bluuebunny/crossref_metadata_2025_split huggingface dataset:
363-OR: Comprehensive Assessment of Glycemic Control after Pancreas Transplantation
Authors: KAUR RAVINDER JEET , REID COREY , THAPA PRABIN , RIZVI SHAFAQ RAZA , MCCRADY-SPITZER SHELLY K. , BATTHULA SREEDHAR , SMITH BYRON H. , DEAN PATRICK , KREMERS WALTER K. , KUKLA ALEKSANDRA , STEGALL MARK D. , KUDVA YOGISH C. 
Published: June 2020

Introduction: Limited data are available about comprehensive metabolic evaluation after Pancreas transplantation (PT) for type 1 diabetes (T1D).
Methods: After IRB approval, we prospectively studied 15 PT recipients at least 1 year post transplant. After a screening visit, subjects underwent Dexcom G4 CGM for one week and Mixed Meal Test (MMT) according to standard procedure.
Results: PT recipient were 53.1 ± 10.6 years old, F/M 12/3, BMI (Kg/m2) 30.8 ± 6 and mean duration of diabetes was 33 ± 12.3 years with 6 ± 5 (1-17) years mean interval from PT to the study. Twelve patients underwent pancreas transplant alone and three underwent simultaneous pancreas kidney transplantation. Baseline values were Hemoglobin 12.3 ± 1.4 (g/dl), HbA1c 5.4 ± 0.6 %, Albumin 4.0 ± 0.3 g/dl, Fructosamine 233 ± 27 (µmol/L), Fasting Glucose 94.3 ± 17.5 mg/dl, C-peptide 2.5 ± 0.9 (ng/ml), eGFR 56.3 ± 25.5 ml/min and AST 23.4 ± 8.5 U/L. MMT revealed Glucose concentration increased from 90.9 ± 9.6 mg/dl at baseline to 140.6 ± 41.5 mg/dl at 30min followed by 123.2 ± 48.0 mg/dl and 115.2 ± 34.6 mg/dl at 60mins and 120 mins respectively. C-peptide was 2.4 ± 0.7 ng/ml at baseline, peaked to 7.5 ± 5.4 ng/ml at 60 mins and was 6.0 ± 3.6 mins and 5.9 ± 2.4 at 30 and 120 mins respectively with insulin peaking from 13.5 ± 5.5 uIU/ml at baseline to 107 ± 81.6 uIU/ml at 30 mins and 85.8 ± 78 uIU/ml and 42.2 ± 23.2 uIU/ml at 60 mins and 120 mins respectively. CGM analysis revealed mean CGM glucose was 120.4 ± 14.8 with SD 26.2 ± 7.7. Glucose control was excellent with 94 ± 9.2% of readings within 70-180mg/dl and 79.8 ± 17.6% within 70-140 mg/dl. Percentage time &lt; 70 mg/dl and &lt; 54 mg/dl were 1.1 ± 1.1% and 0.1 ± 0.4% respectively. Percentage time &gt; 180 and &gt; 250 mg/dl were 4.8 ± 9.3% and 0.4 ± 0.7% respectively. HBGI, LBGI and ADRR were 1.3 ± 1.6, 0.7 ± 0.5 and 17.4 ± 8.9 respectively.
Conclusion: PT recipients demonstrate excellent glucose control on comprehensive assessment one or more years after the procedure. CGM and MMT data are different from normal people.

Disclosure
R. Kaur: None. C. Reid: None. P. Thapa: None. S. Rizvi: None. S.K. McCrady-Spitzer: None. S. Batthula: None. B.H. Smith: None. P. Dean: None. W.K. Kremers: Research Support; Self; AstraZeneca. A. Kukla: None. M.D. Stegall: None. Y.C. Kudva: Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Other Relationship; Self; Abbott.
370-OR: Hepatic FGF21 Expression Is Under the Regulation of the Canonical Wnt Signaling Pathway
Authors: BADAKHSHI YASAMAN , SHAO WEIJUAN , TIAN LILI , JIN TIANRU 
Published: June 2020

