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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.

Inside this issue Up front
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In the News

Study reveals substantial reductions in years lived without disability and overall life expectancy for men and women with diabetes

Read this new research by Associate Professor Dianna Magliano and Dr Lili Huo, Baker IDI Heart and Diabetes Institute, Melbourne, Australia, and colleagues.
For further information contact Christina Hickie in the Press Office (Christina.hickie@bakeridi.edu.au).

New studies reveal large gap in life expectancy between patients with type 1 diabetes and the general population

Read the Australian study by Associate Professor Dianna Magliano and Dr Lili Huo (Baker IDI Heart and Diabetes Institute, Melbourne, Australia) and colleagues
and the Swedish study by Dr Dennis Petrie, University of Melbourne, Carlton, Melbourne, Australia, and Professor Björn Eliasson, University of Gothenburg, Sweden, and colleagues.
Read a commentary on these two studies by Dr Lars Stene, Norwegian Institute of Public Health, Oslo, Norway.
For further information contact Dr Magliano (Dianna.Magliano@bakeridi.edu.au), Dr Petrie (dennis.petrie@unimelb.edu.au) and Professor Eliasson (bjorn.eliasson@gu.se).

Type 1 diabetes linked to 3-fold increase in risk of epilepsy

Read this new research by Dr I-Ching Chou, China Medical University Children's Hospital, Taichung, Taiwan, and colleagues.
For further information contact Dr Chou (iching@mail.cmu.edu.tw).

Current issue: May 2016

May 2016 cover

Click here to view this month's contents

The cover picture shows a three-dimensional reconstruction of an embryonic pancreatic bud developing on top of the iris of a recipient mouse. In the present issue of Diabetologia Ali et al describe how a dorsal pancreatic bud was isolated from a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse embryo on embryonic day 10.5 (E10.5) and transplanted into the anterior chamber of the eye (ACE) of a syngeneic recipient. The development of the engrafted pancreatic bud was monitored by imaging the tissue non-invasively and at high resolution. The representative image on the cover, taken 21 days post-transplantation, shows the pancreatic bud on the iris (reflected light, grey) containing insulin-expressing cell clusters (GFP, green). Insulin expression confirms the presence of beta cells and demonstrates that the ACE supports differentiation and growth of the transplanted mouse pancreatic bud.


Cover credit: L. Selander, Y. Ali and P.-O. Berggren
Rolf Luft Research Center for Diabetes and Endocrinology Photo Library

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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


Adipose tissue macrophages: going off track during obesity
by Lily Boutens, Rinke Stienstra

Tissue macrophages are key cells of our innate immune system. These cells, including those in the adipose tissue, are assigned several tasks, including immune surveillance, phagocytosis and cytokine production. The precise functional output of a macrophage is determined by a variety of local and systemic signals. In a review in this issue, Lily Boutens and Rinke Stienstra summarise the differences in functional output between adipose tissue macrophages (ATMs) in lean and obese adipose tissue. In addition, potential local and systemic signals that shape ATM function are discussed. Disturbances in the balance between these signals may eventually lead to a dysfunctional macrophage promoting the development of adipose tissue inflammation and insulin resistance in obese individuals. The integration of data on transcription and functions executed will greatly help to identify relevant signals that determine ATM behaviour during obesity and aid the search for targeted interventions in individuals with diabetes. [Text supplied by the authors.]

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Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle
by Taylor K. Soderborg, Sarah J. Borengasser, Linda A. Barbour, Jacob E. Friedman

The risk factors for obesity and metabolic diseases begin operating in early life (even in utero) and may permanently change the body's structure, physiology and metabolism, leading to an increased lifetime disease risk and/or disease acceleration. A novel possible mechanistic pathway linking maternal obesity and diabetes with childhood disease involves the effects of maternal metabolic status on early microbiome colonisation of the infant gastrointestinal tract. Early dietary exposures affect the infant gut microbiome, which changes rapidly and reproducibly during the first 24 months of life, with long-lasting effects on the host. Maternal obesity is associated with an altered infant gut microbiome; however, the inciting metabolic factors, and mechanistic links to early disease pathways in the infant, need further study. In a review in this issue, Soderborg et al discuss how maternal metabolism impacts the early infant gut microbiome and how this may lay the seeds for obesity and diabetes disease risk and offer important opportunities for early intervention. [Text supplied by the authors.]

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Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial
by David E. Cummings, David E. Arterburn, Emily O. Westbrook, Jessica N. Kuzma, Skye D. Stewart, Chun P. