bluuebunny/crossref_metadata_2025_split huggingface dataset:
42-OR: The Impact of a Digital Health Coaching Program on a Rural Population
Authors: MOORE JASMINE , RUTLAND SARAH , TRAN VANESSIA T. , STEPHEN BURTON B. 
Published: June 2023

Compared to urban areas, the prevalence of diabetes is higher in rural areas. The effects of diabetes are compounded by barriers endemic to rural populations, such as limited access to care and health education. A digital health coaching (DHC) program may address these barriers. This retrospective analysis explored how a DHC program influenced outcomes among patients with T2DM who live in a rural area. Individuals with T2DM were enrolled in a 6-month condition-specific DHC program via an employer/payor program or physician. A comparative analysis assessed changes in physical, mental, and emotional health metrics among those living in a rural area, defined as areas located outside of a U.S. Census Bureau Urbanized Area (an urban area of 50,000 or more people). Paired t-tests were used to determine differences between the overall average baseline and month 6 scores. From January 1, 2021, to September 30, 2022, 584 rural participants were enrolled in the DHC program. Most participants were female (75%) with an average age of 55. At 6 months, there were significant improvements in diabetes distress scores (2.6 to 2.0, P=0.0007) and HbA1c (8.3 to 7.2, P=0.0071). Participants in the program showed improved outcomes for diabetes-related quality of life measures at 6 months. This analysis suggests that implementing a DHC program that addresses modifiable behaviors and barriers can help reduce the burden of diabetes in a rural population.

Disclosure
J.Moore: None. S.Rutland: None. V.T.Tran: None. B.Burton: None.
423-P: Urinary Extracellular Vesicles in African Americans with Chronic Kidney Disease With and Without Type 2 Diabetes Mellitus
Authors: THETHI TINA K. , BILAL ANIKA , ZAINO MATTHEW S. , ILIUK ANTON , PRATLEY RICHARD E. , NUNEZ LOPEZ YURY O. 
Published: June 2023

Introduction: Type 2 diabetes (T2D) is the leading cause for chronic kidney disease (CKD). Novel biomarkers are critical in early detection of CKD.
Methods: Healthy Eatonville Project (HEP) was a prospective study (n=300, females (F)=71%, T2D 32%, CKD 25%) in historically black community of Eatonville, FL. We characterized EVtrap®-isolated urinary extracellular vesicles (uEV) proteins from a balanced HEP cohort of 48 African Americans (mean age 62y, F=73%, BMI 32.2 kg/m2, T2D 46%) with CKD risk ranging from low, intermediate, to high-very high (H-VH), with and without T2D. Differential expression and coexpression network analyses were implemented.
Results: We detected 5265 uEV proteins, 46 of which were significantly (fold change&gt;1.5, P&lt;0.05, FDR&lt;0.1) differentially expressed (DE) in CKD risk groups. Of those, 24 were significantly upregulated in H-VH risk CKD (Figure Module Pr.1). A set of 15 DE proteins appeared to represent a protective pathway against CKD (Figure Module Pr.2). Key biomarkers of acute kidney injury IGFBP7, TIMP2, and IL18 had significant negative correlations with CKD risk (-0.59 ≤ r ≤ -0.44, P&lt;0.002). Supporting our findings, several of these biomarkers had been previously reported in kidney disease studies.
Conclusion: The uEV proteomic landscape is representative of kidney pathophysiology and suggests potential biomarkers of CKD in Africans Americans.

Disclosure
T.K.Thethi: Other Relationship; Bayer Inc., Novo Nordisk. A.Bilal: None. M.S.Zaino: None. A.Iliuk: None. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. Y.O.Nunez lopez: None.
424-P: Diabetic Kidney Disease (DKD) Worsens CV Outcomes after First-Ever Major Cardiovascular Event in Type 2 Diabetes (T2D)
Authors: GAROFOLO MONIA , LUCCHESI DANIELA , GIAMBALVO MASSIMO , CAPOBIANCO MARTINA , FRANCESCONI PAOLO , PENNO GIUSEPPE , DEL PRATO STEFANO 
Published: June 2023

