bluuebunny/crossref_metadata_2025 huggingface dataset:
566-P: Is a Zoom, Family-Based Intervention Feasible during a Pandemic?
Authors: WONG JESSIE J. , LANNING MONICA S. , NGO JESSICA , WU CHRISTINE A. , HANES SARAH , LINZMEYER HALEY M. , NARANJO DIANA , HOOD KOREY K.
Published: June 2021

Background: Access to psychosocial services is limited, especially during a pandemic. A Zoom-delivered family-based intervention for adolescents with type 1 diabetes has the potential to enhance access to psychosocial services.

Methods: Nine families enrolled in a pilot of a 6-session online (Zoom) intervention for adolescents with type 1 diabetes and their parents during the COVID-19 pandemic. Qualitative and quantitative data were collected via online focus groups and surveys.

Results: Teens’ ages ranged from 12-17 years (M=14.9, SD=1.76) and most self-identified as male (78%). All parents self-identified as female and most families self-identified as non-Hispanic white (78%). Qualitative results revealed that participants found the program to be generally helpful and would recommend the program to others. Perceived benefits included increased parental empathy toward teens, enhanced parental involvement in teens’ diabetes management, and decreased parent-teen conflict. Participants conveyed that these benefits were particularly impactful given increased family contact and tensions related to the COVID-19 pandemic. Identified areas for improvement included adding follow-up group sessions with parents to maintain program impact on parenting over time and to target teens in early adolescence, when family dynamics are more malleable. Quantitative results from paired t-tests of pre-post comparisons revealed no significant differences in teen or parental diabetes distress or depression (all p>0.05), but should be interpreted with caution due to small sample size.

Conclusions: Adolescents with type 1 diabetes and their parents responded positively to this program and found it particularly relevant during the current pandemic. Zoom delivery of these programs may be instrumental in their feasibility, acceptability, and ultimately dissemination in the future.

Disclosure

J. J. Wong: None. M. S. Lanning: None. J. Ngo: None. C. A. Wu: None. S. Hanes: None. H. M. Linzmeyer: None. D. Naranjo: None. K. K. Hood: Consultant; Self; Cecelia Health, Cercacor, LifeScan Diabetes Institute.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK121771-01A1)
569-P: Fear of Nighttime Hypoglycemia: Diabetes Providers Recognize Parents’ Concerns
Authors: MONZON ALEXANDRA , MCDONOUGH RYAN , CUSHING CHRISTOPHER C. , CLEMENTS MARK A. , PATTON SUSANA R.
Published: June 2021

Objective: Pediatric diabetes healthcare providers and parents of youth with type 1 diabetes (T1D) described specific fears regarding nighttime hypoglycemia and behaviors parents engage in at night to avoid nighttime lows (i.e., blood glucose < 70mg/dL).

Methods: We completed semi-structured interviews with 10 diabetes providers (i.e., physicians, nurses, educators) and 15 parents of youth with T1D (Mean parent age= 41.92 ± 5.72 years, Mean child age= 10.96 ± 2.37 years). All children used a continuous glucose monitor and 87% used an insulin pump. Providers described the fears and behaviors parents express in clinic related to their child’s overnight glucose management. Parents described their own fears and behaviors specific to nighttime lows. We transcribed interviews verbatim, and used Framework Matrix Analysis to identify common themes among responses.

Results: Provider and parent interviews converged on several main themes (provider percentages first, parent percentages second). Regarding specific fears, consensus among participants indicated that parents fear overnight lows will harm their child (i.e., death, seizures; 90%, 87%), parents worry they will not hear alarms or wake up to help their child at night (50%, 93%), and parents fear devices will malfunction at night (20%, 67%). Regarding avoidance behaviors, participants reported that parents provide snacks at bedtime to raise glucose levels (70%, 60%), parents set temporary (lower) basal levels (40%, 53%), under-correct at night 20%, 46%), set multiple alarms to wake up during the night to check on their child (80%, 87%), and do not allow their child to attend sleepovers (30%, 80%).

Conclusions: We identified several common fears and avoidance behaviors that may be specific to overnight lows in parents of youth with T1D. As a next step, we will use our qualitative data to inform a new tool to specifically assess parental fear of nighttime hypoglycemia, which will fill a current gap in both research and clinical care for youth with T1D.

Disclosure

A. Monzon: None. R. Mcdonough: None. C. C. Cushing: None. M. A. Clements: Consultant; Self; Eli Lilly and Company, Employee; Self; Glooko, Inc., Research Support; Self; Abbott Diabetes, Dexcom, Inc. S. R. Patton: None.
575-P: Serum Soluble Epoxide Hydrolase-Related Oxylipins Are Associated with Depression and Increased Symptom Severity in T2DM
Authors: ANITA NATASHA Z. , FORKAN NUBAIRA , KAMAL RADIA , NGUYEN MICHELLE M. , YU DI , MAJOR-ORFAO CHELSI , WONG SOPHIE K. , LANCTÔT KRISTA L. , HERRMANN NATHAN , OH PAUL , SHAH BAIJU R. , GILBERT JEREMY , ASSAL ANGELA , SWARDFAGER WALTER
Published: June 2021

