social support and social problem-solving abilities buffer depressive symptoms during stressful life events. To evaluate whether these constructs apply to diagnosis-related distress, we examined the associations among caregiver social support, social problem solving, and depressive symptoms after their children’s T1D diagnoses. We hypothesized that higher social support and higher social problem solving would be related to lower caregiver depressive symptoms.

Methods: Participants included 157 young children (M age=4.46±1.64 years) newly diagnosed with T1D (M days diagnosed = 28.78±15.10) and their primary caregivers (70% Caucasian, 74% married, 90% female) assessed at baseline of an ongoing behavioral RCT. Caregivers self-reported their social support (Protective Factors Survey (PFS)-Social Support), social problem solving abilities (Social Problem Solving Inventory- R:SF; SPSI), and depressive symptoms (Center for Epidemiological Studies-Depression Scale; CES-D).

Results: Overall, 46.5% of caregivers exceeded the clinical cut-off on the CES-D (M=16.60 (11.58)). Further, higher social support (B=-.235,-p=.004) and higher social problem solving abilities (B=-.317,-p<.001) were related to lower caregiver depressive symptoms, controlling for child age/sex, and presence of other caregivers (all p>.05). Higher negative (not positive) problem orientation was related to higher depressive symptoms (B=.373,-p<.001); problem solving styles were unrelated to depressive symptoms (p>.05).

Conclusions: Behavioral interventions focused on promoting positive social support and social problem solving abilities may decrease caregivers depressive symptoms after their children’s initial T1D diagnosis. Replication using longitudinal data is needed.

Disclosure

C.H. Wang: None. M. Sinisterra: None. N. Herrera: None. C. Tully: None. L. Clary: None. M. Monaghan: Research Support; Self; American Diabetes Association. M.E. Hilliard: None. R. Streisand: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102561)
854-P: Effective Use of Computerized Insulin Dose Adjustment Algorithms (CIDAA) on Continuous Glucose Monitoring (CGM) Results in Poorly Controlled Patients by a Clinical Pharmacist: A Proof-of-Concept Project
Authors: DAVIDSON MAYER B. , DAVIDSON JOSH
Published: June 2020

The largest challenge for appropriate adjustment of insulin doses for PCPs is lack of time and for patients is provision of enough blood glucose values. Potential solutions to these two issues are CIDAA for PCPs and CGM for patients. The combination of these two innovations was evaluated in a FQHC serving a poor, mostly minority, medically underserved population.

Poorly controlled diabetic patients (A1C levels >9.0%) are referred to a specially trained clinical pharmacist (CP). The pharmacy department supported CGM (Free Style Libre Pro) for 13 patients, 10 on basal insulin alone and 3 on basal/bolus who had ≥2 visits. Their downloaded CGM results were analyzed by FDA-cleared CIDAA and a report containing recommendations for dose adjustments that the CP could modify or accept was provided within 30 seconds. The mean number of reports was 4.8 which covered a period of 97 days. The glycemic responses are shown in the Table. Total insulin doses increased by 42%.

Conclusion: Analysis of CGM results by CIDAA addresses the two largest challenges of adjusting insulin doses for PCPs and patients. Using both together has the potential of markedly improving A1C levels in poorly controlled insulin-requiring diabetic patients.

Disclosure

M.B. Davidson: None. J. Davidson: Employee; Self; Mellitus Health.
856-P: Video Connect Clinic for Veterans Wearing Diabetes Technology
Authors: AMOLE MOROLAKE , WHYTE LOREN , GHAYEE HANS , LEEY JULIO A.
Published: June 2020

Background: Telehealth has been shown to be effective in the management of chronic disease. We describe our experience using Telehealth for patients wearing insulin pump or continuous glucose monitor (CGM).

Methods: In Sep 2019, a weekly VA video connect clinic (Diabetes VVC) was started for patients on insulin pump or CGM. The clinic is staffed by a registered dietitian, who is a certified diabetes educator and insulin pump trainer. Patients are seen in the telehealth clinic between face-to-face visits with endocrinologist. In these video visits, CGM and pump downloads were reviewed, and specialized diabetes education provided. Sometimes changes in management are suggested after discussion with endocrinologist.

In this retrospective study, several metrics were evaluated: travel distance, type of diabetes, type of insulin pump or CGM, medications, weight, height, BMI, time in rage 70-180mg/dL (when CGM was in use) and recommendations. We also assessed [U1] the number of interactions (visits) with the diabetes team.

Results: 34 patients participated in the VVC leading to 85 encounters. Most of them were males, 88% (30/30). The majority were on CGM alone (25/34) and remaining on CGM and insulin pump (9/34). Their A1c before the first VVC encounter was 8.7% +/-1.5. About 21/34 patients requested additional follow up via VVC appointments, leading to an average of 2.33 encounters during the 3 months study period. Distance travelled one way for face-to-face visit was estimated to be 74.2 miles +/-37.4. Changes in diabetes care was recommended for insulin dosing in 22% (19/85) of encounters. Adjustments in CGM/pump settings recommended in 18% (16/85) of encounters. Overall there were meaningful changes made to diabetes care in 41% of encounters.

Conclusions: The use of telehealth for diabetes care resulted in significant changes in diabetes therapy in a sizeable number of patients and saves time and travel distance. A telehealth clinic supports and enhances patient preference and experience.

Disclosure

M. Amole: None. L. Whyte: None. H. Ghayee: None. J.A. Leey: None.
859-P: Estimated A1C Reduction in High-Risk Patients over Two Years of Using a Digital Diabetes Management Platform
Authors: HERSHCOVITZ YIFAT , DAR SHARON , FENIGER EITAN
Published: June 2020

A Digital Diabetes management platform aims to improve diabetes self-management. Glycemic control is best evaluated by the combination of blood glucose average (BGavg) and A1c. Frequent fluctuation of blood glucose may contribute to diabetes-related complications. Long-term management of type 2 diabetes remains challenging to significant number of patients. This study followed glycemic parameters observed over 2-years.

Method: A retrospective data evaluation study was performed on high-risk users with type 2 diabetes that measured their blood glucose using Dario® platform database for two consecutive years. The study assessed BGavg, estimated A1c (eA1c) values and glycemic variability following 24 months compared to the first month (baseline).

Results: A group of 148 high-risk users with type 2 diabetes, non-Insulin treated was evaluated. Their BGavg was of >180mg/dL (eA1c>8.0) for users taking ∼2 blood glucose measurements per day in the first month and in the 24th month on average. Their BGavg was consistently reduced by 18% and sustained (179±45 vs. 219±56 mg/dL) and eA1c was reduced by 1.5 percentage points (9.26±1.3 vs. 7.86±1.8). Glycemic variability was reduced by 20% (SD: 45 vs. 56) at the end of 2 years. Additional analysis of 220 users with type 2 diabetes,147 started with eA1c >9.0% and 73 started with eA1c >10%, revealed substantial eA1c reduction of 2.0 percentage points (10.31 ± 1.8% vs. 8.36 ± 1.2%) and 2.4 percentage points (11.15 ± 1.2% vs. 8.73% ± 2.1%) from baseline after 2 years, respectively. Glycemic variability was reduced by 20% for both (SD: 55 vs. 69 and 59 vs. 74, respectively).

Conclusion: Overall this study confirms the potential of digital diabetes solutions to sustain glycemic achievements in users with type 2 diabetes over two years. The system may assist the users to experience an actual behavior modification in their diabetes self-management as well as in their long-term routine for self-care.

