bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of Carrier Power to Third-Order Intermodulation Distortion Power Ratio for a Power Amplifier at 5.25 GHz using LINC Method
Authors: Elkhaldi Said , Touhami Naima Amar , Aghoutane Mohamed , Elhamadi Taj-eddin
Published: June 2018

Introduction:

This paper focuses on improving the power amplifier linearity for wireless communications. The use of a single branch of a power amplifier can produce high distortion with low efficiency.

Method:

In this paper, the Linear Amplification with Nonlinear Components (LINC) technique is used to improve the linearity and efficiency of the power amplifier. The LINC technique is based on converting the envelope modulation signal into two constant envelope phase-modulated baseband signals. After amplification and combining the resulting signals, the required linear output signal is obtained. To validate the proposed approach, LINC technique is used for linearizing an amplifier based on a GaAs MESFET (described by an artificial neural network Model).

Conclusion:

Good results have been achieved, and an improvement of about 40.80 dBc and 47.50 dBc respectively is obtained for the Δlower C/I and Δupper C/I at 5.25 GHz.
Вікові особливості стану печінки у хворих на хронічні запальні захворювання кишечника за даними стеатометрії та зсувнохвильової еластометрії
Authors: Stoikevych M.V. , Konenko I.S. , Nedzvetskaya N.V.
Published: June 2018

Актуальність. Стаття присвячена актуальній проблемі — вивченню вікових особливостей структурних змін печінки при хронічних запальних захворюваннях кишечника (ХЗЗК). Мета роботи: вивчити вікові особливості структурних змін печінки при неспецифічному виразковому коліті (НВК) та хворобі Крона (ХК). Матеріали та методи. Проведено обстеження 40 пацієнтів за допомогою неінвазивних методів дослідження — стеатометрії та зсувнохвильової еластометрії (ЗХЕ), у тому числі 27 хворих на НВК, 13 — на ХК. Усі хворі були розподілені на групи залежно від віку (відповідно до класифікації Всесвітньої організації охорони здоров’я: від 25 до 44 років — молодий вік, 45–59 років — середній вік). В обстеження включено 29 пацієнтів молодого та 11 пацієнтів середнього віку. Результати. Встановлено, що зміни печінки мали вікові відмінності. Так, за результатами стеатометрії печінки виявлені зміни, характерні для стеатозу печінки за шкалою NAS, у 32,5 % хворих на ХЗЗК, причому у пацієнтів середнього віку стеатоз печінки виявлявся в 1,8 раза частіше порівняно з хворими молодого віку. За даними ЗХЕ, виявлено зміни жорсткості паренхіми печінки у 14 (35 %) у хворих на ХЗЗК, у вигляді І і ІІІ стадії фіброзу — у 25 та 10 % відповідно. У пацієнтів середнього віку у 2,6 раза частіше зустрічалася І та ІІІ стадія фіброзу печінки. Висновки. Враховуючи отримані дані, хворим на ХЗЗК старшої вікової групи доцільно включати в стандарт діагностики проведення ультразвукового дослідження печінки з зсувнохвильовою еластометрією та стеатометрією, що дозволить своєчасно виявити ознаки жирового переродження печінки та визначити раціональну тактику ведення пацієнта, що буде сприяти зниженню ризику розвитку ускладнень захворювань.
Клінічні форми лактазної недостатності в дітей
Authors: Sorokman T.V. , Popelyuk N.A. , Shvygar L.V.
Published: June 2018

Актуальність. Лактазна недостатність (ЛН) — найбільш часта патологія тонкої кишки, для якої характерний розвиток синдрому порушеного травлення і всмоктування, пов’язаного з відсутністю або недостатньою активністю ферменту лактази. Мета дослідження: вивчити особливості перебігу різних клінічних форм ЛН у дітей. Матеріали та методи. Під спостереженням перебували 40 дітей (21 хлопчик та 19 дівчаток) різних вікових категорій з діагнозом «лактазна недостатність». Проводилося дослідження: копрограма, визначення pH, загальний вміст вуглеводів, навантаження лактозою, вміст лактози в сечі. Оцінка вірогідності здійснювалася за допомогою критерію Стьюдента (t). Результати. Виділено чотири клінічні форми ЛН: перша група — ЛН із повною відсутністю ферменту (алактазія, 4 особи), друга — ЛН із частковою недостатністю ферменту (гіполактазія, 10 осіб), третя — ЛН із лактозурією (4 особи), четверта — транзиторна ЛН (22 особи). Клінічна картина проявлялася рідкими (100 %), пінистими (83,3 %), із кислим запахом (83,3 %) випорожненнями. У третини дітей із ЛН спостерігалися зригування, у 75,0 % — абдомінальні коліки. У всіх дітей відмічалися дефіцит маси тіла та дефіцитні анемії. Висновки. Найбільш часто спостерігається транзиторна (вторинна) лактазна недостатність, що перебігає в легкій формі в дітей різних вікових категорій. Алактазія характерна для дітей до 1 року життя, перебігає з вираженими клінічними ознаками на фоні дефіциту маси тіла та анемії. Гіполактазія перебігає з помірно вираженими клінічними симптомами. ЛН із лактозурією характерна для недоношених дітей.
Explaining Quebec's Social Economy Turn
Authors: Arsenault Gabriel
Published: June 2018

