bluuebunny/crossref_metadata_2025_split huggingface dataset:
443-P: Two-Year Results from a Novel, Patient-Centered, Team-Based Intervention for Patients with Type 2 Diabetes at High Cardiovascular Risk
Authors: ARAFAH ALA , NEELAND IAN , BOURGES-SEVENIER BRENDAN M. , ALBAR ZAINAB , SULLIVAN CLAIRE , AL-KINDI SADEER G. , RAJAGOPALAN SANJAY 
Published: June 2023

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death in patients with type 2 diabetes (T2D). CINEMA is a novel, patient-centered, team-based intervention for patients with T2D/prediabetes with high risk for ASCVD. We present the outcomes from the first 2 years of the CINEMA program.
Methods: Patients with T2D or prediabetes at high risk for CV events (established ASCVD, coronary artery calcium &gt;100 AU, chronic heart failure, chronic kidney disease, and/or metabolic syndrome) were included. Linear mixed effects and generalized linear mixed models were used to assess changes in ASCVD risk factors and guideline-based medication prescriptions over time, respectively.
Results: From May 2020 to September 2022, 426 patients were enrolled in CINEMA; 47% were women and 37% Black, with mean age 60 yrs, mean BMI 36kg/m2, and 48% with established ASCVD. 54% had ≥ 1 follow up visit with median follow up time of 3 months. There were significant reductions in risk factors including HbA1c (-12.1%), LDL-C (-14.2%), BP (-1.8%), and BMI (-2.2%) (P&lt;0.001 for all). SGLT2 inhibitor and GLP-1 RA prescriptions increased from during follow up (20% to 56% and 17% to 66%, respectively).
Conclusion: A multidisciplinary approach to treating patient with type 2 diabetes with the CINEMA program improves ASCVD risk factors and guideline-based medication adherence.

Disclosure
A.Arafah: None. I.Neeland: Consultant; Nestlé Health Science, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Bayer Inc. B.M.Bourges-sevenier: None. Z.Albar: None. C.Sullivan: None. S.G.Al-kindi: None. S.Rajagopalan: Advisory Panel; Novartis, Novo Nordisk, Speaker's Bureau; Novo Nordisk.
445-P: Health Literacy in Patients With Type 2 Diabetes Undergoing Coronary Angiography
Authors: VOGEL JOHANNES , RATZ MAGDALENA , PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , FRICK MATTHIAS , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2023

Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care but also for health care providers. No health literacy data are available for patients undergoing coronary angiography, the standard procedure for the definite evaluation of coronary artery disease (CAD). We therefore recruited 273 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire. A response rate of 83.9% was achieved. Overall, the median health literacy score (HLS) was 13 (interquartile range (IQR): 10.00-15.00), with 61.9% of patients showing adequate (HLS 13-16), 26.0% problematic (HLS 9-12) and 12.1% inadequate (HLS 0-8) health literacy. From the investigated patients, 94 (34.4%) had type 2 diabetes (T2DM) according to ADA criteria. Comparing patients with T2DM vs. subjects who did not have diabetes, no significant differences in median HLS (13, IQR: 4.3 vs. 13.0, IQR: 5.00; p=0.247) could be observed; similarly, there was no significant difference in the proportion of subjects with adequate (60.6% vs. 62.6%; p=0.755), problematic (28.7% vs. 24.6%; p=0.458) and inadequate (10.6% vs. 12.8%; p=0.594) health literacy. We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD, health literacy is suboptimal both in patients with T2DM and in nondiabetic subjects.

Disclosure
J. Vogel: None. M. Ratz: None. T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. M. Frick: None. H. Drexel: None. C.H. Saely: None.
457-P: Ceramides and the Ceramide-Based Risk Scores CERT1 and CERT2 Are Elevated in Patients with the Metabolic Syndrome
Authors: PLATTNER THOMAS , SAELY CHRISTOPH H. , MUENDLEIN AXEL , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , DREXEL HEINZ , LEIHERER ANDREAS 
Published: June 2023

Plasma ceramides, phosphatidylcholines (PC) and the ceramide- and PC-based Coronary Event Risk Test scores CERT1 and CERT2 have recently been shown to predict cardiovascular risk. Their association with the metabolic syndrome (MetS) is unclear and is addressed in the present study. We measured ceramides (Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)) and PCs (PC(36:6), PC(38:5), and PC(32)) in a cohort of 1306 high-risk patients, of whom 580 had the MetS and 728 did not have the MetS. All investigated ceramides and PC(36:6) as well as CERT1 (4.6±3.3 vs. 3.4±3.0) and CERT2 (5.9±2.5 vs. 5.3±2.5) were elevated in patients with the MetS vs. those who did not have the MetS (p&lt;0.001 for all comparisons). In regression analyses adjusting for age, sex, smoking, BMI and LDL-C CERT1 and CERT2 proved to be independent predictors of the MetS, with ORs of 1.14 [95% CI 1.09-1.19] and 1.09 [1.04-1.15], respectively. From our data we conclude that ceramides Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1), phosphatidylcholine PC(36:6) and the ceramide- and PC derived risk scores CERT1 and CERT2 are elevated in Patients with the MetS.