The metabolic hormone FGF-21 is mainly produced and released from the liver in response to nutritional stresses such as starvation, alcohol or ketogenic diet consumption. Body weight lowering and insulin signaling sensitization effects of FGF-21 and its analogues have been demonstrated in animal models or in human subjects. We show here that hepatic FGF-21 mRNA and FGF-21 protein levels were reduced in male LTCFDN, a transgenic mouse line in which canonical Wnt signaling cascade is functionally attenuated due to the expression of dominant negative transcription factor TCF7L2 in the liver, and the reduction is not associated with reduced expression of PPARα, a key transactivator of FGF-21. Furthermore, starvation-induced plasma FGF-21 elevation was also attenuated in male LTCFDN mice.
Utilizing mouse primary hepatocytes, we found that FGF-21 mRNA and FGF-21 protein expression can be increased by Wnt-3a or LiCl treatment. Two evolutionarily conserved TCF binding motifs (TCFB) were then located within the mouse FGF-21 gene promoter. Luciferase and ChIP results suggest that one of them is responsible for β-cat/TCF mediated activation on FGF-21 transcription.It has been shown recently that in mouse brain tanycytes, FGF-21 secretion can be induced by palmitate treatment. We found that in mouse primary hepatocytes, palmitate but not oleate treatment increased expression of the Wnt target gene Ccnd1, which encodes cyclin D1.
Our observations hence suggest that Wnt signaling cascade is involved in hepatic FGF-21 production and secretion, and the positive regulation is likely independent of fibrate/PPARα-mediated induction. Investigations on this novel hepatic signaling axis will strengthen our knowledge on the physiologically significant hormone FGF-21, leading to novel therapeutic avenues in treating impaired metabolism.

Disclosure
Y. Badakhshi: None. W. Shao: None. L. Tian: None. T. Jin: None.

Funding
Canadian Institutes of Health Research (PJT159735)
375-P: Missed Bolus Doses (MBDs) Are Associated with Reduced Time-in-Range (TIR): The Influence of Hypoglycemic Fear
Authors: EDWARDS STEPHANIE S. , HE XUANYAO , JOHNSON JENNAL , MEADOWS ERIC , WANG WENJIE , WOLPERT HOWARD , POLONSKY WILLIAM 
Published: June 2020

Connected insulin pens have potential utility as diagnostic tools to objectively assess MBDs and their impact on glycemic outcomes. This cross-sectional study enrolled 68 people with T1D or insulin-using T2D (A1C ≥ 8%, ≥ 3 insulin boluses/day reported at enrollment). Mean (± SD) age of participants was 48 years (± 12), 44% female, 59% T1D, 51% BMI ≥ 30 and 65% with A1C ≥ 9.0%. Connected pen and blinded CGM data (21 days collected) were used to calculate MBDs (no insulin dose from 2 hrs prior to and 4 hrs after the start of a glucose excursion [defined as &gt; 70 mg/dl rise within 2 hrs, not preceded by a value &lt; 70 mg/dl]). On average, participants had 21.6 MBDs/30 days (range 0-55.8); time-in-range (TIR) was relatively low, 42.6% (± 18.8%) while time-above-range (TAR) was high, 52.8% (± 21.3%). MBD daily frequency was significantly associated with TIR (Spearman’s correlation coefficient [rS] = -0.28, p = 0.02) and TAR (rS = 0.26, p = 0.03). Baseline predictors of MBD included A1C (incidence rate ratio, IRR = 1.118, p = 0.003) and BMI (IRR = 0.969, p = 0.008). Due to differences between T1D and T2D populations (age: 42.5 vs. 55.2 yrs, p &lt; 0.001; BMI: 27.7 vs. 34.1, p &lt; 0.001; diabetes duration: 22.7 vs. 16.0 yrs, p = 0.015, respectively), the groups were analyzed separately. For T2D, MBDs were associated with the Worry, Avoidance, and Maintain High subscales of the Hypoglycemic Fear Survey (HFS-W, A, and MH). MBDs were significantly more common among those with lower HFS-W (IRR = 0.940, p = 0.004), but with higher HFS-A (IRR = 1.140, p = 0.004) and higher HFS-MH (IRR = 1.075, p = 0.040). For T1D, none of the HFS subscales were significantly associated with MBDs. Given the differences in behavioral factors associated with MBDs in T1D and T2D, customized therapeutic approaches to reduce MBDs and improve TIR are likely needed.

