bluuebunny/crossref_metadata_2025 huggingface dataset:
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<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<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<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<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
1237-P: Descriptive Analysis of Long-Term Glycemic Control and Pharmacotherapy in Type 2 Diabetes: Ten-Year Trends in 308,4Indiana Adults
Authors: FU HELEN N. , WEINER MICHAEL , WOLFSON JULIAN , HANNON TAMARA S. , BALIUS PATRICK , SCHLEYER TITUS
Published: May 2022

The purpose of this study was to assess success rates of long-term glycemic control and diabetes drug prescriptions by gender, age and race in a large, state-wide, integrated, electronic health record database in Indiana. Descriptive analysis of a retrospective cohort of 308,4adults with type 2 diabetes observed from 20to 2018 was conducted. The success rate for glycemic control (A1c <7 [<65 y/o] or <8 [>=65 y/o]) was defined as (number of A1c tests meeting target) / (number of A1c tests) in any given year. Sample characteristics included gender, age, race, and diabetes drug prescription rate for twelve classes of diabetes drugs. Analysis of 876,656 year-level observations showed the success rate of glycemic control was steady at 60% with year-to-year change of 0-1% since 2009. It was greater for females (62-64%) than males (57-59%) ; patients aged 65 or above (75-89%) than those below (43-62%) ; and whites (61-63%) than blacks (51-54%) . Biguanides (56-63% = subject n with orders of biguandes in x year/ population n in x year) were most frequently prescribed, followed by sulfonylurea (29-33%) , fast-acting and long-acting insulin (29-32%) . Blacks had more insulin prescription (47-53%) regardless of age group. Costlier drugs were more frequently prescribed among whites vs. non-white: 0.6-1.2% vs. 0.5-0.8 for meglitinides; 10.3-16.7% vs. 1.3-17.3% for DPP-4; 0.5-9.3% vs. 0.2-8.0 for SGLT2i; and 5.3-12.15% vs. 1-11.5% for GLP-1. For blacks who were prescribed insulin (44-53%) , the success rate for glycemic control was lower than for whites (38-43% vs. 46-50%) . The success of longitudinal glycemic control did not improve over a 10-year period among 308,4adults with type 2 diabetes in Indiana. Racial minorities received notably fewer prescriptions for higher-priced drugs such as meglitinide, DPP4, SGLT2, and GLP-1.

Disclosure

H.N.Fu: None. M.Weiner: Stock/Shareholder; AbbVie Inc., Accuray, Inc., Allscripts Healthcare Solutions, Amgen Inc., Boston Scientific Corporation, Bristol-Myers Squibb Company, Crispr Therapeutics Ag Com, Express Scripts Hdlg Co, General Electric Co., Globus Med, Inc., IBM, Integer Hldgs Corp Com, Integra Lifesciences Holdings Corp, Johnson & Johnson, Mallinckrodt PLC, Mead Johnson & Company, LLC., Medtronic, Metlife Inc Com, Mylan N.V., Novo Nordisk A/S, Nuvasive, Inc., Orthofix Medical Inc., Perspecta Inc Com, Pfizer Inc., Resmed, Inc., Roche Pharmaceuticals, Seaspine Hldgs, Inc., Senseonics, Stryker Corp., Teva Pharmaceutical Industries Ltd., Varex Imaging Corp., Varian Med Sys, Inc., Walgreens Boots Alliance, Inc. J.Wolfson: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. P.Balius: None. T.Schleyer: None.

Funding

T15LM012502, UL1TR002529, the Lilly Endowment Physician Scientist Initiative
124-LB: Incidence and Risk Factors of Erythrocytosis following Initiation of Sodium–Glucose Cotransporter 2 Inhibitors in Men with Type 2 Diabetes in Real-World Setting
Authors: GOSMANOV AIDAR R. , GEMOETS DARREN E. , GREEN MARIA A. , SCHUMACHER KAMILYA
Published: May 2022

Background: Analyses of prospective trials consistently demonstrated that therapy with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in type 2 diabetes (T2D) results in mild but significant increase in hematocrit (Hct) . We sought to determine if SGLT-2i therapy poses risk of erythrocytosis (ERY) in routine clinical practice.

Methods: This was a retrospective study of T2D US Veterans who were prescribed an SGLT-2i and had adequate adherence based on the proportion of days covered >80% during 3/2013-12/2019 and baseline Hct<50%. ERY incidence was defined as first Hct>54% within 180 days of an SGLT-2i initiation. The detailed patient data were obtained using the VA Informatics and Computing Infrastructure (VINCI) database. Odds ratio (OR) of ERY risk was calculated by logistic regression models adjusted for case-mix.

Results: We identified 9402 patients (76.0% Whites/14.7% Blacks) with baseline mean±SD age 65.0±8.9 yrs, BMI 34.1±6.3 kg/m2, Hct 41.5±4.1 % and hemoglobin A1c 8.5±1.2 %. By the end of observation period, mean Hct increased from the baseline by 1.74% [95% CI 1.68-1.80] in the entire cohort and 61 patients (0.65% of the cohort) developed ERY. We found that BMI, tobacco use, or obstructive sleep apnea (OSA) were not associated with risk of developing ERY. However, concomitant use of testosterone replacement therapy (TRT) was associated with significant ERY risk compared with SGLT-2i users not on TRT in both unadjusted analyses (OR 12.28 [95% CI 5.29-25.10]) and after adjustments for age, race, BMI, OSA, and tobacco use (OR 7.26 [95% CI 2.95-16.04]) . The risk of ERY was independent of baseline Hct or modality of TRT (topical vs. injectable) .

Conclusions: For the first time, we demonstrated that SGLT-2i initiation in men with T2D in real world clinical setting can result in detectable risk of erythrocytosis. It appears that concomitant TRT can significantly influence that risk. We recommend monitoring for Hct changes following SGLT-2i initiation and, particularly, in those persons who receive testosterone therapy.

Disclosure

A. R. Gosmanov: Research Support; AbbVie Inc., Kowa Research Institute, Inc., Speaker’s Bureau; AstraZeneca. D. E. Gemoets: None. M. A. Green: None. K. Schumacher: None.
1240-P: Real-World Demographics and Clinical Characteristics of Type 2 Diabetes Mellitus Patients in Ontario, Canada
Authors: HOULDEN ROBYN L. , GOLDEN SHANE , SHI WEI ZHE , KUKASWADIA ATIF A. , SHARMA ARUSHI , QUANSAH KOBINA , LIU AIDEN R.
Published: May 2022

Population-based studies of diabetes may be limited by sampling and capture. Our study utilizes the Ontario Diabetes Database, which captures all persons in Ontario, Canada with non-gestational diabetes. Based on sensitive and specific cohort definitions adults with T2DM were identified. Study objectives are to investigate: the demographic and the clinical characteristics of type 2 diabetes patients in Ontario, Canada over a time frame from Apr 1, 2002 to Sept 31, 2017. We also compare the demographics and clinical characteristics of T2DM patient populations from the cohorts to understand the impact T2DM definitions have on characterizing the disease. We identify 1,093,812 and 783,228 in the cohorts (Table 1) . In the sensitive and specific cohorts, the mean age of a patient with T2D is 64 to 65 years old and 52 to 54% are male, respectively. Roughly 56 to 64% of patients have a 1-year mean HbA1c of <7%, with ∼ 25 to 32% at 7.0%-8.5%, respectively. Overall, covariates of interest in our demographics and clinical characteristics analysis are similar for both cohorts. Our results show multiple comorbidities in this population; hypertension (∼ 77-79%) , dyslipidemia (∼55%) , chronic ischemic heart disease (∼28%) and angina (∼21%) . The comorbidities further illustrate a substantial proportion of T2DM patients suffer comorbid heart diseases.

