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Showing 1 - 200 of 2350 Journals sorted alphabetically
3D Printing in Medicine     Open Access  
3D Research     Hybrid Journal   (Followers: 20, SJR: 0.214, h-index: 10)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 1.073, h-index: 25)
AAPS J.     Hybrid Journal   (Followers: 21, SJR: 1.192, h-index: 74)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.718, h-index: 54)
Abdominal Imaging     Hybrid Journal   (Followers: 14, SJR: 0.723, h-index: 60)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 4, SJR: 0.447, h-index: 12)
Academic Psychiatry     Full-text available via subscription   (Followers: 23, SJR: 0.492, h-index: 32)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.135, h-index: 6)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26, SJR: 0.378, h-index: 30)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.355, h-index: 20)
Acoustics Australia     Hybrid Journal  
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.387, h-index: 6)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.624, h-index: 34)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.419, h-index: 25)
Acta Diabetologica     Hybrid Journal   (Followers: 16, SJR: 1.318, h-index: 46)
Acta Endoscopica     Hybrid Journal   (Followers: 1, SJR: 0.113, h-index: 8)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.465, h-index: 23)
Acta Geochimica     Hybrid Journal   (Followers: 6)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.294, h-index: 13)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.818, h-index: 22)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.524, h-index: 32)
Acta Mathematica     Hybrid Journal   (Followers: 12, SJR: 8.021, h-index: 47)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.53, h-index: 29)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.406, h-index: 30)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.451, h-index: 5)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.22, h-index: 20)
Acta Mechanica     Hybrid Journal   (Followers: 21, SJR: 0.898, h-index: 52)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.426, h-index: 29)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7, SJR: 0.525, h-index: 18)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.524, h-index: 14)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.833, h-index: 73)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 1, SJR: 0.348, h-index: 27)
Acta Neuropathologica     Hybrid Journal   (Followers: 5, SJR: 6.61, h-index: 117)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 17)
Acta Parasitologica     Hybrid Journal   (Followers: 10, SJR: 0.581, h-index: 28)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.551, h-index: 39)
Acta Politica     Hybrid Journal   (Followers: 13, SJR: 0.658, h-index: 20)
Activitas Nervosa Superior     Hybrid Journal  
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 6, SJR: 0.103, h-index: 4)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 22, SJR: 0.871, h-index: 15)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 15, SJR: 0.795, h-index: 40)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.774, h-index: 52)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.319, h-index: 15)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 36, SJR: 0.959, h-index: 44)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 19, SJR: 1.255, h-index: 44)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 52, SJR: 1.113, h-index: 14)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.141, h-index: 3)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 27, SJR: 1.397, h-index: 42)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.2, h-index: 4)
Advances in Polymer Science     Hybrid Journal   (Followers: 43, SJR: 0.637, h-index: 89)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 0.79, h-index: 44)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 6)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.882, h-index: 23)
Aerobiologia     Hybrid Journal   (Followers: 3, SJR: 0.511, h-index: 36)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 9, SJR: 0.821, h-index: 49)
African Archaeological Review     Hybrid Journal   (Followers: 16, SJR: 0.612, h-index: 24)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.248, h-index: 6)
AGE     Hybrid Journal   (Followers: 7, SJR: 1.358, h-index: 33)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.337, h-index: 10)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.529, h-index: 55)
Agricultural Research     Hybrid Journal   (Followers: 4)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 49)
Agroforestry Systems     Hybrid Journal   (Followers: 19, SJR: 0.64, h-index: 56)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 11, SJR: 1.732, h-index: 59)
AI & Society     Hybrid Journal   (Followers: 8, SJR: 0.171, h-index: 19)
AIDS and Behavior     Hybrid Journal   (Followers: 13, SJR: 2.006, h-index: 71)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.706, h-index: 19)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 5, SJR: 0.566, h-index: 18)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.388, h-index: 22)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 0.868, h-index: 20)
Algorithmica     Hybrid Journal   (Followers: 8, SJR: 0.898, h-index: 56)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.183, h-index: 20)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 0.729, h-index: 20)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3, SJR: 1.392, h-index: 32)
AMBIO     Hybrid Journal   (Followers: 11, SJR: 1.094, h-index: 87)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.864, h-index: 39)
American J. of Community Psychology     Hybrid Journal   (Followers: 27, SJR: 1.237, h-index: 83)
American J. of Criminal Justice     Hybrid Journal   (Followers: 8, SJR: 0.634, h-index: 13)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 15, SJR: 0.283, h-index: 3)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.175, h-index: 13)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.558, h-index: 35)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 20, SJR: 0.293, h-index: 13)
American Sociologist     Hybrid Journal   (Followers: 12, SJR: 0.18, h-index: 13)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.362, h-index: 83)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.21, h-index: 37)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 7)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 5)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 1.096, h-index: 123)
Anatomical Science Intl.     Hybrid Journal   (Followers: 2, SJR: 0.301, h-index: 26)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.212, h-index: 69)
Animal Cognition     Hybrid Journal   (Followers: 18, SJR: 1.122, h-index: 55)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.156, h-index: 4)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.377, h-index: 32)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.504, h-index: 14)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.167, h-index: 26)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.182, h-index: 94)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.849, h-index: 15)
Annals of Data Science     Hybrid Journal   (Followers: 11)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.857, h-index: 40)
Annals of Finance     Hybrid Journal   (Followers: 29, SJR: 0.686, h-index: 14)
Annals of Forest Science     Hybrid Journal   (Followers: 7, SJR: 0.929, h-index: 57)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.136, h-index: 23)
Annals of Hematology     Hybrid Journal   (Followers: 16, SJR: 1.117, h-index: 62)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.593, h-index: 42)
Annals of Microbiology     Hybrid Journal   (Followers: 10, SJR: 0.402, h-index: 26)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4, SJR: 0.68, h-index: 45)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 1.186, h-index: 78)
Annals of Ophthalmology     Hybrid Journal   (Followers: 12)
Annals of Regional Science     Hybrid Journal   (Followers: 7, SJR: 0.405, h-index: 42)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 9, SJR: 0.553, h-index: 8)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 14, SJR: 1.902, h-index: 127)
Annals of Telecommunications     Hybrid Journal   (Followers: 9, SJR: 0.315, h-index: 25)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.931, h-index: 31)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.992, h-index: 87)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.14, h-index: 57)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.554, h-index: 87)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.354, h-index: 27)
Applications of Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.274, h-index: 20)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 42, SJR: 0.575, h-index: 80)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 16, SJR: 0.267, h-index: 26)
Applied Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.361, h-index: 21)
Applied Composite Materials     Hybrid Journal   (Followers: 49, SJR: 0.705, h-index: 35)
Applied Entomology and Zoology     Partially Free   (Followers: 3, SJR: 0.554, h-index: 34)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.323, h-index: 9)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.541, h-index: 13)
Applied Intelligence     Hybrid Journal   (Followers: 11, SJR: 0.777, h-index: 43)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.358, h-index: 34)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 6, SJR: 0.955, h-index: 33)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.275, h-index: 8)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.37, h-index: 26)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 63, SJR: 1.262, h-index: 161)
Applied Physics A     Hybrid Journal   (Followers: 9, SJR: 0.535, h-index: 121)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 24, SJR: 0.983, h-index: 104)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.677, h-index: 47)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 11, SJR: 0.288, h-index: 15)
Applied Solar Energy     Hybrid Journal   (Followers: 18, SJR: 0.251, h-index: 6)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 4, SJR: 0.351, h-index: 9)
Aquaculture Intl.     Hybrid Journal   (Followers: 22, SJR: 0.613, h-index: 40)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 1)
Aquatic Ecology     Hybrid Journal   (Followers: 33, SJR: 0.646, h-index: 44)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.764, h-index: 39)
Aquatic Sciences     Hybrid Journal   (Followers: 13, SJR: 1.172, h-index: 53)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.345, h-index: 20)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 2, SJR: 0.417, h-index: 16)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 20, SJR: 1.056, h-index: 15)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.397, h-index: 13)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.597, h-index: 29)
Archival Science     Hybrid Journal   (Followers: 58, SJR: 0.804, h-index: 22)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 8, SJR: 0.28, h-index: 15)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 2, SJR: 0.946, h-index: 23)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 4.091, h-index: 66)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.865, h-index: 40)
Archives and Museum Informatics     Hybrid Journal   (Followers: 140)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 5, SJR: 2.841, h-index: 40)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 0.9, h-index: 65)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 14, SJR: 0.846, h-index: 84)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 16, SJR: 0.695, h-index: 47)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.702, h-index: 85)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.039, h-index: 56)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 1.092, h-index: 13)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.198, h-index: 74)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.595, h-index: 76)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 1.086, h-index: 90)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 14, SJR: 1.264, h-index: 50)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 1.2, h-index: 42)
ArgoSpine News & J.     Hybrid Journal   (SJR: 0.102, h-index: 3)
Argumentation     Hybrid Journal   (Followers: 5, SJR: 0.295, h-index: 18)
Arid Ecosystems     Hybrid Journal   (Followers: 2)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.948, h-index: 22)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.797, h-index: 17)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.145, h-index: 8)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.288, h-index: 25)
Artificial Intelligence Review     Hybrid Journal   (Followers: 14, SJR: 0.948, h-index: 48)
