bluuebunny/crossref_metadata_2025 huggingface dataset:
O PRODUTO DO TRABALHO EDUCATIVO NA POLÍTICA DE MONITORAMENTO DA QUALIDADE DA EDUCAÇÃO: NOTAS DE ECONOMIA POLÍTICA
Authors: Araújo Abelardo Bento
Published: June 2018

Com base na economia política, este artigo traz uma discussão teórica sobre as especificidades do trabalho educativo, tendo em vista os problemas de compreensão do que seja seu produto. Colocam-se em pauta as consequências do monitoramento da qualidade da educação, quando esse conjunto de políticas pretende tornar avaliável o trabalho educativo por meio de escores de rendimento em testes em larga escala.
A MAQUINARIA E O AUMENTO NA PRODUTIVIDADE PELO TRABALHO INTELECTUAL: OBSERVAÇÕES A PARTIR DE KARL MARX.
Authors: Araújo Wanderson Pereira
Published: June 2018

Este artigo analisa o trabalho intelectual na complexidade da atividade docente, inserido na formação profissional dos trabalhadores e na produção e aplicação da ciência e da tecnologia no campo da agricultura. Este estudo demonstra a relação do trabalho docente na reprodução ampliada do capital, que aparece ou que pode aparecer como expressão e condição geradora de valor, tendo como base observações de atividades docentes realizadas nos Institutos Federais (IFs). Nesse intento, utilizam-se algumas observações, a partir Karl Marx (em O Capital), em relação à teoria do valor, à categoria trabalho produtivo/improdutivo, bem como a outras, para compreender a dimensão dessa problemática na atualidade.
From Theatrical to Scientific Reviewing: The Case of Nikolay Blatov (1875–1942)
Authors: Lvova Irina , Lvova Dina
Published: June 2018

This paper provides insight into the life of Nikolay Blatov, a Russian professor of accounting who was active in the early 20th century. However, this is not a biographical study in the usual sense. It attempts to apply contextual analysis to one of the aspects of Blatov's career, i.e., writing reviews for the educational literature. The paper shows that Blatov's individual style as a reviewer was determined by his cultural environment: his education and his passion for theater journalism in his young years. The study compares the figures of speech that Blatov employed in his theatrical reviews with those in his later scientific reviews. His rhetoric and style as a theater reviewer enriched his scientific reviewing. The paper also considers Blatov's contribution to developing the rules that governed the narrative of textbooks. He influenced their composition, references, style, and the boundaries within which a textbook's language would remain literary.
The Account Books of the Soranzo Fraterna (Venice 1406–1434) and Their Place in the History of Bookkeeping
Authors: Ryabova Maria
Published: June 2018

This paper contributes to the study of the accounting and legal practice existing in the Venetian Republic in the late Middle Ages. The author examines two account books created by the Soranzo fraterna, a trading firm organized as a family partnership and operating in the first half of the 15th century. The larger of the surviving ledgers, known as the libro real novo, is generally considered to be the earliest extant Venetian example of double-entry bookkeeping. New sources discovered by the author in the State Archives of Venice confirm that the libro real novo represents a compilation of accounts (a so-called estratto) prepared in view of a complicated litigation at the giudici di petizion court. The detailed examination of the judicial conflict in question reveals the purposes behind the composition of this book and the impact that the circumstances of its creation had on the accounting techniques used.

JEL Classifications: M41; N73; N83.
Market Valuation Consequences of Avoiding Taxes While also Being Socially Responsible
Authors: Inger Kerry K. , Vansant Brian
Published: June 2018

In this study, we examine the effects of tax avoidance and Corporate Social Responsibility (CSR) activities on equity market valuation. Economic theory suggests that managers should avoid taxes through any legal means (Friedman 1970), and that CSR activities are of value to the extent that shareholder wealth is maximized (Hales, Matsumura, Moser, and Payne 2016). We hypothesize that while equity market participants may positively value both CSR and tax avoidance, these two actions are viewed as inconsistent with one another when engaged upon contemporaneously, where increased activity of one diminishes the value of the other. Results, using a sample of U.S. public firms during years 2000–2013, support our expectation and show a negative interaction between CSR and tax avoidance. A series of robustness checks provide additional evidence consistent with investors viewing CSR and tax avoidance as contradictory.

JEL Classifications: G32; M41; M49; M410.

Data Availability: Data are available from the public sources cited in the text.
Characterizing Clinical Inertia in a Large, National Database
Authors: RATTELMAN CORI R. , ARORA ANUPAMA , CUDDEBACK JOHN K. , CIEMINS ELIZABETH L.
Published: June 2018

Objective: To characterize clinical inertia in the treatment of diabetes using a large, geographically diverse clinical database.

Study Design: A retrospective descriptive analysis was conducted in a clinical database containing 22 million patient records across 22 health care organizations (HCOs).

Population Studied: A total of 281,000 patients aged 18-75 were included during the 5.5-year study period (1/2012-6/2017). Patients had an outpatient visit in the last 12 months of the study period, an HbA1c in the last 24-30 months (index A1c), and a diagnosis of type 2 DM on a claim or EHR problem list at least 6 months prior to index A1c. A subset of 47,693 patients with an index A1c ≥8 and a prior A1c ≥8 or lack thereof, was observed for four 6-month follow-up periods for actions including a new class of diabetes medication prescribed or an A1c <8. The absence of observable action following index A1c suggests potential “clinical inertia.”

Principal Findings: Six months following an index A1c≥8, 55% of patients received no observable clinical action ranging from 45-65% across HCOs and 18-96% across individual providers. A new diabetes prescription was observed in 35% of patients (7.5% moved into glycemic control, A1c<8) and 10% moved into glycemic control without a new prescription. Patient characteristics associated with increased clinical inertia, i.e., no observable action, during the 6002D and 24-month follow-up periods included black race, low-income insurance, normal body mass index, and being on bolus insulin (all P<.01). Within 24 months, clinical inertia was reduced to 19%, ranging from 13-28% across HCOs.

