bluuebunny/crossref_metadata_2025_split huggingface dataset:
856-P: Long-Term Safety and Efficacy Evaluation of Hydroxychloroquine in T2D
Authors: PAREEK ANIL , CHANDURKAR NITIN , NAIDU KUMAR B. , DICHOLKAR PARNIKA 
Published: June 2023

This prospective, multicentric, phase 4 study enrolled 747 T2D patients uncontrolled (A1c≥7) on Metformin+SU combination to receive add on HCQ 400 mg/day for 52 weeks. Primary outcome measure was, long term safety of HCQ evaluated in ITT population (n=747). Secondary outcomes were post treatment changes in glycemic, lipids and inflammatory parameters. Total of 191 AEs were reported in 111 patients, most were GI related (26.2%), mild in intensity (85%) and unlikely related (70%) to HCQ. Level 1 hypoglycemia was reported in 6.8% patients and mild NPDR in 11 patients. Of the 9 SAEs reported, 8 were unrelated and 1 (anemia) was probably related to HCQ. In mITTc population, the overall fall in A1c, FBG and PPG at week 12, 24 and 52 was significant from baseline. Additionally, a significant fall in TC, LDL-C, non-HDL-C was reported at week 24 and 52 from baseline. Patients were divided in two subgroups based on their baseline hsCRP levels (≤3 or ≥3). Of the 52% females enrolled, more than 60 % had high inflammatory load at baseline. There was significant fall in A1c, FBG, PPG, LDL-C, TC, and non-HDL-C at week 24 and 52 irrespective of baseline hsCRP. However, fall in A1C was significantly more at week 12 and 24 in patients with higher inflammatory load (hsCRP: ≥3) at baseline (p&lt;0.0001). T2D is characterized by chronic low grade inflammation (meta-inflammation). HCQ has significantly reduced glycemic parameters with added benefits on lipids

Disclosure
A.Pareek: None. N.Chandurkar: None. K.B.Naidu: None. P.Dicholkar: None.
858-P: Recruitment Strategies for a Cellular Therapy Study for Type 1 Diabetes
Authors: BENN LEAH , GOU WENYU , NIETERT PAUL J. , CORNIER MARC-ANDRE , NORTON SUSAN , STRANGE CHARLIE , WANG HONGJUN 
Published: June 2023

Mesenchymal stem cells may be a novel T1D treatment based on immunoregulatory and tissue-protective properties. Therefore, an NIDDK sponsored prospective, single center, double blind study of MSCs for new onset T1D (NCT04061746) has generated significant social media interest. This trial is hard to enroll because of a narrow age range (18-30 years) and requirement of a new onset diagnosis (6 months). We evaluated the impact of social media tools, clinicaltrials.gov advertisement, and medical record review (EPIC) to define the optimal screening process for this and future trials. Through clinicaltrials.gov the study piqued the interest of 173 participants. Additionally, the study team has pre-screened 346 patients from an EPIC generated report. Among the 22 patients consented, referrals were received from physicians (N=5), clinicaltrials.gov (N=13), and EPIC reports (N=4). Among those discovered via EPIC list, we depicted the main reasons for study ineligibility (Fig. 1). The study recently launched a social media campaign in December 2022, initially reaching a total of 16,593 viewers. 4,475 viewers (26.97%) interacted with the campaign, and 2 (0.012%) were potentially interested in follow up from the research team. We conclude that clinicaltrials.gov, medical record review, and physician referrals are all critical to screening for new-onset diabetes studies. Other T1D studies might benefit from utilizing these strategies.

