bluuebunny/crossref_metadata_2025 huggingface dataset:
578-P: Impact of COVID-19 on Diabetes Self-Management and Care
Authors: ZUPA MARGARET , PEREZ STEPHANIE , PALMISANO GLORIA , KIEFFER EDITH C. , PIATT GRETCHEN , VALBUENA FELIX , DEVERTS DENISE J. , YABES JONATHAN , HEISLER MICHELE , ROSLAND ANN-MARIE
Published: June 2021

Stay at home orders, changes in business and clinic operations, and financial concerns related to the COVID-19 pandemic may have affected how adults with diabetes obtained food, medications, medical care, and performed diabetes self-management. These impacts may be most pronounced among people in low-resource urban communities. We assessed the experiences of adults with type 2 diabetes participating in a federally-qualified health center diabetes management program. Of 72 patients called, 61 completed telephone surveys from July to October 2020 in Spanish and English. 74% of respondents were Latino with Spanish as their preferred language. Respondents’ mean age was 54 years, 62% were female, and 57% had less than a high school degree. Five patients reported testing positive for COVID-19, and 7 lived with someone who tested positive. Of 33 respondents who worked outside the home before COVID-19, 61% had lost their jobs or now worked fewer hours. When asked how diabetes management behaviors changed during the pandemic, 53% of respondents reported less physical activity, while 25% reported more. 18% reported eating less healthfully, while 38% reported eating more healthfully. 43% found it more difficult to obtain healthy food. 15% reported taking their medications more regularly, while 5% reported less. 61% reported increased difficulty accessing medical care. 41% felt more worried about being able to manage their diabetes during the pandemic and 49% felt more socially isolated. Changes in diabetes self-management behaviors related to COVID-19 were both positive and negative for patients in this low-resource urban setting. Programs supporting patients with diabetes could help patients adapt to pandemic changes by facilitating access to medications and health care, providing virtual support for self-management and other health habits, connecting patients with financial and food security concerns to community resources, and addressing stress and social isolation through virtual diabetes support groups.

Disclosure

M. Zupa: None. A. Rosland: None. S. Perez: None. G. Palmisano: None. E. C. Kieffer: None. G. Piatt: None. F. Valbuena: None. D. J. Deverts: None. J. Yabes: None. M. Heisler: None.

Funding

National Institutes of Health (R01DK116733)
585-P: Buffering Effects of Subjective SES on Parental Depressive Symptoms following Child T1D Diagnosis
Authors: WANG CHRISTINE H. , TULLY CARRIE , MONAGHAN MAUREEN , HILLIARD MARISA E. , STREISAND RANDI
Published: June 2021

Introduction: Parent depression is linked to negative child T1D outcomes. Some studies find that subjective (SSES) and objective socioeconomic status (OSES) are uniquely related to depressive symptoms, but few studies have examined them together in a T1D population. The current study explores the associations among SSES, OSES, and parent mood following child T1D diagnosis.

Method: Participants included 157 parents (62% non-Hispanic white, 77% married, 92% female, 28% public insurance) of young children (Mage=4.46±1.64 years) newly diagnosed (M=29 days post-diagnosis) with T1D. At baseline of a behavioral RCT, parents self-reported on their depressive symptoms (Center for Epidemiological Studies-Depression Scale; CES-D; ≥16=elevated scores), SSES (The MacArthur Scale of Subjective Social Status), and OSES (lower OSES=public insurance; higher OSES=private insurance). χ2 test of independence was used to compare rates of elevated CES-D scores across four OSES/SSES categories (n, % elevated): both lower (n=14; 79%), lower OSES/higher SSES(n=29; 31%), higher OSES/lower SSES(n=49; 48%), and both higher (n=63; 44%).

Results: There was a significant association between OSES/SSES category and parent depressive symptoms, χ2(3, N=153)=8.81, p=.03. Post hoc analyses using Bonferroni corrections indicated one significant group difference: the lower OSES/higher SSES group had significantly lower rates of elevated CES-D scores than the both lower group.

Discussion: During the stressful period following a young child’s T1D diagnosis, higher perceived SES, relative to one’s peers, may be a protective factor against depressive symptoms, specifically for parents with public insurance. Despite having fewer financial resources, these parents reported depressive symptoms similar to parents with private insurance. Future studies using a positive psychology framework may examine methods to improve subjective well-being in parents of children with T1D.

Disclosure

C. H. Wang: None. C. Tully: None. M. Monaghan: None. M. E. Hilliard: None. R. Streisand: None.

Funding

National Institute of Diabetes and Digestive and Kidney Disease (R01DK102561)
587-P: Adherence, Acceptability, and Feasibility of Mobile Ecological Momentary Assessments (mEMA) in Young Adults (YA) with Type 1 Diabetes (T1D) of Racial-Ethnic Minority Status
Authors: LEUNG STEPHANIE , CRESPO-RAMOS GLADYS , FINNAN MOLLY , GONZALEZ JEFFREY S. , AGARWAL SHIVANI
Published: June 2021

Background: YA with T1D of racial-ethnic minority disproportionately experience stress related to social determinants of health (SDOH), which may be associated with hyperglycemia, glycemic variability, and poorer emotional well-being. Mobile EMA methodology uses mobile technology to assess contextually relevant, real-time behavioral and self-report data.

Methods: Coupled with real-time CGM for two weeks, we employed mEMA methodology with three times daily cell phone-delivered surveys to study the association of momentary variations in SDOH-related stress with glycemia in YA with T1D from the Bronx, NY. We report our preliminary findings on acceptability, feasibility, and adherence of mEMA methodology in this ongoing study. We evaluated adherence by real-time app tracking of mEMA survey completion, and evaluated acceptability and feasibility by post-study questionnaires and qualitative interviews.

Results: Thus far, 18 participants have completed the study: (mean age 23 yrs, 11 Hispanic, 7 non-Hispanic Black, mean HbA1c 8.0%). Adherence to assigned daily surveys was high at 85% (753/887 surveys). There were no differences in survey adherence across timepoints. Acceptability was high: participants reported good understanding of mEMA procedures (mean score 4/5 on Likert scale), high satisfaction (mean score 5/5), high willingness to participate again (mean score 5/5), and were very likely to recommend participation to others (mean score 5/5). For feasibility, the most common barrier cited was mEMA app issues (40%, n=7), specifically dropped survey notifications, which interfered with adherence.

Conclusions: YA with T1D of racial-ethnic minority demonstrated high adherence, feasibility, and acceptability of mEMA methods, however there were app-related issues that need closer monitoring. mEMA is a viable tool to study real-time contextual and behavioral factors in minority YA with T1D.

Disclosure

S. Leung: None. G. Crespo-ramos: None. M. Finnan: None. J. S. Gonzalez: None. S. Agarwal: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (5P30DK111022, K23DK115896)
603-P: The Effect of Different Frequency of Autonomous Flash Glucose Monitoring Application on Blood Glucose Control in Patients with Type 1 Diabetes under 14 Years Old
Authors: HU KEYAN , JIANG HONGWEI , ZHANG WINNIE , PENG HUIFANG , LIU JING
Published: June 2021

Objective: To explore the influence of different self-wearing frequency of Flash Glucose Monitoring System (FGMS) on the blood glucose control of children with type 1 diabetes (T1DM), and to analyze the factors that affect the frequency of instrument wearing.

Method: A total of 89 children with T1DM under the age of 14 were recruited. Collect clinical data, baseline indicators and wear FGMS for 2 weeks continuously. The above children were followed up after 3 years, and FGMS was worn again for 2 weeks, the baseline indicators were rechecked, and filled out relevant questionnaires. The children were divided into low-frequency wearing group and high-frequency wearing group according to the frequency of autonomous application of FGMS during follow-up.

Result: The average glucose level and the percentage of time above range in the low-frequency wear group were higher than those in the baseline period (9.05±2.02% vs. 8.63±1.71%, p=0.042;36.52±17.38% vs. 31.16±15.16%, p=0.047) while the time in range is significantly lower (53.23±14.34% vs. 59.94±14.54%, p=0.001). The average blood glucose fluctuation amplitude of the high frequency wearing group improved compared with the previous [8.80 (7.21, 12.09) mmol/L vs. 9.68 (7.65, 12.00) mmol/L, p=0.027]. The results of multivariate logistic regression analysis showed that the guardian's educational background (OR=3.162, 95%CI: 1.024-9.764) and the guardian's attention to the child's blood glucose (OR=2.537, 95%CI: 1.074-5.997) are the frequency of voluntary FGM wearing Independent influencing factors (P<0.05).

Conclusion: Higher frequency application of FGM can significantly improve blood glucose fluctuations and delay the deterioration of the disease. The educational background of the guardian and degree of attention to the condition are the main influencing factors of high frequency wearing FGM.

Disclosure

K. Hu: None. H. Jiang: None. W. Zhang: None. H. Peng: None. J. Liu: None.
605-P: Generating Self-Reported Clinical and Lifestyle Data in Patients Living with T2DM in Qatar
Authors: JANDALI NOOR , ZARZOUR RACHA , FADLELBARI AYMAN M.
Published: June 2021

Background: Lack of localized tools to monitor lifestyle patient data between doctor visits challenges healthcare providers in the Middle East to personalize care to Arabic-speaking patients living with T2DM. This study presents Droobi Health (DH), the first Arabic, digital therapeutic, as an effective tool to increase patient self-reported data and share clinical and lifestyle data between visits efficiently to enable doctors to personalize care without a time burden.

Methods: The Droobi Health app is a digital therapeutic that delivers a online behavior change programs that combines real-human coaching, digital tracking and data analytics to deliver timely and personalized interventions for behavior change. The messaging system is based on the Transtheoretical Model of Behavior Change to encourage users to self-report data on blood glucose, weight, food intake and physical activity. This study described data collected from participants with T2DM (N=44) using DH who completed the 16-week program.

Results: During the 16-weeks, users reported a total 1270 blood sugar logs, 1527 food logs, 3202 activity logs, and 213 weight logs. Users initiated a total of 2880 chat messages with their coach. On average per user, 28.8 blood sugar logs, 34.7 food logs, 72.8 activity logs, and 4.8 weight logs.

Conclusion: This study shows that DH can help healthcare providers generate patient self-reported clinical and lifestyle data between doctor visits, enabling the care team to personalize care based on patients lifestyle.

Disclosure

N. Jandali: None. R. Zarzour: Employee; Self; Droobi Health Technology. A. M. Fadlelbari: Employee; Self; Droobi Health and Technology.
608-P: Relationship between Time-in-Range and Estimated HbA1c Derived from Continuous Glucose Monitoring System in Adults with Type 1 Diabetes Mellitus
Authors: ZHOU YONGWEN , LIU HONGXIA , YANG DAIZHI , AI HEYING , LV JING , MAI XIAODONG , XU WEN , YAO BIN , YAN JINHUA , WENG JIANPING
Published: June 2021

Aims: Time-in-range (TIR) and estimated glycated hemoglobin (eHbA1c), two key metrics derived from continuous glucose monitoring system (CGMS), are valuable for glycemic control. This study is to investigate the relationship between TIR and eHbA1c, and the impact of glycemic variability on their relationship.