Disclosure

R.L. Houlden: Advisory Panel; Novo Nordisk Canada Inc. Research Support; AstraZeneca. Speaker's Bureau; Abbott Diagnostics, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Canada Inc., Sanofi. S. Golden: Other Relationship; Novo Nordisk Canada Inc. W. Shi: Other Relationship; Novo Nordisk Canada Inc. A.A. Kukaswadia: Other Relationship; Novo Nordisk. A. Sharma: Other Relationship; Novo Nordisk Canada Inc. K. Quansah: Employee; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Canada Inc. A.R. Liu: Employee; Novo Nordisk A/S, Novo Nordisk Canada Inc.
1245-P: Outcomes among Veterans with T2D at Time of Departure from Virtual Clinic: A Nationwide, Real World Study
Authors: FELL BRANDON , VANTIEGHEM MICHELLE , MCKENZIE AMY L. , RATNER ROBERT E.
Published: May 2022

Lifestyle interventions for type 2 diabetes (T2D) typically have poor retention, and drop out is often assumed to indicate treatment failure. A partnership between the Veterans Health Administration and Virta Health allows Veterans with T2D to enroll in Virta's clinic, which provides carbohydrate restricted nutrition therapy via continuous remote care. We sought to assess change in clinical outcomes upon clinic departure using medical record data. Percent change in clinical outcomes on a per patient basis from enrollment to time of departure were assessed with one sample t tests. Among 677 enrolled Veterans, 270 (40.0%) departed the clinic within 2 years (283±184 days in treatment; enrollment: age 58±9y, 13% female, 235±47 lb, 179±86 mg/dl glucose, 2.3±0.9 T2D medications) . Weight was significantly reduced at time of departure in all groups initiating nutrition therapy (p<0.05) , although clinically significant weight loss was only achieved among those who left after one year (Table 1) . Percent change in blood glucose was unchanged (p>0.05) despite lower mean glucose which occurred concurrent with medication deprescription in most groups (p<0.05) . These results show that Veterans initiating therapy experienced clinical improvements prior to clinic departure and return to standard care, particularly in weight after one year of treatment and in reduced need for medication to maintain glycemia.

Disclosure

B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp.
1246-P: Risk Factors Associated with In-Hospital Mortality In Patients with COVID-and Type 2 Diabetes in Chile
Authors: VARGAS OSCAR , POBLETE PAMELA , VEGA EDITH , TORO LUIS , GOMEZ PATRICIA C. , VILLARROEL ANA CLAUDIA , GONZALEZ MARIA G. SANZANA , VARGAS CECILIA
Published: May 2022

Background: Risk factors associated with in-hospital mortality (IHM) have been identified among patients with T2D hospitalized for COVID-19, including male sex, elderly, impaired renal function and poor metabolic control. At a local setting, data regarding the impact of these variables are lacking.

Aim: To assess the association between risk factors and IHM in patients with T2D admitted for COVID-19.

Methodology: This is a descriptive observational study. We used electronic health records data provided by a tertiary-level hospital in Chile, between April to July 2020. Included demographic, clinical, and laboratory variables of inpatients with T2D and a positive PCR for SARS-CoV-2. Multiple logistic regression analysis was used to identify predictors of IHM.

Results: We identified 200 individuals. Mean age was 63.0±13.6 years, 59.5% (n=119) were adults aged ≥60 years and 58% were male (n=116) . Mean admission glycemia and A1C were 216±120 mg/dl and 8.8±2.4%, respectively. Median admission serum creatinine was 0.8 mg/dL (p25-p75: 0.6-1.1 mg/dL) . A total of 38 patients (19%) died during hospitalization, of these 26.3% (n=10) died within the first week, 63.2% (n=24) between 2-4 weeks, and 10.5% (n=4) after the first month. Age ≥60 years (OR 2.9, 95%CI [1.3-6.7], p=0.01) and elevated admission serum creatinine (OR 1.28, 95%CI [1.04-1.58], p=0.01) were identified as independent predictors of IHM in multiple logistic regression analysis. No association was identified for sex, admission glycemia or A1C, however 37% of our sample lacked an A1C measurement, which could imply a bias.

