bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inadequate Use of Glucagon in Patients with T1D
Authors: HAYMOND MOREY W. , LIU JINGWEN , BISPHAM JEOFFREY , HICKEY AILEEN , MCAULIFFE-FOGARTY ALICIA H. 
Published: June 2018

Glucagon is an invaluable tool for patients with type 1 diabetes (T1D) who experience severe hypoglycemia, but little is known about the actual use of glucagon in this patient population. This study was undertaken among individuals with T1D or caregivers to assess the perceptions and/or past experiences using the currently available glucagon rescue kits, and factors that might increase its utility in the management of T1D. Survey responses from 264 adults with T1D (mean age 41.2 years [SD 15.5]) and 58 caregivers of a person with T1D (mean age 11.8 years [SD 3.7]) were included in the analyses. Overall the participants were highly educated, predominantly covered by private health insurance, and the majority were on insulin pumps. The survey revealed that the majority of the individuals with T1D had been prescribed glucagon; however, almost a third of the adult patients did not receive any education on its use, and a third of the adult patients did not have a current prescription. Caregivers reported higher percentages of receiving education on glucagon use and also having a current prescription. Of those with severe hypoglycemia who had glucagon available, half did not receive a glucagon injection. The majority of patients who had received glucagon injection reported various problems with the procedure; those who did not receive glucagon injection reported a number of barriers to its use. These data strongly suggest the need for 1) standards of practice that would increase prescribing of glucagon 2) initial and ongoing education on its use and administration 3) development of a glucagon rescue option that would eliminate the complexity relating to current formulations and packaging of rescue glucagon kits.

Disclosure
M.W. Haymond: Advisory Panel; Self; Zealand Pharma A/S. Other Relationship; Self; Xeris Pharmaceuticals, Inc.. J. Liu: None. J. Bispham: None. A. Hickey: None. A.H. McAuliffe-Fogarty: Advisory Panel; Self; Novo Nordisk Inc..
Heart Rate Variability in Patients with Type 1 Diabetes and Hypoglycemia with Different Control of Diabetes Mellitus
Authors: MOSHENETS KATERYNA , PERTSEVA NATALIIA 
Published: June 2018

Background and Aims: To study the correlation of heart rate variability (HRV) in patients with type 1 diabetes mellitus (T1DM) depending on glucose control and hypoglycemia.
Materials and Methods: The study involved 87 patients with T1D, including 45 men (52%), women - 42 (48%). The average age of patients - 26,6±1,48 years, disease duration 11,6±1,42 years, BMI 23,2 ± 0,63 kg/m2. All patients used basic-bolus insulin therapy with daily dose of Units 45±2,26. All patients were conducted with Continuous Glucose Monitoring System (CGMS) and 24-Hour Holter Monitoring (HM) in same time. Echocardiography was used to exclude organic pathology of the heart. Patients were divided to groups according to HbA1c. Group 1 had HbA1c?7,5%; group 2 had HbA1c&gt;7,5%, and subgroups: A-without hypoglycemia, B-with hypoglycemia.
Results. Groups did not differ in the frequency of hypoglycemia. Calculation of results depending on the duration T1DM showed an increase LF/HF (r=0,472; p&lt;0,05). Groups differed significantly according to the following frequency characteristics of heart rate such as VLF, LF, HF (p&lt;0,05). The groups did not differ in other factors. In Group 2B as compared to 2A identified decrease such time-domain indicators of HRV: RMSSD 22,8 ms (15,0; 36,0) vs. 32,6 ms (27,0; 43,0); pNN50 daily 3.50% (1.0; 10.0) vs. 8.50% (6,00-13,50) and daily frequency characteristics HRV: HF 380,0 ms2 (149,0; 715,0) to 719.0 ms2 (475.0, 1153.0) and increased LF/HF 4,35 (4,10; 6,50) vs. 3.30 (2.30; 4.30). All findings are significant (p&lt;0,05). A similar pattern was observed in patients in 1st group.
Conclusions: HRV is lower in patients with bed glucose control (HbA1c&gt;7,5%). The most reliable criteria for assessing changes in HRV are in patients with T1DM are RMSSD, LF, HF and LF/HF are. Hypoglycemia is the most significant factor that reduces the HRV.