Aim: CV prognosis worsens in T2D after a first CV event. We assessed impact of DKD on mortality and subsequent CV events after a first CV event.
Methods: Death rate was recorded over a median 14.1 (IQR 13.8-14.5) years follow-up in 961 T2D subjects. Vital status (Italian Health Card Database) was censored on December 31, 2017 (major CV events available for 947 participants). Effect of DKD (ACR &lt;30/≥30 mg/g) and/or CKD-EPI eGFR ≥60/&lt;60 ml/min/1.73 m2) was determined by Kaplan-Meier (K-M) curves and hazard ratios (HR, 95% CI) by unadjusted and adjusted Cox regression models (age, diabetes duration (DD), sex, smoking, retinopathy, hypertension, dyslipidemia, prior CVD; no-DKD as reference).
Results: At census, 229 subjects were dead (23.8%) and 298 participants out of 947 (31.5%) had a first CV event during a median 13.8 year pre-event follow-up. Compared with free-CV event subjects, those with CVD were older, more often men, with longer diabetes duration, worse CV risk profile, more microvascular complications and CVD before recruitment. During a median 6 yr post-first CV event follow-up 99 subjects died: 57 (27.4%) no DKD, 42 (46.7%) DKD (K-M, p=0.005). Compared to no DKD the latter had an unadjusted HR of 1.76 (1.18-2.63, p=0.005; adjusted 1.69, 1.13-2.52, p=0.011). Death rate increased with DKD worsening with statistically significant HR (unadjusted 3.31, 1.73-6.31, p&lt;0.0001; adjusted 3.32, 1.65-6.64, p=0.001) for ACR≥30/eGFR&lt;60. During a median 3.1 post-first CV event follow-up, a new CV event occurred in 124 subjects: 82 (39.4%) no DKD and 42 (46.7%) DKD (K-M, p=0.019) with unadjusted HR for a new CV event in DKD of 1.40 (0.96-2.03, p=0.077). Rate of a secondary CV event increased across DKD phenotypes with unadjusted (HR 3.42, 95% CI 1.76-6.65, p&lt;0.0001) and adjusted HR of 3.18 (1.57-6.44; p=0.001) for ACR≥30/eGFR&lt;60, respectively.
Conclusions: In T2D subjects, DKD still worsens the risk of mortality and secondary CV events after the occurrence of a first CV event.

Disclosure
M.Garofolo: Consultant; Novo Nordisk, Employee; Eli Lilly and Company. D.Lucchesi: None. M.Giambalvo: None. M.Capobianco: None. P.Francesconi: None. G.Penno: Advisory Panel; Eli Lilly and Company, Bayer Inc., Consultant; Novo Nordisk, AstraZeneca, Boehringer Ingelheim Inc. S.Del prato: Advisory Panel; Abbott Diagnostics, Altimmune, Amarin Corporation, Applied Therapeutics Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Vertex Pharmaceuticals Incorporated, Novartis, Consultant; A. Menarini Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi.
425-P: Renin-Angiotensin System Inhibition in Combination with Glucagon-Like Peptide 1 Receptor Agonist Treatment Improve Levels of a Kidney Fibrosis Biomarker in Persons with Type 2 Diabetes
Authors: MØLLER ALEXANDRA , THÖNI STEFANIE , LAURSEN CLARA F.G. , KARSDAL MORTEN A. , GENOVESE FEDERICA , GULDAGER KRING RASMUSSEN DANIEL 
Published: June 2023

Background: The drug combinations for rewriting trajectories of renal pathologies in type 2 diabetes (DC-ren) study focuses on DKD, a complication of diabetes often accompanied by cardiovascular disease. Novel biomarkers for identifying persons at increased risk of disease progression and predicting treatment response are currently needed. Levels of urinary C3M, a marker of type III collagen degradation, have been shown to correlate with CKD progression, and dulaglutide treatment improved levels of this biomarker compared with insulin glargine in persons with type 2 diabetes (T2D). We investigated the effect of combination therapy on urinary C3M in persons with T2D.
Method: We measured urinary C3M in urine collected at baseline and after years 1, 2, and 3 from 229 individuals with T2D enrolled in the DC-ren study. All persons were on renin-angiotensin system inhibitor (RASi) treatment at baseline and during follow-up. While some persons remained on RASi treatment (n = 184), others received glucagon-like peptide-1 receptor agonist (GLP-1 RA) on top of RASi (n = 45).
Results: The cohort consisted of 48% males (age of 66 ± 8 years and eGFR was 65 ± 17 ml/min/1.73 m2). Lower baseline levels of urinary C3M were associated with lower eGFR, and this relation remained consistent over time. Levels of urinary C3M were higher in persons after treatment with GLP-1 RA in combination with RASi compared to RASi alone (P = 0.034). In adjusted linear models (for the RASi group), an association of current urinary C3M with future eGFR was found (P &lt; 0.01), indicating that urinary C3M is a prognostic risk marker for kidney function decline.
Conclusion: RASi in combination with GLP-1 RA treatment was associated with increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. This anti-fibrotic effect could be a mechanism for the beneficial effects observed with GLP-1 RA treatment on CKD in T2D.

