bluuebunny/crossref_metadata_2025_split huggingface dataset:
11-OR: Youth Empowerment Skills (YES): A Novel Psychosocial Behavioural Intervention for Adolescents with Type 1 Diabetes
Authors: KARIYAWASAM DULMINI , SAQI KHULAT A. , DEHZAD FARANAZ , PENDER SIOBHAN , JONES MARIE , YEMANE NARDOS , GRIFFITHS REBECCA H. , SOUKUP TAYANA , SINGHAM STEPHANIE M. , FORBES ANGUS 
Published: June 2020

Background: The transition from adolescence to young adulthood can be challenging for young people with type 1 diabetes. During this period many young people become disengaged from their health care and can experience increases in adverse diabetes events and diabetes distress.
Study Aim: To deliver a novel psychoeducational programme called Youth Empowerment Skills (YES), using simulation based experiential learning and peer learning to increase diabetes knowledge and social confidence in young people with type 1 diabetes.
Method: The YES programme was delivered in community settings with a youth worker supporting engagement. HbA1c and admission data were collected 12-months pre and post intervention. Follow-up qualitative questionnaires and semi-structured interviews were conducted 6 weeks post-intervention to elicit participant views of the programme. The study was conducted in a South London boroughs with high levels of socioeconomic disadvantage and ethnic diversity.
Results: Data were collected from all participants (n=41), mean age 17.3±2.3 years. Mean HbA1c 12 month prior to attending the programme was (DDCT%) 10.4%±4.8%. There was a reduction of mean HbA1c at 12-months post-intervention to 9.7%± 4.6%m (Δ 0.7%) (p&lt; 0.01). DKA admissions reduced by 55.6% (n=15) over the 12 month follow-up; saving £78,000 in admission avoidance. The programme successfully engaged young people from ethnic minorities (53%) and with high social deprivation (65%). Qualitative data showed perceived improvements in clinical knowledge and psychosocial health. Feedback highlighted active learning sessions and peer support as strengths of the programme.
Conclusion: The study showed that the YES programme was beneficial in improving glycaemic control and reducing diabetes related admissions in adolescents with type 1 diabetes; and encouraged a more positive and accepting attitude towards living with diabetes.

Disclosure
D. Kariyawasam: None. K.A. Saqi: None. F. Dehzad: None. S. Pender: None. M. Jones: None. N. Yemane: None. R.H. Griffiths: None. T. Soukup: None. S.M. Singham: None. A. Forbes: None.
111-OR: MODY3 Diagnosis from Deidentified Pancreatic Tissue Leads to Variant Identification in Living Relatives
Authors: SPARLING DAVID , HALIYUR RACHANA , LINDNER JILL , WEBER LINDA , RAMIREZ ANDREA , BRISSOVA MARCELA , POWERS ALVIN C. 
Published: June 2020

As part of studies to understand human pancreatic islet pathophysiology in type 1 diabetes (T1D), we discovered normal β cell mass in a 33-year-old deceased organ donor with T1D for 17 years. Further analysis revealed the donor’s diabetes resulted from a causative variant in hepatic nuclear factor 1-alpha (HNF1A), associated with Maturity-onset Diabetes of the Young-3 (MODY3) (J Clin Invest 129:246, 2019), which can be treated with sulfonylureas. Review of the donor’s redacted medical chart suggested a family history of diabetes consistent with the known autosomal dominant pattern of inheritance of MODY3. With this clinically-actionable information, we desired to inform the donor’s family. However, de-identified samples are not considered “human subject” research by Institutional Review Boards (IRB), so the family’s identity was unknown with no defined pathway for communicating these findings. Working with a Human Tissue and Organ Research Resource and an organ procurement organization, we developed a new, IRB-approved communication path between those involved in tissue collection, scientific investigation, and the donor’s family and physician. This allowed targeted genetic testing of potentially affected family members, which revealed five living relatives of the donor who carried the HNF1A variant: three adults diagnosed with diabetes before the age of 25 currently treated with insulin and two children (ages 6 months and 3 years) who did not have clinical diabetes. Since none of the identified individuals were known to have MODY3, they will likely benefit from appropriate clinical care and surveillance. This experience demonstrates the need for the scientific community to develop guidelines to address handling, reporting, and use of research findings from de-identified tissue collected for research. Defining ethical avenues for donor family-investigator communications will benefit for both organ donor families and scientific research.

