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Welcome to Diabetologia

Diabetologia publishes original clinical, translational 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.

Inside this issue Up front
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In the News

New study reveals the association between type 2 diabetes and the risk of death from cancer in East and South Asians

Read this new research by Dr Yu Chen (Associate Professor of Epidemiology at the Department of Population Health at NYU School of Medicine) and colleagues, as well as researchers from institutes across America and Asia.
For further information contact Dr Chen (Yu.Chen@nyumc.org).

Current issue: April 2017

April 2017 cover

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The cover picture shows a multicoloured liver under the influence of gut microbes, representing the metabolic variation that both the liver and gut microbiota undergo during metabolic adaptation to a diabetogenic/non-obesogenic high-fat diet. In the present issue of Diabetologia Blasco-Baque et al report the associations between hepatic microRNA expression, liver triacylglycerols and gut microbiota during metabolic adaptation in mice fed a high-fat diet. The authors conclude that hepatic microRNAs appear to link microbial activity and its associated hepatic consequences.


Cover credit: The image was created by M. Serino, Institut National de la Santé et de la Recherche Médicale (Inserm)/ Unité Mixte de Recherche (UMR) 1220, Institut de Recherche en Santé Digestive (IRSD), Toulouse, France using © Irochka - Fotolia.com for the bacteria image, and Servier Medical Art for the liver image (www.servier.fr/smart/banque-dimages-powerpoint), under the Creative Commons Attribution 3.0 France (CC BY 3.0 FR) license (https://creativecommons.org/licenses/by/3.0/fr/).


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Up front

Sally Marshall

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. Sally Marshall, Editor


Emerging role of intestinal microbiota and microbial metabolites in metabolic control
by Hilde Herrema, Richard G. IJzerman, Max Nieuwdorp

Gut microbiota and microbial metabolites (including short-chain fatty acids) have been increasingly associated with the development of metabolic diseases, including obesity and type 2 diabetes. Nevertheless, experimental data showing causality in humans is limited and such data primarily originate from rodent studies. In this issue, Herrema et al comment on two recent rodent studies, one of which investigated the interaction between environmental and genetic factors in microbiota-related metabolic disease development in mice and the other studied the potential mechanism underlying microbiota-driven disease development in rats. Referring to these publications, Herrema et al discuss how specific interventions, including faecal transplantation, gastric bypass and antibiotic treatment, and environmental factors (e.g. experimental facility and dietary challenge), have been shown to causally affect disease development in rodents. They state that, although challenging, multi-omics approaches will provide crucial insight into the systemic role of intestinal microbiota and microbial metabolites in host metabolism. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota and/or its metabolites will have high potential. [Text supplied by the authors.]

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Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry
by Bente B. Johansson, Henrik U. Irgens, Janne Molnes, Paweł Sztromwasser, Ingvild Aukrust, Petur B. Juliusson, Oddmund Søvik, Shawn Levy, Torild Skrivarhaug, Geir Joner, Anders Molven, Stefan Johansson, Pål R. Njølstad

MODY can mimic type 1 or type 2 diabetes. Correct identification of MODY is important for the improvement of diagnosis and management of diabetes. Many patients with a newly discovered MODY diagnosis can switch from insulin injections to oral glucose-lowering agents, thereby improving glucose control and achieving better quality of life. In this issue, Johansson et al describe the first nationwide systematic screening of MODY using next-generation sequencing. They show that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5% and that one-third of these individuals with MODY had not been recognised prior to the study. Since a correct diagnosis can lead to a change in treatment, the authors suggest that molecular screening of all antibody-negative children should be considered in routine diagnostics. This study is an example of how to implement precision medicine in diabetes clinics. This article is the subject of a commentary in this issue by Shields and Colclough. [Text supplied by the authors.]