Disclosure
A.Møller: None. S.Thöni: None. C.F.G.Laursen: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.
426-P: Semaglutide, Empagliflozin, and Cagrilintide Reduce Levels of Serum Endotrophin in Type 2 Diabetic Rats
Authors: MØLLER ALEXANDRA , MELANDER SIMONE A. , LARSEN ANNA T. , LAURSEN CLARA F.G. , GENOVESE FEDERICA , KARSDAL MORTEN A. , GULDAGER KRING RASMUSSEN DANIEL , HENRIKSEN KIM 
Published: June 2023

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) demonstrated cardiovascular (CV) and kidney outcomes benefit in persons with type 2 diabetes (T2D). The long-acting amylin analogue, cagrilintide, is under investigation for the treatment of obesity and T2D. Endotrophin, a pro-fibrotic fragment derived from collagen type VI, is an independent risk marker of mortality, CV and kidney outcomes, and dulaglutide treatment decreased levels of this biomarker compared with insulin glargine in persons with T2D. We investigated for the first time the effect of semaglutide, empagliflozin, and cagrilintide on endotrophin in type 2 diabetic rats.
Method: We measured endotrophin (by the rodent PRO-C6 ELISA) in serum collected at baseline and study end from diabetic ZDF rats treated with either vehicle (n = 10), semaglutide (n = 7), empagliflozin (n = 4), or cagrilintide (n = 10). The dose chosen for semaglutide (50 nmol/kg), empagliflozin (30 mg/kg), and cagrilintide (10 nmol/kg) was based on previous research.
Results: Levels of endotrophin increased significantly during the study in vehicle-treated rats, reflecting the disease progression (median [95% CI] for increase: 182.5 [55.87-298.0], P &lt; 0.01). Interestingly, treatment with semaglutide, empagliflozin, and cagrilintide each attenuated this increase, resulting in significantly lower levels of endotrophin compared to vehicle at study end (P &lt; 0.01), (P &lt; 0.05), and (P &lt; 0.01), respectively.
Conclusion: We developed a novel, robust assay to detect the clinically relevant endotrophin biomarker in rodents. Levels of serum endotrophin increased over time in vehicle-treated rats, which is in line with endotrophin predicting disease progression in persons with T2D. In addition to the beneficial effects on metabolic factors, semaglutide, empagliflozin, and cagrilintide each reduced levels of endotrophin, suggesting a potential effect to reduce fibrosis.

Disclosure
A.Møller: None. S.A.Melander: None. A.T.Larsen: Employee; Nordic Bioscience A/S. C.F.G.Laursen: None. F.Genovese: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. D.Rasmussen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S.
432-P: Role of Patatin-Like Phospholipase Domain–Containing 3 Gene for Kidney Dysfunction in Diabetes Endotypes
Authors: ZAHARIA OANA P. , STRASSBURGER KLAUS , KNEBEL BIRGIT , KUPRIYANOVA YULIYA , KOTZKA JORG , BÓDIS KÁLMÁN , SCHÖN MARTIN , BOMBRICH MARIA , MÖSER CLARA , PRYSTUPA KATSIARYNA , AL-HASANI HADI , SCHRAUWEN-HINDERLING VERA , JANDELEIT-DAHM KARIN , WAGNER ROBERT , RODEN MICHAEL 
Published: June 2023