Conclusions: Lack of clinical action in the 6 months following an A1c ≥8 suggests clinical inertia vs. ADA guidelines. Greater rates in low-income insurance and race/ethnic minority adults suggests potential populations to target to ensure adequate treatment for diabetes. The decline in clinical inertia within 24 months suggests either actions not seen in the data, or later interventions that were ultimately effective.

Disclosure

C.R. Rattelman: None. A. Arora: None. J.K. Cuddeback: Research Support; Self; Novo Nordisk Inc.. Other Relationship; Self; Johnson & Johnson Diabetes Institute, LLC., Merck & Co., Inc., Sanofi US, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. E.L. Ciemins: None.
Treatment Effects of Once-Weekly Dulaglutide vs. Insulin Glargine in Patients with Different Baseline Glycemic Patterns (Based on High/Low Fasting or High/Low Postprandial Glucose)—A Post-Hoc Analysis of the AWARD-2 Clinical Trial
Authors: GIORGINO FRANCESCO , YU MARIA , HAUPT AXEL , MILICEVIC ZVONKO , GARCIA-PEREZ LUIS-EMILIO
Published: June 2018

Insulin glargine (Glar) exerts its action primarily through a decrease in fasting plasma glucose (FPG), whereas dulaglutide (DU), a once-weekly GLP-1RA, targets both fasting and postprandial glucose (PPG). This post-hoc analysis of the AWARD-2 study assessed the efficacy of DU vs. Glar in patients with type 2 diabetes with different glycemic patterns at baseline determined by self-monitoring of blood glucose (fasting glucose [FG] vs. PPG). Patients were categorized into 4 groups based on combinations of low and high FG and PPG, with median baseline values of FG (151 mg/dL) and PPG (182 mg/dL) being used as threshold for low and high, respectively. Analyses were conducted using analysis of covariance. DU showed a statistically significantly greater reduction in A1c compared with Glar for all of the subgroups, except for low FG/high PPG, where the numerical difference was in favor of DU but did not reach statistical significance (Table). Total hypoglycemia was numerically lower for DU vs. Glar in all subgroups. DU showed efficacy on A1c reductions across different baseline glycemic patterns vs. Glar (with the exception of low FG/high PPG), indicating a clinical benefit of targeting both FG and PPG, irrespective of the baseline glycemic phenotype.

Disclosure

F. Giorgino: Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH. Research Support; Self; Eli Lilly and Company, Johnson & Johnson Services, Inc.. Consultant; Self; MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care Health and Digital Solutions, Sanofi. Research Support; Self; Takeda Development Centre Europe Ltd. M. Yu: Employee; Self; Eli Lilly and Company. A. Haupt: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Z. Milicevic: Employee; Self; Eli Lilly and Company. L. Garcia-Perez: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
The Effect of Temperature on the Stability of In-Use Insulin Pens
Authors: KONGMALAI TANAWAN , PREECHASUK LUKANA , JUNNU SARAWUT , MANOCHEEWA SIRIPHAN , SRISAWAT CHATCHAWAN , SRIWIJITKAMOL APIRADEE
Published: June 2018

Background: Improper storage of in use insulin could decrease its potency. Temperature has been shown to have an effect on the stability of insulin. Therefore, the manufacturers recommend to keep an in use insulin at the room temperature (RT), not exceeding 25-30 ๐C. However, The RT in tropical countries are higher than that. Thus far, there are few studies evaluate the effect of temperature on insulin stability, especially insulin pens which are widely used nowadays.

Aim: To investigate the effect of temperature on the stability of basal insulin after opening for 28 days.

Methods: There are four different commercial basal insulin pens, including long and intermediate acting insulin were evaluated (N=5 each). They were opened and stored at 3 different conditions, including: refrigerated (2-8 ๐C), RT and incubator (37 ๐C) for 28 days. An unopened insulin pens from the same batches were stored under standard condition as control (CON). During the study period, the insulin pens were well-mixed and discarded 2 units every day to mimic the daily usage of diabetes patient. The temperature logger was used to record the hourly temperature in RT. After 28 days, the amount of insulin was evaluated using the Ultra-high performance liquid chromatography assay.

Results: Average RT throughout the study period was 29.7 ± 2.8 ๐C. The percentage amount of insulin (mean ± SD) stored at 4oC, RT or 37oC, compared with CON was as follows: 99.0 ± 0.8%, 99.7 ± 2.5%, 101.1 ± 1.2% for long-acting insulin; 97.4 ± 0.7%, 97.2 ± 1.6%, 99.0 ± 1.2% for NPH-1; 101.4 ± 1.1%, 101.5 ± 2.5%, 100.7 ± 2.3% for NPH-2; and 98.7 ± 1.5%, 97.8 ± 1.1%, 98.5 ± 1.7% for NPH-3. There was no statistically significant in the difference. However, there was a trend toward different in AUC between long acting and NPH insulin.

Conclusion: Temperature, as high as 37 ๐C, cyclic temperature and the variability of temperature range from 4 ๐C to room temperature had no effect on the stability of in use insulin pen. We observed the trend toward different in stability between clear insulin analog and turbid NPH insulin.

