bluuebunny/crossref_metadata_2025_split huggingface dataset:
1067-P: A National Physician Survey Examining Clinical Scenarios for Deintensifying Diabetes Medications
Authors: PILLA SCOTT J. , SCHOENBORN NANCY , BOYD CYNTHIA , GOLDEN SHERITA , MATHIOUDAKIS NESTORAS N. , MARUTHUR NISA M. 
Published: May 2022

Many older adults with type 2 diabetes (T2D) are tightly controlled with high hypoglycemia risk medications and may benefit from deintensifying (stopping/reducing) or switching to newer medications. As deintensifying rarely occurs in practice, we aimed to determine how physicians make these decisions. We conducted a national survey of a random sample of US physicians in general medicine, geriatrics, and endocrinology. The survey was designed by a team of patients, caregivers, and physicians, and distributed in 3 mailing waves. Physicians were asked what action they would take in three scenarios of patients with T2D treated below individualized targets: 1) a healthy 79F with HbA1c 6.3% on a sulfonylurea; 2) a 77M with stage 4 kidney disease with HbA1c 7.3% on basal insulin; 3) a 78F with advanced dementia with HbA1c 7.7% on a sulfonylurea. Scenarios started with a base case of the patient reporting no medication issues, then varied hypoglycemia history, health, and patient preferences. Statistical comparisons used multinomial logistic regression accounting for clustering. We received 427 responses to date, response rate 27%. In the base case, 57% of physicians made no change to the high-risk medication, 16% switched, 12% decreased, 12% stopped, and 3% increased. Decreasing/stopping occurred over twice as often in scenario 1 than other scenarios (p&lt;0.001) . In scenario variations, hypoglycemia of any severity led &gt;95% of physicians to decrease, stop or switch the high-risk medication. Worsening health status also caused substantially more deintensification, but polypharmacy, financial barriers, and patient preference did not. Endocrinologists were 3-5 times as likely to switch medications compared to other specialties (p&lt;0.001) . Overall, we found clinical inertia to deintensify high-risk diabetes medications, especially in medically complex patients with HbA1c &gt;7.0%. Hypoglycemia and worsening health were strong motivators to deintensify or switch to newer medications.

Disclosure
S.J.Pilla: None. N.Schoenborn: None. C.Boyd: Other Relationship; Dynamed, UpToDate. S.Golden: Advisory Panel; Abbott Diabetes, Medtronic. N.N.Mathioudakis: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions.

Funding
National Institutes of Health (1R24AG064025 and 1K23DK128572)
1069-P: A National Physician Survey of Perspectives on Deintensifying Diabetes Medications
Authors: PILLA SCOTT J. , WANG ISABELLE J. , SCHOENBORN NANCY , BOYD CYNTHIA , GOLDEN SHERITA , MATHIOUDAKIS NESTORAS N. , MARUTHUR NISA M. 
Published: May 2022

Deintensifying diabetes medications rarely occurs for older adults with type 2 diabetes (T2D) despite many being tightly controlled with hypoglycemia-inducing medications. We conducted a national survey of US physicians to understand their perspectives on deintensification for older adults with T2D. The survey was designed by a team of patients, caregivers, and physicians, and distributed to a random sample of physicians in general medicine, geriatrics, and endocrinology in three mailing waves. Respondents rated the importance of deintensifying, and of switching to a medication with a better risk/benefit profile, on 5-point Likert scales; the frequency of these actions in the past 3 months; and barriers/facilitators. We received 427 completed surveys to date, response rate 27%. The Figure shows physicians’ responses. Our findings show that the vast majority of US physicians view deintensifying diabetes medications as important to the care of older adults, although they accomplish this infrequently. Major barriers were physicians’ views that patients were reluctant to change medications or to allow their glucose to be higher. Adverse events, especially hypoglycemia, were strong facilitators, as was reducing cost of therapy. Geriatricians reported deintensifying more often than other specialties. Endocrinologists switched medications more often and were more concerned about short-term hyperglycemia.

Disclosure
S.J.Pilla: None. I.J.Wang: None. N.Schoenborn: None. C.Boyd: Other Relationship; Dynamed, UpToDate. S.Golden: Advisory Panel; Abbott Diabetes, Medtronic. N.N.Mathioudakis: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions.

