bluuebunny/crossref_metadata_2025_split huggingface dataset:
2324-PUB: Assessment of the Effectiveness of Risk Minimization Measures for Concentrated Insulin Lispro 200 Units/ml: A Multinational Study
Authors: ALI AYAD K. , EWING MELISSA 
Published: June 2019

This study evaluated the impact of additional risk minimization measures on healthcare professional (HCP) and patient understanding and behavior regarding the risk of hypoglycemia and/or hyperglycemia due to medication errors associated with administration of insulin lispro 200 units/ml (U-200) in U.S. and EU. The additional risk minimization measures for U-200 included a direct HCP letter, and a patient communication. Web and telephone cross-sectional surveys were administered to HCPs involved in the treatment and management of patients with diabetes who are aware of U-200, and adult patients with diabetes who have been prescribed U-200 in France, Germany, Sweden, and U.S.
A total of 424 HCPs (278 in U.S., 146 in EU) and 307 patients (300 in U.S., 7 in EU) completed the surveys. Among HCPs, 46% (U.S.=56%, 95% CI=50%-62%; EU=27%, 95% CI=20%-35%) were aware U-200 is not approved for transfer to different insulin delivery device; however, HCPs knowledge of appropriate U-200 prescribing was high: 95% indicating correct strength on prescription (U.S.=98%, 95% CI=95%-99%; EU=91%, 95% CI=85%-95%); and 73% answered that dose conversion is not necessary when changing patients between insulin lispro strengths (U.S.=80%, 95% CI=75%-84%; EU=60%, 95% CI=51%-68%). The vast majority of patients in U.S. (97%, 95% CI=94%-99%) were aware that U-200 should only be injected using the prefilled pen in which it is supplied. In U.S., 78% (95% CI=73%-83%) of patients and 92% (95% CI=88%-95%) of HCPs indicated it is always necessary to carry a backup pen.
In conclusion, this study showed in general that the additional risk minimization measures effectively communicated the key safety messages to the majority of HCPs. Patient recruitment in EU was challenging due to the stringent data protection regulations which makes the collection of meaningful pharmacovigilance-related data for patients in EU very difficult.

Disclosure
A.K. Ali: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. M. Ewing: Employee; Self; Eli Lilly and Company.
2326-PUB: The Correction Factor (CF) and Carbohydrate-to-Insulin Ratio (CIR) Are More Correlated to Each Other than to the Total Daily Dose (TDD)
Authors: SOCHA JILLAINE , KING ALLEN B. 
Published: June 2019

The accepted bolus dosing factor estimation formulas are CIR = 450/TDD and CF = 1700/TDD. These formulas were not based on controlled studies. We have combined two of our previously published well-controlled studies to reevaluate these relationships. Both studies (30 pump treated T1DM and 11 pump- or multiple daily dose-treated T1 or 2 subjects) established the basal insulin dose by frequent glucose testing while on a controlled diet and meal omissions to assess the post-meal period. Then CIR was determined by the return of the 2-4 h post meal plasma glucose (PG) to ± 20% of the pre-meal and the CF was independently determined by greatest PG reduction during the 2-4th hour after a corrective bolus following hyperglycemia induced by a reduction (about 30%) of the basal insulin. CIR = CF/4.49 (r = 0.940), CIR = 295/TDD (r =0.720) and CIR = 107/TBD (r = 0.7310). The strong relationship between CIR and CF may be explained by CF is a measure of the ∆ PG/U and CIR is a measure of the anticipated ∆ PG/U and both are expressions of the insulin sensitivity of the same tissue bed. If one bolus dosing factor is established, the other could better be estimated using CF = CIR*4.5 than from TDD. The usual order of titration is TBD, then CIR and CF and finally TDD is calculated. After TBD is established and before bolus dosing factors and TDD, CIR = 100/TBD would be a better estimate than 450/TDD.