Disclosure
S.S. Edwards: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. X. He: Employee; Self; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company. E. Meadows: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. W. Wang: None. H. Wolpert: Employee; Self; Eli Lilly and Company. W. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Roche Diabetes Care. Consultant; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Onduo, Sanofi US, Xeris Pharmaceuticals, Inc.

Funding
Eli Lilly and Company
378-P: Real-Time Inpatient Hypoglycemia Intervention Reduces the Rate of Recurrent Severe Hypoglycemia
Authors: GORANTLA YAMUNA , YAP SARA ELIZABETH T. , GUERRA YANNIS , FOGELFELD LEON 
Published: June 2020

Hypoglycemic events are a common inpatient safety issue; over half are preventable. There are no studies of real-time detection/response to prevent recurrence of hypoglycemia. We evaluated the effectiveness of real-time electronic hypoglycemia surveillance program (REHSP) to reduce the rate of recurrent severe hypoglycemic events (RHE) in hospitalized patients.
REHSP is driven by a multidisciplinary team of endocrinologists and nurse practitioners who review an electronic database of all inpatient hypoglycemia events in the last 24hrs. Recommendations to reduce RHE are given to primary teams and appropriate response is monitored.
We compared recurrence rates of severe hypoglycemia (BG &lt;50 mg/dL) in inpatients with at least one severe hypoglycemic event (index event) 1 year Pre-REHSP vs. 1 year Post-REHSP implementation. RHE were defined as severe hypoglycemia occurring 20 hours and more after the index event (based on CMS criteria). The primary outcomes were rates of RHE and appropriate response by the primary teams.
The Table shows that demographic and clinical characteristics were similar in both groups. In the Post-REHSP group the rates of RHE and length of stay declined significantly and the appropriate response of the teams significantly increased.
This study highlights the potential of reducing recurrent hypoglycemia through real-time intervention.

Disclosure
Y. Gorantla: None. S.T. Yap: None. Y. Guerra: None. L. Fogelfeld: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Gan & Lee Pharmaceuticals, Gilead Sciences, Inc., Merck & Co., Inc., Sanofi.
388-P: Real-World Associations between Glucose Management Indicator and CGM-Derived Metrics of Hypoglycemia
Authors: WALKER TOMAS C. , DOWD ROBERT , WELSH JOHN , NORMAN GREGORY J. , PARKER ANDREW SCOTT , PRICE DAVID A. 
Published: June 2020

Early randomized controlled trials (RCTs) showed a strong inverse relationship between A1C and severe hypoglycemia (SH) risk, which could potentially limit therapy intensification and resulted in some guidelines suggesting increased A1C goals in at-risk patients. Subsequently, RCTs demonstrated that real-time continuous glucose monitoring (CGM) alters this relationship and attenuates SH risk associated with low A1C values ≥6.5%. The glucose management indicator (GMI) reflects average CGM glucose and correlates with A1C. This analysis uses real-world evidence to explore the relationship between GMI and hypoglycemia exposure. Data were from an anonymized convenience sample of 151,315 U.S.-based Dexcom G6 CGM app users with good device adherence evidenced by having uploaded ≥80% of possible CGM values in 3Q 2019. Hypoglycemia exposure was reported as the percentage of glucose values &lt;70 or &lt;54 mg/dL (level 1 or level 2 hypoglycemia, respectively). The Figure shows hypoglycemia and the number of users in six GMI categories. Although there are small, incremental increases in hypoglycemia until GMI is &lt;6.5%, time spent in level 1 and level 2 hypoglycemia remains below the consensus goals of &lt;4% and &lt;1% for users with GMI values ≥6.5%. On average, CGM users with GMI values ≥6.5% have acceptably low rates of hypoglycemia, obviating the need to relax GMI goals as a strategy to reduce the risk of SH.