Disclosure

T. Kongmalai: None. L. Preechasuk: None. S. Junnu: None. S. Manocheewa: None. C. Srisawat: None. A. Sriwijitkamol: None.
Ultra-rapid Lispro (URLi) Reduces Postprandial Glucose Excursions vs. Humalog® in Patients with T1D at Multiple Meal-to-Dose Timing Intervals
Authors: PLUM-MOERSCHEL LEONA , LEOHR JENNIFER , LIU RONG , REDDY SHOBHA , DELLVA MARY A. , LIM SHUFEN , MEI TENG LOH , KNADLER MARY P. , HARDY THOMAS , KAZDA CHRISTOF M.
Published: June 2018

URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection. This 2-part, randomized, double-blind, Phase 1b study evaluated the differences in PK and PD between URLi and insulin lispro (Humalog®; HL) in 30 patients with T1D. Part A used a 6´period crossover design to evaluate safety and compare PK and postprandial glucose response to solid mixed meal tolerance tests (MMTT) with URLi or HL at different injection to mealtime intervals (-15, 0, and +15 min). Part B evaluated the safety, PK, and PD during 2 weeks of multiple daily dosing (immediately before a meal) in a parallel design. In Part A, URLi reduced glucose excursions (assessed as change in area under the concentration curve vs. time [∆AUC]) during the first 2 hours (∆AUC0-2h) and entire 5 hours (∆AUC0´5h) of the MMMT regardless of dose timing (Fig). URLi reduced ∆AUC0-2h by 103% (p=0.008), 39% (p=0.031), and 16% (p=0.096), and ∆AUC0-5h by 40% (p=NS), 44% (p=0.097), and 42% (p=0.026) vs. HL at -15, 0, and +15 min (significance level =0.1. The PK and PD profiles for URLi and HL were sustained after 2 weeks of outpatient dosing (Part B). Similar number of hypoglycemic events occurred between treatments during MMTTs. During 2 weeks of outpatient dosing, the number of events was lower for URLi vs. HL. Local tolerability was similar between treatments.

Disclosure

L. Plum-Moerschel: None. J. Leohr: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Accenture. Stock/Shareholder; Spouse/Partner; Accenture. R. Liu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. S. Reddy: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. S. Lim: None. M. Loh: Employee; Self; Eli Lilly and Company. M.P. Knadler: Other Relationship; Self; Eli Lilly and Company. T. Hardy: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C.M. Kazda: Employee; Self; Eli Lilly and Company.
Low Doses of Dasiglucagon Consistently Increase Plasma Glucose (PG) Levels in Hypoglycemia and Euglycemia in People with Type 1 Diabetes Mellitus (T1DM)
Authors: HOVELMANN ULRIKE , BRAENDHOLT OLSEN MINNA , MOURITZEN ULRIK , LAMERS DANIELA , KRONSHAGE BIRGIT , HEISE TIM
Published: June 2018

To develop a dual hormone artificial pancreas (DHAP) a liquid stable glucagon component is needed. Currently available glucagon products have limited stability after reconstitution and are therefore not suited for DHAP usage. Dasiglucagon is a novel liquid stable glucagon analog, which does not require mixing prior to use. In this randomized double-blind trial 17 patients with T1DM received four single subcutaneous doses (0.03, 0.08, 0.2 and 0.6 mg) of dasiglucagon (4 mg/ml) under hypoglycemic (plasma glucose (PG) 56-66 mg/dL) or euglycemic (PG 100 mg/dL) conditions. For comparison, identical doses of Lilly GlucagonTM (GLUCA) were investigated at euglycemia. In the euglycemic setting dasiglucagon showed rapid and dose-dependent PG-increases of mean 39, 56, 72 and 80 mg/dL at 30 minutes post-dosing (30, 49 and 71 mg/dl for GLUCA) (Figure). During hypoglycemia, dasiglucagon provided similar PG-increases of 24, 64, 87 and 94 mg/dL 30 minutes post dose and rapidly corrected PG levels to normoglycemia (PG ?70 mg/dL) with a median time of 14, 10, 6 and 6 minutes.

In conclusion, low doses of dasiglucagon rapidly and effectively increase PG from euglycemia and hypoglycemia in a titratable manner. Therefore, dasiglucagon should be a good candidate for use in dual-hormone closed-loop AP systems.Figure. Different Doses of Dasiglucagon and GLUCA, PG Levels (Mean ±SEM).

Disclosure

U. Hovelmann: None. M. Braendholt Olsen: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Zealand Pharma A/S. U. Mouritzen: Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. D. Lamers: None. B. Kronshage: None. T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi.
Self-Managed Titration with Insulin Glargine 300 U/mL (Gla-300) Can Achieve Similar Efficacy to Physician-Led Titration Regardless of Prior Insulin Status in People with T2DM—Results from TAKE CONTROL
Authors: DELGADO ELIAS , BONNEMAIRE MIREILLE , DAUCHY ARNAUD , DONICOVA VIERA , KVAPIL MILAN , TENTOLOURIS NIKOLAOS , POPESCU LUIZA , RUSSELL-JONES DAVID
Published: June 2018

Many people with T2DM do not achieve HbA1c goals in clinical practice, owing in part to sub-optimal basal insulin titration. TAKE CONTROL, a 24-week, multicenter, randomized, open-label, parallel-group study, compared the efficacy and safety of a Gla-300 titration algorithm (fasting self-monitored plasma glucose >130 mg/dL, +3 U; <80 mg/dL, −3 U), when self-managed or led by physicians. Overall, improved glycemic control without increased hypoglycemia was seen with self-titration. Here, we report results stratified by prior insulin use. At baseline, mean HbA1c was higher in the insulin-naïve vs. prior-insulin group (Table). In both groups, self-titration and physician-led titration resulted in similar HbA1c reduction. For confirmed or severe hypoglycemia, there was no evidence of heterogeneity between titration approaches for both glycemic thresholds (≤70 mg/dL or <54 mg/dL). Glycemic goal achievement with Gla-300 using self-titration was similar to that reported for physician-led titration, regardless of prior insulin use, but with reduced or similar risk of hypoglycemia. Empowering people with T2DM to self-titrate their basal insulin effectively upon Gla-300 initiation, or after switching to Gla-300, can improve glycemic target achievement without increasing hypoglycemia.

