bluuebunny/crossref_metadata_2025_split huggingface dataset:
397-P: BETTER Understanding Hypoglycemia in Type 1 Diabetes (T1D)
Authors: CHENG RAN , TALEB NADINE , MESSIER VIRGINIE , TALBO MERYEM K. , ROY-FLEMING AMÉLIE , RABASA-LHORET RÉMI , BRAZEAU ANNE-SOPHIE 
Published: June 2020

Introduction: For patients living with T1D, hypoglycemia is the most frequent complication and obstacle in achieving optimal glycemic control with potentially significant adverse implications on individuals’ quality of life. To improve hypoglycemia prevention and management, the BETTER registry for people living with T1D was launched in April 2019 in the province of Quebec, Canada.
Methods: Participants self-register online in the BETTER registry and are asked to answer a series of questionnaires (3 phases). We report the preliminary results of phase I among participants of ≥14 years old, which aims to provide a comprehensive portrait of the population with T1D.
Results: Mid-December 2019, 718 individuals (64.6% female, age 41.8±15.4 years old, duration of diabetes 22.4±14.7 years, 93.2% with T1D and 6.7% with LADA, 71.2% with HbA1c &lt;8%) have registered. Of the participants, 99.6% were currently on insulin therapy (46.7% on insulin pumps, 51.2% on insulin injections, 1.7% using both), and 77.3% were using continuous or flash glucose monitoring. They reported, on average, 6.27±7.42 episodes of hypoglycemia (&lt;54 mg/dl) in the last month. Since their diagnosis, 47.8% of participants had at least one episode of severe hypoglycemia (SH: requiring help from another person or use of glucagon or hospitalization or loss of consciousness). Among those who reported SH in the last 12 months (n=91), the average number of episodes was 2.34±3.37 during this period. When asked what hypoglycemia represents using one word, one-fifth of participants used the word “weak” or “weakness."
Conclusion: In a contemporary group of patients widely using technology for T1D management, hypoglycemia remains frequent. The growing BETTER registry will allow further understanding of this challenging reality and enable future research aiming to reduce hypoglycemia episodes.

Disclosure
R. Cheng: None. N. Taleb: None. V. Messier: Other Relationship; Self; Eli Lilly and Company. M.K. Talbo: None. A. Roy-Fleming: None. R. Rabasa-Lhoret: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc. Board Member; Self; Merck & Co., Inc., Sanofi. Research Support; Self; Eli Lilly and Company, Novo Nordisk A/S, Novo Nordisk A/S, Sanofi. A. Brazeau: None.

Funding
Canadian Institutes of Health Research (JT1-157204); JDRF (4-SRA-2018-651-Q-R)
4-OR: Diabetes Duration and the Relative Importance of Cardiovascular Risk Factors in Type 1 Diabetes
Authors: FAHRMANN ELKE R. , DRISCOLL HENRY 
Published: June 2020

Based on a Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) report and their own findings, Pittsburgh Epidemiology of Diabetes Complications investigators concluded that the relative impact of HbA1c and kidney disease in type 1 diabetes (T1D) on cardiovascular disease (CVD) varies according to T1D duration. We investigate the relative importance of HbA1c and other CVD risk factors during ∼ 30 years of DCCT/EDIC follow-up within the primary (RET-: subjects with a mean T1D duration of 2.6 years and without retinopathy at baseline) and within the secondary DCCT cohort (RET+: subjects with a mean T1D duration of 8.6 years and with mild to moderate retinopathy at baseline). CVD included fatal/nonfatal myocardial infarction (MI) or stroke, silent MI, revascularization, confirmed angina, or congestive heart failure. Cox regression models with robust error variances were used to find the most significant CVD risk factors (p&lt;0.05) within RET- and within RET+. The importance of risk factors was determined by evaluating the z value, a measure of association strength between risk factor and CVD. In case of hazard assumption violation, time by covariate interaction was included in model. DCCT enrolled 1441 subjects (age 13-39); 115 of 715 RET+ subjects and 69 of 726 RET- subjects had a CVD event. For RET+, the most important risk factors were baseline (B) age (z ∼4.2), time dependent (T) mean (M) systolic blood pressure (SBP) (z ∼4.0), any severe hypoglycemia (z ∼3.7), and TM HbA1c (z ∼3.2). Other significant risk factors included B autonomic neuropathy, TM insulin dose, TM LDL, T current (C) ACE inhibitor use, TC insulin regimen and B severity of retinopathy but not T1D duration. For RET-, B age, TM HbA1c, TC triglycerides and TM SBP with an increasing CVD effect over follow-up time were significant. The relative importance of CVD risk factors in a young T1D cohort varies according to microvascular complications, which correlate with T1D duration.