Disclosure
T.C. Walker: Employee; Self; Dexcom, Inc. J. Welsh: Employee; Self; CSL Behring. G.J. Norman: Employee; Self; Dexcom, Inc. A. Parker: Employee; Self; Dexcom, Inc. Stock/Shareholder; Self; Dexcom, Inc. D.A. Price: Employee; Self; Dexcom, Inc.
413-P: The New Myokine Myonectin Is Significantly Associated with Type 2 Diabetes in Patients with Peripheral Artery Disease
Authors: MUENDLEIN AXEL , GEIGER KATHRIN , LEIHERER ANDREAS , ZACH CHRISTINA , VONBANK ALEXANDER , SAELY CHRISTOPH H. , HEINZLE CHRISTINE , FRAUNBERGER PETER , DREXEL HEINZ 
Published: June 2020

The novel myokine myonectin is predominantly expressed in skeletal muscle and is involved in the regulation of metabolic homeostasis. A putative association between myonectin and type 2 diabetes mellitus (T2DM) has been discussed controversially in current literature. The association between myonectin and T2DM in subjects peripheral artery disease (PAD) has not been investigated at all and is addressed in the present study. We measured myonectin in 224 patients with sonographically proven PAD, of whom 93 had T2DM (41.5%). Myonectin concentrations were significantly decreased in PAD patients with T2DM compared to nondiabetic PAD patients (median 2.00, interquartile range [1.19-3.35] versus 2.63 [1.58-3.88] ng/ml; p=0.030). Analysis of covariance revealed that the association between myonectin and T2DM remained significant after adjusting for age, sex, body mass index, LDL-cholesterol, smoking, as well as systolic and diastolic blood pressure (F=5.42; p=0.021). Further, plasma myonectin significantly correlated with HbA1c (spearman’s rho=-0.164; p=0.015), but not with levels of fasting glucose or 2-hour glucose in oral glucose tolerance tests (rho=-0.059; p=0.387 and rho=-0.148; p=0.053, respectively). We conclude that plasma myonectin levels are significantly associated with T2DM in patients with PAD.

Disclosure
A. Muendlein: None. K. Geiger: None. A. Leiherer: None. C. Zach: None. A. Vonbank: None. C.H. Saely: None. C. Heinzle: None. P. Fraunberger: None. H. Drexel: None.
423-P: The A Body Shape Index and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events and Mortality in Patients with Established Cardiovascular Disease
Authors: VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , MAECHLER MAXIMILIAN , SPRENGER LUKAS , LEIHERER ANDREAS , PURIN DANIELA , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2020

The A Body Shape index (ABSI) is a validated measure of visceral adiposity that is calculated based on waist circumference, height and BMI. Its power to predict cardiovascular events and mortality in patients with established cardiovascular disease (CVD) is unclear and is addressed in the present study. We prospectively recorded cardiovascular events in a large cohort of 1546 patients with established CVD (1299 patients with angiographically proven stable coronary artery disease and 247 patients with sonographically verified PAD) over a mean follow-up time of 9.7±4.6 years. At baseline, the ABSI was higher in patients with type 2 diabetes (T2DM; n=502) than in those who did not have diabetes (8.4±0.6 vs. 8.3±0.5; p&lt;0.001). Prospectively, the ABSI significantly predicted the incidence of cardiovascular events (n=749) and death (n=619) after adjustment for age, gender, smoking, hypertension, LDL cholesterol, HDL cholesterol, and T2DM (standardized adjusted HRs 1.11 [1.03-1.19]; p=0.006 and 1.18 [1.09-1.27]; p&lt;0.001, respectively). T2DM in turn also significantly predicted cardiovascular events and death in this fully adjusted model independently from the ABSI, with adjusted HRs of 1.37 [1.17-1.0]; p&lt;0.001 and 1.40 [1.18-1.6]; p&lt;0.001, respectively. We conclude that the ABSI and T2DM are mutually independent of cardiovascular events and mortality in patients with PAD.