Conclusion: Our study confirms that older age and elevated admission serum creatinine are risk factors for IHM in patients with T2D hospitalized for COVID-19. These results reinforce the importance of identifying risk factors to improve outcomes related to COVID-during in-hospital stay of patients with T2D. We must promote A1C measurement at admission for all patients with diabetes or hyperglycemia.

Disclosure

O.Vargas: None. P.Poblete: None. E.Vega: None. L.Toro: None. P.C.Gomez: None. A.Villarroel: None. M.G.Sanzana gonzalez: None. C.Vargas: None.
1247-P: Subgroup Analysis of Diabetic Patients Living in Tibet Plateau
Authors: SUYUAN WANG , ZHANG CHENGHUI
Published: May 2022

Background: recently, a novel subgroups of adult-onset diabetic patients has been reported. Their work implied that type 2 diabetic patients can be classified into four groups. However, the utility of this classification method in Tibet populations and the clinical character of each cluster of Tibetan patients is unknown.

Methods: this is a cross-sectional study, patients newly diagnosed with type 2 diabetes was analyzed. Data was collected from hospital information system (HIS) , and homoeostasis model assessment 2 of β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR) was calculated using fasting glucose and fasting C-peptide by HOMA calculator. The age at onset of diabetes, Hba1c, BMI, HOMA2-B and HOMA2-IR was used for clustering. K-means cluster method was used with k value of 4. The stability of each cluster was assessed by resampling the dataset and computing Jaccard similarities. All statistical analysis was performed on R and fpc package.

Result: A total of 581 patients was enrolled, the four clusters with similar clinical aspect is observed in Tibetan population and the average jaccard similarities is over 0.7. The same as Ji's result, the largest subgroup is mild age-related diabetes cluster (MARD) 255 out of 581 (44.3%) patients is classified into this cluster. And 147 (25.6%) patients is classified into mild obesity related diabetes (MOD) . The proportion of severe insulin- resistant related diabetes (SIRD) (1.4%) is lower and those of severe insulin-deficient related diabetes (SIDD) (28.7%) is higher compared to Ji's study. This result implies that there may be more severe insulin-deficient patients and less severe insulin-resistant patients in Tibet plateau.

Discussion: in this study, we found out that the cluster method developed by Emma Ahlqvist is suitable for Tibetan population, compared to the rest Chinese population, there're more severe insulin-deficient patient, and less severe insulin-resistance patients.

Disclosure

W.Suyuan: None. C.Zhang: None.
125-OR: Association between Preventive Podiatric Care and Outcomes of New Diabetic Foot Ulceration among Patients with End Stage Renal Disease
Authors: TAN TZE-WOEI , ARMSTRONG DAVID G. , CHONG CHYI CHYI , HAMILTON-COTTER NICHOLAS J. , KSHIRSAGAR ONKAR S. , MARRERO DAVID G. , COTTER DENNIS J.
Published: May 2022

Objective: To assess the association between foot care by podiatric surgeons and outcomes of new diabetic foot ulceration (DFU) among patients with end-stage renal disease (ESRD) .

Methods: We used the 2015 and 2016 claim data from the United States Renal Data System to identify patients (≥ 40 years and on dialysis for ≥ 12 months) with a new diagnosis of DFU. The patients were stratified into intervention or control cohort based on whether they received any foot care by a podiatric surgeon within 12 months before the diagnosis of a new DFU. Patients were followed from the index DFU date until December 31, 2018. The study outcome was amputation-free survival (composite endpoint of mortality and major amputation) . Adjusted comparisons between preventive foot care and its association with outcomes were performed by Cox-regression analysis after propensity score matching for age, gender, race, hospitalizations, and Charlson Comorbidity Index (CCI) .