Disclosure

E. Delgado: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Speaker's Bureau; Self; Esteve, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Lilly. Research Support; Self; Menarini Group. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A. Dauchy: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. V. Donicova: None. M. Kvapil: None. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. D. Russell-Jones: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly and Company, Novartis, Novo Nordisk, Sanofi.
Metoclopramide Restores the Sympathoadrenal Response to Hypoglycemia in a Novel Model of HAAF
Authors: VIEIRA DE ABREU ADRIANA , AGRAWAL RAHUL , HOWE PARKER , FISHER SIMON J.
Published: June 2018

We sought to develop a novel animal model of hypoglycemia-associated autonomic failure (HAAF) and investigate the pathological process involved. We previously noted that recurrent 2-deoxyglucose (R2DG) administration induced hypoglycemia unawareness (indicated by a blunted food intake response to hypoglycemia). We now evaluate whether R2DG also induces an impaired counterregulatory response and whether this pathological process is mediated by dopaminergic receptor activation. Sprague-Dawley rats were randomized to one of three, 3-day treatments: 1) recurrent saline (Control), 2) R2DG (200 mg/kg/d, SQ), or 3) R2DG and antecedent pretreatment with the dopaminergic antagonist metoclopramide (R2DG+Meto, 3 mg/kg/d, IP). On the fourth day, all rats underwent hyperinsulinemic (50 mU/kg/min) hypoglycemic (∼50 mg/dl) clamps. Notably, recurrent 2DG abrogated the epinephrine response to hypoglycemia as compared to controls. In addition to restoring hypoglycemia awareness (i.e., the food intake response to hypoglycemia), metoclopramide normalized the epinephrine response to hypoglycemia in 2DG treated rats. Glucagon showed a similar pattern of suppression with R2DG and restoration with R2DG+Meto. In this model of HAAF, our data identifies a novel role of dopaminergic receptor activation in the development of HAAF and a potential role for metoclopramide as a potential therapeutic agent to prevent HAAF.

Disclosure

A. Vieira de Abreu: None. R. Agrawal: None. P. Howe: None. S.J. Fisher: None.
The Effect of Age on Short-Term Insulin Intensive Therapy for Patients with New Diagnosis Type 2 Diabetes
Authors: WAN XUESI , HUANG ZHIMIN , XU LIJUAN , LI YANBING
Published: June 2018

According to our previous study, short-term intensive insulin therapies by CSII can improve β-cell function by eliminating glucotoxicity in newly diagnosed patients. It's interesting that young patients seems to recover better than old patients. The purpose of this study is to clarify the effect and mechanism of age on T2DM remission from short-term intensive insulin therapies. An observation of 160 patients with newly diagnosed T2DM (n=160, 103 male, aged 50±10 ys,HbA1C 11±2.1%) after 2-week therapy was studied remission rate. They were divided to young group (age<50ys)(n=77) and old group (n=83). After 1-year of the termination of intensive therapy, there are obviously more remission patients in the young group than the old group (57/77 vs. 48/83, p<0.05). As the Table showed below, the young have statistically lower FPG, Cholesterol, LDL-C, Free Fatty Acid and better HOMA-B just after therapy (p<0.05). These results indicated that age might affect the remission rate mainly by the better improved metabolism of both glucose and lipids. Moreover, the results of HOMA-B has shown that younger will be easier to recover beta cell function.Young gruop at baselineYoung gruop after therapyOld group at base lineOld group after therapyFPG (mmol/L)11.84±0.356.±0.1311.79±0.366.73 ±0.18Cholesterol (mmol/L)5.69 ±0.145.04 ±0.16.±0.135.73 ±0.12HDL-C (mmol/L)1.±0.031.21 ±0.031.18 ±0.031.25 ±0.03LDL-C (mmol/L)3.81 ±0.133.36 ±0.104.±0.133.87 ±0.10Free Fatty Acid (mEq/L)0.59 ±0.020.50±0.030.68 ±0.050.61 ±0.04HOMA-β22.37±1.7775.02±6.6225.13±2.2656.38±3.85HOMA-IR3.99 ±0.272.12 ±0.154.02 ±0.272.24 ±0.12

Disclosure

X. Wan: None. Z. Huang: None. L. Xu: None. Y. Li: None.
Results of an Interim Analysis of a Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of ZGN-1061 in Patients with Obesity and Type 2 Diabetes
Authors: KIM TERRI , ZHUANG DONGLIANG , HUGHES THOMAS E. , KIM DENNIS D. , TAYLOR KRISTIN
Published: June 2018

ZGN-1061 (1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor being developed to improve glycemic control in type 2 diabetes. This clinical trial investigated the effect of 12 weeks of subcutaneous (SC) 1061 (0.05, 0.3, 0.9 mg or placebo) administered every 3 days on A1C, safety, and tolerability. Stable noninsulin diabetes therapy was permitted. The study included 129 patients; an interim analysis was conducted on a subset of patients at week 8. Baseline characteristics of the interim ITT population (N=57): 54% male, 77% white, (mean±SD) age 54±8 years, A1C 8.7±1.0%, BMI 37.2±6.4 kg/m2. At week 8, the LS mean±SE change in A1C for placebo was 0.2±0.1% (N=13) vs. -0.4±0.2% with 0.9 mg 1061 (N=13, LS mean±SE difference -0.6±0.2%, p<0.02). In patients with week 12 measurements, the change in A1C was 0.4±0.2 (N=12) vs. -0.5±0.2 (N=8, difference -0.9±0.3, p<0.01). There were trends for weight loss and improved fasting plasma glucose with 0.9 mg 1061 vs. placebo as well as improvements in biomarkers, including hsCRP (week 8 -2.1±2.2 mg/L vs. 1.0±2.1, ns), adiponectin (1.0±0.3 ug/mL vs. -0.1±0.3, p<0.05), leptin (-6.9±1.9 ng/mL vs. 2.1±1.7, p<0.05), FGF-21 (0.026±0.014 ng/mL vs. 0.000±0.013; ns), and postprandial glucose AUC (p<0.01). Improvements in efficacy measures with the lower doses of 1061 were variable. There were no serious or severe adverse events (AEs) and no subjects withdrew due to an AE. The most common AE (1061>placebo) was upper respiratory tract infection. The 1061 pharmacokinetic profile indicated that exposure was within target levels for efficacy and safety and there were no changes in thrombosis markers (e.g., D-dimer). In this interim analysis, 1061 produced improvements in glycemic control and metabolic biomarkers consistent with MetAP2 inhibition. 1061 was also well tolerated with no safety signals in all doses tested. Week 12 results from the full analysis dataset will be presented.

