bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of KLF2 by Exercise Activates eNOS to Improve Vasodilatation in Diabetic Mice
Authors: Luo Jiang-Yun , Cheng Chak Kwong , Gou Lingshan , He Lei , Zhao Lei , Zhang Yang , Wang Li , Lau Chi Wai , Xu Aimin , Chen Alex F. , Huang Yu 
Published: June 2023

Diabetic endothelial dysfunction associated with diminished endothelial nitric oxide (NO) synthase (eNOS) activity accelerates the development of atherosclerosis and cardiomyopathy. However, the approaches to restore eNOS activity and endothelial function in diabetes remain limited. The current study shows that enhanced expression of Krüppel-like factor 2 (KLF2), a shear stress-inducible transcription factor, effectively improves endothelial function through increasing NO bioavailability. KLF2 expression is suppressed in diabetic mouse aortic endothelium. Running exercise and simvastatin treatment induce endothelial KLF2 expression in db/db mice. Adenovirus-mediated endothelium-specific KLF2 overexpression enhances both endothelium-dependent relaxation and flow-mediated dilatation, while it attenuates oxidative stress in diabetic mouse arteries. KLF2 overexpression increases the phosphorylation of eNOS at serine 1177 and eNOS dimerization. RNA-sequencing analysis reveals that KLF2 transcriptionally upregulates genes that are enriched in the cyclic guanosine monophosphate–protein kinase G–signaling pathway, cAMP-signaling pathway, and insulin-signaling pathway, all of which are the upstream regulators of eNOS activity. Activation of the phosphoinositide 3-kinase–Akt pathway and Hsp90 contributes to KLF2-induced increase of eNOS activity. The present results suggest that approaches inducing KLF2 activation, such as physical exercise, are effective to restore eNOS activity against diabetic endothelial dysfunction.

Article Highlights
Exercise and statins restore the endothelial expression of Krüppel-like factor 2 (KLF2), which is diminished in diabetic db/db mice. Endothelium-specific overexpression of KLF2 improves endothelium-dependent relaxation and flow-mediated dilation through increasing nitric oxide bioavailability. KLF2 promotes endothelial nitric oxide synthase (eNOS) coupling and phosphorylation in addition to its known role in eNOS transcription. KLF2 upregulates the expression of several panels of genes that regulate eNOS activity.
Metformin Disrupts Signaling and Metabolism in Fetal Hepatocytes
Authors: Swenson Karli S. , Wang Dong , Jones Amanda K. , Nash Michael J. , O’Rourke Rebecca , Takahashi Diana L. , Kievit Paul , Hennebold Jon D. , Aagaard Kjersti M. , Friedman Jacob E. , Jones Kenneth L. , Rozance Paul J. , Brown Laura D. , Wesolowski Stephanie R. 
Published: June 2023

Metformin is used by women during pregnancy to manage diabetes and crosses the placenta, yet its effects on the fetus are unclear. We show that the liver is a site of metformin action in fetal sheep and macaques, given relatively abundant OCT1 transporter expression and hepatic uptake following metformin infusion into fetal sheep. To determine the effects of metformin action, we performed studies in primary hepatocytes from fetal sheep, fetal macaques, and juvenile macaques. Metformin increases AMP-activated protein kinase (AMPK) signaling, decreases mammalian target of rapamycin (mTOR) signaling, and decreases glucose production in fetal and juvenile hepatocytes. Metformin also decreases oxygen consumption in fetal hepatocytes. Unique to fetal hepatocytes, metformin activates stress pathways (e.g., increased PGC1A gene expression, NRF-2 protein abundance, and phosphorylation of eIF2α and CREB proteins) alongside perturbations in hepatokine expression (e.g., increased growth/differentiation factor 15 [GDF15] and fibroblast growth factor 21 [FGF21] expression and decreased insulin-like growth factor 2 [IGF2] expression). Similarly, in liver tissue from sheep fetuses infused with metformin in vivo, AMPK phosphorylation, NRF-2 protein, and PGC1A expression are increased. These results demonstrate disruption of signaling and metabolism, induction of stress, and alterations in hepatokine expression in association with metformin exposure in fetal hepatocytes.

Article Highlights
The major metformin uptake transporter OCT1 is expressed in the fetal liver, and fetal hepatic uptake of metformin is observed in vivo. Metformin activates AMPK, reduces glucose production, and decreases oxygen consumption in fetal hepatocytes, demonstrating similar effects as in juvenile hepatocytes. Unique to fetal hepatocytes, metformin activates metabolic stress pathways and alters the expression of secreted growth factors and hepatokines. Disruption of signaling and metabolism with increased stress pathways and reduced anabolic pathways by metformin in the fetal liver may underlie reduced growth in fetuses exposed to metformin.
131-OR: Glycemic Measures in Childhood as Predictors of Future Diabetes-Related Microvascular Complications
Authors: VAZQUEZ LAURA , VAZQUEZ ARREOLA ELSA , HANSON ROBERT L. , SINHA MADHUMITA 
Published: June 2023

The United States Preventive Services Task Force recently questioned the benefits of risk-based screening for prediabetes/T2D in asymptomatic children with overweight/obesity due to lack of long-term health outcomes data. We examined associations of HbA1c and 2-hour post-load plasma glucose (2-hr PG), obtained during childhood (5 - &lt;18 years) in a longitudinal study in an American Indian community (1965-2007), with future albuminuria [albumin creatinine ratio (ACR) ≥ 30 mg/g], severe albuminuria (ACR ≥ 300 mg/g), and retinopathy (at least one microaneurysm or hemorrhage or proliferative retinopathy on direct ophthalmoscopy). We compared the performance of childhood glycemic measures in predicting these complications using area under the ROC curve (AUC). In children without T2D at baseline, higher HbA1c (HR=3.09 per 1%, 95% CI: 1.17-8.22) and 2-hr PG (HR= 1.48 per 1 mmol/L, 95% CI: 1.31-1.67) significantly increased retinopathy risk. Children with T2D based on baseline HbA1c had the highest incidence of albuminuria, severe albuminuria, and retinopathy compared to those with prediabetes and normal HbA1c levels. AUCs for HbA1c, 2-hr PG, or FPG were not significantly different (Figure). Higher levels of glycemia in childhood associated with future microvascular complications demonstrating the utility of screening tests performed in high-risk children in predicting long-term health outcomes.

Disclosure
L.Vazquez: None. E.Vazquez arreola: None. R.L.Hanson: None. M.Sinha: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1785-PUB: Dyslipidemia Management in Patients with the First Acute Coronary Event—A Retrospective Observational EMR-Based RWE Study
Authors: CHRISTOPHER JOHANN , GUPTA ANKUR , PAKSHIRAJAN BALAJI , KOTAK BHAVESH P. , GAURAV KUMAR , RATHOD RAHUL T. , HUSSAIN NAQVI SYED MUJTABA , KANURU VASU PRAVEEN C. , T ABHISHEK 
Published: June 2023

Backgroud: The understanding of the current state of evidence-based lipid management after ACS is critical for improving outcomes after the first coronary event. The present study was conducted to evaluate the real-world prescribing patterns of statin therapy over one year in adults presenting with the first ACS event.
Material & Methods: The data of 527 patients with the first event of ACS receiving Statins based therapy from 10 healthcare centers across India were considered for the analysis starting from January 2018 to December 2020. The various doses of Statins based therapy at the time of ACS event and at Visit 1 and at the end of 12 months and the percentage of patients who have achieved guideline LDL levels were analysed.
Results: The most common statins used are Atorvastain 80mg & 40mg, Rosuvastatin 40mg OD. Dose of Atorvastatin & Rosuvastatin was reduced from High intensity to moderate intensity in 21.97% & 2.64% patients during visit 1. After 12 months, the dose of Atorvastatin was further reduced in 7.98% and 31.20% on Rosuvastatin. The desired LDL as per Indian & global guidelines of &lt;30mg/dl, &lt;55mg/dl, &lt;70mg/dl, &lt;100mg/dl is achieved in only 2.66%, 19.37%, 47.94%, 91.52% patients on statin based therapy respectively.
Conclusion: The Doses of statins were reduced from High intensity to moderate/low intensity therapy despite patients were not achieving desired LDL levels as per Indian & Global guidelines. The present study emphasizes the use of right intensity statins in ACS patients to achieve desired cardiac outcomes.

Disclosure
J.Christopher: None. A.Gupta: None. B.Pakshirajan: None. B.P.Kotak: Employee; Dr. Reddy’s Laboratories Ltd. K.Gaurav: None. R.T.Rathod: None. M.Syed: None. V.C.Kanuru: None. A.T: None.
1797-PUB: Perspectives of Primary Care Providers on the Acceptability of a Brief Video to Decrease the Use of Diabetes-Stigmatizing Language
Authors: JOINER KEVIN , AGAPIOU ALEXANDRA , ADAMS MACKENZIE , PIATT GRETCHEN 
Published: June 2023

Diabetes stigma is recognized to negatively impact health-related outcomes and quality of life in adults living with type 2 diabetes (T2D). The American Diabetes Association provides guidance for health care providers to decrease the use of diabetes-stigmatizing language. The aim of this qualitative study is to explore primary care providers’ (PCPs’) perspectives on the acceptability of a brief video that we developed to decrease the use of diabetes-stigmatizing language in patient-PCP encounters. PCPs were recruited online from professional organizations and via snowball sampling to participate in a single individual interview via Zoom (December 2021- October 2022). Trained interviewers conducted the interviews via Zoom using a semi-structured interview guide. A qualitative descriptive approach was used in the analysis. Eighteen PCPs were interviewed (44% aged 30-39 years old, 78% female, 78% non-Hispanic White, and 50% nurse practitioners). Qualitative description resulted in 3 major themes. Some PCPs perceive that the language used in patient-PCP encounters appears to play an outsized role in the culture of the clinic as far as endorsing or confronting diabetes stigma. Some PCPs perceive that they already advocate for decreasing the use of diabetes-stigmatizing language by being a role model for fellow PCPs and other colleagues. Some PCPs voiced their perspectives about the potential barriers to shifting PCPs away from the use of diabetes-stigmatizing language, including differing points of view regarding practices for establishing authority and the difficulties of breaking engrained habits. These findings support the acceptability of the video among PCPs for addressing diabetes-stigmatizing language in patient-provider encounters in primary care.

Disclosure
K.Joiner: None. A.Agapiou: None. M.Adams: None. G.Piatt: None.
1800-PUB: The Long-Term Effect of Glucagon-Like Peptide 1 Receptor Agonists on Glycemic Control Is Predominantly Related to Weight Loss
Authors: AL-BADRI MARWA , DHAVER SHILTON E. , SALAH TAREQ , KIBAA KARIM , KHATER ABDELRAHMAN , MCCARRAGHER RYAN , DEMATTOS LILY , AL-ROOMI FATIMAH , HAMDY OSAMA 
Published: June 2023

Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, they also induce weight loss by hypothalamic suppression of appetite. However, it is not clear if weight reduction is the main driver for glycemic improvement.
We retrospectively evaluated 256 patients with T2D; treated with either exenatide (n=84), dulaglutide (n=99), or semaglutide (n=73) without interruption for 2.5 years. Body weight and A1C were measured every 6 months. Average age was 61.8±11.9 yrs, 51.5% female, diabetes duration 12.9±8.3 yrs, weight 103.1±20.7 kg, BMI 35.7±7.5 kg/m2 and A1C 8.2±1.5%. We classified them collectively and in each medication group into tertiles according to percentage weight loss at 2.5 years. One tertile gained weight and the other 2 lost weight. In the entire cohort, A1C strongly correlated with weight change (p&lt;0.001). The average weight change in each tertile was -12.2±5.7%, -3.5±1.4%, and +2.8±3.4% respectively. The average change in A1C was -0.98±1.8%, -0.56±1.4% and -0.19±1.9 respectively. The same observations were reproducible in each medication group (Figure 1).
These data strongly suggest that long-term improvement in glycemic control with GLP-1 RAs is predominantly related to percentage weight loss, and the one third that gained weight had a nonsignificant change in A1C.

Disclosure
M.Al-badri: None. S.E.Dhaver: None. T.Salah: None. K.Kibaa: None. A.Khater: None. R.Mccarragher: None. L.Demattos: None. F.Al-roomi: None. O.Hamdy: Advisory Panel; Abbott Nutrition, Nemaura Medical, L-Nutra Inc., Twin Health, Consultant; Sanofi, Research Support; Novo Nordisk, Eli Lilly and Company, Gilead Sciences, Inc., Stock/Shareholder; Healthimation.
1815-PUB: Overactive Bladder Syndrome—An Emerging Complication of SGLT2 Inhibitor–Associated Urogenital Infections
Authors: GAUTAM ASHISH , AGRAWAL PRABHAT K. , PURSNANI NIKHIL , YADAV SHAILENDRA K. , GUPTA VINAY , DHAWAN ANCHAL 
Published: June 2023

Introduction: Recurrent urogenital infections (UGI) are common side effect of SGLT2i’s. Incidence of UGI’s is varies from 0% to 14.4 % including all SGLT2i’s & special population groups. Moderate or recurrent UGI causes prolonged morbidity even after treatment like incontinence, increased frequency & overactive bladder syndrome (OAB). OAB is defined symptomatically by presence of urgency, with or without urge incontinence without apparent pathological or metabolic disease. Exact etiology is still obscured. We conducted this retrospective observational study among people with DM2 who recovered from UGI due to SGLT2i’s
Aims and Objectives: Retrospectively assess disorders of micturition developed after recovery from SGLT2i’s associated UGI.
Methods: Two hundred & thirty-four subjects having DM2 who suffered SGLT2i’s associated any of UGI during previous 3 months, defined clinically or by microbiological investigations were enrolled. Exclusions h/o UGI before SGLT2i’s use, BPH, urogenital defects & uncontrolled glycaemic targets. After recovery from UGI following data was collected 1, increase in urinary frequency 2, prolonged burning or itching during micturition 3, urgency & dribbling 4, straining 5, incontinence 6, asymptomatic.
Result: Out of 273, subjects 173 (M 110, F 63) were asymptomatic after recovery whereas 37 (M 17, F 20) developed urgency & dribbling. There was significant association between UGI & urgency & dribbling, X2=143.1, p&lt;.00001. Frequencies of other complications were also high suggesting significant association between UGI & complication after recovery, X2=39.0, p&lt;.00001. Out of 100 symptomatic subjects 41 were male & 59 were female, X2 with Yates correction is 3.538. The p-value is .059978. Not significant at p&lt;.05
Conclusion: OAB is a common complication developed after recovery from post SGLT2i’s associated urogenital infections. Both genders are equally prone. Urgency & dribbling are most common among all symptoms

Disclosure
A.Gautam: None. P.K.Agrawal: None. N.Pursnani: None. S.K.Yadav: None. V.Gupta: None. A.Dhawan: None.
1827-PUB: Multidisciplinary Patient-Centered Care Delivered Remotely Improves Glycemic Outcomes and Patient Reported Outcomes
Authors: MINSKY NOGA , AHARON-HANANEL GENYA , JABARIN AMNA , ARNON LIAT , MOROZOV NICOLE , HALPERIN DANIA , SHALOM MOSHE , TARSHISH ELIZABETH , KOLOBOV TATYANA , TIROSH AMIR , TAMIR ORLY 
Published: June 2023

Lack of access to specialized multidisciplinary teams familiar with advanced technologies for T1D care remains a barrier to achieving glycemic targets and patient-centered goals. Since launching a T1D virtual clinic in 2018, we have treated 123 adults with T1D who had previously received standard care. There was a significant improvement in glycemic indices and in validated and self-originated patient reported outcome measures at 6 and 12 months as compared to baseline (table 1). Mean baseline HbA1c was 8.1%, and this improved to 7.6% and 7.3% at 6 and 12 months respectively (p&lt; 0.001). Average sensor glucose declined by 5.5% over 6 months (p&lt;0.001). While TIR increased significantly by 10.4% over 12 months, TBR decreased. Diabetes Treatment Satisfaction Questionnaire scores improved significantly, as did Diabetes Self-Management Questionnaire scores. According to a 5-point scale survey, there was improved satisfaction with the availability of the physician, nurse and dietitian beyond the appointment time and with the guidance received beyond scheduled visits. Remote care was associated with improved satisfaction regarding saving time and reducing expenses by curtailing office visits. In conclusion, transitioning from a standard T1D care to a virtual clinic is associated with improved glycemic control, higher patient satisfaction and better self-care behaviors.

Disclosure
N.Minsky: None. A.Tirosh: Advisory Panel; Medtronic, Novo Nordisk, Sanofi, Eli Lilly and Company, Research Support; Medtronic, Sanofi, Speaker's Bureau; Medtronic, Novo Nordisk, Sanofi, Eli Lilly and Company. O.Tamir: Other Relationship; Novo Nordisk. G.Aharon-hananel: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. A.Jabarin: None. L.Arnon: None. N.Morozov: None. D.Halperin: None. M.Shalom: None. E.Tarshish: None. T.Kolobov: None.

Funding
European Foundation for the Study of Diabetes (9366); Israel Ministry of Health
1831-PUB: Improving Accessibility of Patients with Type 1 Diabetes to Treatment by a Diabetes Nurse Practitioner
Authors: WAIZINGER ORIT 
Published: June 2023

Background: Treatment of type 1 diabetes (T1D) is complex, requires therapeutic intensity and understanding patient needs. The COVID-19 pandemic has led to a rapid and dramatic increase in the use of telemedicine to maintain treatment continuum and response to patients. Dedicated software, developed to transfer data from patients’ glucose sensors and insulin pumps to the treating team, facilitates personalized therapeutic interventions. Diabetes Nurse Practitioners (DNPs) have the knowledge, treatment skills and expertise for analyzing patient data transferred by the software; hence, they are an essential resource for managing diabetes treatment in these patients. The lack of suitable infrastructure and staff members who specialize in T1D has led to the establishment of a dedicated DNP unit within a diabetes clinic in Israel. The unit’s services are provided by frontal and telemedicine sessions to patients aged 18-40 with T1D. Its aims include continuous and regular monitoring of patients, achieving glycemic control according to patients’ personal targets, and preventing acute and late complications. The DNP provides comprehensive advice and training, assesses, and evaluates the patients' conditions, adjusts their therapy and refers them to appropriate care providers based on their medical and emotional conditions. Each session lasts 30-45 minutes. The summary of each session is sent to the diabetes doctor and to the primary clinic’s team.
Methods: Analysis of patient data treated by the dedicated DPN unit between January and July 2022.
Results: A total of 143 patients underwent 537 sessions; 55% were frontal visits and 44.4% were telemedicine visits (online or by phone). improved glycosylated hemoglobin was noted in 61% of patients. One patient was hospitalized.
Conclusions: DNPs are an important factor for improving the quality of care of patients with T1D by providing personalized care, continuous contact and better access to services through remote consultation.

Disclosure
O.Waizinger: None.
1838-PUB: Impact of COVID-19 on New-Onset Pediatric Diabetes Diagnoses
Authors: SIMMS KATHERINE , GREEN SARAH , SHAH MAMTA , SAREINI MEDINA , CHIN CINDY 
Published: June 2023

Introduction: Global trends show an increased number of pediatric patients with newly diagnosed diabetes who present in severe diabetic ketoacidosis (DKA) during the COVID-19 pandemic.
Methods: Medical records were reviewed for pediatric patients &lt;18 years of age with new onset diabetes mellitus (DM) diagnosed two years pre-pandemic and two years during the COVID pandemic. Data collected included demographic, biochemical, and hospitalization data.
Logistic regression was used to investigate the relationship between BMI, hemoglobin A1c, duration of hospital stay, DKA, and pandemic time frame.
Results: A total of 175 cases of new onset DM were diagnosed during the study period; 54% post-pandemic. This represents a 16% increase in incident cases in the post-pandemic period. The sample was 55.4% male, 74.9% White/Caucasian, and 33.1% non-Hispanic. Type 1 DM comprised 136 cases. Inpatient diagnoses were the same in both the pre- and post-pandemic periods, n=75. Outpatient diagnoses during the pandemic period (n=19) were significantly higher than in the pre-pandemic period (n=6), X2(1) = 5.83, p &lt; 0.05. The overall logistic regression model was statistically significant, X2(7) =18.35, p &lt; 0.05. Hemoglobin A1c (p &lt; 0.05, OR = 0.756, 95% CI [0.606, 0.945]) and length of hospital stay (p &lt; 0.05, OR = 0.586, 95% CI [0.381, 0.902]) were significantly different between the two time periods, but BMI percentile (p = 0.869) and bicarbonate levels (p = 0.962) were not.
Discussion: There was an increased incidence of new onset DM diagnosed in pediatric patients post-COVID. Surprisingly, outpatient cases accounted for the increased number. This study showed that during the pandemic, patients presented with a higher hemoglobin A1c and stayed longer in the hospital than prior to the pandemic.

Disclosure
K.Simms: None. S.Green: None. M.Shah: None. M.Sareini: None. C.Chin: None.
1839-PUB: Baseline FFA and IR after One Year of TB Treatment in People with Prediabetes—Pilot Study from South India
Authors: KUMPATLA SATYAVANI , DEVARAJAN ARUTSELVI , KORNFELD HARDY , VISWANATHAN VIJAY 
Published: June 2023

Background: Association of TB and prediabetes (PreDM)/insulin resistance (IR) and FFA remains unclear. Aim was to assess FFA and IR in TB with and without PreDM and to see the changes in IR in PreDM after 1 year of TB treatment.
Methods: A prospective study done from Jan 2017 to Sep 2019 in people with newly diagnosed PTB and PreDM (OGTT) in TB clinics and grouped as TB without PreDM (n=30) (group1) and TB with PreDM (n=37) (group2). Control without TB/PreDM (n=30) was included. Anthropometric, and biochemical details were noted. Insulin was measured by electro chemiluminescence and FFA by enzymatic end point method. IR was calculated by HOMA.
Results: Age was similar in groups (1vs.2; 40vs44). 2 hr glucose was significantly higher in group 2 than group1 (162vs. 108;p&lt;0.001). BMI, WC, fasting glucose and HbA1c were similar between groups. Mean IR was higher in group 2 than group1 (1.3vs.1; p=0.7). Median FFA was higher in TB PreDM (20.9) than without Pre DM (17.8) and control (14.9) (Figure1). High FFA (23vs.20) (p=0.4) and high IR (1 vs. 0.6) (p=0.2) were observed in BMI ≥vs.&lt;18.5 among TBPreDM. In group 2, baseline IR was high (0.82) and reduced to 0.71 and also those who remained PreDM (0.52) and who reverted to normal (0.44 from 0.71) after 1 year completion of TB treatment.
Conclusion: High FFA and IR was noted in TBPreDM and those with high BMI. Improvement in IR was noted 1 year after completion of TB treatment.

Disclosure
S.Kumpatla: None. A.Devarajan: None. H.Kornfeld: None. V.Viswanathan: None.

Funding
Indian Department of Biotechnology and Civilian Research; Development Foundation Global (USB1-31149-XX-13)