Funding
National Institutes of Health (1R24AG064025 and 1K23DK128572)
1077-P: Assessing the Relationship among Multimorbidity, Psychosocial Factors, and Clinical Outcomes in Older Adults Living in Rural Appalachia
Authors: SMALLS BRITTANY L. , ADEGBOYEGA ADEBOLA , SIMON-OKUBE PATIENCE , WESTGATE PHILIP , SCHOENBERG NANCY 
Published: May 2022

Type 2 diabetes (T2DM) is a significant public health burden in rural Appalachian Kentucky, with an estimated one in four older adults diagnosed with T2DM. To determine factors associated with T2DM, we assessed the relationship between multimorbidity (MM) , psychosocial factors, and clinical outcomes among 148 older adults with T2DM along with one or more comorbid conditions, living in rural Appalachian Kentucky. A community-based sample of Appalachian residents provided data on diabetes knowledge, chronic conditions in addition to T2DM, demographics, and clinical measures (HbA1c, blood pressure) using point-of-care methods.The sample population (N=148) had an average age of 72.2 years (± 5.4) and were mostly women (66%) and White (98%) , reflecting the region’s demographics. The average HbA1c was 7.6 (±1.3) and systolic and diastolic blood pressure were 145.2 (±20.8) mmHg and 81.9 (±12.6) mmHg, respectively. Participants reported having 2.3 (±1) chronic conditions in addition to T2DM. As for psychosocial factors, participants reported average score stress 20.7 (±9.1) , distress 26.7 (±10.7) , and social support 115.0 (±15.9) . There was a significant relationship between MM and HbA1c (β=0.27, SE=0.13, p=0.04) and stress (β=0.23, SE=0.08, p=0.004) . However, distress, social support, disability, and depression did not have significant relationships with MM in this sample.These findings elucidate the burden of MM in older adults who are living with T2DM in a rural environment. Though MM is not unique to the aging population, understanding how MM effects clinical outcomes and T2DM related psychosocial factors is important. In most cases, properly managing T2DM could reduce (or prevent) severity and complications of comorbid conditions. Thus, identifying psychosocial factors that are associated with clinical outcomes provides a pathway for targeted interventions to improve health outcomes for this vulnerable population.

Disclosure
B.L.Smalls: None. A.Adegboyega: None. P.Simon-okube: None. P.Westgate: None. N.Schoenberg: n/a.

Funding
NIDDK RDK112136NIDDK K01DK116923
1079-P: Effectiveness and Safety of Empagliflozin in Routine Care: Results from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: HTOO PHYO T. , TESFAYE HELEN , PAIK JULIE M. , WEXLER DEBORAH J. , NAJAFZADEH MEHDI , GLYNN ROBERT , DERUAZ-LUYET ANOUK , FARSANI SOULMAZ F. FAZELI , KOENEMAN LISETTE , SCHNEEWEISS SEBASTIAN , PATORNO ELISABETTA 
Published: May 2022

EMPRISE is a 5-year monitoring program that evaluates the effectiveness and safety of empagliflozin (EMPA) using Medicare and 2 U.S. commercial claims [2014-20 (2018 for Medicare) ]. We identified 190,226 patients ≥18 years with type 2 diabetes initiating EMPA or a dipeptidyl peptidase-4 inhibitors (DPP-4i) , and followed them up for heart failure hospitalization in primary (HHF-Specific) or any discharge positions (HHF-Broad) , a composite of myocardial infarction (MI) and stroke, and all-cause mortality (ACM) (Medicare only) . Safety outcomes were lower-limb amputations (LLA) , non-vertebral fractures, diabetic ketoacidosis (DKA) , acute kidney injury (AKI) , renal and bladder cancers (CA) . We estimated pooled HR (95% CI) after propensity score matching, adjusting for 143 baseline covariates. Compared to DPP4i, EMPA was associated with a reduced risk of HHF [HHF-Specific: 0.47 (0.41, 0.55) ; HHF-Broad: 0.67 (0.62, 0.72) ], a similar risk of the composite of MI or stroke [0.92 (0.84, 1.02) ], and a reduced risk of ACM [0.56 (0.46, 0.68) ]. EMPA was associated with a reduced risk of AKI [0.73 (0.68, 0.78) ], an increased risk of DKA [1.88 (1.51, 2.34) ], and a similar risk of LLA, fractures, and renal and bladder CA. Our findings support the cardiovascular effectiveness of EMPA in routine care with a safety profile in line with documented information.

