bluuebunny/crossref_metadata_2025 huggingface dataset:
381-P: Real-Time Ward-Level Monitoring of Nurse Performance Level Is able to Demonstrate Improved Management of Inpatient Hypoglycemia following an Education Intervention
Authors: SAINSBURY CHRISTOPHER , SKIVINGTON CHRISTINE , ROBERTSON MARIE , JONES GREGORY C. , CLELAND STEPHEN J.
Published: June 2020

Aims: The aims of this study were (a) to demonstrate that analyses of glucometer data/metadata can reveal real-time ward-level patient-centred outcomes relevant to hypoglycemia (b) to test whether a 6-month education and mentoring intervention improved relevant performance levels.

Methods: Ward glucometer data were analysed for periods of 9 months before and after the intervention in 9 wards (256 beds) in a large Scottish teaching hospital. Results were compared with 9 control wards, matched for size, specialty and acuity. Hypoglycemia was defined as <4mmol/l (72mg/dl). Process control charts were constructed for each clinical unit. At each hypoglycemic event, +1 (success) or -1 (fail) was generated for TTR (time to repeat CBG) and TTHR (time to hypo resolution). The gradient of the plot represents performance level, allowing comparison pre- and post-intervention for both ward groups.

Results: Total hypo events = 5187. Significant improvements in performance level were demonstrated in the intervention wards but not the control wards in TTR at 10, 15, 20 and 30 mins and TTHR at 10, 15 and 20 mins (Table).

Conclusions: This study demonstrates the utility of the process control charts in CBG-related patient outcomes, and quantifies the significant improvement in hypoglycemic management derived from an education intervention.

Disclosure

C. Sainsbury: Consultant; Self; MyWay Digital Health. Research Support; Self; Sanofi. Speaker’s Bureau; Self; AstraZeneca. C. Skivington: None. M. Robertson: None. G.C. Jones: None. S.J. Cleland: None.

Funding

Sanofi
387-P: Glycemic Outcomes in Baseline Hemoglobin A1c Subgroups in the International Diabetes Closed-Loop (IDCL) Trial
Authors: EKHLASPOUR LAYA , RAGHINARU DAN , LUM JOHN , BROWN SUE A. , BUCKINGHAM BRUCE A.
Published: June 2020

Using a closed loop system significantly improves time in range (TIR) in patients with type 1 diabetes (T1D). In a 6-month RCT, 112 subjects were assigned to closed-loop control (Tandem Control-IQ) after obtaining two weeks of baseline CGM data from sensor-augmented pump therapy. We compared glycemic outcomes from baseline to end of study among subgroups classified by baseline HbA1C level. Participants’ mean age was 33±16 (range 14-71 yrs) and mean baseline HbA1C was 7.4±1.0 (range 5.4% to 10.6%). All HbA1c subgroups showed an improvement in TIR due to reduction of both hyperglycemia and hypoglycemia (Table). Those with HbA1c <6.5% improved mostly by reducing nocturnal (MN to 6 AM) hypoglycemia. Those with HbA1c ≥8.5% improved mostly by reducing daytime and nocturnal hyperglycemia. Participants with lower HbA1c at baseline reduced their overnight hypoglycemia the most, likely due to the system’s automated basal insulin adjustment. For those with higher HbA1c at baseline, increased TIR came mostly from hyperglycemia reduction, likely due to automated basal insulin adjustment in day and night. These participants likely also benefitted from hourly automatic correction boluses during the day. All HbA1c subgroups benefitted from automated insulin delivery.

Disclosure

L. Ekhlaspour: None. D. Raghinaru: None. J. Lum: None. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (UC4108483); University of Virginia; Tandem Diabetes Care
39-LB: Progress in Diabetic Foot Ulcer Healing with Standard of Care Therapy Alone: A Meta-analysis
Authors: PARKS VIRGINIA E. , CRISOLOGO PETER , LAVERY LAWRENCE A. , BANKS JAMINELLI , LIETTE MICHAEL D. , JOHNSON LANCE
Published: June 2020

Background: The purpose of this study was to evaluate whether or not standard of care treatment of diabetic foot ulcers has improved over the past 20 years as measured by the percentage of ulcers healed within set periods of time. Previously reported percentages of wound healing were 24% at 12 weeks and 31% at 20 weeks.

Methods: A meta-analysis was performed to review the control groups of randomized clinical trials in the treatment of diabetic foot ulcers. The mean percentage of ulcers healed at defined end points were then compared to percentages of ulcers healed at corresponding end points reported 20 years ago. A literature search was performed to identify articles published before December 30, 2019, to identify randomized controlled clinical trials that included human subjects with diabetic foot ulcers. The control arm was required to include wound debridement, dressing changes, and offloading.

Results: The literature search yielded 16 randomized clinical trials that fit the selection criteria to be included in the meta-analysis. Analysis of the percentage of wounds healed with standard of care therapy alone yielded the following results: 6 weeks (14.9% ± 13.0%), 12 weeks (33.4% ± 18.2%), 20 weeks (43% ± 0%).

Conclusions: The results of this meta-analysis of the available evidence suggest that the percentage of diabetic foot ulcers healed with standard of care therapies alone have improved over the past 20 years. However, the percentage of ulcers healed at each of these endpoints remains low and demonstrates continued challenges in healing diabetic foot ulcers.