Disclosure

T. Kim: Employee; Self; Zafgen. D. Zhuang: Employee; Self; Zafgen. T.E. Hughes: Board Member; Self; Zafgen. Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen. D.D. Kim: Employee; Self; Zafgen. K. Taylor: Employee; Self; Zafgen.
Real-World Health Outcomes of Insulin Glargine 300 U/mL (Gla-300) vs. Insulin Glargine 100 U/mL (Gla-100) in Patients with Type 1 (T1D) and Type 2 Diabetes (T2D) in the Canadian LMC Diabetes Patient Registry—The REALITY Study
Authors: ABITBOL ALEXANDER , BROWN RUTH E. , JIANDANI DISHAY , SAURIOL LUC , ARONSON RONNIE
Published: June 2018

This retrospective cohort study evaluates real-world health outcomes in patients with T1D and T2D initiating Gla-300 or Gla-100 as part of their usual therapy in the largest specialist-led clinic group in Canada, between January 2015 and August 2017. The primary outcome was HbA1c change at 3-6 months. Four separate cohorts were evaluated. In the T1D cohort, 299 patients transferred from Gla-100 to Gla-300 had a significant HbA1c reduction of -0.2 ± 1.2%, with no change in weight, hypoglycemia or basal insulin dose (Table). Similarly, 488 patients with T2D transferred from Gla-100 to Gla-300 had a significant HbA1c reduction of -0.47 ± 1.37%, with no change in weight, hypoglycemia or basal insulin dose. In patients with T2D transferred from NPH or detemir (n=343), Gla-300 had a significantly greater reduction in HbA1c than Gla-100 (-0.30 ± 2.2%), with no change in weight, hypoglycemia or basal insulin dose in either group. For insulin-naïve T2D patients (n=1448), there were no significant differences between Gla-300 and Gla-100 in adjusted HbA1c or weight. Patients with T1D and T2D in a national specialist-led registry, who transferred from their usual basal insulin to Gla-300, significantly reduced their HbA1c, without increasing weight, basal insulin dose, nor hypoglycemia incidence.

Disclosure

A. Abitbol: Research Support; Self; JDRF, JA DeSeve Foundation, Lexicon Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Pfizer Inc., AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Senseonics, Gilead Sciences, Inc.. Speaker's Bureau; Self; Amgen Inc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Employee; Self; LMC Diabetes & Endocrinology. Speaker's Bureau; Self; LMC Diabetes & Endocrinology, Valeant Pharmaceuticals International, Inc.. Consultant; Self; Valeant Pharmaceuticals International, Inc.. R.E. Brown: None. D. Jiandani: None. L. Sauriol: Employee; Self; Sanofi. R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc..
Progression from Prediabetes to Type 2 Diabetes (T2DM) in 303 Hypogonadal Men With and Without Testosterone Treatment—Eight-Year Real-Life Data from a Registry
Authors: SAAD FARID , HAIDER AHMAD , HAIDER KARIM S.
Published: June 2018

Background: Hypogonadism predicts T2DM and is highly prevalent in men with prediabetes.

Methods: Pooled data from 2 ongoing urological registries. 303 men had prediabetes by HbA1c according to ADA definition. 220 received treatment with 3-monthly injections of testosterone undecanoate (TU; T-group), 83 served as controls (CTRL). Anthropometric and metabolic parameters were measured over 8 years.

Results: Mean follow-up: 6.6 years (T-group), 5.6 years (CTRL). Mean age: 60.6±9.6 years. Under TU, HbA1c decreased from 5.9±0.2 to 5.5±0.3% at 8 years (p<0.0001). In CTRL, HbA1c increased from 5.9±0.2 to 6.1±0.6% (p<0.0005). At the last observation, all 220 patients (100%) in the T-group had an HbA1c <6.5%. In CTRL, 35 men (42.2%) had progressed to T2DM with HbA1c >6.5% The TyG index, a surrogate parameter for insulin resistance, decreased in the T-group from 9.3±0.4 to 9.0±0.4 at 8 years. In CTRL, the index increased from 8.9±0.6 to 9.3±0.4 at 8 years. At baseline, 158 men (52.1%) were obese, 126 men (41.6%) were overweight and 19 (6.3%) had normal weight. Weight decreased from 96.7±12.3 to 89.0±9.6 kg in the T-group and increased from 92.9±10.4 to 98.2±6.3 kg in CTRL. Waist circumference decreased from 104.2±7.1 to 98.2±6.5 cm in the T-group and increased from 102.5±9.7 to 106±3.2 cm in CTRL. Weight loss was 9.2±8.3% at 8 years in the T-group. In CTRL, weight increased by 9.2±3.9% at 8 years (p<0.0001 for all). Adherence to TU was 100 per cent as all injections were performed and documented in the office.

Conclusion: Testosterone therapy prevented progression from prediabetes to T2DM in hypogonadal men while more than 40% of untreated hypogonadal men developed T2DM. This effect may have been supported by sustained weight loss and been mediated by the invariable increase in lean mass achieved by testosterone.

Disclosure

F. Saad: Employee; Self; Bayer AG. Stock/Shareholder; Self; Bayer AG, Novo Nordisk A/S. A. Haider: Research Support; Self; Bayer AG. K.S. Haider: Other Relationship; Self; Bayer AG.
Relationship of Ethnicity to Clinical Outcomes in iGlarLixi-Treated Patients with Type 2 Diabetes
Authors: MORA PABLO , CHAO JASON , SAREMI ARAMESH , DEX TERRY A , ROBERTS MICHELLE , UMPIERREZ GUILLERMO E
Published: June 2018

Pharmacogenetic studies have shown significant differences among racial and ethnic groups. This post-hoc analysis of 2 30-week phase 3 trials of patients with type 2 diabetes uncontrolled on metformin ± oral antidiabetes drugs (OADs) (LixiLan-O: NCT02058147) or basal insulin ± OADs (LixiLan-L: NCT02058160) determined the safety of iGlarLixi vs. insulin glargine (iGlar) among Hispanic and non-Hispanic patients.

Analysis of variance/covariance was used for continuous variables and χ2/Cochran-Mantel-Haenszel for categorical variables. A generalized linear model using negative binomial distributions with factors of treatment arm and ethnicity, covariates of age and baseline weight or BMI, and log exposure as offset, was used for symptomatic hypoglycemia (plasma glucose ≤70mg/dL) rates. Adjusted hypoglycemia rates used the same model with mean values of age and baseline weight or BMI.

Across studies 20% (353/1730) of all patients were Hispanic. At baseline, Hispanic patients had significantly lower body weight, BMI, and fasting plasma glucose vs. non-Hispanic patients (all, P<0.001). Overall, clinical outcomes were similar for Hispanic and Non-Hispanic patients, regardless of drug type (Figure). However, iGlarLixi demonstrates better glycemic control in both Hispanic and non-Hispanic patients, with similar safety outcomes to iGlar.

Disclosure

P. Mora: Advisory Panel; Self; Novo Nordisk Inc.. Consultant; Self; Sanofi US. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi US. J. Chao: None. A. Saremi: Employee; Self; Sanofi US. T.A. Dex: Employee; Self; Sanofi US. Stock/Shareholder; Self; Pfizer Inc., Merck Sharp & Dohme Corp., Teva Pharmaceutical Industries Ltd.. M. Roberts: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..
Addition of GLP-1 Therapy to Insulin in C-Peptide-Positive Patients with Type 1 Diabetes
Authors: KUHADIYA NITESH D. , PROHASKA BENJAMIN , GHANIM HUSAM , DANDONA PARESH
Published: June 2018

We have previously demonstrated that the addition of liraglutide to insulin significantly improves the glycemic control in patients with type 1 diabetes (T1D) with undetectable c-peptide. We have now investigated whether the addition of GLP-1 therapy to insulin in c-peptide positive patients with T1D will increase the c-peptide concentrations and improve the glycemia further with reduced insulin requirements. We conducted a retrospective analysis of 11 Caucasian patients with detectable c-peptide and positive GAD-65 antibodies treated with GLP-1 therapy for 12±1 weeks (baseline c-peptide: 0.43±0.09 ng/ml; baseline HbA1c: 10.63±0.87%; mean age: 43±5 years; mean age of diabetes diagnosis: 37±5 years; mean duration of diabetes: 6±2 years; mean BMI: 23± 1Kg/m2; mean body weight: 71±2 kg; 6 females, 5 males). At the end of 12± 1 weeks of GLP-1 therapy; c-peptide concentrations increased significantly from 0.43±0.09 to 1.42±0.42ng/ml(p=0.01); HbA1c fell from 10.63± 0.87% to 7.45± 0.52%(p<0.01), body weight fell from 71±2.0 kg to 69±2 kg(p=0.06) and total insulin dose fell by 64% from 34.45±5.73 to 12.27±4.01 units(p<0.01). 5 out of 11 patients did not require any insulin. 9 patients were initiated on liraglutide: 0.6 mg subcutaneous(sc) daily for one week, 1.2 mg daily for second week and then 1.8 mg daily thereafter. One out of these 9 patients did not tolerate 0.6 mg daily dose and stopped it due to nausea in the first week. 2 patients were initiated on dulaglutide(0.75 mg sc once a week for 2 weeks and then 1.5 mg once a week thereafter). We conclude that addition of GLP-1 therapy in GAD-positive and C-peptide positive patients with type 1 diabetes (T1D) results in 3.5 fold increase in c-peptide concentrations with improved glycemic control and more than 60% reduction in insulin requirements over a period of 12 weeks. Long term studies are needed to establish the durability of these benefits.

Disclosure

N.D. Kuhadiya: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Janssen Scientific Affairs, LLC.. Advisory Panel; Self; AstraZeneca. Consultant; Self; Dexcom, Inc.. B. Prohaska: None. H. Ghanim: None. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca.
Are We Misdiagnosing Diabetic Foot Osteomyelitis?
Authors: CRISOLOGO PETER A. , LA FONTAINE JAVIER , DAVIS KATHRYN , LAVERY LAWRENCE A.
Published: June 2018

Rationale and Aim: To compare the incidence of osteomyelitis based on different operational definitions using the gold standard of bone biopsy.

Methods: We prospectively enrolled 35 consecutive patients who met the criteria of ?21 years of age, a moderately or severely infection based on the Infectious Diseases Society of America. Bone samples were obtained from all participating patients either by percutaneous bone biopsy or intraoperative if the patient required surgery in the operating room. Bone samples were analyzed for conventional culture, histology examination, and16S rRNA qPCR. We evaluated five definitions for osteomyelitis: 1. traditional culture 2. traditional histology 3. genetic sequencing 4. traditional culture and histology 5 genetic sequencing and histology.

Results: There was significant variability in the incidence of osteomyelitis based on the criteria for diagnosis. Traditional cultures identified significantly more cases of osteomyelitis than histology alone (68.6% vs. 45.7%, p=0.02). In every case that histology reported osteomyelitis; the bone culture was positive using traditional culture methods and genetic sequencing. 16S rRNA testing identified more cases of osteomyelitis compared to histology (82.9% vs. 45.7%, p=0.001) and compared to traditional cultures (82.9% vs. 68.6%, p=0.31). When both histology and traditional culture (68.6%) or histology and genetic sequencing based cultures (82.9%) were used to define osteomyelitis the incidence of osteomyelitis did not change.

Conclusions: There is considerable variability in the incidence of osteomyelitis based on how the gold standard of bone biopsy is defined in diabetic foot infections.

Disclosure

P.A. Crisologo: None. J. La Fontaine: None. K. Davis: None. L.A. Lavery: Speaker's Bureau; Self; Osiris Therapeutics, Inc., Integra LifeSciences. Research Support; Self; Cardinal. Speaker's Bureau; Self; Smith & Nephew. Research Support; Self; EO2. Consultant; Self; Aplion, Harbor MedTech, Boehringer Ingelheim GmbH, Medline Industries, Inc..
Heterologous Adipose–Derived Mesenchymal Stem Cells and Vitamin D Supplementation in Patients with Recent–Onset Type 1 Diabetes Mellitus–Six Months Follow-Up
Authors: DANTAS JOANA R. , CABRAL DEBORA A. , PEREIRA KARINA , PEREIRA MARIA F. , SOUTO DEBORA L. , NOLASCO MATHEUS , SOARES MARINA O. , GABBAY MONICA , COURI CARLOS E. , CLAUDIO-DA-SILVA CESAR S. , REBELATTO CARMEN K. , DIB SERGIO A. , OLIVEIRA JOSE EGIDIO P. , ZAJDENVERG LENITA , RODACKI MELANIE
Published: June 2018

Objective: To evaluate the safety and efficacy of 6 months followup of infusion of heterologous adipose tissue derived mesenchymal stem cells (ADMSCs) of healthy donors + daily cholecalciferol (VD) in patients with recentonset T1D.

Methods: In this prospective open trial, patients with recentonset T1D between 1635 y/o received a single infusion of heterologous ADMSCs (kg x 106) + daily oral VD (2.000UI). Glycated hemoglobin (HbA1c), basal and stimulated Cpeptide (CP) after a mixed meal, insulin dose, adverse events, and glycemic variability (GV) through continuous glucose monitoring (CGM) were assessed at baseline (T0), after 3 (T3) and 6 (T6) months. Patients were compared to controls with recentonset T1D included in previous study that received 1) standard insulin treatment (INS); 2) insulin and VD. Chisquare and Wilcoxon tests were used for statistical analysis.

Results: Six patients (3 males) with mean age of 27 ± 7.1 y/o underwent ADMSC + VD intervention. There were no differences in insulin dose/kg (p=0.6), peak CP (p=0.75) and area under the curve of stimulated CP (p=0,25). All patients had increase in basal CP (p=0.03). HbA1c improved at T3 (0.03), with no difference at T6 (p=0.07). GV did not change after intervention. Increase in Basal CP and stimulated CP were similar between groups, ADMSCs+VD, VD and INS (Basal CP=100% vs. 58.8% vs. 45%, respectively, p=0.057, and stimulated CP=66.7% vs. 58.8% vs. 25% p= 0.058). One patient developed central retinal vein occlusion at T3, with resolution at T6 and another had recurrence of a benign ovarian tumor at T6.

Discussion: In patients with T1D, heterologous ADMSCs + VD supplementation is feasible and appears to be safe after 6 months of followup and resulted in improvement of basal CP. Although GV did not change after the infusion, all patients had an excellent glycemic control, preserved βcell function and low insulin requirements after the intervention with little complications.

Disclosure

J.R. Dantas: None. D.A. Cabral: None. K. Pereira: None. M.F. Pereira: None. D.L. Souto: None. M. Nolasco: None. M.O. Soares: None. M. Gabbay: None. C.E. Couri: None. C.S. ClaudiodaSilva: None. C.K. Rebelatto: None. S.A. Dib: None. J.P. Oliveira: None. L. Zajdenverg: None. M. Rodacki: Research Support; Self; Faperj. Speaker's Bureau; Self; Allergan, Novo Nordisk A/S. Speaker's Bureau; Spouse/Partner; Biogen.
IMG-1 Is Able to Normalize Blood Glucose Levels by Inhibiting Glucagon Levels in a Type 2 Diabetic Rat Model
Authors: POLLETT JONATHAN B. , THAI NGOC
Published: June 2018

IMG-1 is a novel therapeutic compound for the treatment of diabetes. Ten-week-old diabetic ZDF rats were treated with IMG-1 either intravenously (IV) or per oral (PO) once a day and compared to no treatment over a thirty-five-day period. Weights and glucose levels were monitored twice a week. IMG-1 treated animals showed a marked decrease in BG levels within a week, (average BG levels of 179mg/dl for IMG-1 (IV) and 135mg/dl for PO). This finding was enduring for the entire 35-day period. Untreated controls had significantly elevated BG levels throughout the study, with average levels exceeding 400 mg/dl (481 mg/dl). Hemoglobin A1c (Hb1Ac) was measured at days 0 and 35. IMG-1 treated animals had significantly lower Hb1Ac (IV, 9.7%-> 7.4%) and PO (10.8% ->7.5%) while the untreated group maintained increased Hb1Ac levels (10.2%->12.3%). There was no significant difference in insulin levels between untreated and IMG-1 treated groups at any time point suggesting IMG-1 decreased insulin resistance. Glucagon levels were reduced in both IV and PO IMG-1 treated animals at days 15 (from 115pg/ml and 119pg/ml to 90pg/ml and 92pg/ml, respectively) and 35 (89pg/ml and 92pg/ml). Control animals had no significant difference in glucagon levels throughout the entire study. Based on these results, it appears that IMG-1 is able to normalize both blood sugar in ZDF animals and lower HbA1c and decrease glucagon levels without elevating insulin levels in these animals.