Disclosure
P.T.Htoo: Employee; Johnson & Johnson. S.Schneeweiss: Consultant; Aetion, Inc., Research Support; Boehringer Ingelheim International GmbH. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. H.Tesfaye: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. M.Najafzadeh: None. R.Glynn: Research Support; Amarin Corporation, AstraZeneca, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. A.Deruaz-luyet: Employee; Boehringer Ingelheim International GmbH, Other Relationship; IQVIA Inc., Sanofi. S.F.Fazeli farsani: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.
108-OR: The Effect of Human Pregnancy on Morphology of the Endocrine Pancreas
Authors: EGAN AOIFE M. , HER TRACY K. , VELLA ADRIAN , MATVEYENKO ALEKSEY 
Published: May 2022

In animal models, pregnancy is associated with distinct morphological and functional adaptations in the endocrine pancreas, particularly characterized by β cell hyperplasia and hypertrophy. Failed islet adaptation to increased metabolic demands in pregnancy contributes to the development of gestational diabetes. However, the effects of pregnancy on the remodeling of human endocrine pancreas remain largely unknown. To address this, we used human pancreatic autopsy specimens from 8 women who died during pregnancy or within 6 weeks postpartum (P/PP) , and 16 women who were matched by age and body mass index (BMI) to serve as controls (CON) who were not pregnant at death. Subjects had a complete autopsy with pancreatic tissue of adequate quality/quantity stored and a corresponding medical record. Consecutive pancreatic sections were co-immunostained for key islet cell markers including Insulin, Glucagon and Glucagon-Like Peptide-1 (GLP-1) as well as a marker of cell proliferation (Ki-67) . Although the pancreatic fractional insulin area (β cell area) was comparable between P/PP and CON groups, the glucagon and the GLP-1 positive areas were substantially increased ∼2-fold in the P/PP group (p&lt;0.05) . Our analysis also revealed an increase in the proportion of GLP-1/glucagon double positive islet cells (p&lt;0.05) in PP/P subjects, suggesting a modulatory effect of pregnancy in favor of increased islet GLP-1 production in α cells. Consistently, P/PP subjects demonstrated an increase in α cell expression of prohormone convertase 1/3 (PC1/3) (p&lt;0.05) , an enzyme responsible for the proteolytic cleavage of GLP-1 from proglucagon. Finally, the frequency of both β and α cell proliferation was comparable between groups (p&gt;0.05) . While prior pre-clinical studies have focused solely on functional and morphological changes in pancreatic β cells, our data suggest that proglucagon gene products (glucagon and GLP-1) may play an underappreciated role in (or serve as markers of) the metabolic changes impacting human pregnancy.

Disclosure
A.M.Egan: None. T.K.Her: None. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk. A.Matveyenko: None.

Funding
National Institutes of Health (K12 HD065987/HD/NICHD)
1080-P: Sex-Specific Associations between Risk-Factor Control and Incident CVD in Diabetic Patients
Authors: WANG XUAN , MA HAO , FONSECA VIVIAN , QI LU 
Published: May 2022

Background: Women with diabetes are at higher risk of CVDs than men. We investigated the associations between the degree of risk factor control and CVD in women and men with diabetes.
Methods: A total of 16,760 diabetes patients from UK Biobank were included. The exposure was the number of optimized risk factors including HbA1c level &lt;53 mol/mol (7%) , blood pressure &lt;140/90 mm/Hg, and non-HDL-cholesterol &lt;130 mg/dl.
Results: During a mean follow-up of 8.4 years, 2000 incident CVD were documented, including 1685 IHD and 412 stroke. Number of risk-factor control was inversely associated with the risks of IHD, stroke and total CVD, and such associations were stronger in women than men (P for interaction with sex=0.012, 0.018 and 0.017, respectively) . The two most important risk factors for men were blood pressure and non-HDL-cholesterol, while for women were HbA1c and non-HDL-cholesterol. In addition, as compared with non-diabetic controls, the diabetes-related risk of CVD was theoretically eliminated when 2 or more risk-factors were under control in women, and 3 risk-factors were under control in men.
Conclusion: Among diabetes patients, to control the risk factors within the target range benefit more in women than men in preventing subsequent risk of CVD. Our findings highlight the importance of raising awareness of control of risk factors and provide evidence for the sex-specific priority of control strategies.

Disclosure
X.Wang: None. H.Ma: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. L.Qi: None.