Disclosure
A. Vonbank: None. B. Larcher: None. A. Mader: None. M. Maechler: None. L. Sprenger: None. A. Leiherer: None. D. Purin: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
440-P: Decreased Peripheral Perfusion Measured by Perfusion Index Is a Novel Indicator for Cardiovascular Death in Patients with Type 2 Diabetes and Established Cardiovascular Disease
Authors: OKADA HIROSHI , OKADA YUKI , FUKUI MICHIAKI 
Published: June 2020

We investigated the role of peripheral perfusion as an indicator for cardiovascular death in patients with type 2 diabetes and established cardiovascular disease (CVD). This retrospective cohort study included 1080 patients with type 2 diabetes and history of CVD recruited from the outpatient clinic at Matsushita Memorial Hospital in Osaka, Japan. Peripheral perfusion is assessed using the perfusion index (PI), which represents the level of circulation through peripheral tissues. PI was measured using a Masimo SET Radical-7 (Masimo Corporation, Irvine, CA) instrument. The median age and PI values were 74 years (range: 67-79 years) and 2.6% (range: 1.1-4.3%), respectively. The average duration of follow up was 871 ± 265 days. During follow-up duration, 60 patients died due to CVD. The adjusted Cox regression analysis demonstrated that the risk of developing cardiovascular death was higher in the first quartile (HR, 5.84; 95% CI, 2.23 to 20.16) or second quartile (HR, 3.00; 95% CI, 1.05 to 10.81) of PI than that in the highest quartile (fourth quartile) of PI. PI (per 1% decrease) was associated with the development of cardiovascular death (HR, 1.38; 95% CI, 1.15 to 1.64). PI could be a novel indicator of cardiovascular death in patients with type 2 diabetes and established CVD.

Disclosure
H. Okada: None. Y. Okada: None. M. Fukui: None.
445-P: Network Meta-analysis of Seven Glucagon-Like Peptide-1 Receptor Agonists: A Focus on Cardiovascular Outcome Trials Data
Authors: ALFAYEZ OSAMAH , ALKHEZI OMAR , ALMUTAIRI ABDULAALI R. 
Published: June 2020

Objective: To indirectly compare glucagon like peptide-1 receptor agonists (GLP-1RA) cardiovascular outcome trials (CVOTs) using network meta-analysis (NMA).
Methods: We searched Medline to retrieve CVOTs that involved GLP-1RA. We conducted NMAs using binomial likelihood logit link model for the following outcomes: CV death, myocardial infarction (IM), stroke, and death from any cause. After running both fixed effects and random effects models for each outcome, we identified the best fit model that has the smallest deviance information and the average posterior residual deviance. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA) in reporting this NMA.
Results: After screening, a total of seven GLP-1RA CVOTs were included. The NMA results showed that oral semaglutide was statistically better than exenatide (HR 0.47, CI: 0.21-0.99), dulaglutide (HR 0.46, CI: 0.20-0.97), albiglutide (HR 0.45, CI: 0.19-0.97), and lixisenatide (HR 0.43, CI: 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (&gt;90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.
Conclusion: The indirect comparison of GLP-1RAs using CVOTs data showed that oral semaglutide is preferred over most of the GLP-1RAs in reducing CV death and death from any cause events. The ranking probability showed that once weekly semaglutide and oral semaglutide are the most likely to be ranked first in reducing the outcomes of interest.