Disclosure
D. Sparling: None. R. Haliyur: None. J. Lindner: None. L. Weber: None. A. Ramirez: None. M. Brissova: None. A.C. Powers: None.
1114-P: Comparison of Remogliflozin and Canagliflozin as Add-On Therapy in Indian Uncontrolled T2DM Subject
Authors: SHANKAR ANAND 
Published: June 2020

Aim: Remogliflozin is a new SGLT2i for the treatment of type 2 diabetes mellitus approved in India. The primary objective of this study was to compare remogliflozin to canagliflozin in patient populations with inadequately controlled (HbA1c&gt;8%) and already treated with either diet/exercise, metformin plus a DPP-4i.
Method: 120 uncontrolled T2DM subjects (HbA1c&gt;8%) who were on optimum tolerable dose of metformin plus a DPP-4i, were selected for this real world observational trial. Primary end point was change from baseline in HbA1C at 12 weeks. Secondary end points included change in fasting plasma glucose (FPG) and post prandial plasma glucose (PPPG), and percent change in body weight. Safety was assessed based on adverse event (AE) like hypoglycemia reports.
Result: A comparable reduction in HbA1c were observed from baseline at the end of 12 weeks in both groups, remogliflozin 100 mg (N=60) (1.96%) (p&gt;0.001)and canagliflozin 300 mg (N=60) (1.67%)(p&gt;0.001), but inter group p value was non-significant(p=0.023). A similar significant reduction was demonstrated in both FPG (47.98% vs. 41.23%) and PPPG (49.81% vs. 42.89%) in remogliflozin group compared to canagliflozin group respectively. The proportion of patients who achieved an HbA1C &lt; 7% at 12 weeks was 51% in the remogliflozin group and 43% in the canagliflozin group. Statistically significant more weight loss was observed in remogliflozin arm compared to canagliflozin arm (-1.38 kg vs. -0.88 kg)(p&gt;0.001). The overall incidence of hypoglycemia (minor) was higher in patients treated with canagliflozin as compared to the patients treated with remogliflozin. The two groups differ in their cost effect, as treatment with canagliflozin group was 4.3 fold costlier than with remogliflozin till 3 months of treatment.
Conclusion: Effectiveness of remogliflozin is as comparable with canagliflozin as GLA. In country like India where cost is matter for compliance remogliflozin can be substitute of canagliflozin.

Disclosure
A. Shankar: None.
1119-P: Alleviating Carbohydrate Counting Burden in Type 1 Diabetes (T1D) with the Artificial Pancreas and Empagliflozin (EMPA)
Authors: HAIDAR AHMAD , YALE JEAN-FRANÇOIS , LOVBLOM LEIF ERIK , CARDINEZ NANCY , ORSZAG ANDREJ , FALAPPA CESAR M. , GOUCHIE-PROVENCHER NIKITA , FATHI ANAS EL , ELDELEKLI DEVRIM , SCARR DANIEL , PERKINS BRUCE A. 
Published: June 2020