Disclosure
K. Moshenets: None. N. Pertseva: None.
Lipocalin-Type Prostaglandin D2 Synthase (L-PGDS) Knockout Mice Exhibits Hepatosteatosis Mediated by Enhanced Cd36 Hepatic Expression as a Result of Hyperinsulinemia
Authors: KUMAR SUNIL , PALAIA THOMAS , HALL CHRIS , LEE JENNY , STEVENSON MATTHEW , RAGOLIA LOUIS 
Published: June 2018

Hepatosteatosis is strongly associated with hyperinsulinaemia and obesity. Previously, we demonstrated accelerated atherosclerosis and impaired glucose tolerance in L-PGDS knockout (KO) mice. Interestingly, L-PGDS KO mice also exhibit hyperinsulinemia on high fat diet in a time-dependent manner. In this study, we investigated the role of L-PGDS on liver pathophysiology using L-PGDS KO mice compared to control C57BL/6 mice) (n=6/group). Mice were kept on high fat diet (60% fat) for 14 weeks and all parameters were measured initially and at 4-, 8- and 14-weeks post high fat diet. Data were analyzed by unpaired t-test or one-way ANOVA where appropriate with p&lt;0.05 deemed significant. Fasting insulin, blood glucose and calculated HOMA-IR were determined. KO mice showed significantly higher HOMA-RI 19.3± 4.62 and 19.7±4.74 at 8 and 14 weeks, respectively, compared to the C57BL/6 mice, which were 7.73±1.14 and 10.1±1.87 at 8 and 14 weeks, respectively. Hepatic Cd36 protein expression was significantly increased at 14 weeks in KO mice compared to the control. Liver steatosis directly correlated with elevated serum triglyceride levels, which significantly increased to 81.7±3.24 and 82.8±1.63 mg/dl at 8 and 14 week,s respectively, compared to the initial level of 64.1±5.66 mg/dl Control serum triglyceride levels were 61.1±3.49 and 73.6±3.2 mg/dl at 8 and 14 weeks, respectively. Furthermore, immunohistochemistry staining of lipid showed severely more liver steatosis in KO mice at all-time points when compared to control mice. Interestingly, KO mice always weighed less compared to the control mice at all-time points, which suggests that L-PGDS partially or fully contributes towards the development of hepatosteatosis independent of body weight. We conclude that L-PGDS is an essential component of hepatic metabolic substrate utilization and may play a significant role in diabetes-related steatosis.

Disclosure
S. Kumar: None. T. Palaia: None. C. Hall: None. J. Lee: None. M. Stevenson: None. L. Ragolia: None.
A Novel Continuous Glucose Monitoring System Accurately Detects Existing and Impending Hypoglycemia
Authors: CALHOUN PETER , JOHNSON TERRI , BALO ANDREW , PRICE DAVID A. 
Published: June 2018

Autonomous real-time continuous glucose monitors (rtCGM), unlike intermittently scanned continuous glucose monitors (isCGM), can proactively warn users of impending hypoglycemia. This study assessed the likelihood of realized hypoglycemia when an alert is triggered in the novel factory-calibrated rtCGM system ("G6 FC" Dexcom). Subjects wearing a G6 rtCGM participated in 1 to 3 in-clinic sessions where venous YSI plasma glucose measurements were sampled every 15 minutes. Three types of hypoglycemic alerts were assessed: “Low” (&lt;70 mg/dL), “Urgent Low” (&lt;55 mg/dL), and the new “Urgent Low Soon” (≤55 mg/dL within 30 minutes). YSI glucose values were linearly interpolated to give estimated glucose values between YSI glucose measurements. The first “Low” and “Urgent Low” alerts were matched with actual and interpolated YSI values within ±15 minutes. The first “Urgent Low Soon” alerts were matched with actual and interpolated YSI values within 30 minutes after the alert. The Table shows 77% of “Low” alerts and 86% of “Urgent Low” alerts correctly warned of a hypoglycemic event (YSI reading below 70 mg/dL) within ±15 minutes. There were 480 “Urgent Low Soon” alerts, 86% of which correctly predicted a hypoglycemic event in the next 30 minutes. The G6 FC CGM System provides accurate alerts to patients which could facilitate actions to prevent or minimize hypoglycemia.
Table.Hypoglycemic rates during a "Low" or "Urgent Low" alertType of alertNumber of alertsNumber (%) of alert events with a nadir YSI&lt;55 mg/dL&lt;70 mg/dL&lt;90 mg/dLLow620185 (29.8%)478 (77.1%)596 (96.1%)Urgent Low410249 (60.7%)353 (86.1%)394 (96.1%)