Disclosure
O. Alfayez: None. O. Alkhezi: None. A.R. Almutairi: None.
447-P: Bone Mineral Density Is Associated with Subclinical Atherosclerotic Cardiovascular Disease in Elderly Men with Type 2 Diabetes
Authors: CHEN YAO , WANG XINGCHUN , MA BINGWEI , QU SHEN , WEI DONG 
Published: June 2020

The incidence of osteoporosis is controversial in type 2 diabetes(T2DM). There have been few studies to explore the influencing factors of bone mineral density (BMD) in old diabetic men. This study aimed to investigate the association of BMD with subclinical atherosclerotic cardiovascular disease in diabetic men. 295 diabetic men over 55 years old were enrolled divided into two groups: subclinical PAD and non-subclinical PAD group with age-, BMI-, and duration of diabetes- matched. The subclinical PAD was defined by ankle brachial index (ABI)≤0.9. BMD (at right hip, femoral neck and lumbar spine1-4 (L1-L4) by dual-energy X-ray absorptiometry), bone metabolic markers, ABI and routine anthropometric parameters were measured. Results showed that the incidence of osteoporosis had no difference(37.6% vs. 36.4 %,P=0.865). BMD at right hip were significantly lower in subclinical PAD group than non-subclinical PAD group (0.83±0.27g/cm2 vs. 0.92±0.16g/cm2, P=0.004). The T-score and Z-score at right hip, and T-score at femoral neck were significantly lower(-1.10±0.88vs. -0.69±0.97, P=0.005; -0.39±0.82 vs. -0.07±0.96, P=0.03;-1.36±0.92 vs. -0.99±1.04, P=0.02). BMD, T-score and Z-score at right hip were significantly associated with ABI(r=0.165,P=0.004; r=0.174,P=0.003, r=0.133,P=0.022).
In conclusion, BMD was associated with subclinical PAD in elderly men with type 2 diabetes. It suggests that vascular health, even in its early stages, is linked to bone health in elderly men with type 2 diabetes.

Disclosure
Y. Chen: None. X. Wang: None. B. Ma: None. S. Qu: None. D. Wei: None.
45-LB: Introduction of the Diabetes Exercise Perception (DEEP-1) Questionnaire for Assessing Perceived Attitudes and Challenges in Athletes with Type 1 Diabetes
Authors: SCOTT SAM N. , FONTANA FEDERICO Y. , HAYES CHARLOTTE A. , LAGROU PETER H. , ZUEGER THOMAS , SOUTHERLAND PHIL , STETTLER CHRISTOPH 
Published: June 2020

Background and Aims: Little is known about individual perspectives and challenges faced by elite-level athletes living with type 1 diabetes and where they turn to for advice. Currently, there is no validated tool to assess this. We aimed to generate and pilot test the Diabetes ExErcise Perception (DEEP-1) questionnaire in a group of professional endurance athletes with type 1 diabetes to investigate perceived attitudes and challenges.
Methods: The online questionnaire consists of a range of open and closed questions, focusing on 4 key areas related to diabetes management and exercise: 1) Technology; 2) Sleep and Recovery; 3) Glucose Management; and 4) Nutrition. Sixteen professional cyclists with type 1 diabetes (age 27 ± 4 years; HbA1c 6.8 ± 0.5%) were asked to anonymously complete the questionnaire using SurveyMonkey.com. Data were then analyzed descriptively.
Results: Fifteen participants responded. In this cohort, 90% showed an interest in using technology for improved exercise performance and 89% for glucose management, although 28% felt unaware of newer technologies. Glucose was perceived as being generally well regulated; however, according to the responses, more attention needs to be focused overnight and pre/during exercise. Sleep quality was rated as an important factor affecting exercise performance by 80% of respondents. 93% of participants identified nutrition as an area for improved performance, with 25% reporting a lack of education in this area.
Conclusions: This pilot study highlights the importance of an individualized approach to diabetes management and high-level exercise performance. Future work should validate the DEEP-1 questionnaire in a larger sample size using individuals with a range of physical activity levels. Such a tool may provide a useful and time-efficient means for health care professionals to gain deeper insight into their patients’ attitudes and challenges regarding exercise.

Disclosure
S.N. Scott: None. F.Y. Fontana: None. C.A. Hayes: Other Relationship; Self; Novo Nordisk A/S. P.H. Lagrou: None. T. Zueger: None. P. Southerland: None. C. Stettler: None.