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Differential methylation of genes in individuals exposed to maternal diabetes in utero
by Peng Chen, Paolo Piaggi, Michael Traurig, Clifton Bogardus, William C. Knowler, Leslie J. Baier, Robert L. Hanson

Individuals exposed to diabetes in utero (i.e. offspring whose mothers had diabetes during their pregnancy) are at high risk for developing type 2 diabetes and obesity. It has been proposed that epigenetic factors may be partly responsible for this risk, but there is a lack of identification of specific epigenetic changes that are associated with exposure to diabetes in utero. In this issue, Chen et al compare genome-wide DNA methylation profiles of Pima Indians exposed to diabetes in utero with those not exposed to diabetes in utero. They identify 39 separate genomic regions at which DNA methylation differed between the groups. At several of these regions, DNA methylation was also associated with obesity, impaired insulin secretion or risk of developing type 2 diabetes. Their findings suggest that intrauterine exposure to diabetes may influence epigenetic factors, such as DNA methylation, and that these epigenetic factors may influence metabolic processes that lead to type 2 diabetes. [Text supplied by the authors.]

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Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes
by Laura Marroqui, Reinaldo S. Dos Santos, Anne Op de beeck, Alexandra Coomans de Brachène, Lorella Marselli, Piero Marchetti, Decio L. Eizirik

Three hallmarks of pancreatic islets in early human type 1 diabetes are overexpression of HLA class I, endoplasmic reticulum (ER) stress and beta cell apoptosis. Interferon-α (IFNα) is also expressed in human islets from individuals with type 1 diabetes and it is proposed that this cytokine is a common mediator of these three phenomena. In this issue, Marroqui et al report that IFNα induces hyperexpression of MHC class I proteins, inflammation and the ER stress response in human beta cells, sensitising these cells to another cytokine, IL-1β, leading to their death by apoptosis. These novel observations place IFNα as a central modulator of excessive inflammatory and ER stress responses in the early stages of type 1 diabetes, contributing to the progressive destruction of pancreatic beta cells and to the triggering of autoimmunity in genetically predisposed individuals. Hence, these findings suggest that targeting IFNα may be a promising adjuvant therapy in the early stages of type 1 diabetes. [Text supplied by the authors.]

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Improved glycaemia in high-fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels
by Joshua R. Willard, Breanne M. Barrow, Sakeneh Zraika

Neprilysin is a peptidase which, like dipeptidyl peptidase-4 (DPP-4), cleaves and inactivates glucagon-like peptide-1 (GLP-1). It is unknown whether, under conditions associated with type 2 diabetes (i.e. elevated glucose levels and high-fat-diet induced obesity), neprilysin deficiency enhances active GLP-1 and, thereby, improves blood glucose levels. In this issue, Willard, Barrow and Zraika report that neprilysin-deficient mice fed a high-fat diet exhibit increased active GLP-1 levels in plasma, as well as improved glucose tolerance, insulin sensitivity and beta cell function. Further, the authors observed that high-fat-fed neprilysin-deficient mice had reduced plasma DPP-4 activity. These findings suggest that neprilysin inhibitors may have clinical purpose for the treatment of type 2 diabetes. [Text supplied by the authors.]

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Inside this issue

Up front

Up front April 2017

Commentaries

Towards a systematic nationwide screening strategy for MODY
Beverley Shields, Kevin Colclough

Emerging role of intestinal microbiota and microbial metabolites in metabolic control
Hilde Herrema, Richard G. IJzerman, Max Nieuwdorp

Articles

Clinical Science and Care

Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes
Graham R. Law, Mark S. Gilthorpe, Anna L. Secher, Rosemary Temple, Rudolf Bilous, Elisabeth R. Mathiesen, Helen R. Murphy, Eleanor M. Scott

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Epidemiology

Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry
Bente B. Johansson, Henrik U. Irgens, Janne Molnes, Paweł Sztromwasser, Ingvild Aukrust, Petur B. Juliusson, Oddmund Søvik, Shawn Levy, Torild Skrivarhaug, Geir Joner, Anders Molven, Stefan Johansson, Pål R. Njølstad

Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012
Cécile Billionnet, Delphine Mitanchez, Alain Weill, Jacky Nizard, François Alla, Agnès Hartemann, Sophie Jacqueminet

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Genetics

Differential methylation of genes in individuals exposed to maternal diabetes in utero
Peng Chen, Paolo Piaggi, Michael Traurig, Clifton Bogardus, William C. Knowler, Leslie J. Baier, Robert L. Hanson

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Islet Studies

Interferon-α mediates human beta cell HLA class I overexpression, endoplasmic reticulum stress and apoptosis, three hallmarks of early human type 1 diabetes
Laura Marroqui, Reinaldo S. Dos Santos, Anne Op de beeck, Alexandra Coomans de Brachène, Lorella Marselli, Piero Marchetti, Decio L. Eizirik

Reciprocal regulation of mTOR complexes in pancreatic islets from humans with type 2 diabetes
Ting Yuan, Sahar Rafizadeh, Kanaka Durga Devi Gorrepati, Blaz Lupse, Jose Oberholzer, Kathrin Maedler, Amin Ardestani

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Immunology and Transplantation

Targeted deletion of Traf2 allows immunosuppression-free islet allograft survival in mice
Jeanette E. Villanueva, Stacey N. Walters, Mitsuru Saito, Elisabeth K. Malle, Nathan W. Zammit, Katherine A. Watson, Robert Brink, Nicole L. La Gruta, Stephen I. Alexander, Shane T. Grey

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Metabolism

Associations between hepatic miRNA expression, liver triacylglycerols and gut microbiota during metabolic adaptation to high-fat diet in mice
Vincent Blasco-Baque, Berengère Coupé, Aurelie Fabre, Sandra Handgraaf, Pierre Gourdy, Jean-François Arnal, Michael Courtney, Carole Schuster-Klein, Beatrice Guardiola, François Tercé, Rémy Burcelin, Matteo Serino

Improved glycaemia in high-fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels
Joshua R. Willard, Breanne M. Barrow, Sakeneh Zraika

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Pathophysiology and Complications

Type 1 diabetic patients with peripheral neuropathy have pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile
Adam D. Farmer, Anne Grave Pedersen, Birgitte Brock, Poul Erik Jakobsen, Jesper Karmisholt, Sahar D. Mohammed, S. Mark Scott, Asbjørn Mohr Drewes, Christina Brock

Inflammation and N-formyl peptide receptors mediate the angiogenic activity of human vitreous humour in proliferative diabetic retinopathy
Sara Rezzola, Michela Corsini, Paola Chiodelli, Anna Cancarini, Imtiaz M. Nawaz, Daniela Coltrini, Stefania Mitola, Roberto Ronca, Mirella Belleri, Liliana Lista, Dario Rusciano, Mario De Rosa, Vincenzo Pavone, Francesco Semeraro, Marco Presta

AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin
Emma Börgeson, Ville Wallenius, Gulam H. Syed, Manjula Darshi, Juan Lantero Rodriguez, Christina Biörserud, Malin Ragnmark Ek, Per Björklund, Marianne Quiding-Järbrink, Lars Fändriks, Catherine Godson, Kumar Sharma

Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes
Mohammed Abdelsaid, Maha Coucha, Sherif Hafez, Abdul Yasir, Maribeth H. Johnson, Adviye Ergul

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Letters

PCSK9 inhibition and the global diabetes epidemic
Luca Mascitelli, Mark R. Goldstein

Re-addressing the 2013 consensus guidelines for the diagnosis of insulitis in human type 1 diabetes: is change necessary?
Martha L. Campbell-Thompson, Mark A. Atkinson, Alexandra E. Butler, Ben N. Giepmans, Matthias G. von Herrath, Heikki Hyöty, Thomas W. Kay, Noel G. Morgan, Alvin C. Powers, Alberto Pugliese, Sarah J. Richardson, Peter A. In’t Veld

Re-addressing the 2013 consensus guidelines for the diagnosis of insulitis in human type 1 diabetes: is change necessary? Reply to Campbell-Thompson ML, Atkinson MA, Butler AE et al [letter]
Marcus Lundberg, Peter Seiron, Sofie Ingvast, Olle Korsgren, Oskar Skog

Erratum

Erratum to: Non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes
Emily J. Gallagher, Zara Zelenko, Aviva Tobin-Hess, Ulrich Werner, Norbert Tennagels, Derek LeRoith

List of Referees

Referees 2016

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