Disclosure
P. Calhoun: Employee; Self; Dexcom, Inc.. Stock/Shareholder; Self; Dexcom, Inc. T. Johnson: Employee; Self; Dexcom, Inc. A. Balo: Employee; Self; Dexcom, Inc. D.A. Price: Employee; Self; Dexcom, Inc..
Machine Learning Identification of Multiple Predictively Equivalent Risk Models for Severe Hypoglycemia in Patients with Type 2 Diabetes
Authors: MA SISI , SCHREINER PAMELA , ZMORA RACHEL , SEAQUIST ELIZABETH R. , CHOW LISA S. 
Published: June 2018

Severe hypoglycemia (SH), hypoglycemia requiring medical assistance and either blood glucose ≤ 50 mg/dL or glucose administration, instills fear in patients treated for diabetes. While risk models for SH may categorize an individual’s risk, incomplete or unavailable (“missing”) data limit clinical application. To circumvent the “missing” data issue, we used machine learning to identify multiple predictively equivalent risk models for SH in patients with type 2 diabetes (T2DM). Data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (n=10,251) were analyzed. Over ACCORD follow-up (mean 4.7± SD 1.4 years), 721 incident SH events were observed. We examined 95 candidate risk factors for model construction. Multiple predictively equivalent risk models (n=194) for SH were induced using the SurvTIE* algorithm (an adaptation of TIE* algorithm to survival outcome) and constructed with Cox regression and time-varying covariates. For each risk model, the number of risk factors ranged from 18-23 (median = 19). Unbiased performance estimations of c-index 0.78±0.03 were obtained from repeated cross-validation. Table 1 shows several unique models with equivalent predictive ability. In patients with T2DM, multiple predictively equivalent risk models for SH can be identified, potentially personalizing model selection when data are “missing.”

Disclosure
S. Ma: None. P. Schreiner: None. R. Zmora: None. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company, Sanofi, Zucera, InfoMed, 360 consulting. Other Relationship; Self; Novo Nordisk Inc. L.S. Chow: Research Support; Self; Eli Lilly and Company, National Institute of Diabetes and Digestive and Kidney Diseases.
Canagliflozin (CANA) vs. Other Antihyperglycemic Agents on the Risk of Below-Knee Amputation (BKA) for Patients with T2DM—A Real-World Analysis of &gt;700,000 U.S. Patients
Authors: RYAN PATRICK , BUSE JOHN B. , SCHUEMIE MARTIJN , DEFALCO FRANK , YUAN ZHONG , STANG PAUL , BERLIN JESSE A. , ROSENTHAL NORM 
Published: June 2018

Sodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for treatment of T2DM; some SGLT2i have reported a CV benefit and some reported a risk of BKA. U.S. claims databases were analyzed using a prespecified protocol to examine CANA-associated effects on BKA and hospitalization for heart failure (HHF) vs. other SGLT2i and non-SGLT2i. Analyses used a propensity score adjusted new user design with numerous sensitivity analyses. The 4 databases included 142K new users of CANA, 110K of other SGLT2i, and 460K of non-SGLT2i AHAs. Meta-analysis results are reported when heterogeneity across databases was not substantial (I2 &lt;0.4). There was no evidence of increased risk of BKA with CANA vs. non-SGLT2i or other SGLT2i in on-treatment or ITT analyses (Table). HHF benefits were demonstrated in these analyses, consistent with clinical trials. Similar BKA and HHF results were seen in a subgroup with established CV disease. In this large comprehensive analysis, neither CANA nor other SGLT2i showed an increased risk of amputation vs. non-SGLT2i. Because on-treatment median exposure was &lt;6 months, future observational studies with longer duration are needed. This study helps to further characterize the potential benefits and harms of SGLT2i as observed in routine clinical practice to complement the evidence from clinical trials and prior observational studies.

