bluuebunny/crossref_metadata_2025 huggingface dataset:
888-P: Day vs. Nighttime Performance of Continuous Glucose Monitoring Systems in Children with Type 1 Diabetes during a Diabetes Summer Camp
Authors: RAMI-MERHAR BIRGIT , NAGL KATRIN , BERGER GABRIELE , SCHÜTZ ANNA , ABERER FELIX , MADER JULIA K.
Published: June 2020

Continuous subcutaneous glucose monitoring (CGM) use is increasing in diabetes care. Still there are concerns with regard to sensor accuracy especially at night.

Aim of the Study: To assess accuracy of commonly used CGM systems at a 2 week diabetes camp in children with type 1 diabetes (T1D) ages 9-14 years.

Out of 38 children, 37 routinely wore a CGM system throughout the camp. Baseline characteristics: age 11.0 (9.9;12.1) years; 57% girls; HbA1c 7.2% (6.9; 7.7); diabetes duration 3.6 (2.7; 6.3) years (median (interquartile range)). Capillary glucose measurements were performed prior to main meals, at bedtime and whenever deemed necessary by medical staff after thoroughly cleaning the finger tips. Calibrations of Medtronic Enlite was performed twice daily when glycemia was stable. All concomitantly available data pairs were used for the analysis. Night-time was defined as period when children were supposed to be in bed (10 PM until 7 AM).

Sensor distribution: 51% Abbott Libre, 35% Medtronic Enlite, 14% Dexcom G6.

CGM accuracy shown in Table 1: MARD in % (interquartile range)).

Sensor performance of the adequately calibrated Medtronic system outperformed the factory-calibrated sensors in most situations. All sensors performed worse in hypoglycaemia. During the nights the MARD was higher, potentially due to pressure artefacts.

Disclosure

B. Rami-Merhar: Advisory Panel; Self; Abbott. Speaker’s Bureau; Self; Eli Lilly and Company, Medtronic. K. Nagl: None. G. Berger: None. A. Schütz: None. F. Aberer: None. J.K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Medtronic, Prediktor Medical, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis.
889-P: Online Education Improves Clinical Knowledge/Competence Related to Use of Newer CGM Technologies and Standardized Reports
Authors: LARKIN AMY , LACOUTURE MICHAEL , LE ANNE
Published: June 2020

Educational design included a “test, then teach” approach to elicit cognitive dissonance, with evidence-based feedback provided following each learner response. A repeated pairs pre-/post-assessment study design with 3 case-based questions and 1 confidence question was used. A chi-square test and Cramer’s V (<0.05 no effect; 0.06-0.15 small effect, 0.16-0.30 medium effect, >0.30 large effect) were used to measure educational impact. Data were collected from February 4, 2019 to March 4, 2019.In total, 84 ENDOs and 415 PCPs answered all pre-/post-assessment questions and were included in the analysis. In addition, 33% of ENDOs and 35% of PCPs reported increased confidence interpreting and using glucose data from an AGP report.

This study demonstrates the success of interactive, case-based education on improving interpretation and clinical application of data from an AGP report. Future education on this topic should focus on different patient case scenarios in cardiology in order to give cardiologists a chance to apply guidelines and data to various types of patients in real-world clinical scenarios.

Disclosure

A. Larkin: None. M. LaCouture: None. A. Le: None.

Funding

Abbott Diabetes Care
904-P: Therapeutic Decisions Based on Interval Analysis of Blood Glucose Curves of Ambulatory Glucose Profile Help Improving Blood Glucose and Glycemic Variability
Authors: MAKKAR BRIJ M. , SOOTA KIRTI , GUPTA VIPUL , SHARMA JUGAL K. , KHURANA GIRISH , CHAWLA RAJEEV , JAGGI SHALINI , THACKER HEMANT
Published: June 2020

Background: India is a low-middle income country and cost constraints affect use of emerging technologies in diabetes management. Ambulatory Glucose Profile(AGP) using Libre-pro(Abbott) to assess 14 days ambulatory blood glucose(BG) levels and glucose variability(GV) is used sparingly due to cost concern. Many physicians use interval analysis based on AGP data retrieval at 5-7 days to modify treatment and also evaluate its impact on BG levels at 14 days. However, there is little or no published data on this.

Aim: To assess whether treatment modifications based on interval analysis of daily glucose curves during AGP can improve glucose levels and reduce glucose variability METHOD We analyzed records of 40 type 2 diabetes(T2D) patients(27 men, 13 women, age 17-78 years) who had undergone AGP using Libre-pro and in whom interval analysis of daily BG curves was performed at 7 days. In these patients data was retrieved and analyzed at 7th day during AGP and treatment was modified based 0-7day data. AGP was continued and complete data was retrieved at 14th day. Comparison was made for average BG and for time in-, above- and below target range, before and after the 7th day treatment modifications.