Québec has been structuring and promoting a social economy sector since the mid-1990s. What explains this specificity of the Québec social model? Careful process tracing analysis reveals that the mobilization of Québec’s left in the mid-1990s, followed by coalition engineering during the 1996 economy and employment summit, account for Québec’s distinct trajectory. Consistent with power resource theory (PRT), at the agenda-setting stage, protagonists of Québec’s social economy policies were associated with the left. Contrary to what is assumed by PRT, however, at the decision stage, the right’s consent to social economy policies was not conditioned by a weak bargaining position or by a fear of antagonizing voters.RÉSUMÉLe Québec appuie et structure un secteur de l’économie sociale depuis le milieu des années 1990. Comment expliquer cette spécificité du modèle social québécois? Une analyse attentive du retraçage des processus révèle que la mobilisation de la gauche québécoise au milieu des années 1990, suivie d’une coalition autour de l’économie sociale formée au moment du Sommet sur l’économie et l’emploi en 1996, expliquent la trajectoire distincte du Québec. De façon cohérente avec la théorie des ressources de pouvoir (PRT), à l’étape de la mise à l’agenda, les protagonistes des politiques visant à appuyer l’économie sociale au Québec étaient associés à la gauche. Contrairement à ce qui est supposé par la PRT, cependant, à l’étape de la prise de décision, l’appui de la droite à ces politiques ne reposait pas nsur un faible rapport de force ou sur une crainte de s’aliéner les électeurs.
A Survey over Mechanisms for Reducing Free Riding Behaviour in Structured P2P Networks
Authors:   Department of Computer Engineering, Mizoram University, Aizawl-796004, India, Nath Prem
Published: June 2018

P2P (peer-to-peer) overlays have attracted many researchers due to increase in Internet based P2P applications. A P2P overlay is a distributed system in which the independent nodes participate at their will to share resources in distributed manner. P2P overlays are designed for wired based communication systems but today P2P applications are becoming popular in wireless networks even in multi-hop wireless networks. Routing mechanism in P2P overlays is based on IP infrastructure and many protocols are deployed successfully for efficient and fair P2P applications. However, there are many challenges in designing and deployment of efficient and fair protocols for the P2P overlays. These overlays suffer from many challenges such as dynamic overlay management, lack of robust trust model, counterfeit content distribution, free riding, poor resource search scalability, security, etc. The churn rate of nodes (join and leave of nodes) in the P2P overlay makes overlay management and resource searching more challenging. The free riding nature of the nodes in a P2P overlay is undesirable and it creates unfairness in the P2P overlay. There are several mechanisms proposed such as Eigen Trust model, tit-for-tat policy, point-based incentive policy, Page Rank policy, layered taxation, advertisement of incentive, etc. for encouraging fairness in the P2P overlays. I have presented in-depth survey over free riding behaviour, its effect, and existing mechanisms to reduce free riding in structured P2P overlays.
An inconvenient source? Attributes of science documentaries and their effects on information-related behavioral intentions
Authors: Yeo Sara K. , Binder Andrew R. , Dahlstrom Michael F. , Brossard Dominique
Published: June 2018

We investigate the impact of a science documentary on individuals' intention to engage in information-related behaviors by experimentally testing the effects of source type (scientist, politician, or anonymous source) and communication setting (interview or lecture) using a manipulated clip from the documentary, ‘An Inconvenient Truth’. Our results indicate that, compared to anonymous sources, use of authoritative ones result in greater intention to engage in some information-related behaviors. Additionally, our results suggest that increased intentions to engage in exchanging information can be attributed to negative affect induced by the clip featuring a politician. Implications for documentary films and science communication are discussed.
Os limites do debate teórico da desindustrialização no Brasil: uma crítica a partir da perspectiva da formação nacional
Authors: Esposito Mauricio
Published: June 2018

O objetivo desse artigo é apresentar o marco geral do debate sobre a desindustrialização no Brasil e apontar, a partir da perspectiva da formação nacional, os limites e insuficiências do mesmo. No artigo argumentamos que os ortodoxos, ao não levarem em conta as especificidades das economias subdesenvolvidas, apresentam análises simplistas sobre a desindustrialização no Brasil, tanto em relação às causas e consequências, como na própria definição desse processo. Os heterodoxos, por sua vez, apesar de considerarem fatores que vão muito além dos ortodoxos, desconsideram a problemática da formação nacional. Assim, os autores não questionam os condicionantes estruturais responsáveis pela desindustrialização no Brasil, apenas apontam o momento em que a crise se deflagrou, deslocando a análise da história.
Interpretando el pensamiento complejo: un acercamiento a Lev S. Vygotsky
Authors: González García Victoria
Published: June 2018

El contexto actual se caracteriza por su complejidad y multi-dimensionalidad. Por lo tanto, los razonamientos reduccionistas y causales, dominantes en la época del industrialismo, se han vuelto obsoletos. Hoy en día son necesarias habilidades depensamiento crítico y complejo para, por una parte, comprender el contexto en el que nos desarrollamos y, por otra parte, actuar en él mediante la construcción de procesos, respuestas y soluciones a los escenarios multidimensionales, complejos y diversos a los que nos enfrentamos día con día. En el actual cambio de época histórica contamos con herramientas intelectuales para comprender, con mayor profundidad, los aportes de Lev S. Vygotsky, quien no solo fue un hombre de su tiempo, sino que hoy, más que en cualquier otra época, cobra gran actualidad. Esto se debe a que su pensamiento secaracterizó por ser crítico y de una complejidad extraordinaria.
La investigación en la formación de educadores: algunas estrategias para la Escuela de Ciencias de la Educación de la UNED Costa Rica
Authors: Campos Céspedes Jensy
Published: June 2018

En este documento se presentan algunas reflexiones en torno a la importancia de la investigación en las carreras de Educación y tiene el propósito de recordar la necesidad de fortalecer el quehacer investigativo y la articulación de las funciones sustantivas dela universidad en los procesos académicos desarrollados por las unidades formadoras de docentes, a fin de propiciar un quehacer asentado en la investigación orientada al desarrollo. De acuerdo con las características actuales, la investigación aplicada a lapráctica docente y a los fenómenos que afectan los procesos educativos han de ser los principales insumos requeridos para la gestión del conocimiento y la formación de profesionales en Educación, capaces de aprender a aprender y con competencias para gestionar conocimiento. Ello supone una resignificación de la educación en los procesos de construcción de un nuevo imaginario de sociedad caracterizado por la inclusión y el desarrollo. En este sentido, se reconoce que la gestión del conocimientono solo impacta en el desarrollo del currículo, sino que tiene resonancia en la construcción y reconstrucción de la educación y del educador.
La Transversalidad de Género en la Educación Superior: propuesta de un modelo de implementación
Authors: Durán Rodríguez María Martha
Published: June 2018