Disclosure
P. Ryan: Employee; Self; Janssen Research & Development, LLC. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. M. Schuemie: Employee; Self; Janssen Research & Development, LLC. F. Defalco: Employee; Self; Janssen Research & Development, LLC. Z. Yuan: Employee; Self; Janssen Research & Development, LLC. P. Stang: Employee; Self; Janssen Research & Development, LLC. J.A. Berlin: Employee; Self; Johnson & Johnson, LLC. N. Rosenthal: Employee; Self; Janssen Research & Development.
Increased Fluctuation of Measured Glucose in Critically Ill Patients Is an Independent Predictor of Mortality
Authors: KANAPARTHY NAGA SASIDHAR , MATHEWS SHERIN ELSA , KALLUR KAMALA RAMYA 
Published: June 2018

Background: Extreme glucose values in critically ill patients have been studied and shown to be predictors of mortality. In addition, glucose fluctuation is also proposed to have been a determinant of poor outcome. In our study, we attempt to understand whether there is a relation between the fluctuations of glucose in critically ill patients to their mortality.
Methods: Data was obtained from "Medical Information Mart for Intensive Care III" database between 2001 and 2012. Fluctuation was measured as coefficient of variance of glucose (CVG). Patients were split into four groups based on the CVG of glucose levels during their ICU stay, namely Group 1: &lt;25%, Group 2: 25%-50%, Group 3: 50%-100% and Group 4: &gt;100%. Outcomes were measured at 3-day mortality interval and the relative risk was compared across the four groups. Multinomial logistic regression with length of stay, prednisone administration and Simplified Acute Physiology Score (SAPS) II as variables were run to assess the relative risk ratios (RRR) of increased CVG with mortality.
Results: A total of 45,302 adult ICU admissions were considered, 82.1% (n=37,192) had no diabetes, 17.6% (n=7,952) were type 2 diabetic (T2DM) and 0.04% (n=168) were type 1 diabetic (T1DM). The RRR for 3-day mortality, among the nondiabetics compared to the base outcome (Group 1) was 1.51 (p&lt;0.0001) in Group 2, 3.76 (p&lt;0.0001) in Group 3 and 2.17 (p=0.10) in Group 4. Among T2DM, the RRR for 3-day mortality was 1.04 (p=0.7) in Group 2, 2.97 (p&lt;0.0001) in Group 3, 14.03 (p=0.025) in Group 4. Due to the small number of observations for T1DM, they were excluded.
Conclusion: In nondiabetics there was higher mortality at a lower CVG as compared to the diabetics. In diabetics the increased mortality was observed at slightly higher CVG. In patients admitted to critical care units, increased fluctuation in glucose during their ICU admission is an independent predictor of mortality and additional caution should be taken to avoid wide fluctuations.

Disclosure
N. Kanaparthy: None. S. Elsa Mathews: None. K. Kallur: None.
Inhibition of Drp1-Mediated Mitochondrial Fission Protects Diabetic Heart against Ischemia-Reperfusion Injury
Authors: DING MINGGE , FENG JIAHAO , LI ZEYANG , FU FENG 
Published: June 2018