Disclosure

V.E. Parks: None. P. Crisologo: None. L.A. Lavery: Advisory Panel; Self; Acelity, Bayer AG. Consultant; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Smith & Nephew. J. Banks: None. M.D. Liette: None. L. Johnson: None.
39-OR: Secular Trends in Glucose-Lowering Drug Utilization, Glycemic Control, and Severe Hypoglycemia in Adults with Diabetes between 2002 and 2016 in Hong Kong
Authors: YANG AIMIN , WU HONGJIANG , LAU ERIC S. , MA RONALD C. , KONG ALICE P. , SO WING YEE , LUK ANDREA , CHAN JULIANA C. , CHOW ELAINE
Published: June 2020

Introduction: There has been a shift towards new classes of glucose lowering drugs (GLDs) in the past decade but no improvements in glycemic control or hospitalization rates due to severe hypoglycemia (SH) in previous surveys. We examined secular trends in GLDs utilization, glycemic control and rate of SH among people with diabetes, mainly type 2 diabetes, in Hong Kong which introduced a territory-wide, team-based diabetes care model since 2000.

Methods: Using population-based data from the Hong Kong Diabetes Surveillance Database consisting mainly of Chinese living a westernized lifestyle, we estimated the annual age- and sex-standardized proportion of GLDs classes, mean hemoglobin A1c (HbA1c) levels and SH rates in 763,809 diabetes patients aged ≥20 years between 2002-2016. We used Joinpoint regression to examine secular trends over time.

Results: In 2002-2016, use declined for sulfonylureas (50.7% to 28.9%) but increased for metformin (47.8% to 57.3%) and dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.01% in 2007 to 7.0%). The proportion of patients with HbA1c of 6.0-7.0% increased from 25.6% to 37.2% while the rate of SH declined from 4.4 to 1.7 per 100 person-years. The main improvement in annual mean HbA1c occurred between 2007 and 2014, decreasing from mean (SD) 7.8 (1.6)% to 7.4 (1.7)% (p<0·001). The 20-44 age group had the highest proportion of HbA1c>9% with rising proportions not treated with any GLDs (from 4.3% to 10.5%).

Conclusion: Prescription of GLDs has changed dramatically in Hong Kong in the past 15 years in line with treatment guidelines and introduction of new drugs. The modest but important improvement in HbA1c since 2007 coincided with widening reform of diabetes services in primary care and introduction of DPP-4i. Poor glycemic control and low utilization of GLDs in the youngest age group calls for targeted treatment strategies and ongoing surveillance.

Disclosure

A. Yang: None. H. Wu: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. W. So: None. A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp & Dohme Corp. J.C. Chan: None. E. Chow: None.

Funding

Chinese University of Hong Kong
390-P: Household Food Security and Fear of Hypoglycemia in Youth and Young Adults with Diabetes and Parents of Youth with Diabetes
Authors: REID LAUREN A. , ZHENG SIYU , MENDOZA JASON A. , REBOUSSIN BETH A. , SAUDER KATHERINE A. , SAYDAH SHARON , LAWRENCE JEAN M. , JENSEN ELIZABETH T. , HENKIN LEORA , FLORY KATE , KNIGHT LISA M. , PIHOKER CATHERINE , DOLAN LAWRENCE M. , LIESE ANGELA D.
Published: June 2020

Hypoglycemia is a common acute complication in diabetes that is often treated with carbohydrate-rich snacks or drinks. For individuals with diabetes and household food insecurity (HFI), uncertain availability of food may increase fear of hypoglycemia (FOH). FOH may prevent individuals from optimal diabetes management.

We analyzed data from 1,603 adult (≥18 years, mean 23.7 years, 80% type 1 diabetes [T1D], 20% type 2 diabetes [T2D]) and 592 youth (10.0-17.9 years, mean 15.2 years, 100% T1D) participants in the SEARCH for Diabetes in Youth Study. Adult participants and parents of youth participants completed the U.S. Household Food Security Survey, where ≥3 food insecure conditions or behaviors indicate HFI. Adults, youth, and parents of youth completed the Hypoglycemia Fear Survey that provides a behavior subscale (scores 0-60), worry subscale (scores 0-72), and total score (sum of subscales). We examined the association of HFI with FOH with general linear models, adjusting for socioeconomic, demographic, and clinical covariates.

Approximately 20% of adults and 17% of youth had HFI. Adults with T1D reporting HFI (vs. no HFI) had increased FOH (+3 units for behavior, +11 units for worry, +14 units for total), after adjustment for covariates (all p<0.0001). Parents of youth with T1D reporting HFI had a 3 unit increase in worry FOH (p=0.03). Adults with T2D reporting HFI had increased FOH (+8.9 units for total, +6 units for worry; all p<0.01). Youth with T1D reporting HFI did not differ in FOH than those not reporting HFI.

This research suggests that among adults with diabetes and parents of youth with T1D, those with HFI are more likely to experience FOH than those without HFI. Implementation of common approaches to ameliorate risk of hypoglycemia such as carrying snacks is problematic for people who are food insecure. Providers could consider HFI when discussing hypoglycemia and fear thereof with their patients.

Disclosure

L.A. Reid: None. S. Zheng: None. J.A. Mendoza: None. B.A. Reboussin: None. K.A. Sauder: None. S. Saydah: None. J.M. Lawrence: None. E.T. Jensen: None. L. Henkin: None. K. Flory: None. L.M. Knight: None. C. Pihoker: None. L.M. Dolan: None. A.D. Liese: None.

Funding

National Institutes of Health (1UC4DK108173, 1R01DK117461-01)
391-P: Predictive Low Glucose Suspend (PLGS) Necessitates Less Carbohydrate (CHO) Supplementation to Rescue Hypoglycemia: Need to Revisit Current Hypoglycemia Treatment Guidelines
Authors: PINSKER JORDAN E. , BARTEE AMY , KATZ MICHELLE , LALONDE AMY , JONES RICHARD , DASSAU EYAL , WOLPERT HOWARD
Published: June 2020

PLGS systems have been demonstrated to limit hypoglycemia. Reduced insulin during suspensions may avoid the need for rescue CHO or lessen the amount of CHO needed. The approximately 20-hour inpatient evaluation of the Lilly investigational AID system’s PLGS feature, including a basal up-titration period to activate the PLGS and investigator-directed administration of rescue CHO, allowed assessment of hypoglycemia prevention and treatment requirements. Ten subjects with type 1 diabetes (40% male, mean age 39.0±13.0 years, A1C 7.2±0.6%, and insulin usage 0.6±0.2 U/kg/day) were studied. There were 59 suspensions, with all subjects experiencing suspensions during which CHO were not administered. Only six suspensions were associated with rescue CHO and five suspensions were associated with hypoglycemia (CGM glucose <70 mg/dL for ≥15 minutes), see Table. No rescue CHO were given during or after insulin suspension for the overnight basal up-titration. Rescue CHO consisted of median 9g CHO (range: 5-16g). No episode required repeat CHO administration. New hypoglycemia treatment guidelines for PLGS users should reflect that PLGS reduces CHO requirements for hypoglycemia rescue. This guidance will be important to minimize rebound hyperglycemia and needless calorie intake from hypoglycemia over-treatment.

Disclosure

J.E. Pinsker: Advisory Panel; Self; Medtronic. Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Tandem Diabetes Care. Speaker’s Bureau; Self; Tandem Diabetes Care. A. Bartee: None. M. Katz: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. A. LaLonde: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Jones: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. E. Dassau: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., DreaMed Diabetes, Tandem Diabetes Care, Xeris Pharmaceuticals, Inc. Speaker’s Bureau; Self; Roche Diabetes Care. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. H. Wolpert: Employee; Self; Eli Lilly and Company.
393-P: Technology Use and Hypoglycemia in Type 1 Diabetes: Insights from the BETTER Registry
Authors: TALEB NADINE , DESJARDINS KATHERINE , HAAG SARAH , PREVOST MELINDA , RABASA-LHORET RÉMI , BRAZEAU ANNE-SOPHIE
Published: June 2020

The BETTER registry launched in April 2019 aims to understand the burden (frequency, severity) of hypoglycemia from people with T1D’s perspective and to evaluate the role of technologies in its prevention and management.

Methods: BETTER registry includes several online surveys and is being conducted in Quebec, Canada. Preliminary results of the 2ndsurvey about technology use, CSII and FGM/CGM, in relation to hypoglycemia are reported.

Results: By Dec 2019, 457 persons with T1D (> 14 y.o.) have completed the 2ndsurvey (44.0±15.7 y.o., 67.2 % females, 48.0% CSII users, 80% FGM/CGM users in past 12 months). Main reasons for opting for technology: A) CSII (n=219): glucose control with exercise (72.6%), elevated HbA1c (42.9%), nocturnal hypoglycemia (35.2%) as well as overall hypoglycemia severity and frequency (26.0%). Interestingly, 65.3% reported less hypoglycemia after adopting CSII. B) FGM/CGM (n=365): easier to follow glucose levels (77.5%), stop/reduce capillary measurements (69%), easier glucose control with exercise (68.5%). Table1 shows comparisons between technology users vs. non users: CSII and FGM/CGM users reported better glucose control, more hypoglycemia episodes (probably due to better diagnosis) that are corrected at higher BG levels.

Conclusion: This database will improve the understanding of technologies roles in hypoglycemia detection, prevention and treatment to optimize their use.

Disclosure

N. Taleb: None. K. Desjardins: None. S. Haag: None. M. Prevost: 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)
394-P: Inpatient Hypoglycemia: Opportunity to Prevent
Authors: MEHROTRA NEHA , ATALAY HANDE , KORYTKOWSKI MARY T. , MON SANN YU
Published: June 2020

Introduction: Inpatient hypoglycemia is commonly associated with high mortality and morbidity. Several factors contribute to hypoglycemia in patients with diabetes, and not all causes are inevitable. However, it is important to recognize the causes of hypoglycemia to prevent further episodes. We investigate the potential causes of hypoglycemic episodes in our community hospital as part of a quality improvement project. Our aim is to reduce risks of hypoglycemia by identifying potential preventable etiologies and educate providers and the nursing team.

Methods: A retrospective chart review of patients was performed for all non-critically ill diabetic patients who experienced point of care blood glucose<70mg/dl testing between March to June 2019 (n=63). Potential causes of each hypoglycemia episode were reviewed retrospectively by a single endocrinologist.

Results: The mean age was 62.3 years+/-17.1, 63.5% males, BMI (mean 33.31+/-20.8kg/m2), 79.4% type 2 diabetes with mean A1C 8.2+/-1.6%. Median length of hospital stay was 6 days. 16(25.4%) patients had >2 episodes of hypoglycemia and 15 patients (23.9%) had severe hypoglycemia (defined as blood glucose < or = to 45 mg/dl). 8 patients (12%) were readmitted within 7 days and 20 patients (31%) had readmission within 30 days.

The most common cause of hypoglycemia was due to basal insulin excess (n=17 patients, 27%), overuse of sliding scale (n=16 patients, 25.4%), reduce food intake (n=11 patients , 25.4%), inpatient use of premixed insulin (n=6 patients, 9.5%) and use of sulfonylurea (n=2 patients, 3.2%). Two other hypoglycemic events appeared to occur when steroids dose was tapered without insulin dose adjustments.

Conclusion: The results demonstrate that several major causes of hypoglycemia are preventable and reinforce the need for determination of the cause of these events as a way of modifying therapy to prevent further episodes.

Disclosure

N. Mehrotra: None. H. Atalay: None. M.T. Korytkowski: None. S. Mon: None.
407-P: Cardiac and Retinal Imaging Studies Suggest Comparable Protective Factors between Cardiovascular Disease and Retinopathy in Long Duration Type 1 Diabetes
Authors: YU MARC GREGORY , SHAH HETAL , WOLFSON EMILY , BAHNAM VANESSA , GAUTHIER JOHN , CAI QIZHE , JHA VIBHAV , TSAO CONNIE , KING GEORGE L.
Published: June 2020

In the Joslin Medalist Study (“Medalists”), which enrolled people with ≥50 years of type 1 diabetes (T1D), factors have been shown to individually protect against vascular complications, such as proliferative retinopathy (PDR), and possibly, cardiovascular disease (CVD). However, shared protective factors against these disease outcomes have not been demonstrated. Recently, Medalists underwent cardiac computed tomography (CT; n=67) and cardiac magnetic resonance imaging (CMR; n=54) for assessment of coronary artery calcification (CAC) and myocardial and aortic structure and function, respectively; as well as optical coherence tomography angiography for assessment of superficial (SCP) and deep (DCP) retinal capillary plexus density (n=28 eyes). In this cohort, CAC severity was associated with self-reported CVD history (p=0.04). CAC>200 was associated with PDR (p=0.03) and with lower density of both SCP (p=0.002) and DCP (p=0.047). Among the CMR parameters, lower ascending aortic distensibility, indicating higher stiffness, was found among participants with PDR (p=0.009), and was also associated with lower SCP density (p=0.037). Meanwhile, measures of myocardial strain (longitudinal, circumferential, and radial) were significantly lower in women and in those with CAC>200 (all p<0.05); likewise, Medalists with CAC>200 were also less likely to be female (p=0.02). The common association of CAC and aortic stiffness with PDR and SCP density suggests that protective markers of progression to angiogenesis (PDR) may have similarities with those protecting against coronary calcification and aortic dysfunction. Furthermore, the results highlight the important relationship between CAC, gender, and myocardial biomechanics in Medalists. Future proteomic and metabolomic studies using circulatory and retinal biosamples could be helpful in identifying common factors that can delay the onset of CVD and PDR.

Disclosure

M. Yu: None. H. Shah: None. E. Wolfson: None. V. Bahnam: None. J. Gauthier: None. Q. Cai: None. V. Jha: None. C. Tsao: None. G.L. King: Research Support; Self; Janssen Pharmaceuticals, Inc.

Funding

American Diabetes Association (9-18-CVD1-005 to M.G.Y.); Thomas J. Beatson, Jr. Foundation (2185, 20008, 2800200)
415-P: Remnant Cholesterol in Patients with Established Coronary Artery Disease Predicts Cardiovascular Events Both among Patients with Type 2 Diabetes and among Nondiabetic Subjects
Authors: SAELY CHRISTOPH H. , MAECHLER MAXIMILIAN , MADER ARTHUR , LARCHER BARBARA , SPRENGER LUKAS , KLEMENT MARGARETHA , PURIN DANIELA , LEIHERER ANDREAS , MUENDLEIN AXEL , VONBANK ALEXANDER , DREXEL HEINZ
Published: June 2020

Remnant cholesterol, which is calculated as total cholesterol minus LDL cholesterol minus HDL cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict cardiovascular events in patients with established coronary artery disease (CAD) is unclear and is addressed in the present study. We enrolled 1350 consecutive patients with angiographically proven stable CAD. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.4±4.8 years. At baseline, remnant cholesterol was significantly higher in patients with T2DM (n=428) than in nondiabetic subjects (29±24 vs. 24±22 mg/dl; p<;0.001). During follow-up, 651 of our patients suffered cardiovascular events; the event rate was significantly higher in patients with T2DM than in nondiabetic subjects (56.9 vs. 44.9%; p<;0.001). Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index and LDL cholesterol independently predicted cardiovascular events in the total study population (standardized adjusted HR 1.15 [1.07-1.23]; p<;0.001), and in patients with T2DM as well as in nondiabetic subjects (standardized adjusted HRs 1.19 [1.05-1.35]; p=0.006 and 1.12 [1.02-1.23]; p=0.010, respectively). From our data we conclude that remnant cholesterol in patients with established CAD predicts cardiovascular events both among patients with T2DM and among nondiabetic subjects.