We aimed to assess whether adding Empa to the artificial pancreas can alleviate the burden of carbohydrate counting without degrading glucose control. We conducted a randomized, open-label, crossover, non-inferiority trial in 30 adults with T1D (age 40±15 years, A1c 7.6±0.7%). Each participant used the artificial pancreas on 5 non-consecutive days at home (9-14 hours/day) with: Empa 25mg and (i) carbohydrate counting, (ii) simple meal announcements (pressing a button, no carbohydrate counting), and (iii) no meal announcements (fully automated), and with: no Empa and (iv) carbohydrate counting (control arm) and (v) simple meal announcements. The fully automated artificial pancreas with Empa was inferior to the artificial pancreas with carbohydrate counting without Empa (mean glucose 10.0±1.6 vs. 8.5±1.5 mmol/L, p&lt;0.001), but the artificial pancreas with simple meal announcement and Empa was non-inferior (8.5±1.4 mmol/L, non-inferiority p-value with a pre-specified margin of 0.75 mmol/L = 0.003). Time spent below 3.9 mmol/L was minimal in all interventions. No diabetic ketoacidosis was observed; mean ketones levels were 0.22±0.18 and 0.13±0.11 mmol/L, with and without Empa, respectively (p&lt;0.001). We conclude that SGLT2 inhibition added to the artificial pancreas may alleviate the need for carbohydrate counting but does not allow a fully closed-loop system.

Disclosure
A. Haidar: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., Eli Lilly and Company. J. Yale: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Board Member; Self; Diagnos. Research Support; Self; Bayer Inc., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk A/S, Sanofi. L. Lovblom: None. N. Cardinez: None. A. Orszag: None. C.M. Falappa: None. N. Gouchie-Provencher: None. A. El Fathi: None. D. Eldelekli: None. D. Scarr: None. B.A. Perkins: Consultant; Self; Abbott, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Other Relationship; Self; Medtronic.

Funding
Diabetes Canada
1123-P: Stress Cardiac Biomarkers and Adverse Cardiac Outcomes in the CANagliflozin CardioVascular Assessment Study (CANVAS)
Authors: SATTAR NAVEED , XU JIALIN , BUTLER JAVED , MAHAFFEY KENNETH W. , SHAW WAYNE , ROSENTHAL NORM , GUTSTEIN DAVID E. , HANSEN MICHAEL K. , JANUZZI JAMES 
Published: June 2020

SGLT2 inhibitors reduce risk of major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF) in patients with type 2 diabetes (T2D), but mechanisms remain unclear. We examined effects of canagliflozin vs. placebo on 3 prognostic biomarkers in CANVAS, as well as their predictive ability for outcomes of interest.
High sensitivity cardiac troponin T (hs-cTnT; Roche Diagnostics), soluble (s)ST2 (Critical Diagnostics), and insulin-like growth factor binding protein 7 (IGFBP7; Roche Diagnostics) were measured in up to 3680 participants at baseline, 1 y, and for hs-cTnT and sST2, 6 y. Conventional statistical methods adjusting relevant covariates were used to relate biomarkers to risk for incident MACE or HHF.
Higher concentration of all 3 biomarkers was associated with higher adjusted risk for incident MACE or HHF, with C-index improvements beyond covariates for MACE or HHF (Table). In terms of treatment effect, no biomarkers were differentially altered by 1 y but where data existed, both hs-cTnT (n=915; treatment coefficient [95% CI]: -0.064 [-0.121, -0.007]; p=0.027) and sST2 (n=828, treatment coefficient [95% CI]: -0.129 [-0.248, -0.010]; p=0.033) were reduced significantly at 6 y.
Among patients with T2D, concentrations of hs-cTnT, sST2, and IGFBP7 were associated with risk for MACE and HHF. Canagliflozin slowed longer term (6 y) increases in hs-cTnT and sST2.

Disclosure
N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. J. Xu: Employee; Self; Janssen Research & Development, LLC. J. Butler: Consultant; Self; Amgen, Array BioPharma, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, CVRx, G3 Pharmaceuticals, Innolife Co., Ltd., Janssen Pharmaceuticals, Inc., Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Relypsa, Inc., VIfor. K.W. Mahaffey: Consultant; Self; Medscape, Mitsubishi, Myokardia, NIH, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, UCSF. Research Support; Self; Afferent, Amgen, Apple, Inc, AstraZeneca, Cardiva Medical, Inc, Daiichi, Ferring, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, NIH, Novartis, Sanofi, St. Jude, Tenax. W. Shaw: Employee; Self; Janssen Pharmaceuticals, Inc. N. Rosenthal: None. D.E. Gutstein: Employee; Self; Janssen Research & Development, LLC. M.K. Hansen: Employee; Self; Janssen Research & Development, LLC. J. Januzzi: Consultant; Self; Roche Diagnostic USA. Research Support; Self; Janssen Pharmaceuticals, Inc.