Artificial Life and Robotics     Hybrid Journal   (Followers: 9, SJR: 0.231, h-index: 14)
Asia Europe J.     Hybrid Journal   (Followers: 5, SJR: 0.247, h-index: 9)
Asia Pacific Education Review     Hybrid Journal   (Followers: 11, SJR: 0.371, h-index: 17)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.676, h-index: 50)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 12, SJR: 0.353, h-index: 13)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.19, h-index: 15)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 19, SJR: 1.006, h-index: 14)
Asian Business & Management     Hybrid Journal   (Followers: 9, SJR: 0.41, h-index: 10)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 9)
Asian J. of Criminology     Hybrid Journal   (Followers: 5, SJR: 0.263, h-index: 8)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.681, h-index: 15)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.195, h-index: 5)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  

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Journal Cover Acta Diabetologica
  [SJR: 1.318]   [H-I: 46]   [16 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1432-5233 - ISSN (Online) 0940-5429
   Published by Springer-Verlag Homepage  [2350 journals]
  • Advances in micro- and nanotechnologies for the GLP-1-based therapy and
           imaging of pancreatic beta-cells
    • Authors: Faruk H. Moonschi; Corey B. Hughes; George M. Mussman; John L. Fowlkes; Chris I. Richards; Iuliana Popescu
      Pages: 405 - 418
      Abstract: Therapies to prevent diabetes in particular the progressive loss of β-cell mass and function and/or to improve the dysregulated metabolism associated with diabetes are highly sought. The incretin-based therapy comprising GLP-1R agonists and DPP-4 inhibitors have represented a major focus of pharmaceutical R&D over the last decade. The incretin hormone GLP-1 has powerful antihyperglycemic effect through direct stimulation of insulin biosynthesis and secretion within the β-cells; it normalizes β-cell sensitivity to glucose, has an antiapoptotic role, stimulates β-cell proliferation and differentiation, and inhibits glucagon secretion. However, native GLP-1 therapy is inappropriate due to the rapid post-secretory inactivation by DPP-4. Therefore, incretin mimetics developed on the backbone of the GLP-1 or exendin-4 molecule have been developed to behave as GLP-1R agonists but to display improved stability and clinical efficacy. New formulations of incretins and their analogs based on micro- and nanomaterials (i.e., PEG, PLGA, chitosan, liposomes and silica) and innovative encapsulation strategies have emerged to achieve a better stability of the incretin, to improve its pharmacokinetic profile, to lower the administration frequency or to allow another administration route and to display fewer adverse effects. An important advantage of these formulations is that they can also be used at the targeted non-invasive imaging of the beta-cell mass. This review therefore focuses on the current state of these efforts as the next step in the therapeutic evolution of this class of antidiabetic drugs.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-017-1086-7
      Issue No: Vol. 55, No. 5 (2018)
  • Identification of megakaryocytes as a target of advanced glycation end
           products in diabetic complications in bone marrow
    • Authors: Benfang Wang; Jianjiang Yu; Ting Wang; Ying Shen; Dandan Lin; Xin Xu; Yiqiang Wang
      Pages: 419 - 427
      Abstract: Aims To define the possible effect of diabetic conditions on megakaryocytes, the long-know precursors of platelets and lately characterized modulator of hematopoietic stem quiescence–activation transition. Methods Megakaryoblastic MEG-01 cell culture and TPO/SCF/IL-3-induced differentiation of human umbilical blood mononuclear cells toward megakaryocytes were used to test effects of glycated bovine serum albumin (BSA-AGEs). The ob/ob mice and streptozotocin-treated mice were used as models of hyperglycemia. MTT was used to measure cell proliferation, FACS for surface marker and cell cycle, and RT-qPCR for the expression of interested genes. Megakaryocytes at different stages in marrow smear were checked under microscope. Results When added in MEG-01 cultures at 200 μg/ml, BSA-AGEs increased proliferation of cells and enhanced mRNA expression of RAGE, VEGFα and PF4 in the cells. None of cell cycle distribution, PMA-induced platelet-like particles production, expression of GATA1/NF-E2/PU-1/IL-6/OPG/PDGF in MEG-01 cells nor TPO/SCF/IL-3 induced umbilical cord blood cells differentiation into megakaryocyte was affected by BSA-AGEs. In the ob/ob diabetic mice, MKs percentages in marrow cells and platelets in peripheral blood were significantly increased compared with control mice. In streptozotocin-induced diabetic mice, however, MKs percentage in marrow cells was decreased though peripheral platelet counts were not altered. Gene expression assay showed that the change in MKs in these two diabetic conditions might be explained by the alteration of GATA1 and NF-E2 expression, respectively. Conclusions Diabetic condition in animals might exert its influence on hematopoiesis via megakaryocytes—the newly identified modulator of hematopoietic stem cells in bone marrow.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1109-z
      Issue No: Vol. 55, No. 5 (2018)
  • Comparative safety and efficacy of insulin degludec with insulin glargine
           in type 2 and type 1 diabetes: a meta-analysis of randomized controlled
    • Authors: Xiao-Wen Zhang; Xin-Lin Zhang; Biao Xu; Li-Na Kang
      Pages: 429 - 441