Disclosure

C.H. Saely: None. M. Maechler: None. A. Mader: None. B. Larcher: None. L. Sprenger: None. M. Klement: None. D. Purin: None. A. Leiherer: None. A. Muendlein: None. A. Vonbank: None. H. Drexel: None.
419-P: Type 2 Diabetes, Congestive Heart Failure, and Nonalcoholic Fatty Liver Disease
Authors: MAECHLER MAXIMILIAN , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , SPRENGER LUKAS , LEIHERER ANDREAS , PURIN DANIELA , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2020

Nonalcoholic fatty liver disease (NAFLD) is associated with both type 2 diabetes (T2DM) and congestive heart failure (CHF). T2DM is highly prevalent in CHF patients; however, the single and joint associations of T2DM and CHF with NAFLD have not been investigated yet. This issue therefore is addressed in the present study. We investigated 202 patients with CHF and 670 controls who did not have signs or symptoms of CHF and in whom significant coronary artery disease was ruled out angiographically. The presence of NAFLD was determined using the validated fatty liver index (FLI). The prevalence of T2DM was 47.0% in CHF patients and 22.1% in controls (p<0.001). FLI and prevalence of NAFLD (FLI≥60) in non-CHF subjects without T2DM were 49±28 and 38.6%, respectively. They were significantly higher in non-CHF T2DM patients (70±25, p<0.001 and 68.5%, p<0.001, respectively), in CHF patients without T2DM (63±23, p<0.001 and 58.6%, p<0.001, respectively) and in CHF patients with T2DM (73±24, p<0.001 and 78.0%, p<0.001, respectively). In multivariate analysis of covariance, T2DM and CHF proved to be mutually independent predictors of FLI after adjustment for age, sex, BMI, LDL-C, history of smoking and hypertension (F=21.47; p<0.001 and F=53.92; 0<0.001, respectively); concordantly, T2DM and CHF independently predicted the presence of NAFLD in logistic regression analyses, with adjusted odds ratios of 2.49 [1.55-3.99]; p<0.001 and 6.97 [3.95-12.29]; p<0.001, respectively.

We conclude that T2DM and CHF are mutually independent predictors of NAFLD.

Disclosure

M. Maechler: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. L. Sprenger: None. A. Leiherer: None. D. Purin: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
427-P: Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Are Mutually Independent Predictors of Cardiovascular Events in Patients with Established Cardiovascular Disease
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , MAECHLER MAXIMILIAN , LARCHER BARBARA , SPRENGER LUKAS , MADER ARTHUR , PURIN DANIELA , KLEMENT MARGARETHA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ
Published: June 2020

Nonalcoholic Fatty Liver Disease (NAFLD) is associated with insulin resistance, type 2 diabetes (T2DM) and cardiovascular disease. However, data on NAFLD in patients with established cardiovascular disease (CVD) are scarce. We therefore aimed at investigating its association with T2DM as well as its impact on cardiovascular event risk in a large series of 1518 patients with established CVD (1274 patients with angiographically proven coronary artery disease and 244 patients with sonographically proven peripheral artery disease), using the validated fatty liver index for the diagnosis of NAFLD. At baseline, the prevalence of NAFLD was significantly higher in patients with T2DM than in nondiabetic subjects (61.3 vs. 39.8%; p<0.001) respectively. Prospectively, we recorded 738 cardiovascular events over a mean follow-up period of 9.7±4.6 years. Cardiovascular event risk was significantly higher in NAFLD patients than in those who did not have NAFLD (52.0 vs. 46.4%; p=0.040) and in patients with T2DM than in nondiabetic subjects (58.2 vs. 44.8%; p<0.001). Cox regression models adjusting for conventional cardiovascular risk factors proved NAFLD and T2DM to be mutually independent predictors of cardiovascular events, with adjusted hazard ratios of 1.44 [1.19-1.74]; p<0.001 and 1.45 [1.24-1.9]; p<0.001, respectively. We conclude that NAFLD and T2DM are mutually independent predictors of cardiovascular events in patients with established CVD.

Disclosure

C.H. Saely: None. A. Vonbank: None. M. Maechler: None. B. Larcher: None. L. Sprenger: None. A. Mader: None. D. Purin: None. M. Klement: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
433-P: Type 2 Diabetes and Risk of Cardiovascular Events in Peripheral Artery Disease vs. Coronary Artery Disease Patients
Authors: SPRENGER LUKAS , VONBANK ALEXANDER , LARCHER BARBARA , MADER ARTHUR , MAECHLER MAXIMILIAN , KLEMENT MARGARETHA , PURIN DANIELA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: June 2020

The prevalence of type 2 diabetes (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. How cardiovascular risk compares between PAD and CAD patients when analyses are stratified by the presence of T2DM is unclear and is addressed in the present study. We prospectively recorded cardiovascular events over 7.6±5.0 years in 253 patients with PAD, of whom 41.9% had T2DM and in 923 patients with stable CAD, of whom 26.7% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=147) and PAD patients with T2DM (PAD/T2DM+; n=106). The cardiovascular event rate was lowest in CAD/T2DM- patients (40.5%). It was significantly higher in CAD/T2DM+ patients (50.2%; p=0.007), in PAD/T2DM- patients (55.2%; p<0.001), and in PAD/T2DM+ patients (67.6%; p<0,001), who in turn were at a higher risk than CAD/T2DM+ or PAD/T2DM- patients (p<0.001 and p=0.013, respectively). Further, cardiovascular risk was significantly higher in PAD/T2DM- than in CAD/T2DM+ patients (p<0.001). Cox regression analysis after multivariate adjustment confirmed that PAD versus CAD (HR=2.58 [2.12-3.15]; p<0.001) more strongly than the presence of T2DM (HR=1.55 [1.30- 1.85]; p<0.001) predicted cardiovascular events. We conclude that even when compared to CAD PAD confers a higher risk than T2DM. PAD patients without diabetes are at a higher risk than the extremely high risk patients with the combination of CAD and T2DM; risk is exceedingly high in PAD patients with T2DM.