Results: Analysis of AGP records showed a significant reduction in 7-14 days mean BG levels after intervention at 7th day as compared to 0-7 days mean(152.11±35.29 vs. 173.23±46.4mg/dl, p=0.025). Time in target range increased from 32.33±22.51% to 41.82±21.67% but was not statistically significant(p=0.059). Time above target range decreased significantly from 62.78±25.54% to 50.85±25.86%(p=0.041) while change in time below target range was non-significant(4.97±6.91% vs. 6.62±7.66%, p=0.32).

Conclusion: Treatment decisions based on Interval analysis of AGP data are effective in significantly reducing blood glucose levels and glucose variability in type 2 diabetes patients. Time in range also increased but was statistically not significant.

Disclosure

B.M. Makkar: Advisory Panel; Self; Abbott, AstraZeneca, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Eris Lifesciences, Novartis AG, Novo Nordisk Inc., Sanofi, USV Private Limited. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc. K. Soota: None. V. Gupta: Advisory Panel; Self; Intas Pharmaceuticals Ltd., Sun Pharmaceutical Industries Ltd. J.K. Sharma: None. G. Khurana: None. R. Chawla: None. S. Jaggi: None. H. Thacker: None.
911-P: Independent Accuracy Verification of a Smartphone App’s Blood Glucose Prediction Algorithm
Authors: KRIVENTSOV STANISLAV , HAYERI AMIR
Published: June 2020

Smartphone applications have become important health management tools for patients with diabetes. In particular, short-term blood glucose predictions offered by some apps can help reduce the frequency and duration of hypo- and hyperglycemic events, which makes the accuracy of such predictions essential for better glycemic control.

In this paper, we describe the results of an in-silico study designed to measure the predictive accuracy of the algorithm of our smartphone app. In this study, an FDA-approved blood glucose simulator was used by an independent third party to generate 180 days of realistic glycemic data for 300 virtual patients under 3 different study protocols. This data (about 225 million blood glucose points with accompanying food, insulin, and exercise information) was sent consecutively, one temporal point at a time to avoid the possibility of future data leakage, to our predictive module, which generated personalized predictions of blood glucose levels for the next 60 minutes and sent the results back to the third party to be used in accuracy metrics calculation. Several versions of the predictive algorithm were tested, including one using only CGM data, and another that also took into account recent food, insulin, and exercise events.

In the end, for CGM-only models trained on 20,000 prior blood glucose points from the same patient, 93.16% of 30-minute predictions and 79.54% of 60-minute predictions ended in Parkes Zone A (clinically accurate), and 99.71% of 30-minute predictions and 98.82% of 60-minute predictions in Parkes Zones A and B (clinically acceptable). For the models that used additional inputs, Parkes Zone A percentages improved to 98.67% of 30-minute predictions and 92.51% of 60-minute predictions, while Parkes Zones A and B percentages rose to 99.99% of 30-minute predictions and 99.72% of 60-minute predictions. For both models, the high degree of accuracy achieved in the study shows the usability of our approach for real-time glycemic predictions.

Disclosure

S. Kriventsov: Employee; Self; Bio Conscious Tech. A. Hayeri: Other Relationship; Self; Bio Conscious Technologies INC (DBA Diabits).
918-P: Effectiveness of Freestyle Libre Flash Glucose Monitoring System on the Diabetes Distress among Type 1 Diabetes: A Prospective Study
Authors: ALDAWISH MOHAMMED
Published: June 2020

Aim: The purpose of this study was to investigate the intervention of flash glucose monitoring system (FGM) on the diabetes related distress among young type 1 diabetes.

Methods: A 12 weeks prospective study was carried out among 187 children and adolescents (aged 13-19 years, 56.7% female) with T1D, who used conventional finger-pricking method for self-testing the glucose. The trial was conducted between March 2019 and July 2019. For carrying out the study, the FGM sensors were placed on each participant, at the baseline visit, by a trained diabetes educator. In addition, a trained interviewer handed over the 28-item T1-Diabetes Distress Scale (T1-DDS) questionnaire to each patient, at the baseline and at 12 weeks of the study in order to collected Diabetes Distress (DD) score.

Results: In comparison to the baseline (finger pricks), the subdomains of DD such as: powerlessness (P = 0.0001), management distress (P = 0.0001), hypoglycemia distress (P = 0.0001), negative social perceptions (P = 0.0001), eating (P = 0.0001), physician distress (P = 0.0001), friend/family distress (P = 0.0001) and total T1-DDS score (P = 0.0001) were significantly decreased at 12 weeks after switching the patients from finger pricks to flash FGM. Similarly, after switching the patients to FGM, there were notable decrease were found on the clinical variable such as HbA1c at 12 weeks. After 12 weeks, we also observed significant decrease in hypoglycemia and interestingly, the frequency of glucose checking were increased among the FGM users.

Conclusion: the findings of this study evidently illustrated that after switching the patients from finger pricks to flash FGM, significant improvement were observed on DD related clinical parameters. However, further studies are required, for ascertaining whether the prolonged and consistent use of the FGM system will result in improved outcomes.