Disclosure
J. Socha: None. A.B. King: None.
2329-PUB: Transitioning T2DM Patients to Basal-Bolus Insulin Leads to Sustainable A1C Improvement
Authors: BARRY ROMIYA , JOHNS DON , REES BUDDUG 
Published: June 2019

This is a post hoc analysis of a multi-country study of adults with type 2 diabetes transitioned from basal-only to basal-bolus insulin therapy. Patients were randomized 1:1 to deliver mealtime insulin using either a wearable delivery device (PAQ Meal) or a pen (NovoLog FlexPen®). We report the proportion of patients overall who achieved A1C ≤8% and A1C ≤7% by Week 24 and sustained the improvement through Week 44 when using a basal-bolus regimen. Baseline A1C ranged from 7.0 - 11.8% (patients, n=274). By week 24, 84.7% (232/274) of patients achieved A1C ≤ 8% (LOCF) which continued at 84.8% (184/217 completers) at Week 44. Overall, 77.9% (169/217) of patients saw a reduction of at least 1% in A1C by Week 44. Although, patients with higher baselines achieved a greater reduction of A1C, patients with lower baselines were significantly more likely to achieve A1C ≤ 7%. Reduction in A1C ≤ 7% was sustained by 63.6% (138/217) of patients through Week 44. Initiating a basal-bolus regimen and titrating based on morning and mealtime blood glucose levels saw the mean total daily dose increase from 47IU (basal only) at study entry to 121IU (basal-bolus) at Week 24 (0.8:1 basal:bolus). Only 6 severe hypoglycemic events occurred during the study. This study shows that transitioning from basal insulin-alone to basal-bolus insulin therapy, regardless of delivery mechanism, safely reduces and manages A1C levels in T2DM patients.

Disclosure
R. Barry: Consultant; Self; CeQur Corporation. D. Johns: Consultant; Self; CeQur Corporation. B. Rees: None.
2331-PUB: Effectiveness of Insulin Glargine 300 units/mL in Treating Patients with T2DM Uncontrolled by Basal Insulin in Real-Life Settings in the Czech Republic (TOPAZ Study)
Authors: PRAZNY MARTIN , FLEKAč MILAN , JELINEK PETR , MASKOVA JANA 
Published: June 2019

Objective: To evaluate the clinical effectiveness of Gla-300 units/mL (Gla-300) in the treatment of patients with type 2 diabetes (T2DM) uncontrolled by basal insulin in real-life clinical settings in the Czech Republic (TOPAZ study).
Methods: TOPAZ was a prospective, multi-centric, non-interventional, 6-month study. Of the 312 patients screened, 289 were evaluated at month 6. The primary objective was the change of HbA1c after 6 months. The proportion of patients with HbA1c &lt;7% DCCT (&lt;53 mmol/mol), and those with a decrease of at least 0.5% of HbA1c at month 6, change in FPG, body weight and insulin dose at months 3 and 6 were analysed as secondary objectives. Incidence of hypoglycaemia, adverse events and patient treatment satisfaction (DTSQ) were also assessed.
Results: HbA1c decreased significantly after 6 months (mean change 0.9 ± 1.1% DCCT [-9.9 ± 11.6 mmol/mol], p &lt; 0.0001). HbA1c target &lt; 7% DCCT was achieved in 17.6% of patients, 66.1% of patients showed mean HbA1c decrease of -1.5 ± 0.8%. At month 6, FPG decreased (mean change from baseline -1.8 ±3.1 mmol/L) as well as the incidence of hypoglycaemia decreased by 49% (p ˂ 0.0001) while no weight gain was observed. No significant safety signals were identified. Patients reported significantly better satisfaction with the treatment with Gla-300 (p &lt; 0.0001).
Conclusion: In a real-world setting, switching to Gla-300 in T2DM patients uncontrolled with any other basal insulin was associated with improved glycemic control and reduced risk of hypoglycaemia without weight gain, while patients′ satisfaction with treatment increased.

Disclosure
M. Prazny: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Board Member; Self; Bayer AG. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker's Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis, Servier, Teva Pharmaceutical Industries Ltd. M. Flekac: None. P. Jelinek: Employee; Self; Sanofi. J. Maskova: Other Relationship; Self; Sanofi-Aventis.

Funding
Sanofi; Neox Clinical Research
2334-PUB: Evolution of the Designs of the Sitagliptin (SITA) Pediatric Clinical Studies
Authors: SHANKAR R. RAVI , POZHARSKAYA VERONIKA P. , LEIGHT KELLIE , NEWFIELD RON S. , DEEB ASMA , GARCIA RAYMUNDO , ROSARIO CARMEN A. , SAHA CHANDAN K. , SHEHADEH NAIM , SAMOILOVA YULIA , ENGEL SAMUEL S. , JALALUDIN MUHAMMAD Y. , ZEITLER PHILIP , KAUFMAN KEITH D. 
Published: June 2019

Approved antihyperglycemic therapies for pediatric patients with T2D are currently limited to metformin (MET) and insulin. SITA is being evaluated in 3 studies in patients 10-17 years of age with T2D: SITA as initial oral therapy, MK-0431 P083; SITA as add-on to MET administered as a fixed dose combination (FDC), MK-0431A P170; and SITA as add-on to MET extended-release administered as a FDC of SITA and MET XR, MK-0431A XR P289. The studies, conducted to fulfill post-marketing requirements, and a Pediatric Investigation Plan (EU), were initiated between 2011 and 2013; enrollment completed in 2018. Study protocols were amended since initiation to accommodate regulatory agency requirements, reduce patient burden related to study conduct, and improve patient accrual. Major amendments to the protocols, their rationales, and their impacts are summarized (Table) and demonstrate the flexibility that may be required to enroll such studies. The impact on enrollment of 2 amendments common to all 3 studies were quantifiable. Of patients randomized after approval of an amendment that broadened the A1C entry criterion (from lower limit of 7.0% to 6.5%), ∼34% in P083, ∼20% in P170 and ∼20% in P289 had a baseline A1C between 6.5% and 6.9%. Of patients randomized after approval of an amendment to include patients on background insulin, 11% of patients in P083, 22% in P170, and 19% in P289 enrolled on background insulin.

Disclosure
R. Shankar: Employee; Spouse/Partner; AstraZeneca. Employee; Self; Merck & Co., Inc. Employee; Spouse/Partner; NGM Biopharmaceuticals. V.P. Pozharskaya: Employee; Self; Merck & Co., Inc. K. Leight: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.S. Newfield: Research Support; Self; Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eli Lilly and Company, University of California and Rady Children's Hospital, San Diego. A. Deeb: None. R. Garcia: None. C.A. Rosario: None. C.K. Saha: Research Support; Self; Indiana University School of Medicine. N. Shehadeh: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. Y. Samoilova: None. S.S. Engel: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. M.Y. Jalaludin: Advisory Panel; Self; Novo Nordisk Inc. Research Support; Self; Merck Sharp & Dohme Corp., Novo Nordisk Inc. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. K.D. Kaufman: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc.

Funding
Merck & Co., Inc.
2337-PUB: Impact of Treatment with Insulin and Other Hypoglycemic Drugs on 5'-AMP-Activated Protein Kinase Activity in Leukocytes of Patients with Type 2 Diabetes
Authors: PUSHKAREV VIKTOR V. , SOKOLOVA LIUBOV K. , PUSHKAREV VOLODYMIR M. , VATSEBA TAMARA , TRONKO MYKOLA D. 
Published: June 2019

Background: The leukocytes play an essential role in the development of pathological conditions such as diabetes and its complications. The 5'-adenosine monophosphate-activated protein kinase (AMPK), which usually is inhibited in T2D, controls the energy balance of the cell.
Aim: To study the phosphorylation of AMPK α-subunit (Thr172), and thus its activation, in blood cells at combined T2D patients treatment with insulin, metformin and dapagliflozin.
Methods: To determine the amount of phospho-AMPK (phospho-threonine 172) enzyme-linked immunosorbent assay (ELISA) kit ab154468 (Abcam, UK) was used. The results of the study are presented as M ± SD, n = 3-6. To compare the data groups, Student's t-test was used. Values of P ≤ 0.05 were considered as significant.
Results: It has been shown that metformin increased the activity of AMPK in the leukocytes of patients with T2D more than 3-6 times compared with patients before treatment. Dapagliflozin increases the activity of AMPK and enhances the effect of metformin in the leucocytes of patients with T2D. The mechanisms of drug interaction and the consequences of their antagonism are discussed.
Conclusion: AMPK activity in leukocytes may be additional indicator of the effectiveness of the hypoglycemic drugs action and status of the disease.

Disclosure
V.V. Pushkarev: None. L.K. Sokolova: None. V.M. Pushkarev: None. T. Vatseba: None. M.D. Tronko: None.
2339-PUB: Effect of IDegLira on HbA1c and Weight: Data from the Association of British Clinical Diabetologists (ABCD) IDegLira Audit
Authors: NORONHA SEAN , LUMB ALISTAIR N. , BICKERTON ALEX , SIM SING YEE , GALLEN IAN W. , ADAMSON KAREN , RYDER ROBERT E. 
Published: June 2019

Unique in the UK armoury of injectable agents for diabetes, the combination IdegLira offers the clinical advantages of degludec and liraglutide, with the convenience of a once daily injection. The ABCD IDegLira audit, commenced in April 2017, is a nationwide audit evaluating whether the favourable effects of IDegLira on HbA1c and weight previously shown in clinical trials translate into similar advantages when the agent is used in real clinical practice. Data to date has been obtained nationwide via two routes: a physician populated online audit tool and a cloud-based IT system (Eclipse), capable of integrating with existing primary care systems to facilitate audit, risk stratification and patient empowerment. The inclusion criteria were people with type 2 diabetes started on IDegLira, who had HbA1c and weight measured at baseline and 6 months into treatment. Baseline values were defined as the most recent values in the 6-month period prior to initiation of IDegLira. Endpoint data was accepted within a collection window of +/- 45 days. We identified thirty-five patients for HbA1c (15M, 20F, mean ± SD age 57.4 ± 8.2) and twenty-eight patients for weight (13M, 15F, mean ± SD age 75.0 ± 8.6). Baseline HbA1c and weight were compared with the 6-month values with 2-sided p-values using a paired T Test. Mean ± SD HbA1c fell by 1.43% ± 2.04, from 10.17% ± 1.93 to 8.73% ± 1.74 (p&lt;0.0005). Mean ± SD weight fell by 0.53kg ± 5.77, from 105.24kg ± 24.44 to 104.71kg ± 24.17 (p=0.63). These findings confirm that real world experience with IDegLira is consistent with trial evidence, showing statistically significant reductions in HbA1c and a lack of weight gain. IDegLira is therefore a valuable option when treatment intensification is required in patients with type 2 diabetes. Given that the total yearly cost of IDegLira is less than separate degludec and liraglutide at the equivalent dose, these data would support use of the combination product.

Disclosure
S. Noronha: None. A.N. Lumb: Advisory Panel; Self; Dexcom, Inc., Novo Nordisk A/S. Consultant; Self; LifeScan, Inc. Speaker's Bureau; Self; Abbott, Novo Nordisk A/S. Other Relationship; Self; Abbott. A. Bickerton: Employee; Self; MyWay Digital Health. S. Sim: None. I.W. Gallen: None. K. Adamson: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest.

Funding
Association of British Clinical Diabetologists
234-LB: Incidence Trends of Diabetic Ketoacidosis at and after Diagnosis of Type 1 Diabetes in British Columbia, Canada
Authors: KAO KUNG-TING , ISLAM NAZRUL , FOX DANYA A. , AMED SHAZHAN 
Published: June 2019

Objective: Diabetic ketoacidosis (DKA) is a preventable complication in youth with type 1 diabetes (T1D). This study aimed to estimate the incidence trend of DKA at T1D diagnosis (DKA-AT, defined as DKA within 14 days of T1D diagnosis) and after T1D diagnosis (DKA-AFTER, defined as DKA after 14 days of T1D diagnosis) from 2002 to 2012 in British Columbia, Canada.
Methods: We used a previously described population-based cohort of individuals diagnosed with T1D at &lt;20 years of age. DKA episodes were identified using ICD9/10 codes (250.1X/E101X). Incidence rate ratio (IRR) was estimated using Poisson regression and trends in DKA rates were examined using Joinpoint regression analyses.
Results: 2615 incident cases of T1D were identified between 2002 and 2012, of which 847 (32.4%) were diagnosed with DKA-AT. 52% were male. The rates of DKA-AT by year ranged between 24.1% (2008) and 37.3% (2006). No sex differences were observed. The IRR was 2.0 (95% CI: 1.6, 2.5; p&lt;0.001) for those diagnosed with T1D at 0-4 years compared to those diagnosed at 15-19 years old, after adjusting for the trend by fiscal year. In the same period, 1886 episodes of DKA-AFTER were identified with a consistent increase from 5.3% (2002) to 9.5% (2012). The IRR for DKA-AFTER in children 0-4 years old at diabetes diagnosis was 9.13 (95% CI: 7.73, 10.77; p&lt;0.001). After adjusting for the increasing trend by fiscal year, females had higher rates of DKA-AFTER than males (IRR 1.45, 95% CI: 1.33, 1.59; p&lt;0.001). The average annual percent change for DKA-AFTER was 4.91% (95% CI: 2.69, 7.18; p&lt;0.001).
Conclusions: DKA-AT incidence remained unchanged while the incidence of DKA-AFTER increased over time, with the greatest burden in those diagnosed at a younger age. Targeted interventions are needed to raise public awareness to prevent DKA-AT and to educate patients and families in preventing DKA-AFTER.

Disclosure
K. Kao: None. N. Islam: None. D.A. Fox: None. S. Amed: None.
234-OR: Modified Endothelial Progenitor Cell (EPC) Transplantation May Improve Diabetic Kidney Disease (DKD)
Authors: KUNDU NABANITA , ASICO LAUREANO D. , BANERJEE JAIDEEP , JOSE PEDRO A. , SEN SABYASACHI 
Published: June 2019

Introduction: Diabetic kidney disease (DKD) is a major complication of diabetes, which is associated with sclerotic glomerular disease and poor perfusion. Therefore, improving the renal perfusion may help to halt or reverse the kidney injury. We want to investigate whether transplanting genetically modified EPC by silencing apoptosis gene p53 may promote vasculogenesis and improve renal perfusion. We also wanted to compare p53shEPC with another possible cell therapy such as mesenchymal stromal cell (MSC) (unmodified).
Method: Hyperglycemia and proteinuria in STZ-induced type1-diabetic mice were confirmed at 8 weeks post STZ, followed by transplantation of 0.3 million p53shEPCs, NullEPCs, mouse MSC (mMSC) or saline (control) under each kidney capsule. Urine protein and plasma creatinine were estimated weekly. Perfusion was measured by laser Doppler at sacrifice at week 4 followed by renal histology and qRTPCR.
Results: Reduction of proteinuria was observed in p53shEPC transplantation group compared to null (1.3 fold). Plasma creatinine of p53sh-EPCs group was less than nullEPC (2.7 fold) but similar to MSC transplanted animals (1.5 fold). Increased perfusion was noted p53sh-EPC group compared to NullEPC, MSC and saline (1.2, 2.4 and 3.0 fold respectively). Markers for angiogenesis, such as eNOS (2.6, 1.6 fold respectively) and VEGFA (1.2, 1.5 fold respectively) increased more with post p53shEPC transplantation compared to nullEPC and MSC. We noted heart rate (HR) reduction post p53shEPCs transplantation compared to null whereas HR actually increased in mMSC transplanted mice. Kidney histology following Isolectin-β4 staining showed significant improvement in sclerosed glomerular vascular tufts, with p53shEPC delivery, compared to null, MSC and saline.
Conclusion: Transplantation of p53sh-EPC improved proteinuria, perfusion, and vascular gene mRNAs compared to NullEPCs, MSCs and saline. Modified EPC transplantation may have a prominent cell therapy role in DKD.

Disclosure
N. Kundu: None. L.D. Asico: None. J. Banerjee: Employee; Self; Osiris Therapeutics, Inc. P.A. Jose: None. S. Sen: None.

Funding
American Heart Association
2343-PUB: Reduction of HbA1c after SGLT2 Inhibitors Correlate with Change in Plasma Osmolarity but Not with Elevation of Hematocrit in Japanese Patients with Type 2 Diabetes
Authors: WADA YOSHIHARU , HAMAMOTO YOSHIYUKI , NAKATANI YOSHIHISA , FUJIKAWA JUN , IWASAKI YORIHIRO , YOSHIJI SATOSHI , AIZAWA-ABE MEGUMI , IWASAKI KANAKO , HONJO SACHIKO , HAMASAKI AKIHIRO 
Published: June 2019

Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors is expected its hematopoietic effect for treatment of the anemia in chronic renal failure. However, it is still unclear whether the effect is independent from its antidiabetic effect. In this study, we investigated correlations between hematocrit elevation, HbA1c reduction or parameters reflecting diuretic change in patients with type 2 diabetes (T2D). A total of 46 patients (male: n = 33, age: 54.6 ± 10.4 [mean ± SD] years, BMI: 29.2 ± 4.3 kg/m2, HbA1c: 8.7 ± 1.0%) with T2D who were newly administered SGLT2 inhibitors from July 2014 to November 2016 were retrospectively identified. The patients with HbA1c less than 7.0% at the baseline or who showed decrease in hematocrit or increase in HbA1c were excluded. Changes in HbA1c, hematocrit, urine specific gravity, uric acid, serum creatinine and plasma osmolarity levels between before and 30 days after the administration of the drugs were evaluated. Plasma osmolarity was calculated by the formula (2 x (Na [mEq/l] + K [mEq/l])) + (BUN [mg/dl]/2.8) + (glucose [mg/dl]/18). HbA1c was decreased (-0.68 ± 0.50%; p = 0.001) and hematocrit (2.1 ± 1.4%; p = 0.002) and urine specific gravity (0.008 ± 0.009 g/ml; p &lt; 0.001) were increased significantly. However, uric acid, serum creatinine and plasma osmolarity did not show change. Changes in HbA1c and plasma osmolarity showed significant correlation (r = -0.31; p = 0.03) whereas changes in hematocrit and plasma osmolarity did not (r = -0.01; p = 0.94). HbA1c showed no significant correlation with hematocrit, serum creatinine, uric acid or urine specific gravity; hematocrit also did not have significant correlation with serum creatinine, uric acid or urine specific gravity.
In conclusion, our data suggest that the elevation of hematocrit and decrease in HbA1c after the administration of SGLT2 inhibitors have different relation with parameters reflecting diuretic effects.

Disclosure
Y. Wada: None. Y. Hamamoto: Speaker’s Bureau; Self; Novo Nordisk A/S. Y. Nakatani: None. J. Fujikawa: None. Y. Iwasaki: None. S. Yoshiji: None. M. Aizawa-Abe: None. K. Iwasaki: None. S. Honjo: None. A. Hamasaki: None.