      Abstract: Aims To determine the safety and efficacy of insulin degludec versus glargine in patients with type 1 (T1D) and type 2 (T2D) diabetes mellitus. Methods Databases were searched until July 5, 2017. We included randomized controlled trials comparing degludec with glargine in diabetic patients, each with a minimum of 16 weeks of follow-up. Results Eighteen trials with 16,791 patients were included. Degludec was associated with a statistically significant reduction in risk for all confirmed hypoglycemia at the maintenance treatment period [estimated rate ratio (ERR) 0.81; 95% confidence interval (CI) 0.72‒0.92; P = 0.001], nocturnal confirmed hypoglycemia at the entire (ERR 0.71; 95% CI 0.63‒0.80; P < 0.001) and maintenance treatment period (ERR 0.65; 95% CI 0.59‒0.71; P < 0.001), all irrespective of the pooled diabetic populations and follow-up durations. The differences in the rate of hypoglycemia were more pronounced in nocturnal period and maintenance period and in T2D than T1D patients. Degludec reduced the incidence of severe hypoglycemia in T2D [ERR 0.65; (0.52; 0.89); P = 0.005] but not T1D patients. HbA1c concentration was slightly higher in degludec over glargine but was not clinically relevant [estimated treatment difference (ETD) 0.03; 95% CI − 0.00 to 0.06%; P = 0.06]. Fasting plasma glucose level was lower in degludec-treated patients (ETD − 0.28 mmol/L; 95% CI − 0.44 to − 0.11 mmol/L; P = 0.001). Several subgroup analyses showed largely consistent findings. The rates of adverse events including total mortality and cardiovascular events were not significantly different between two treatment strategies. Conclusions Insulin degludec appears to have better safety in reducing hypoglycemic events with similar efficacy compared with insulin glargine.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1107-1
      Issue No: Vol. 55, No. 5 (2018)
  • Association between IgH enhancer hs1.2 and type 1 diabetes
    • Authors: Rossella Cianci; Pietro D’Addabbo; Giovanni Gambassi; Serena Lolli; Eliseo Serone; Alessandro Rizzi; Dario Pitocco; Franco Pandolfi; Domenico Frezza
      Pages: 443 - 448
      Abstract: Aim To investigate the association of alleles of the 3′ immunoglobulin heavy-chain regulatory region 1 (3′RR-1) enhancer hs1.2 in patients with type 1 diabetes (T1D). Methods Eighty-one patients with T1D [among which 12 had concomitant coeliac disease (CD) and 25 an autoimmune thyroid disease (AITD)] were compared to 248 healthy individuals. All subjects were recruited from the same geographical area. Blood samples were collected from all patients and a nested PCR was performed to amplify the core of the 3′RR-1 and detect the alleles of the hs1.2 enhancer. Results Allele distribution in healthy individuals was significantly different when compared to that of patients with T1D (p < 0.01). Even greater differences were detected comparing allele distribution of patients with T1D alone versus those with concomitant CD, but not versus those with concomitant AITD. The frequency of *2 allele is increased by 23% in patients with T1D and CD. Conclusions The present study establishes that the multiallelic hs1.2 enhancer of the 3′RR-1 is associated with T1D, with higher frequency when there is co-occurrence of CD. This evidence has been previously observed in other immune diseases.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1103-5
      Issue No: Vol. 55, No. 5 (2018)
  • Two-hour post-challenge glucose is a better predictor of adverse outcome
           after myocardial infarction than fasting or admission glucose in patients
           without diabetes
    • Authors: Sudipta Chattopadhyay; Anish George; Joseph John; Thozhukat Sathyapalan
      Pages: 449 - 458
      Abstract: Aims We evaluate prevalence of new abnormal glucose tolerance (AGT) in post-MI survivors without known diabetes (DM) if guidelines are followed and compare the ability of admission (APG), fasting (FPG) and 2-h post-load plasma glucose (2h-PG) to predict prognosis. Methods A total of 674 patients were followed up for 4 years for incidence of major adverse cardiovascular events (MACE) of cardiovascular death, non-fatal re-infarction or non-haemorrhagic stroke. Ability of models including APG, FPG and 2h-PG to predict MACE was compared. Results Of the total, 93–96% of impaired glucose tolerance and 64–75% of DM would be missed with current guidelines. MACE was higher in the upper quartiles of 2h-PG. When 2h-PG and FPG were included simultaneously in models, only 2h-PG predicted MACE (HR 1.12, CI 1.04–1.20, p = 0.0012), all cause mortality (HR 1.17, CI 1.05–1.30, p = 0.0039), cardiovascular mortality (HR 1.17, CI 1.02–1.33, p = 0.0205) and non-fatal MI (HR 1.10, CI 1.01–1.20, p = 0.0291). Adding 2h-PG significantly improved ability of models including FPG (χ2 = 16.01, df = 1, p = 0.0001) or FPG and APG (χ2 = 17.36, df = 1, p = 0.000) to predict MACE. Model including 2h-PG only had the lowest Akaike’s information criteria and highest Akaike weights suggesting that this was the best in predicting events. Adding 2h-PG to models including FPG or APG with other co-variates yielded continuous net reclassification improvement (NRI) of 0.22 (p = 0.026) and 0.27 (p = 0.005) and categorical NRI of 0.09 (p = 0.032) and 0.12 (p = 0.014), respectively. Adding 2 h-PG to models including only FPG, only APG and both yielded integrated discrimination improvement of 0.012 (p = 0.015), 0.022 (p = 0.001) and 0.013 (p = 0.014), respectively. Conclusions AGT is under-diagnosed on current guidelines. 2h-PG is a better predictor of prognosis compared to APG and FPG.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1114-2
      Issue No: Vol. 55, No. 5 (2018)
  • Comparative evaluation of pharmacokinetics and pharmacodynamics of insulin
           glargine (Glaritus ® ) and Lantus ® in healthy subjects: a double-blind,
           randomized clamp study
    • Authors: Ashima Bhatia; Shraddha Tawade; Mushtaque Mastim; Eliford Ngaimisi Kitabi; Mathangi Gopalakrishnan; Manish Shah; Sridhar Yeshamaina; Joga Gobburu; Maharaj Sahib; Dipak Thakur; K. M. Prasanna Kumar
      Pages: 461 - 468
      Abstract: Aims The objective of the study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an insulin glargine formulation, Glaritus® (test) with the innovator’s formulation Lantus® (reference) using the euglycemic clamp technique in a single-dose, double-blind, randomized, two sequences, four-period replicate crossover study in healthy volunteers (n = 40). Methods Subjects received subcutaneous administration of the insulin glargine (0.4 IU/kg) formulation at two occasions for test and reference and a 20% glucose solution was infused at variable rate to maintain euglycemia for 24 h. Results Both PK [area under the plasma concentration time curve (AUC0–24 h) and maximum insulin concentration (Cmax)] and PD endpoints [area under glucose infusion rate time curve (AUCGIR0–24) and maximum glucose infusion rate (GIRmax)] demonstrated bioequivalence of Glaritus to Lantus with the 90% confidence interval of geometric mean ratio of test to reference entirely contained within 0.80–1.25. Both formulations showed equivalent geometric least-square mean LSM value (0.08 nmol/L) for Cmax. The geometric LSM AUC0–24 h value for Glaritus® (1.09 h nmol/L) was comparable to Lantus (1.05 h nmol/L). Median Tmax values were also identical (12 h for both), and median t1/2 values were also equal (18 h for both). For GIRTmax, the difference between the means for the two was not statistically significant. No AEs related to study formulations were reported, and both products were well tolerated. Conclusions The test product (Glaritus) was found to be bioequivalent to the reference product (Lantus). Clinical trial registration number CTRI/2015/06/005890;
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1113-3
      Issue No: Vol. 55, No. 5 (2018)
  • Optical coherence tomography angiography discerns preclinical diabetic
           retinopathy in eyes of patients with type 2 diabetes without clinical
           diabetic retinopathy
    • Authors: Dan Cao; Dawei Yang; Zhongning Huang; Yunkao Zeng; Jun Wang; Yunyan Hu; Liang Zhang
      Pages: 469 - 477
      Abstract: Aims To investigate changes in retinal vascular plexuses and choriocapillaris in patients with type 2 diabetes mellitus (DM2) without diabetic retinopathy (DR) and healthy controls using optical coherence tomography angiography (OCTA). Methods A total of 71 DM2 and 67 healthy control subjects were included. All subjects underwent OCTA examination (RTVue-XR Avanti; Optovue, Fremont, CA, USA). Average vessel density in superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris, parafoveal vessel density in SCP and DCP, FAZ area (mm2) in SCP, microaneurysms and capillary nonperfusion were taken into analysis. Results Parafoveal vessel density in both SCP and DCP decreased in the eyes without clinical DR compared to normal controls (p < 0.001). Diabetic patients with no signs of DR also had a significant reduction in average vessel density of SCP, DCP and choriocapillaris (p < 0.001, p < 0.001 and p = 0.006, respectively). No significant difference was found in FAZ area of SCP between DM2 eyes and healthy controls (p = 0.253). The average vessel density of SCP and DCP is not correlated with HbA1c or serum creatinine in DM2 patients. Microaneurysms seen in OCTA but not in fundus examination were found in 8 out of the 71 (11.3%) diabetic eyes, and capillary nonperfusion was noted in 18 of 71 diabetic eyes. Conclusions We demonstrated that OCTA can identify preclinical DR before the manifestation of clinically apparent retinopathy in diabetic eyes. DM2 patients without DR have SCP, DCP and choriocapillaris impairment. Our results suggested that OCTA might be a promising tool for regular screening of diabetic eyes for DR.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1115-1
      Issue No: Vol. 55, No. 5 (2018)
  • The risk of type 2 diabetes mellitus according to the categories of body
           mass index: the Korean Genome and Epidemiology Study (KoGES)
    • Authors: Ju Young Jung; Sung Keun Park; Chang Mo Oh; Jae-Hong Ryoo; Joong-Myung Choi; Young Joon Choi
      Pages: 479 - 484
      Abstract: Aims Obesity is an established risk factor for type 2 diabetes mellitus (T2DM). However, there is limited information on the pattern of relationship between the risk for T2DM and body mass index (BMI) categories including underweight and overweight. Thus, this study was to evaluate the risk of T2DM according to BMI categories defined by Asian-specific cutoff of BMI. Methods 7660 non-diabetic Koreans were grouped into five BMI categories (underweight, normal, overweight, obese and severe obese) defined by Asian-specific cutoff of BMI and followed up for 10 years to monitor the development of T2DM. With a reference of normal BMI group, Cox proportional hazards assumption was used to calculate hazard ratios (HRs) and their 95% confidence intervals for T2DM in five groups. Subgroup analysis was conducted by gender and age (40–59 years and 60–69 years). Results Baseline mean value of metabolic factors like fasting glucose, HOMA-IR, total cholesterol and the proportion of impaired fasting glucose increased proportionally to the level of BMI categories. Underweight group had the higher proportion of impaired glucose tolerance than normal and overweight group. In all subgroups, underweight, overweight, obese and severe obese group had the higher HRs for T2DM than normal group, but statistical significance was only found in overweight, obese and severe obese group. Conclusions The risk of T2DM tends to increase proportionally to the level of BMI categories from overweight to severe obese group. Further studies should be considered to identify the incidental relationship between underweight and T2DM.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1112-4
      Issue No: Vol. 55, No. 5 (2018)
  • Work-loss years among people diagnosed with diabetes: a reappraisal from a
           life course perspective
    • Authors: Mikaela B. von Bonsdorff; Monika E. von Bonsdorff; Maija Haanpää; Minna Salonen; Tuija M. Mikkola; Hannu Kautiainen; Johan G. Eriksson
      Pages: 485 - 491
      Abstract: Aims Early exit from the workforce has been proposed to be one of the unfavorable consequences of diabetes. We examined whether early exit from the workforce differed between persons who were and were not diagnosed with diabetes during their work career. Methods The cohort included 12,726 individuals of the Helsinki Birth Cohort Study, born between 1934 and 1944. Using data from nationwide registers, the cohort was followed up from early adulthood until they transitioned into retirement or died. Work-loss years were estimated using the restricted mean work years method. Results During a follow-up of 382,328 person-years for men and 349 894 for women, 36.8% transitioned into old age pension and 63.2% exited workforce early. Among men, 40.5% of those with and 32.8% of those without diabetes transitioned into old age pension (p=0.003). The corresponding numbers for women were 48.6% and 40.4% (p = 0.013), respectively. Mean age at exit from the workforce was 60.1 (95% confidence interval [CI], 59.6 to 60.7) years among men with diabetes and 57.6 (95% CI, 57.2 to 58.0) years among men without diabetes (p = 0.016). Among women, corresponding ages were 61.4 (95% CI, 60.8 to 61.9) years for those with diabetes and 59.5 (95% CI, 59.3 to 59.7) years for those without diabetes (p < 0.001). The difference in mean restricted work-loss years according to diabetes was 2.5 (95% CI 0.5 to 4.6) for men and 1.9 (95% CI 1.0 to 2.8) for women. Conclusion Among individuals followed up throughout their work career, those with a diabetes diagnosis exited the workforce approximately two years later compared to those without diabetes.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1119-x
      Issue No: Vol. 55, No. 5 (2018)
  • Heterogeneity of gestational diabetes (GDM) and long-term risk of diabetes
           and metabolic syndrome: findings from the RADIEL study follow-up
    • Authors: Emilia Huvinen; Johan G. Eriksson; Saila B. Koivusalo; Nora Grotenfelt; Aila Tiitinen; Beata Stach-Lempinen; Kristiina Rönö
      Pages: 493 - 501
      Abstract: Aims To assess the metabolic health of obese and non-obese women at high GDM risk 5 years postpartum. Methods This is a secondary analysis of the 5-year follow-up of the RADIEL GDM prevention study including 333 women at high GDM risk (BMI ≥ 30 kg/m2 and/or previous GDM). Five years postpartum metabolic health was assessed including anthropometric measurements, oral glucose tolerance test, lipid metabolism, and body composition as well as medical history questionnaires. For the analysis, we divided the women into four groups based on parity, BMI, and previous history of GDM. Results Five years postpartum impaired glucose regulation (IFG, IGT, or diabetes) was diagnosed in 15% of the women; 3.6% had type 2 diabetes. The highest prevalence was observed among obese women with a history of GDM (26%), and the lowest prevalence (8%) among primiparous obese women (p = 0.021). At follow-up 25–39% of the obese women fulfilled the diagnostic criteria for the metabolic syndrome, in the non-obese group 11% (p < 0.001). This was associated with body fat percentage. The non-obese group, however, faced metabolic disturbances (IFG, IGT, diabetes, or metabolic syndrome) at a significantly lower BMI (p < 0.001). Among women who were non-obese before pregnancy, 5 years postpartum, the obesity prevalence based on BMI was 14% and based on body fat percentage 58%. Conclusions The prevalence of impaired glucose regulation and metabolic syndrome is high 5 years postpartum among women at high risk of GDM. There are high-risk women also among the non-obese, who develop metabolic derangements already at a lower BMI. Clinical trial registration,, NCT01698385.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1118-y
      Issue No: Vol. 55, No. 5 (2018)
  • SGLT-2 inhibitors and the risk of infections: a systematic review and
           meta-analysis of randomized controlled trials
    • Authors: Robert Puckrin; Marie-Philippe Saltiel; Pauline Reynier; Laurent Azoulay; Oriana H. Y. Yu; Kristian B. Filion
      Pages: 503 - 514
      Abstract: Aims There is concern about the infection-related safety profile of sodium–glucose co-transporter 2 (SGLT-2) inhibitors. We aimed to determine the effect of SGLT-2 inhibitors on genitourinary and other infections via systematic review and meta-analysis of randomized controlled trials (RCTs). Methods We conducted a systematic search of Medline, EMBASE, Cochrane Central Register of Controlled Trials, and to identify double-blinded RCTs enrolling ≥ 50 patients with type 2 diabetes which compared an SGLT-2 inhibitor to placebo or active comparator. Two independent reviewers extracted data and appraised study quality. Data were pooled using random-effects models. Results Eighty-six RCTs enrolling 50,880 patients were included. SGLT-2 inhibitors increased the risk of genital infections compared to placebo (relative risk [RR] 3.37, 95% CI 2.89–3.93, I2 0%) and active comparator (RR 3.89, 95% CI 3.14–4.82, I2 0.3%). The risk of urinary tract infection (UTI) was not increased with SGLT-2 inhibitors compared to placebo (RR 1.03, 95% CI 0.96–1.11, I2 0%) or active comparator (RR 1.08, 95% CI 0.93–1.25, I2 22%). In drug-specific analyses, only dapagliflozin 10 mg daily was associated with a significantly increased risk of UTI compared to placebo (RR 1.33, 95% CI 1.10–1.61, I2 0%). SGLT-2 inhibitors were associated with a reduced risk of gastroenteritis (RR 0.38, 95% CI 0.20–0.72, I2 0%) but did not affect the risk of respiratory tract infections. Conclusions/interpretation SGLT-2 inhibitors are associated with an increased risk of genital tract infections. Although there is no association overall between SGLT-2 inhibitors and UTI, higher doses of dapagliflozin are associated with an increased risk.
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-018-1116-0
      Issue No: Vol. 55, No. 5 (2018)
  • Soluble programmed death-1 ligand 1(sPD-L1) is significantly reduced in
           the serum of type 1 diabetes patients
    • Authors: Xiaohong Chen; Heming Guo; Sicheng Li; Cuiping Liu; Sisi Ding; Yun Huang; Chen Fang; Ji Hu
      Pages: 515 - 517
      PubDate: 2018-05-01
      DOI: 10.1007/s00592-017-1081-z
      Issue No: Vol. 55, No. 5 (2018)
  • Transcutaneous oxygen pressure as a predictor for short-term survival in
           patients with type 2 diabetes and foot ulcers: a comparison with
           ankle–brachial index and toe blood pressure
    • Authors: K. Fagher; P. Katzman; M. Löndahl
      Abstract: Aims Ankle–brachial index (ABI) is the most commonly used test when diagnosing peripheral vascular disease and is considered a marker for cardiovascular risk. Transcutaneous oxygen pressure (TcPO2), a test associated with microvascular function, has in several studies shown better correlation with diabetic foot ulcer (DFU) healing. Whether a low TcPO2 could be a marker for mortality in the high-risk population of DFU patients has not been evaluated before. The aim of this study was to evaluate the predictive value of TcPO2 in comparison with ABI and toe blood pressure (TBP) on 1-year mortality in type 2 diabetes patients with DFU. Methods Type 2 diabetes patients aged ≤ 90 years, with one DFU who attended our multidisciplinary DFU-unit during year 2013–2015 and were screened with TcPO2, ABI and TBP were retrospectively evaluated. One-year mortality was assessed from the national death register in Sweden. Results A total of 236 patients (30% women) with a median age of 76 (69–82) years were evaluated in this study. Within 1 year, 14.8% of the patients died. TcPO2 < 25 mmHg was associated with a higher 1-year mortality compared with TcPO2 ≥ 25 mmHg (27.7 vs. 11.6%, p = 0.003). TBP and ABI did not significantly influence 1-year mortality. In a Cox regression analysis adjusted for confounders, TcPO2 was independently predicting 1-year mortality with a hazard ratio for TcPO2 < 25 mmHg of 2.8 (95% CI 1.34–5.91, p = 0.006). Conclusions This study indicates that a low TcPO2 is an independent prognostic marker for 1-year mortality among patients with type 2 diabetes and DFU.
      PubDate: 2018-04-30
      DOI: 10.1007/s00592-018-1145-8
  • Searching peripheral blood mononuclear cells of children with viral
           respiratory tract infections preceding islet autoimmunity for viruses by
           high-throughput sequencing
    • Authors: Markus Hippich; Alexandra Oleynik; Komal Jain; Christiane Winkler; Ricardo C. Ferreira; Ezio Bonifacio; Anette-Gabriele Ziegler; Thomas Briese
      PubDate: 2018-04-23
      DOI: 10.1007/s00592-018-1138-7
  • An increased waist-to-hip ratio is a key determinant of atherosclerotic
           burden in overweight subjects
    • Authors: Roberto Scicali; David Rosenbaum; Antonino Di Pino; Philippe Giral; Philippe Cluzel; Alban Redheuil; Salvatore Piro; Agata Maria Rabuazzo; Francesco Purrello; Eric Bruckert; Antonio Gallo
      Abstract: Aims The association of overweight status and cardiovascular disease is not clear. In this study we aimed to investigate coronary atherosclerotic disease, evaluated as coronary artery calcium score (CACs), in overweight patients with or without abdominal obesity as defined by waist-to-hip ratio (WHR). Methods We enrolled 276 patients aged between 40 and 70 years, with a body mass index of 25–29.9 kg/m2 and at least one cardiovascular risk factor. Exclusion criteria were history of diabetes, cardiovascular or renal disease. Patients were stratified in high WHR (H-WHR) or low WHR (L-WHR) group according to WHR (≥ 0.85 for women and ≥ 0.90 for men) and underwent multi-detector computed tomography for CACs. Mean carotid intima-media thickness (IMT) and plaque presence were equally assessed. Results CACs was higher in the H-WHR group compared to L-WHR (9.05 [0.0–83.48] vs 0.0 [0.0–64.7] AU, p < 0.01); the prevalence of CACs > 0 in the H-WHR group was significantly higher than subjects with L-WHR (59.6% vs 38.5%, p < 0.001). Moreover, H-WHR group had higher mean IMT (0.64 [0.56–0.72] vs 0.59 [0.55–0.67] mm, p < 0.05) and higher carotid plaque prevalence (63.7% vs 50.8%, p < 0.05) compared to subjects with L-WHR. Logistic regression showed that H-WHR was associated with presence of CACs and carotid plaque (p < 0.01). In a multiple linear regression, WHR was positively associated with CACs and IMT (p < 0.01). Conclusions H-WHR is a marker of coronary and peripheral atherosclerotic burden in overweight patients.
      PubDate: 2018-04-21
      DOI: 10.1007/s00592-018-1144-9
  • Ten-year comparative analysis of incidence, prognosis, and associated
           factors for dialysis and renal transplantation in type 1 and type 2
           diabetes versus non-diabetes
    • Authors: Carlo Bruno Giorda; Paolo Carnà; Mario Salomone; Roberta Picariello; Giuseppe Costa; Barbara Tartaglino; Roberto Gnavi
      Abstract: Aims To study the incidence of and the factors associated with renal dialysis and transplantation in type 1 (T1DM) and type 2 diabetes (T2DM). Methods Data on individuals who had received dialysis treatment or renal transplant between 1 January 2004 and 31 December 2013 were extracted from the regional administrative database (Piedmont, Italy), and the crude (cumulative) incidence of dialysis was calculated. Overall cumulative survival was estimated using the Kaplan–Meier method and compared using the log-rank test. Poisson regression was used to estimate adjusted rate ratios for potential predictors of renal transplant or death. Results A total of 7401 persons started dialysis treatment during the decade, with a 10-year cumulative crude incidence of 16.8/100,000. Incidence was stable and consistently eightfold higher in persons with T2DM (tenfold higher in T1DM) compared to those without diabetes. The risk of dialysis in T1DM was about double that of T2DM. The mortality rate was significantly higher in diabetics than in non-diabetes (241.4/1000 vs. 153.99/1000 person-years). During the decade 2004–2013, 893 patients underwent a kidney transplant. Transplantation rates were significantly lower for diabetics than non-diabetics (16.5/1000 vs. 42.9/1000 person-years). Conclusions In the past decade, the incidence of dialysis has stabilized in both the general population and in diabetics in whom it remains far higher by comparison. Also mortality rates are higher, with a worse prognosis for T1DM. Diabetes poses a barrier to allotransplantation, and efforts should be made to overcome this limitation.