Results: Among the 51,362 ESRD patients included, 16,156 (31.5%) received podiatric care within 12 months before their index DFU. Compared to the control cohort, the intervention cohort was older, likely to be female (44% vs. 39%) , and more likely to have peripheral artery disease (64.2% vs. 49.5%) . The overall major amputation rate was 9.6% during study follow-up (intervention: 9.3% vs. control: 9.8%) . A Kaplan-Meier estimate indicated that foot care before index DFU was associated with increased amputation-free survival based on the Log Rank test (p<0.0001) . In addition, the multivariable analysis demonstrated that foot care prior to index DFU was associated with a lower risk of death or major amputation in both the unmatched (Hazard ratio [HR] 0.92, 95% Confidence Interval [CI] 0.90, 0.93, p<0.0001) and matched cohorts (HR 0.82, 95% CI 0.79, 0.85, p<0.0001) .

Conclusion: Among patients with end stage renal disease, preventive podiatric care appears to improve amputation-free survival for DFU.

Disclosure

T.Tan: None. D.G.Armstrong: None. C.Chong: None. N.J.Hamilton-cotter: None. O.S.Kshirsagar: None. D.G.Marrero: None. D.J.Cotter: None.

Funding

National Institutes of Health (K23DK122126)
1252-P: The Comparison of One-Year Prevalence of Anti-Influenza Vaccination among Czech, Slovak, and EU Patients with Diabetes
Authors: BRUNEROVA LUDMILA , LUSTIGOVA MICHAELA , NOVAK LAURA , URBANOVÁ JANA , SMEJKALOVA ANNA , BROZ JAN
Published: May 2022

Background: Influenza infection represents a significant health problem associated with multiple complications including death. Patients with diabetes are more threatened by severe course of influenza in comparison with non-diabetic population. Anti-influenza vaccination is a key preventive measurement. The study compares one-year (2013-2014) prevalence of anti-influenza vaccination in the Czech, Slovak and EU population with regard to diabetes.

Methods: A sample of Czech (4441 participants, 16%/725 persons with diabetes, 42% men) and Slovak population (3446 participants, 12%/413 persons with diabetes, 41% men) ≥ 45 years of age from European Health Interview Survey 2014 (EHIS) . The data was collected from interviews. The diagnosis of diabetes was based on the self-report of the participants. Student´s t- test and X2 test were used for statistical analyses.

Results: One year prevalence of anti-influenza vaccination in Czechia was 12.4/17/11.6% (whole group, diabetic group, non-diabetic group) , in Slovakia 13/16.7/8.9% (NS) and in average in the European Union 24.7/41/22.5%. In subanalyses according to age, significant difference of one-year prevalence of anti-influenza vaccination was observed only in the age category ≥ 75 years (15.7% in Czechia vs. 24.1% in Slovakia, p = 0.05) . Furthermore, no differences in vaccination prevalence were found in regard to comorbidities (bronchial asthma, COPD, cardiovascular diseases) , family income, education, presence of obesity, alcohol consumption and smoking between Czech and Slovak patients with diabetes.

Conclusions: Czech and Slovak diabetic patients 45+ reveal low anti-influenza vaccination prevalence as compared to average in EU. There were no differences in vaccination prevalence between Czech and Slovak diabetic patients according to age subgroups, except for the very old. Surprisingly, there were no differences in the vaccination prevalence according to the presence of other comorbidities.

Disclosure

L.Brunerova: None. M.Lustigova: None. L.Novak: None. J.Urbanová: Advisory Panel; Lilly. A.Smejkalova: None. J.Broz: None.

Funding

Progres Q36.MH CZ - DRO (“Kralovske Vinohrady University Hospital - FNKV, 00064173”)
1253-P: Thirty-Day Readmission Rate and Economic Burden among Type 2 Diabetes with Coexisting Chronic Systolic Heart Failure and Atrial Fibrillation
Authors: FATUYI MICHAEL , PEREIRA LEANNE , SHARMA VIVEK , KHOKHLOV LEONID , NAMDARIZANDI VAHID , ELABIDIN AWFA ZAIN , ORJI RICHARD T. , SHEMISA KAMAL
Published: May 2022

Introduction: We sought to determine the 30-Day Readmission rate (30-DRr) for patients with Type 2 Diabetes (T2DM) with coexisting Chronic Systolic Heart failure (cSHF) and Atrial Fibrillation (AF) , readmission rate mortality, & healthcare utilization in the United States.