Se discute en este artículo sobre el origen y concepto de Transversalidad de Género, y su importancia en la Educación Superior. Se realiza una propuesta de modelo de implementación y se puntualiza en el área académica, sus fortalezas y limitaciones.
Malacofauna y Carcinofauna asociada a Rhizophora mangle (L, 1753) en un estuario: río Ranchería, La Guajira, Colombia
Authors: Molina Bolivar Geomar
Published: June 2018

Se estudiaron atributos de la malacofauna y carcinofauna asociados a las raíces sumergidas de Rhizophora mangle y su relación con factores fisicoquímicos en el estuario del río Ranchería (La Guajira). Los muestreos se realizaron entre septiembre (2014) y marzo (2015) en cinco sitios; Desembocadura (DB), El Mirador (EM), Villa Fátima (VF), El Pasito (EP) y Valle de Los Cangrejos (VC). Las especies se colectaron cada 15 días en cada muestreo y lugar. Se cortaron al azar dos raíces sumergidas, para así obtener los organismos, los cuales fueron fijados en formalina al 10% y preservados en alcohol al 70%. Igualmente se determinaron algunas variables fisicoquímicas del agua, como oxígeno disuelto, salinidad, temperatura y nutrientes (amonio, nitrato y fosforo total). Una vez cuantificados e identificados los organismos se determinó: Abundancia absoluta (Ab), riqueza específica (Margalef – R1) y diversidad (Shannon-Wiener). En total se colectaron 1513 individuos, de los cuales 398 fueron moluscos, distribuidos en las clases bivalva y gasterópoda. La familia Mytilidae fue más representativa y la especie más abundante Mytiliopsis leucophaeta (298 inds.). Se colectó un total de 1115 organismos del subfilum crustacea, de las cuales las familias Palaemoenidae y Aoridae presentaron el mayor número de especies. La especie más abundante fue Americorophium brevis (712 inds.). La principal riqueza especifica (R1=3,23) y diversidad (H´=2,12) se dio en VF, mientras que los menores valores de estas variables se presentaron en EM (R1=0,44; H´=0,37). Se concluyó que, aunque la composición de la comunidad se muestra relativamente diferente a nivel espacial durante el periodo estudiado, no se encontró una relación estadísticamente significativa de esta condición biológica con respecto a los factores fisicoquímicos estudiados.
Cuantificación de gases de efecto invernadero en la Sede de Occidente de la Universidad de Costa Rica
Authors: Chassoul Acosta María José , Marin L. Rolando , Morales  C. María Alejandra , Fallas M. María Fernanda
Published: June 2018

La Sede de Occidente de la Universidad de Costa Rica está conformada por el recinto de San Ramón y el recinto de Grecia. Fue fundada en abril de 1968 y actualmente cuenta con una población de aproximadamente 3100 estudiantes y 911 funcionarios, los cuales se distribuyen entre ambos recintos. Con el propósito de alinearse al compromiso de la Universidad de Costa Rica de ser Carbono Neutro en el año 2020, la Sede decidió cuantificar los GEI generados por las actividades realizadas, para luego establecer una estrategia de mitigación y poder disminuir el impacto ambiental causado. Para la cuantificación primero se identificaron las diferentes fuentes emisoras de cada instalación física, luego se realizó la recolección de datos y por último se calculó la cantidad de toneladas de carbono equivalente emitidas de acuerdo a los factores de emisión establecidos por el Instituto Meteorológico Nacional. Esto permitió determinar que la Sede genera 267,35 toneladas de CO2-e, de las cuales 93% corresponde al recinto de San Ramón y 7% al recinto de Grecia.
Conversatorio. Estrategias de construcción de paz en contextos de crisis: acciones para la protección de niñas, niños y adolescentes
Authors: Posgrado y Sociedad Revista
Published: June 2018

Abel Saraiba, psicólogo especialista en Derecho de Familia y Niñez, coordinador del Programa Creciendo sin Violencia del Centro Comunitario de Aprendizaje (CECODAP), Venezuela. Accesible en http://videoteca_vau.uned.ac.cr/videos/video/3358/#view-chat
The optical properties of bismuth germanium oxide single crystals
Authors: Golubovic Aleksandar , Gajic Rados , Chen Changkang , Valcic Andreja
Published: June 2018

Bi12GeO20 single crystals were grown by the Czochralski technique. Suitable
polishing and etching solutions were determined. Reflection spectra were
recorded in the wave numbers range 20-5000 cm-1, and compared with the
spectra of Bi12SiO20 single crystals to study the position of the phonon
modes. The optical constants of the Bi12GeO20 single crystals were obtained
using Kramers-Kronig analysis. The obtained results are dicussed and
compared with published data.
A study of the behaviour of some substituted 1,2,4-triazoline-3-thiones in different media
Authors: Arman-Zubic Lucijana , Perisic-Janjic Nada , Lazarevic Marija
Published: June 2018

The acid-base behaviour of 4-phenyl-5-(4-R-benzyl)-1,2,4-triazoline-3-thione
(1(R = OH); 2(R = OC2H5)) was studied in aqueous sulfuric acid and sodium
hydroxide solutions. Three ionisation equilibria of compound 1 (pKBH3+ =
-4.64, pKBH2 = 7.50, pKBH- = 10.06) and two ionisation equilibria of
compound 2 (pKBH2+ = -4.82, pKBH = 7.45) were found. The first equilibrium
belongs to the protonation of 1,2,4-triazoline-3-thione, while the second
belongs to the dissociation of the same part of the molecule. The third
equilibrium represents the dissociation process of the phenolic OH group of
compound 1. The kinetics of hydrolysis of compounds 1 and 2 were studied in
high concentrated sulfuric acid solutions. The hydrolysis follows an
irreversible first-order consecutive reaction path.
Electrochemical behaviour of copper in N,N-dimethylformamide + 0.5 M potassium perchlorate solution
Authors: Vojinovic V. , Komnenic V. , Pjescic M. , Mentus S.
Published: June 2018

The electrochemical deposition and dissolution of copper in 0.0025 M CuSO4 +
N,N-dimethylformamide + 0.5 M KClO4 solution was examined by the rotating
disc and potentiodynamic methods. Both platinum and copper were used as
working electrodes. A wide polarization range -1 to +2 V vs. SCE, and
several temperatures between 25 and 55?C were encompased. The Cu/electrolyte
interface was found to be permanently out of equilibrium, as a consequence
of the development of a passivating layer. In accordance with the classic
theory of a copper electrode in acidified aqueous solutions, the cathodic
and anodic Tafel lines of metallic copper define a unique value of the
exchange current density, however, their slopes do not correspond to the
classic theory.
The alcoholysis of 1,2,2-trimethylpropyl-methylfluorophosphonate
Authors: Micevic Mladjen , Petrovic Slobodan
Published: June 2018

The alcoholysis of 1,2,2-trimethylpropyl-methylfluorophosphonate (soman) was
examined with a series of alkoxides and in corresponding alcohols: methanol,
ethanol, 1-propanol, 2-propanol, 2-methoxyethanol and 2-ethoxyethanol. Soman
reacts with the used alkoxides in a second order reaction, first order in
each reactant. The kinetics of the reaction between
1,2,2-trimethylpropyl-methylfluorophosphonate and ethanol in the presence of
diethylenetriamine was also examined. A third order reaction rate constant
was calculated, first order in each reactant. The activation energy,
frequency factor and activation entropy were determined on the basis of the
kinetic data.
Low-Dose IL-2 Signaling Is Specifically Impaired in Regulatory T Cells from T1D Patients
Authors: PRIETL BARBARA , KOFLER SELINA , STANZER STEFANIE , OBERMAYER-PIETSCH BARBARA M. , PIEBER THOMAS R. , SOURIJ HARALD
Published: June 2018

Background: The response to interleukin-2 (IL-2) is essential for the stability and function of regulatory T cells (Tregs) in vivo. Impaired IL-2 receptor signaling might play a crucial role in the decreased function of Tregs in autoimmunity but might also contribute to the increased suppressive capacity of Tregs in cancer. In this study we aimed to examine differences in the phosphorylation of STAT5 as a downstream measure of IL-2 signaling in type 1 diabetes (T1D), rheumatoid arthritis (RA), colo-rectal cancer (CRC) and healthy controls.

Material and Methods: Phosphorylation of STAT5 was quantified in 10 T1D, 10 RA, 10 CRC and 10 healthy control samples. Freshly drawn whole blood was stimulated with increasing amounts of IL-2 [0, 0.5, 1, 5, 10 U/ml] for 30 minutes. The expression of phosphorylated STAT5 (pSTAT5) in Tregs was quantified by flow cytometry.

Results: Tregs from T1D patients showed significantly decreased levels of pSTAT5 when compared to healthy controls after stimulation with 0.5 U IL-2 (mean fluorescence intensity, MFI: 896 ± 502 vs. 3435 ± 1035, p<0.001) and after stimulation with 1 U IL-2/ml (MFI: 1095 ± 942 vs. 3835 ± 1415, p=0.004). Tregs from RA patients showed decreased levels after stimulation with 0.5 U IL-2/ml (p=0.043) but not after stimulation with 1U IL-2/ml when compared to healthy controls. No significant differences between cells from CRC patients and controls were found. Stimulation with 5 or 10 U IL-2/ml led to comparable levels of pSTAT5 in all investigated samples.

Conclusion: The response towards low doses of IL-2 is significantly decreased in Tregs from T1D and RA patients. This might contribute to the loss of tolerance and increased autoimmunity in those diseases. However, low dose IL2 signaling does not seem to be involved in the increased suppressive capacity of Tregs in CRC patients.

Disclosure

B. Prietl: None. S. Kofler: None. S. Stanzer: None. B.M. Obermayer-Pietsch: None. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc..
Pharmacodynamics of 100 vs. 200 Units of U500 Regular Insulin in Obese Subjects with T2DM
Authors: KUMAR ANJALI , SHRESTHA RUPENDRA T. , TADDESE ABDISA S. , MOHEET AMIR , KHOWAJA AMEER , OLAWSKY EVAN A. , EBERLY LYNN E. , SEAQUIST ELIZABETH R.
Published: June 2018

Practitioners often consider using U500 regular insulin (U500) in obese patients with T2DM who take >100 units of insulin/day. To compare the pharmacodynamic effects of 2 doses of U500 in such patients, we did a randomized double blind cross over study in which 100 or 200 units (U) SQ of U500 was given once and IV glucose was then given as necessary to maintain euglycemia (EU). Subjects stopped their own insulin at least 12 hours before the U500 dose and were kept on an insulin drip overnight to target EU. Subjects were NPO for 8 hours before and 4 hours after U500 dosing. Meals with 30 gm of carbohydrate were given at hours 4, 9, 13, 26, 30. Rate of U500 onset was determined by measuring the area under the curve (AUC) of IV glucose given hours 0-4, the peak infusion rate achieved hours 0-4, and the time at which IV glucose was started. Duration of action was determined by measuring the time IV glucose was required to maintain EU. The effect of the each dose on glucose lowering was determined by measuring the AUC of the IV glucose given to maintain EU for the entire study. 3F, 9M completed the study (age 54 ± 5 years, BMI 36.0 ± 3.3 kg/m2, total daily insulin dose 174 ± 40 units, mean ± SD).

We conclude the duration of action of U500 is longer following administration 200 vs. 100. However, no differences were found in rate of onset or total amount of glucose required to maintain EU. Future studies should examine the pharmacodynamics of repeated doses of U500 in similar subjects.

{6E9A1FC8-900A-4232-972F-0B0D186440A8}Dose100 units U500200 units U500Total glucose given 0-4 hours after U500 dose (mg/kg)5.3 ± 6.54.7 ± 5.6Peak infusion rate achieved 0-4 hours after U500 (mg/kg/min)5.3 ± 3.84.2 ± 1.9Time following injection the glucose infusion was started to maintain EU (hours)2.6 ± 1.32.2 ± 1.0Duration of action (hours)11.0 ± 5.616.5 ± 6.4p=0.031Total glucose required to maintain euglycemia (mg/kg)18.5 ± 20.720.1± 13.3

Disclosure

A. Kumar: None. R.T. Shrestha: None. A.S. Taddese: None. A. Moheet: None. A. Khowaja: None. E.A. Olawsky: None. L.E. Eberly: None. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company, Sanofi, Zucera, InfoMed, 360 consulting. Other Relationship; Self; Novo Nordisk Inc..
The Characteristics of Patients with Long Remission after Short-Term Insulin Intensive Therapy
Authors: WAN XUESI , LIU JUAN , HUANG ZHIMIN , LIU LIEHUA , LI YANBING
Published: June 2018

In our previous study, some patients with newly diagnosed type 2 diabetes mellitus can maintain euglycaemia without hypoglycemic agents after 2-week intensive insulin therapies for long time. But the others didn’t respond well to the treatment. To identify patients who would get long-remission from this treatment, a retrospective study was conducted to compared the characters between them. An observation of 160 patients with newly dignosed T2DM (103 male, aged 50±10 ys,HbA1C 11±2.1%) after2-week therapy was studied remission rate. After the termination of short-term CSII, 65.6% patients maintained long-remission more than 1-year, 18.1%patients got short-remission less than 1-year, and 16.3% patients didn’t get remission from the therapy. Age, BMI and glucose metabolism at baseline were not significantly different among three groups. As the table below showed, the long-remission patients have statistically lower FPG, PPG, A1c and better HOMA-B just after therapy.

In conclusion, the beta cell function (which test by HOMA-B) might affect the remission rate mainly by the better improved metabolism of glucose.non-remission group at baselinenon-remission group after therapyshort-remission group at baselineshort-remission group after therapylong-remission group at baselinelong-remission group after therapyBMI24.24 ±3.0024.29 ±3.0024.99 ±4.0024.68 ±3.0025.59 ±3.0025.27 ±3.00FPG12.94 ±3.007.79 ±1.5012.13 ±3.006.34 ±1.2011.45 ±3.006.08 ±1.30PPG19.10 ±6.0010.87 ±3.0017.84 ±5.00 8.38 ±2.00 17.86 ±6.00 7.73 ±2.00 GHbA1C11.69 ±2.0010.09 ±1.0011.23 ±2.009.70 ±2.00 10.73 ±2.009.16 ±2.00 HOMA-B15.27 ±8.0038.49 ±19.00 21.45 ±16.0067.61

Disclosure

X. Wan: None. J. Liu: None. Z. Huang: None. L. Liu: None. Y. Li: None.
The Impact of Different Initial Insulin Dose Regimens in Short-Term Intensive Insulin Therapy
Authors: XINWEI HUANG
Published: June 2018

Objective: To compare the effects of different initial insulin dose regimens during the short-term insulin intensive treatment in newly diagnosed type 2 diabetes patients, in order to investigate the rational of formula based initiation regimen.

Methods: Fifty six patients with newly diagnosed type 2 diabetes, 33 males and 23 females, aged 27-65 years old, BMI 25.43 ± 2.90 kg/m2, were randomly assigned into 2 groups: the formula group (whose insulin dose was initiated according to the formula recommended in our previous study, 28 cases) and the empirical group (according to current guidelines, 28 cases). Short-term intensive insulin therapy was performed, and the glycemic goal was gradually achieved. The time to glycemic goal(TGG), TDD-1, the frequency of hypoglycemia and the glycemic variability were compared.

Results: The average TGG in the formula group(2.68 ± 1.44 days) is shorter than that in the empirical group (3.61 ± 1.60 days, P <0.05). There is no significant difference in the initial insulin dose (44.28 ± 9.10 IU, P> 0.05) of the formula group compared with the TDD-1 (46.91 ± 13.26 IU), whereas the initial insulin dose (34.09 ± 5.21 IU, P <0.05)of the empirical group is less than TDD-1. Compared with the TDD-1, while 70% of the estimate TDD-1(eTDD-1),which is calculated according to the formula as the initial insulin regimen,may not meet the requirements (P <0.001), 100% of the eTDD-1 is also too much for them (P <0.001).All the indicators for glycemic variability such as mean MBG, MGSD, M value, MAGE and LAGE during the initial three days are not significantly different between the two groups (P> 0.05). There is also no significant difference between 2 groups in the incidence of hypoglycemia(P> 0.05).

Conclusion: Formula based initial insulin regimen is helpful in shortening TGG without increasing within-day glycemic variability or hypoglycemia events.It is recommended that 80% of the eTDD-1 can be used as the initial insulin regimen for the intensive treatment in most newly diagnosed T2DM patients.

Disclosure

H. Xinwei: None.
Effect of Combination Therapy with Liraglutide plus Canagliflozin on HGP and HbA1c vs. Each Therapy Alone in T2DM
Authors: ABDUL-GHANI MUHAMMAD , ALI ALI M. , MARTINEZ ROBERT A. , ADAMS JOHN M. , CERSOSIMO EUGENIO , TRIPLITT CURTIS L. , DEFRONZO RALPH A.
Published: June 2018

Background: We previously have shown that SGLT2 inhibitors cause an increase in HGP accompanied with an increase in plasma glucagon concentration. We hypothesized that the increase in plasma glucagon concentration is, at least in part, responsible for the increase in HGP. The aim of the present study was to examine whether inhibition of glucagon secretion by liraglutide can prevent the increase in HGP.

Research Design and Methods: 51 T2DM patients (age=51±1 yr; 40% female; BMI=34.6±0.7; diabetes duration=6.8±0.8 yr; FPG=175±7; HbA1c=8.3±0.1%) were randomized to receive for 16 weeks: (i) canagliflozin 300 mg; (ii) liraglutide 1.8 mg; or (iii) canagliflozin 300 mg plus liraglutide 1.8 mg. HGP (measured with 3-3H-glucose infusion) and plasma glucagon concentration were measured before and after 16 weeks of treatment.

Results: Canagliflozin monotherapy caused a significant reduction in HbA1c (-1.1±0.2%, p<0.01) accompanied with an increase in plasma glucagon concentration (by 28%, p<0.05) and HGP (by 15%, p<0.05) which lasted for 16 weeks. Conversely, liraglutide monotherapy caused a 1.6±0.5% (p<0.01) reduction in HbA1c accompanied by a small (6%) reduction in HGP (P=NS) without significant change in fasting plasma glucagon concentration. The combination of canagliflozin plus liraglutide caused a greater reduction in HbA1c (1.9±0.5%, p<0.vs. canagliflozin and p=NS vs. liraglutide) and attenuated the increase in fasting plasma glucagon and basal HGP at 16 weeks.

Conclusion: These results: (1) support a possible role for increased plasma glucagon levels in the long term maintenance of increase in HGP caused by SGLT2i, and (2) suggest that factors other than/in addition to glucagon contribute to the initiation of the increase in HGP.

Disclosure

M. Abdul-Ghani: None. A.M. Ali: None. R.A. Martinez: None. J.M. Adams: None. E. Cersosimo: Research Support; Self; AstraZeneca, VeroScience, LLC.. Speaker's Bureau; Self; AstraZeneca, Sanofi, Janssen Pharmaceuticals, Inc., Eli Lilly and Company. C.L. Triplitt: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Eli Lilly and Company. Consultant; Self; Sanofi, Novo Nordisk Inc. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc..
Qualitative and Quantitative Effect of IDegLira Compared with the Nonfixed Administration of Degludec and Liraglutide
Authors: KOUTSOVASILIS ANASTASIOS , SOTIROPOULOS ALEXIOS , PAPADAKI DESPINA , BLETSA EVDOXIA , KOKOTOS GEORGIOS , KOUNELAKIS IOANNIS , BOUSBOULAS STAVROS , PEPPAS THEODOROS
Published: June 2018

Introduction: The efficacy and safety of IDegLira and the benefits of its complementary mode of action have been examined in the large global DUAL clinical trial program.

Aim: The aim of this study is to examine the qualitative and quantitative effect of IDegLira compared to the non-fixed adiministration of degludec and liraglutide.

Methods: Uncontrolled type 2 diabetes (T2D) patients (n=473) were included in the study. 158 patients on oral antidiabetic drugs (OADs) switched to OADs and IDegLira (Group A), 163 on OADs and liraglutide switched to degludec and the existing therapeutic regime (Group B) and 152 patients on degludec and OADs switched to liraglutide and the existing treatment (Group C). All patients also received metformin while none of them received sulfonylurea. Follow-up was 12 months and changes in HbA1c, cardiometabolic risk factors, and treatment adherence (with the 8-item Morisky Medication Adherence Scale) were recorded.

Results: There was no difference at baseline between the three Groups as to age (p=0.224), diabetes duration (p=0.322), HbA1c (8.56±1.12, p=0.116) and BMI (32.14±3.56, p=0.142). The mean HbA1c after 12 months was 6.79±0.77, 7.14±1.19, 7.18±1.07 (p=0.033) for Groups A, B and C respectively. More patients achieved the therapeutic target for HbA1c in Group A (p=0.048). The weight change was -3.2±1.2 Kg for Group A, 1.2±1.1 Kg for Group B and -4.3±1.7 Kg for Group C (p<0.001). There was no difference in the hypoglycemic episodes between the three Groups (p=0.251). Greater adherence was achieved in Group A compared to Group B and C (7.58±1.08, 6.38±1.28 and 6.44±1.16, p=0.031). Total insulin dose was lower for Group A (p=0.040).

Conclusions: Uncontrolled patients on oral antidiabetic drugs when switched to a therapeutic regimen with IDegLira achieved a significant improvement in their glycemic control with a significant adherence to their therapeutic regimen while the adherence in a non-fixed combination was not significant enough.

Disclosure

A. Koutsovasilis: None. A. Sotiropoulos: None. D. Papadaki: None. E. Bletsa: None. G. Kokotos: None. I. Kounelakis: None. S. Bousboulas: None. T. Peppas: None.
Possibility of Liraglutide for Prevention of Dementia Progression in Patients with Type 2 Diabetes
Authors: YOSHIDA MAMI , MORIMOTO TAKAKO , OH ERIKO , YAMAMOTO NAOMUNE , NAGATA KOUJI , SAEKI AKIO , SASAKI EUN , YOSHIDA SHIGERU , KUZUYA TAKESHI , OHSAWA NAKAAI , SUGINO MASAKAZU
Published: June 2018

Purpose: The aim of this study was to assess the efficacy of liraglutide on prevention of dementia in elderly patients with type 2 diabetes (T2DM).

Subjects and methods: We studied 34 (male 8/female 26) outpatients with 65 years or older, whose HbA1c was over 7.0% by other antidiabetic treatment. We administrated liraglutide 0.3mg before breakfast for the first week, 0.6mg for the second week, and 0.9mg after the third week. 34 subjects in the liraglutide group (G group) [8 males/ 26 females, 75.7±7.8 years old, HbA1c 7.5 ± 0.38%] were followed-up for 3 years. We examined Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on MRI, max-IMT measured by carotid artery echo, visceral fat area, HbA1c, FPG, serum HDL/LDL level, and TG, both before and after the treatment.10 patients in the linagliptin group (D group) in which ages, HbA1c, visceral fat, and VSRAD were matched with G group were used as controls.

Result: After 3 years, VSRAD was not changed in G group and was significantly deteriorated in D group (G group: 1.22±0.73→1.19±0.73 (NS) vs. G group: 1.36±0.87→1.53±0.99 (p = 0.022)). Max IMT was significantly improved in G group (2.42±1.65→2.14±1.40 (p =0.035) vs. 2.25±1.19→2.19±1.01(NS)). Visceral fat was significantly reduced in G group (137.1±54.0→128.0±59.3 (p <0.01) vs. 114.3±55.8 → 116.5±66.2 (NS)). HbA1c (7.5±0.38 → 6.8±0.46 vs. 7.3±0.55 → 6.9±0.42%), FPG (137±19 → 121±11 vs. 135 ±21 → 118±16 mg/dl), were significantly improved in both groups (p<0.01). No hypoglycemia requiring medical intervention was observed. Lipid was significantly improved only in TG in G group (TG: 162±53→145±34 (p <0.01) vs. 185±45→159±48 mg/dl (NS)). There was no onset of dementia.

Conclusion: Liraglutide improved the glycemic control, lipid profile, and visceral obesity of elderly patients with T2DM for 3 years. In addition, the hippocampal atrophy and arteriosclerosis were not deteriorated, suggesting the possibility of being effective for prevention of dementia.

Disclosure

M. Yoshida: None. T. Morimoto: None. E. Oh: None. N. Yamamoto: None. K. Nagata: None. A. Saeki: None. E. Sasaki: None. S. Yoshida: None. T. Kuzuya: None. N. Ohsawa: None. M. Sugino: None.
Sodium-Glucose Cotransporter 2 Inhibitors for Type 1 Diabetes Mellitus—Systematic Review and Meta-analysis
Authors: YAMADA TOMOHIDE , HOSOE JUN , SHOJIMA NOBUHIRO , YAMAUCHI TOSHIMASA , KADOWAKI TAKASHI
Published: June 2018

Additional treatment for type 1 diabetes is an unmet need. We investigated the efficacy and safety of adding Sodium-glucose co-transporter 2 inhibitors (SGLT2is) to insulin in patients with type 1 diabetes mellitus by performing meta-analysis. Prospective randomized, placebo-controlled trials investigating insulin and SGLT2is in adults with type 1 diabetes were assessed. We searched electronic databases up to November 2017. Meta-analysis was performed by a random effects model. Two reviewers independently extracted information and evaluated study quality with the Cochrane risk-of-bias tool. Among about 1300 studies identified, 14 studies were investigated (N=4,591). Meta-analysis revealed that SGLT2i therapy significantly reduced HbA1c by 0.4% (95% confidence interval [CI]: 0.35, 0.46; P<0.001; I2=0%), fasting plasma glucose by 1.14 mmol/l (0.8,1.47), body weight by 2.68 kg (2.0, 3.36), and systolic blood pressure by 3.37 mmHg (1.46, 5.28). In addition, the total daily insulin dose decreased by 6.0 units (4.9, 7.1), bolus insulin decreased by 3.6 units/day (2.0, 5.3), and basal insulin decreased by 4.2 units/day (2.2, 6.3). There was no significant increase of hypoglycemia or severe hypoglycemia. However, SGLT2i therapy increased diabetic ketoacidosis [OR: 3.38 (1.74, 6.56)] and genital tract infection [OR: 3.44 (2.34, 5.07)].

In summary, SGLT2i therapy might be advantageous for type 1 diabetes. However, use of this combination should be considered carefully.

Disclosure

T. Yamada: None. J. Hosoe: None. N. Shojima: None. T. Yamauchi: Research Support; Self; Novo Nordisk Inc., Daiichi Sankyo Company, Limited, Sanofi, Takeda, Tanabe-Mitsubishi. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.
Ipragliflozin, a SGLT2 Inhibitor, Reduced Body Weight and Fat Mass but Not Muscle Mass in Japanese Type 2 Diabetic Patients Treated with Insulin—A Randomized Clinical Trial
Authors: MORINO KATSUTARO , INOUE HIDEKA , FUSE KEIKO , TANAKA SACHIKO , KONDO KEIKO , ARIMA HISATOMI , MIURA KATSUYUKI , SATO DAISUKE , OHASHI NATSUKO , IDA SHOGO , MIYAZAWA ITSUKO , SEKINE OSAMU , UGI SATOSHI , MAEGAWA HIROSHI ,   SUMS-ADDIT-1 STUDY GROUP
Published: June 2018

Objective: Weight gain is a common problem in the insulin treatment. SGLT2 inhibitors are expected to reduce body weight (BW) due to negative energy balance. Previous reports suggested that BW reduction is achieved mainly by loss of body fat, and ∼20% of reduction is by lean mass. However, the efficacy of SGLT2 inhibitor on BW and body composition remains unclear. We examined these in the Japanese T2DM treated with insulin.

Methods: The study was an open label randomized controlled trial. Primary endpoint was the change in BW from baseline to week 24 between the two groups. Fifty overweight patients (BMI > 23) who had inadequate glycemic control with insulin treatment were randomly assigned to ipragliflozin (Ipra) or standard treatment (Con) and followed for 24 weeks. Body composition was assessed by DEXA and impedance method.

Results: The change in BW was significantly larger in Ipra compared to Con. Ipra showed significant larger reduction of HbA1c. Total fat mass was reduced in the Ipra compared to Con mainly due to lower limb fat and trunk fat. Total muscle mass was maintained at lower limbs and trunk but tended to be reduced at arm in Ipra.

Conclusion: Ipragliflozin treatment for 24 weeks resulted in reduction of BW mainly due to fat mass at lower limb and trunk. Reduction of the muscle mass at lower limb may be protected by anti-gravity effect.

Disclosure

K. Morino: Research Support; Self; Astellas Pharma US, Inc., AstraZeneca, Sunstar Inc., CMIC Pharmascience, Kowa Pharmaceutical. H. Inoue: None. K. Fuse: None. S. Tanaka: None. K. Kondo: None. H. Arima: Advisory Panel; Self; Kyowa Kirin. Speaker's Bureau; Self; Takeda Japan, Daiichi Sankyo Company, Limited. K. Miura: None. D. Sato: None. N. Ohashi: None. S. Ida: None. I. Miyazawa: None. O. Sekine: None. S. Ugi: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K. H. Maegawa: Speaker's Bureau; Self; Astellas Pharma US, Inc.. Research Support; Self; Astellas Pharma US, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Nippon Boehringer Ingelheim Co. Ltd.. Research Support; Self; Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Daiichi Sankyo Company, Limited, Takeda Pharmaceutical Company. Speaker's Bureau; Self; Takeda Pharmaceutical Company, Novo Nordisk A/S, Eli Lilly and Company.
The Effect of Empagliflozin on Metabolic Parameters in Nonobese Nondiabetic Model of Metabolic Syndrome
Authors: TRNOVSKA JAROSLAVA , HÜTTL MARTINA , MARKOVÁ IRENA , OLIYARNYK OLENA , MALINSKA HANA , KAZDOVA LUDMILA , HALUZIK MARTIN
Published: June 2018

Empagliflozin (EMPAG), an SGLT2 inhibitor, improves glucose metabolism by increasing urinary glucose output. EMPA-REG OUTCOME study documented cardiovascular (CV) benefits of EMPAG in patients with type 2 diabetes (T2DM) and history of a CV event. This work was undertaken to investigate complex effects of EMPAG in hereditary hypertriglyceridemic rats (HHTg), a non-obese, nondiabetic model of metabolic sydrome. HHTg rats are characterized by the presence of dyslipidemia and insulin resistance without obesity or hyperglycemia. 8 months old male HHTg rats were fed a standard diet (SD) or SD enriched by EMPAG in a dose of 10 mg/kg body weight/day for 6 weeks. EMPAG treatment suppressed an increase in body weight despite greater average food intake in EMPAG relative to control group. EMPAG administration induced glycosuria (+99%; P<0.001) and decreased fasting glycemia (-21%; P<0.02). Plasma lipid profile in postprandial state revealed a decrease in triglycerides (-34%; P<0.001) and insulin (-36%;P<0.01), increase in HDL cholesterol (+17%; P<0.01) and free fatty acids (+36%; P<0.02). Systemic ketone bodies concentrations were unchanged with simultaneous decrease in 14C-palmitic acid oxidation in the myocardium suggesting ketone bodies utilization by this tissue. EMPAG improved parameters of oxidative stress (SOD: +24%; P<0.03; GSH-Px: +31%; P<0.01; TBARS: -17%; P<0.003) in the kidney and decreased glycogen content in the liver and muscle by 39% and 13%; respectively (P<0.01). EMPAG improved insulin sensitivity of white adipose tissue (+13%; P<0.05) and decreased relative weight of perirenal adipose tissue (-13%; P<0.01).

In conclusion, in nondiabetic rats with MS, EMPAG improved insulin sensitivity of WAT, dyslipidemia and oxidative stress in the kidney. Combination of these factors may partially explain CV benefits of EMPAG in T2DM and suggests the possibility of similar benefits in patients with metabolic syndrome without diabetes.

Disclosure

J. Trnovska: None. M. Hüttl: None. I. Marková: None. O. Oliyarnyk: None. H. Malinska: None. L. Kazdova: None. M. Haluzik: None.
Adiponectin Attenuates NLRP3 Inflammasome by Modulating AMPK-ROS Pathway
Authors: WANG FANG , WANG LINGHAO , LIU YUXING , YUAN JINGJING , MO ZHAOHUI
Published: June 2018

Adiponectin is an adipocyte-derived cytokine that exerts antidiabetic and anti-atherogenic properties and has been shown to enhance insulin sensitivity and promote lipid metabolism in obesity-linked diseases through the anti-inflammatory action. However, the detail mechanism of the anti-inflammatory effect of adiponectin remains unknown. In the present study, we found that in 50 patients with newly diagnosed type 2 diabetes (T2D), the circulating levels of adiponectin correlate inversely with IL-18 (r = -0.64, P < 0.01). On this basis and in vitro, we demonstrated that adiponectin significantly attenuates IL-18 secreation from LPS+PA-induced THP-1 cells (P < 0.01). In addition, we reported here that adiponectin inhibits IL-18 by suppressing NLRP3 inflammasome activation. Importantly, we found that adiponectin suppressed LPS+PA (palmitic acid)-induced ROS production, which is required for NLRP3 inflammasome activation. Furtherly, we, for the first time, described that adiponectin attenuates NLRP3 inflammasome activation by modulating AMPK-ROS signaling pathway, as the reason that suppression of AMPK with small interfering RNA (siRNA) abolished adiponectin-mediated inhibition of ROS and NLRP3 inflammasome. In vivo studies with STZ-induced diabetic mice models, we showed that adenovirus-mediated overexpression of adiponectin decreased triglycerides and cholesterol in the serum of diabetic mice. Meanwhile, adiponectin decreased CD68 positive macrophages infiltrated in adipose tissue. Furthermore, adiponectin reduced activation of NLRP3 inflammasome in liver and white adipose tissue (WAT) with western blot assay. Taken together, we report a new mechanism that adiponectin alleviates inflammation through NLRP3 inflammasome inhibition by modulating AMPK-ROS pathway, which may have therapeutic implications for T2D and the related metabolic diseases.

Disclosure

F. Wang: None. L. Wang: None. Y. Liu: None. J. Yuan: None. Z. Mo: None.