Disclosure
T.Plattner: None. A.Leiherer: None. C.H.Saely: None. A.Muendlein: None. A.Vonbank: None. A.Mader: None. L.Sprenger: None. M.Maechler: None. B.Larcher: None. H.Drexel: None.
464-P: The Triglyceride–Glucose Index and Type 2 Diabetes Are Mutually Independent Predictors of Major Cardiovascular Events in Patients with Coronary Artery Disease
Authors: PLATTNER THOMAS , VONBANK ALEXANDER , MADER ARTHUR , SPRENGER LUKAS , MAECHLER MAXIMILIAN , LARCHER BARBARA , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2023

The triglyceride-glucose index (TyG) is a validated biomarker of insulin resistance. Its power to predict major cardiovascular events (MACE) in patients with established coronary artery disease (CAD) is unclear and is addressed in the present study. We enrolled 1032 consecutive patients with angiographically proven CAD. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.1±5.1 years. At baseline, the TyG index was significantly higher in patients with T2DM (n=346) than in nondiabetic subjects (9.3±0.7 vs. 8.7±0.5; p&lt;0.001). During follow-up, 435 of our patients suffered MACE. The event rate was significantly higher in patients with T2DM than in nondiabetic subjects (48.7 vs. 39.4%; p=0.005). The TyG index in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index, and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.40 [1.20-1.65], p&lt;0.001); HRs in patients with T2DM and in nondiabetic subjects were 1.51 [1.18-1.93], p=0.001 and 1.16 [0.89-1.50], p=0.271, respectively, with no evidence of an interaction between TyG and T2DM (p=0.440). With T2DM additionally entered into the regression model, TyG on tee total study population predicted MACE independently from the presence of T2DM (HR 1.32 [1.10-1.57], p=0.003) while T2DM remained independently predictive of MACE after adjustment for TyG (HR 1.29 [1.04-1.59]; p=0.020). From our data we conclude that the TyG index and T2DM are mutually independent predictors of MACE in patients with established CAD.

Disclosure
T. Plattner: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
469-P: Direct Medical Costs Associated with Cardiovascular Complications for Adults with Type 2 Diabetes—Evidence from a U.S. Retrospective Study
Authors: BAE JAY P. , THIEU VIVIAN , LAGE MAUREEN J. , BOYE KRISTINA 
Published: June 2023

Introduction: Cardiovascular (CV) disease is a major cause of morbidity and mortality for people with diabetes. This study examines the annual medical costs of newly identified CV complications for adults with type 2 diabetes (T2D).
Methods: Optum’s de-identified Clinformatics® Data Mart data from 1/1/2015 - 6/30/2021 was used to examine a cohort of adults with T2D identified with a CV complication, with first such date identified as the index date. Descriptive statistics examined the direct medical costs (inpatient, emergency, and outpatient) associated with each complication in the 1st and 2nd year post index date. Complications included heart failure (HF), myocardial infarction (MI), stroke (STRK), hospitalization with a diagnosis of unstable angina (HUA), coronary revascularization (CR), and hypertension (HTN).
Results: There were 167,046 patients with an average of 1.2 conditions of interest each. HTN (12.3%), STRK (12.1%), and HF (10.6%) were the most common complications. In the 1st year post index date, HUA, MI, and HF were the most expensive complications. In the 2nd year post index date, costs of each complication ranged from 1.7% (CR) to 65.0% (HTN) of 1st year costs (see Figure).
Conclusion: Results illustrate the costs associated with CV-related complications for T2D and helps to quantify the economic burden that T2D imposes on U.S. healthcare systems.

Disclosure
J.P.Bae: None. V.Thieu: None. M.J.Lage: Consultant; Eli Lilly and Company. K.Boye: Employee; Eli Lilly and Company.
477-P: Thalamic Mitochondrial and Neuronal Function Is Preserved in Painful Diabetic Peripheral Neuropathy—A Multimodal Magnetic Resonance Imaging Study
Authors: SLOAN GORDON P. , TEH KEVIN , SELVARAJAH DINESH , TESFAYE SOLOMON 
Published: June 2023

Aims: Previous neuroimaging studies have demonstrated cerebral structural, functional, and vascular alterations in Painful-Diabetic Peripheral Neuropathy (DPN). We present a multi-modal Magnetic Resonance Imaging (MRI) study to determine the structure, and neuronal and mitochondrial function of the thalamus in Painful-DPN.
Methods: A total of 49 participants were enrolled, 38 with type 2 diabetes (9 without DPN [No-DPN]; 11 with Painless-DPN; and 18 with Painful-DPN) and 11 healthy volunteers (HV). Participants underwent detailed clinical and neurophysiological assessments, and multi-modal MR imaging of the thalami bilaterally including: Proton-Magnetic Spectroscopy (1H-MRS); 31-Phosphorus MRS (31P-MRS); and brain morphometric analysis. We calculated the N-acetyl aspartate to choline (NAA:Cho), a measure of neuronal function, and inorganic phosphate (Pi) to ATP (Pi:ATP), a measure of mitochondrial function.
Results: There were no significant differences in thalamic volume between groups (ANOVA, p=0.927). There was a significant group effect in both metabolite ratios: NAA:Cho (ANOVA, p=0.013); Pi:ATP (p=0.021). The NAA:Cho was numerically the lowest in Painless-DPN, reaching significance compared with HV (p=0.001) and Painful-DPN (p=0.019). Additionally, the Pi:ATP was significantly higher in Painless-DPN compared with HV (p=0.013) and Painful-DPN (p=0.008). There was also a significant correlation between the NAA:Cho and Pi:PCr (Pearson’s r -0.336, p=0.034).
Conclusion: This is the first study to determine perform cerebral 1H- and 31P-MRS in human DPN. We have demonstrated altered 1H- and 31P-MRS ratios in Painless- but not Painful-DPN, suggesting that mitochondrial dysfunction may underlie thalamic neuronal dysfunction in Painless-DPN. Conversely, in Painful-DPN, preservation of thalamic mitochondrial and neuronal function may be involved in the maintenance of neuropathic pain signaling.

Disclosure
G.P.Sloan: None. K.Teh: None. D.Selvarajah: None. S.Tesfaye: Advisory Panel; Bayer Inc., Wörwag Pharma GmbH & Co. KG, Angelini, Speaker's Bureau; Viatris Inc., Nevro Corp., Procter & Gamble, Novo Nordisk, Berlin-Chemie AG.
481-P: 10kHz SCS Restores Mechanical and Thermal Neural Processing in a Rodent Model of Painful Diabetic Neuropathy
Authors: LEE KWAN , LEE DONGCHUL , WANG DONG , KAGAN ZACHARY B. , BRADLEY KERRY 
Published: June 2023

A recent randomized controlled trial of 10 kHz spinal cord stimulation (SCS) in patients with painful diabetic neuropathy (PDN) has demonstrated significant and durable improvements in neurologic status, particularly sensory restoration of the foot (Petersen et al 2021, Argoff et al 2023). In order to gain further mechanistic insight into the improvements in sensory processing by 10kHz SCS, we analyzed the receptive field (RF) size and responses of spinal dorsal horn (DH) neurons to mechanical and thermal stimuli of the paw in a PDN rat model. For PDN-model, Rats were given a single effective dose of streptozotocin (STZ), while Naïve animals were injected with 0.9% saline. Four groups were studied: Naïve, STZ, STZ+ShamSCS, and STZ+10kHzSCS. Rats were anesthetized with urethane and a laminectomy was performed for DH neurons recording. We analyzed RF size and the response of DH neurons to vibrotactile stimulation and thermal sensation. Both the Naïve and STZ+10kHzSCS groups had significantly smaller RFs than the STZ Control and STZ+ShamSCS groups. In response to a 1 Hz vibration frequency, Naïve and STZ+10kHzSCS groups had higher peak power spectral density (PSD) of DH firing than STZ+ShamSCS, and PSD for the STZ+10kHzSCS group was statistically higher than for the STZ Control group. Response of DH neurons showed no significant differences between groups during the thermal stimulation, but the post-stimulus firing rates for the STZ+10kHzSCS group were significantly higher compared to STZ Control and STZ+ShamSCS. These data suggest that 10 kHz SCS amplified the DH response to large fiber (vibration) and small fiber (warm) signals and normalized the receptive field of the paw (acuity) in PDN rats. In diabetes, where peripheral sensory compromise from chronic hyperglycemia can lead to loss of protective sensation, such ‘tuned amplification’ as provided by 10 kHz SCS in the central nervous system may compensate for the reduced functionality seen in the peripheral sensory systems.

