bluuebunny/crossref_metadata_2025_split huggingface dataset:
1216-P: Prevalence of SGLT2i and GLP1RA Use among U.S. Adults with Type 2 Diabetes
Authors: LIMONTE CHRISTINE , HALL YOSHIO , TRIKUDANATHAN SUBBULAXMI , TUTTLE KATHERINE R. , HIRSCH IRL B. , DE BOER IAN , ZELNICK LEILA 
Published: May 2022

Objective: To determine the prevalence of sodium-glucose contransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1RA) use among adults with type 2 diabetes (T2D) in the United States.
Methods: We studied adults with T2D and eGFR ≥30mL/min/1.73m2 who participated in the National Health and Nutrition Examination Survey (NHANES) , focusing on the 2017-2020 examination cycle. We tested prevalence of SGLT2i and GLP1RA use among subgroups based on demographic variables and relevant comorbidities, including chronic kidney disease (CKD) , congestive heart failure (CHF) , and atherosclerotic cardiovascular disease (ASCVD) . We compared use of SGLT2i and GLP1RA to other glucose-lowering medications and assessed trends from prior NHANES cycles.
Results: Among 1,375 participants studied in 2017-2020, mean age was 60 years, 46% were women, 13% self-identified as non-Hispanic Black, 10% self-identified as Mexican American, 37% had CKD, 8.5% had CHF, and 23% had ASCVD. The prevalence of SGLT2i and GLP1RA use was 5.8% and 4.4%, respectively. SGLT2i were used by 7.2% of adults with CKD or CHF, and GLP1RA were used by 3.5% of adults with ASCVD. Differences in SGLT2i or GLP1RA use were observed by age, race, ethnicity, and health insurance status. Biguanides, sulfonylureas, DPP-4 inhibitors, and insulin were used more frequently than SGLT2i or GLP1RA. Overall, prevalence of SGLT2i but not GLP1RA use increased significantly from 2013-2014 to 2017-2020.
Conclusions: SGLT2i and GLP1RA use is low among adults with T2D, including among those with strong indications. Enhanced implementation of these agents is crucial to improving kidney and cardiovascular outcomes and mitigating health disparities in T2D.

Disclosure
C.Limonte: None. Y.Hall: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. L.Zelnick: None.

Funding
This work was supported by an unrestricted fund from the Northwest Kidney Centers. CPL was funded by NIDDK grant T32DK007467 and the American Kidney Fund Clinical Scientist in Nephrology grant program. Additional funding was provided by R01DK126373, R01DK125084, R01DK088762.
1217-P: The Impact of Diabetes on Mortality and Clinical Outcomes in Hospitalized Patients with COVID-in the Capital Region of Denmark
Authors: KLIIM-HANSEN VIVIAN , NYELAND MARTIN E. , GASBJERG LÆRKE S. , JIMENEZ-SOLEM ESPEN , PETERSEN TONNY S. , ELLEGAARD ANNE-MARIE , KNOP FILIP K. , CHRISTENSEN MIKKEL B. 
Published: May 2022

During the COVID-pandemic, patients diagnosed with diabetes have been overrepresented among patients admitted to hospital with COVID-19. We explored the impact of diabetes on mortality and clinical outcomes in hospitalized patients with COVID-in the Capital Region of Denmark. All patients from the Capital Region of Denmark admitted to hospital with COVID-in the period from February 2020 to March 2021 were included. Patients with a diabetes diagnosis were compared to patients without a diabetes diagnosis in multivariable adjusted analyses. The primary outcome was death within 30 days from hospitalization. Secondary outcomes included time to discharge, use of oxygen treatment, referral to intensive care unit, and use of respirator. Among 3,997 hospital admitted patients, 1,186 had diabetes (1,090 type 2 diabetes; 96 type 1 diabetes) . The patients with diabetes were 59% men, 72±13 years (mean±standard deviation) with BMI 28±6.4 kg/m2, while patients without diabetes were 51% men, 67±years with BMI 26±5.8 kg/m2. Within 30 days, 292 (24.6%) patients with diabetes died compared to 521 (18.5%) without diabetes (adjusted odds ratio (aOR) 1.28 (95% CI 1.02-1.6) for death) . Patients with diabetes were 24% less likely to be discharged alive at any given time compared to patients without diabetes with a hazard ratio of 0.76 (0.70-0.81) . aOR for oxygen treatment was 1. (0.97-1.47) , for referral to intensive care unit 1.37 (1.01-1.85) , and for use of respirator 1. (0.86-1.65) . We found that hospitalized COVID-patients with diabetes had a 28% higher risk of dying within 30 days and were 19% more likely to receive intensive care treatment than hospitalized COVID-patients without diabetes.

Disclosure
V.Kliim-hansen: None. M.E.Nyeland: None. L.S.Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. E.Jimenez-solem: None. T.S.Petersen: None. A.Ellegaard: n/a. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. M.B.Christensen: None.

Funding
Novo Nordisk Foundation (NNF20SA0062873)
122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart
Authors: GOEDEKE LEIGH , MA YINA , ZHANG JIASHENG , GUERRERA NICOLE , WU XIAOHONG , ZHANG DONGYAN , KAHN MARIO , ZHANG XIAN-MAN , YOUNG LAWRENCE H. , SHULMAN GERALD I. 
Published: May 2022

Several studies highlight the potential for SGLT2 inhibitors (i) to exert their cardioprotective effects by shifting myocardial fuel utilization towards ketone oxidation. However, direct in vivo measurements of cardiac mitochondrial substrate oxidation in awake rodents during heart failure are lacking, and whether SGLT2i-mediated increases in ketone availability and oxidation are able to improve cardiac efficiency remains unclear. Here, we examined the effect of acute SGLT2 inhibition with dapagliflozin (dapa) on cardiac function and mitochondrial metabolism in awake male Sprague Dawley rats 2 weeks after induction of heart failure by permanent ligation of the left anterior descending coronary artery. Echocardiography and in vivo metabolic flux studies were performed 4-6 h after oral dapa (1.5 mg/kg) or vehicle treatment in sham-surgerized rats and rats with myocardial infarction (MI) . Acute dapa treatment caused a 15% decrease in fasting plasma glucose concentrations and 50% increase in fasting plasma NEFAs, whole-body βOHB turnover and plasma βOHB levels in sham and MI rats (all P&lt;0.05 vs. VEH) . Dapa treatment decreased left ventricular (LV) [14C]deoxyglucose uptake and relative rates of pyruvate oxidation to total mitochondrial oxidation (VPDH/VCS) by 40-60%. Dapa treatment also caused a 60% increase in relative rates of LV ketone oxidation to total mitochondrial oxidation (VβOHB/VCS) in sham and MI rats (all P&lt;0.05 vs. VEH) , independently of changes in cardiac metabolic gene expression. Interestingly, the dramatic shift in substrate utilization caused by acute dapa treatment did not significantly alter cardiac output or LV ejection fraction. Acute dapa treatment also did not significantly alter myocardial acetyl-CoA content, malonyl-CoA content, ATP/ADP ratios or ATP/AMP ratios in the LV myocardium remote from the infarct.
Conclusion: Taken together, these results demonstrate that single-dose dapa treatment, which acutely decreased LV myocardial pyruvate oxidation and increased LV ketone oxidation, was not sufficient to alter cardiac output or LV ejection fraction.

Disclosure
L. Goedeke: Other Relationship; The Liver Company, Inc. . G. I. Shulman: Advisory Panel; 89bio, Inc., AstraZeneca, Equator Therapeutics, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Consultant; DiCerna Pharmaceuticals, Inc., Novo Nordisk, Other Relationship; Generian Pharmaceuticals, iMetabolic Biopharma Corporation, Maze Therapeutics, The Liver Company, Stock/Shareholder; Levels Health, Inc. . Y. Ma: None. J. Zhang: n/a. N. Guerrera: None. X. Wu: None. D. Zhang: None. M. Kahn: None. X. Zhang: None. L. H. Young: None.

Funding
NIH (P30 DK045735 and K99 HL150234) , AstraZeneca (NCR-19-20028)
1221-P: Clinical Significance of Autoantibody Measurement for Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 in the Plasma
Authors: YAMAGATA HIROKI , ONISHI SHUNICHIRO , YOSHIDA TOMOHIKO , HIWASA TAKAKI , TAKEMOTO MINORU 
Published: May 2022

Background: Polyclonal autoantibodies against various proteins that do not cause autoimmune diseases have been reportedly observed in the serum. The presence of polyclonal antibodies against glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have been observed in the blood of patients who have not previously used the GLP-1 receptor agonist. Therefore, this study aimed to investigate the clinical significance of measuring anti-GIP and GLP-1 autoantibodies (Abs) in the plasma. Two groups consisted of 1healthy donors (HD) and 274 patients with diabetes mellitus (DM) were investigated. AlphaLISA was used to measure both GIP and GLP-1 Abs. This study was approved by the ethical review board of our university (approval number 21-Im-03) .
Results: The serum concentration of anti-GIP Abs was significantly greater in the DM group than in the HD group (2697.6 ± 1998 vs. 2277.6 ± 821, p = 0.0001) , while the levels of anti-GLP-1 Abs were not different between the two groups. Since the concentration of anti-GIP Abs was significantly related to age, binary logistic regression analysis was perfomed for adjusting the age factor to reveal that anti-GIP Abs were greater with DM than without (OR: 1.0004; 95% CI 1.0001-1.001, p = 0.049) . Discussion: Several autoantibodies have been reportedly used as markers for various diseases, such as atherosclerosis, diabetes, and cancers. We found that the patients with DM had greater serum levels of anti-GIP Abs than those without it, indicating that the functions of GIP are inhibited in the presence of anti-GIP Abs in patients with DM. Since GIP is an insulinotropic intestinal hormone and the GLP-1/GIP dual agonist have been demonstrated to reduce both HbA1c and body weight, the functions of GIP inhibited by anti-GIP Abs may worse glucose metabolism.
Conclusions: The patients with DM showed higher levels of anti-GIP autoantibodies.

Disclosure
H.Yamagata: None. S.Onishi: None. T.Yoshida: None. T.Hiwasa: None. M.Takemoto: None.
1225-P: Urinary Metal Exposures and Risk of All-Cause and Cause-Specific Mortality in U.S. Adults with Diabetes
Authors: YANG JINGLI , LO KENNETH , LI JINHUI , ZHOU YANQIU , YANG QINGHUA , YANG AIMIN 
Published: May 2022

Introduction: Whether environmental exposure to heavy metals is associated with long-term mortality in adults with diabetes remains controversial. We evaluated the associations of urinary metal levels (antimony [Sb], arsenic, barium, cadmium [Cd], cesium, cobalt [Co], lead [Pb], platinum [Pt], mercury, molybdenum, and uranium) with risk of all-cause, cardiovascular disease (CVD) , cancer, and diabetes related mortality in U.S. adults with diabetes in the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2014.
Methods: We conducted a prospective cohort analysis of 14,975 adults in NHANES 1999-2014 surveys followed up until end of 2014. We used Cox regression model to examine the hazard ratio (HR) of outcomes adjusted for potential risk factors at baseline. Urinary metal levels were creatinine-adjusted, and log 10-transformed to reduce skewness.
Results: Of 14,975 adults, 2,167 (14.5%) had diabetes at baseline. During a mean follow-up of 7 years, 475 (21.9%) died (113 CVD, 92 cancer, and 138 diabetes related mortality) . The age of the participants ranged from 20 to 85 years. Urinary Cd (HR=1.87, 95% CI: 1.29-2.71) , Pb (HR=1.55, 95% CI: 1.12-2.15) , Co (HR=1.65, 95% CI: 1.23-2.20) , Sb (HR=1.59, 95% CI: 1.18-2.14) , Pt (HR=1.40, 95% CI: 1.15-1.70) was associated with higher all-cause mortality. In cause-specific analysis, urinary Cd, Pb, and Pt level was associated with high cancer mortality. Urinary Cd, Co, Sb, and Pt was associated with diabetes related mortality, while Sb and Pt was associated with increased CVD related mortality.
Conclusion: Urinary Cd, Pb, Co, Sb, Pt levels was associated with all-cause mortality and cause-specific mortality in adults with diabetes. More studies on the association of toxic metals with death risk in people with diabetes are warranted.

Disclosure
J.Yang: None. K.Lo: None. J.Li: None. Y.Zhou: None. Q.Yang: None. A.Yang: None.
1226-P: Cadmium Exposure and Long-Term Risk of All-Cause and Cause-Specific Mortality in Adults with and without Diabetes: A Population-Based Cohort Study
Authors: YANG QINGHUA , YANG JINGLI , YANG AIMIN 
Published: May 2022

Introduction: Whether environmental exposure to cadmium (Cd) is associated with long-term mortality in adults with and without type 2 diabetes (T2D) is unclear. We examined the association of urinary Cd level with risk of all-cause, cardiovascular disease (CVD) and cancer mortality in U.S. adults in the National Health and Nutrition Examination Survey (NHANES) .
Methods: We performed a prospective analysis of 11765 adults with (n=1900) and without (n=9865) T2D in NHANES 1999-2014 surveys followed up until 2014. We used Cox regression model to estimate the hazard ratio (HR) of outcomes with creatinine-adjusted Cd levels in urine adjusting for age, sex, education, ethnicity, body mass index, smoking status, and medical comorbidities (CVD, hypertension, dyslipidemia and chronic kidney disease) and other ten urinary metal levels.
Results: Of 11765 adults, 10.8% died, and 2.3% and 2.5% died due to CVD and cancer respectively during a median follow-up of 6.7 years. The median (IQR) level of urinary Cd was 0.25 (0.14-0.47) ug/g of creatinine. Per log 10-transformed unit urinary Cd increase was associated with higher risk of all-cause mortality in both with (HR=1.87, 95% CI: 1.29-2.71) and without (HR=2.22, 95% CI: 1.76-2.80) T2D, and CVD (HR=2.42, 95% CI: 1.42-4.13) and cancer (HR=4.01, 95% CI: 2.76-5.83) mortality in adults without T2D. Neutral risk of CVD (HR=1.45, 95% CI: 0.64-3.28) and caner (HR=2.42, 95% CI: 1.00-5.83) mortality were observed in T2D.
Conclusions: Urinary Cd was associated with long-term mortality and varied by diabetes. Further studies on the association of environmental exposure toxic metals with long-term risk of death risk are warranted.

Disclosure
Q.Yang: None. J.Yang: None. A.Yang: None.
1228-P: Medication Adherence and Cardiometabolic Control in American Indians with Type 2 Diabetes: Pilot Study
Authors: NELSON TARAH N. , YAO YINGWEI , DEVAUGHAN-CIRCLES ASHLEY , WILKIE DIANA J. , SCARTON LISA 
Published: May 2022

Introduction: American Indians (AIs) have high rates of type 2 diabetes (T2D) and comorbidities. Mortality risk is increased by uncontrolled cardio-metabolic factors and significantly reduced by antihypertensive, glucose- and lipid-lowering medication adherence. Medication adherence is low among AIs living in non-Indian Health Services (IHS) healthcare settings, but little is known about medication adherence among AIs who primarily receive their medications from IHS/tribal facilities. The study aim was to identify cardio-metabolic control factors (hemoglobin A1c [HbA1c], low density lipoprotein [LDL-C], and systolic blood pressure [SBP]) and antihypertensive, glucose- and lipid-lowering medication adherence in adults with T2D who use Choctaw Nation of Oklahoma (CNO) Health Services.
Methods: Enrolled CNO tribal members with T2D over 18 years of age with at least one pharmacy visit and at least one HbA1c measure in 2017 (N=5,970, mean age 58.0±13.4, 52% female) were included in this descriptive pilot study. We used the earliest values of HbA1c, LDL-C and SBP in the measurement period. Medication adherence (proportion of days covered [PDC]) was calculated using 2017 CNO electronic health record (EHR) data. Medication classes included biguanides, statins, and ACE/ARBs.
Results: Fifty-six percent had HbA1c measurements above the target of 7%, 42% had LDL-C greater than 100mg/dL, and 63% had SBP above target of 130 mmHg. Thirty-six percent had both HbA1c and SBP levels above target. The percentage of patients with PDC ≥.80 was 63% for biguanides, 66% for statins, and 70% for ACE/ARBs.
Discussion/Conclusions: Previous studies have reported similar findings for cardio-metabolic control factors as well as higher medication adherence rates. Future studies should focus on examining prescription and pharmacy refill data longitudinally and should include a subgroup of patients to understand facilitators of and barriers to medication adherence not available within EHR data.