Identify the molecular basis linking diabetes with MI/R injury is scientifically important and may provide effective therapeutic approaches. Recent studies indicated that enhanced Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission is involved in both diabetic hearts and ischemic hearts. We hypothesized that inhibition of Drp1-mediated mitochondrial fission may be effective to reduce MI/R injury in diabetic hearts. High-fat diet and streptozotocin-induced diabetic mice were subjected to MI/R or sham operation. Mdivi-1 (1.2 mg/kg), a small molecule inhibitor of Drp1 or vehicle was administrated 15 min before the onset of reperfusion. Outcome measures included mitochondrial morphology, mitochondrial function, myocardial injury, cardiac function and oxidative stress. Mitochondrial fission was significantly increased following MI/R as evidenced by enhanced translocation of Drp1 to mitochondria and decreased mitochondrial size. Delivery of Mdivi-1 into diabetic mice markedly inhibited Drp1 translocation to the mitochondria and reduced mitochondrial fission following MI/R. Inhibition of Drp1-mediated mitochondrial fission increased mitochondrial complex I/II/III/IV activities and ATP content and improved cardiac function following MI/R (n = 8, P &lt; 0.01). Moreover, inhibition of Drp1 reduced myocardial infarct size (28.7 ± 4.2% vs. 45.3 ± 4.7% n = 8, P &lt; 0.01) and serum cardiac troponin and lactate dehydrogenase activities. These cardioprotective effects were associated with decreased cardiomyocyte apoptosis and malondialdehyde production and increased activities of antioxidant enzyme manganese superoxide dismutase (n = 8, P &lt; 0.01). These data suggest that Drp1-mediated mitochondrial fission may be a potential novel therapeutic target for diabetic cardiac complications.

Disclosure
M. Ding: None. J. Feng: None. Z. Li: None. F. Fu: None.
Effects of Glucose and Blood Pressure Variability on Oxidative Stress in Type 2 Diabetes with Hypertension
Authors: OHARA MAKOTO , NAGAIKE HIROE , YAMAMOTO TAKESHI , HAYASHI TOSHIYUKI , FUKUI TOMOYASU , HIRANO TSUTOMU 
Published: June 2018

Aims: This study was performed to evaluate the effects of glucose variability (GV) and blood pressure variability (BV) on oxidative stress in type 2 diabetes patients with hypertension.
Methods: Fifty-seven inpatients with type 2 diabetes (studied from May 2015 to august 2017) underwent continuous glucose monitoring (CGM) and ambulatory BP monitoring (ABPM) in a cross-sectional study. The plasma total oxidant capacity against N,N-diethylparaphenylendiamine was measured as a marker of oxidative stress using the d-ROMs test. The GV, mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), and area under the postprandial plasma glucose curve (AUCPP) were measured by CGM. The BV, mean blood pressure (MBP), max blood pressure (MaxBP), minimum blood pressure (MinBP), and standard deviation of blood pressure (BPSD) during the systole (S) and diastole (D) were measured by ABPM over daytime (day), nighttime (night), and 24-hour (24) periods.
Results: The 57 participants were 65.3±12.9 years old, with a disease duration of 14.7±12.4 years and HbA1c of 8.5±1.2 %. In univariate analysis, MAGE (r=0.446,p&lt;0.001), night DBPSD (r=0.323,p=0.014), and eGFR (r=0.287, p=0.030) were significantly correlated with the d-ROMs. In the stepwise multiple regression analysis, MAGE (β=0.344, t=3.075, p=0.003), night DBPSD (β=0.230, t=2.034, p=0.047), eGFR (β=-0.234, t=-2.137, p=0.037), and smoking (β=0.315, t=2.873, p=0.006) were identified as independent factors contributing to the d-ROMs (multiple R2 = 0.363).
Conclusions: Daily glucose variability and nighttime systolic blood pressure variability are associated with oxidative stress in type 2 diabetes with hypertension.