Disclosure

M. Aldawish: None.
92-LB: Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes
Authors: AWAL HASSAN , NANDULA SESHAGIRI RAO , KUNDU NABANITA , SEN SABYASACHI
Published: June 2020

Introduction: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes and chronic kidney disease (CKD) leading to poor regeneration of endothelium. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP-4 inhibitors such as Linagliptin (LG) on CVD risk in patients with type 2 diabetes with established CKD has not been established.

Hypothesis: Linagliptin, a DPP-4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD)

Methods: 31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 DM subjects (30-70 years old), A1c of 6.5-10%, CKD Stage 1-3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as Arterial stiffness, biochemistry, resting energy expenditure were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value <0.05 considered significant.

Results: A double positive CD34/CD184 cell count had a statistically significant increase (p<0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (SOD2, Catalase and CPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p<0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). Urinary exosome protein examining podocyte health (Podocalxyin, Wilms tumor and Nephrin) showed reduction or improvement.

Conclusions: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks.

Disclosure

H. Awal: None. S. Nandula: None. N. Kundu: None. S. Sen: None.
921-P: Liraglutide Improves NAFLD in Patients with Type 2 Diabetes
Authors: BASU DEBASIS , CHAUDHURI SOUMYABRATA ROY , DEKA NILAKSHI
Published: June 2020

Introduction: The present study was conducted to evaluate the effects of Liraglutide on NAFLD in patients with type 2 diabetes mellitus (T2DM) with elevated transaminases.

Methods: A total of 62 patients (male-38, female-24) with age group of 30-75 years, treated with Liraglutide 1.2 mg/1.8 mg OD were included in the study. Selected clinical and demographic profile were recorded for all patients at baseline and follow-up. The hepatic steatosis was assessed using liver elastography (Fibroscan).

Results: After a mean follow-up of 26 weeks, in 62 patients (meeting appropriate present inclusion criteria), there was significant reduction in weight from 88.63±8.6 kg (Mean ± SD) to 80.47±6.7 kg (p<0.001), as computed by paired t-test. The Mc-Nemar’s test also demonstrated a significant higher proportion of patients with reversibility of stage of fibrosis from baseline to follow-up, p=0.003. This is accompanied by significant reduction in the AFRI score from a baseline median(IQR) of 1.84 (1.61-2.73) to 1.26(1.19-1.48) (p<0.001), as computed by Wilcoxon signed rank test. At baseline, 6 had fibrosis stage 2, of which 4 regressed to stage 1 and 2 had no significant fibrosis at baseline; 24 had stage 3 fibrosis, of which 20 regressed to stage 2, 2 to stage 1 and 2 had no significant fibrosis at follow-up. Remaining 32 had stage 4 fibrosis, of which 12 had stage 3, 18 had stage 2 and only 2 had stage 1 fibrosis at follow-up. ALT and AST decreased from 47.65±4.65 to 24.31±5.43 and 29.67±2.21 to 17.65±4.59 respectively. There was also significant improvement in glycaemic control with reduction in HbA1c from 8.56 ± 0.56% to 7.21 ± 0.34%, p<0.001 along with significant reduction in systolic blood pressure from 133.26±11.39 mmHg to 122.81±7.29 mmHg (p<0.001) and diastolic blood pressure from 87.17±6.04 mmHg to 82.91±4.33 mmHg (p<0.001).

Conclusion: Liraglutide significantly reduces hepatic fibrosis and effectively cause reversal of elevated transaminases along with weight loss and blood pressure reduction in addition to good glycaemic control.

Disclosure

D. Basu: None. S. Roy Chaudhuri: None. N. Deka: None.
93-LB: Preferences and Health State Utilities Associated with Routes of Administration for Oral Semaglutide, Injectable Semaglutide, and Dulaglutide
Authors: BOYE KRISTINA , CUTTS KATELYN , STEWART KATIE , NORRBACKA KIRSI , GARCÍA-PÉREZ LUIS E. , MATZA LOUIS S.
Published: June 2020

Objective: Previous studies have examined health state utilities (which are preference weightings for use in cost-effectiveness analyses) associated with injectable GLP-1 receptor agonists for treatment of type 2 diabetes (T2D). An oral formulation of semaglutide (sema) has recently become available. This study estimates health state utilities representing preferences associated with routes of administration for daily oral sema and two weekly injectable GLP-1 receptor agonists.

Methods: Participants with T2D in the UK valued four health state vignettes (drafted based on drug labels and device instructions for use) in time trade-off interviews to estimate preference-based utility scores. The vignettes had identical descriptions of T2D, but differed in treatment process: (1) daily simple oral treatment (tablets without specific administration requirements), (2) daily oral sema (tablet with administration requirements per product label), (3) weekly dulaglutide (dula) injection, (4) weekly sema injection.

Results: Interviews were completed by 201 participants (52.7% male; mean age=58.7). Preferences among routes of administration varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral sema, 0.878 for dula injection, and 0.859 for sema injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences among the four utility scores (p<0.01), except the comparison between oral sema and dula which was not significant (p=0.49).

Conclusions: While some participants preferred daily oral treatment, others preferred one of the weekly injections. Results suggest that patient preferences for routes of administration cannot be compared using only the simplest descriptions (e.g., “oral” vs. “injectable”). The details of treatment administration and treatment frequency have an impact on preference and should be considered.