Disclosure
K.Lee: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. D.Wang: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.
482-P: Behavioral Assessment of 10kHz Spinal Cord Stimulation–Mediated Pain Relief in a Rat Model of Painful Diabetic Neuropathy
Authors: WANG DONG , LEE DONGCHUL , LEE KWAN , KAGAN ZACHARY B. , BRADLEY KERRY 
Published: June 2023

Painful diabetic neuropathy (PDN) is a serious complication of diabetes and occurs in approximately 20% of diabetic patients. In a recent RCT, 10kHz spinal cord stimulation (10kHz SCS) was shown to be a promising therapy for PDN, in both pain reduction and possible neurological improvements (Petersen et al 2021). In this study, we aimed to observe the behavioral effects of 10kHz SCS on PDN using streptozotocin (STZ)-induced diabetic rats.
We established four testing groups: Naïve controls, STZ controls, STZ+Sham SCS, and STZ+10kHz SCS. A single effective dose (60 mg/kg) of the cytotoxic agent STZ caused the rats to become hyperglycemic within 72 hours and lasted for several weeks. These STZ-injected rats also showed a significant and continuous reduction in body weight in comparison to Naïve control rats. Using the von Frey test for mechanical allodynia, we observed that 14 days of 24h/day low-intensity (30% of motor threshold) 10kHz SCS significantly elevated the mechanical pain withdrawal thresholds compared to STZ controls or STZ+Sham SCS animals, reaching statistical equivalence to Naïve controls. In a thermal preference assay, all animals exhibited a training effect towards less activity and more preference to the room temperature side vs the non-painful heat side of a two-temperature chamber over the several-week protocol. We found that STZ-injected animals demonstrated significantly less exploration activity in the 10min testing periods compared to Naïve controls but neither the thermal preference nor the total distance they traveled were restored after 14 days of 10kHz SCS.
Our results demonstrate that 10 kHz SCS resulted in behavioral outcomes reflective of the mechanical pain reduction in the PDN rodent model. These findings provide supporting evidence for the recent RCT data and underscore the conclusion that 10kHz SCS can effectively treat patients with refractory PDN.

Disclosure
D.Wang: Employee; Nevro Corp. D.Lee: Employee; Nevro Corp. K.Lee: Employee; Nevro Corp. Z.B.Kagan: Employee; Nevro Corp. K.Bradley: Employee; Nevro Corp.
487-P: Cardiovascular Autonomic Function in Long COVID-19 Individuals With and Without Diabetes
Authors: FLEISCHER JESPER , GUNARATNAM SEJAL V.G. , HUANG YIYUAN , ANG LYNN , CHARLES MORTEN , KATONA AIMEE , BAKER NICOLE , MIZOKAMI-STOUT KARA R. , KUEI LIN YU , VASBINDER ALEXI , HAYEK SALIM , BUSUI RODICA 
Published: June 2023

Coronavirus disease 2019 (COVID-19) has been associated with a broad spectrum of long-term complications. These include the development and progression of severe autonomic dysfunction, particularly among people with diabetes. We evaluated cardiovascular autonomic (CAN) function in a cross-sectional study in 47 adults with long COVID-19 with (N=21, mean age 61 years, 43% women, mean A1c 6.2%) and without type 2 diabetes mellitus (T2DM) (N=26, mean age 58 years, 65% women) and compared them with T2DM without COVID-19 (N=45, mean age 57 years, 42% women, mean A1c 7.8%). CAN was assessed with cardiovascular autonomic reflex tests (30:15 ratio, E.I ratio, Valsalva ratio) and indices of heart rate variability (SDNN, RMSSD). We used pairwise comparison and Analysis of Covariance (ANCOVA) both adjusted for age, gender, race, and BMI to compare the groups. In a pairwise comparison higher heart rate (HR) and lower CAN measures (SDNN, RMSSD, Valsalva) were found in T2DM with COVID-19 compared to T2DM without COVID-19. Lower HR and lower Valsalva were found in COVID-19 individuals without T2DM compared to T2DM without COVID-19. When comparing the three groups, lower Valsalva were found in COVID-19 individuals with and without T2DM compared to T2DM without COVID-19 (Figure). These data suggest that COVID-19 exacerbates CAN in patients with T2DM and impacts CAN in people without T2DM at a magnitude similar to that of T2DM patients.

