bluuebunny/crossref_metadata_2025_split huggingface dataset:
864-P: Hyperglycemia Drives Glycemic Variability in Patients with Type 2 Diabetes (T2DM)
Authors: OLAWSKY EVAN A. , ZHANG YUAN , ALVEAR ALISON C. , EBERLY LYNN E. , CHOW LISA S. 
Published: June 2020

We performed quantified glycemic variability using continuous glucose monitoring (CGM) in people with T2DM at high (n=10) or low (n=8) 5-year risk for hypoglycemia to examine if high 5 year risk for hypoglycemia was associated with more short-term (2 weeks) glycemic variability and hypoglycemia.
Methods: Participants with T2DM [10W/8M, mean(SD): age: 59.5 (12.3) years], HbA1c: 7.6% (1.3%), fructosamine: 303 (46) umol/l] were preclassified as high or low 5 year risk for hypoglycemia. Each participant wore 2 blinded CGMs (1 Freestyle LibrePro/arm) for 2 weeks.
Results: HbA1c and fructosamine did not differ between groups. (Table1) The test/retest coefficient of variation (CV) measures the variation between glucose variability metrics from two sensors on the same person, adjusted for the mean of a given metric. The 2 sensors had the strongest test-re-test (&lt;0.1) for CV, SD, Mean, and MODD. In both the high and low risk group, HbA1c correlated with glycemic measures (r:0.4 to 0.7). In the low risk group, fructosamine (r:0.6 to 0.9) correlated with glycemic measures better than HbA1c.
Conclusions: Regardless of 5 year risk status, short-term hypoglycemia was infrequent and not different between groups. Hba1c and fructosamine correlated with glycemic variability. Glycemic variability was less in the low risk than high risk group, supporting that high glucose (≥180 mg/dL) drives much of the glycemic variability in T2DM.

Disclosure
E.A. Olawsky: None. Y. Zhang: None. A.C. Alvear: None. L.E. Eberly: None. L.S. Chow: None.

Funding
Academic Health Center (FRD17.08); National Institutes of Health (UL1TR002494)
867-P: Ongoing Manufacturer-Led Clinical Surveillance of Two Blood Glucose Monitoring Test Strip Systems
Authors: SETFORD STEVEN J. , KATZ LAURENCE B. , GRADY MIKE , MACLEOD KIRSTY , CAMERON HILARY 
Published: June 2020

There are no requirements for manufacturers of blood glucose monitoring systems (BGMS) to ensure their products continue to meet accuracy claims post-launch. Reported here is an on-going manufacturer-initiated clinical surveillance programme for two globally distributed BGMS: OneTouch Verio and OneTouch Select Plus, launched in 2009 and 2015 respectively.
Test strip batches were randomly and routinely sampled from the manufacturer’s (LifeScan Inc.) finished product and tested in clinic using capillary blood from subjects with diabetes (testing performed by professional staff). BGMS accuracy was determined against a reference instrument (results in Table). A small number of ’control’ batches were also sent to clinic on a repeat basis for on-going assessment of test variability (data not included in analysis).
Both products met clinical accuracy requirements for all years as defined by EN ISO 15197:2015 (min. 95% of all BGMS values within ±15 mg/dL of reference at blood glucose (BG) &lt;100 mg/dL or ±15% at BG ≥100 mg/dL). Furthermore, the OneTouch Verio product, available in U.S. markets, met the clinical accuracy criterion as proposed in current FDA guidance (min. 95% of all BGMS values within ±15% of reference at all BG levels).
The manufacturer advocates that all manufacturers of glucose monitoring systems for diabetes patients adopt and maintain a similarly robust surveillance program.

Disclosure
S.J. Setford: Employee; Self; LifeScan Scotland. L.B. Katz: Employee; Self; LifeScan, Inc. M. Grady: Employee; Self; LifeScan, Inc. K. Macleod: Employee; Self; LifeScan Scotland. H. Cameron: None.
874-P: Variation of Measured HbA1c from Predicted HbA1c on Freestyle Libre
Authors: MUTHABATHULA JAYASRI , GRIXTI LYDIA , FLETCHER-SALT TAMSIN , NAYAK ANANTH U. 
Published: June 2020

Aims/objectives: To explore the variation of the predicted HbA1c in the Free Style Libre (FSL) flash glucose monitoring from the simultaneous measured laboratory HbA1c (IFCC) value.
Methods: We included all patients (n=114) with adequate data on FSL download who also had HbA1c estimation in the biochemistry laboratory as a part of follow-up review after FSL initiation for glycaemia management in diabetes. The date of measured HbA1c estimation was used in the FSL download to obtain a predicted HbA1c (2 months data download). The difference between the measured HbA1c and predicted HbA1c was calculated to obtain the variation between the two.
Results: The measured HbA1c prior to and post FSL initiation were 68.2±15.1 and 59.9±1.2 mmol/mol respectively, i.e the HbA1c improved by mean 8.3 mmol/mol (std. error 0.99) (P&lt;0.001, paired sample t-test). The mean time duration between the pre and follow-up HbA1c estimations was 5.3±1.9 months. The predicted HbA1c on FSL download at follow-up was 61.8±10.1 mmol/mol. The correlation between the mean blood glucose on FSL and predicted HbA1c was significant (r=0.999) which would be expected as the predicted HbA1c was calculated from mean glucose in FSL. There was a significant correlation between measured HbA1c and predicted HbA1c was (r=0.86, P&lt;0.001) The difference between the measured and predicted HbA1c was minus 2.3±7.2 mmol/mol with a wide range (minus 35 to +12 mmol/mol) with the difference being clinical significant (&gt;10 mmol/mol difference) in 18.4% of the cohort.
Conclusions: This study confirms the variation of the measured HbA1c from that predicted from FSL flash glucose download data could be clinically significant in about a fifth of individuals. Variety of factors could contribute to such variation and may have clinical implications while managing individuals with diabetes.

Disclosure
J. Muthabathula: None. L. Grixti: None. T. Fletcher-Salt: None. A.U. Nayak: None.
875-P: Utilization of Continuous Glucose Monitors Is Associated with Reduction in Inpatient and Outpatient Emergency Acute Diabetes Events Regardless of Prior Blood Test Strip Usage
Authors: HIRSCH IRL B. , KERR MATTHEW S.D. , ROBERTS GREGORY J. , SOUTO DIANA , NABUTOVSKY YELENA , BERGENSTAL RICHARD M. 
Published: June 2020

Despite its potential benefits, access to continuous glucose monitors (CGMs) is often restricted based on blood glucose monitoring frequency. We aim to study if CGM efficacy depends on blood test strip (TS) usage prior to CGM initiation.
IBM MarketScan™ Commercial Claims and Medicare Supplemental databases were used in this retrospective, observational analysis. MarketScan contains insurance billing claims for inpatient, outpatient and pharmacy expenses. Cohort requirements included: de novo CGM purchase in 2017 Q1-2018 Q2, type 1 or type 2 diabetes, ≥18 years old, fast- or short-acting insulin, ≥ 6-months pre-CGM observation time. Blood TS usage was determined based on purchases 6 months pre-CGM. Primary outcome was acute diabetes events (ADE): hospitalization with hyper-/hypoglycemia as the primary diagnosis or outpatient emergency associated with a code of hyper-/hypoglycemia. Andersen-Gill Cox regression compared event rates 6-months pre-/post-CGM.
The cohort (n=12,521, age 43.8±15.2 years, 50.8% male, 77% type 1) experienced a reduction in ADE from 0.245 to 0.132 events/patient-year (HR: 0.54 [0.49 0.59]; P:&lt;0.001). A similar reduction was seen in patients using &lt;4 and ≥4 TS per day. A reduction was seen in all TS usage groups.
Initiation of CGM use was associated with reduced ADE regardless of baseline blood TS usage.

Disclosure
I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod. M.S.D. Kerr: Employee; Self; Abbott. G.J. Roberts: Employee; Self; Abbott. D. Souto: Employee; Self; Abbott. Y. Nabutovsky: Employee; Self; Abbott. R.M. Bergenstal: Consultant; Self; Ascensia Diabetes Care, Johnson & Johnson. Other Relationship; Self; Abbott, Dexcom, Inc., Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Onduo, Roche Diabetes Care, Sanofi, UnitedHealth Group.
88-OR: Glyoxalase-1 Gene Transfer Attenuated Diastolic Dysfunction in Female db/db Mice
Authors: BIDASEE KESHORE 
Published: June 2020

Background: More than 25% of middle-aged people living with diabetes mellitus (DM) have myocardial dysfunction including early onset diastolic dysfunction (DD), harbingers for symptomatic heart failure and frequent hospitalizations. This DD which is more prevalent in females than in males is associated with increased systemic inflammation, coronary microvascular dysfunction, myocardial fibrosis/stiffness and ischemia. Here we show using the db/db mouse model of DM that the diverse pathobiologies associated with DD are originating from accumulation of the glycolysis by-product, methylglyoxal (MG) arising from inflammation-induced downregulation of the MG-degrading enzyme glyoxalase-1 (Glo1).
Methods/Results: At six month of age, female db/db mice developed degree I-II DD, with increases in E:e’ ratio, and isovolumetric relaxation time. Speckle tracking analyses also indicated increased global longitudinal and circumferential strains. Histopathological analyses of ex vivo hearts showed increased amounts of the inflammation-induced protein vascular adhesion protein-1 (VAP-1), reduced level of Glo1, increased MG and the MG-adduct, MG-H1, microvascular leakage, micro-ischemia and fibrosis. Time to decay of myocytes evoked Ca2+ transient was also increased. Administration of a single injection of an engineered adeno-associated virus that uses the promoter of an inflammation-induced protein, endothelin-1 (AAV2/9-Endo-Glo1) to express Glo1 in hearts of three months db/db mice, attenuate coronary microvascular leakage, ischemia, fibrosis and myocardial and myocyte dysfunction, establishing a cause-effect relationship between MG accumulation and myocardial dysfunction in db/db mice.
Conclusions: These new data implicates accumulation of MG as a contributing cause of myocardial dysfunction type 2 DM. They also show that an AAV driven by the promoter of an inflammation-induced protein to express Glo1 in hearts of db/db mice can successfully attenuate DD.

Disclosure
K. Bidasee: None.
882-P: Resolution of Hypoglycemia Using CGM Data
Authors: NORLANDER LISA M. , SATAM KEYUREE , HANES SARAH , BUCKINGHAM BRUCE A. 
Published: June 2020

Background: Continuous glucose monitors (CGM) are the new standard for detecting hypoglycemia in T1D. No guidelines have been published that address monitoring during the return to euglycemia.
Methods: CGM data was gathered from 50 children and adolescents (ages 7-17) attending a week-long diabetes camp. All campers were treated according to camp protocol with 10-20g of carbohydrates depending on the size of the child and severity of hypoglycemia.
Results: 241 hypoglycemic events were analyzed using CGM data. 57 events had a nadir &lt;54 mg/dl and 184 were 54 to &lt;70 mg/dl. When measuring 15 min from the nadir, 89% of the &lt;70 mg/dl group had risen above 70 mg/dl vs. only 47% of the &lt;54 mg/dl group. During the day, a nadir &lt;54 mg/dl took an average of 19 min to return to &gt;70 mg/dl vs. 27 min at night. Nadirs &lt;70 mg/dl took an average of 11 min during the day and 12 min at night to return to &gt;70 mg/dl. Duration of hypoglycemia for nadirs &lt;54 mg/dl vs. &lt;70 mg/dl averaged 40 min vs. 18 min. Mean duration of hypoglycemia for the &lt;54 mg/dl group was 35 min during the day vs. 49 min at night. Mean duration of hypoglycemia for the &lt;70 mg/dl group was 18 min during the day and 20 min at night.
Conclusion: The depth of CGM hypoglycemia can help guide when to obtain a meter BG when treating hypoglycemia. If the glucose is &lt;70 but &gt;54 mg/dl, 89% will resolve within 15 min of the nadir; however less than 50% of those &lt;54 mg/dl will have responded by 15 min and should have a meter BG if sensor is not &gt;70 mg/dl at 15 min.

Disclosure
L.M. Norlander: None. K. Satam: None. S. Hanes: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care.
89-OR: FGFR1/MAPKs/AP-1 Signaling Mediates Cardiomyopathy in Streptozotocin-Induced Type 1 Diabetes
Authors: CHEN XIONG , WANG YAFENG , SHEN FEIXIA 
Published: June 2020

Diabetic cardiomyopathy is a complex entity associated with multiple contributing mechanisms and consequent manifestations in the clinic. Emerging evidence implicates that increased activity of fibroblast growth factor receptor 1 (FGFR1) is required during induced cardiac damage and remodeling. However, little is known about the roles of FGFR1 on diabetic cardiomyopathy (DCM). We hypothesized that the high-concentration glucose (HG)/diabetes induced cardiac pathophysiological and malfunctional alterations are linked to the activation of FGFR1. We tested this hypothesis by challenging cultured cardiomyocytes with high-concentration glucose and myocardium of streptozotocin (STZ)-induced type 1 diabetic mice (T1D). This study indicated that FGFR1 phosphorylation was increased in myocardium of streptozotocin (STZ)-induced type 1 diabetic mice (T1D) and cultured cardiomyocytes to high-concentration glucose. The inactivation of FGFR1 by selective inhibitors AZD4547, neutralized the increased FGFR1 phosphorylation and significantly reduced myocardial structural and functional deficits in type 1 diabetic mice. In vitro, overexpression of FGFR1 by lentivirus-transfection aggravated HG-induced fibrosis and hypertrophy in cardiomyocytes. Blocking FGFR1 by AZD4547 or CRISPER-Cas9 knockout, HG-induced fibrosis and hypertrophy in cardiomyocytes were significantly decreased. Then, GSEA analysis of RNA-sequencing implied that collagen5a1(Col5a1) and periostin (Postn) were associated with fibrosis and myosin heavy chain 4/7/8/9 (Myh4/7/8/9) were associated with hypertrophy. Analysis by PASTAA database and confirmatory tests by inhibiting FGFR1 or MAPKs indicated that MAPKs/AP-1 plays a crucial role in FGkFR1-mediated cardiomyocyte injuries challenged by HG. These results reveal an unrecognized FGFR1/MAPKs/AP-1 signaling axis involved in the development and progression of DCM and suggest that AZD4547 might be a potential agent for treating DCM.

Disclosure
X. Chen: None. Y. Wang: None. F. Shen: None.

Funding
National Natural Science Foundation of China (81700335)
890-P: Durability of Continuous Glucose Monitoring (CGM) Use in Young Children, Teens, and Young Adults with Type 1 Diabetes (T1D)
Authors: DESALVO DANIEL , KANAPKA LAUREN , BAUZA COLLEEN , XIE CICILYN , DIMEGLIO LINDA , LAFFEL LORI M. , MILLER KELLEE 
Published: June 2020

Use of CGM can optimize glycemic control; however, consistency of CGM use in youth and teens/young adults with T1D has been low in prior studies. We assessed 1-year use of Dexcom CGM in young children (ages 2 to &lt;8y) in the Strategies to Enhance New CGM in Early Childhood (SENCE) study and in teens/young adults (ages 14 to &lt;25y) in the CGM Intervention in Teens and Young Adults (CITY) study. Analyses included average # of days/week and percent of CGM wear time over 4 weeks prior to 6 and 12-month study visits. CGM use data from month 6 and 12 months are shown in the Table. For 84 youth in SENCE, median # days/week of CGM use was 7.0 with CGM being used 92% of time at 12 months; 79% were using CGM 7 days/week and only 2% discontinued CGM altogether. In 70 teens/young adults in CITY, median # of days/week of CGM use was 6.8, with CGM being used 86% of time at 12 months; 46% were using CGM 7 days/week and 9% discontinued CGM. At 12 months 88% of SENCE participants and 97% of CITY participants using CGM reported dosing insulin with CGM without using confirmatory fingerstick blood glucose value; 54% and 55%, respectively used remote monitoring features. CGM use in cohorts of very young children, teens and young adults was higher than previously reported. Improved CGM features, including mobile app data display, remote monitoring and non-adjunctive approval for dosing insulin, likely contributed to increased use.

Disclosure
D. DeSalvo: Consultant; Self; Dexcom, Inc., Insulet Corporation. L. Kanapka: None. C. Bauza: None. C. Xie: None. L. DiMeglio: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US. K. Miller: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.
892-P: Comparison of Dexcom G6 CGM with Self-Monitoring Blood Glucose in Young Adults with Type 1 Diabetes: The Millennial Study
Authors: THABIT HOOD , MUBITA WOMBA M. , FULLWOOD CATHERINE , AZMI SHAZLI , URWIN ANDREA , DOUGHTY IAN M. , LEELARATHNA LALANTHA , PAUL-PRABHU JOSHI 
Published: June 2020

Improving glycaemic control in young people with type 1 diabetes (T1D) remains challenging. No study has specifically evaluated efficacy and usability of DexCom G6 CGM in this cohort. Adolescents and young adults with T1D (age 16 to 25 years old) on multiple daily insulin injections (MDI) or insulin pump therapy (CSII) were recruited into an 8-week, open-label, randomised, crossover design clinical trial. Participants monitored daily glucose levels either with DexCom G6 CGM or self-monitoring blood glucose (SMBG) in random order during two 8-week study periods. Blinded CGM was applied for a 3-week period during the control phase. Data from 29 participants were analysed (mean±SD age 21.3±2.3years, 16 [55.2%] female, baseline A1c 78.7±14.4mmol/mol, diabetes duration 13.1±5.1years, BMI 25.4±4.7kg/m2, CSII/MDI users= 17/12). The primary outcome, time spent in target range (70-180mg/dl) as recorded by CGM was significantly higher during CGM compared to the control period (see Table). CGM use reduced mean sensor glucose and time spent above target. A1c level was also reduced by 8.9mmol/mol (95% CI -4.3 to -13.3, p&lt;0.005) in the CGM period. Time spent below target increased on CGM, no episodes of severe hypoglycaemia or DKA occurred. Median sensor use was 86% during the study.
In conclusion, CGM use improves time in target and A1c levels in young people with T1D.

Disclosure
H. Thabit: Research Support; Self; Dexcom, Inc. W.M. Mubita: None. C. Fullwood: None. S. Azmi: None. A. Urwin: None. I.M. Doughty: None. L. Leelarathna: Advisory Panel; Self; Abbott Laboratories, Medtronic, Novo Nordisk A/S, Sanofi. Research Support; Self; Dexcom, Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. J. Paul-Prabhu: None.

Funding
Dexcom, Inc.
893-P: Miniaturized, User-Insertable Wireless Continuous Glucose Monitoring System with Next Generation Speed, Accuracy, and Longevity
Authors: MUJEEB-U-RAHMAN MUHAMMAD , NAZARI MEISAM HONARVAR , SENCAN MEHMET 
Published: June 2020

The accuracy, response speed, cost, and size are important determinants of the performance of a Continuous Glucose Monitoring (CGM) system. Current CGM systems either require (i) percutaneous wires with bulky skin-worn transmitters, frequent removal/insertion, and thousands of dollars, or (ii) bulky implants, special semi-surgical procedures, and frequent recalibrations. By integrating modern semiconductor and nano technologies, IMS invented miniaturized (0.1mmx0.6mmx3mm i.e., smaller than a sesame seed) fully wireless, minimally invasive subdermal CGM platform. The sensor is user-insertable under the skin using an injector and is also user-removable. It is powered via an external smartwatch transmitter using standard RFID technology. This enables low power RF communication with the transmitter. The transmitter uses a bluetooth low-energy link to send the data to a smartphone reader enabling machine-learning based decision support.
IMS has verified the system through extensive in-vitro and in-vivo testing; the latest test for more than 1 month in a porcine model (Figure 1). The sensor shows fast response speed, best-in-class accuracy, and highly biocompatible operation due to use of standard materials and small size. We are currently working to get FDA IDE for first-in-human study.
Figure 1. Sensor Performance Results (a) using FDA iCGM (b) Clarke Error Grid.

Disclosure
M. Mujeeb-U-Rahman: None. M. Honarvar Nazari: None. M. Sencan: Employee; Self; Integrated Medical Sensors.

Funding
National Institutes of Health (DK109811, DK111001)
898-P: Benefit of Continuous Glucose Monitoring (CGM) in Reducing Hemoglobin A1c Is Sustained through 12 Months of Use among Adolescents and Young Adults with Type 1 Diabetes (T1D)
Authors: MILLER KELLEE , KANAPKA LAUREN , BAUZA COLLEEN , LAFFEL LORI M. 
Published: June 2020

The CGM Intervention in Teens and Young Adults (CITY) trial demonstrated reductions in hemoglobin A1c (HbA1c) and hypoglycemia using CGM compared with intermittent blood glucose monitoring over a 6-month period. To determine if this improvement would be sustained, we evaluated outcomes in participants who continued CGM use through 12 months. The study was completed by 70 of 74 (95%) in the CGM group (43% female, median age 17 yrs, 67% non-Hispanic white, and 47% insulin pump users). Central-lab measured HbA1c and CGM measured glycemic outcomes at 12 months were compared with baseline (CGM at baseline was masked). HbA1c decreased from 8.9% at baseline to 8.3% at 12 months (p&lt;0.001) (Table). Time spent in range 70-180 mg/dL was 38% at baseline and 41% at 12 months (P=0.3). Median percent time &lt;70 mg/dL was reduced from 3.4% (49 min/day) at baseline to 1.1% (16 min/day) at 12 months (p&lt;0.001). Similar improvements were observed for time &lt;54 mg/dL with a decrease from a median of 1.0% (14 minutes/day) at baseline to 0.1% (&lt;2 minutes/day) at 12 months. Glycemic variability measured by coefficient of variation was reduced from 42% at baseline to 37% at 12 months (p&lt;0.001). These results demonstrate improvements in outcomes for teens and young adults with CGM use over a 12-month period with substantial improvements in HbA1c and reductions in hypoglycemia.

Disclosure
K. Miller: None. L. Kanapka: None. C. Bauza: None. L.M. Laffel: Advisory Panel; Self; Roche Diabetes Care. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Insulogic LLC, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi US.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.