Methods: Using the 2017-2018 National Readmission Database, we conducted a retrospective analysis of patient discharges with T2DM as a principal diagnosis and cSHF&AF as a secondary diagnosis. Readmission was defined as the first admission for any non-trauma diagnosis within 30 days of the index admission. The outcomes were 30DRr, readmission mortality rate & resource utilization defined by LOS, Average & Total patient charges/hospital costs.

Results: A total of 29,967 index hospitalization for T2DM with co-existing cSHF & AF; mean age was 71.4years, & 69.8% males. In-hospital mortality rate for index admission was 2.89%, while 30-DRr was 17.5% (Figure 1) . The In-hospital mortality rate was 6.78% among this group of readmitted patients, compared to index admission (6.78% vs. 2.89%, adjusted p=0.0001) . The total hospital days associated with readmission were 34,691 days, with a total hospital cost burden of $78,400,000 & a total economic burden on patients of $344,000,000.

Conclusion: T2DM with cSHF&AF had a high number of 30-DRr, associated with incremental mortality & high health care burden.

Disclosure

M.Fatuyi: n/a. L.Pereira: None. V.Sharma: None. L.Khokhlov: None. V.Namdarizandi: None. A.Zain elabidin: None. R.T.Orji: None. K.Shemisa: Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, ESPERION Therapeutics, Inc., Merck & Co., Inc., Pfizer Inc.
1254-P: Genetic Prediction of C-Peptide Trajectory before Type 1 Diabetes Diagnosis in TrialNet
Authors: TRIOLO TAYLOR M. , PARIKH HEMANG M. , TOSUR MUSTAFA , GOTTLIEB PETER , ORAM RICHARD A. , ONENGUT-GUMUSCU SUNA , KRISCHER JEFFREY , RICH STEPHEN S. , STECK ANDREA , REDONDO MARIA J.
Published: May 2022

Modeling the course of C-peptide decline in autoantibody (Ab) positive individuals is important for type 1 diabetes (T1D) prediction and implementation of T1D prevention trials. Single nucleotide polymorphisms in TCF7L2, JAZF1, SLC30A8, INS, PTPRK, G6CP2, CLEC16, PTPN22 and HLA genes are associated with persistent C-peptide at or after T1D diagnosis. We sought to determine whether 12 SNPs in these genes and the T1D genetic risk score-2 (GRS2) can predict C-peptide trajectory before diagnosis of T1D. We studied Ab positive at-risk participants in the TrialNet Pathway to Prevention Study who had ImmunoChip data (N=1217, age at initial screen (mean±SD) 16.1±12.7 years, 51.5% female, 81.0% non-Hispanic white) . Over a mean follow up of 3.4±2. years, 255 (21.0%) developed multiple Ab and 336 (27.6%) developed clinical T1D. We analyzed the influence of these 12 SNPs and the T1D GRS2 on C-peptide AUC during progression from single to multiple Abs, from single Ab to clinical T1D, and from multiple Abs to clinical T1D. Analyses were adjusted for baseline C-peptide AUC, age, glucose AUC, BMI Z-score and HbA1c; the presence of high-risk HLA haplotypes (DR3 and DR4-DQ8) ; and the first 3 principal components. The type 2 diabetes (T2D) -associated TCF7L2 rs7901695 and rs4506565 SNPs were significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p<0.04) and neared significance for the single-to-multiple Ab transition (p=0.05) . Additionally, lower T1D GRS2 was significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p=0.01) . We observed trend associations of lower C-peptide AUC with JAZF1 SNP rs864745 in both single Ab-to-T1D and multiple Ab-to-T1D progression (both p=0.06) , and with SNPs in SLC30A8 and INS in multiple Abs to T1D (p=0.and 0.08, respectively) .