Recent studies identified distinct endotypes of diabetes with differences in metabolic features and in risk for diabetes-related comorbidities. Of note, persons allocated to the severe insulin resistant diabetes (SIRD) endotype, who show increased prevalence of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), are more frequently carriers of the G-allele in the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene. This SNP associates with increased risk of NAFLD yet the association between the presence of the PNPLA3 SNP and CKD remains controversial. The present study examined whether this SNP differently associates with CKD in endotypes of recent-onset diabetes. Participants with newly diagnosed diabetes (n=707) from the prospective German Diabetes Study underwent k-means clustering, genotyping, magnetic resonance spectroscopy to determine hepatocellular lipid content (HCL) and laboratory analyses to calculate the glomerular filtration rates (eGFR). SIRD had the lowest eGFR and highest HCL compared to severe insulin deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes clusters (all p&lt;0.05). HCL was negatively associated with eGFR (r=-0.287, p&lt;0.01) across all groups. Further stratification by PNPLA3 G-allele carrier status did not reveal any association between HCL and eGFR in any of the diabetes types, irrespective of G-allele carrier status. However, with declining eGFR the proportion of G-allele carriers increased from 44% for eGFR &gt;60 ml/min to 52% for eGFR &lt;60 ml/min (p&lt;0.05). In conclusion, increased hepatic lipid content is associated with reduced kidney function across all diabetes endotypes. This association is independent of the presence of the PNPLA3 polymorphism in newly diagnosed diabetes, but there might be role for PNPLA3 for the severity of CKD.

Disclosure
O.P. Zaharia: None. K. Strassburger: None. B. Knebel: None. Y. Kupriyanova: None. J. Kotzka: None. K. Bódis: None. M. Schön: None. M. Bombrich: None. C. Möser: None. K. Prystupa: Other Relationship; Berlin-Chemie AG. H. Al-Hasani: None. V. Schrauwen-Hinderling: None. K. Jandeleit-Dahm: None. R. Wagner: Speaker's Bureau; Novo Nordisk, Sanofi. Advisory Panel; Daiichi Sankyo. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis. Consultant; TARGET PharmaSolutions, Inc. Research Support; Sanofi.

Funding
German Research Foundation; European Foundation for the Study of Diabetes; German Diabetes Association; German Federal Ministry of Education and Research; Heinrich Heine University
434-P: Urinary Proteome Classifiers in Prediabetes Clusters
Authors: SCHORK ANJA , FRITSCHE ANDREAS , SCHLEICHER ERWIN D. , PETER ANDREAS , HENI MARTIN , STEFAN NORBERT , JUMPERTZ VON SCHWARTZENBERG REINER , MISCHAK HARALD , SIWY JUSTYNA , BIRKENFELD ANDREAS L. , WAGNER ROBERT 
Published: June 2023

Objective: Patients with prediabetes have recently been classified into 6 prediabetes clusters, that stratify the risk of diabetes and complications. Cluster 1, 2 and 4 are low risk-clusters while cluster 3, 5 and 6 are high-risk clusters. Of notice, especially patients of cluster 6 have an elevated risk of nephropathy despite their low diabetes risk. To investigate if differences across clusters can be captured from urine peptidome, we studied differences in pre-specified urinary peptidome classifiers across age and sex matched participants from 6 prediabetes clusters (n=249, median age 46 (IQR 39 - 54) years, BMI 30.4 (26.9 - 39.4) kg/m², HbA1c 5.5 (5.3 - 5.8) %).
Methods: Peptides in spot urine samples collected at the University Hospital Tuebingen from 11/2004 to 11/2012 were investigated using capillary electrophoresis coupled mass spectroscopy. The following classifiers based on multiple urine peptides had been developed to detect different conditions and were assessed: CKD273 (chronic kidney disease, CKD), validated in a large clinical cohort), HF1 and HF2 (heart failure), CAD238 (coronary artery disease, CAD), Col_death (collagen type-1 turnover), solid_tumor (solid tumor). Matsuda index and NEFA insulin sensitivity index (ISI) were used for estimation of insulin sensitivity.
Results: The urinary peptidome classifiers CKD273, HF2 and CAD238 were significantly different between prediabetes clusters, with elevated values in cluster 6 compared to the healthiest cluster 2. These classifiers also correlated with Matsuda index and NEFA ISI. Classifiers HF1, Col_death and solid_tumor did not associate with prediabetes clusters or insulin sensitivity indices.
Conclusions: Beyond corroboration of a previously described increased risk of CKD, urinary peptidome classifiers suggest elevated risk of heart failure and coronary artery disease in persons of the prediabetes cluster 6. This could underlie increased mortality in this group, independent of diabetes development.