      PubDate: 2018-04-20
      DOI: 10.1007/s00592-018-1142-y
  • Characterization of circulating leukocytes and correlation of leukocyte
    • Authors: Maria Apostolopoulou; Barbara Menart-Houtermans; Ruth Ruetter; Bettina Nowotny; Ulrich Gehrmann; Daniel Markgraf; Julia Szendroedi; Nanette C. Schloot; Michael Roden
      Abstract: Aims Infiltration of pancreatic islets with different leukocyte subtypes likely contributes to deterioration of glycemia in diabetes mellitus. Different subsets of leukocytes have been previously associated with type 1 or type 2 diabetes. This study aimed at examining these subsets at different stages of diabetes progression and possible relationships with metabolic parameters. Methods A total of 206 patients, 76 with type 1 and 130 with type 2 diabetes, were studied within the first year of diabetes diagnosis. In addition, 31 patients with type 1 and 73 with type 2 diabetes were examined at 5 years after diagnosis. Whole body insulin sensitivity was assessed by hyperinsulinemic–euglycemic clamps; insulin secretion by glucagon stimulation tests and white blood cells were analyzed by flow cytometry. Results The percentage of peripheral CD8+ cells was 15% lower in patients with type 1 diabetes at 5 years than in patients at diabetes onset and correlated positively with fasting glycemia, total cholesterol and high-sensitive C-reactive protein (hsCRP) (all r > 0.37, p < 0.05), but not with insulin secretion. Patients with type 2 diabetes had 7% higher percentages of CD4+ cells after 5 years than those at diagnosis. CD4+ cells correlated with hsCRP (r = 0.36, p < 0.05), whereas CD8+ cytotoxic T-cells did not correlate with any metabolic parameter. Conclusion CD8+ T-cells associate with worse glycemia, lipidemia and inflammation after 5 years of type 1 diabetes, whereas CD4+ T-cells associate with increased inflammation after 5 years upon onset of type 2 diabetes.
      PubDate: 2018-04-16
      DOI: 10.1007/s00592-018-1143-x
  • Insulin-mimetic effects of short-term rapamycin in type 1 diabetic
           patients prior to islet transplantation
    • Authors: Stefano Benedini; Federica Ermetici; Silvia Briganti; Roberto Codella; Ileana Terruzzi; Paola Maffi; Rossana Caldara; Antonio Secchi; Rita Nano; Lorenzo Piemonti; Rodolfo Alejandro; Camillo Ricordi; Livio Luzi
      Abstract: Background The immunosuppressive drug rapamycin may influence insulin sensitivity in insulin-responsive tissues. Aims This study aimed at evaluating the effectiveness of rapamycin pre-treatment before pancreatic islet allotransplantation (ITx) in patients with type 1 diabetes mellitus (T1DM). Methods Forty-one T1DM patients were studied. Thirteen patients with poor glycemic control underwent a short-term rapamycin treatment before ITx (Group 1), and they were compared to 28 patients undergoing ITx without rapamycin pre-treatment (Group 2). Outcomes were daily insulin requirement (DIR), fasting blood glucose, HbA1c, C-peptide and the SUITO index of beta-cell function. A subgroup of patients pre-treated with rapamycin before ITx underwent euglycemic hyperinsulinemic clamp with [6,6-2H2] glucose before and after ITx to evaluate insulin sensitivity. Results We found a significant reduction in DIR after rapamycin pre-treatment (− 8 ± 6 U/day, mean ± SD, p < 0.001) and 1 year after ITx. DIR reduction 1 year after ITx was greater in Group 1 as compared to Group 2 (− 37 ± 15 vs. − 19 ± 13 U/day, p = 0.005) and remained significant after adjusting for gender, age, glucose and baseline HbA1c (beta = 18.2 ± 5.9, p = 0.006). Fasting glucose and HbA1c significantly decreased 1 year after ITx in Group 1 (HbA1c: − 2.1 ± 1.4%, p = 0.002), while fasting C-peptide (+0.5 ± 0.3 nmol/l, p = 0.002) and SUITO index increased (+57.4 ± 39.7, p = 0.016), without differences between the two groups. Hepatic glucose production decreased after rapamycin pre-treatment (− 1.1 ± 1.1 mg/kg/min, p = 0.04) and after ITx (− 1.6 ± 0.6 mg/kg/min, p = 0.015), while no changes in peripheral glucose disposal were observed. Conclusions Rapamycin pre-treatment before ITx succeeds in reducing insulin requirement, enhancing hepatic insulin sensitivity. This treatment may improve short-term ITx outcomes, possibly in selected patients with T1DM complicated by insulin resistance. Clinical Trial NCT01060605; NCT00014911.
      PubDate: 2018-04-13
      DOI: 10.1007/s00592-018-1141-z
  • GlyCulator2: an update on a web application for calculation of glycemic
           variability indices
    • Authors: Konrad Pagacz; Konrad Stawiski; Agnieszka Szadkowska; Wojciech Mlynarski; Wojciech Fendler
      PubDate: 2018-04-13
      DOI: 10.1007/s00592-018-1140-0
  • Correction to: Two-hour post-challenge glucose is a better predictor of
           adverse outcome after myocardial infarction than fasting or admission
           glucose in patients without diabetes
    • Authors: Sudipta Chattopadhyay; Anish George; Joseph John; Thozhukat Sathyapalan
      Abstract: Unfortunately, name of co-author “Thozhukat” was misspelled in the original publication and the same is corrected here. The original article has been corrected.
      PubDate: 2018-03-05
      DOI: 10.1007/s00592-018-1122-2
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