Disclosure

L. Sprenger: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. M. Maechler: None. M. Klement: None. D. Purin: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
435-P: Novel Approach to the Detection and the Treatment of Vulnerable Coronary Plaques Using Color Mapped Coronary CT Angiography and Optimal Medical Therapy Including Anti-PCSK9 Antibody
Authors: HIRAI AIZAN , KONDO SEIYA , GOTO TOSHIO , HIRAI KEIJI , KAMIYA NORIFUMI , TANABE YUKI , KOMESU ISAO , MOROMIZATO HIDEKAZU , NAKAZATO JUN , IKEJIMA SHIN , SUNAGAWA HIROSHI , KIDO TERUHITO
Published: June 2020

Background: Coronary CT angiography (CCTA) has been applied to detect vulnerable plaques having low attenuation of CT value and positive remodeling which have been associated with acute coronary syndrome. The present study was performed to establish a novel approach to qualitative and quantitative analysis of coronary plaque, especially early detection of high-risk plaque by visualizing intra-plaque localization of necrotic core and the evaluation of plaque stabilizing effect of optimal medical therapy (OMT) including anti-PCSK9 antibody.

Methods: We developed color mapped CCTA. The vulnerable plaques are identified by red color (CT attenuation: 0-30) and yellow color (CT attenuation: 30-60). The effect of OMT including anti-PCSK9 antibody on the vulnerable plaques in diabetic patients was studied.

Results: Color mapped CCTA clearly demonstrated the presence of necrotic core (red in yellow sign) in vulnerable plaque. After 12 months administration of anti-PCSK9 antibody, an improvement of vulnerable plaque e.g., disappearance of necrotic core in vulnerable plaque was observed.

Conclusion: Color mapped CCTA provides a new insight into early detection of high-risk plaque by visualizing intra-plaque localization of necrotic core, also contributes to the evaluation of drugs which may improve vulnerable plaques.

Disclosure

A. Hirai: None. S. Kondo: None. T. Goto: None. K. Hirai: None. N. Kamiya: None. Y. Tanabe: None. I. Komesu: None. H. Moromizato: None. J. Nakazato: None. S. Ikejima: None. H. Sunagawa: None. T. Kido: None.
438-P: Prediction of Heart Failures for Diabetics Only Using Major Longitudinal Lab Test Results
Authors: KOSEKI AKIRA , OHKO TAKUYA , KUDO MICHIHARU , MAKINO MASAKI , SUZUKI ATSUSHI
Published: June 2020

Background: In the presence of a large data set of electronic health records (EHRs), predicting the future diabetic complications is of importance for decision making in the medical treatments. Using modern machine learning techniques, it is generally becoming easier to build complex models to predict the future. While complex models are giving good prediction performance, simple models should be more useful in terms of interpretability and practicality in the real medical fields. For example the less the explanatory variables such as lab tests are used for the model, the more useful it is. Our interests thus lie in whether accurate prediction is possible when using less and major explanatory variables to make a model to predict the future diabetic complications.

Method: In this paper, we make a prediction model of heart failures for diabetics in half, 1, 3, 5 years using 13 longitudinal lab tests records including hemoglobin A1c, fasting blood glucose, low-density cholesterol, high-density cholesterol, triglycerides, uric acid, serum creatinine, estimated glomerular filtration rate, proteinuria, albuminuria, gamma-glutamyl transpeptidase, alanine transaminase, aspartate transaminase, from which we extracted several longitudinal statistics for input variables. We also compared the prediction performance using several major machine learning algorithms.

Results: In prediction of future heart failures in half, 1, 3, 5 years, AUC of 0.77, 0.79, 0.79, and 0.80 were marked when using Logistic Regression. Comparing algorithms for half year prediction, ensemble algorithms outperformed Logistic Regression. The AdaBoost algorithm marked AUC of 0.82.

Conclusion: We observed that when using only 13 longitudinal lab tests records, future heart failure prediction is successfully made by using modern machine learning algorithms.

Disclosure

A. Koseki: Employee; Self; IBM. T. Ohko: Employee; Self; IBM. M. Kudo: Employee; Self; IBM. M. Makino: None. A. Suzuki: Research Support; Self; Chugai Pharmaceutical Co., Ltd., Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
44-OR: PAR2-Regulated MIF Secretion from Non-Immune Cells in Adipose Tissue Is a Key Mechanism Involved in the Development of Metabolic Dysfunction
Authors: HUANG YIHENG , CHEN LIUJUN , QI YADAN , QI DAKE
Published: June 2020

Macrophage migration inhibitory factor (MIF) is a cytokine that is increased in obesity and contributes to metabolic dysfunction. Our present study describes a novel mechanism by which fatty acids activate non-immune cells to increase MIF secretion in adipose tissue, initiating cross-talk between preadipocytes and adipocytes. High fatty acids specifically induce protease-activated receptor 2 (PAR2) activation in preadipocytes, which downregulates pref-1 expression and release. Preadipocyte factor 1 (Pref-1) has an autocrine-paracrine action to inhibit the release of MIF from both preadipocytes and adipocytes. Thus, the loss of Pref-1 secretion during high fat feeding is responsible in part for both increased MIF secretion in adipose tissue and the rise in plasma MIF levels that ensues. The physiological consequences are most evident in adipose tissue. Genetic deletion of Par2 confirms the importance of this mechanism in mice, protecting against high fat diet-induced metabolic dysfunction. Importantly, this novel mechanism is also operative in adipose tissue from obese human subjects. These results provide the scientific rationale to consider whether strategies to either block Par2 expression or augment Pref-1 secretion might improve metabolic health in obesity or type 2 diabetes.

Disclosure

Y. Huang: None. L. Chen: None. Y. Qi: None. D. Qi: None.
448-P: Secondary Analyses to Assess the Profound Effect of Empagliflozin on Endothelial Function in Patients with Type 2 Diabetes and Established Cardiovascular Diseases: The Placebo-Controlled Double-Blind Randomized EMBLEM Trial
Authors: TANAKA ATSUSHI , NODE KOICHI , INVESTIGATORS EMBLEM TRIAL
Published: June 2020

Background: Recent clinical trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors reported improved cardiovascular outcomes in patients with type 2 diabetes (T2D) with a high risk of cardiovascular events. However, the mechanisms of these clinical effects on endothelial function are not fully understood.

Methods: The EMBLEM trial in patients with T2DM and cardiovascular disease (CVD) demonstrated no effects of 24 weeks of empagliflozin treatment on endothelial function assessed by reactive hyperemia peripheral arterial tonometry. This secondary analysis of the EMBLEM trial included a detailed evaluation of the effect of empagliflozin treatment on endothelial function, its association with clinical variables, and the clinical characteristics of responders or non-responder to treatment.

Results: Among 47 patients randomized into the empagliflozin group, 21 (44.7%) patients showed increases in reactive hyperemia index (RHI) after 24 weeks of intervention, and no significant difference in clinical characteristics between patients whose RHI increased (at least >0) or did not increase. There was also no significant difference between the treatment groups in the proportion of patients who had a clinically meaningful change (≥15%) in log-transformed RHI. No correlation was observed between changes in RHI and clinical variables, such as vital signs and laboratory parameters.

Conclusions: 24 weeks of empagliflozin treatment in patients with T2DM and established CVD did not affect peripheral endothelial function, and that was not associated with changes in clinical variables, including glycemic parameters. These findings emphasize that the improved cardiovascular outcomes observed in the recent trials on SGLT2 inhibitors are attributable, at least in the early phase, to mechanisms other than direct amelioration of endothelial function.

Disclosure

A. Tanaka: Consultant; Self; Kowa Company, Ltd. Research Support; Self; GlaxoSmithKline plc. Speaker’s Bureau; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. K. Node: None.

Funding

Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance
453-P: Cell-Specific Role of Insulin in an In Vivo Model of Restenosis
Authors: GONZALEZ MAREL , MORI YUSAKU , GUO JUNE , DINGWELL LUKE S. , GIACCA ADRIA
Published: June 2020

The effects of insulin on the vasculature remains a hotly debated and controversial topic. Its role on endothelial cells (ECs) is thought to be vasculoprotective, whereas its effects on vascular smooth muscle cells (SMCs) are mainly mitogenic according to in vitro data. We have previously demonstrated a suppressive effect of insulin treatment on neointimal growth in rodent models of restenosis under conditions of normal insulin sensitivity that was abolished in insulin resistant conditions. The objective of this study was to determine the endothelial-and SMC-specific effects of insulin treatment on neointimal growth in a murine model of restenosis. Mice were generated by crossing loxP-flanked insulin receptor (IR) mice with mice overexpressing tamoxifen-inducible Cre recombinase under the control of Tie2 (endothelial-specific receptor tyrosine kinase) or SMMHC (smooth muscle myosin heavy chain) promoters. Mice were fed with standard chow and implanted with insulin pellet (0.1 U/day) or sham (control) three days prior to undergoing femoral artery wire injury. Lastly, femoral arteries were collected for morphological analysis 28 days after wire injury. Tamoxifen-induced Tie2-Cre+ mice showed decreased IR expression in ECs compared with Tie2-Cre-, with no change in IR expression in SMCs. Neointimal area in Tie2-Cre- mice was reduced following insulin treatment, whereas it was unaffected in Tie2-Cre+ mice. Similarly, tamoxifen-induced SMMHC-Cre+ mice showed a reduction in IR expression in SMCs, but not in the ECs, compared to SMMHC-Cre- mice. In SMMHC-Cre- mice, neointimal area was decreased with insulin treatment; however, insulin surprisingly failed to have the same effects in SMMHC-Cre+ mice. These data demonstrate that insulin action in both ECs and SMCs is required for the antirestenotic effect of insulin in insulin sensitive conditions.

Disclosure

M. Gonzalez: None. Y. Mori: Research Support; Self; Taisho Pharmaceutical Co., Ltd. J. Guo: None. L.S. Dingwell: None. A. Giacca: None.
46-LB: Exercise Improves Endothelial Function Associated with Alleviated Inflammation and Oxidative Stress of Perivascular Adipose Tissue in Type 2 Diabetic Mice
Authors: WANG JINJU , POLAKI VENKATA , CHEN SHUZHEN , BIHL JI
Published: June 2020

Perivascular adipose tissue (PVAT), a type of adipose tissue which surrounds blood vessels, has been considered as an active component of blood vessel walls and involved in vascular homeostasis. Recent evidence shows that increased inflammation and oxidative stress in PVAT contribute to endothelial dysfunction in type 2 diabetes (T2D). Exercise is an important non-pharmacological approach for vascular diseases. However, there is limited information regarding whether the beneficial effects of exercise on vascular function is related to PVAT status. In this study, we investigated whether exercise can decrease oxidative stress and inflammation of PVAT and promote the improvement of endothelial function in a T2D mouse model. Diabetic db/db (5-wk old) mice performed treadmill exercise (10 m/min) or keep sedentary for 8 wks. Body weight, fasting blood glucose levels, glucose and insulin tolerance were determined. The cytokines (IL-6, IL-10, IFN-r, TNF-a) and adiponectin levels, macrophage polarization in PVAT, and oxidative stress and nitric oxide expression in vascular wall were evaluated. The leukocyte adhesion ability of aorta endothelial cells isolated from the db/db mice was analyzed. Our data showed that: 1) Exercise decreased body weight and the fasting blood glucose level as well as improved glucose tolerance and insulin sensitivity in T2D mice. 2) Exercise increased adiponectin and IL-10 levels, decreased IFN-r, IL-6, TNF-a levels and promoted M1 to M2 polarization in PVAT. 3) Exercise decreased superoxide production in the vascular wall of diabetic mice, accompanied with increased nitric oxide bioavailability. 4) Exercise decreased the adhesion of diabetic aorta endothelial cells to leukocytes, accompanying with decreased ICAM-1 and VCAM-1 expression.

In conclusion, our data suggest that exercise improved endothelial function by attenuating the oxidative stress and inflammation in PVAT.

Disclosure

J. Wang: None. V. Polaki: None. S. Chen: None. J. Bihl: None.

Funding

American Diabetes Association (1-17-IBS-187 to J.B.)
462-P: AT-001, a Next Generation Aldose Reductase Inhibitor with Improved Selectivity and Specificity, Protects from Cellular Damage Associated with Hyperglycemia
Authors: PERFETTI RICCARDO , YEPURI GAUTHAM , QUADRI NOSIRUDEEN A. , RAMASAMY RAVICHANDRAN , GHANNAM AMEEN F. , SHENDELMAN SHOSHANA
Published: June 2020

The generation of Reactive Oxygen Species (ROS) and Advanced Glycation Endproducts (AGE’s) resulting from chronic tissue exposure to elevated levels of glucose has been identified as a key modulator of diabetic complications including diabetic cardiomyopathy. Abnormal activation of the polyol pathway converts excess glucose to sorbitol, generating ROS and AGEs. This conversion is catalyzed by the enzyme Aldose Reductase. Inhibition of Aldose Reductase, the rate limiting enzyme in the polyol pathway, reduces the production of sorbitol, attenuates increases in NADH, and down-regulates the synthesis of ROS.

Methods and Results: Cultured human adult cells (NHK) were exposed to elevated glucose [25mM] to simulate hyperglycemic conditions in diabetic tissue in the presence/absence of Aldose Reductase inhibitor AT-001 [0.18nM]. AT-001 dose selection was based on previous dose response studies. Cytosolic oxidative stress was evaluated and quantified using dihydroethidium (DHE) staining and quantitated via colorimetric assessment. Mitochondrial-specific oxidative stress ROS levels were quantitated using MitoSOX staining. AT-001 prevented the production and accumulation of ROS as assessed by both DHE quantitation and MitoSOX staining, demonstrating effective inhibition of polyol pathway associated damage to these cells.

Conclusions: AT-001 effectively prevented cellular damage caused by oxidative stress under hyperglycemic conditions warranting further investigation of AT-001 in the treatment of diabetic complications. AT-001 is currently being evaluated in a pivotal phase 2/3 study (ARISE-HF NCT 04083339) to treat diabetic cardiomyopathy and prevent progression to overt heart failure and also includes sub-analyses for retinopathy and diabetic peripheral neuropathy.

Disclosure

R. Perfetti: Stock/Shareholder; Self; Applied Therapeutics. G. Yepuri: None. N.A. Quadri: None. R. Ramasamy: Consultant; Self; Applied Therapeutics. A.F. Ghannam: Employee; Self; Applied Therapeutics Inc. Stock/Shareholder; Self; Sanofi US. S. Shendelman: Employee; Self; Applied Therapeutics. Stock/Shareholder; Self; Applied Therapeutics.

Funding

Applied Therapeutics (NCT04083339)
467-P: Brown Fat Original Mir-30b Targeting Renal RUNX1 to Improve Diabetic Nephropathy
Authors: GUAN MEIPING
Published: June 2020

It has been verified that adipose tissue was the major source of circulating microRNAs (miRNA), which could target downstream genes in distant organs such as liver. Here we show that brown adipose tissue (BAT) transplantation from healthy mice donor could reactivate endogenous BAT activity of diabetic mice induced by high fat diet (HFD) and streptozotocin (STZ) injection. BAT activation increased circulating miR-30b level and significantly improved diabetic nephropathy. In vitro, miR-30b was significantly downregulated by TGF β1 in HK-2 cells. In vivo, agomiR-30b was directly administered to the BAT of diabetic mice (0.25nmol/g body weight) twice per week for 4 consecutive weeks. Over-expressing miR-30b markedly decreased fibronectin expression, coupled with downregulated Runt-related transcription factor 1(Runx1) and snail family zinc finger 1 (Snail1) in the kidney of diabetic mice, while silencing of miR-30b displayed the opposite features. Next, knockdown or overpression of Runx1 both in vitro by using siRUNX1 or pCMV-RUNX1, and in vivo by AAV-U6-shRunx1 or AAV-EF1a-Runx1 respectively, could mimic the above phenotype of miR-30b mimic and inhibitor treatment respectively. Moreover, Runx1 promoted TGFβ1-induced fibrosis through upregulating PI3K pathway. These results suggest that BAT transplantation ameliorates diabetic nephropathy in mice through reactivating endogenous BAT and increasing circulating miR-30b level, which subsequently target renal Runx1 and Snail1, to improve renal fibrosis. BAT-original miRNAs might be a promising target for kidney protection in diabetes mellitus.

Disclosure

M. Guan: None.

Funding

National Natural Science Foundation of China (81870612, 81628004, 31400992, 81470047); Guangdong Science and Technology Project (2019A1515011997)