In conclusion, T2D-associated SNPs in the TCF7L2 gene and lower T1D GRS2 predict higher C-peptide particularly in progression from multiple Abs to clinical T1D.

Disclosure

T.M.Triolo: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. H.M.Parikh: None. M.Tosur: Advisory Panel; Provention Bio, Inc. P.Gottlieb: Advisory Panel; Janssen Research & Development, LLC, ViaCyte, Inc., Other Relationship; IM Therapeutics, Research Support; Caladrius Biosciences, Inc., Immune Tolerance Network, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Precigen, Inc., Tolerion, Inc. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. S.Onengut-gumuscu: None. J.Krischer: None. S.S.Rich: None. A.Steck: None.

Funding

NIH K12 DK094712NIH RDK121843NIH RDK124395
1268-P: Underlying T Cell Receptor Methylation Defects in Type 1 Diabetes Associated with Quantitative Defects
Authors: KUHTREIBER WILLEM , LEE AMANDA H. , ARISTARKHOVA ANNA , DIAS HANS F. , NG NATHAN , BIEN STEPHANIE A. , FAUSTMAN DENISE L.
Published: May 2022

The T cell receptor (TCR) is a central regulator of the adaptive immune system. Efficient structural organization and signaling of TCR/CD3 underlies the development and function of T cells. T cell maturation defects are associated with autoimmunity, suggesting an underlying defect in TCR selection. To explore quantitative defects as a cause for altered TCR selection at the level of the TCR/CD3 protein complex, we compared TCR expression densities on CD4 T cells from subjects with type 1 diabetes (T1D) (n=80) and nondiabetes controls (n=37) . We also investigated a quantitative defect in genes in the TCR/CD3 genome for possible underlying overmethylation in T1D. All 13 gene regions of the TCR segments and all 4 versions of CD3 proteins were studied for methylation and protein differences in T1D vs. controls. Significant quantitative defects in TCR and CD3 proteins were observed in CD4+ T cells of patients with T1D vs. controls. As a cause for these defects, the TCR complex genes and associated CD3 genes were overmethylated, resulting in downregulated cell surface expression. Evaluation of TCRαβ expression in CD4+ T cells at the protein level confirmed methylation patterns, showing that the population of TCRαβ+ cells was significantly reduced in T1D vs. controls (p=0.005) . The MFI density of TCRαβ antibody in T1D was also significantly decreased vs. controls (p=0.01) . All CD3 genes except CD3ε had hypermethylated patterns in T1D, confirmed by RNAseq analysis. The percentage CD3+ T cells in the CD4+ T cell population was reduced in T1D vs. controls (p=0.04) , as was the MFI of CD3+ T cells (p=0.02) . Patients with T1D have quantitative defects in the TCR/CD3 protein complex, resulting in decreased expression. It is recognized that TCR triggering is affected by intermolecular distance between TCR proteins and that activation diminishes when proximity is increased between TCR surface proteins. In T1D, this might be a novel mechanism for failed T cell selection leading to autoimmunity.

Disclosure

W.Kuhtreiber: None. A.H.Lee: None. A.Aristarkhova: None. H.F.Dias: None. N.Ng: None. S.A.Bien: Employee; Adaptive Biotechnologies. D.L.Faustman: None.
1272-P: Genomic Rearrangement in Noncoding Region of Chromosome 1 Leads to Spontaneous Obesity and Type 2 Diabetes
Authors: WHITE DONNELL , WU JIAN , LAUTERBOECK LOTHAR , KANG SUNG WOOK , ELGAZZAZ MONA , ALAHARI SURESH , LAZARTIGUES ERIC D. , YANG QINGLIN
Published: May 2022