Disclosure

K. Boye: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Eli Lilly and Company. K. Cutts: Employee; Self; Evidera. K. Stewart: Employee; Self; Evidera. K. Norrbacka: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L.E. García-Pérez: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. L.S. Matza: Employee; Self; Evidera.
930-P: Efficacy of Oral Semaglutide According to Race: An Exploratory Subgroup Analysis of the PIONEER Trial Program
Authors: DESOUZA CYRUS , AMOD ASLAM , KALLENBACH KLAUS , LIN PETER J. , NIELSEN MORTEN ABILDLUND , SØRRIG RASMUS , MONTANYA EDUARD
Published: June 2020

The global PIONEER program investigated the efficacy and safety of oral semaglutide, a glucagon-like peptide-1 receptor agonist. Patients with type 2 diabetes were randomized to once-daily oral semaglutide (3, 7 or 14 mg, or flexibly dosed [flex]), placebo, or active comparator (empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg). This exploratory subgroup analysis evaluated the effect of race on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of treatment (week 26, 52 or 78). Data were analyzed from PIONEER 1-5, 7 and 8 by race (White, Asian, Black/African American). Baseline characteristics were generally similar across subgroups except for BW, which was lower in Asian patients. Generally, greater HbA1c reductions were observed with oral semaglutide 14 mg/flex vs. comparators across subgroups (Table). In PIONEER 1, 4 and 8, there was a significant interaction between treatment and race, with greater HbA1c reductions and estimated treatment differences in Asian patients than in other subgroups (Table). Overall, BW reductions were greater for oral semaglutide vs. comparators, regardless of subgroup and without significant interactions between treatment and race. Our findings in this exploratory subgroup analysis suggest that, in some PIONEER trials, Asian patients achieve greater HbA1c reductions than other race groups when treated with oral semaglutide.

Disclosure

C. Desouza: Consultant; Self; AstraZeneca, Bayer AG, Novo Nordisk A/S. A. Amod: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi-Aventis, Servier. Consultant; Self; Servier. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk A/S, Sanofi-Aventis, Servier. K. Kallenbach: None. P.J. Lin: Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch + Lomb, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Mead Johnson Nutrition, Merck & Co., Inc., Novo Nordisk Inc., Sun Pharmaceutical Industries Ltd. Other Relationship; Self; Elsevier. M. Abildlund Nielsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. R. Sørrig: Employee; Self; Novo Nordisk A/S. E. Montanya: Advisory Panel; Self; Sanofi. Consultant; Self; Novartis Pharmaceuticals Corporation. Employee; Spouse/Partner; Almirall. Speaker’s Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S.

Funding

Novo Nordisk A/S
933-P: Greater Reductions in HbA1c and Body Weight with Once-Weekly Semaglutide vs. Comparators across Baseline BMI Subgroups: A Post Hoc Analysis of SUSTAIN 1-5 and 7-10
Authors: ARODA VANITA R. , FRENKEL OFIR , FRIAS JUAN P. , HINDSBERGER CHARLOTTE , GYLVIN SILAS H. , ROUX CAREL LE , MADSBAD STEN
Published: June 2020

In the SUSTAIN trial program, once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for treatment of type 2 diabetes, significantly reduced HbA1c and body weight (BW) vs. all comparators, with a safety profile consistent with the GLP-1RA class. Patient factors (e.g., BMI) may impact therapeutic choices. This post-hoc analysis of SUSTAIN 1-5 and 7-10 evaluated change from baseline to end of treatment in HbA1c and BW with OW semaglutide vs. comparator by baseline BMI subgroup. On-treatment without rescue medication data were evaluated in the full analysis set. Mixed model for repeated measurements analyses evaluated interaction between treatment and BMI subgroup by trial. Overall, 572, 1,867, 2,103 and 2,217 subjects with BMI <25, ≥25-<30, ≥30-<35 and ≥35 kg/m2, respectively, were evaluated. Estimated treatment difference for change in HbA1c favored semaglutide vs. comparator in most subgroups, and for BW favored semaglutide vs. comparator in all subgroups (Table). In general, treatment-by-subgroup interactions were nonsignificant (p>0.05); however, BW reduction was greater with semaglutide 1.0 mg vs. insulin with increasing BMI (p=0.005).

In summary, semaglutide resulted in greater reductions in HbA1c and BW vs. comparators in SUSTAIN 1-5 and 7-10; this effect was generally observed across BMI subgroups.

Disclosure

V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. O. Frenkel: Employee; Self; Novo Nordisk A/S, Roche Pharma. J.P. Frias: Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., LifeScan, Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Allergan plc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi. Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. C. Hindsberger: Consultant; Self; Novo Nordisk A/S. S.H. Gylvin: Employee; Self; Novo Nordisk A/S. C. le Roux: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., GI Dynamics Inc., Herbalife International of America, Inc., Johnson & Johnson, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Lilly Diabetes. Stock/Shareholder; Self; Keyron. S. Madsbad: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S.

Funding

Novo Nordisk A/S
942-P: Treatment of Weight Regain after Bariatric Surgery: Real-World Comparative Outcomes
Authors: GAZDA CHELLSE , ALMANDOZ JAIME , LINGVAY ILDIKO , CLARK JOHN
Published: June 2020

After bariatric surgery, people frequently do not achieve a healthy weight and/or regain weight. There is limited outcomes data on anti-obesity medications in patients with prior bariatric surgery. GLP-1RAs promote weight loss by decreasing gastric motility and appetite, yet post-prandial levels of GLP-1 are elevated after bariatric surgery. We evaluated weight outcomes in patients with prior bariatric surgery seen in an academic medical center’s weight management program. We compared the following groups: intensive lifestyle modification (ILM) vs. any GLP-1 RA (GLP-1) vs. any non-GLP-1 RA weight loss agents (non-GLP-1) vs. combination of weight loss agents including GLP-1 RA (GLP-1 combination). We included patients with a history of bariatric surgery, at least two clinic visits, and no anti-obesity medications at the initial visit. Data was extracted from the Electronic Medical Record and confirmed by manual chart review. All patients were counseled on lifestyle modification for weight loss. The two GLP-1-based treatment groups had significantly greater % weight loss at 3- and 6-months compared to the ILM group (Figure). In multivariable regression model, adjusting for baseline age and sex, surgery type did not (p=0.2 and p=0.97 for 3- and 6-mo analyses) influence outcome. GLP-1 RA therapies (alone or in combination) are effective for weight loss in patients with prior bariatric surgery, regardless of surgery type.

Disclosure

C. Gazda: None. J. Almandoz: None. I. Lingvay: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Janssen Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk A/S, Sanofi, TARGET PharmaSolutions, Valeritas, Inc. Other Relationship; Self; Novo Nordisk A/S. J. Clark: None.
953-P: Real-World Effectiveness of Once-Weekly Semaglutide (Sema OW) from a U.S. Commercially Insured and Medicare Advantage Population
Authors: VISARIA JAY , UZOIGWE CHIOMA , SWIFT CAROLINE , PAPROCKI YUREK M. , WILLEY VINCENT
Published: June 2020

Background: This study presents real-world evidence on effectiveness of sema OW in a large cohort of T2D patients.

Methods: Claims and lab result data were used to identify T2D patients who initiated sema OW between 2/1/18 - 4/30/19 (index as first claim). Patients selected had ≥1 A1c result within ≤3 months pre- and ≥3 months post-index. All patients and a group of patients persistent on sema OW (those with a sema OW prescription with days supply dispensed overlapping/in proximity of date of post-index A1c measurement) were assessed for A1c changes and were split into 4 subgroups: GLP-1 naïve, GLP-1 experienced and either group with pre-index A1c >9%.

Results: Of 1,888 patients initiating sema OW, 57.8% were GLP-1 naïve. A1c was significantly reduced in all patients (-0.9%) and subgroups (p<0.001, Figure 1). Persistent patients achieved a 1.1% A1c reduction, with similar or greater reductions across subgroups when compared to all patients. Attainment of A1c <7% increased from 23% pre- to 49% post-index for all patients (20 to 30% pre to post increase in each subgroup, all p<0.001).

Conclusion: Initiation of sema OW was associated with significant reduction in A1c and an increase in reaching A1c <7% regardless of a prior history of GLP-1 use. Sema OW also provides significant change in A1c among patients whose A1c was not controlled on their previous GLP-1.

Disclosure

J. Visaria: None. C. Uzoigwe: Employee; Self; Novo Nordisk Inc. C. Swift: Employee; Self; Novo Nordisk Inc. Stock/Shareholder; Self; Novo Nordisk Inc. Y.M. Paprocki: Employee; Self; Novo Nordisk Inc. Stock/Shareholder; Self; Novo Nordisk A/S. V. Willey: Employee; Self; HealthCore.

Funding

Novo Nordisk
972-P: Liraglutide Attenuates Lipid-Induced Microvascular Insulin Resistance in Humans
Authors: LOVE KAITLIN , JAHN LINDA , HARTLINE LEE , LIU ZHENQI
Published: June 2020

Insulin recruits skeletal and cardiac muscle microvasculature to increase insulin and nutrient delivery, but this action is lost in insulin resistant states. Glucagon-like peptide 1 (GLP-1) improves microvascular perfusion in humans with obesity and the GLP-1 receptor agonist liraglutide attenuates muscle microvascular insulin resistance (IR) in rodents. To examine whether GLP-1 receptor agonism improves insulin’s microvascular actions in humans with acute IR, 18 healthy human subjects randomly received a systemic infusion of either saline or lipid emulsion (20%, 45 mL x 1 h and then 30 mL x 4 h) for 5 h or lipid emulsion for 5 h + liraglutide pre-treatment (0.6, 1.2, then 1.8 mg daily SC each x 2 days) with euglycemic insulin clamp (1 mU/kg/min) superimposed for the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow-mediated dilation (FMD), pulse wave velocity (PWV), and augmentation index (AI) were determined before and after insulin clamp.

Compared with saline admission, insulin failed to increase MBV following lipid infusion in both skeletal (28.4 ± 14.1% vs. -1.3 ± 9.6% respectively, p=0.011) and cardiac (28.4 ± 14.1% vs. -1.3 ± 8.9%, p=0.027) muscle, consistent with acute IR induced by lipid infusion in both microvascular beds. Liraglutide pre-treatment improved insulin-mediated increases in MBV in the presence of lipid infusion in skeletal (8.9 ± 13.5%, p=0.117 vs. saline) and cardiac (12.6 ± 12.1%, p=0.101 vs. saline) muscle. There was no significant change in PWV, AI, or FMD amongst admissions. Glucose infusion rates were not significantly different amongst admissions (saline 6.02 ± 0.52, lipid 5.58 ± 0.62, vs. liraglutide + lipid 5.46 ± 0.46 mg/kg/min).

In conclusion, liraglutide pretreatment effectively ameliorates lipid-induced skeletal and cardiac muscle microvascular IR in healthy humans. These data provide a mechanistic insight into the metabolic and cardiovascular benefits of GLP-1 receptor agonism seen in humans with obesity and type 2 diabetes.

Disclosure

K. Love: None. L. Jahn: None. L. Hartline: None. Z. Liu: None.

Funding

American Diabetes Association (1-17-ICST-059 to Z.L.); National Institutes of Health (1R01DK102359-01A1)
974-P: Network Meta-analysis of Once Weekly Glucagon-Like Peptide-1 Receptor Agonists: A Focus on Cardiovascular Safety and Mortality
Authors: ALFAYEZ OSAMAH , ALMOHAMMED OMAR A. , ALKHEZI OMAR , AL YAMI MAJED S.
Published: June 2020

Objective: To indirectly compare once weekly exenatide, semaglutide, albiglutide and dulaglutide regarding cardiovascular (CV) safety and mortality using network meta-analysis (NMA).

Methods: PubMed was searched to identify glucagon like peptide-1 receptor agonists (GLP-1RA) outcome trials (CVOTs) to date. The outcomes of interest were CV death, myocardial infarction (IM), nonfatal MI, stroke, nonfatal stroke, death from any cause, and hospitalizations for heart failure (HF). An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. Data were extracted by two independent reviewers and risk of bias was assessed in the same manner.

Results: The NMA results showed no significant differences among the four GLP-1RAs regarding most of the outcomes. However, albiglutide when compared to exenatide was associated with lower risk of MI (HR 0.76, 95% Cl: 0.60-0.96)] and nonfatal MI (HR 0.76, 95% Cl: 0.60-0.97). The ranking probability showed that semaglutide had the highest probability to be ranked first in reducing MI (55%), nonfatal MI (55%), stroke (87%), and nonfatal stroke events (87%). For CV death and death from any cause, exenatide had the highest probability to be ranked first at 30% and 45% respectively. Lastly, for hospitalizations for HF, albiglutide was ranked first with a probability of 55% followed by placebo.

Conclusion: This NMA did not show significant differences among the treatments. However, based on the ranking results, semaglutide seems to be the preferred agent over the other once weekly GLP-1RAs in patients with diabetes and CV risk.

Disclosure

O. Alfayez: None. O.A. Almohammed: None. O. Alkhezi: None. M.S. Al Yami: None.
975-P: Effect of Late Bolus Injections on Glycemic Variability Studied by Connected Pens
Authors: JENDLE JOHAN H. , HARTVIG NIELS V. , KAAS ANNE , MOLLER JONAS , MÅRDBY ANN-CHARLOTTE M. , CATRINA SERGIU-BOGDAN
Published: June 2020

Mealtime injection of bolus insulin is critical for maintaining good glycemic control in patients with type 1 diabetes (T1D). It has previously been shown in a real-world setting that patients using connected pens had fewer missed mealtime injections of bolus doses as well as improved time-in-range (TIR) compared to baseline. This subgroup post-hoc study examined the effect of using connected pens on timing of bolus doses in adults and the relationship between timing of the insulin dose and glycemic variability. In a non-interventional study, conducted at 12 Swedish diabetes clinics, connected pens with bolus and/or basal insulin were prescribed to adults with T1D. Injection- and continuous glucose monitoring (CGM) data were collected at routine clinic visits. CGM data were also uploaded at home. These data were used by healthcare providers (HCPs) and patients during visits at the clinic. Meals were subsequently detected based on the CGM signals using the clinically validated Glucose Rate Increase Detector algorithm. A bolus dose given 60-120 minutes after the estimated start of the meal was defined as a late-bolus dose. In total 96 patients with 2238 days of acceptable CGM coverage (≥ 70%) were included in the analysis. The mean number of late-bolus doses decreased from 0.32 per day (95% CI [0.26;0.39]) at baseline to 0.18 per day [0.13;0.27] at follow-up, corresponding to a 42% reduction (p = 0.005). A significant correlation between the timing of the bolus dose and the coefficient of variation (CV) of the CGM signal was found; each 10-minute delay of the bolus dose was associated with an increase of 0.5% CV (p < 0.0001) on average. This study confirms that timely injection of bolus doses relative to meals is correlated with a more stable glycemic control. Also, the results indicate that timely bolus dosing can be a challenge in everyday life but that data from connected pens may help support patient behavior through improved interaction with HCP.

Disclosure

J.H. Jendle: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. N.V. Hartvig: Employee; 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. S. Catrina: None.
986-P: Assessment of Adhesive Patches for an Extended-Wear Infusion Set
Authors: ZHANG GINA , CHATTARAJ SARNATH , ANSELMO EVAN , HOFFMAN LANCE , TRAN MICHELLE , BONDY SHANNON
Published: June 2020

Objective: The durability of wearable devices, e.g., insulin infusion sets (IIS), is challenged by external factors such as friction, movement, stretch, moisture, and skin viscoelasticity. Such factors are difficult to investigate in non-clinical settings. We assessed 3 new adhesive patches and compared them to those used with current Medtronic infusion sets to determine which would be suitable for an extended wear infusion set with intended wear time of up to 7 days.

Method: Seventy-five adults were recruited in 3 studies to wear 2 patch variants each on conventional IIS sites, for up to 8 days. Non-functional Medtronic pumps were used to simulate use conditions. The primary outcome was wear time. Secondary outcomes included edge lift and descriptive user feedback (e.g., appearance, comfort, irritation score, residue upon removal, and removal discomfort).

Results: The results (Figure 1) demonstrated that the 7-day survival rate for existing IIS patches varied from ∼70% to ∼90%. These data indicated that the hub form factor played an insignificant role in the adhesive patch wear time. Two of three new adhesive patches had a 7-day survival rate ≥95% without significantly impacting user experience (i.e., wear comfort or skin reactions).

Conclusion: In the simulated-use studies, two new adhesive patches met the primary and secondary outcomes for use with an extended wear infusion set.

Disclosure

G. Zhang: None. S. Chattaraj: Employee; Self; Medtronic. E. Anselmo: Employee; Self; Medtronic. L. Hoffman: None. M. Tran: None. S. Bondy: Employee; Self; Medtronic. Stock/Shareholder; Self; Medtronic.
989-P: Type 1 Diabetes: Real-World Insulin Injection Patterns
Authors: CATRINA SERGIU-BOGDAN , HARTVIG NIELS V. , KAAS ANNE , MOLLER JONAS , MÅRDBY ANN-CHARLOTTE M. , JENDLE JOHAN H.
Published: June 2020

Multiple daily insulin injections are an integral part of life for patients with type 1 diabetes (T1D). Moreover, patients’ schedules can change from day-to-day, further complicating T1D management. This study aimed to analyze daily injection patterns for patients with T1D. This post-hoc observational study included children and adults with T1D from Sweden using NovoPen® 6 with bolus insulin (primarily insulin aspart) and/or basal insulin (primarily insulin degludec). Injection data were uploaded via the Glooko® cloud system. Daily bolus and basal injections timing profiles were documented, weighting each dose relative to the total daily dose. Time difference between two consecutive basal insulin injections was used to evaluate basal timing variation. In total 159 adults and 47 children were included in the analysis, with a total of 38678 days of bolus injections and 17869 days of basal injections. The mean bolus daily injection profile displayed peaks at typical mealtimes but with substantial variation across patients and between adults and children (Figure 1). In those receiving insulin degludec timing of consecutive basal injections differed by more than 6 hr in ∼9% of the injections for adults and 7% for children. These real-world data give a unique insight into the bolus and basal adherence of pediatric and adult patients with T1D. Furthermore, the results illustrate the flexibility needed for basal injections to enable optimal management of T1D.

Disclosure

S. Catrina: None. N.V. Hartvig: Employee; 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. J.H. Jendle: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Sanofi.
993-P: Comparison of Artificial-Intelligence Decision Support for Multiple Daily Injection Therapy with Automated Insulin Delivery after 3 Months of Use in Silico
Authors: TYLER NICHOLE S. , HILTS WADE , MOSQUERA-LOPEZ CLARA M. , WILSON LEAH M. , DODIER ROBERT , YOUSSEF JOSEPH EL , CASTLE JESSICA R. , JACOBS PETER G.
Published: June 2020

While automated insulin delivery (AID) systems are now commercially available, over 40 percent of people with type 1 diabetes manage their insulin with multiple daily injection therapy (MDI). AID systems can improve time-in-range in adults, however it is not clear if optimal MDI therapy can achieve the same glycemic targets. We have previously shown that a K-nearest-neighbors decision support system (KNN-DSS) for MDI can deliver safe recommendations and achieves high agreement with endocrinologists. Here, we report glycemic outcomes as we compare KNN-DSS with two artificial pancreas systems: fading-memory-proportional-derivative (FMPD), and model-predictive control (MPC).