Disclosure
L.Benn: None. W.Gou: None. P.J.Nietert: None. M.Cornier: Consultant; Novo Nordisk, Alnylum, Letsgetchecked, Research Support; Novartis Pharmaceuticals Corporation, Amgen Inc., Kaneka. S.Norton: None. C.Strange: None. H.Wang: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK118529, DK120394, DK105183, DK125454); U.S. Department of Veterans Affairs (I01BX004536)
859-P: Study of Oral Antihyperglycemic Agents in the Hospital—A Multinational Perspective
Authors: FAYFMAN MAYA , HOCHBERG IRIT , MAGEE MICHELLE F. , RASHIED AMMAR A. , JAGANNATHAN RAM , BLANCO GERARDO , MARIE MORENO EMMELIN , PASQUEL FRANCISCO J. , UMPIERREZ GUILLERMO 
Published: June 2023

Oral antidiabetic drugs (OAD) are commonly used in the hospital setting despite limited safety and efficacy data.
To better understand the safety and efficacy of inpatient use of OAD, we pooled data from three healthcare systems in the US and Israel between from 2008-2018 (N=78,947). Treatment with OAD in the hospital was compared to Insulin (I) and OAD+Insulin (OAD+I). Patients on OAD were slightly older than those on I or OAD+I (67 vs 64 vs 65, respectively), more likely to admitted to surgical services (OAD: 33%; I: 21%, OAD+I: 23%, p&lt;0.0001), and to have lower admission blood glucose (Blood glucose (BG): (161 vs 200 vs 192 mg/dl, p&lt;0.0001). The average length of stay was 4-5 days for all groups. We performed propensity score matching by age, sex, Carlson Comorbidity Index, service (medicine or surgery), admission BG and creatinine to assess glycemic control and outcomes (Table). The primary outcome was good glycemic control with defined as mean hospital BG of 80-180 mg/dL and no hypoglycemia. Compared to I, patients treated with OAD were more likely to have good glycemic control [Odds Ratio (OR): 2.07 (95% CI: 1.85, 2.31)] and less hypoglycemia defined by BG &lt;70mg/dL [OR: 0.63 (95% CI: 0.54, 0.74)]. No differences in rate of lactic acidosis were observed.
In summary, patients treated with OAD had better in-hospital inpatient glycemic control, lower rates of hypoglycemia and no difference in lactic acidosis as compared to Insulin.

Disclosure
M.Fayfman: None. I.Hochberg: Other Relationship; Eli Lilly and Company, Novo Nordisk. M.F.Magee: None. A.A.Rashied: None. R.Jagannathan: None. G.Blanco: None. E.Moreno: None. F.J.Pasquel: Consultant; Dexcom, Inc., Medscape, Research Support; Dexcom, Inc., Ideal Medical Technologies. G.Umpierrez: Research Support; Abbott, Dexcom, Inc., Baxter.
86-OR: Self-Organized Insulin-Producing ß-Cells Differentiated from Human Omentum-Derived Stem Cells
Authors: HWANG YONGSUNG 
Published: June 2023

Human omentum-derived mesenchymal stem cells (hO-MSCs) possess a great potential to differentiate into multiple lineages and have self-renewal capacities, allowing them to be utilized as patient-specific cell-based therapeutics. Although various stem cell-derived insulin-producing β-cells have been proposed for the treatment of diabetes mellitus, developing an efficient method to establish highly functionalized insulin-producing β-cells remains a challenging task. Here, we aimed to develop a novel cell culture platform that could regulate important cell-cell/cell-matrix interactions by introducing a fibroblast growth factor 2 (FGF2)-immobilized matrix that can support cell adhesion, proliferation, and differentiation of hO-MSCs into insulin-producing β-cells. Our initial findings demonstrated that cells cultured on an FGF2-immobilized matrix were able to self-organize into insulin-producing β-cell-like progenitors, as evident from the upregulation of pancreatic β-cell-specific markers such as PDX-1, Insulin, and Glut-2. Furthermore, heparan sulfate proteoglycan, gap junction proteins including Cx36 and Cx43, and cell adhesion molecules such as E-cadherin and Ncam1 were significantly upregulated, leading to cell maturation and insulin secretion in the pancreatic niche environment. These results suggest that our novel platform could promote β-cell differentiation and glucose-stimulated insulin secretion from hO-MSCs by enhancing cell-cell junction proteins such as connexins (Cx36, Cx43), E-cadherin, and N-cam. Such a cell culture platform can offer novel strategies to obtain functional pancreatic β-cells from a patient-specific cell sources, ultimately enabling better treatments for diabetes mellitus.

Disclosure
Y.Hwang: None.

Funding
National Research Foundation of Korea (2019R1A5A8083404)
863-P: Effect of Bashan Tea Drink, a Vegetable Plant-Based Compound Tea Drink, on Blood Glucose in Type 2 Diabetic Patients
Authors: NI CHENGMING , SUN ZILIN , ZHOU XIAOYING , YAO SHENGHONG 
Published: June 2023

Background: The Bashan drink is a vegetable plant-based compound tea drink combing several pure plant ingredients. Plant-based ingredients are rich in phytochemicals, which can regulate human metabolic enzymes. For instance, catechin-rich green tea can reduce insulin resistance, increase insulin sensitivity and improve postprandial blood glucose.
Objective: To observe the effects of Bashan on blood glucose (BG) in type 2 diabetes (T2DM) patients by a standardized mashed potato meal and continuous BG monitoring.
Methods: A total of 29 patients (23 males, age 49.64±1.71years, HbA1c 8.49±0.42%) with T2DM who were newly diagnosed or failed to achieve glycemic control using antidiabetic monotherapy were included in the study. Subjects were randomized to take either 180ml of Bashan or water 3 times a day directly after meals for 2 weeks, with a 1-week washout period. Before and after the intervention, subjects were detected BG for 240 min after a mashed potato meal (368.5 kcal: 61.4 g carbohydrate, 7.4 g protein and 8.9 g fat). Average blood glucose(ABG) were collected from the continuous glucose monitors. Data are presented as means ± SEM, and P &lt; 0.05 was considered statistically significant.
Results: Four subjects were excluded for not completing the study. Compared with water, drinking Bashan significantly improved the ABG on day 10 to 12 (Bashan vs water: day 10, 7.37 ± 0.40 mmol/L vs 8.03 ± 0.45 mmol/L, P = 0.029; day 11, 7.17 ± 0.36 mmol/L vs 8.12 ± 0.59 mmol/L, P = 0.032; day 12, 6.90 ± 0.36 mmol/L vs 7.86 ± 0.54 mmol/L, P = 0.018). Drinking Bashan decreased HOMA2-IR and increased Homa2-%β, though not of statistical significance. (HOMA2-IR: Bashan day 14: 1.80 ± 0.17, day 1: 1.97 ± 0.19 vs water day 14: 1.83 ± 0.15, day 1: 1.80 ± 0.18, P &gt;0.05; HOMA2-%β: Bashan day 14: 86.26±9.02, day 1: 73.40 ± 8.24 vs water day 14: 74.29 ± 7.46, day 1: 71.42 ± 7.27, P &gt;0.05).
Conclusion: Drinking Bashan continuously can improve ABG, and can potentially improve insulin resistance and β cell function.

Disclosure
C.Ni: None. Z.Sun: None. X.Zhou: None. S.Yao: None.
864-P: Effects on Glycemic Control by Combination Therapy of Gliclazide-Metformin and Insulin in Type 2 Diabetes Mellitus Patients
Authors: SAIFUDDIN MOHAMMAD 
Published: June 2023

Background: Diabetes mellitus is most common non-communicable diseases. Purpose of this study was to observe the effects on glycemic control by combination therapy of gliclazide-metformin and insulin in type 2 diabetes mellitus patients according to baseline HbA1c, fasting blood glucose (FBG) and blood glucose 2 hours after breakfast.
Methods: An observational study was conducted at Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka and Outpatient Department of Ibrahim General Hospital, Mirpur, Dhaka over a period of one year (July 2018 to June 2019). Total 110 type 2 diabetic patients were selected purposively. The patients were divided into two groups. In group I, 55 patients treated with gliclazide (80mg) and metformin (500mg) combination therapy twice daily for consecutive 12 weeks and in group II, 55 patients treated with Insulin (premixed 30/70) twice daily for consecutive 12 weeks.
Results: After 12 weeks of treatment HbA1c level reduced from (mean ± SD) 8.94 ± 0.91 to 7.82 ± 1.86 in group I and 10.07 ± 1.28 to 7.90 ± 1.01in group II. FBG level reduced from 10.05 ± 1.57 to 7.96 ± 1.62 in group I and 11.61 ± 2.62 to 7.60 ± 1.23 in group II. Blood glucose 2 hours ABF level reduced from 14.00 ± 2.04 to10.99 ± 1.41 in group I and 16.70 ± 3.61to 10.71 ± 1.52 in group II. In group I, 36.4% patients achieved HbA1c target level, 40% patients achieved FBG target level and 25.5% patients achieved blood glucose 2 hrs ABF target level. In group II, 29.1% patients achieved HbA1c target level, 56.4% patients achieved FBG target level and 29.1% patients achieved blood glucose 2 hrs ABF target level
Conclusion: This study showed improvement in the overall glycemic control (HbA1c, FBG and blood sugar 2hours ABF) during the study period. Both groups of drugs are effective in controlling blood glucose but individual group has unique beneficial effect.
Key words: Type 2 diabetes mellitus, Glycemic control, Glicazide-Metformin

Disclosure
M.Saifuddin: None.
867-P: Empagliflozin-Based Quadruple Therapy vs. Insulin Glargine–Based Therapy in Type 2 Diabetes—Three-Year Follow-up Data
Authors: JEONG KU EU , OH TAEKEUN 
Published: June 2023

Objectives: To directly compare the long-term effectiveness and durability of sodium glucose co-transporter 2 (SGLT2) inhibitor, an empagliflozin-based quadruple therapy and insulin glargine-based therapy in patients with poorly controlled type 2 diabetes (T2D).
Research Design and Methods: Eligibility for this 3-year, open-label, prospective observational study was T2D patients (HbA1c, 7.5 - 12.0%) despite three distinct OADs (metformin, 2000 mg/day; dipeptidyl peptidase-4 inhibitor, maximal dose; and glimepiride ≥6 mg/day) between January 2017 and December 2021. Empagliflozin (25 mg/day, n = 167) or insulin glargine (n = 166) was added as the next agent. Outcomes included the time-to-treatment adjustment, changes in HbA1c level, and safety. Propensity score matched comparison and Kaplan-Meier estimation analysis were used.
Results: The estimated median time to treatment adjustment for empagliflozin group was 36.1 months (95% confidential interval [CI], 31.1 - 41.2), which was significantly longer than 18.3 months for the insulin glargine-based therapy (95% CI, 14.5 - 22.0). The mean change in HbA1c from baseline to month 36 were -1.5±1.0% and -1.0±1.4% in the empagliflozin group and the insulin glargine group, respectively (P=0.043). FPG showed a similar trend, although there was no statistical significance (-61.3±54.5 mg/dL vs -4.0±97.5 mg/dL, empagliflozin and insulin glargine group, respectively, P=0.129). Body weight showed a significant decrease in the empagliflozin group (-3.1±3.7 kg, P=0.003), whereas a significant increase in the insulin glargine group (3.2±2.6 kg, P&lt;0.001).
Conclusions: This study demonstrated that the effectiveness of empagliflozin as a quadruple combination therapy has been sustained for 3 years. In general, empagliflozin treatment was better than insulin glargine-based combination therapy.

Disclosure
E.Ku: None. T.Oh: None.
870-P: Empagliflozin and the Risk of Gout—Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: TESFAYE HELEN , PAIK JULIE M. , ZABOTKA LUKE , HTOO PHYO T. , SCHMEDT NIKLAS , KOENEMAN LISETTE , SEMAN LEO J. , WEXLER DEBORAH J. , PATORNO ELISABETTA 
Published: June 2023

Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout. Empagliflozin lowers serum urate levels by enhancing its urinary excretion. Using claims data from 2 commercial insurance datasets and Medicare (2014-2019), we evaluated the association between treatment with empagliflozin and the risk of incident gout in routine clinical practice. After excluding patients with a history of gout or gout medications, we identified 102,262 pairs of 1:1 propensity score-matched adults with T2D initiating empagliflozin or a DPP4 inhibitor (DPP4i) (Cohort 1), and 131,216 pairs initiating empagliflozin or a GLP-1 receptor agonist (GLP-1RA) (Cohort 2). We estimated pooled HR and RD/1,000 PY with their 95% CI adjusting for 141 baseline covariates and conducted stratified analyses within multiple subgroups (Table). Over a mean follow-up of ~8 months on treatment, the risk of gout was lower in patients initiating empagliflozin compared with patients initiating DPP4i [HR, 0.69 (0.60, 0.79); RD -2.27 (-3.08, -1.46)] or GLP-1RA [HR 0.83 (0.73, 0.94); RD -0.99 (-1.66, -0.32)]. Results were consistent within sex, age, BMI, HF, CKD subgroups and among users of diuretics (Table). In clinical practice, the initiation of empagliflozin was associated with a lower risk of incident gout compared with the initiation of DPP4i or GLP-1RA.

Disclosure
H.Tesfaye: None. J.M.Paik: None. L.Zabotka: None. P.T.Htoo: Employee; Johnson & Johnson. N.Schmedt: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.J.Seman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. D.J.Wexler: Other Relationship; Novo Nordisk A/S. E.Patorno: Research Support; Boehringer Ingelheim Inc., National Institutes of Health, Patient-Centered Outcomes Research Institute, US Food and Drug Administration.
874-P: Effect on Renal Function of SGLT2i Treatment in Hospitalized Patients with Type 2 Diabetes—A Real-World Study
Authors: BASHKIN AMIR , KRUZEL-DAVILA ETTY , TZFONI ITAI 
Published: June 2023

Background: SGLT2-I use is expanding greatly; however, temporary treatment hold is recommended in high risk states for kidney failure. Hospitalization is often associated with such risk, so the present study aimed to evaluate the effect on kidney function of SGLT2-I treatment in-hospital.
Methods: This retrospective case-control study conducted in internal medicine patients included only those treated with SGLT2-I for &gt;24 hours, and creatinine level was tested up to 48 hours before the start of treatment and after the end. Change in renal function was determined per eGFR (CKD-EPI formula). Factors most influencing in-hospital renal function were identified using backward regression.
Results: Among 186 patients included, 66.7% (124) were male, mean age 66.4±8.3 years. Main reasons for hospitalization were atherosclerotic CVD 23.7% (44), heart failure 17.2% (32), and infectious disease 15.6% (29). Median in-hospital SGLT2-I use was three days (interquartile range 2-5 days) and 73.1% (144) received SGLT2-I before hospitalization. Prior eGFR was not low in most participants: in 65.1% (121) &gt;60 ml/min/1.73 m2, and in only 13.4% &lt;45. A high correlation was found between eGFR before and after treatment (r=0.8, p&lt;0.001), with no drop in eGFR for the majority; however in 21% (39) it declined &gt;10%, in 11.3% (21) &gt;20%, in 4.8% (9) &gt;30%, and in only 2.7% (5) &gt;40%. The following factors were found to be significantly associated with a decrease in eGFR both &gt;20% and &gt;30%, including in-hospital initiation of SGLT2-I, in-hospital furosemide treatment, a background of insulin treatment, and age &gt;70 years. In 93 patients treated with SGLT2-I prior to hospitalization and who did not receive in-hospital furosemide, none had a drop in eGFR &gt;30% and only two &gt;20%.
Summary: In-hospital SGLT-2 treatment in type 2 diabetes is likely very safe from a renal standpoint in those treated pre-admission with SGLT2-I and not receiving furosemide.

Disclosure
A.Bashkin: None. E.Kruzel-davila: None. I.Tzfoni: None.
878-P: Absolute Amount of Urinary Glucose Excretion, Not the Change, Is the Measure Determinant for the Effects of SGLT2 inhibitors
Authors: HAMAMOTO YOSHIYUKI , YAMADA YUICHIRO , SEINO YUTAKA 
Published: June 2023

SGLT2 inhibitors exhibit hypoglycemic effect via increased urinary glucose excretion (UGE) by inhibiting glucose reabsorption in the kidney. Although the effects of SGLT2 inhibitors are theoretically dependent on UGE, clinical trials have shown renoprotective effect even in severely impaired kidney function. Thus, we aimed to investigate the relationship between UGE and various parameters before and after the administration of SGLT2 inhibitors. The patients newly administered SGLT2 inhibitors and measured 24-hour UGE before and after the administration during hospitalization for diabetes education were included. Body weight (BW), blood ketone levels, hematocrit (Ht), eGFR, and 7-point SMBG (DBG) were measured, and the correlations between the parameters before(b-), after (a-) and the change (Δ-) were analyzed by simple linear regression. A total of 32 patients (age 59.3±10.9 years, 19 males) were included (empagliflozin 5, tohogliflozin 6, dapagliflozin 2, canagliflozin 4, luseogliflozin 15). The mean A1C and BW were 8.8±1.2% and 77.7±11.5kg, and mean UGE, average of DBG at baseline were 15.4 ± 27.5g/day and 10.3±2.0mM/L, respectively. As shown in table, ΔDBG showed correlation only with UGE before and after administration but not with ΔUGE. In conclusion, hypoglycemic effect of SGLT2 inhibitors is dependent on absolute amount of UGE but not on ΔUGE after administration.

Disclosure
Y.Hamamoto: None. Y.Yamada: Speaker's Bureau; Novo Nordisk Pharma Ltd., Teijin Pharma Limited, Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd. Y.Seino: Research Support; Terumo Corporation, Nippon Boehringer Ingelheim, Arkray Marketing, Taisho Pharmaceutical Holdings Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Speaker's Bureau; Merck & Co., Inc., Nippon Boehringer Ingelheim, Arkray Marketing, Taisho Pharmaceutical Holdings Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd.
88-LB: The Microvascular Effects of the Noninsulin Standard Antidiabetic Medications—A Literature Systemic Review of Randomised Controlled Clinical Studies
Authors: WEN SONG 
Published: June 2023

Backgrounds: As many advances have been made in recent decades in the understanding of the pathophysiology of diabetic macrovascular complications and novel pharmacological approach, few investigations on the importance and how the hypoglycemic medications that are currently available in reducing diabetic microvascular complications, though this amelioration can be achieved via intensive glycemic control such as insulin therapy. This study reviews the implications of diabetic microvascular complications by non-insulin antidiabetic medications.
Methods: We searched and screened the literature of randomized clinical trials that reported the effects of drugs on diabetic microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR) from multiple clinical databases. We extracted the indices of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) or urinary albumin excretion rate (UAE), and indices for DPN or DR. Comparisons were made between certain classes of non-insulin antidiabetic medications.
Main Results: The analyses showed the urinary albumin to creatinine ratio (UACR) or urinary albumin excretion rate (UAE) showed variations in both the effects and significance of the decline. In addition, due to the unavailable of a unified standard metric index on DPN or DR, we compiled different common measures on the DPN or DR, and also found disparities in both the effect and significance of each medication.
Conclusions: Till now, all the reviewed non-insulin hypoglycemic medications showed different degrees of preventing diabetic microvascular complications. As emerging or ongoing trials will reveal the implications of diabetic microvascular prevention, more results with higher quality in comparative efficacy between different classes of non-insulin antidiabetic medications could serve as more powerful evidence for recommendation and utilized in clinical personalized treatment practices.

Disclosure
S. Wen: None.

Funding
Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP0202118)