Disclosure

J.B. Pollett: Employee; Self; Imagine Pharma. N. Thai: Board Member; Self; Imagine Pharma.
Dapagliflozin Suppresses Plasma Hepcidin Concentrations
Authors: GHANIM HUSAM , HEJNA JEANNE M. , ABUAYSHEH SANAA , SHAH TANVI , KUMAR JAGDESH , BATRA MANAV , DANDONA PARESH
Published: June 2018

Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit. One possible mechanism is glycosuria and polyuria and the loss of fluid from the vascular compartment. However, since type 2 diabetes is a pro-inflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in pro-inflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis. Twenty-two patients with type 2 diabetes and normal renal function (mean age: 62.1±1.7 years) were randomly treated with placebo or dapagliflozin 10 mg daily for 12 weeks. In the dapagliflozin group, there was a fall in HbA1c from 7.1±0.2% to 6.7±0.2% (p<0.05), increase in hemoglobin concentration from 13.2±0.8g/L to 13.8±0.4g/L (p<0.05) and in Hct from 40.2±1.3% to 41.9±1.8% (p<0.05). Plasma concentration of hepcidin fell from 265±26ng/mL to 215±24ng/mL (p<0.05). There was no significant change in any of these indices in the placebo group. Since one of the mechanisms through which hepcidin inhibits erythropoiesis is the suppression of the expression of ferroportin, which transports iron from iron storage cells into plasma, we also measured ferroportin expression in peripheral blood mononuclear cells. The expression of this transporter was not altered. We conclude that dapagliflozin suppresses hepcidin concentrations significantly, consistent with an increase in erythropoiesis and hematocrit but by a mechanism not involving ferroportin expression.

Disclosure

H. Ghanim: None. J.M. Hejna: None. S. Abuaysheh: None. T. Shah: None. J. Kumar: None. M. Batra: Speaker's Bureau; Self; Eli Lilly and Company. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca.
Bedside Blind Bone Biopsy (B4) for Suspected Diabetic Foot Osteitis–A Reliable Tool to Manage Medical Treatment?
Authors: FÉRON FLORINE , GAUTHIER DIANE-CÉCILE , GAUTIER JEAN-FRANÇOIS , KEVORKIAN JEAN-PHILIPPE
Published: June 2018

Performed by a diabetologist, B4 has been recently shown as an easy and safe procedure. To assess Exclusive Medical Treatment (EMT: offloading, wound care ± antibiotherapy) determined by B4 in suspected Diabetic Foot Ulcer (DFU) osteitis, we compared DFU outcome between proved (B4+) and ruled out osteitis (B4-) with microbial culture.A prospective observational study was conducted in our Diabetology Unit during a 16-month period (12.17.2015-09.04.2017). Among 244 patients admitted with DFU, we included 31 (13%) consecutive patients with type 2 diabetes mellitus (T2DM) and clinical and/or radiological suspicion of osteitis. For each, B4 was decided by our DFU multidisciplinary board. B4 was performed ≥ 2 weeks after antibiotics discontinuation in case of prior exposure. A 6-weeks targeted antibiotherapy was indicated for proven osteitis by prolonged culture (B4+). In case of negative cultures (B4-), no antibiotherapy was prescribed. The primary outcome was the complete DFU healing with EMT at 6 months.Patients characteristics and results are summarized in Table 1. Around 50% of suspected osteitis was B4-, which prevented from unneeded antibiotics without poorer healing outcomes.B4 might be a reliable tool for managing EMT in suspected DFU osteitis.

Disclosure

F. Féron: None. D. Gauthier: None. J. Gautier: None. J. Kevorkian: None.
Pioglitazone Alters the Cargo Composition of Circulating Exosomes in Subjects with Type 2 Diabetes
Authors: NUNEZ LOPEZ YURY O. , PRATLEY RICHARD E.
Published: June 2018

Pioglitazone (PIO) is an agonist of peroxisome proliferator-activated receptor-γ (PPARγ) which is predominantly expressed in adipose tissue and improves insulin sensitivity in patients with type 2 diabetes (T2D). We hypothesized that PIO effects are mediated, at least in part, by changes in the cargo composition (specifically, miRNAs) of circulating exosomes. We tested this hypothesis in a 3-month trial in which 24 patients with T2D who were well-controlled (HbA1c ≤ 7.0%) with diet/exercise or metformin were randomized to either PIO or placebo (PLA) treatment (NCT00656864). Levels of 42 miRNAs expressed in adipocyte exosomes were measured in exosomes isolated from fasting plasma samples obtained before and after treatment. Levels of exosomal miR-374b-5p, miR-20a-5p, miR-7-5p, and miR-195-5p changed significantly (fold change > 1.5, P < 0.05, FDR < 0.17) in response to PIO treatment relative to PLA (Figure). Changes in exosomal miRNAs correlated with changes in fasting glucose and insulin levels (r > 0.4, P < 0.05, FDR < 0.1). These data suggest that the change in the abundance of specific miRNAs in circulating exosomes may serve as a biomarker of response to PIO and that exosomal miR-374b-5p, miR-20a-5p, miR-7-5p, and miR-195-5p might play mechanistic roles in long-range inter-organ crosstalk.

Disclosure

Y.O. Nunez Lopez: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc..