bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preference Differences between Insulin Glargine and MK-1293 Pens among Patients with Diabetes and Certified Diabetes Educators
Authors: ALEMAYEHU BERHANU , DIBONAVENTURA MARCO , NGUYEN ALLISON M. , CRUTCHLOW MICHAEL 
Published: June 2018

This study sought to develop and implement a usability/preference survey to compare the pen devices used with innovator insulin glargine and MK-1293 (Pen X). Type 1 and type 2 diabetes patients and certified diabetes educators (CDEs) in the U.S., Canada, and the UK were recruited from commercial panels. Several rounds of qualitative research with both groups were conducted to develop and refine the survey. Respondents were asked to perform two mock injections (into a cushion pad) for each of the two insulin pens. Pen order was randomized and after each set of injections, respondents completed the survey. Non-inferiority analyses were conducted to compare ratings of the pens as the primary analysis; two-tailed tests were also conducted. 296 respondents completed the study (177 patients and 119 CDEs). The mean age was 53.2 years for patients and 49.4 years for CDEs; 55.9% and 1.7% were male, respectively; 27.1% of patients were type 1 and 72.9% were type 2. Both patients (66.7%) and CDEs (58.0%) preferred Pen X overall. Individual ratings are reported in Table. The qualitative research results indicated our measure had appropriate content validity for assessing pen preferences. The main results suggested that the appearance and function of Pen X is non-inferior to the insulin glargine pen from the perspective of both patients and CDEs and, in many cases, superior.Table. Patients (N=177)CDEs (N=119)Rated insulin glargine pen higherRated both pens identicallyRated Pen X higherRated insulin glargine pen higherRated both pens identicallyRated Pen X higherOverall, this pen would be "easy to teach" my patients to use (CDEs only)------8.4%71.4%20.2%†Overall, this pen was “easy to learn” to use6.8%70.1%23.2%*12.6%67.2%20.2%†Selecting the correct dose each time with this pen was…(1=Difficult, 6=Easy)4.5%74.6%20.9%*8.4%69.7%21.8%*Pushing down the injection button/knob was…(1=Difficult, 6=Easy)8.5%57.6%33.9%*22.7%38.7%38.7%†The injection was smooth.13.6%57.6%28.8%*28.6%37.0%34.5%The instruction booklet is ‘user friendly’.4.0%34.5%61.6%*4.2%17.6%78.2%*Which pen would you prefer?21.5%11.9%66.7%*23.5%18.5%58.0%**p&lt;.in non-inferiority and superiority analysis; †p&lt;.only in non-inferiority analysis

Disclosure
B. Alemayehu: Employee; Self; Merck & Co., Inc. M. DiBonaventura: Employee; Self; Pfizer Inc.. Consultant; Self; Merck & Co., Inc. A.M. Nguyen: Employee; Self; Merck & Co., Inc. M. Crutchlow: Employee; Self; Merck & Co., Inc.. Consultant; Spouse/Partner; Novo Nordisk Inc., Zealand Pharma A/S, XOMA Corporation.
Decrease in Proportion of CD24hiCD38hi Beta Cells and Impairment of Their Regulatory Capacity in Type 1 Diabetes Patients
Authors: WANG YUESHU , WANG XING , QIN YAO , ZHANG MEI 
Published: June 2018

Several studies have shown a subset of B cells play an important role in regulating the autoimmune response via the production of interleukin-10 known as B10 cells. However, the role of B10 cells in type 1 diabetes (T1D) and their relevance to the maintenance of peripheral tolerance in humans remains elusive. The aim of this study was to investigate the role of B10 cells in the pathogenesis of T1D. Peripheral mononuclear blood cells of 62 patients with T1D and 74 healthy volunteers were included. We showed that B10 cells in human peripheral blood belonged to a CD24hiCD38hi B cell subpopulation. Additionally, CD24hiCD38hi B cells from healthy individuals possessed regulatory capacity, inhibited IFN-γ, TNF-α and IL-17 production and promoted IL-4 production and Foxp3 expression of CD4+ T cells via an IL-10-dependent pathway. Compared with healthy controls, the proportion of B10 cells in patients with T1D was significantly lower (5.6±3.5% vs. 6.9±3.3%; P &lt;0.05), produced less IL-10 (15.4±4.3% vs. 29.0±4.5%; P &lt;0.001), and lacked the regulatory capacity. Pearson correlation analysis showed that the frequency of circulating B10 cells were negatively correlated with the frequency of CD4+IFN-γ+ and CD4+TNF-α+ T cells(r=-0.3and r=-0.360,P=0.037 and P=0.021, respectively), and positively correlated with the frequency of CD4+ CD25+ Foxp3+ T cells(r=0.018,P=0.001). There was also a negatively correlation between the frequency of circulating B10 cells and HbA1c(r=-0.339,P=0.010). These data provide direct evidence that there is a deficiency of circulating CD24hiCD38hi B cells in peripheral blood of patients with T1D, which might take part in the T1D immune imbalance, involved in the development of T1D.

Disclosure
Y. Wang: None. X. Wang: None. Y. Qin: None. M. Zhang: None.
Delivery of Low Basal Rates in Different Insulin Pumps—An Accuracy Evaluation
Authors: ZIEGLER RALPH , KAMECKE ULRIKE , WALDENMAIER DELIA , HAUG CORNELIA , FRECKMANN GUIDO 
Published: June 2018

Insulin pumps are commonly used in the therapy of children with type 1 diabetes, among other reasons due to the flexible continuous delivery of low basal rates. The standard EN 60601-2-24 describes test settings and procedures for the evaluation of infusion pumps in general; however, no acceptance criteria related to insulin delivery accuracy are stipulated. Most manufacturers’ specifications are limited to the accuracy of basal rates ≥1 U/h, while far lower basal rates are common in children.
In this study, the accuracy of a 0.1 U/h basal rate delivery of different insulin pumps was evaluated in an experimental setting based on EN 60601-2-24. The insulin pumps Accu-Chek® Insight, Accu-Chek® Spirit Combo, Animas® Vibe®, MiniMed® 640G, Paradigm® Veo™ and mylife™ OmniPod® were tested with different infusion sets (IIS). Measurements were based on the determination of weight increase of water-filled, oil-covered beakers placed on balances into which insulin was delivered by the pumps. Pumps were installed outside of the balance with the infusion set or a steel pipe (for the patch pump), respectively, connected to the beaker. After priming, a basal rate of 0.1 U/h was run for 72 h while weight increases were recorded. Each combination of insulin pump and IIS was tested 9 times. The total and the mean delivery over 1-h windows were calculated.
Large differences in total delivery were observed between the tested systems (+4.1% to +24.4% of the expected). During the first 24 h, all deviations were &gt;10% from the expected rate. Evaluation of 1-h windows showed that 31% to 80% of results were within ±15% of the weight increase expected with the set basal rate and large variations between the individual 1-h windows.
With the low basal rate tested in this study, delivery rates calculated from weight increases showed marked deviations from what was expected for this rate. When using insulin pumps in children with low insulin demands, it has to be considered that the basal rate might not be delivered as accurate and as consistent as expected.

Disclosure
R. Ziegler: Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Sanofi-Aventis. Speaker's Bureau; Self; Animas Corporation. U. Kamecke: None. D. Waldenmaier: None. C. Haug: None. G. Freckmann: Speaker's Bureau; Self; Ascensia Diabetes Care. Research Support; Self; Ascensia Diabetes Care. Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Roche Diabetes Care Health and Digital Solutions. Research Support; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Abbott, Novo Nordisk Inc.. Consultant; Self; Sensile Medical AG. Speaker's Bureau; Self; Ypsomed AG.
Meta-analysis vs. Single Trial (OpT2mise Study) Data to Assess Cost-Effectiveness of Simple CSII Devices in T2DM in the U.S.
Authors: WAHLQVIST PETER , WARNER JAY L. , PICKUP JOHN C. 
Published: June 2018

Continuous subcutaneous insulin infusion (CSII) in T2DM improves HbA1c and reduces insulin dosage vs. multiple daily injections (MDI). However, for T2DM traditional CSII can be costly and overly sophisticated. Emerging evidence shows T2DM can be treated with limited numbers of fixed basal rates and simple bolusing (‘simple CSII’) e.g., PAQ®, a 3-day wearable device (CeQur Corporation, Marlborough, MA), as alternatives to traditional CSII. This analysis investigated cost-effectiveness in the U.S. of simple CSII vs. MDI in poorly controlled T2DM, assuming similar efficacy of traditional and simple CSII. The analysis used data from a systematic review of relationships between reduced HbA1c and increased life-expectancy and quality-adjusted life-years (QALYs). Relationships between baseline HbA1c and simple CSII vs. MDI HbA1c treatment difference were based on data from either a 5-trial meta-analysis or a large single trial (OpT2mise study). Incremental cost-effectiveness ratios of costs per QALY gained below 1xGDP per capita (2016: USD 57,467) were defined as ‘highly cost-effective’ and below 3xGDP as ‘cost-effective’. Using meta-analysis data, simple CSII devices can be cost-effective below a unit cost about $18, and below $26 per patient per day using OpT2mise data. In either case, simple CSII is potentially a highly cost-effective treatment option in poorly controlled T2DM.

Disclosure
P. Wahlqvist: Employee; Self; CeQur (Wales) Ltd. J.L. Warner: Employee; Self; CeQur Corporation. J.C. Pickup: Advisory Panel; Self; Medtronic, Roche Diabetes Care Health and Digital Solutions. Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions, CeQur Corporation. Consultant; Self; CeQur Corporation. Advisory Panel; Self; Novo Nordisk A/S. Consultant; Self; Medtronic. Speaker's Bureau; Self; Berlin-Chemie AG, Elsevier.
Characterization of T Cells Reactive to Hybrid Insulin Peptides in the Peripheral Blood of in Type 1 Diabetes Patients
Authors: BAKER ROCKY L. , DELONG THOMAS , GOTTLIEB PETER , HASKINS KATHRYN M. 
Published: June 2018

We recently established, using the NOD mouse model, that hybrid insulin peptides (HIPs), formed spontaneously in islet beta-cells by fusion of insulin C-peptide fragments to peptides of Chromogranin A (ChgA) or Islet Amyloid Polypeptide (IAPP), are ligands for diabetogenic CD4 T cell clones. The goal of this study was to investigate whether HIP-reactive T cells were indicative of ongoing autoimmunity in human T1D patients.
To investigate their relevance to human disease, we used IFN-gamma ELISPOT to determine whether HIP-reactive T cells with an inflammatory phenotype were present in PBMCs of new onset T1D patients. We observed that PBMCs from new onset T1D patients responded to 8 of 16 HIPs tested and that nearly half of the patients tested responded to one or more HIPs.
We used a CFSE based assay to further characterize T cells reactive to HIP peptides. CD4+CFSEdimCD25+ T cells were sorted single into single wells using FACS and cloned. T cell clonality was confirmed using TCR deep sequencing and T cell reactivity to specific HIPs was confirmed by ELISA. A total of 6 T cell clones were isolated and show a variety of TCR usage. One T cell clone was isolated from the same patient on two different blood draws, indicating a high frequency of this T cell clone in the peripheral blood. While all the T cell clones isolated secreted IFN-gamma in response to HIPs, they also produced other inflammatory cytokines such as TNF-alpha and GM-CSF and reacted to HIPs in the low nanomolar range.
Our findings provide new evidence that HIP-reactive T cells are critical players in the pathogenesis of T1D and indicate that HIP-reactive T cells present in the peripheral blood can potentially serve as a biomarker of disease in a subset of patients.

Disclosure
R.L. Baker: None. T. Delong: None. P. Gottlieb: Advisory Panel; Self; Bristol-Myers Squibb Company. Research Support; Self; Caladrius Biosciences, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; ImmunoMolecular Therapeutics. Consultant; Self; Kamada. Research Support; Self; JDRF, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., MacroGenics, Inc., Pfizer Inc.. Advisory Panel; Self; Viacyte, Inc.. Research Support; Self; GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.. K.M. Haskins: None.
Multiple Oral Insulin (ORMD-0801) Doses Elicit a Cumulative Effect on Glucose Control in T2DM Patients
Authors: ELDOR ROY , NEUTEL JOEL , HOMER KENNETH E. , KIDRON MIRIAM 
Published: June 2018

Efforts to overcome the narrow therapeutic index of subcutaneously delivered insulin, have propelled the development of orally delivered alternatives. The enteric-coated ORMD-0801 oral insulin capsule has been shown to provide effective glucose control in both type 1 and type 2 diabetes patients. In this single-center, randomized, double-blind, placebo-controlled, three-way crossover study, 31 adult T2DM patients were treated with a placebo capsule during the first three days of three 1-week treatment periods, followed by five days of treatment with an oral placebo (n=31) or a 460 IU insulin capsule, delivered one (qd; n=20), two (bid; n=21) or three (tid; n=20) time per day. Run-in (Days 1-3) vs. treatment (Days 4-8) period continuous glucose monitoring (CGM) data were compared, as were pre- vs. post-treatment insulin and c-peptide levels. Patients were of a mean age of 57.5±7.8, and most were male (61.3%) and Caucasian (80.6%). Mean placebo-adjusted change from baseline in 24-hour glucose (all run-in days vs. all treatment days) ranged from -7.65 mg/dL for qd to -9.91 mg/dL for tid, with a more dramatic change observed in subjects with higher glucose (&gt;190 mg/dL; n=17) at baseline (-12.44 mg/dL (qd) and -18.43 (tid)). Pre- vs. posttreatment and placebo vs. active treatment c-peptide and insulin ratios were similar across all regimens. ORMD-0801 was well tolerated and did not elicit any serious adverse effects. The vast majority of hyperglycemic events were recorded during placebo treatment (n=27), while hypoglycemic events were evenly distributed across treatment groups (≤5/group). Thus, multiple-dose ORMD-0801 regimens safely provide for improved glucose control, which is expected to be enhanced with more extended treatment. Its impact may be of particular benefit to patients uncontrolled by current drug regimens.

Disclosure
R. Eldor: Consultant; Self; Oramed Pharmaceuticals, Inc.. Speaker's Bureau; Self; AstraZeneca, Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Medtronic. J. Neutel: None. K.E. Homer: None. M. Kidron: Employee; Self; Oramed Pharmaceuticals, Inc..
Impact of Switching from Twice-Daily Basal Insulin to Once-Daily Insulin Glargine 300 U/mL (Gla-300) in Patients with Type 1 Diabetes (T1DM)—Phase 4 OPTIMIZE Study, Belgian Cohort
Authors: MATHIEU CHANTAL , STELLA PETER , BRUHWYLER JACQUES , ALEXANDRE KATHY 
Published: June 2018

The 28-week, prospective, multicenter, open-label OPTIMIZE study, conducted in Belgium and Canada, evaluated treatment optimization with once-daily (OD) Gla-300 in combination with a prandial rapid-acting insulin analog in adults with T1DM previously uncontrolled (HbA1c 8-10%) on twice-daily (BID) basal insulin as part of basal-bolus therapy.
The intent-to-treat (ITT) and safety populations of the Belgian cohort comprised 48 patients (52.1% women); mean (SD) age 51.7 (12.8) years and mean (SD) body mass index 28.2 (4.9) kg/m². Prior to the study, 37.5% were on insulin glargine 100 U/mL and 62.5% were on insulin detemir. There was a statistically significant reduction in HbA1c from baseline to month 6 (primary endpoint, p&lt;0.0001). No significant changes were observed in basal or prandial insulin dose, or in total or nocturnal hypoglycemic event rates. Statistically significant improvements were seen in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) total and perceived hyperglycemia scores (p&lt;0.05) (Table), and in the patient satisfaction score for number of injections (p=0.004).
Switching from a BID basal insulin analog to OD Gla-300 in this challenging T1DM population was associated with a statistically significant improvement in HbA1c levels and better overall treatment satisfaction.

Disclosure
C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott. P. Stella: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Bruhwyler: Other Relationship; Self; Sanofi. K. Alexandre: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi.
Patient Input for Design of a Type 1 Diabetes (T1D) Decision Support Smartphone Application
Authors: WILSON LEAH M. , GABO VIRGINIA , TYLER NICHOLE S. , REDDY RAVI , JACOBS PETER G. , CASTLE JESSICA R. 
Published: June 2018

The complexity of T1D results in inadequate glucose control for patients which can lead to acute and chronic complications. We are developing a decision support smartphone application (app) for patients using multiple daily injection (MDI) therapy and continuous glucose monitoring (CGM). This app will use glucose trends, insulin dosing, and physical activity to provide recommendations for titration of insulin dosing to improve glycemic control.
We performed an online survey of patients age 18-80 with T1D from a diabetes specialty clinic, targeting MDI users, to determine current needs and preferences of candidates for decision support tools. Twenty-seven respondents are included in the analysis: mean age of 39.4 years, 54% female, 17.5 years mean duration of T1D, 89% use MDI. A total of 41% of respondents used CGM 50-100% of the time with all checking their CGM &gt;6 times per day. Over 90% use a smartphone, 88% have the phone with them 75-100% of the time. Only 19% used an app to calculate insulin doses, while 81% were interested in using an app to manage diabetes.
Participants wanted the following features in a decision support app: hypoglycemia avoidance (89%), insulin dose calculation (78%), behavioral change suggestions (74%), predicted glucose trends (70%), and insulin-on-board (70%). Many expressed low confidence in their ability to manage glucose during exercise (51%). Most respondents were interested in viewing predicted glucose trends prior to exercise (85%). Preferences about alerts to improve glucose control were varied with 44% saying they would be comfortable with 1-3 alerts per day. Preferences about alerts for predicted hypoglycemia were also varied; 11% would want to be alerted 5 minutes prior, 19% 15 minutes, 44% 30 minutes, and 26% &gt;1 hour.
These survey results confirm the need for and interest in a smartphone-based decision support app that will assist with management of T1D. The results will enable intelligent app design to better meet the needs of end users.

Disclosure
L.M. Wilson: None. V. Gabo: None. N.S. Tyler: None. R. Reddy: None. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies. J.R. Castle: Consultant; Self; Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk Inc..
Late and Missed Meal Boluses with Multiple Daily Insulin Injections
Authors: NORLANDER LISA M. , ANDERSON STACEY , LEVY CAROL J. , EKHLASPOUR LAYA , LAM DAVID W. , HSU LIANA , LOEBNER SARAH E. , OGYAADU SELASSIE J. , O'MALLEY GRENYE , LEVISTER CAMILLA M. , BRETON MARC D. , BUCKINGHAM BRUCE 
Published: June 2018

Background: Using sensor augmented pump data, late or missed meal boluses have shown a strong correlation with higher A1c levels, particularly in adolescents. With the Type Zero InControl Phone connected to a Dexcom G5 sensor and Novo insulin pens with memory and connectivity it is now possible to evaluate for late and missed meal boluses in MDI users.
Methods: For this study 326 days of CGM data were evaluated from 24 subjects (mean age 33, range 15-59 years). Seven days of data were analyzed on starting the system and 7 days 1 month later. Overall 1,173 meals were evaluated. Meals were determined by either the subject manually recording the meal, or if the CGM was &gt;70 mg/dl and there was a &gt;70 mg/dl rise within 2 hours. A late meal bolus was defined when the CGM increased &gt;50 mg/dl from baseline prior to an insulin dose. A missed meal bolus was defined by no insulin dose within 2 hours from the start of the CGM rise.
Results: 27% (range 8 to 55%) of meals had either a late or missed meal boluses: 13% (range 2-30%) were late and 14% (range 2 to 38%) were missed. There was no correlation with age or gender. There was a positive correlation with the percentage of missed meal boluses and A1c levels (p=0.019), but no correlation with the percentage of late meal boluses and A1c levels. There were no significant differences in missed or late meal boluses when comparing the first week of use to using the system one month later.
Conclusion: The rate of late or missed meal boluses is high for both adults and adolescents using MDI therapy, and missed meal boluses correlated with higher A1c levels. Having this information may provide significant insight to patients and help clinicians provide advice to MDI patients.

Disclosure
L.M. Norlander: None. S. Anderson: Research Support; Self; Medtronic. Consultant; Self; Senseonics. C.J. Levy: Advisory Panel; Self; Medtronic MiniMed, Inc.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Dexcom, Inc.. L. Ekhlaspour: None. D.W. Lam: None. L. Hsu: None. S.E. Loebner: None. S.J. Ogyaadu: None. G. O'Malley: None. C.M. Levister: None. M.D. Breton: Stock/Shareholder; Self; TypeZero Technologies, Inc.. Speaker's Bureau; Self; Ascensia Diabetes Care. Consultant; Self; Sanofi. Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions. Research Support; Self; Dexcom, Inc., Ascensia Diabetes Care, Senseonics. B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company.