Disclosure
A.Schork: None. A.L.Birkenfeld: None. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. A.Fritsche: Advisory Panel; Novo Nordisk, Lilly, Sanofi, Boehringer-Ingelheim, Speaker's Bureau; AstraZeneca, SYNLAB Holding Deutschland GmbH. E.D.Schleicher: None. A.Peter: None. M.Heni: Advisory Panel; Boehringer-Ingelheim, Sanofi, Research Support; Boehringer Ingelheim Inc., Speaker's Bureau; Lilly, Bayer Inc., Sanofi, Boehringer-Ingelheim, Novo Nordisk, Amryt Pharma Plc. N.Stefan: Advisory Panel; Pfizer Inc., Research Support; Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Jumpertz von schwartzenberg: Other Relationship; Sanofi, Amgen Inc., Lilly, Novo Nordisk. H.Mischak: Stock/Shareholder; Mosaiques Diagnostics. J.Siwy: Employee; Mosaiques-Diagnostics GmbH.
435-P: Remnant-C as an Independent Risk Factor for End-Stage Renal Disease in Patients with Type 2 Diabetes—A Nationwide Population-Based Cohort Study
Authors: ROH EUN 
Published: June 2023

Few studies have investigated the association between remnant-C and the progression of diabetic nephropathy. We aimed to evaluate the association between remnant-C and the risk of newly developed end-stage renal disease (ESRD) in patients with type 2 diabetes in a nationwide cohort of Korean adults. The risk of incident ESRD according to remnant-C levels was analyzed by Cox proportional hazard models. During the median follow-up period of 9 years, 11,615 individuals (1.4% of the total population) developed ESRD. The serum concentrations of remnant-C was associated with 7% higher risk of ESRD per every 10 mg/dL increase. In multivariable-adjusted analyses, participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.15 (95% CI 1.09-1.22) in the second quartile, 1.26 (95% CI 1.20-1.33) in the third quartile, and 1.47 (95% CI 1.40-1.55) in the fourth quartile, compared with the lowest quartile. Furthermore, the magnitude of the increased risk for incident ESRD in individuals with higher remnant-C quartiles was significant in participants aged 50 years or older. These results suggest that remnant-C concentration is an independent risk factor for the development of ESRD in patients with type 2 diabetes.

Disclosure
E.Roh: None.
447-P: Using the Cambridge Risk Score to Predict New Hyperglycemia and Complications in Surgical Patients without Diabetes
Authors: LEE HANNAH , HARTFIELD PHILLIP J. , SINSON GRANT , WANG MARJORIE C. , DAWSON APRILL Z. , THORGERSON ABIGAIL , MENDEZ CARLOS E. 
Published: June 2023

Perioperative hyperglycemia is associated with adverse surgical outcomes and increased mortality, and when occurring in patients without history of diabetes, this is termed new hyperglycemia (NH). The Cambridge Risk Score (CRS) is a screening tool for type 2 diabetes that is associated with NH, yet its application in a surgical population has not been studied. Our study examined the association between CRS, NH, and complications in patients undergoing elective surgery. In this retrospective cross-sectional study of adult surgical patients admitted to a tertiary care center over 4 years, subjects with NH (blood glucose ≥140 mg/dL in nondiabetics) were identified, and the CRS was calculated. CRS, NH, and clinical outcomes were adjusted for race/ethnicity, payor type, and Elixhauser Comorbidity Index. Patients were stratified by surgery type (cardiac/vascular, general, orthopedic, and neurologic), and multivariate regression analyses assessed the association between CRS, NH, and clinical outcomes. Of 10,531 subjects included in the study, 24% developed NH. After adjusting for covariates, the CRS was significantly associated with the development of complications (odds ratio [OR], 2.09 [1.69, 2.59]; p&lt;.001) and NH (OR, 1.95 [1.66, 2.29]; p&lt;.001). When stratifying by surgery type, CRS was significantly associated with NH, length of stay, and complications in the neurosurgery and orthopedic surgery cohorts, but not cardiac/vascular or general surgery. NH, when adjusted for covariates, was associated with 30-day readmission rates (OR, 1.52 [1.23, 1.86]; p&lt;.001) and length of stay (linear model estimate, 0.61 [0.57, 0.66]; p&lt;.001), but not with complication outcomes. CRS was associated with the development of NH and complications in elective neurological and orthopedic surgery patients and could help identify high-risk surgical patients. Further study should evaluate if treatment of NH is associated with better outcomes in CRS high-risk patients.

Disclosure
H.Lee: None. P.J.Hartfield: None. G.Sinson: None. M.C.Wang: Consultant; Medtronic, Zimmer Biomet. A.Z.Dawson: None. A.Thorgerson: None. C.E.Mendez: Speaker's Bureau; Siemens.