Disclosure
E.R. Fahrmann: None. H. Driscoll: None.
400-P: High Levels of Glycemic Coefficient of Variation Are Associated with Higher Hypoglycemia Episodes in T1D Adults in a Brazilian Tertiary Hospital
Authors: BRASIL THAIS B. , SPOSITO ANDREI C. , ADACHI BEATRIZ , VOLPINI WALKYRIA M. , PAVIN ELIZABETH J. 
Published: June 2020

People with type 1 diabetes (T1D) have a higher risk of hypoglycemia (H), especially in the presence of high glycemic excursion, increasing cardiovascular mortality. The coefficient of variation (CV) allows current assessment of glycemic control and therapeutic adequacy. This cross-sectional study investigated the associations among H episodes, CV, glycemic variability (GV), and T1D clinical and laboratory parameters. Sixty T1D patients aged ≥18 years and followed for at least six months in a Brazilian Public Tertiary Hospital were included. Three seven-point glycemic profiles were performed in consecutive days, totalizing 21 blood glucose tests. The indicators GV, standard deviation (SD)/glycemic mean (mg/dL) and CV, SD/glycemic mean were calculated from data record in the monitor. H was classified as H1:&lt;70 and ≥54mg/dL and H2:&lt;54mg/dL. Statistical analysis was performed with Spearman correlation and Mann-Whitney (p&lt;0.05 was considered significant). Of all, 73.3% were women, aged 34.7 ± 2.3 years, T1D duration: 22.5 ± 9.7 years, HbA1c 8.8 ± 1.8%, GV 70.9 ± 25.9mg/dL (goal&lt;50) and CV 42.8 ± 9.6% (goal&lt;36%). H occurred in 76.7%, and H2 in 50% of T1D patients. H1 was positively correlated with CV (p&lt;0.0001) and T1D duration (p&lt;0.0271); negatively with mean of glycemia (p&lt;0.0001), and glycemia above target (&gt;180mg/dL) (p&lt;0.0004). H2 was positively correlated with CV (p&lt;0.0005); blood glucose below target (&lt;70mg/dL) (p&lt;0.0001), and reported weekly frequency of hypoglycemia (p&lt;0.0470). T1D patients presented high VC and GV. Only CV had a significant correlation with H1 and H2 episodes. Education about quickly hypoglycemia treatment is highly required, mainly in the presence of asymptomatic episodes. Systematic glycemic monitoring and continuing education in diabetes, targeting insulin dose adjustments, glycemic goals, healthy food orientation, and physical activity may reduce life risks of this population.

Disclosure
T.B. Brasil: None. A.C. Sposito: None. B. Adachi: None. W.M. Volpini: None. E.J. Pavin: None.
401-P: Mortality, Major Adverse Cardiovascular Events (MACDE), and Diabetic Complications in Men with Hypogonadism and Type 2 Diabetes (T2DM) Receiving Long-Term Treatment with Testosterone Undecanoate Injections (TU): 11-Year Real-World Data
Authors: HAIDER AHMAD , HAIDER KARIM S. , SAAD FARID 
Published: June 2020

Background: Men with hypogonadism are at increased risk of MACE and mortality. Studies in men with T2DM show that testosterone therapy (TTh) reduces both MACE and mortality.
Methods: In a registry of 858 men with hypogonadism, 356 men (41.5%) had T2DM. 178 received testosterone undecanoate injections (TU) 1000 mg/12 weeks (T-group) and 178 opted against treatment (CTRL). MACE, mortality, and diabetic complications were recorded and compared between groups.
Results: Mean baseline age in the T-group and CTRL was 61.8±5.1 and 63.6±4.9 years, respectively. Mean follow-up in T-group vs. CTRL was 7.4 and 8.3 years, respectively. 69 patients (38.8%) in the T-group and 70 (39.3%) in CTRL had a history of cardiovascular disease (myocardial infarction, stroke, or coronary artery disease diagnosis) (p=0.9135). Baseline smoking prevalence was 41.6% (74 men) in the T-group and 38.2% (68 men) in CTRL (p=0.5161). The T-group had significantly worse baseline risk factor profile than CTRL: BMI (36.5±4.5 vs. 33.4±5.3 kg/m²), systolic blood pressure (163.0±13.3 vs. 145.6±14.6 mmHg), LDL (4.7±0.9 vs. 4.1±1.4 mmol/L), HbA1c 9.4±1.4 vs. 7.8±0.7% (p&lt;0.0001 for all). Mortality: during the entire observation period, 13 patients (7.3%) died in the T-group vs. 48 (27.0%) in CTRL (p&lt;0.0001). MACE: in the T-group, there were no cases of myocardial infarction or stroke. In CTRL, there were 55 cases of myocardial infarction (30.9%) and 45 cases of stroke (25.3%). Diabetic complications: in the T-group vs. CTRL, the incidence of retinopathy was 3.4% and 16.9% (p&lt;0.0001), nephropathy 0.6% and 4% (p&lt;0.05), polyneuropathy 6.2% and 54.8% (p&lt;0.0001), diabetic foot syndrome 0% and 9.6% (p&lt;0.0001).
Conclusions: Long-term treatment with TU in men with hypogonadism and T2DM significantly reduces MACE and mortality, as well as diabetic complications compared to untreated controls.