Funding
Janssen Research & Development, LLC
1131-P: Clinical, Demographic, Provider, and Formulary Characteristics Associated with Initiation of a SGLT2i or GLP-1RA among Medicare Beneficiaries with Type 2 Diabetes on Prior Oral Agents: A Cohort Study
Authors: LUO JING , HERNANDEZ INMACULADA , GABRIEL NICO , GELLAD WALID F. 
Published: June 2020

Using 2014-2016 claims data from a random 5% sample of Medicare beneficiaries, we sought to describe characteristics associated with initiation of a SLT2i or GLP-1RA, focusing on measures of plan generosity (e.g., the number of drugs covered with no or minimal copays). Our cohort included beneficiaries with type 2 diabetes who had at least 1 prescription claim for an oral diabetes medication in the 180 days before the start of follow-up (1/1/2015). To identify new initiators of these agents, we excluded beneficiaries who filled any insulin, SGLT2i or GLP-1RA prior to the index date or who died before 12/31/16. We developed multivariable logistic regression models controlling a priori for age, race, region, prior medication use, claims-based measures of diabetes severity and clinical comorbidities, provider specialty and measures of formulary generosity. Of 103,112 eligible beneficiaries (mean age 73, 57% female), 5,076 (4.9%) initiated a SGLT2i or GLP-1RA between 1/1/15-12/31/16. After adjusting for all baseline characteristics, beneficiaries in plans covering 2 or more target drugs in preferred tiers (i.e., 1-3) were more likely (adjusted odds ratio [aOR] 1.18 [95% CI, 1.05 to 1.32]) to initiate one of these medications than patients enrolled in plans covering 0 drugs. Other characteristics associated with higher odds included: age&lt;65 (aOR 1.78 [95% CI, 1.64 to 1.92]), diabetic retinopathy (aOR 1.19 [95% CI, 1.08 to 1.31], obesity (aOR 1.49 [95% CI, 1.38 to 1.62) and having baseline medications prescribed by an endocrinologist (aOR 1.68 [95% CI, 1.49 to 1.89]. Black race (aOR 0.66 [95% CI, 0.60 to 0.73]) and CKD (aOR 0.84 [95% CI, 0.76 to 0.92]) were associated with lower risk of initiation. After controlling for a large number of prespecified covariates, Medicare beneficiaries with type 2 diabetes with more generous prescription drug coverage were more likely to initiate a SGLT2i or GLP-1RA.

Disclosure
J. Luo: Consultant; Self; Alosa Health. I. Hernandez: None. N. Gabriel: None. W.F. Gellad: None.

Funding
National Center for Advancing Translational Sciences (KL2TR001856)
1137-P: Anti–Skeletal Muscle Atrophy Effect of Luseogliflozin via Lipidome Modification in db/db Mice
Authors: BAMBA RYP 
Published: June 2020

It has been controversial that the sodium glucose cotransporter-2 inhibitor (SGLT2i) have a protective effect for muscle atrophy. We previously reported that muscle atrophy in Db/Db mice were improved by luseogliflozin via upregulation of foxo1 expression. Here we show that systemic or local lipidome were altered in Db/Db mice, which were modified by luseogliflozin. Additionally, we investigated the underling molecular mechanisms between altered lipidome and gene expressions in the atrophic soleus muscle. Eight-week-old mice were fed a standard diet or the standard diet with added luseogliflozin (0.01% w/w in chow) for 8 weeks. The mice were divided into the following three genotype/dietary groups: Db/m mice without (w/o) SGLT2i, Db/Db w/o SGLT2i, and Db/Db with SGLT2i. Concentration of stearate acids in blood in Db/Db mice with SGLT2i decreased compared to that without. The expression of scd1 or foxo1 increased in Db/Db mice w/o SGLT2i and decreased in Db/Db mice with SGLT2i. Stearate acids in blood increased in Db/Db mice, which increased stearate acids in skeletal muscle. Increased stearate acid concentration in skeletal muscle stimulates the expression of scd1, on the other hand, the administration of luseogliflozin decreased stearate acids in blood and skeletal muscle, which decreased the expression of scd1 in skeletal muscle.

Disclosure
R. Bamba: Research Support; Spouse/Partner; Taisho Pharmaceutical Co., Ltd.
1141-P: Effects of SGLT2 Inhibitors on Nighttime Sympathetic Nerve Activity, Heart Rate, Blood Pressure Variability, and Glycemic Variability in Type 2 Diabetic Patients
Authors: ONISHI TETSUROU , SHIODA YOSHINOBU , MORI YUTAKA 
Published: June 2020

Objective: SGLT2 inhibitors (SGLT2i) were examined for their effects on nighttime sympathetic nerve activity in type 2 diabetic patients.
Methods: A total of 15 type 2 diabetic outpatients with poor glycemic and body weight control despite conventional antidiabetic therapy (HbA1c, 7.7 ± 1.1%; BMI, 27.6 ± 3.8 kg/m2) were given dapagliflozin (Dapa) 5 mg/day for 3 months. Patients were compared before and 3 months after Dapa treatment for Low frequency/High frequency (LF/HF) ratios at 5-minute intervals as index of sympathetic verve activity through spectrum analysis of heart rate variability, blood pressure (BP) variability at 30-minute intervals, glucose variability at 5-minute intervals using concurrent Holter electrocardiogram, ambulatory blood pressure monitoring, and continuous glucose monitoring. Blood samples were drawn from these patients after 30 minutes of bed rest before and 3 months after Dapa treatment to measure their plasma catecholamine values. Outcome measures of the study included the area under the curve for LF/HF ratios (AUC-LF/HF ratio), mean BP values during sleep, extent of nighttime BP dip, and mean glucose/SD of glucose values during sleep.
Results: HbA1c and body weight were significantly decreased with Dapa. Again, the nighttime AUC-LF/HF ratio and plasma noradrenalin values, as well as the heart rate, systolic BP (SBP) and diastolic BP (DBP) values during the same hours, were significantly decreased, and the extent of nighttime BP dip was also significantly increased, in those achieving weight reductions with Dapa. In contrast, these findings were not observed in 3 patients failing to achieve weight reductions with Dapa.
Conclusions: Study results suggest that reductions in sympathetic nerve activity associated with the SGLT2i treatment may be closely associated with SGLT2i-mediated weight reductions.

Disclosure
T. Onishi: None. Y. Shioda: None. Y. Mori: None.
1142-P: Comparison of Hospitalization for Heart Failure (HHF) among Patients with Type 2 Diabetes Mellitus (T2DM) and Macroalbuminuria Initiated on Canagliflozin (CANA) or a DPP-4
Authors: PILON DOMINIC , DURKIN MICHAEL , MANCEUR AMEUR , GHELERTER ISABELLE , LAFEUILLE MARIE-HÉL , LEFEBVRE PATRICK 
Published: June 2020

This study compared the risk of HHF in T2DM patients with macroalbuminuria initiated on CANA or DPP-4 using real-world insurance claims data.
Adults with a T2DM diagnosis and a urine albumin-to-creatinine ratio &gt;300 mg/g or albumin excretion rate &gt;300 mg/day, initiated on CANA or DPP-4 after 03/29/2013, with at least 6 months of pre-initiation insurance eligibility were selected from Optum’s ClinformaticsTM Data Mart database (03/2012-03/2019). Patients were excluded if they notably had a diagnosis for T1DM, acute kidney injury, or stage 5 chronic kidney disease at baseline. The observation period was censored at the earliest of the index drug discontinuation, a claim for a drug from the alternate index cohort (DPP-4 or CANA), or the end of eligibility or data. Inverse probability of treatment weighting (IPTW) accounted for differences in baseline demographics, clinical characteristics, and healthcare costs. HHF events were defined as inpatient stays with a diagnosis of heart failure (ICD-9: 428.x; ICD-10: I50.x). Rates of HHF events per 100 patient-years (PY) were calculated and weighted Cox proportional hazards model accounting for repeated measurement was used to estimate the hazard ratio (HR), 95% confidence interval (CI), and p-value.
A total of 759 patients were initiated on CANA and 1,892 on a DPP-4. After IPTW balanced baseline characteristics, mean age was ∼64 years old, ∼40% were female, and mean HbA1c was ∼9.0%. Among CANA and DPP-4 patients, respectively, the mean observation period was 5.4 and 6.6 months and the rate of HHF events per 100 PY was 0.57 and 3.73. At 12 months, the hazard for HHF was 74% lower among patients initiated on CANA relative to patients initiated on DPP-4 (HR [95%CI]: 0.26 [0.07-0.91]; p=0.0343).
In this real-world analysis of patients with T2DM and macroalbuminuria during the initial months on therapy, patients on CANA had a significantly lower risk of HHF events compared to patients on DPP-4.

Disclosure
D. Pilon: Consultant; Self; Janssen Scientific Affairs, LLC. M. Durkin: Employee; Self; Janssen Scientific Affairs, LLC. A. Manceur: Employee; Self; Analysis Group, Inc. I. Ghelerter: Employee; Self; Analysis Group, Inc. M. Lafeuille: Other Relationship; Self; Janssen Scientific Affairs, LLC. P. Lefebvre: Consultant; Self; Janssen Scientific Affairs, LLC.

Funding
Janssen Scientific Affairs, LLC
1149-P: Effect of SGLT2 on Cardiovascular Events in Type 2 Diabetic Patients with Atrial Fibrillation
Authors: ZHANG YUAN , CHEN YIXIN , DENG JUNHAO , HU PENGWEI , TANG ZEFANG , MEI JING , LI SHOACHUN 
Published: June 2020

Background: Previous studies have suggested that Sodium Glucose Cotransporter-2(SGLT2) inhibitor may play cardio-protective role in type 2 diabetes mellitus (T2DM) patients. However, its effects on cardiovascular events for T2DM patients with atrial fibrillation (AF) have less been addressed. Therefore, we performed a large-scale multi-center retrospective study to explore the potential value of SGLT2 in the treatment of T2DM patients with AF.
Method: We thoroughly searched the IBM Explorys database for T2DM patients with AF from January 2010 to January 2015. The patients were included or excluded with strict criteria. Primary outcomes were cardiovascular disease (CVD) events including myocardial infarction (MI) and stroke happened in 5 years after T2DM diagnose. Cox proportional hazards models with propensity-score-matching were adopted to assess the effect of SGLT2 inhibitor use and CVD events.
Result: Among 1,573,330 T2DM patients, 44048(7.3%) patients were once treated with SGLT2 drugs. A total of 88,096 propensity score-matched T2DM patients were included in the analysis according to a thorough including criteria. After adjusting for age, gender, disease history, other antidiabetic drugs and anti-coagulate drugs, the use of SGLT2 inhibitor was associated with a 11% decreased risk of MI [Hazard Ratio(HR): 0.90 (95% confidence interval(CI):0.84, 0.94), p = 0.002] compare to non-SGLT2 user. However, no significant protective effect was found in stroke risk (HR: 0.94 (95% CI: 0.86, 1.03), p = 0.194). Besides, insulin was associated with increased risk of developing MI (HR: 1.09 (95% CI: 1.01, 1.18)).
Conclusion: In conclusion, our study suggests that SGLT2 inhibitor has positive effects on the control of MI for T2DM patients with AF. However, no significant effect was found for stroke risk in this multi-center cohort. More high-quality randomized controlled trials are required to confirm cardio-protective roles of SGLT2 for T2DM patients with AF in the future.

Disclosure
Y. Zhang: None. Y. Chen: None. J. Deng: None. P. Hu: None. Z. Tang: None. J. Mei: None. S. Li: None.