bluuebunny/crossref_metadata_2025_split huggingface dataset:
128-LB: Sodium–Glucose Cotransporter-2 Inhibitors and Risk of Retinal Vein Occlusion among Patients with Type 2 Diabetes: A Propensity Score–Matched Cohort Study
Authors: LEE MIN-KYUNG , HAN KYUNGDO , KWON HYUK-SANG , ROH YOUNG-JUNG 
Published: June 2021

Objective: To assess the association between use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and retinal vein occlusion (RVO) using data from the National Health Insurance Service in South Korea.
Research Designs and Methods: We used an active comparator, new user design and nationwide data from 2014 to 2017. Based on a 1:1 propensity score match, we included 47 369 new users of SGLT2 inhibitors and 47 369 users of other glucose-lowering drugs (oGLD). The mean follow-up time for the primary intention-to-treat analysis was 2.57 years. We used the Cox proportional hazards regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for RVO. Based on the main outcome, a prespecified subgroup analysis was undertaken.
Results: During follow-up of 2.57 years, the incidence rate of RVO was 2.19 and 1.79 per 1000 person-years in patients treated with SGLT2 inhibitors and oGLD, respectively. The use of SGLT2 inhibitors was associated with an increased risk of RVO compared with oGLD use (HR 1.264, 95% CI 1.056-1.513). In the subgroup analyses, a significant interaction with SGLT2 inhibitors was observed for age and estimated glomerular filtration rate (eGFR); the HR for RVO was higher in patients aged ≥60 years and those with eGFR &lt;60 mL/min/1.73m2 than in others.
Conclusions: In a matched cohort study, we found that SGLT2 inhibitors were associated with a significantly increased risk of RVO. The elderly and patients with chronic kidney disease were at higher risk for RVO.

Disclosure
M. Lee: None. K. Han: None. H. Kwon: None. Y. Roh: None.
129-OR: Glycolytic Enzymes and Creatine Kinase Locally Regulate KATP Channel Activity in Both ß- and a-Cells
Authors: HO THUONG , POTAPENKO EVGENIY , MERRINS MATTHEW J. 
Published: June 2021

The ATP-sensitive potassium channel (KATP) is a key regulator of membrane potential and islet hormone secretion. In ß-cells, it has been previously showed that the local activity of pyruvate kinase (PK) can sufficiently raise ATP/ADP to induce KATP closure, thus providing a another route to trigger membrane depolarization parallel to mitochondrial oxidative phosphorylation. Here, using direct single-channel measurements of KATP in both ß-and the lesser studied α-cells, we provide evidence for a larger network of metabolic enzymes that operate in the vicinity of KATP channels to fine-tune their activity. We found that the phosphofructokinase product fructose-1,6-bisphosphate (FBP), which oscillates in ß-cells, can induce KATP closure by its metabolism through the glycolytic chain including aldolase, GAPDH, phosphoglycerate kinase, phosphoglycerate mutase, enolase and finally PK. Strikingly, while withholding the substrates at GAPDH, we observed that FBP can independently inhibit KATP channels by direct action. In addition, we further provide evidence that creatine kinase (CK) activity can either oppose or enhance KATP closure, depending on the reaction direction. Finally, we demonstrated that lactate has an activating effect on KATP.
In summary, these data provide evidence for the direct regulation of KATP by two metabolites, FBP and lactate, and identify two local ATP/ADP controllers, the glycolytic complex and the creatine kinase system in both ß-cells and α-cells.

Disclosure
T. Ho: None. E. Potapenko: None. M. J. Merrins: None.
132-LB: The Safety and Efficacy of Canagliflozin in Women with Polycystic Ovary Syndrome: A Randomized Control Trial
Authors: CAI MEILI , ZHANG YUQIN , QU SHEN , ZHANG MANNA 
Published: June 2021

Objectives: To determine the safety and efficacy of canagliflozin in Polycystic Ovary Syndrome (PCOS) patients with insulin resistance (IR) and investigate whether canagliflozin was non-inferiority to metformin in PCOS patients with IR.
Methods: A randomized open-label study (ratio 1:1) was conducted in the department of endocrinology, Shanghai Tenth people’s Hospital between July 2019 and March 2021. PCOS women aged 18-45 years with IR were enrolled and randomly assigned to either canagliflozin 100 mg (n = 32) or metformin 1500-2000 mg (n = 35) daily for 12 weeks. The primary outcome was the changes in HOMA-IR before and after 12 weeks treatment. The secondary outcome were the changes in anthropometric, body composition, menstrual frequency, hormonal and metabolic parameters.
Results: A total of 53 subjects in the canagliflozin (n=27) and metformin group (n=26) have completed follow-up. Both canagliflozin (5.4±4.1 vs. 3.2±1.9; P=0.001) and metformin (4.7±3.5 vs. 3.6±3.0; P=0.009) can significantly improve HOMA-IR after 12 weeks in PCOS patients with IR. There was no significant difference in the changes of HOMA-IR (canagliflozin: −2.3 ± 3.2 vs. metformin: -1.4 ± 2.4; P = 0.222) between the two groups. According to a secondary endpoint analysis, the canagliflozin group resulted in significantly low uric acid than the metformin group. The changes in anthropometric, body composition, menstrual frequency, sex hormone and other metabolic parameters were comparable between two groups. Gastrointestinal reaction (including nausea, vomiting and Diarrhea) (57.14 %) and pruritus vulvae (6.25%) were the main adverse events in the metformin group and Canagliflozin group, respectively. There were none serious adverse events in both groups.
Conclusion: Our study showed that canagliflozin was not significantly inferior to metformin in PCOS patients with IR, which suggested SGLT2 inhibitor should be considered as an effective drug in the treatment of patients with PCOS.

Disclosure
M. Cai: None. Y. Zhang: None. S. Qu: None. M. Zhang: None.

Funding
National Natural Science Foundation of China (81601269)
134-LB: Efficacy and Safety of Dapagliflozin in Type 1 Diabetes: The RISING-STAR Study
Authors: HAMAGUCHI MASAHIDE , YAMAZAKI MASAHIRO , TANAKA TORU , ISHII MICHIYO , OKADA HIROSHI , MITSUHASHI KAZUTERU , KITAGAWA NORIYUKI , HASEGAWA GOJI , FUKUI MICHIAKI 
Published: June 2021

Background and Objective: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, two-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction.
Method: The basal insulin dose to total daily insulin dose (TDD) ratio was defined as less than 40% in group A and more than 40% in group B. Group B was instructed to reduce basal insulin dose, while group A was not.
Results: Twenty-nine patients in group A and 28 patients in group B were included in the analysis due to withdrawal of consent before the start of the study. The frequency of hypoglycemia before and after the intervention was 0.23 times/day in group A to 0.26 times/day and 0.19 times/day in group B to 0.23 times/day, with no significant difference between the two groups (P=0.69). The frequency of ketosis, a secondary endpoint, also increased significantly after the intervention, from 0.013 times/day to 0.086 times/day in Group A (p=0.013) and from 0.013 times/day to 0.059 times/day in Group B (p=0.011). Time In Range on FGM improved from 63.6% to 69.7% in group A and from 59.0% to 69.1% in group B. MAGE improved from 121.7 mg/dL to 105.0 mg/dL in group A and from 123.4 mg/dL to 108.0 mg/dL in group B. DTSQ showed a significant improvement in question 2 regarding hyperglycemia in both groups after the intervention, from 3.6 to 2.5 (p=0.008) in group A and from 3.7 to 2.8 (p=0.017) in group B.
Conclusion: In the patients who were able to self-adjust their insulin dose, there was no significant difference in the number of hypoglycemia occurrences after concomitant use of dapagliflozin with or without instruction to reduce basal insulin dose. Concomitant use of dapagliflozin resulted in less glycemic variability, prolonged TIR and improved patient satisfaction regarding with hyperglycemia.

Disclosure
M. Hamaguchi: Research Support; Spouse/Partner; AstraZeneca K. K. M. Yamazaki: None. T. Tanaka: None. M. Ishii: None. H. Okada: None. K. Mitsuhashi: None. N. Kitagawa: None. G. Hasegawa: None. M. Fukui: None.

Funding
AstraZeneca K.K.; Ono Pharmaceutical Co., Ltd.
138-LB: Managing Hyperglycemia in Patients on an Insulin Pump: A Quality Improvement Study
Authors: YUEN ALEXA , TABATABAIE VAFA 
Published: June 2021

During the transition from multiple daily injections to an insulin pump, diabetic patients need to engage in an intense period of learning to operate their pumps successfully. Inpatient endocrinology consultants note that some new users of insulin pumps fail to manage hyperglycemia correctly and present to the hospital in diabetic ketoacidosis. We found these patients often did not know when to use manual injections instead of their pumps or did not have backup insulin pens or syringes at home. To better understand this issue, a baseline survey of diabetic patients on insulin pumps was conducted from February to September 2020. The survey was administered to 52 subjects identified though appointments scheduled with the diabetes clinic. The questionnaire asked: 1) How would you respond if your sugar remained elevated an hour after administering a correction bolus through the pump? 2) Do you have insulin syringes or pens at home? The first question reflects events that would occur in the setting of an insulin pump failure. Any response that did not include a manual injection was considered incorrect. Our data showed that 85% of respondents had backup insulin supplies. 33% of patients overall responded appropriately to the pump failure scenario. Of the subjects who had insulin supplies, 39% responded correctly. Further analyses revealed that there is a significant relationship between having supplies and responding appropriately to hyperglycemia in pump failure. There was no relationship between patients’ answers and gender or age. Results of this survey will be used to modify the electronic template for diabetes clinic visits in order to help ensure that patients have appropriate supplies and training in identifying pump malfunctions and handling hyperglycemia. As part of this quality improvement project, patients will be surveyed again after implementation of the new template to assess whether the rates of possessing backup insulin supplies and of appropriate responses to hyperglycemia increased.

Disclosure
A. Yuen: None. V. Tabatabaie: None.
140-LB: Improving Translation of Diabetes Management Practices in Community Primary Care
Authors: THOMAS CELESTE C. , PEEK MONICA E. , PAUL CARLIE , ALLISON MARGARET , HEILBRUN ANNA , TILMON SANDRA , THOMPSON ROSHAWNDA , THOMAS DAVIEL P. , JOHNSON DANIEL C. 
Published: June 2021

Objective: To evaluate the feasibility of using an innovative workforce development model, Project ECHO (Extension for Community Health Outcomes), to improve knowledge and self-efficacy around diabetes management practices among PCPs serving urban, under-resourced communities in the Chicago area.
Methods: The Project ECHO model was applied to the management of medically and socially complex diabetes. For this series, a multidisciplinary subject matter expert team met with 30 PCPs from 12 health centers across the Chicago area for 17 weekly videoconferencing telementoring sessions. PCPs completed knowledge tests and self-efficacy surveys prior to the first session. During each hourly session, after a short didactic, PCPs presented de-identified patient cases for discussion and received evidence-based guidance and mentorship with a focus on individualized care. After series completion, PCPs repeated surveys. Post-program semi-structured interviews were conducted.
Results: Increase in self-efficacy for treating complex diabetes reached the goal of 10% (p=.0007); the percentage of knowledge questions answered correctly increased from 39% to 62% (p&lt;.0001). Participants reported increased comfort with and use of newer therapeutic agents. Participants reported taking the complicated psychosocial contexts of patients more in mind and adapting treatment regimens accordingly. One participant noted: “I was able to pick up pointers on how to talk to patients and how to motivate them asking the right questions about what is challenging for you, what can we do, and offer treatment, offer support accordingly.”
Conclusion: Among PCPs serving under-resourced communities in the Chicago area, ECHO-Chicago: Complex Diabetes improved confidence and knowledge in complex diabetes management. Interviews demonstrate changes in clinical practices. Continued application of the ECHO model to medically and socially complex diabetes care is likely to be useful in under-resourced communities.

Disclosure
C. C. Thomas: None. M. E. Peek: None. C. Paul: None. M. Allison: None. A. Heilbrun: None. S. Tilmon: None. R. Thompson: None. D. P. Thomas: None. D. C. Johnson: None.

Funding
Chicago Center for Diabetes Translation Research
145-LB: Glycemic Control Is Not an Independent Predictor of Mortality or Length of Stay for Patients Hospitalized with Coronavirus 2019 (COVID-19)
Authors: JAKOBY MICHAEL G. , WILLIAMS VANESSA , WARD STACEY , LEE SCOTT K. , BUHNERKEMPE MICHAEL , IZUORA KENNETH 
Published: June 2021

Diabetes mellitus (DM) is an important prognostic factor for coronavirus 2019 (COVID-19). However, studies of hospital glycemic control and outcomes controlled for factors that affect morbidity and mortality in pneumonia (PNA) are limited. We conducted a multicenter retrospective cohort study of patients ≥ 18 years (N=108) admitted to either the ICU or noncritical units January 1, 2020 to September 29, 2020 with a clinical diagnosis or radiographic evidence of PNA, laboratory confirmation of COVID-19, and DM or newly diagnosed hyperglycemia, defined as admission plasma glucose &gt; 126 mg/dL or one or more random plasma glucose measurements &gt; 200 mg/dL. Co-primary endpoints were mortality, ICU length of stay (LOS), and total hospital LOS stratified by mean capillary blood glucose (CBG) for hospitalization. Endpoints were compared by logistic, linear, or Poisson regressions controlling for demographic variables, prehospital HbA1c, residence, pneumonia severity index score, Sequential Organ Failure Assessment score (ICU patients), pulmonary consultation, infectious diseases consultation, and study site. Patients treated with dexamethasone (N=42) were evaluated separately from untreated patients. There was no difference in mortality for patients with mean hospital CBG &lt; 180 mg/dL (30.1%) or ≥ 180 mg/dL (20.0%, P=0.24). Median total hospital LOS was 8 (5-15) and 8 (6-16) days for patients with mean CBG &lt; 180 mg/dL or ≥ 180 mg/dL, respectively (P=0.35), and there was no difference in ICU LOS by glycemic status (P=0.19). No measures of glycemic control were independent predictors of mortality or LOS in multivariable regression analyses, and results were unaffected by dexamethasone treatment status. In this study controlling for multiple validated PNA prognostic factors, hospital glycemic control did not have a significant effect on mortality or LOS for patients with DM or newly diagnosed hyperglycemia hospitalized with COVID-19.

Disclosure
M. G. Jakoby: None. V. Williams: None. S. Ward: None. S. K. Lee: None. M. Buhnerkempe: None. K. Izuora: None.
146-LB: Association of Serum 1,5-Anhydroglucitol with Severe COVID-19 in T2D patients
Authors: SONIA GAZTAMBIDE , BUTTON ERIC A. , ZULUETA MIRELLA , ARANA EUNATE , DE LA HOZ ANA B. , MENDIZABAL LEIRE , DEL OLMO JUAN , MUÑOZ RAQUEL , SIMON LAUREANO , CASTANO LUIS 
Published: June 2021

Background: Hyperglycemia worsens the prognosis and severity in Covid-19 patients.
Objective: To assess the impact of glycemic control on COVID-19 severity.
Methods and Findings: Data from 460 individuals collected in Spain between April and July 2020 was analyzed in a cross-sectional study: healthy, Sars-Cov-2 negative (group 0, N = 197), Sars-Cov-2 positive, with mild COVID-19 symptoms (group 1, N = 113), Sars-Cov-2 positive, with severe COVID-19 symptoms who required hospitalization (group 2, N = 150) at Hospital Universitario Cruces in Bilbao, Spain. Fasting blood glucose, HbA1c and serum 1,5-anhydroglucitol (1,5-AG, indicator of hyperglycemic excursions over the prior 1-2 weeks) were measured. Differences in 1,5-AG (normal range &gt;10µg/mL) were observed between all three groups (mean 1,5-AG of 21.19, 18.99, 14.64 µg/mL, respectively) when compared by an unpaired t-test. 1,5-AG levels across groups decreased with increasing severity, with the hospitalized patients (group 2) showing the greatest difference when compared to healthy individuals, p value &lt; 0.0001. Logistic regression analysis showed that 1,5-AG had a mild positive association with increased COVID-19 severity (group 0 vs. group 2: AUC = 0.69, p value &lt; 0.0001). A previous T2D diagnosis did not show association with COVID-19 severity (group 0 vs. group 2: AUC = 0.58, p value &lt; 0.0001). Analysis of patients with a previous diagnosis of T2D showed a robust positive association between 1,5-AG and COVID-19 (group 0 vs. group 2, AUC = 0.79, p value 0.008). There was no association between HbA1c or fasting glucose with severity. Combination of 1,5-AG and HbA1c was similar than 1,5-AG alone (AUC = 0.80, p value 0.028).
Conclusions: Glycemic fluctuations in T2D patients may contribute to severe COVID-19. Measurement of serum 1,5-AG in T2D patients might help clinicians quickly identify diabetes patients at risk of severe COVID-19. These patients may benefit from more intensive management, treatment and vaccine prioritization.

Disclosure
G. Sonia: None. L. Castano: None. E. A. Button: Employee; Self; Precision Diabetes, Inc. M. Zulueta: Employee; Self; Patia Europe. E. Arana: None. A. B. De la hoz: None. L. Mendizabal: Employee; Self; PATIA. J. Del olmo: None. R. Muñoz: None. L. Simon: Board Member; Self; Oncomatryx Biopharma, S. L, Patia Biopharma, SA de CV, Patia Europe S. L., Permedika Entrepeneurs, S. L, SunRock, S. L, Employee; Self; Oncomatryx Biopharma, S. L, Patia Biopharma, SA de CV, Patia Europe S. L., PatiaCan, SA de CV, Permedika Entrepeneurs, S. L, Other Relationship; Self; Oncomatryx Biopharma, S. L, Patia Biopharma, SA de CV, Quimatryx, S. L, Stock/Shareholder; Self; Helenes Ventures, S. L, Nelum, Corp, Oncomatryx Biopharma, S. L, Patia Biopharma, SA de CV, Patia Europe S. L., PatiaCan, SA de CV, Permedika Entrepeneurs, S. L, Stemcell Therapeutics, S. L, SunRock, S. L.
147-LB: Targeted Intervention for At-Risk Patients with Diabetes to Reduce Readmissions
Authors: HARRIS ASHLEY , GRDINOVAC KRISTINE 
Published: June 2021

With benefits to patient outcomes, provider burden, and health system costs, the goal of reducing hospital readmissions for patients with diabetes mellitus (DM) is multifaceted. Current studies have neither elucidated a clear approach to accurately identify at-risk patients nor implemented reliable interventions to significantly reduce readmissions. We trialed a Quality Improvement project utilizing a diabetes Nurse Practitioner (NP)/Certified Diabetes Care and Education Specialist (CDCES) to see at-risk patients during initial hospitalization and in close clinic follow-up after discharge with an endpoint of reducing future readmissions. Over 21 months, 79 hospitalized patients with DM were identified as high-risk for readmission. Identifying factors included previous admission, DKA/HHS, new DM diagnosis, new to insulin, high-dose steroid use, or provider discretion. The NP/CDCES provided DM management, education, and coordinated discharge. Patients were called shortly after discharge and had a 2-4 week clinic follow-up with the NP/CDCES. The primary endpoint was number of readmissions 180 days post-discharge after NP/CDCES intervention versus number of previous readmissions pre-intervention. Change in hemoglobin A1C, time to post-hospital phone call, and time to outpatient follow-up were also evaluated. Pre- and post-intervention readmission rates remained unchanged; average pre-intervention readmissions per patient was 1.7 versus 1.88 post-intervention readmissions (p=0.74). However, a secondary endpoint of reduction in A1C was statistically significant, with a mean decrease in A1C of 0.97% per patient (p=0.0025). Time to post-hospital phone call and early follow-up did not affect readmission rates. While targeted inpatient-to-outpatient intervention for high-risk patients with DM did not reduce readmission rates, our data suggests coordinated inpatient intervention with close hospital follow-up may improve A1C in high-risk patients with diabetes.

Disclosure
A. Harris: None. K. Grdinovac: None.
15-OR: The COVID-19 Pandemic and New-Onset Pediatric Type 2 Diabetes
Authors: MARKS BRYNN E. , KHILNANI ANEKA , MEYERS ABBY , ESTRADA DORIS E. , BOUGHTON JENNIFER , GAI JIAXIANG , STREISAND RANDI , MONAGHAN MAUREEN 
Published: June 2021

Introduction: Reports are emerging about the impact of the COVID-19 pandemic on pediatric T1D, however few studies have explored pediatric T2D. We aimed to investigate changes in T2D initial clinical presentation and patient demographic characteristics during COVID-19.
Methods: A retrospective cross-sectional review of youth diagnosed with T2D during the COVID-19 pandemic (3/11/2020-11/30/2020) and in the time matched period in 2019 was conducted at a pediatric tertiary care center. BMI Z-score (&gt;1.64), age (&gt;8) and the absence of DKA and autoantibodies at diabetes diagnosis (A1c &gt;6.5%) were used to screen for T2D, with confirmation by chart review. Chi-square, Fisher’s exact, and independent samples t-tests were used for analyses.
Results: During the pandemic, cases of T2D increased 233% from 2019 (n=36, Mage=14.1±2.6 years, 56% F) to 2020 (n=84, Mage=14.6±2.2 years, 42% F). Rates of new onset T2D increased as the pandemic continued, from 4-8 per month in April-June to 20 and 16 cases, respectively, in October and November. Only 3 youth were actively infected with COVID-19 at T2D diagnosis. Rates of DKA at diagnosis increased from 6% in 2019 to 21% in 2020 (p=0.03), with 6 cases of hyperosmolar DKA during the pandemic as compared to none in 2019. Before the pandemic, 53% of youth diagnosed with T2D were Black, compared to 77% during the pandemic (p=0.03). Similar increases were seen among those with public insurance, rising from 67% to 86% (p=0.02).
Conclusions: Cases of T2D and severity of initial presentation increased during the first 9 months of the COVID-19 pandemic, particularly among Black and publicly insured youth. These findings align with prior reports highlighting the disproportionate impact of the COVID-19 pandemic on racial/ethnic and socioeconomically disadvantaged communities. As few youth were infected with COVID-19 at T2D diagnosis, pandemic-related social distancing measures may also have disproportionate impacts on these communities and serve to worsen pre-existing health disparities.

Disclosure
B. E. Marks: None. A. Khilnani: None. A. Meyers: None. D. E. Estrada: None. J. Boughton: None. J. Gai: None. R. Streisand: None. M. Monaghan: None.