We utilized a platform accepted by U.S. Food and Drug Administration for the evaluation of artificial pancreas technologies, the UVA-Padova simulator. In silico, 100 adults with varying insulin sensitivities, weight, and insulin dosing behaviors underwent a 3-arm study comparing KNN-DSS, FMPD, and MPC algorithms. Each UVA-Padova subject received a unique study meal pattern that was repeated across study arms. The two primary outcome measures were % time-in-range and % time-in-hypoglycemia. Secondary outcome measures included LGBI and HGBI risk index.

The KNN-DSS was able to achieve 79.6 ± 15.4 %time-in-range after 12 weeks compared with 83.6 ± 8.3% for the MPC and 84.2 ± 9.24% for the FMPD. The KNN-DSS achieved comparable time below 70 mg/dL (0.79%, [0 1.6]) with the MPC-AP (0.62%, [0 1.8]) and FMPD (0%, [0 0.72]). The KNN-DSS also achieved comparable LGBI (2.55) with the MPC-AP (2.68). This simulation assumes perfect adherence to insulin dosing regimens, and while % time-in-range may be higher than expected, the results indicate that decision support in MDI may yield comparable glycemic outcomes with automated insulin delivery systems if people are compliant. Results of this study will be used to guide the design of an upcoming human clinical trial.

Disclosure

N.S. Tyler: None. W. Hilts: None. C.M. Mosquera-Lopez: None. L.M. Wilson: None. R. Dodier: None. J. El Youssef: None. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc. Consultant; Self; ADOCIA, Dexcom, Inc., Zealand Pharma A/S. Other Relationship; Self; Pacific Diabetes Technologies, Roche Diabetes Care. P.G. Jacobs: Consultant; Self; SFC Fluidics. Research Support; Self; Dexcom, Inc. Stock/Shareholder; Self; Pacific Diabetes Technologies. Other Relationship; Self; AgaMatrix.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D001)
Association of Long-term Change and Variability in Glycemia With Risk of Incident Heart Failure Among Patients With Type 2 Diabetes: A Secondary Analysis of the ACCORD Trial
Authors: Segar Matthew W. , Patel Kershaw V. , Vaduganathan Muthiah , Caughey Melissa C. , Butler Javed , Fonarow Gregg C. , Grodin Justin L. , McGuire Darren K. , Pandey Ambarish
Published: June 2020

OBJECTIVE

To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS

Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF.

RESULTS

The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08–1.75] and for ≥10% increase 1.55 [1.19–2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17–1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability.

CONCLUSIONS

Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.
The Association Between Age of Onset of Type 2 Diabetes and the Long-term Risk of End-Stage Kidney Disease: A National Registry Study
Authors: Morton Jedidiah I. , Liew Danny , McDonald Stephen P. , Shaw Jonathan E. , Magliano Dianna J.
Published: June 2020

OBJECTIVE

The long-term risk of end-stage kidney disease (ESKD) in type 2 diabetes is poorly described, as is the effect that younger age of diabetes onset has on this risk. Therefore, we aimed to estimate the effect of age of onset on the cumulative incidence of ESKD from onset of type 2 diabetes.

RESEARCH DESIGN AND METHODS

This study included 1,113,201 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2002 until 2013. The NDSS was linked to the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index.

RESULTS

Between 2002 and 2013, there were 7,592 incident cases of ESKD during 7,839,075 person-years of follow-up. In the first 10–15 years following the onset of diabetes, the incidence of ESKD was highest in those with an older age of onset of diabetes, whereas over longer durations of diabetes, the incidence of ESKD became higher in those with younger-onset diabetes. After 40 years of diabetes, the cumulative incidence of ESKD was 11.8% and 9.3% in those diagnosed with diabetes at ages 10–29 and 30–39 years, respectively. When death from ESKD without renal replacement therapy was included, the incidence of ESKD remained higher in older-onset diabetes for the initial 20 years, with no clear effect of age thereafter.

CONCLUSIONS

The long-term risk of ESKD in type 2 diabetes is high, which disproportionately affects those with younger onset of diabetes because they are more likely to survive to longer diabetes durations.
Individual and combined associations of modifiable lifestyle and metabolic health status with new-onset diabetes and major cardiovascular events: the China Cardiometabolic Disease and Cancer Cohort (4C)-Study
Authors: Li Mian , Xu Yu , Wan Qin , Shen Feixia , Xu Min , Zhao Zhiyun , Lu Jieli , Gao Zhengnan , Chen Gang , Wang Tiange , Xu Yiping , Zhao Jiajun , Chen Lulu , Shi Lixin , Hu Ruying , Ye Zhen , Tang Xulei , Su Qing , Qin Guijun , Wang Guixia , Luo Zuojie , Qin Yingfen , Huo Yanan , Li Qiang , Zhang Yinfei , Chen Yuhong , Liu Chao , Mu Yiming , Wang Youmin , Wu Shengli , Yang Tao , Chen Li , Yu Xuefeng , Yan Li , Deng Huacong , Ning Guang , Bi Yufang , Wang Weiqing
Published: June 2020

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

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

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

Conclusions:
We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular
events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health,
highlighting the importance of lifestyle modification regardless of the present
metabolic status.