Disclosure

Y. Hershcovitz: Employee; Self; DarioHealth. S. Dar: Employee; Self; DarioHealth. E. Feniger: Employee; Self; DarioHealth.
902-P: Introducing Continuous Glucose Monitoring Technology at Diagnosis in Pediatric Type 1 Diabetes: A Proof-of-Concept Study
Authors: HIERS PAUL , ADAMS JANEY , FILIPP STEPHANIE L. , HALLER MICHAEL J.
Published: June 2020

Diabetes technology is changing and integral for diabetes care. Our hypothesis is patients who start using continuous glucose monitoring (CGM) technology at diagnosis will have better clinical outcomes and higher levels of satisfaction and lower levels of burden than patients who initiate CGM therapy later in the course of their disease management.

Methods: This quality improvement study offered Freestyle Libre CGM to all patients newly diagnosed with T1D. The primary outcome was improvement in self-reported treatment satisfaction as measured by the Diabetes Treatment Satisfaction Questionnaire-Parent (DTSQ-P). Secondary outcomes included adolescent treatment satisfaction, fear of hypoglycemia, diabetes distress, burden, and QOL. Measures were given at baseline and 3 months. Data for participants was compared with retrospective data from age-matched controls who did not receive a Libre at diagnosis.

Results: 26 parent-child dyads between the ages of 4-17 years old participated in the study. Preliminary results showed improved DTSQ-parents scores 47.1 ± 8.0 to 50 ± 9.9 over the 3 month study. Please see tables for parent and child version of DTSQ- DDS, PedQL, FOH, PAID results.

Conclusions: There were trends towards improved satisfaction and QOL scores. This shows supportive data for improved quality and satisfaction measures in using CGM technology starting at diagnosis.

Disclosure

P. Hiers: None. J. Adams: None. S.L. Filipp: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc.

Funding

Diabetes Action Research and Education Foundation (468)
92-OR: EMC10, a Novel Serum Predictor for Coronary Artery Disease, Exerts an Impact on the Development of Atherosclerosis via Negatively Modulating Endothelial Insulin Signaling
Authors: JING YU , WANG XINRU , YU YIFEI , CHEN KUANGYANG , JIN SHUOSHUO , LI YANLIANG , WANG XUANCHUN
Published: June 2020

Cardiovascular disease is the leading cause of global mortality, accounting for about one third of deaths worldwide. Secreted proteins from metabolically regulated organs are released into circulation and exert impacts on the pathogenesis of cardiovascular disease. In this study, we identified a novel secreted protein, EMC10, that might influence the development of atherosclerosis. We initially observed that serum EMC10 is significantly decreased in patients with coronary artery diseases evidenced by coronary artery stenosis over 50 percent, compared with those suffering stenosis less than 50%. In addition, we found that the levels of serum Emc10 are even lower in patients who meanwhile suffered from hypertension. After adjusted for age, BMI, hypertension, and diabetes, the regression analysis revealed that serum EMC10 is an independent predictor for coronary artery diseases. To determine the role of EMC10 in cardiovascular disease, we established Emc10 whole body knockout mice and found that both the systolic and diastolic blood pressure are significantly decreased in EMC10 KO mice in comparison to wild type ones. Furthermore, in vitro experiments showed that EMC10 significantly decreases the insulin-stimulated phosphorylations of both Akt and eNOS, and conversely, significantly increases VCAM-1 mRNA in endothelial cells. Collectively, these preliminary data suggest EMC10 leads to endothelial insulin resistance and plays a role in the development of atherosclerosis, by which EMC10 is involved in the pathogenesis of cardiovascular disease. Our findings establish Emc10 as a novel modulator of endothelial insulin signaling and a potential target for the intervention of diabetic vascular diseases.

Disclosure

Y. Jing: None. X. Wang: None. Y. Yu: None. K. Chen: None. S. Jin: None. Y. Li: None. X. Wang: None.

Funding

National Natural Science Foundation of China (81370936); Science and Technology Commission of Shanghai Municipality (18140902100)
925-P: Risk of Cardiovascular Events and Serious Hypoglycemia Comparing Patients with Type 2 Diabetes Initiating a GLP-1 Receptor Agonist or Basal Insulin: A Propensity-Score Matched Cohort Study
Authors: LUO JING , PAWAR AJINKYA , WEXLER DEBORAH J. , KIM DAE H. , KIM SEOYOUNG C. , PATORNO ELISABETTA
Published: June 2020

Prior head-to-head open label trials comparing selected GLP-1RA(s) versus basal insulin(s) did not evaluate cardiovascular outcomes. Using 2 large U.S. commercial claims databases (Optum and Truven MarketScan) from 01/2012 to 12/2017, we assessed the risk of a composite cardiovascular outcome (MI, stroke) and serious hypoglycemia defined by validated claims-based algorithms comparing 26,308 patients with type 2 diabetes (mean age 58, mean HbA1c 8.6%) with prior or concurrent metformin therapy newly initiating an injectable GLP-1RA or basal insulin (Table). We estimated pooled incidence rates, meta-analyzed hazard ratios and 95% CI adjusting for >140 baseline clinical characteristics, including HbA1c. Baseline clinical characteristics were well-balanced in the two groups after 1:1 propensity score matching. In an as-treated analysis, the median follow-up was 148 days. Compared to basal insulin, initiating a GLP-1RA was associated with a lower risk of MI or stroke (HR 0.68 [95% confident interval (CI), 0.51 to 0.90]) and lower risk of serious hypoglycemia (HR 0.38 [95% CI, 0.25 to 0.57]). These results support recent clinical treatment guidelines that recommend starting a GLP-1RA before basal insulin for patients with type 2 diabetes with inadequate glycemic control despite metformin.

Disclosure

J. Luo: Consultant; Self; Alosa Health. A. Pawar: None. D.J. Wexler: Other Relationship; Self; Novo Nordisk A/S. D.H. Kim: None. S.C. Kim: Research Support; Self; AbbVie Inc., Bristol-Myers Squibb. E. Patorno: Other Relationship; Self; Boehringer Ingelheim International GmbH.

Funding

Brigham and Women’s Hospital
928-P: Dulaglutide Has Higher Adherence and Persistence than Semaglutide and Exenatide QW: 6-Month Follow-Up from U.S. Real-World Data
Authors: MODY REEMA , YU MARIA , NEPAL BAL K. , KONIG MANIGE , GRABNER MICHAEL
Published: June 2020

The objective of this retrospective real-world observational study was to compare 6-month (mo) adherence and persistence among patients (pts) initiating weekly GLP-1 receptor agonists (GLP-1RA), dulaglutide (DU) vs. semaglutide (SEMA) or DU vs. exenatide QW (EQW) BCise pen in the U.S., using claims from the HealthCore Integrated Research Database (HIRD®) between August 2017 and June 2019 (index date=earliest GLP-1RA fill date). Pts ≥18 yrs old, with T2D, no claim for GLP-1 RAs in the 6 mos pre-index period, ≥1 claim for DU, SEMA or EQW during the index period, and continuous enrollment 6 mos pre- and post-index were included. DU users were propensity-matched 1:1 to SEMA (3,852 pairs) or EQW (1,879 pairs) users. Matched cohorts (DU:SEMA/DU:EQW) were balanced in baseline characteristics and the mean age was 54/55 years with approximately 49/51% males, respectively. At 6 mos, DU users were more likely to be adherent [Proportion of Days Covered (PDC)≥80%] than SEMA (odds ratio [OR]=1.986, 95% CI=[1.81, 2.18]) or EQW users (2.06 [1.81, 2.34]) (table). Cox regression showed that DU users were less likely to discontinue therapy than SEMA (hazard ratio [HR]= 0.71, 95% CI=[0.66, 0.76]) or EQW users (0.59 [0.53, 0.65]) (table). At 6-mos follow-up, pts initiating DU had higher medication adherence, and were more persistent to their treatment, compared to pts initiating either SEMA or EQW.

Disclosure

R. Mody: Employee; Self; Eli Lilly and Company. M. Yu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; LifeLabs. Stock/Shareholder; Self; Eli Lilly and Company. B.K. Nepal: None. M. Konig: Employee; Self; Eli Lilly and Company. M. Grabner: Research Support; Self; Eli Lilly and Company.
945-P: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Cohort Study to Evaluate the Efficacy and Safety of 12 Once-Weekly Subcutaneous Doses of PB-119 to Patients with Type 2 Diabetes Mellitus as Monotherapy
Authors: XU MIN ,   PEGBIO STUDY GROUP
Published: June 2020

Background: PB119 (polyethylene glycol exenatide) which is a novel once-weekly subcutaneous GLP-1RA, has good pharmacokinetic properties. As a GLP-1RA, it shows a good safety profile and provides solid glycemic control while doesn’t need dose titration. We aimed to assess the efficacy and safety of PB119 monotherapy in Chinese patients with T2DM.

Methods: In this phase 2 study, we randomly assigned 251 patients (1:1:1:1) to receive 3 doses of PB119 (75ug, 150ug, 200ug) or dose-matched placebo using permuted-block randomization, with a block size of 12 and without stratification. Eligible patients were men or women (aged 18-70 years) with T2DM who had a BMI of 18.5-35.0 kg/m², were on a diet and exercise regimen and untreated at least 3 months prior to screening. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least 1 dose of study drug and had both baseline and at least 1 post-baseline HbA1c value. Safety was assessed in all patients who received at least 1 dose of study drug. ClinicalTrials.gov NCT03520972.

Findings: At the end of week 12, the least squares mean change in HbA1c from baseline was -0.39% (95% CI -0.60 to -0.19) in the placebo group, -1.11% (-1.32 to -0.91) in the 75ug group, -1.57% (-1.78 to -1.37) in the 150ug group and -1.41% (-1.61 to -1.20) in the 200ug group. Compared with the placebo group, the change in HbA1c between baseline and week 12 was significant in all PB119 (p<0.001) groups. Significant reductions in TC and TG were observed in 150ug and 200ug groups (P<0.05), while the reductions in body weight and LDL-C were significant in 200ug group (P<0.05). There were no reports of drug-related serious adverse events or severe hypoglycemia.

Disclosure

M. Xu: None.
946-P: The GLP-1 Receptor Agonist GL0034 Activates Central Regions Controlling Glucose Homeostasis and Feeding Behavior
Authors: PICARD ALEXANDRE , TARUSSIO DAVID , THENNATI RAJAMANNAR , BURADE VINOD S. , THORENS BERNARD
Published: June 2020

Background: GL0034 is a novel glucagon-like peptide-1 receptor (GLP-1R) agonist showing glucose-lowering effects with increased insulin and C-peptide levels, reduced plasma glucagon levels, long-term reduction in HbA1C, and reduced body weight when tested in type 2 diabetic mice. At equivalent doses, these effects were significantly higher than those obtained with other GLP-1R agonists used clinically. We evaluated whether GL0034 administration activated brain regions involved in the control of energy homeostasis, which could explain the beneficial effects of this agonist.

Methods: C57BL/6 mice received SC injections of saline, GL0034 (12 or 24 nmol/kg), or semaglutide (12 or 24 nmol/kg). The mice were euthanized 2 hours after dosing and their brains were fixed with paraformaldehyde. Cryosections were prepared from the entire brain; c-fos expression was assessed by immunohistochemistry.

Results: We observed induction of c-fos expression in response to GL0034 SC injections in the area postrema and the nucleus tractus solitarius of the dorsal vagal complex and in the parabrachial nucleus and locus coeruleus. Lower levels of c-fos expression were detected in the central amygdala, subfornical organ, vascular organ of the lamina terminalis, and ventromedial preoptic nucleus. No significant staining could be observed in the hypothalamus, including the arcuate nucleus and the dorsomedial hypothalamus. These results were qualitatively comparable after GL0034 and semaglutide SC injections.

Conclusion: These results indicate that SC injection of GL0034 activates several central brain regions, which control energy homeostasis through regulation of autonomic nervous activity and feeding behavior, potentially impacting food preference and motivated feeding behavior. These central effects may combine with the direct stimulation of pancreatic beta cells and insulin secretion by GL0034 to ensure efficient control of glucose homeostasis.

Disclosure

A. Picard: None. D. Tarussio: None. R. Thennati: None. V.S. Burade: Employee; Self; Sun Pharmaceutical Industries Ltd. B. Thorens: Other Relationship; Self; Servier.
954-P: GLP-1–Experienced Patients Switching to Once-Weekly Semaglutide in a Real-World Setting (EXPERT Study)
Authors: LINGVAY ILDIKO , KIRK ANDREAS ROSS , LOPHAVEN SØREN , WOLDEN MICHAEL L. , SHUBROOK JAY H.
Published: June 2020

Introduction: The effect of once-weekly (OW) subcutaneous semaglutide, a glucagon-like peptide-1 (GLP-1) analog for the treatment of T2D, has been examined in GLP-1-naïve patients only. Here, we examined glycemic control and weight management in GLP-1-experienced patients switching from another GLP-1 to semaglutide in a real-world setting, using U.S. prescription data.

Methods: Adults (≥18 years old) with T2D were identified in the Explorys (IBM Watson Health) U.S. electronic medical records database (data cut-off 12/5/19). Included patients had ≥1 prescription for semaglutide (index/switch date), a prescription for any other GLP-1 (baseline) in the previous year, and separate HbA1c/weight measurements at 6 or 12 months post-index and in the 90-day pre-index period.

Results: Patients with valid HbA1c (N=365) and weight (N=480) data had similar baseline characteristics. Both the full 6-month cohorts and subgroups with 12-month data had significant HbA1c and weight reductions (Figure). Significant HbA1c improvement at 6 months was sustained at 12 months, whereas weight loss was more pronounced with longer follow-up. HbA1c and weight changes were independent of previous GLP-1 used (p>0.05 between GLP-1s).

Conclusions: Switching to OW semaglutide from another GLP-1 was associated with significant HbA1c and weight reductions in routine clinical practice, independent of previous GLP-1 used.

Disclosure

I. Lingvay: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk A/S, Sanofi, TARGET PharmaSolutions, Valeritas, Inc. Other Relationship; Self; Novo Nordisk A/S. A. Kirk: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. S. Lophaven: Consultant; Self; Novo Nordisk A/S. M.L. Wolden: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.H. Shubrook: Advisory Panel; Self; Bayer U.S., Eli Lilly and Company, Novo Nordisk Inc., Sanofi US.

Funding

Novo Nordisk A/S
976-P: Evaluation of Hybrid Closed-Loop Insulin Delivery System for Patients with Type 1 Diabetes in Real-World Clinical Practice: A One-Year Qualitative Observational Study
Authors: ELDIB AHMED H. , TOMAH SHAHEEN , DHAVER SHILTON E. , GARDNER HANNAH , TASABEHJI MHD WAEL , ALBADRI MARWA , ATAKOV-CASTILLO ASTRID , TOSCHI ELENA , HAMDY OSAMA
Published: June 2020

The MiniMed™ 670G (670G) is the first FDA approved hybrid closed-loop insulin delivery system for patients with type 1 diabetes (T1D). In Auto Mode, the integrated continuous glucose monitor (CGM) captures glucose values every five minutes and, via a built-in algorithm, the 670G system automatically adjusts basal insulin delivery targeting a glucose value of 120 mg/dL. Impact of the use of 670G system on patient reported outcomes in people with T1D are limited. Data over one year of use in real world-clinical practice were collected. We evaluated 53 patients with T1D (mean age 46.8±11.8 years, 62% females, body weight 82.5±17.6 kg, BMI 28.7±5.5, HbA1c 7.6±0.8%) who started 670G at the Joslin Clinic between December 2017 and December 2019. Data were collected at baseline and after 12 months. We assessed SROs by administering surveys: 36 Item Short-Form Health Survey (SF 36), Pittsburgh Sleep Quality Index (PSQI), and hypoglycemia fear survey/worry scale (HFS_W). We also measured HbA1c, % time-in-range at baseline and 12 months, and % time in auto mode (TiAM) for the two weeks preceding the final study visit. At 12 months, A1C decreased by 0.3±0.1% from baseline (p<0.01) and % time-in-range increased by 7.9±3.1% from baseline (p=0.015) with no correlation between either of them and %TiAM (p=0.3, p=0.2 respectively). Physical functioning increased by 47.5% from baseline (p<0.001), and HFS_W improved significantly by -16.0% from baseline (p=0.017). At 12 months, average %TiAM was 60.4±33.7% and was not associated with clinical outcomes or SROs. We conclude that use of 670G for a year in real-world clinical practice was associated with significant improvement in A1C, % time-in-range, physical functioning and hypoglycemia fear. Neither of these improvements at 12 months was related to %TiAM.

Disclosure

A.H. Eldib: None. S. Tomah: Stock/Shareholder; Self; Amarin Corporation. S.E. Dhaver: None. H. Gardner: None. M. Tasabehji: None. M. Albadri: None. A. Atakov-Castillo: None. E. Toschi: None. O. Hamdy: Consultant; Self; Abbott, AstraZeneca, Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Healthimation, LLC.
Individual and Combined Associations of Modifiable Lifestyle and Metabolic Health Status With New-Onset Diabetes and Major Cardiovascular Events: The China Cardiometabolic Disease and Cancer Cohort (4C) Study
Authors: Li Mian , Xu Yu , Wan Qin , Shen Feixia , Xu Min , Zhao Zhiyun , Lu Jieli , Gao Zhengnan , Chen Gang , Wang Tiange , Xu Yiping , Zhao Jiajun , Chen Lulu , Shi Lixin , Hu Ruying , Ye Zhen , Tang Xulei , Su Qing , Qin Guijun , Wang Guixia , Luo Zuojie , Qin Yingfen , Huo Yanan , Li Qiang , Zhang Yinfei , Chen Yuhong , Liu Chao , Mu Yiming , Wang Youmin , Wu Shengli , Yang Tao , Chen Li , Yu Xuefeng , Yan Li , Deng Huacong , Ning Guang , Bi Yufang , Wang Weiqing
Published: June 2020

OBJECTIVE

We aimed to determine the individual and combined associations of lifestyle and metabolic factors with new-onset diabetes and major cardiovascular events among a Chinese population aged ≥40 years.

RESEARCH DESIGN AND METHODS

Baseline lifestyle information, waist circumference, blood pressure, lipid profiles, and glycemic status were obtained in a nationwide, multicenter, prospective study of 170,240 participants. During the up to 5 years of follow-up, we detected 7,847 individuals with new-onset diabetes according to the American Diabetes Association 2010 criteria and 3,520 cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure.

RESULTS

On the basis of 36.13% (population-attributable fraction [PAF]) risk attributed to metabolic risk components collectively, physical inactivity (8.59%), sedentary behavior (6.35%), and unhealthy diet (4.47%) moderately contributed to incident diabetes. Physical inactivity (13.34%), unhealthy diet (8.70%), and current smoking (3.38%) significantly contributed to the risk of major cardiovascular events, on the basis of 37.42% PAF attributed to a cluster of metabolic risk factors. Significant associations of lifestyle health status with diabetes and cardiovascular events were found across all metabolic health categories. Risks of new-onset diabetes and major cardiovascular events increased simultaneously according to the worsening of lifestyle and metabolic health status.

CONCLUSIONS

We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health, highlighting the importance of lifestyle modification regardless of the present metabolic status.
Síndrome de Crouzon clásico y síndrome de Crouzon asociado a Acantosis Aigricans: reporte clínico familiar
Authors: Loor Morán Yaira Yvette , Briones Andriuoli Rebeca Ruth , Echeverría Lolín Indrid Mayumi , Córdova Alcívar Gabriel Eduardo , Moncayo Hinojosa María Paola
Published: June 2020

El síndrome de Crouzon es una anomalía o defecto congénito de patrón hereditario autosómico dominante caracterizado por el cierre prematuro de las suturas craneales, cuyas alteraciones darán como resultado cambios morfológicos en cráneo y cara. La mutación se origina en el brazo largo del cromosoma 10, que genera un cambio en el gen FGFR2 y, en caso de estar asociado a acantosis nigricans, la mutación se localiza en el FGFR3 con afección del brazo corto del cromosoma 4. Se reportan cuatro casos clínicos con dichas patologías dentro de un linaje familiar.
Pengaruh Pengembangan Karir, Motivasi Kerja Dan Pemberian Kompensasi Terhadap Loyalitas Kerja Karyawan (Studi Kasus Pada Karyawan PT. Tribun Berita Online)
Authors: Willy Rizky Utami Vivilia Aninditya Vrisna , Dwiatmadja Christantius
Published: June 2020

This study aims to determine the effect of career development variables, work motivation and compensation in PT. Tribun Berita Online partial and simultant on the level of employee loyalty. This research has three hypotheses tested that will be explained, where the three hypotheses will be explained partial tested. This study uses a statistical analysis using the IBM SPSS Statistics Application 23. The data of the research respondents were obtained as many as 62 respondents using the characteristics of regular employee with more than 2 years (> 2 years). The results of this study simultant there is an influence between career development, work motivation and compensation for employee loyalty at PT. Tribun Berita Online. However, only partial tested career development variables have a positive effect on employee work loyalty, but work motivation and compensation don’t have a partial tested effect on work loyalty.
PENGARUH LAMA PERENDAMAN PANGKAL SETEK DALAM LARUTAN NAA (NAPTHALENE ACETIC ACID) PADA PERTUMBUHAN SETEK LADA
Authors: Nisa Syaicha Fachrun , Nurmauli Niar , Edy Akari , Sugiatno Sugiatno
Published: June 2020

Effect of soaking duration on base stem cuttings in NAA solution (Naphthalene Acetic Acid) on the growth of pepper The need for pepper is increasing along with the development of the food industry with the basic ingredients of pepper. The determining factor of the quality of pepper produced comes from the seeds used. This study aims to determine the effect of soaking DURATION on pepper cuttings (Piper nigrum L.) in the Napthaleneacetic Acid (NAA) solution. The study was conducted in October 2018 until February 2019 in the greenhouse and Plant Science Laboratory of the Faculty of Agriculture, University of Lampung, Bandar Lampung. This study uses a completely randomized group design (RKTS). The treatment of immersion base cuttings in NAA (N) solution concentrates 500 ppm consisting of : without NAA (n0), immersion 0 minutes (n1), soaked 15 minutes (n2), soaked 30 minutes (n3), soaked 60 minutes (n4), and soaked 120 minutes (n5). Homogeneity of variability between treatments was tested by Bartlet Test and data additivity was tested by Tukey test, then continued with Variance Analysis (ANARA). Comparison of the middle value with the orthogonal comparison test at α level of 5%. The results showed that: (1) giving NAA affected the number of roots in the book, the fresh weight of the roots in the book, the dry weight of the roots in the book, the total number of roots, and the total fresh weight of the roots; (2) administration of NAA by immersion is better than dipping in the number of roots in the book, the fresh weight of the roots in the book, the dry weight of the roots in the book, the total number of roots, and the total fresh weight of the roots; and (3) length of soaking cuttings in NAA solution has no effect on the growth of pepper cuttings.