Funding
National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024) , the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616)
1081-P: Blood Pressure Variability Is Associated with Risk of Heart Failure, Elevated NT-proBNP, and High-Sensitivity Troponin: Results from MESA
Authors: NUYUJUKIAN DANIEL S. , ZHOU JIN , KOSKA JURAJ , NWABUO CHIKE , BERTONI ALAIN , SHEA STEVEN , REAVEN PETER 
Published: May 2022

The association between blood pressure variability (BPv) and heart failure (HF) is incompletely studied. This association, and its links with biomarkers of HF and cardiac injury, were examined in the community-based Multi-Ethnic Study of Atherosclerosis (MESA) . Resting seated BP was measured thrice; the average of the last two measures was used for analysis, and visit-to-visit BPv (coefficient of variation-CV) was assessed over 5 visits. Biomarkers of HF (N-terminal B-type natriuretic peptide: NT-proBNP) and cardiac injury (high-sensitivity troponin-T: hs-cTnT) , respectively, at exams 1, 3 and 5 were ascertained. With 9.4 years median follow-up in 6,785 individuals, 385 HF events occurred. In adjusted time-dependent models including CVD risk factors, BMI, BP medications, and cumulative mean BP, BPv (CV-SBP and CV-DBP) was associated with risk of clinical HF (e.g., CV-SBP HR=1.16, p=0.03) . Similar patterns were seen regardless of T2D status. The associations were stronger for HF with reduced ejection fraction (EF) vs. preserved EF. When excluding those with baseline NT-proBNP &gt;450 pg/mL or hs-cTnT &gt;14 ng/L, the association between BPv and HF became stronger. CV-SBP and CV-DBP were also associated with elevated exam 5 NT-proBNP (&gt;450 pg/mL: OR=1.74, and OR = 1.32, p&lt;0.001) . We saw a positive relationship between CV-SBP and exam 1 to exam 5 changes in NT-proBNP (p=0.001) and hs-cTnT (p&lt;0.001) as well as elevated hs-cTnT (&gt;14 ng/L; OR=1.18, p&lt;0.001) . Our data strongly support an association between BPv and both clinical HF and elevated NT-proBNP, and the association was greater in those with reduced vs. preserved EF. The association between BPv and clinical HF was related to deleterious changes in subclinical markers of myocardial injury and heart failure.

Disclosure
D.S.Nuyujukian: None. J.Zhou: Research Support; Dexcom, Inc. J.Koska: None. C.Nwabuo: None. A.Bertoni: None. S.Shea: Research Support; National Heart, Lung, and Blood Institute. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc.

Funding
NIH/NHLBI (F32HL156626) NIH/NHLBI (R21HL150374) NIH/NHLBI (R21HL150268) NIH/NHLBI (R01HL138969)
1086-P: Cardiovascular Effectiveness of SGLT2 Inhibitors: Head-to-Head Comparisons
Authors: ABRAHAMI DEVIN , D’ANDREA ELVIRA , PAIK JULIE M. , WEXLER DEBORAH J. , EVERETT BRENDAN M. , KIM SEOYOUNG C. , PATORNO ELISABETTA 
Published: May 2022

In placebo-controlled cardiovascular (CV) outcome trials, SGLT2 inhibitors (SGLT2i) reduced the risk of CV events in patients with T2D and CV disease. However, not all trials showed consistent CV benefits across individual SGLT2i. We assembled a cohort of adults with T2D (median age 62, 57% male) , newly treated with an SGLT2i (canagliflozin, dapagliflozin, empagliflozin) from Medicare and two US commercial healthcare claims databases (4/2012 - 12/2020) . We assessed the risk of a composite event of myocardial infarction (MI) or stroke (MI/stroke) , its individual components, hospitalization for heart failure (HHF) , and mortality. To account for differences between initiators of different SGLT2i, we reweighed each group using inverse probability of treatment weights, adjusting for &gt;130 baseline characteristics. In each database, hazard ratios (HRs) and 95% CI were estimated using Cox proportional hazards models and results were pooled using random-effects models. Compared to canagliflozin, the most frequently used SGLT2i during the study period, dapagliflozin and empagliflozin had a similar risk of MI/stroke, though empagliflozin was associated with a reduced risk of HHF [HR (95% CI) = 0.73 (0.57-0.94) ], over a median 0.65 years of follow-up. Individual SGLT2i showed a similar risk of other outcomes (Table) . This study suggests that SGLT2i have similar effectiveness on most CV outcomes and mortality in patients with T2D.