Disclosure
J.Fleischer: None. A.Vasbinder: None. S.Hayek: None. R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter & Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. S.V.G.Gunaratnam: None. Y.Huang: None. L.Ang: None. M.Charles: Research Support; Novo Nordisk Foundation, Speaker's Bureau; Novo Nordisk A/S, Boehringer-Ingelheim. A.Katona: None. N.Baker: None. K.R.Mizokami-stout: None. Y.Lin: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK119083, P30DK020572); Steno North American Fellowships 2021; Novo Nordisk Foundation (21OC0072180)
496-P: Diabetic Retinopathy in Youth with Type 2 Diabetes—Data from Three Academic Health Centers
Authors: CHANNA ROOMASA , SHAH AMY S. , SHAH VEERAL S. , BAHRAINIAN MOZHDEH , BROWN ELIZABETH A. , ALVIN LIU T.Y. , MAGELLA BLISS , LEHMANN HAROLD , ABRÀMOFF MICHAEL D. , WOLF RISA M. 
Published: June 2023

Diabetic retinopathy (DR) is a microvascular complication of type 2 diabetes (T2D) and a major cause of vision loss worldwide. The TODAY study reported a DR prevalence of 51% among patients with youth onset T2D (average T2D duration 13.3 years, mean age of 26.4 years). Prevalence rates of DR in youth-onset T2D with shorter duration and younger age is unclear.
In a multicenter analysis, eye exams or retinal images from patients with youth-onset T2D at Cincinnati Children’s, Johns Hopkins, and University of Wisconsin were assessed for presence of DR using t-tests and fisher’s exact test.
The study included 228 youth (mean age 16.5±3.5years, mean T2D duration 3.0±2.6 years). Seven participants (3%) were positive for DR. Compared to youth negative for DR (n=221), those with DR (n=7) had a longer duration of diabetes (5.3±3.1 v. 2.9±2.6years, p=0.015) and higher hemoglobin A1c at the time of the diabetic eye exam (10.0±2.1 v. 7.5±2.6%, p=0.012). There were no differences in age, race/ethnicity, sex, or types of medication prescribed between those with and without DR. Of those with DED, when compared to all other ethnicities, NH Black youth had a higher rate of positive diabetic eye exams (p=0.04).
Our study found a lower prevalence of DR in youth with T2D at younger age and shorter duration of diabetes. Further work is needed to determine the inflection point when the incidence of DR increases.

Disclosure
R.Channa: None. R.M.Wolf: Research Support; Dexcom, Inc., Boehringer Ingelheim Inc. A.S.Shah: None. V.S.Shah: None. M.Bahrainian: None. E.A.Brown: None. T.Liu: None. B.Magella: None. H.Lehmann: None. M.D.Abràmoff: Board Member; Digital Diagnostics, Consultant; AbbVie Inc., NovaGo Therapeutics AG, Other Relationship; Digital Diagnostics, Stock/Shareholder; Digital Diagnostics.

Funding
National Eye Institute (R01EY033233, 5K23EY030911-03)
501-P: Differences in Disease Severity and Treatment for Diabetes-Related Retinopathy between Type 1 and 2 Diabetes Mellitus
Authors: BREEN JAMES M. , COOPER AMELIA , STEVENS HENRY , COOPER BLAKE A. 
Published: June 2023

Background: Diabetes-related retinopathy (DR) is a neurovascular complication of both type 1 (T1D) and type 2 (T2D) diabetes, the prevalence of which strongly correlates to both the duration of diabetes and blood glucose levels. DR severity level has been reported to be worse in patients with T1D than in T2D but few studies have reported on treatment outcomes.
Objective: To determine differences in the level of DR, central subfoveal thickness (CST), and treatment outcomes for those with T1D and T2D.
Methods: A retrospective chart review.
Covariates: age, sex, type of DM, last A1c, level of retinopathy, and visual acuity.
Primary Outcome: Level of DR. Secondary Outcomes: CST, IVI use, and frequency for DME. ICD-10 codes identified 10,026 patients with diabetes who were seen in 2021 at Retina Associates in Kansas City. Retrospectively screened 1,000 consecutive patient medical records from this cohort and excluded those with incomplete records and those who had a second diagnosis that could cause macular edema.
Results: Characteristics of 321 patients with DR and treatment needs are described in the table below and used for analysis. Conclusions: Comparing those with T1D and T2D we found a statistical difference in those with T1D being younger, having less HTN, and higher levels of DR. Despite these findings there was no difference in visual acuity and need or frequency of intravitreal injections.

Disclosure
J.M.Breen: None. A.Cooper: None. H.Stevens: None. B.A.Cooper: Advisory Panel; Genentech, Inc., Speaker's Bureau; Regeneron, Optomed.