Disclosure
T.N. Nelson: None. Y. Yao: None. A. DeVaughan-Circles: None. D.J. Wilkie: Other Relationship; eNursing llc. L. Scarton: None.
123-OR: Shotgun LC/MS Proteomics Uncovers Potential Markers of Diabetic Foot Osteomyelitis
Authors: SHERWOOD AMBER , RUBITSCHUNG KATIE L. , CRISOLOGO PETER , HWANG HELENA , LAVERY LAWRENCE A. , OZ ORHAN K. 
Published: May 2022

Osteomyelitis is the leading cause of non-traumatic lower limb amputation in patients living with diabetes. The pathophysiology of diabetic foot osteomyelitis (DFO) is complex and incompletely understood. Using FFPE bone biopsies obtained from patients with suspicious clinical presentation of DFO, we characterized the proteome of bone infection in the diabetic microenvironment. A discovery LC/MS approach was used to identify molecules of interest in subjects diagnosed with DFO versus no DFO based on histopathology findings. In total, 2,135 proteins were identified across 18 DFO and 12 non-DFO TMT labeled samples. After applying data filtering and imputing missing values, 668 proteins were retained for statistical analysis. Of 66 significant proteins (p&lt;0.05) , 8 demonstrated twofold abundance decreases in DFO with respect to non-DFO samples, while 8 proteins were enriched by at least onefold. Ontological analysis suggested that proteins regulating chemokine signaling and integrin mediated cascades are reduced in DFO, potentially resulting in suppression of downstream MAPK pathways, and impairing inflammatory response and cellular adhesion. Our analysis demonstrates that archived FFPE samples are a rich source for elucidating molecular mechanisms associated with diabetic foot infection and may improve accuracy of diagnosis, contribute to novel therapeutic approaches, and uncover new disease biomarkers.

Disclosure
A.Sherwood: None. K.L.Rubitschung: None. P.Crisologo: None. H.Hwang: None. L.A.Lavery: Advisory Panel; Acera Surgical Inc., Uluru, Research Support; Integra, Smith+Nephew, Tissue tech. O.K.Oz: None.

Funding
American Diabetes Association (1-17-ICTS-056) ;
1231-P: Using Natural Language Processing (NLP) to Understand Self-Reported Barriers and Enablers to Treatment Adherence in Type 2 Diabetes (T2D) Using Data from the International Diabetes Management Practices Study (IDMPS)
Authors: CHAN JULIANA C. , GAGLIARDINO JUAN J. , ILKOVA HASAN M. , RAMACHANDRAN AMBADY , MBANYA JEAN CLAUDE , SHESTAKOVA MARINA V. , ROLLOT MELISSA , BLANCHON MARGOT , HAYAT PAUL , CHANTELOT JEAN-MARC , ASCHNER PABLO 
Published: May 2022

Introduction: IDMPS is an international, observational study to assess care practices and clinical profiles of people with diabetes in developing countries. Treatment non-adherence is a major barrier to treatment effectiveness. Open-ended self-reported reasons for omitting or adhering to glucose-lowering drugs in people with T2D were analyzed.
Methods: NLP and clustering methods were used to analyze responses on omitting medications (Q1) , not taking medications as prescribed (Q2) , and methods to improve adherence (Q3) , with Q1+2 responses merged as reasons for ‘omission’.
Results: Of 2475 participants from 13 countries (mean ± SD age 58 ± 12 years, 49% male, diabetes duration ± 8 years, 43% on insulin) , 85%, 79%, and 37% had responses for Q1-3 respectively. Of these, 36% had responses indicative of non-adherence, 62% of adherence, and 2% uncertain responses (Q1+2) . Non-adherent patients were younger (55 ± 12 vs. 60 ± 12 years) , had shorter diabetes duration (± 8 vs. 12 ± 9 years) , and higher HbA1c (8.3 ± 1.9 vs. 7.9 ± 1.8 %) vs. adherent patients (all p&lt;0.001) . Patient responses for adherence/non-adherence are shown in Figure.
Conclusions: Conflicts with daily routine are the main barrier to therapy adherence, while planning and habit formation can improve adherence.

Disclosure
J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. J.Chantelot: Employee; Sanofi, Stock/Shareholder; Sanofi. P.Aschner: Advisory Panel; Merck & Co., Inc., Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. J.J.Gagliardino: None. H.M.Ilkova: Advisory Panel; Novo Nordisk. A.Ramachandran: None. J.Mbanya: Advisory Panel; Novo Nordisk, Sanofi, Servier Laboratories. M.V.Shestakova: None. M.Rollot: Other Relationship; Sanofi. M.Blanchon: Other Relationship; Sanofi. P.Hayat: Other Relationship; Sanofi.

Funding
Sanofi