Disclosure
D.Abrahami: None. E.D’andrea: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. B.M.Everett: Consultant; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Lilly, Provention Bio, Inc., UpToDate, Other Relationship; American Heart Association, Research Support; Novo Nordisk. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

Funding
Patient-Centered Outcomes Research Institute (DB-2020C2-20326)
1089-P: Importance of Cardiorenal Complications for Prognosis in Persons with Type 1 Diabetes and Controls
Authors: HALLSTRÖM SARA , WIJKMAN MAGNUS O. , LUDVIGSSON JOHNNY , EKMAN PER , PFEFFER MARC A. , WEDEL HANS , ROSENGREN ANNIKA , LIND MARCUS 
Published: May 2022

Background: Historically, life expectancy in persons with type 1 diabetes (T1D) has been shorter than the general population, but earlier studies did not stratify patients according to cardiorenal complications.
Methods: T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141) . Mortality rates from 2002 to 20were estimated in persons with T1D overall and after stratification for prevalent cardiovascular and renal disease.
Results: In persons with T1D, mean age was 32.4 years and 44.9% were women. Age- and sex- adjusted mortality rates decreased over time in both groups but remained significantly higher in those with T1D during 2017 to 2019. In T1D persons ≥45 years without previous renal or cardiovascular complications (approximately 50% of persons in this age group) similar standardized mortality rates were observed, over time compared with controls, with slightly lower mortality in T1D persons during the last period, 5.55 (95% CI 4.51-6.60) vs. 7. (95% CI 6.75-7.40) deaths per 1,000 person years (Figure) .
Conclusion: Excess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on differentiated treatment is needed to close the gap in mortality for persons with T1D.

Disclosure
S. Hallström: None. M.O. Wijkman: None. J. Ludvigsson: Advisory Panel; Dompé. Research Support; Diamyd Medical. M.A. Pfeffer: Consultant; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia Therapeutics, GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Peerbridge, Sanofi. Research Support; Novartis Pharmaceuticals Corporation. Other Relationship; DalCor Pharmaceuticals, National Heart, Lung, and Blood Institute. A. Rosengren: None. M. Lind: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. Research Support; Eli Lilly and Company, Novo Nordisk.

Funding
ALF [ALFGBG-717211] and [ALFGBG-966173], grants from the Novo Nordisk foundation, Swedish Heart and Lung Foundation [20180589], [20210679], Swedish Research Council [2018-02527] [VRREG 2019-00193], and the Gothenburg Society of Medicine.
1090-P: Prevalence of Diabetic Cardiomyopathy in an Electronic Health Record–Based Cohort
Authors: SEGAR MATTHEW W. , PATEL KERSHAW , VADUGANATHAN MUTHIAH , CHANDRA ALVIN , WILLETT DUWAYNE L. , PANDEY AMBARISH 
Published: May 2022

Introduction: Diabetic cardiomyopathy (DbCM) is characterized by abnormal cardiac structure/function, associated with incident HF, and has a 67% prevalence in the community. However, the prevalence of DbCM in a real-world, electronic health record (EHR) system is not known.
Methods: Adult patients with DM in a single center EHR free of CVD with available data on HF risk factors were included. The presence of DbCM was defined using different definitions (Figure) . DbCM prevalence was compared across subgroups with differences assessed using the chi-squared test. Adjusted logistic regression models were constructed to evaluate significant predictors of DbCM.
Results: Among 1,921 individuals with DM, prevalence of DbCM in the overall cohort was 8.7% and 64.4% in the most and least restrictive definitions, respectively. Across all definitions, increasing age and Hispanic ethnicity was associated with higher proportion of DbCM (Figure A,D) . No consistent differences in DbCM prevalence were observed across sex and race-based subgroups across definitions (Figure B-C) . In multivariable-adjusted logistic regression, higher creatinine and longer QRS duration were associated with higher risk of DbCM across all definitions.
Conclusions: In a single-center, EHR cohort, the prevalence of DbCM was up to 64.4%. Increasing age and Hispanic ethnicity had a higher prevalence of DbCM.

Disclosure
M.W.Segar: None. K.Patel: None. M.Vaduganathan: Advisory Panel; American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi, Other Relationship; Novartis and Galmed , Research Support; Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Sanofi, Speaker's Bureau; Novartis and Roche Diagnostics. A.Chandra: None. D.L.Willett: None. A.Pandey: Advisory Panel; Lilly, Consultant; Tricog, Research Support; Applied Therapeutics, Gilead Sciences, Inc.