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Welcome to Diabetologia

Diabetologia publishes original clinical and experimental research within the field of diabetes. We are interested in papers that convey new information or insight into any aspect of the condition, ranging from basic science to clinical applications. These are judged in terms of their scientific quality, novelty, relevance and interest to our broadly based readership.

Statement of Principle

EASD releases joint Statement of Principle with ADA, AACE and TES (November 2014)

In the News

High energy breakfast with low energy dinner helps control blood sugar in people with type 2 diabetes

Download this new research by Professor Daniela Jakubowicz and Professor Julio Wainstein, Wolfson Medical Center, Tel Aviv University, Israel, Professor Bo Ahrén, Lund University, Sweden and Professor Oren Froy, Hebrew University of Jerusalem, Israel and colleagues.
For further information contact Professor Jakubowicz (daniela.jak@gmail.com) or Professor Froy (oren.froy@mail.huji.ac.il).


(posted online 22.01 h GMT Tuesday 24th February 2015)

Sleep restriction increases free fatty acids in healthy men

Download this new research by Dr Josiane Broussard, Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA, and colleagues at the University of Chicago, IL, USA and the University of Wisconsin Hospitals and Clinics, Madison, WI, USA.
For further information contact Dr Broussard (josiane@uchicago.edu) or John Easton, Senior Science Writer, The University of Chicago Medicine (john.easton@uchospitals.edu). Office: 773 795-5225, Cell: 773 322-7380.


(posted online 09.00 h GMT Thursday 19th February 2015)

Current issue: March 2015

March 2015 cover

Click here to view this month's contents

The cover picture shows a coloured transmission electron micrograph of a section through a bladder cancer cell. Peroxisome proliferator activated receptor γ (PPARγ) is overexpressed in bladder tumours. Pioglitazone (a PPARγ agonist used in the treatment of type 2 diabetes) has been associated with increased risk of bladder cancer in observational studies, but results are conflicting. In the present issue of Diabetologia, Levin et al report results from a large, pooled, multipopulation analysis indicating no increase in risk of bladder cancer with pioglitazone or rosiglitazone use.



Cover credit: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY

Download the high resolution cover image

Up front

Juleen Zierath

Competition for publication in Diabetologia is greater than ever, and less than 20% of papers are accepted. Of all the high-quality papers that appear in this month's issue I want to share with you five articles that I find to be of particular interest. These will be featured 'up front' in the print issue and here on our website. Juleen R. Zierath, Editor


Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes
by Silvio E. Inzucchi, Richard M. Bergenstal, John B. Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L. Peters, Apostolos Tsapas, Richard Wender, David R. Matthews

The EASD and ADA produced a position statement about the glycaemic treatment of type 2 diabetes in 2012. This statement was widely quoted and the necessary patient-centred nature of the decision-making was emphasised. Since that time, new trials and new therapies meant that revision of the statement was warranted, and the paper included in this issue, which should be read in the context of the previous, comprehensive paper, is the update that was mandated by the EASD and ADA executive boards.
This paper focuses on important new aspects. First, the role of sodium-glucose co-transporter 2 inhibitors, now widely available and used as an additional oral glucose-lowering therapy, usually in combination with other agents. Second, because insulin treatment is the final common treatment when the insulin secretory capacity is severely reduced, this update outlines the combination of insulin with GLP-1 agonists as an attractive alternative. The paper also includes updated summary figures. [Text supplied by the authors.]

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Epigenetic mechanisms in diabetic complications and metabolic memory
by Marpadga A. Reddy, Erli Zhang, Rama Natarajan

In this issue, Reddy et al summarise emerging evidence that changes occur in epigenetic histone modifications, DNA methylation and non-coding RNAs under diabetic conditions. These changes in the epigenome alter chromatin structure and accessibility to transcription factors, leading to aberrant gene expression associated with diabetic complications. Persistence of such epigenomic changes could explain 'metabolic memory', the phenomenon of prolonged harmful effects of prior inadequate glycaemic control, or prolonged benefits of good glycaemic control. Advances in high-throughput sequencing technologies and epigenome-wide association studies in experimental models and clinical cohorts are providing insights into hitherto unknown mechanisms underlying diabetic complications. These data could lead to the development of much needed new biomarkers and drugs for the early detection and treatment of debilitating complications. [Text supplied by the authors.]

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Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis
by Daniel Levin, Samira Bell, Reijo Sund, Sirpa A. Hartikainen, Jaakko Tuomilehto, Eero Pukkala, Ilmo Keskimäki, Ellena Badrick, Andrew G. Renehan, Iain E. Buchan, Samantha L. Bowker, Jasjeet K. Minhas-Sandhu, Zafar Zafari, Carlo Marra, Jeffrey A. Johnson, Bruno H. Stricker, Andrè G. Uitterlinden, Albert Hofman, Rikje Ruiter, Catherine E. de Keyser, Thomas M. MacDonald, Sarah H.Wild, Paul M. McKeigue, Helen M. Colhoun, on behalf of the Scottish Diabetes Research Network Epidemiology Group and the Diabetes and Cancer Research Consortium

Observational studies have demonstrated an increased risk of bladder cancer in patients using pioglitazone. These findings have led to withdrawal of the drug in France and Germany. Consequently, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have advised that the drug should be avoided in patients with current or previous bladder cancer. In this issue, Levin et al report results of an analysis of international data on several cohorts, funded by the European Foundation for the Study of Diabetes. They found no relationship between cumulative exposure to pioglitazone and bladder cancer. By focusing on cumulative exposure, the possibility of allocation bias affecting the results is reduced. The multicentre nature of this study allows the findings to be generalisable. These results should provide some reassurance to patients previously exposed to pioglitazone regarding the risk of bladder cancer, but future analyses with longer follow-up of exposed individuals are warranted. [Text supplied by the authors.]

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ABO and Rhesus blood groups and risk of type 2 diabetes: evidence from the large E3N cohort study
by Guy Fagherazzi, Gaëlle Gusto, Françoise Clavel-Chapelon, Beverley Balkau, Fabrice Bonnet

In this issue, Fagherazzi et al present the results of an analysis of the links between blood group and diabetes risk in 82,104 women from the large prospective E3N cohort in France, followed between 1990 and 2008. The main finding was that, compared with women with blood group O, women with blood group A were 10% more likely to develop type 2 diabetes and those with blood group B blood were 21% more likely. The authors suggest that effects of blood group on diabetes should be investigated in future clinical and epidemiological studies. Further pathophysiological research is also needed to determine why individuals with blood group O have a lower risk of type 2 diabetes. [Text supplied by the authors.]

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GLP-1-oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice
by Robert W. Schwenk, Christian Baumeier, Brian Finan, Oliver Kluth, Christine Brauer, Hans-Georg Joost, Richard D. DiMarchi, Matthias H. Tschöp, and Annette Schürmann

Oestrogen is known to have beneficial effects on metabolism, but cannot be used in clinical practice because of its mitogenic potential. A glucagon-like peptide-1 (GLP-1)-oestrogen conjugate, which selectively delivers oestrogen to tissues expressing the GLP-1 receptor, has recently been reported to decrease food intake and obesity in mice. In this issue, Schwenk et al report that normoglycaemia and islet integrity are preserved in diabetes-prone New Zealand obese (NZO) mice treated with GLP-1-oestrogen during a sustained carbohydrate challenge. The protective effects of the conjugate far exceeded those of GLP-1 alone, and appeared to be the result of the combined hypothalamic action of GLP-1 and oestrogen. Thus, targeted delivery of oestrogen into metabolically relevant organs could potentially offer a safe way of exploiting the glucose-lowering potential of the steroid. [Text supplied by the authors.]

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Inside this issue

In Memoriam

Donald F. Steiner, MD, 1930–2014
Kenneth S. Polonsky, Arthur H. Rubenstein

Commentaries

Fetal growth and the ethnic origins of type 2 diabetes
Michael R. Skilton

Targeting 12-lipoxygenase as a novel strategy to combat the effects of inflammation on beta cells in diabetes
Jan A. Ehses, Marc Y. Donath

Position Statement

Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes
Silvio E. Inzucchi, Richard M. Bergenstal, John B. Buse, Michaela Diamant, Ele Ferrannini, Michael Nauck, Anne L. Peters, Apostolos Tsapas, Richard Wender, David R. Matthews

Reviews

Epigenetic mechanisms in diabetic complications and metabolic memory
Marpadga A. Reddy, Erli Zhang, Rama Natarajan

Role of islet microRNAs in diabetes: which model for which question?
Claudiane Guay, Romano Regazzi

Articles

Clinical Science and Care

The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study
Kwok-Leung Ong, Andrzej S. Januszewski, Rachel O’Connell, Alicia J. Jenkins, Aimin Xu, David R. Sullivan, Philip J. Barter, Wei-Ting Hung, Russell S. Scott, Marja-Riitta Taskinen, Anthony C. Keech, Kerry-Anne Rye

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Epidemiology

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE)
Claire M. Nightingale, Alicja R. Rudnicka, Christopher G. Owen, Sian L. Newton, Jennifer L. Bales, Angela S. Donin, Cathy M. McKay, Phillip J. Steer, Debbie A. Lawlor, Naveed Sattar, Derek G. Cook, Peter H. Whincup

Dose–response relationships between sedentary behaviour and the metabolic syndrome and its components
Keith P. Gennuso, Ronald E. Gangnon, Keith M. Thraen-Borowski, Lisa H. Colbert

Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis
Daniel Levin, Samira Bell, Reijo Sund, Sirpa A. Hartikainen, Jaakko Tuomilehto, Eero Pukkala, Ilmo Keskimäki, Ellena Badrick, Andrew G. Renehan, Iain E. Buchan, Samantha L. Bowker, Jasjeet K. Minhas-Sandhu, Zafar Zafari, Carlo Marra, Jeffrey A. Johnson, Bruno H. Stricker, Andrè G. Uitterlinden, Albert Hofman, Rikje Ruiter, Catherine E. de Keyser, Thomas M. MacDonald, Sarah H. Wild, Paul M. McKeigue, Helen M. Colhoun, on behalf of the Scottish Diabetes Research Network Epidemiology Group and the Diabetes and Cancer Research Consortium

Glucose, blood pressure and cholesterol levels and their relationships to clinical outcomes in type 2 diabetes: a retrospective cohort study
Evangelos Kontopantelis, David A. Springate, David Reeves, Darren M. Ashcroft, Martin Rutter, Iain Buchan, Tim Doran

ABO and Rhesus blood groups and risk of type 2 diabetes: evidence from the large E3N cohort study
Short Communication
Guy Fagherazzi, Gaëlle Gusto, Françoise Clavel-Chapelon, Beverley Balkau, Fabrice Bonnet

Fasting serum levels of ferritin are associated with impaired pancreatic beta cell function and decreased insulin sensitivity: a population-based study
Linéa Bonfils, Christina Ellervik, Nele Friedrich, Allan Linneberg, Camilla H. Sandholt, Marit E. Jørgensen, Torben Jørgensen, Torben Hansen, Oluf Pedersen, Kristine H. Allin

Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study
Satoyo Ikehara, Adam G. Tabák, Tasnime N. Akbaraly, Adam Hulmán, Mika Kivimäki, Nita G. Forouhi, Hiroyasu Iso, Eric J. Brunner

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Genetics

SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes
Short Communication
Marine Germain, Marcus G. Pezzolesi, Niina Sandholm, Amy J. McKnight, Katalin Susztak, Maria Lajer, Carol Forsblom, Michel Marre, Hans-Henrik Parving, Peter Rossing, Iiro Toppila, Jan Skupien, Ronan Roussel, Yi-An Ko, Nora Ledo, Lasse Folkersen, Mete Civelek, Alexander P. Maxwell, David-Alexandre Tregouet, Per-Henrik Groop, Lise Tarnow, Samy Hadjadj

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Islet Studies

Selective inhibition of 12-lipoxygenase protects islets and beta cells from inflammatory cytokine-mediated beta cell dysfunction
David A. Taylor-Fishwick, Jessica Weaver, Lindsey Glenn, Norine Kuhn, Ganesha Rai, Ajit Jadhav, Anton Simeonov, Angela Dudda, Dieter Schmoll, Theodore R. Holman, David J. Maloney, Jerry L. Nadler

Ins1 Cre knock-in mice for beta cell-specific gene recombination
Bernard Thorens, David Tarussio, Miguel Angel Maestro, Meritxell Rovira, Eija Heikkilä, Jorge Ferrer

MafA is critical for maintenance of the mature beta cell phenotype in mice
Wataru Nishimura, Satoru Takahashi, Kazuki Yasuda

IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice
Clara Y. Westwell-Roper, Cyrus A. Chehroudi, Heather C. Denroche, Jaques A. Courtade, Jan A. Ehses, C. Bruce Verchere

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Metabolism

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance
Mark J. W. Hanssen, Roel Wierts, Joris Hoeks, Anne Gemmink, Boudewijn Brans, Felix M. Mottaghy, Patrick Schrauwen, Wouter D. van Marken Lichtenbelt

Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes
Stephanie T. Chung, Daniel S. Hsia, Shaji K. Chacko, Luisa M. Rodriguez, Morey W. Haymond

GLP-1–oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice
Robert W. Schwenk, Christian Baumeier, Brian Finan, Oliver Kluth, Christine Brauer, Hans-Georg Joost, Richard D. DiMarchi, Matthias H. Tschöp, Annette Schürmann

Pre-gestational vs gestational exposure to maternal obesity differentially programs the offspring in mice
Isaac E. Sasson, Alexa P. Vitins, Monica A. Mainigi, Kelle H. Moley, Rebecca A. Simmons

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Pathophysiology and Complications

Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study
Ayman A. M. Osman, Lars B. Dahlin, Niels O. B. Thomsen, Simin Mohseni

Diabetes reduces mesenchymal stem cells in fracture healing through a TNFα-mediated mechanism
Kang I. Ko, Leila S. Coimbra, Chen Tian, Jazia Alblowi, Rayyan A. Kayal, Thomas A. Einhorn, Louis C. Gerstenfeld, Robert J. Pignolo, Dana T. Graves

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Errata

Erratum to: ‘Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice’ and ‘Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway’
C. Zhang, C. McFarlane, S. Lokireddy, S. Bonala, X. Ge, S. Masuda, P. D. Gluckman, M. Sharma, R. Kambadur

Erratum to: Modulation of p75NTR prevents diabetes- and proNGF-induced retinal inflammation and blood–retina barrier breakdown in mice and rats
Barbara A. Mysona, Mohammed M. H. Al-Gayyar, Suraporn Matragoon, Mohammed A. Abdelsaid, Mona F. El-Azab, H. Uri Saragovi, Azza B. El-Remessy

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