Disclosure
A. Haider: None. K.S. Haider: None. F. Saad: Consultant; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Bayer AG.

Funding
Bayer AG
409-P: Engineered Cardiac Tissues: A Novel In Vitro Model to Investigate the Pathophysiology of Diabetic Cardiomyopathy
Authors: WANG XIANG , ZHENG YANG , KELLER BRADLEY B. , CAI LU 
Published: June 2020

Rodent diabetic models have advanced our understanding of the pathophysiology of diabetic cardiomyopathy (DCM), however these models require long timelines to display DCM, and also display confounding influences inherent to in vivo models, but in vitro cardiomyocyte cultures could not reflect the structure-function relationship specific to the heart. Over the past 2 decades, engineered cardiac tissues (ECTs) have emerged as robust 3D in vitro models to investigate cardiac tissue maturation, structure-function relationships, cardiac injury response and repair. Advanced glycation end-products (AGEs), the proteins or lipids that become glycated in response to hyperglycemia, produce diabetes-associated tissue injury via receptor (RAGE) activating reactive oxygen or nitrogen species (ROS/RNS). Therefore, we developed a ECT model to investigate cardiac injury produced by AGEs. We used ECTs composed of neonatal murine cardiac cells and found: (1) AGEs at 150 µg/ml did not cause significant cytotoxicity (necrosis, detected by medium LDH or apoptosis, detected by c-caspase 3), but negatively impacted ECT function by 9-day treatment; (2) AGEs triggered fibrotic (Collagen I-α1, Collagen III-α1, FN1) and hypertrophic (ANP and β-MHC) responses on day 3 - 9 after treatment; (3) AGE also increased ECT’s oxidative stress (3-NT, 4-HNE, HO-1, CAT, SOD2) and inflammation (PAI-1, TNF-α, NF-κB, ICAM); (4) All AGE-induced oxidative stress, inflammation, fibrotic response and hypertrophy and ECT dysfunction were prevented by the RAGE inhibitor FPS-ZM1 or by inhibiting ROS/RNS production via NAC. Thus, AGEs-treated neonatal murine ECTs recapitulate key cellular and molecular pathophysiological features of DCM and can serve as a robust ex vivo model to investigate cell-cell specific pathways relevant to DCM along with cardioprotective strategies. This model even has a great potential to directly investigate the effect of diabetes on human ECTs if human iPSC can be introduced.

Disclosure
X. Wang: None. Y. Zheng: None. B.B. Keller: None. L. Cai: None.
41-LB: Effectiveness of a Two-Year Peer Support Diabetes Education Intervention Implemented in a Semiurban Mayan Community in the Yucatan, Mexico
Authors: CASTILLO-HERNÁNDEZ KAREN G. , LAVIADA HUGO , ESPINOSA-MARRÓN ALAN , MOLINA FERNANDA 
Published: June 2020

Type 2 diabetes (T2D) prevalence in adults has increased significantly in Mexico in recent years. In the Mayan population, factors like poverty and language barriers intensify the problems of living with T2D. Peer support is a promising approach to diabetes care as it helps patients to support each other throughout their everyday lives. This program was first evaluated by our group in Komchen, a rural mayan community, where peer support had significant reductions in A1c levels at 4 and 8 months of follow-up. The aim of this study is to assess the effects of a two-year peer support education program for patients with T2D in a semi-urban Mexican Mayan community.
Methods: Patients with previous diagnosis of T2D were recruited from the community clinics (n=156) and randomized to: 1) Participants invited to attend the Education Program (EP)delivered by a certified diabetes educator; or 2) Participants were invited to attend the EP plus peer support meetings (PSM) facilitated by leaders with type 2 diabetes.
Results: Unlike our experience in Komchen, adherence to the EP in Conkal, a more populated and urbanized town, was lower: 80% in Komchen vs. 33% in Conkal, the same fact occurred for PSM. We found a relevant clinical difference in A1c level between groups (Figure 1) although difference was not statistically significant.
Conclusions: It remains a tendency to maintain or decrease A1C levels through time on intervention groups compared to the control.