Methods: The CGMS data were collected from baseline and follow-up visits in a clinical trial (NCT03522870) and yearly visits in the Guangdong Type 1 Diabetes Translational Medicine Study. Adult patients with type 1 diabetes (≥18 yrs) who had available CGM data for > 3 days were included. Correlation between TIR and eHbA1c was explored according to different stratification of glycemic variability assessed by glucose coefficient of variation (CV). Predicted TIR in the fixed eHbA1c value was calculated via the linear regression equations performed in the respective interquartile group of CV.

Results: From March 2014 to July 2020, a total of 260 CGMS data were collected. The mean wearing time of available CGM data was 11.8±3.8 days, and the mean value of TIR, eHbA1c, and CV was 62.9±14.1%, 7.2±0.8%, and 39.4±8.1%, respectively. There was a strong negative correlation between TIR and eHbA1c (R=-0.83, P<0.001). For patients with stable glycemic variability (CV<36%), the correlation between the two metrics was stronger (R=-0.95) while in the unstable group the coefficient was decreased (R=-0.80). Based on the regression equations, the predicted %TIR value was decreased across the ascending quartiles with 73.0% in the lowest quartile of CV (<25th quartile, <33.8%), 67.4% in 25th - 50th quartile (33.8-39.2%), 61.4% in 50th - 75th quartile (39.2-44.9%) and 58.5% in the highest quartile (>75th quartile, CV >44.9%) when eHbA1c was set as 7%.

Conclusions: There is a strong correlation between TIR and eHbA1c in adult patients with type 1 diabetes. Patients with lower glycemic variability usually have higher %TIR in the same eHbA1c level.

Disclosure

Y. Zhou: None. J. Weng: None. H. Liu: None. D. Yang: None. H. Ai: None. J. Lv: None. X. Mai: None. W. Xu: None. B. Yao: None. J. Yan: None.

Funding

National Key Research and Development Program of China (2017YFC1309600)
61-OR: Glycemic Control and Depressive Symptoms among Minority Women with Type 2 Diabetes Enrolled in the Women In Control (WIC2) Diabetes Medical Group Visit (DMGV) Study
Authors: GARDINER PAULA , CRUZ BARBARA M. , BRAGG ALEXA , WINTER MICHAEL , MELO KATHERINE , HOWARD JESSICA M. , MITCHELL SUZANNE
Published: June 2021

Background: Comorbid depression is associated with poor diabetes control. DMGVs improve glycemic control and depressive symptoms among patients with type 2 diabetes (T2DM). The WIC2 study compared the effectiveness of an eight-week DGMV conducted in a virtual world platform vs. an in-person format to improve diabetes outcomes for 288 minority women with uncontrolled T2DM (HbA1c ≥8.0%).

Objective: We conducted a secondary data analysis of the WIC2 clinical trial data to examine the association between improvements in depressive symptom burden (PHQ-8) and improvements in HbA1c among participants enrolled in the WIC2 study.

Methods: We measured mean changes in PHQ-8 and HbA1c at baseline, 9-weeks, and 6-months post-enrollment among 288 WIC2 participants. We performed logistic regression to examine the association between a reduction in depressive symptoms per PHQ-8 (-5 points) and reduction in HbA1c (-0.4%) at 9-weeks and 6-months. We used multivariable logistic regression to adjust for potential confounders, including age, education, and study arm.

Results: At baseline, nearly half of WIC enrollees reported mild (29.5%), moderate (17.4), or severe (1.7%) depressive symptoms. Their mean PHQ-8 score was 5.5 (SD 5.0) and mean A1c was 9.93% (SD 1.74). From baseline to 6-months, 17.4% (n=41) achieved a 5-point decrease in PHQ-8; among this subset, the mean PHQ-8 score was 10.49 (SD 4.69), indicative of moderate depression at baseline. Of these 41 participants, 68.3% (n=28) also achieved the threshold A1c improvement at 6-months. After controlling for study arm, education, and age, participants with 5-pt or greater reduction in PHQ-8 score from baseline to 6-months had 2.45 times the odds (CI: 1.16, 5.18) of achieving 0.4% or greater reduction in A1c.

Conclusion: Improvements in depressive symptom burden correlate with improvements in diabetes management among women with uncontrolled T2DM.

Disclosure

P. Gardiner: None. B. M. Cruz: None. A. Bragg: None. M. Winter: None. K. Melo: None. J. M. Howard: None. S. Mitchell: Other Relationship; Self; See Yourself Health LLC, Speaker’s Bureau; Self; Merck Sharp & Dohme Corp.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK10653)
62-LB: The Effect of Do-It-Yourself Real-Time Continuous Glucose Monitoring on Psychological and Glycaemic Variables in Children with Type 1 Diabetes: A Randomised Crossover Trial
Authors: ELBALSHY MONA , STYLES SARA , HASZARD JILLIAN J. , GALLAND BARBARA , CROCKET HAMISH , JEFFERIES CRAIG A. , WILTSHIRE ESKO , TOMLINSON PAUL , DE BOCK MARTIN , WHEELER BENJAMIN J.
Published: June 2021

Background: Continuous glucose monitoring (CGM) can decrease fear of hypoglycaemia (FOH) and improve glycaemic control among those affected by type 1 diabetes (T1D). No studies to date have examined the impact of using Do-It-Yourself Real-Time Continuous Glucose Monitoring (DIY RT-CGM) on psychological and glycaemic outcomes. The primary aim of this study was to investigate the effect of DIY RT-CGM compared to intermittently scanned CGM (isCGM) on parental FOH.

Methods: Child-parent dyads were recruited for this multicentre randomised crossover trial. Children with T1D were aged 2-13 years and were current isCGM users. Families had 6 weeks of using DIY RT-CGM with parental remote monitoring (intervention) and 6 weeks of isCGM plus usual diabetes care (control) in a random order with a four-week washout period. FOH was assessed by the hypoglycaemia fear survey. Standard CGM based glycaemic variables were collected via Tidepool. Parental satisfaction was assessed by the diabetes treatment satisfaction questionnaire (DTSQ).

Results: The study included 55 child-parent dyads; child mean age 9.1±2.8 years. There was no evidence of an effect on parental FOH, -0.1 (95% CI: -0.3, 0.1, p-value 0.4). Time-in-range (%3.9-10mmol/L) favoured DIY RT-CGM over isCGM (54.3%±13.7 vs. 48.1%±13.6), adjusted mean difference, 5.7% (95% CI 1.8, 9.6, p-value 0.004). There was no evidence of a difference between DIY RT-CGM and isCGM for time spent in hypoglycaemia. Parents reported higher DTSQ scores following DIY RT-CGM compared to isCGM, adjusted mean difference 5.3 (95% CI: 2.3, 8.2, p-value <0.001).

Conclusion: The use of DIY RT-CGM versus isCGM did not improve parental FOH, however time in range and parental satisfaction with diabetes treatment were significantly improved, suggesting DIY RT-CGM with remote monitoring may offer families clinically important benefits over isCGM in regards to these aspects of T1D management.

Disclosure

M. Elbalshy: None. B. J. Wheeler: Research Support; Self; Dexcom, Inc., i-SENS, Inc., Medtronic, Ypsomed Group. S. Styles: None. J. J. Haszard: None. B. Galland: None. H. Crocket: None. C. A. Jefferies: None. E. Wiltshire: None. P. Tomlinson: None. M. De bock: None.
630-P: Improved Glucose Control for People with Diabetes Who Enrolled in a Multi-Chronic Condition Remote Monitoring Platform
Authors: LIU SUSIE , PAINTER STEFANIE L. , JAMES ROBERTA , KOMPALA TEJASWI , SHAH BIMAL
Published: June 2021

Background: Remote monitoring platforms (RMP) with personalized coaching continue to scale and have shown to be an effective tool for self-monitoring blood glucose (BG) and blood pressure (BP) for individuals with diabetes (DM) and hypertension (HTN). With HTN being a common risk factor for individuals with DM, it’s important to understand how RMPs can support individuals with both DM and HTN.

Methods: Members were enrolled in a multi-chronic condition RMP with access to both DM and HTN programs. Using Propensity Score Matching to ensure no statistical differences in age, gender, race, DM type, insulin dependence, self-reported HbA1c, median zip code income, and zip code, two sample populations were constructed of those who were enrolled in DM only and DM+HTN between 1/1/2019 and 6/30/2019 and active on the platform for at least 1 year. For robust results, Bootstrapped Propensity Score Matching was used with 2,000 iterations. Paired t-test was used to compare reduction in estimated a1c at 6- and 9-months. Due to COVID-19, outcomes at 12-months were not evaluated.

Results: No statistical differences between DM only (n=888) and DM+HTN (n=888) groups in age (56 vs. 56), gender (50% vs. 48% female), race (59% vs. 62% Caucasian), diabetes type (95% vs. 95% T2DM), insulin dependent (24% vs. 27%), started uncontrolled (49% vs. 50%), and self-reported HbA1c at time of registration (7.3% vs. 7.3%). Average estimated HbA1c reductions at 6 months were -0.46% for DM only and -0.65% for DM+HTN (p = 0.011). Reduction was similar at 9-month though no longer statistically different with values of -0.42% vs. -0.57%, respectively.

Conclusions: Members enrolled in both DM+HTN versus DM only had improved glucose control within 6-months indicating RMPs that support multiple chronic conditions may have better outcomes. Future study is required to better understand the drivers of the clinical improvement for multiple conditions.

Disclosure

S. Liu: Employee; Self; Livongo, Teladoc Health. S. L. Painter: Employee; Self; Livongo. R. James: Employee; Self; Livongo, Teladoc Health, Stock/Shareholder; Self; Livongo, Teladoc Health. T. Kompala: Consultant; Self; Eli Lilly and Company, Employee; Self; Livongo. B. Shah: Employee; Self; Teladoc Health, Stock/Shareholder; Self; Teladoc Health.
636-P: Diabetes Providers Value CGM Data Despite Challenges in Data Review Process
Authors: KOMPALA TEJASWI , WONG JENISE C. , NEINSTEIN AARON B.
Published: June 2021

People with diabetes (PWD) benefit from continuous glucose monitoring (CGM), yet CGM uptake in the US remains low. While diabetes care providers are key facilitators of CGM provision, data on provider behavior related to CGM use and CGM generated data is limited.

In March 2020, we conducted a national survey of providers caring for PWD on CGM-related opinions, facilitators and barriers to CGM prescription, data review practices, and reimbursement. Descriptive statistics were used to report prevalence of Likert scale answers to a 55-question survey.

Of 182 survey respondents caring for PWD using CGM, 75% were at academic medical centers, 66% were endocrinologists, and 70% practiced in urban settings. Nearly 70% of providers reported CGM use in a majority of their patients with type 1 diabetes. CGM use in patients with type 2 diabetes was low, with half the providers reporting <10% CGM use. All respondents believed CGM improved quality of life and could help optimize diabetes control. Nearly all providers reviewed CGM data each visit (94%) and directly involved patients in data review (90%). Only 14% of providers reviewed CGM data outside of a scheduled visit without prompting from patients or their family members. Most providers (81%) reported their CGM data review was valued by patients although only half (55%) reported having adequate time or an efficient process to do so. Most providers included CGM data in the electronic health record but only 41% had an efficient process for data capture. The majority of providers (79%) sought reimbursement for CGM interpretation during a visit, but a minority (41%) sought reimbursement for interpretation outside of visits.

Despite uniform support for CGM by providers, inadequate time and inefficient data review processes are ongoing challenges. Improvements in data access and integration, supportive clinical infrastructure, and decreased administrative burden to obtain CGM, are facilitators of effective use of CGM-data by providers and necessitate ongoing attention.

Disclosure

T. Kompala: Consultant; Self; Eli Lilly and Company, Employee; Self; Livongo. J. C. Wong: Advisory Panel; Self; Provention Bio, Inc., Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. A. B. Neinstein: Consultant; Self; Eli Lilly and Company, Intuity Medical , Medtronic, Roche Diabetes Care, Steady Health.
648-P: Glucose-Dependent Insulinotropic Polypeptide (GIP) Induces Lipolysis during Stable Basal Insulin Substitution and Hyperglycemia in Men with Type 1 Diabetes
Authors: NIELSEN CHRIS N. , HEIMBÜRGER SEBASTIAN M. NGUYEN , CALANNA SALVATORE , HOLST JENS J. , VILSBØLL TINA , KNOP FILIP K. , CHRISTENSEN MIKKEL B.
Published: June 2021

Glucose-dependent insulinotropic polypeptide (GIP) contributes importantly to postprandial insulin secretion, and - perhaps primarily due to this insulinotropic effect - affects glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during hyperglycemia and stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide negative), aged [mean±SD: 26±4 years; BMI: 24±2 kg/m2; HbA1c 7.3±0.8%) were studied in a randomized, double-blind, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusions and decreased during placebo infusions (baseline-subtracted area under the curve (bsAUC): 703±407 vs. -262±240 µmol/L × min, respectively, P<0.001). Free fatty acids increased only during GIP infusions (bsAUC: 5,431±6,393 during GIP vs. -74±2,363 µmol/l × min during placebo infusion, P<0.05). Plasma concentrations of glucose, insulin, and glucagon were similar during GIP and placebo infusions (P=NS). Compared to placebo, GIP increased plasma glycerol and free fatty acids in patients with type 1 diabetes during hyperglycemia and stable basal insulin levels. With this experimental design it was possible to clearly identify an important effect of GIP on lipolysis in humans.

Disclosure

C. N. Nielsen: None. S. M. Nguyen heimbürger: Speaker’s Bureau; Self; AstraZeneca. S. Calanna: Employee; Self; Novo Nordisk A/S. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. M. B. Christensen: None.
65-OR: Autoantibody Levels at Seroconversion Improve Prediction to Type 1 Diabetes Beyond Autoantibody Type and Number
Authors: NG KENNEY , ANAND VIBHA , VEIJOLA RIITTA , MAZIARZ MARLENA , WAUGH KATHLEEN , HAGOPIAN WILLIAM , ACHENBACH PETER ,   T1DI STUDY GROUP
Published: June 2021

While associations between the type and number of islet autoantibodies and progression to type 1 diabetes (T1D) have been reported, the effect of titer values is less well understood. We aim to quantify the ability of autoantibody titers at seroconversion to improve T1D onset prediction.

Prospective cohorts in Finland, Germany, Sweden, and the US have followed 24662 children at increased genetic risk for development of islet autoantibodies and T1D. For the 1400 who seroconverted (523 developed T1D), the titers of insulin autoantibodies (IAA), glutamic acid decarboxylase autoantibodies (GADA), and insulinoma antigen-2 autoantibodies (IA2A) at time of initial and confirmed seroconversion, i.e., the respective first and consecutive second autoantibody-positive serum sample, were normalized (to log multiples of upper limit of normal) and analyzed. Prediction models using multivariate logistic regression with inverse probability censored weighting (IPCW) were trained using 10-fold cross validation. Discriminative power for disease was estimated using the IPCW concordance index (c-index) with 95% confidence intervals estimated via bootstrap. Multivariate Cox proportional hazards models were used to quantify the impact of the autoantibody titers.

A baseline model with covariates for data source, sex, HLA-DR/DQ genotype, and age at initial and confirmed seroconversion had a performance of 64 c-index; 95% CI 62-65. Significant improvement was observed after adding IAA, GADA, IA2A positivity indicators at initial and confirmed seroconversion (74; 72-75). Adding the corresponding autoantibody titers resulted in significant additional gains (76; 75-76). Adjusted hazard ratios (HR) from the Cox model showed that autoantibody titers at confirmed seroconversion were predictive of diabetes (HR 1.29; 95% CI 1.20-1.38 for IAA, 1.12; 1.07-1.18 for GADA, and 1.19; 1.15-1.25 for IA2A, all p<0.001).

Islet autoantibody titers at seroconversion improve T1D prediction.

Disclosure

K. Ng: Employee; Self; IBM. V. Anand: None. R. Veijola: None. M. Maziarz: None. K. Waugh: None. W. Hagopian: None. P. Achenbach: None. T1di study group: n/a.

Funding

JDRF (1-IND-2019-717-I-X)
658-P: Sustained Glucagon Effect on Cardiovascular Renal and Metabolic Disorders Mediated by a Long-Acting Glucagon Analog, HM15136, in Animal Disease Models
Authors: LEE JONG SUK , LEE SEON MYEONG , KIM JUNG KUK , PARK EUNJIN , LEE JONGSOO , KIM DAEJIN , KIM YOUNG HOON , CHOI IN YOUNG
Published: June 2021

Obesity is an increasing health problem worldwide, implicated with various metabolic disorders such as cardiovascular disease and chronic kidney disease (CKD). Previously, we showed that chronic treatment of HM15136, a long-acting GCG analog, led to robust body weight loss (BWL) in rodent obese models. Moreover, recent studies unveiled a novel role of GCG in vasodilation and inflammation. So, we hypothesized that HM15136 improve chronic metabolic disorders via direct action in addition to secondary effect to BWL. Here, we investigated potential therapeutic effect of HM15136 in animal models of cardiovascular renal and metabolic diseases. In DIO mice, BW, liver triglyceride (TG), and blood cholesterol (CHO) were measured, and all measurements were significantly reduced by HM15136 treatment (-37.5, -72.7, -78.4% vs. vehicle for BW, liver TG, blood CHO at day 17). Next, to explore therapeutic effect of HM15136 on cardiovascular renal diseases, spontaneously hypertensive rats, known model for hypertensive CKD, were used. Interestingly, abnormal elevation in blood pressure and renal function markers such as urine albumin/creatinine ratio (-23.6% vs. SHR vehicle at day 46) was meaningfully reduced by HM15136 treatment. In unilateral ureteral obstruction mice, known as acute kidney injury model, similar results were observed (-17.6%, -48.2% vs. vehicle for serum creatinine, kidney pro-collagen1α1 at day 12). Consistently, increase of vasodilation markers in rat aorta and inhibition of human primary podocyte apoptosis were confirmed, explaining underlying mechanism for these beneficial effects. Therefore, HM15136 could mitigate obesity and related complications especially hypertension and CKD. Hence, mechanistic study results highlight the essential role of direct GCG engagement in improvement of cardiovascular renal and metabolic diseases. Further studies are needed to assess a clinical relevance of these findings.

Disclosure

J. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. J. Kim: Employee; Self; Hanmi Pharmaceutical. E. Park: Employee; Self; Hanmi Pharmaceutical. J. Lee: Employee; Self; Hanmi Pharmaceutical. D. Kim: Employee; Self; Hanmi Pharmaceutical. Y. Kim: None. I. Choi: Employee; Self; Hanmi Pharmaceutical.
682-P: Novel Dual Glucagon and Glucagon-Like Peptide-1 Receptor Agonist LY3305677 Improves Glucose Control, Reduces Body Weight, and Increases Energy Expenditure in Mice
Authors: CHEN YANYUN , MEZO ADAM , COSKUN TAMER , SONG MIN , ROELL WILLIAM C. , BOKVIST KRISTER B. , MOYERS JULIE S. , THOMAS MELISSA K. , VALENZUELA FRANCISCO , QU HONGCHANG
Published: June 2021

LY3305677 (LY) is a synthetic peptide analog of mammalian oxyntomodulin with a fatty acyl side chain to extend time action. LY functions are mediated by binding and activation of both glucagon (GcgR) and glucagon-like peptide-1 (GLP-1R) receptors. LY is bound with potent binding affinity (Ki) to human and mouse GcgR (Ki: 17.7 nM and 15.9 nM, respectively) and GLP-1R (Ki: 28.6 nM and 25.1 nM, respectively). LY dose-dependently stimulated insulin secretion in mouse pancreatic islets (EC50: 5.2 nM) and in mice. In oral glucose tolerance tests of diet-induced obese (DIO) and streptozotocin-induced diabetic mice, a single subcutaneous (SC) dose of LY significantly reduced glucose area under the curve by up to 65%. SC injections of LY to DIO mice dose-dependently reduced serum triglycerides and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels and dose-dependently increased FGF21 (fibroblast growth factor 21) levels. In DIO mice treated over 18 days, LY 30 nmol/kg reduced body weight to a greater extent (33%) than semaglutide 60 nmol/kg (12%), and decreased food intake by 50% compared to vehicle. At Day 18, LY 30 nmol/kg group lost 33% of initial bodyweight, which was primarily due to 70% reduced fat mass. LY reduced liver triglycerides by greater than 70% and increased serum ketones by more than 3-fold compared to vehicle, suggestive of increased fatty acid oxidation. LY decreased body weight in both GcgR knock-out (KO) and GLP-1R KO mice, indicating that activation of both receptors contributed to greater weight loss. To assess potential changes in energy expenditure, DIO mice were treated chronically with SC LY (15 nmol/kg), semaglutide (60 nmol/kg), or vehicle. LY, but not semaglutide, increased energy expenditure as compared with vehicle. These preclinical studies indicate that novel dual GcgR and GLP-1R agonist LY may have potential to enhance metabolic health by improving dyslipidemia, hyperglycemia, or obesity.

Disclosure

Y. Chen: None. H. Qu: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. A. Mezo: None. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Song: None. W. C. Roell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. B. Bokvist: Employee; Self; Eli Lilly and Company, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Self; Johnson & Johnson, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J. S. Moyers: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. F. Valenzuela: None.

Funding

Eli Lilly and Company
700-P: Glucotab-Based Basal-Bolus Insulin Therapy for Inpatient Glycemic Control Using Insulin Degludec
Authors: MADER JULIA K. , BAUMANN PETRA M. , ABERER FELIX , HOCHFELLNER DANIEL A. , SIMIC AMRA , BYTYQI LIRIE , POETTLER TINA , HOELL BERNHARD , FAHRLEITNER-PAMMER ASTRID , PIEBER THOMAS , BECK PETER
Published: June 2021

Guidelines recommend insulin therapy and the use of clinical decision support systems to manage hyperglycemia and diabetes mellitus in hospitalized patients. The aim of the study was to evaluate glycemic control using insulin degludec in an algorithm driven electronic decision support system in hospitalized patients with type 2 diabetes (T2D). The electronic decision support system GlucoTab® was applied for diabetes management in 30 hospitalized patients with T2D (18 women, age 74.1±10.9 years, HbA1c 71±23mmol/mol, BMI 28.6±5.6kg/m2, diabetes duration 14.9±15.1 years, creatinine 1.5±1.2mg/dl, length of hospital stay 9.1±4.0 days). Insulins degludec and aspart were used for basal-bolus insulin therapy. Blood glucose was tested four times daily using a point-of-care device integrated into the hospital information system. The overall mean blood glucose (BG) value was 144±53 mg/dl (mean pre-enrolment BG 211±84mg/dl). BG measurements were in 74.9% in the range of 70-<180 mg/dl. BG measurements in the ranges <40mg/dl, <70mg/dl, 180-<300 and ≥300mg/dl were observed in 0.0%, 1.5%, 22.9% and 0.7% of all measurements, respectively. Total daily insulin dose was 34.0±19.9 U (bolus insulin dose 18.7±13.1 U, basal insulin dose 16.0±7.9 U). Adherence to the algorithm-calculated total daily insulin dose was 93.2%; adherence to inject the algorithm-calculated basal and bolus insulin doses was high (99.0% and 85.3%). Basal-bolus therapy using GlucoTab® covered 80.8±19.9% of the patients’ total hospital stay. Glycemic control using insulin degludec in an algorithm driven electronic decision support system could safely be established in the hospital setting with high adherence to algorithm advice.

Disclosure

J. K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Roche Diabetes Care, Speaker’s Bureau; Self; Abbott Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, Stock/Shareholder; Self; decide Clinical Software GmbH. T. Pieber: Advisory Panel; Self; ADOCIA, Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk A/S. P. Beck: Employee; Self; decide Clinical Software GmbH, Stock/Shareholder; Self; decide Clinical Software GmbH. P. M. Baumann: None. F. Aberer: None. D. A. Hochfellner: None. A. Simic: None. L. Bytyqi: None. T. Poettler: None. B. Hoell: Employee; Self; decide Clinical Software GmbH. A. Fahrleitner-pammer: None.

Funding

Novo Nordisk
714-P: Assessment of the Patient Transition Experience to Hybrid Closed-Loop Insulin Pump Therapy
Authors: DISSANAYAKE ASHINI , CHOW ERIC , WHITE ADAM , KAPELUTO JORDANNA E. , MACKENZIE-FEDER JESSICA , SCHROEDER BENJAMIN , PAWLOWSKA MONIKA
Published: June 2021

Hybrid closed-loop (HCL) insulin pump therapy is a promising development for the management of type 1 diabetes (T1D), but little is known about the transition period to HCL in a real-world setting. Here, we present novel data evaluating the HCL transition experience and its effect on diabetes distress. We evaluated 32 out of 150 anticipated participants who were about to transition (Arm A), or had recently transitioned (Arm B), from standard pump therapy to the MiniMed™ 670G HCL pump. Patients completed a baseline and 6-month post-transition diabetes distress survey using the T1-DDS. In the follow-up survey, patients’ trust in HCL and treatment satisfaction were also assessed. Finally, post-survey interviews were conducted for patients to elaborate on the successes and struggles of their HCL transition experience. No significant differences were observed between the 2 arms, so the sample was analyzed as a whole. After 6 months on HCL, significant reductions were observed in overall diabetes distress (p<0.0001), as well as powerlessness (p<0.005), management (p<0.001), hypoglycemia (p<0.005), and eating (p<0.0005) distress. Most patients (56%) indicated difficulty trusting HCL, however 80% reported that trust improved over time. Patient satisfaction was high (81%), however only 47% indicated that HCL met their expectations, 56% would recommend HCL to others, and 66% indicated frustration with the transition to HCL. Patients were divided on whether HCL increased (41%) or decreased (47%) the workload required to manage their T1D (12% neutral). Over half of patients (59%) felt that HCL was too complicated. Patients were divided on whether HCL was too much of a “hassle” to use (31% yes, 38% no, 31% neutral). Emerging themes from the qualitative data include numerous alarms, loss of sleep, and necessity of “phantom carbing.” Overall, HCL therapy significantly reduces diabetes distress, but the patient transition experience is varied in terms of trust, satisfaction, and comfort with the technology.

Disclosure

A. Dissanayake: None. E. Chow: None. A. White: Advisory Panel; Self; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Canada Inc. J. E. Kapeluto: None. J. Mackenzie-feder: None. B. Schroeder: Advisory Panel; Self; AstraZeneca, Novartis Pharmaceuticals Canada Inc. M. Pawlowska: Advisory Panel; Self; Novo Nordisk.
72-OR: HDL Particle Concentration Predicts Incident Coronary Artery Disease (CAD) in Type 1 Diabetes (T1D)
Authors: COSTACOU TINA , VAISAR TOMAS , BORNFELDT KARIN , ORCHARD TREVOR J. , HEINECKE JAY
Published: June 2021

We have shown that elevated HDL cholesterol (HDL-C) levels (≥80 mg/dL) associate with increased CAD risk in women with T1D. Furthermore, HDL-C levels are not necessarily cardioprotective in nondiabetic individuals, suggesting that the cholesterol content of HDL does not accurately assess CAD risk. We thus determined whether two other HDL metrics, HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC), predicted incident CAD in a large cohort of childhood onset T1D (n=550). At baseline, mean age was 27.8 yrs, T1D duration was 19.6 yrs and 49% were women. HDL-P was assessed by calibrated ion mobility analysis and CEC was quantified with validated assays in cAMP stimulated J774 cells and in ABCA1-expressing BHK cells. CAD was defined as CAD death, myocardial infarction and/or revascularization. During a median follow-up of 26 yrs, we observed 203 incident CAD cases (36.9%). At baseline, incident cases were older, more likely to have smoked, have hypertension, longer duration of T1D, higher non-HDL-C and markers of kidney disease and inflammation. Cases were also more likely to have lower HDL-P concentrations but similar CEC to non-cases. Cox models with backward elimination were constructed for each HDL metric, allowing for potential confounding variables, including HDL-C. In separate multivariable models, higher concentrations of total HDL-P (T-HDL-P, HR=0.88, 95% CI: 0.83-0.92) and 3 major HDL subpopulations - small (S-HDL-P, HR=0.78, 0.67-0.92), medium (M-HDL-P, HR=0.79, 0.71-0.88) and large-sized (L-HDL-P, HR=0.74, 0.61-0.89) particles - associated with a lower CAD incidence whereas HDL-C did not. Higher total CEC in J774 cells also predicted lower CAD risk (HR=0.74, 0.55-0.996) after similar adjustments, but became non-significant after further adjusting for HDL-P. ABCA1-specific CEC did not predict CAD. Our results suggest that increased HDL-P levels are cardioprotective in T1D, in contrast to HDL-C and CEC which did not independently predict CAD.