Obesity is a major health risk for type 2 diabetes, along with many other disease conditions. We discovered spontaneous obese mice among a conditional transgenic mouse line (Floxed-stop Overexpression of IF1, or FEI) , which was originally generated and maintained for Cre-mediated conditional transgenic IF1 expression. Severe obesity became a fixed phenotype in FEI mice after inbreeding for 5-6 generations. Targeted-Locus-Amplification (TLA) analyses revealed that a rearrangement occurred in upstream sequences (48,224,9 to 48,248,586) of the transgenic integrated site, and are duplicated downstream at a non-coding region of chromosome 1. Early-onset obesity was consistent in both male and female FEI mice with progressive weight gain from 2 months and reached 50-60 grams at 6-8 months. Body composition analyses revealed that FEI mice have markedly increased fat mass and modestly increased lean mass compared to wild-type (WT) mice. Consistently, the FEI mice exhibited increased peripheral fat pads and dyslipidemia. The FEI mice exhibited increased food intake but reduced systemic metabolic rates. Moreover, we detected increased fed and fasting blood glucose, insulin, and leptin with impaired glucose and insulin tolerance in FEI mice as early as 6 weeks of age. Histology analyses with H&E staining revealed markedly enlarged adipocytes with crown-like structures on visceral white adipose tissue sections and increased fat deposition in liver sections from FEI mice. RNAseq analyses on RNA samples from subcutaneous white adipose tissues demonstrate the upregulation of adipogenesis and inflammation genes. These results indicate that the FEI mouse line is a novel obese mouse model with genomic rearrangement in a non-coding region, which may serve as cis-regulatory elements for obese genes. Further studies on these mice should yield novel and translational insight into the molecular and metabolic mechanisms underlying obesity development with complex genetic traits.

Disclosure

D.White: None. J.Wu: None. L.Lauterboeck: None. S.Kang: None. M.Elgazzaz: None. S.Alahari: None. E.D.Lazartigues: None. Q.Yang: None.
128-LB: Real-World A1C Changes and Prescribing Provider Types among T2DM Patients Initiating Treatment with Once-Weekly (OW) Semaglutide
Authors: FRAZER MONICA S. , SWIFT CAROLINE , SARGENT ANDREW , LESZKO MICHAEL , BUYSMAN ERIN , ALVAREZ SARA B. , NOONE JOSHUA , GAMBLE CORY L.
Published: May 2022

Purpose: Characterize A1c changes and characteristics among patients with T2DM initiating OW semaglutide (sema) , by baseline A1c ≥9% and <9%.

Methods: Retrospective analysis using medical and pharmacy claims data between 01/01/2017-12/31/2020 from commercial and Medicare Advantage with Part D insurance enrollees, age 18+. Patients had ≥1 claim for OW sema (first claim=index date) , ≥1 T2DM diagnosis, continuous enrollment for 12 months before and including index (baseline) and 12 months after (follow-up) and were excluded if pregnant. Results were stratified by whether patient’s last baseline A1c value was ≥ or <9%.

Results: Patients initiating OW sema with ≥1 baseline A1c value (n=7,653) had a mean age of 59 years, 51.4% were female, and 62.5% had commercial coverage. Among patients with baseline and follow-up A1c value (n=6,042) , mean A1c change was -0.8 (1.6) . Among a subset of patients with ≥90 days of continuous OW sema treatment and at least 1 A1c value after 90 days of treatment (n=3,456) , the A1c ≥9% group had a mean A1c reduction -2.5%. While many study patients had index claims prescribed by primary care and internal medicine providers (46.1% overall) , a higher percentage of patients with A1c <9% had OW sema prescribed by an endocrinologist (28.5% vs. 25.5%; p=0.008) .

Conclusions: Results suggest that OW sema is an effective T2DM treatment in the real-world, especially among patients with A1c ≥9% prior to treatment initiation. Additionally, patients with T2DM in this study were more often prescribed OW sema by primary care physicians than by endocrinologists.

Disclosure

M. S. Frazer: None. C. Swift: Employee; Novo Nordisk. A. Sargent: None. M. Leszko: None. E. Buysman: None. S. B. Alvarez: Employee; Novo Nordisk, UnitedHealth Group. J. Noone: Employee; Novo Nordisk. C. L. Gamble: Employee; Novo Nordisk.