Depression in T2DM is associated with inflammation (e.g., interleukin-6 [IL-6]), but specific inflammatory pathways, and depressive symptoms involved, have not been identified. Cytochrome P450s (CYP450s) convert dietary fatty acids into pro-resolving epoxides but soluble epoxide hydrolase (sEH) metabolizes these into inactive diols, thereby limiting their anti-inflammatory benefits. We hypothesized that sEH oxylipins (diols and epoxides) will be associated with depression and increased symptom severity in T2DM. Patients with T2DM were diagnosed with depression (Structured Clinical Interview, DSM-5) and matched 1:1 to non-depressed patients for sex, HbA1c and BMI. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry. All analyses controlled for IL-6, measured by ELISA. Diol/epoxide ratios were calculated to estimate sEH pathway flux. Among 20 depressed and 20 non-depressed patients (mean age 58.9±8.5, mean HbA1c 7.0±0.9%, 65% women), the 17,18 sEH derived eicosapentaenoic acid (EPA) diol was higher in depressed participants (F(1,37)=5.753, p=0.022). Somatic, negative affective, and anhedonic symptoms were screened (Center for Epidemiological Studies-Depression Scale). Three diol/epoxide oxylipin ratios were associated with higher somatic symptoms in the depressed group: the 16,17 docosahexaenoic acid (DHA) derived ratio (β=0.489, p=0.007), and both linoleic acid derived ratios (9,10 [β=0.549, p=0.017] and 12,13 [β=0.547, p=0.003]). The 14,15 arachidonic acid derived ratio was associated with higher negative affective symptoms (β=0.559, p=0.006). These associations were not found in non-depressed T2DM. This increased flux of omega-3 and omega-6 fatty acids through the sEH pathway associated with depression and symptom severity suggests the potential role of sEH inhibitors for T2DM-related depressive symptoms.

Disclosure

N. Z. Anita: None. P. Oh: None. B. R. Shah: None. J. Gilbert: Speaker’s Bureau; Self; Abbott Diabetes, Amgen Canada, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi. A. Assal: None. W. Swardfager: None. N. Forkan: None. R. Kamal: None. M. M. Nguyen: None. D. Yu: None. C. Major-orfao: None. S. K. Wong: None. K. L. Lanctôt: None. N. Herrmann: None.

Funding

Canadian Institutes of Health Research; Banting & Best Diabetes Centre; National Institute of Diabetes and Digestive and Kidney Diseases
577-P: Complexity of Antidiabetic Medication Regimen Is Associated with Increased Diabetes-Related Distress in Patients with Type 2 Diabetes
Authors: LUZURIAGA MARIA GRACIA , LEITE RAFAEL , AHMED HAMMAD , SAAB PATRICE G. , GARG RAJESH
Published: June 2021

Objective: Diabetes-related distress is present in a high proportion of people with type 2 diabetes mellitus (T2DM). We hypothesized that complexity of the antidiabetic medication regimen is a factor that increases diabetes-related distress.

Research Design and Methods: We studied 74 consecutive patients with T2DM managed at a tertiary care center. Patients were screened for diabetes-related distress using the Diabetes Distress Scale-2 (DDS-2). A Diabetes Medication Complexity Scoring (DMCS) system was developed to objectively assess the diabetes medication complexity. Based on DMCS, participants were categorized into one of three groups: low (n = 26), moderate (n = 22) and high (n = 26) medication complexity.

Results: The prevalence of diabetes-related distress (DDS-2 ≥6) was 34.6% in the low, 36.4% in the moderate, and 69.2% in the high complexity groups (χ2(2) = 7.75, p= 0.021). Complexity groups were similar on sociodemographic characteristics, diabetes duration, BMI and blood pressure as well as the prevalence of hypertension, hyperlipidemia and hypoglycemic episodes over the last year (ps>0.05). The prevalence of microvascular complications varied as a function of low (28%), moderate (45%), and high (76%) regimen complexity (χ2(2) = 11.8, p = 0.003). One-way ANOVA showed significant complexity group differences for HbA1c (F(2,70) = 5.47, p = 0.006) with higher HbA1c in the high and moderate complexity groups than in the low group. Analysis of covariance adjusting for HbA1c showed that DDS-2 significantly differed as a function of complexity group (F (2,69) = 3.93, p = .024). The model explained 16.2% of the variance in DDS-2 (R2 = 0.162). Post hoc analyses revealed that diabetes-related distress was significantly greater for the high (DDS-2 = 6.6) complexity group compared to the moderate complexity group (DDS-2 = 4.5) (p = .031).

Conclusions: A complex antidiabetic medication regimen is associated with high levels of diabetes distress.

Disclosure

M. Luzuriaga: None. R. Leite: None. H. Ahmed: None. P. G. Saab: None. R. Garg: None.
602-P: Validity of a Feeling-State Tag Accompanying Blood Glucose (BG) Measurements in a Digital Remote Diabetes Management Program (RDMP)
Authors: DZUBUR ELDIN , FAN LUDI , JAMES ROBERTA , LU WEI , MEADOWS ERIC , PEREZ-NIEVES MAGALY , SHAH BIMAL
Published: June 2021

Background: Diabetes is thought to have a bi-directional relationship with mental health, including stress. Therefore, it is increasingly important to understand stress of patients with diabetes in real-time. Despite extensive use and success of RDMPs, there is limited psychometric research on the development of real-time measures of stress in the context of RDMPs. The objective of this study is to examine the validity of a stress tag among participants in an RDMP.

Methods: Participants in the study (ages 8-92) were enrolled in Livongo for Diabetes, an RDMP offering a glucometer that prompts user to endorse a feeling-tag to provide behavioral context to BG readings. Participants also received smartphone surveys at baseline, 6 months, and 12 months containing a two-item Diabetes Distress Scale SF. Repeated BG and stress data from the first 12 months of the program were aggregated to 3-month windows surrounding the smartphone surveys. Two-part generalized linear mixed models were used to test association between stress tags and DDS-SF.

Results: Participants (N=470) were, on average, 59.69 years old, 50% female, and 80% White, with 91% reporting type 2 diabetes and 36% reporting insulin usage. Two-part models revealed that each additional point on the DDS-SF scale was associated with a 46% increased likelihood (95% CI: 1.23-1.75) of any stress tag at that time point (z=4.25, p<0.001). When stress tags were endorsed, each additional point on the DDS-SF scale was associated with a 14% (95% CI: 1.04-1.26) increase in the proportion of stress tags for that time period (z=2.72, p<0.01).

Conclusions: The study found that a stress tag during glucometer use was associated with DDS-SF. In the context of an RDMP, a stress indicator allows for real-time data analysis, and thus a better understanding of a patient's experience with their disease. Future studies may seek to understand the extent to which such stress measures can be used to predict lapses in medication adherence.

Disclosure

E. Dzubur: Employee; Self; Livongo, Teladoc Health, Stock/Shareholder; Self; Livongo, Teladoc Health. L. Fan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. R. James: Employee; Self; Livongo, Teladoc Health, Stock/Shareholder; Self; Livongo, Teladoc Health. W. Lu: Employee; Self; Teladoc Health. E. Meadows: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. M. Perez-nieves: Employee; Self; Eli Lilly and Company. B. Shah: Employee; Self; Teladoc Health, Stock/Shareholder; Self; Teladoc Health.
611-P: Users with High-Risk Type 2 Diabetes Experience a Change in Blood Glucose Levels Using Digital Therapeutic Platform
Authors: HERSHCOVITZ YIFAT , DAR SHARON , MANEJWALA OMAR , BACHER DROR
Published: June 2021

Introduction: Digital therapeutic platforms are often used to assist users in maintaining target blood glucose levels and to prevent diabetes complications. Digital engagement can play a central role in supporting behavioral changes to manage diabetes. Such platforms allow evaluation of patient's blood glucose levels in real time and intervene based on actual behavioral and clinical indicators. The study examines the ratios of blood glucose levels over time based on real world data in one such platform.

Method: A retrospective data evaluation study was performed on the DarioTM data base. A population (“high-risk users”) of all users with type 2 diabetes activated during 2017-2020 who took measurements with Dario in the first 2 months and who started with an average blood glucose above 180 mg/dL was evaluated. The ratios assessed were target range (70-180 mg/dL) and high blood glucose (>180 mg/dL) readings over a year. Socioeconomic status was matched by applying zip code data to census.gov data.

Results: For 11,101 users, the average ratio of target range readings (70-180 mg/dL) was significantly increased from 28.4% to 54.8% (P<0.001). Average high events ratio (>180 mg/dL) was significantly reduced from 71.3% to 44.4% over a full year usage (P<0.001). The change appeared in the earliest months and was maintained over a year. Average number of days between measurements, i.e., “recency” was 3.3 days. A subset of Spanish language app users (N=169) was also evaluated, and comparable trends were observed. Matching Census.gov data on study population showed that 20% of users resided in low income zip codes, 70% in middle and 10% in upper income zip codes.

Conclusion: Digital therapeutic platforms may promote behavior modification in high-risk patients with type 2 diabetes to create sustainable outcomes. The study revealed that the digital diabetes platform has the potential to enhance self-care behaviors across socioeconomic statuses and among different language speakers.

Disclosure

Y. Hershcovitz: Employee; Self; DarioHealth. S. Dar: Employee; Self; DarioHealth. O. Manejwala: Employee; Self; DarioHealth, Stock/Shareholder; Self; DarioHealth. D. Bacher: Employee; Self; DarioHealth.
623-P: Should We Continue Using HbA1c for Treatment Adjustment in Patients with Type 2 Diabetes?
Authors: TOTOMIROVA TZVETELINA , ARNAUDOVA MILA
Published: June 2021

According current guidelines, treatment decision in patients with type 2 diabetes is based on HbA1c, reflecting approximately recent three months control. But there are many data showing that HbA1c is an insufficient control assessment tool omitting to present glucose fluctuations and variability. Continuous glucose monitoring (CGM) is used for insulin dose adjustment but is rarely used in type 2 diabetes patient treatment determination. In our study we compare the results derived from non-real time CGM and HbA1c to find out which could be more useful for drug prescription decision in patients with type 2 diabetes. We studied 85 patients with type 2 diabetes (35 women, 50 men; age 43.93±10.87 years, disease duration 21.91±6.07 years) receiving different treatment regimens (31 on oral therapy, 33 treated with premixed insulin, 21 on multiple insulin injections). Patients performed Non-Real Time Continuous Glucose Monitoring by using iProTM for seven days and HbA1c was measured at the end of this period. No difference in HbA1c level was found in three groups. HbA1c showed moderate negative correlation to percentage of time within the limits derived from CGM (r1= -0.654; r2= -0.674; r3= -0.521) with no dependence on therapeutic regimen. Moderate positive correlation was found between HbA1c and time spent above the limit and moderate negative correlation with time within the limit. CGM was more precise than HbA1c in defining patients with good control (p<0.05). HbA1c correlates badly with overall glucose excursion (r1=-0.096, r2=0.200, r3=0,377). No difference was found between studied groups in regard to CGM percentage of time spent within the limits, above and below the limits, as well as to AUC above upper limit. We conclude that CGM is more precise than HbA1c in diabetes control assessment and thus in treatment adjustment. Much more information is received from CGM ant the latter gives opportunity to find the most appropriate drug and to achieve optimal results.

Disclosure

T. Totomirova: None. M. Arnaudova: None.
624-P: Sustained Effect in Diabetes Management Using a Digital Workflow and Decision Support System in Home Health Care
Authors: KOPANZ JULIA , SCHOLLE LARA K. , LICHTENEGGER KATHARINA M. , AMBROSCH GISELA , LIBISELLER ANGELA , ABERER FELIX , PANDIS MARLENE , DONSA KLAUS , TRUSKALLER THOMAS , PIEBER THOMAS , MADER JULIA K.
Published: June 2021

Introduction: Basal insulin is the first choice for geriatric persons with type 2 diabetes (T2D) who require insulin therapy. A digital workflow and decision support system (GlucoTab@MobileCare) with an integrated basal or basal-plus insulin algorithm has demonstrated to be an effective and safe treatment in geriatric persons with T2D receiving home health care during a three months study period. The aim of this study was to investigate the long-term effect on diabetes management following treatment by GlucoTab@MobileCare.

Methods: Diabetes related aspects (glycemic control, acute hospital admissions, general practitioner (GP) consultations under routine conditions) were assessed in nine patients (5 female, age 77±10 years, BMI 27.7±4.7 kg/m2, HbA1c 60±13 mmol/mol [start of intervention] vs. 57±12 mmol/mol [end of intervention]) during the three months study intervention, six months before (n=9) and six months after (n=8, due to the death of one patient) study intervention. Data from electronic health records and diabetes documentation were analyzed.

Results: Mean fasting blood glucose (BG) was 212±72 mg/dL before, 156±33 mg/dL during and 162±42 mg/dL after intervention. During the study, no acute hospital admissions due to BG derailments were observed. Eight derailments before and four derailments after intervention occurred. Causes for diabetes-related emergency department (ED) admissions were hyperglycemia (n=10), hypoglycemia (n=1) and undefined (n=1). Nine of the twelve admissions resulted in hospitalizations. GPs were consulted for diabetes management 19-times before and 16-times after GlucoTab@MobileCare treatment. Reasons for consultations were routine check-up (n=12), therapy adjustment (n=22) and HbA1c measurement (n=1).

Conclusion: A sustained effect on glycemic control with reduced requirements for hospital admissions was observed six months after GlucoTab@MobileCare treatment, whereas GP consultations were not affected.

Disclosure

J. Kopanz: None. 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. 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. L. K. Scholle: None. K. M. Lichtenegger: None. G. Ambrosch: None. A. Libiseller: None. F. Aberer: None. M. Pandis: None. K. Donsa: Stock/Shareholder; Self; decide Clinical Software GmbH. T. Truskaller: None.
628-P: Accuracy of Continuous Glucose Monitoring (CGM) for Inpatient Diabetes Management
Authors: WRIGHT JORDAN J. , WILLIAMS ALEXANDER , WEAVER RITA , WILLIAMS JONATHAN M. , BAO SHICHUN
Published: June 2021

In the hospitalized patient with diabetes (DM), adequate glucose control requires frequent measurement of point-of-care (POC) blood glucose. Use of inpatient continuous glucose monitoring (CGM) could reduce workload on the staff, increase ease and frequency of glucose assessment, provide continuous glucose trends, and decrease nurse exposure to infectious patients, but data on accuracy of CGM in the hospital setting is limited. We conducted an observational study of 44 adult patients with DM who were admitted to our hospital non-intensive care units from July-October 2020. After placement of Abbott 14-day Freestyle Libre CGM sensors, patients continued to receive standard POC glucose measurement using the Accu-Chek device. Insulin dosing was based on POC data. 44% percent of participants were female, and 69% had type 2 DM. Median weight was 100.1 kg (IQR 89.0 - 109.5) and median age was 56.6 years (IQR 47.9 - 63.5). Relative to POC glucose measurement, the CGM mean absolute relative difference (MARD), %15/15, and %20/20, three standard measures of CGM accuracy, were 21.4%, 32.6%, and 47.9% respectively. CGM paralleled POC glucose, but CGM readings were consistently lower compared to POC by 20.9% (IQR 12.4 - 28.6). The variation did not change with POC glucose levels or sensor wear-time, though most data (82%) were from the first three days of sensor wear. On multiple regression analysis, participant age, sex, weight, DM type, baseline renal function, and admission HbA1c did not contribute to variation in individual’s MARDs.

In conclusion, we report the accuracy of the Freestyle Libre CGM relative to POC measurements in hospitalized patients. CGM was lower than POC at all glucose levels, and accuracy did not change with other clinical variables measured. Future studies evaluating newer generations of CGMs relative to standardized plasma glucose measurements will further determine the safety and efficacy of using these new technologies for insulin dosing and glucose alerts in hospitalized patients.

Disclosure

J. J. Wright: None. A. Williams: None. R. Weaver: None. J. M. Williams: None. S. Bao: None.
633-P: Optimizing Workflow for Remote Diabetes Data Download: University of Pittsburgh Experience
Authors: KARSLIOGLU-FRENCH ESRA , SISTLA DIVYA , MEYER ANNA C.
Published: June 2021

Background: As CMS started to reimburse videovisits during public health emergency, virtual diabetes care became routine for diabetes clinics. Since better diabetes care depends on review of data, at UPMC, we created a workflow to facilitate diabetes data download before virtual visits. Best practices for virtual diabetes data download is not known.

Objective: To analyze the diabetes technology data download workflow efficiency in our clinic for virtual visits.

Methods: At University of Pittsburgh endocrine clinic, staff reaches out to patients with diabetes who are scheduled for videovisits one week before their appointment with instructions on how to download glucometer, insulin pump and/or CGM data. We completed a retrospective chart review to understand the effectiveness of this workflow in obtaining data before visits.

Results: August 2020 to January 2020, our clinic staff reached out to 1197 patients with diabetes via secure portal before their videovisits to obtain diabetes data download. Patients used Tidepool software to download their pumps and glucometers or cloud technology for CGM data sharing. 164(14%) patients were on insulin pump(with or without CGM), 159(13%) patients had a CGM alone and 874(73%) patients had a glucometer alone. 190(15%) patients uploaded their data to Tidepool, 150 (12%) patients shared their CGM data via cloud using their cell phone apps.873(73%) patients did not download their blood sugar data before appointment, most of these patients had glucometer only. The barriers to sharing data virtually were reported by 104 patients. 25/104 (25%) of patients had no access to a computer. 6 patients (5%) reported having a glucometer that does not have compatibility with Tidepool software. 35/104 (32%) of patients reported not having cable to download their data.

Conclusion: The most common barrier for patients to share their diabetes technology data was lack of cables. Diabetes clinics should analyze their remote diabetes data workflows to troubleshoot barriers.

Disclosure

E. Karslioglu-french: None. D. Sistla: None. A. C. Meyer: None.
639-P: GIP Receptor Agonism Enhances Weight Loss from Either a Biased or an Unbiased GLP-1 Receptor Agonist in DIO Mice
Authors: COGHLAN MATTHEW P. , O’FARRELL LIBBEY , SHOWALTER AARON D. , WAINSCOTT DAVID B. , STUTSMAN CYNTHIA , CARDONA GUEMALLI , CABRERA OVER , ALSINA-FERNANDEZ JORGE , WILLARD FRANCIS S. , SLOOP KYLE , COSKUN TAMER
Published: June 2021

GIP receptor (GIPR) agonism enhances the reduction of food intake and weight loss induced by GLP-1 receptor (GLP-1R) agonism. Recently, GLP-1R agonists have been described that exhibit biased agonism as determined using cells engineered to facilitate measuring the two canonical signaling pathways engaged upon binding the GLP-1R. Such “biased agonists” retain the ability to activate the G alpha S/cyclic AMP (cAMP) pathway to a similar magnitude as native GLP-1 but exhibit markedly weaker ability to induce receptor recruitment of beta-arrestin. The prototype biased GLP-1R agonist Exendin-Phe1 (Ex-Phe1) is reported to exhibit greater weight and glucose control in diet-induced obese (DIO) mice than its unbiased parent Exendin-4 (Ex4). Herein, we investigated whether the enhanced weight loss of Ex-Phe1 erodes the ability of GIPR agonism to further enhance the efficacy of GLP-1R agonism. The peptides were first characterized in vitro to validate the biased nature of Ex-Ph1. In cells expressing either the human or murine GLP-1R, Ex-Phe1 activated cAMP signaling to a similar magnitude as GLP-1 and Ex4 but with approximately 5-fold lower potency than Ex4. The maximum effect of Ex-Phe1 upon human or mouse GLP-1R recruitment of beta-arrestin was 20% compared with full efficacy for Ex4 relative to GLP-1. In this assay Ex-Phe1 was marginally less potent than Ex4. In a 14-day osmotic minipump DIO mice study, Ex4 and Ex-Phe1 each dose dependently reduced food intake and lowered body weight. Ex-Phe1 was 10-fold more potent than Ex4, and at the maximum dose, delivered superior weight loss. Combination treatment with d-Ala-GIP resulted in similar additional body weight loss to that achieved by either Ex-Phe1 or Ex4 alone by enhancing food intake reduction and increasing energy expenditure. D-Ala-GIP alone had no effect on body weight. These findings indicate that GIPR agonism enhances GLP-1R agonism mediated weight loss irrespective of the pathway bias nature of the latter.

Disclosure

M. P. Coghlan: Employee; Self; Eli Lilly and Company. K. Sloop: Employee; Self; Eli Lilly and Company. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. L. O’farrell: None. A. D. Showalter: None. D. B. Wainscott: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. C. Stutsman: None. G. Cardona: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. O. Cabrera: None. J. Alsina-fernandez: None. F. S. Willard: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
64-LB: Glucose Control after Initiation of Flash Glucose Monitoring in Type 2 Diabetes Managed with Basal Insulin: A Retrospective Real-World Chart Review Study from the U.S.
Authors: CARLSON ANDERS L. , DANIEL TIMOTHY D. , DESANTIS ANDREA , JABBOUR SERGE , KARSLIOGLU-FRENCH ESRA , KRUGER DAVIDA F. , MILLER EDEN , OZER KEREM
Published: June 2021

This retrospective, real-world, chart review study determined the effectiveness of the FreeStyle Libre® Flash Glucose Monitoring System on HbA1c when used by adults with type 2 diabetes (T2D) in a real-world setting between 3 months to 6 months after starting FreeStyle Libre. The study population included adults on a basal insulin regimen for at least 1 year, with HbA1c between 8.0 and 12.0% (64 to 108 mmol/mol), using FreeStyle Libre regularly for at least 3 months. Pregnant patients were excluded, as were patients on dialysis.

A total of 100 records from basal insulin using patients with T2D from 8 clinical sites in the US were included in this chart review. Mean HbA1c was 9.4±1.0% (79.2±11.1 mmol/mol), prior to FreeStyle Libre use, age was 56.0±10.3 years, BMI was 36.1±7.8 kg/m2 and average duration of insulin use 4.5±3.5 years (mean±SD); 96.0% of patients were on oral anti-diabetic medications in addition to basal insulin and 52.0% were male. HbA1c results were recorded between 90 to 194 days from the start of use of FreeStyle Libre, between December 2017 and March 2020. To minimise selection bias records were selected on a systematic basis.

After at least 3 months of using FreeStyle Libre in addition to their usual clinical care, HbA1c (primary outcome) was significantly reduced by 1.4±1.3% (mean±SD); p<0.0001. Sub-group analysis by baseline HbA1c (<9.0%, ≥9.0%) showed both groups significantly reduced HbA1c; with reductions of 0.8±0.7%, p<0.0001 and 1.7±1.4%, p<0.0001, respectively.

This real-world, chart review study concluded that people with T2D on basal insulin therapy, using FreeStyle Libre for between 3 to 6 months significantly reduced HbA1c.

Disclosure

A. L. Carlson: Board Member; Self; JDRF, Other Relationship; Self; Medtronic, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Omnipod, Sanofi, UnitedHealth Group. T. D. Daniel: Advisory Panel; Self; Abbott Diabetes, Bayer Healthcare Pharmaceuticals Inc. A. Desantis: None. S. Jabbour: None. E. Karslioglu-french: None. D. F. Kruger: Advisory Panel; Self; Abbott Diabetes, Novo Nordisk, Sanofi US, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Novo Nordisk, Speaker’s Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Self; Pendulum Therapeutics. E. Miller: Advisory Panel; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc., Research Support; Self; Pendulum Therapeutics, Research Support; Spouse/Partner; Abbott Diabetes. K. Ozer: Research Support; Self; Abbott Diabetes, AbbVie Inc., Eli Lilly and Company, Novo Nordisk, Senseonics, Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk.

Funding

Abbott Diabetes Care
68-OR: Artificial Intelligence and Disparities in Pediatric Type 1 Diabetes Care: Predictive Model Performance Varies by Age and Sex
Authors: FERRO DIANA , WILLIAMS DAVID D. , PATTON SUSANA R. , MCDONOUGH RYAN , CLEMENTS MARK A.
Published: June 2021

Background and Aim: We can use predictive models to intensify care among youth with type 1 diabetes (T1D) who are predicted to experience a rise in hemoglobin A1c (HbA1c), yet little is known about the impact of age and sex on the performance of machine learning-based models. We evaluated the performance of a model to predict 90-day change in HbA1c by sex and age.

Method: We applied supervised machine learning (random forest + natural language processing with 305 data features) to electronic health record data from May 2013 to December 2018 for 1725 youth aged 1-20 years with T1D seen at a Midwest US diabetes center with 11 sites. Eligible encounters included those with an HbA1c measurement >70 days (median 106 days; IQR 94,132) after baseline, with resampling of youth who had multiple eligible encounters. We evaluated model performance characteristics (sensitivity, positive predicted values [PPV]) by age and sex to evaluate for disparities in performance.

Results: Median youth age was 14.3 years (IQR=10.9, 16.5), with 50.9% female and 17% non-Hispanic, non-white. Sensitivity and PPV of the model for predicting HbA1c rise of ≥0.3% were 12.4% and 47.2%, in the overall cohort, 13.8% and 51.4% in males, and 10.9% and 0.4% (p<0.05) in females, respectively. Across age strata, senstivitity for males vs. females was 12.7% vs. 13% and 14.9% vs. 10.9% in youth 0-9 and 9-18 years old, respectively. PPV for males vs. females was 41% vs. 36% (p<0.05), 54% vs. 43%, and 33.3% vs. 57.1% (p<0.05) in youth 0-9 and 9-18 respectively.

Conclusions: Predictive models used in clinical practice should be examined for disparities in performance across groups. Our present predictive model exhibits disparities in performance characteristics by sex and age. Whether the model performs differently among groups defined by race, ethnicity, socioeconomic status, and treatment modalities remains to be determined; such disparities have the potential to exacerbate disparities in healthcare delivery.

Disclosure

D. Ferro: None. D. D. Williams: None. S. R. Patton: None. R. Mcdonough: None. M. A. Clements: Consultant; Self; Eli Lilly and Company, Employee; Self; Glooko, Inc., Research Support; Self; Abbott Diabetes, Dexcom, Inc.
686-P: The Association of British Clinical Diabetologists (ABCD) United Kingdom Nationwide Semaglutide Audit
Authors: CRABTREE THOMAS S.J. , BICKERTON ALEX , SENNIK DEVESH K. , ROHILLA ANURITA , SIVAPPRIYAN SIVA , BARNES DENNIS , CULL MELISSA L. , GALLEN IAN W. , ADAMSON KAREN , RYDER ROBERT E.
Published: June 2021

In January 2019, the ABCD nationwide semaglutide audit was launched with the aim of providing real world evidence on semaglutide use in UK clinical practice.

Methods: Data were extracted from the ABCD audit tools and included providing they had sufficient follow-up data. Data were analysed in Stata SE 16. A planned sub-analysis of those switched from any other glucagon like peptide receptor-1 agonist (GLP1-RA) was performed.

Results: 1467 patient data sets were included with a mean±SD age 58.9 years ±11.1, weight 106.4kg ±23.2, BMI 36.8kg/m2 ±7.4, HbA1c 9.4% ±1.7 (79.1mmol/mol±18.6). This population is significantly different to the randomised control trial populations which had mean weight approx. 93kg and mean HbA1c approx. 8.2% (66mmol/mol). Median diabetes duration 10.6 years (IQR 5-14.7); 55.3% were male. The median follow-up period was 0.6years (IQR 0.4-0.8). In this cohort mean changes in HbA1c -1.2% (95% CI -1.1, -1.3) or -13.2mmol/mol (95% CI -11.8, -14.5) (P<0.0001), weight of -4.6kg (95% CI -3.9, -5.2; P<0.0001) and BMI -1.5kg/m2 (95% CI -1.3, -1.7, P<0.0001) were noted from baseline across the population as a whole. 319 (21.75%) were switched from an alternative GLP1-agonist. Further changes in HbA1c of -0.8% (95% CI -0.6, -1.0) or -7.8mmol/mol (95% CI -5.4, -10.1)(P<0.0001) and weight (-3.4kg; 95% CI -2.4, -4.3; P<0.0001) were noted following the switch to semaglutide.

Conclusion: This early analysis demonstrates the differences between our real-world cohort and the more stringently controlled randomised control trial cohorts - in the UK semaglutide is being used in people with diabetes who are heavier and with higher HbA1c levels at baseline. Additional reductions in HbA1c and weight were observed in those switching from alternative GLP1-RAs.

Disclosure

T. S. J. Crabtree: Other Relationship; Self; Novo Nordisk, Sanofi. R. E. Ryder: Other Relationship; Self; Novo Nordisk. A. Bickerton: None. D. K. Sennik: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. A. Rohilla: None. S. Sivappriyan: None. D. Barnes: None. M. L. Cull: None. I. W. Gallen: None. K. Adamson: None.

Funding

Association of British Clinical Diabetologists
701-P: Feasibility of an Investigational Extended Wear Infusion Set for Insulin Pump Therapy (IPT) in People with Type 1 Diabetes Mellitus
Authors: O’NEAL DAVID N. , VENKATESH NISHA , BROWN KATRIN , EKINCI ELIF I. , FOURLANOS SPIROS , KASTNER JASMIN R. , MACISAAC RICHARD , MUCHMORE DOUGLAS B.
Published: June 2021

Background: Reliable insulin delivery is critical in the management of type 1 diabetes. Limitations of insulin pump therapy (IPT) are the maximum cannula life of three days, and a reported failure rate of 15-25% prior to this, which may impact glycemia and quality of life.

Objective: We aimed to determine the feasibility of a prototype cannula for an extended wear infusion set.

Materials and Methods: CapBio’s SteadiFlow technology (Capillary Biomedical, Irvine, CA, USA) consists of a cannula with a soft outer polymer reinforced by an internal metal coil to prevent kinking and three additional side ports to reduce the risk of cannula blockages. Adults with type 1 diabetes using IPT participated in a study with three study periods. For each period a new infusion set was inserted for an intended wear of 7 days. During Period 1 saline was infused via the investigational set through an additional insulin pump. During Periods 2 and 3 insulin lispro was delivered via the investigational set connected to the participant’s own insulin pump. Results are expressed as mean (SD).

Results: Twenty participants (Medtronic 640G [n=11]; 670G [n=3]; Tandem t-slim X2 [n=6]) with type 1 diabetes (age 44Y [14]; HbA1c 7.3% [0.6]/56mmol/mol [6]; female 50%) were studied. The 7-day survival rates of the prototype cannula set were 19/20 (95%) for period one and 36/41(88%) for periods two and three combined. No serious adverse events were reported. Mild infusion site reactions occurred in 7 participants. Hyperglycemia was reported as an adverse event in 7 participants resulting in premature cannula removal in 4 cases (occurring, respectively, on Days 1, 2, 5, and 6 during Weeks 2 or 3). Infusion site infection caused the 5th premature removal (on Day 3). Post-removal, no kinked cannulas were observed.

Conclusions: These study results confirm the feasibility of the extended-life investigational cannula. Larger, randomised studies are required to confirm these preliminary observations.

Disclosure

D. N. O’neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. N. Venkatesh: None. K. Brown: None. E. I. Ekinci: None. S. Fourlanos: Advisory Panel; Self; Pfizer Foundation, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. J. R. Kastner: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. D. B. Muchmore: Consultant; Self; Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc., Zucara Therapeutics Inc., Stock/Shareholder; Self; Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc.
707-P: Use of Advanced Insulin Delivery Systems Is Not Associated with Fear of Hypoglycemia or Diabetes Treatment Satisfaction in Children and Their Caregivers with Type 1 Diabetes
Authors: ABDULHUSSEIN FATEMA , WONG JENISE C.
Published: June 2021

Hypoglycemia occurs frequently in children with type 1 diabetes (T1D). However, the relationship between fear of hypoglycemia (FOH) and use of diabetes technology with different insulin delivery systems has not been well studied. Similarly, little is known about the relationship of diabetes treatment satisfaction with advances in diabetes technology in the pediatric population. Caregivers of children 6-17 years with T1D (n=104, 84% female caregivers, median T1D duration 5.3 years, mean GMI 7.5 ± 0.7%, 93% insulin pump users, 92% CGM users) using any insulin delivery system (8% MDI, 0.05% pump alone, 31% sensor augmented pump, 23% predictive low glucose suspend, 38% hybrid closed loop) completed the Hypoglycemia Fear Survey - Parent (HFS-P) and the Diabetes Treatment Satisfaction Questionnaire - Parent (DTSQ-P). Youth 13-17 years (n=35, 56% males) also completed the HFS - Child (HFS-C) and DTSQ - Child (DTSQ-C). Linear regression was used to look for associations between HFS and DTSQ scores and clinical factors, and paired t-tests were used to compare scores between caregivers and youth. Female caregivers had higher mean HFS Worry and Behavior scores than male caregivers (Worry 1.4 ± 0.18 vs. 0.88 ± 0.16, p=0.004; Behavior 4.9 ± 0.39 vs. 3.9 ± 0.3, p=0.008). Longer duration of diabetes, duration of pump use, and duration of CGM use were all associated with higher mean HFS-C Worry scores, but not with HFS-P Worry scores. The use of different insulin delivery systems was not associated with any HFS scores. Caregivers had a higher mean HFS Behavior score (4.8 ± 0.29) than youth (2.2 ± 0.078) (p <0.0001). The only clinical factor that was associated with a lower DTSQ-P score was higher GMI (β-coefficient -0.22 ± 0.11, p=0.05). These data suggest that despite recent advancements in diabetes technology, FOH and diabetes treatment satisfaction still remain significant concerns and need to be addressed in clinical contexts.

Disclosure

F. Abdulhussein: None. J. C. Wong: Advisory Panel; Self; Provention Bio, Inc., Research Support; Self; Dexcom, Inc., Tandem Diabetes Care.
710-P: Real-World Evaluation of Glycemic Outcomes by Prior Therapy for People with Type 1 and Type 2 Diabetes Onboarding to Control-IQ Technology
Authors: MORBERG JOHN W. , SINGH HARSIMRAN , MCELWEE-MALLOY MOLLY , HABIF STEPHANIE , CONSTANTIN ALEXANDRA
Published: June 2021

Previous research has demonstrated significantly improved glycemic outcomes in people with type 1 diabetes (PWT1D) and type 2 diabetes (PWT2D) who initiated use of Control-IQ technology by updating their existing pump software. This study examined glycemic outcomes by prior therapy (excluding software updaters) for PWT1D and PWT2D after they onboarded to Control-IQ technology. We performed retrospective analyses involving PWT1D and PWT2D from the US who purchased a new Tandem pump with Control-IQ technology and uploaded their pump data to t:connect® web application from Tandem Diabetes Care as of December 7, 2020. In all, 29,732 participants (94% T1D, 6% T2D) were included in the analysis. Median age of the sample was 40 years and majority had been using an insulin pump as prior therapy (66%) while 34% were transitioning from MDIs. After receiving their Tandem pump, prior pump users started using Control-IQ technology earlier (median days: T1D=16, T2D=16) than prior MDI users (T1D=21 days, T2D=23 days), mainly reflecting additional training provided to prior MDIs to onboard successfully to the new system. After 180 days of starting Control-IQ technology, for prior pump users with T1D, TIR was 74% (median, IQR 65-81%) and time below <70mg/dl (TBR) was 1.2% (IQR 0.6-2.1%). For prior pump users with T2D, TIR was 76% (IQR 69-82%) and TBR was 0.5% (IQR 0.2-1.0%). For participants transitioning from MDI, Control-IQ technology resulted in TIR of 74% (IQR 64-83%) and 0.9% TBR (IQR 0.4-1.7%) for PWT1D and 74% TIR (IQR 63-84%) and 0.3% TBR (IQR 0.1-0.6%) for PWT2D. Irrespective of prior therapy, PWT1D changed their pump settings (e.g., basal rates, carbohydrate ratio) more frequently (median: 3) vs. PWT2D (median: 2). Using Control-IQ technology, both PWT1D and PWT2D (irrespective of prior therapy) achieved very similar TIR outcomes. However, T2D users showed lower rates of hypoglycemia (TBR) vs. their T1D counterparts.

Disclosure

J. W. Morberg: Employee; Self; Tandem Diabetes Care. H. Singh: Employee; Self; Tandem Diabetes Care. M. Mcelwee-malloy: Employee; Self; Tandem Diabetes Care. S. Habif: Employee; Self; Tandem Diabetes Care. A. Constantin: Employee; Self; Tandem Diabetes Care.
719-P: Caloric Intake, Appetite, and Body Composition Outcomes of Long-Term Intranasal Insulin (INI) Administration: A Substudy of the Memory Advancement by INI in Type 2 Diabetes (MemAID) Study
Authors: BECERRA LAURA APONTE , KHAN FAIZAN , NGO LONG H. , NOVAK VERA , MANTZOROS CHRISTOS ,   MEMAID COLLABORATORS, GAVRIELI A. , UPADHYAY J.
Published: June 2021

Centrally administered insulin stimulates the reward system to reduce appetite in response to food intake in animal studies. Previous studies in humans have shown mixed results, suggesting INI may decrease appetite, body fat, and weight in non-obese and young males, but this hypothesis has not been tested in elderly with and without type 2 diabetes. This randomized, doubled blind trial consisted of 24 weeks of treatment with either 40 IU of INI (Novolin® R) or Placebo (sterile saline) once daily in elderly adults from MemAID. The primary outcome was the INI effect on food intake, and secondary outcomes included appetite, anthropometric measures, and body composition. In exploratory analyses, we tested the effect of INI on these outcomes when contrasting individuals by gender, BMI, and type 2 diabetes. Randomization included 121 participants, of which 89 (42 women, 53%; age 65±9 years; 46 INI, 52%; 38 diabetes, 43%) completed baseline and at least one intervention visit. Of those, 70 completed treatment (31 diabetes). There was no INI effect on caloric intake on any of the secondary outcomes. Sub-analyses comparing participants within the INI group also showed no differential effect on primary and secondary outcomes. We did not observe an overall INI effect on food intake, appetite, anthropometric measures, and body composition. However, whether insulin resistance may limit the effect of INI in participants without type 2 diabetes remains to be explored. Further research on the mechanisms underlying the potential effect of INI on appetite centrally is warranted (NCT02415556).

Disclosure

L. Aponte becerra: None. F. Khan: None. L. H. Ngo: Consultant; Self; Five Islands Consulting, Other Relationship; Self; Radiological Society of America. V. Novak: Advisory Panel; Spouse/Partner; Endonovo Therapeutics, Inc., Consultant; Spouse/Partner; Dysimmune Foundtation, Other Relationship; Spouse/Partner; Oxford University Press. Memaid collaborators (a. gavrieli, j. upadhyay): n/a. C. Mantzoros: Advisory Panel; Self; Amgen Inc., GENFIT, Intercept Pharmaceuticals, Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK103902); U.S. Food and Drug Administration (IND107690); Novo Nordisk (ISS-001063), Medtronic (NERP15-0310); World Health Organization (UTN-U111-1175-1588)