Disclosure

T. Costacou: None. T. Vaisar: Consultant; Self; AstraZeneca. K. Bornfeldt: None. T. J. Orchard: None. J. Heinecke: None.

Funding

National Institutes of Health (HL130153, DK34818)
727-P: The Association between Missed Basal Insulin Injections and Glycemic Control in Adults with Type 1 Diabetes Mellitus
Authors: EKBERG NEDA RAJAMAND , HARTVIG NIELS V. , KAAS ANNE , MOLLER JONAS , MÅRDBY ANN-CHARLOTTE M. , ADOLFSSON PETER
Published: June 2021

Basal insulin injections are important for glycemic control in patients with type 1 diabetes mellitus (T1DM); however, patients may forget or skip doses. This study explored the adherence to basal insulin injections and the association of the pattern of missed basal insulin doses with glycemic control in patients with T1DM. A prospective real-world study was conducted in Sweden in patients with T1DM who began using a smart insulin pen for basal and/or bolus insulin administration together with their usual continuous glucose monitoring (CGM). This analysis included adults receiving basal insulin degludec, with at least one 14-day period with ≥70% CGM coverage. Outcomes aggregated over each 14-day period included: number of missed basal insulin doses (≥40 hrs between doses), time in range (TIR 70­-180 mg/dL), time above range (TAR level 1 >180-250 mg/dL; level 2 >250 mg/dL), time below range (TBR level 1 54-<70 mg/dL; level 2 <54 mg/dL), mean glucose level, glucose management indicator (GMI) and coefficient of variability (%CV). Data were analyzed by mixed models with patient ID as random effect. Overall, 32 patients (mean age, 35.6 yrs) had 315 14-day periods of acceptable CGM coverage. The probability that a patient missed ≥1 basal insulin dose over a 14-day period was 22% and patients with high %CV had a higher probability (47%) of having a missed dose. Each missed basal insulin dose over a 14-day period was associated with a significant reduction in TIR (−2.61% [−0.63 hrs], p <0.001) and a corresponding statistically significant increase in TAR level 2 (+2.89% [+0.69 hrs], p <0.001), mean glucose level (+7.9 mg/dL, p <0.001) and GMI (+0.19%, p <0.001); no significant association was found with %CV, TBR or TAR level 1. This study demonstrates that missed basal insulin injections are associated with changes in TIR and GMI; as such, there is a significant need for tools, such as smart pens that provide downloadable data, to empower patients to improve insulin adherence.

Disclosure

N. Rajamand ekberg: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk. N. V. Hartvig: Research Support; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. A. Kaas: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. J. Moller: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. A. M. Mårdby: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. P. Adolfsson: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Other Relationship; Self; Dexcom, Inc., Glooko, Inc., Novo Nordisk, Tandem Diabetes Care.
753-P: Senolytics Improve Diabetes Measures in Type 2 Diabetic Nonhuman Primates: A Pilot Study
Authors: RUGGIERO ALISTAIRE D. , BLOCK MASHA , DAVIS MATTHEW , VEMURI RAVICHANDRA , ORR MIRANDA E. , KAVANAGH KYLIE
Published: June 2021

Senescent cells accumulate in adipose tissue (AT) with obesity, causing local inflammation and dysfunction. Senescent cells in aging nonhuman primate (NHP) AT correlated with metabolic disease measures in our previous work. In this pilot study, we evaluated the senolytic combination dasatinib plus quercetin (D+Q) on AT senescent cell burden and systemic metabolic health in obese NHPs with naturally occurring type II diabetes (T2D; n=3). Selected NHPs remained stable on insulin therapy for six months prior to the study. NHPs were given a single oral dose of D (5mg/kg) plus Q (50mg/kg). Blood samples were collected 1 week prior to, and 4 and 8 weeks post-treatment. Abdominal subcutaneous (SQ) AT biopsies were taken before and 1 week after dosing. Senescence-associated beta galactosidase (SA-β-gal) staining showed 24% reductions in AT senescent cell burden. Two animals had large reductions in the senescence biomarker plasminogen activator inhibitor 1 (mean=55%). Dramatic improvements in A1c, fasting glucose (FBG), cholesterol (TPC) and triglycerides (TG) were reported in all subjects, in the absence of weight loss. A1c decreased by 1-2% and FBG by > 100mg/dL (Cohen’s d = 3.81 and 2.78). Post-prandial glucoses were unchanged. Similarly, TPC and TG reduced by >25mg/dL and > 130mg/dL (Cohen’s d = 0.73 and 1.55). Improvements in fasting and overall glycemic measures, and lipid profiles suggest effects on hepatic metabolism. Reductions in creatinine were also seen post-treatment without changes in urea, which may indicate reduced muscle catabolism. Our results show a single D+Q treatment has potent and long-lasting effects for improved metabolism in T2D.

Disclosure

A. D. Ruggiero: None. M. Block: None. M. Davis: None. R. Vemuri: None. M. E. Orr: None. K. Kavanagh: None.

Funding

National Heart, Lung, and Blood Institute (R01HL142930)