Disclosure
K.G. Castillo-Hernández: None. H. Laviada: None. A. Espinosa-Marrón: None. F. Molina: None.

Funding
AstraZeneca Mexico (D1843L00017)
414-P: Hand-Grip Strength and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events and of Mortality in Patients with Established Cardiovascular Disease
Authors: LARCHER BARBARA , VONBANK ALEXANDER , MADER ARTHUR , MAECHLER MAXIMILIAN , SPRENGER LUKAS , LEIHERER ANDREAS , PURIN DANIELA , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2020

Impaired skeletal muscle function is involved in the pathogenesis of type 2 diabetes (T2DM) as well as of cardiovascular disease (CVD). Hand grip strength (HGS) is a simple, inexpensive and non-invasive diagnostic parameter for muscle function. Its association with cardiovascular events and mortality in patients with established CVD is unclear and is addressed in the present study. We prospectively recorded cardiovascular events over a mean follow up time of 8.9±3.2 years in a cohort of 876 patients with established CVD (672 patients with angiographically proven coronary artery disease and 204 patients with sonographically proven peripheral artery disease). From our patients, 274 (31.3%) had T2DM at baseline; HGS did not differ significantly between patients with T2DM and nondiabetic subjects (35.3±11.9 vs. 36.6±11.9 kg; p=0.082). Prospectively, cardiovascular events occurred in 387 patients, and 278 patients died during follow-up. T2DM and low HGS after multivariate adjustment in Cox regression models proved to be mutually independent predictors of cardiovascular events (adjusted HR 1.52 [1.23-1.89]; p&lt;0.001 and standardized adjusted HR 0.85 [0.74-0.99]; p=0.032, respectively) as well as mortality (adjusted HR 1.79 [1.39-2.29]; p&lt;0.001 and standardized adjusted HR 0.69 [0.58-0.83]; p&lt;0.001, respectively). We conclude that low HGS and T2DM are mutually independent predictors of cardiovascular events as well as of mortality in patients with established CVD.

Disclosure
B. Larcher: None. A. Vonbank: 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.
416-P: Change in Extent of Coronary Artery Disease in People with and without Diabetes Undergoing Coronary Angiography
Authors: KIBURG KATERINA V. , MACISAAC ANDREW I. , SUNDARARAJAN VIJAYA , MACISAAC RICHARD 
Published: June 2020

Objective: To assess whether improvements in preventative care for people with diabetes have resulted in a relative decrease in the burden of coronary artery disease (CAD) compared to people without diabetes.
Methods: All patient-level linked coronary angiography and hospital separation data at a large Australian tertiary referral hospital between 2013 and 2019 were obtained. Indication for angiography and extent of CAD were based on original classification by treating cardiologists, classified as no disease, mild, moderate or severe. Propensity scores were estimated to match people with and without diabetes on a 1:1 ratio. Ordinal logistic regression models were fitted to assess trends in CAD severity in people with and without diabetes over time with adjusted odds ratios (adjOR) reported.
Results: For 3,016 people identified in the coronary angiography database and matched using propensity scores, 1508(50%) were diagnosed with diabetes. Angiographic evidence of CAD was detected in 1155(77%) and 1257(83%) people without and with diabetes. For people with diabetes there was an increased risk of more extensive CAD in 2018 compared to 2013 (adjOR: 2.02 95% C.I. 1.36, 2.99). This risk appears to have been attenuated in 2019 with no significant change in CAD burden between 2013 and 2019 (adjOR: 1.33 95% C.I. 0.90, 1.98). In contrast, there was no effect of time on CAD burden in people without diabetes.
Conclusions: The initial increase in severity of disease burden seen in our study for people with diabetes compared to those without diabetes may represent improved CAD screening rather than suboptimal application of preventative therapies. Possibly, greater recent use of newer glucose lowering medications with cardiovascular protective effects accounts for the attenuation of CAD burden in 2019 for people with diabetes. These findings highlight the importance of aggressive risk factor modification for people with diabetes to minimize the development and progression of CAD.

Disclosure
K.V. Kiburg: None. A.I. MacIsaac: None. V. Sundararajan: None. R. MacIsaac: None.
432-P: Creatinine-to-Cystatin C Ratio in Relation to Intima-Media Thickness in Patients with Type 2 Diabetes
Authors: SHIN JANG YEL 
Published: June 2020

Skeletal muscle mass (SM) was shown to be inversely related to cardiovascular disease (CVD) and mortality in some studies. However, the causal relationship between SM and CVD is not fully understood. Recently, creatinine-to-cystatin C ratio (Cr/cysC) has been suggested to be a useful surrogate marker for an estimation of SM. In the present study, we investigated whether Cr/cysC was related to intima-media thickness (IMT) in subjects with type 2 diabetes. A total of 459 patients with type 2 diabetes were recruited. Serum Cr and cysC were measured. All subjects were divided into three groups by gender-specific tertiles of Cr/cysC. We assessed carotid IMT using B-mode ultrasound. High IMT was defined as ≥ 75 percentiles of gender-specific maximal IMT. We checked body compositions using dual-energy X-ray absorptiometry. Patients with the highest tertile of Cr/cysC were younger and had higher prevalence of current smoking and regular exercise (RE) compared with those with the lowest. Also, they had higher values of Cr, fasting glucose (FG), HOMA-IR, and appendicular SM (ASM)/BMI, but had lower values of waist circumference (WC), cysC, Cr-based estimated glomerular filtration rate (Cr-eGFR), and IMT than those with the lowest. In the Pearson correlation, Cr/cysC was negatively related to age, BMI, and Cr-eGFR, but showed positive associations with FG and ASM/BMI in both genders. While WC and body fat percent were negatively associated with Cr/cysC in women alone. The odd ratios (ORs) for high IMT after adjusted for age were 0.76 (95% CI, 0.46-1.27) in the middle and 0.45 (95% CI, 0.25-0.79) in the highest, respectively. The OR in the highest was maintained significant after further adjustments for hypertension, current smoking, RE, BMI, WC, blood pressure, HDL, triglyceride, C-reactive protein, FG, HOMA-IR, and Cr-eGFR.
In conclusion, the present study showed that higher Cr/cysC was significantly related to the protection of risk for high IMT independently of multiple metabolic risk factors.

Disclosure
J. Shin: None.
434-P: Possible Mechanisms of Cardioprotective Effects of Metformin in Patients with Type 2 Diabetes and Chronic Heart Failure
Authors: HOŠKOVÁ EVA , KOPECKY JAN , VELEBA JIRI , MALINSKA HANA , VELEBOVA KATERINA , MELENOVSKY VOJTECH , PELIKANOVA TEREZIE 
Published: June 2020

Background and Aims: Metformin (MET) treatment in patients with type 2 diabetes (T2D) and chronic heart failure (HF) is associated with better cardiovascular outcomes. Possible mechanism of cardioprotective effect of metformin may be a reduction of dicarbonyl and oxidative stress. In particular, a reduction of methylglyoxal levels (MG). The aim of our study was to evaluate the effect of MET on cardiac structure, cardiac function and exercise capacity in patients with T2D and HF.
Materials and Methods: A randomized, double-blind, placebo-controlled, crossover study in a total time of six months testing the effect of 3- month usage of MET (2 g/day) vs. placebo. A group of 44 treatment naive patients with T2D and HF were included. At the beginning and at the end of each intervention period various metabolic tests were done including echocardiography, spiroergometry, and parameters of dicarbonyl stress like MG, Glutathione (GSH), glutathione disulfide (GSSG), and the activity of Glyoxalase1 (GLO-1).
Results: MET treatment led to a decrease in HbA1c levels (∆ MET vs. placebo: -3.39 ± 5.33mmol/mol, p = 0.00007), and fasting plasma glucose levels (∆MET vs. placebo: -0.381 ± 1.1mmol/l; p = 0.00145). MET had no effect on oxygen consumption at the maximum tolerated load during spiroergometry (VOmax) (∆MET vs. placebo: -0.142 ± 1.18ml/kg/min; p = 0.64). MET did not affect left ventricular ejection fraction (∆MET vs. placebo: -0.789 ± 6.32%; p = 0.53). The levels of MG didn’t change after MET (∆ MET vs. placebo: 0.0306 ± 0.13nmol/ml; p = 0.19). The activity of GLO-1 was not affected too (∆ MET vs. placebo: 0.0073 ± 0.017 mmol/min/mg Hb; p = 0.22).
Conclusion: MET treatment is safe in patients with severe heart failure. Our results do not support the evidence that one of the cardioprotective pathways of metformin is through reducing dicarbonyl stress.

Disclosure
E. Hošková: None. J. Kopecky: None. J. Veleba: None. H. Malinska: None. K. Velebova: None. V. Melenovsky: None. T. Pelikanova: None.

Funding
Institute for Clinical and Experimental Medicine 00023001)