Disclosure
M. Ohara: None. H. Nagaike: None. T. Yamamoto: None. T. Hayashi: None. T. Fukui: None. T. Hirano: Speaker's Bureau; Self; Novo Nordisk Inc., AstraZeneca.
Relationship between Sleep Disordered Breathing during Rapid Eye Movement Sleep and Coronary Risk Factors in Patients with Type 2 Diabetes Mellitus
Authors: UCHIDA TAKAYASU , NISHIMURA AKIHIRO , KIKUNO SHOTA , NAGASAWA KAORU , OKUBO MINORU , KASAI TAKATOSHI , NARUI KOJI , MORI YASUMICHI 
Published: June 2018

Sleep disordered breathing (SDB) is associated with hypertension, poor glycemic control and dyslipidemia. In general, apnea events are more prominent during rapid eye movement (REM) sleep than non-REM (NREM) sleep. Reportedly, only REM-AHI is associated with hypertension and HbA1c. We examined which SDB parameters are associated with BP, HbA1c and lipid profile in type 2 diabetes (T2D) patients.
We analyzed 185 T2D patients who underwent polysomnography after excluding patients with pulmonary diseases, central sleep apnea, treated SDB or REM sleep &lt; 30 minutes. We performed multiple linear regression analyses to predict BP, HbA1c and lipid profiles adjusted for known risk factors.
Patients characteristics (mean±SD/median(IQR)): age 58.0 ± 11.8 yo, BMI 26.0 (24.1-28.9) kg/m2, systolic BP 134 ± 19.1 mmHg, mean BP 97.5 ± 13.8 mmHg, HbA1c 7.4 (6.8-8.4) %, TG 143 (97-195) mg/dL, non-HDL cholesterol 143 (120-163) mg/dL, REM-AHI 35.1 (21.1-53.1) /h. The analyses revealed REM-AHI was independently associated with systolic and mean BP whereas NREM-AHI was not (Fig. 1). No statistically significant association was observed between REM-AHI and HbA1c or lipid profile.
REM-AHI was associated with systolic and mean BP in T2D patients. BP alteration associated with SDB during REM sleep may be an important pathophysiology linking between SDB and cardiovascular diseases.

Disclosure
T. Uchida: None. A. Nishimura: None. S. Kikuno: None. K. Nagasawa: None. M. Okubo: None. T. Kasai: None. K. Narui: None. Y. Mori: None.
Next Generation of Spontaneous Diabetic Model of ZDSD Rats with Intact Leptin Signaling Develop Cardiac Dysfunction and Compromised Cardiac Reserve
Authors: SUN GAO , ZHANG GUODONG , WANG YIXIN 
Published: June 2018

Introduction: Cardiomyopathy is the leading cause of morbidity and mortality among all complications of type 2 diabetic (T2D) and obese patients. Diabetic cardiomyopathy (DC) is characterized by an initial cardiac hypertrophy followed by thinning of the cardiac walls with declines in both systolic and diastolic functions, which ultimately leads to heart failure. No rodent models fully captured phenotypes of DC. The ZDSD rat, a new generation of T2D rat model with intact leptin signaling features with slow onset of diabetes and obesity, which closely mimics the development of the disease in patients. Here we sought to evaluate the cardiac function during the development of metabolic syndromes in ZDSD rats.
Methods: 12 male ZDSD rats and age-matched SD controls were monitored for blood pressure, glucose, and cardiac function using echocardiography. Animals were also challenged with 1 mg/kg dobutamine for the assessment of cardiac reserve.
Results: ZDSD rats developed hypertension from age of 18 weeks. Their left ventricular (LV) functions were compromised along with changes in cardiac morphology. At resting state, ZDSD rats showed LV hypertrophy from age of 18 to 22 weeks after which cardiac walls became thinner with larger LV volume. At 34 weeks old, both ejection fraction (EF) and transmitral E/A ratio declined. Upon treatment with dobutamine for 5 minutes, SD rats reached almost 98% EF, while the values of ZDSD were 91% at 30 and 34 weeks old, suggesting the loss of LV contractility the animals.
Conclusion: ZDSD rats which carry multiple dysmetabolic phenotypes are spontaneously hypertensive with reduction in LV function and cardiac reserve which resembles ultrasonic symptoms of diabetic cardiomyopathy patients. Therefore, ZDSD rats may serve as a suitable preclinical model to study potential therapeutic approaches to treat cardiomyopathy with presence of metabolic syndromes.

Disclosure
G. Sun: None. G. Zhang: None. Y. Wang: None.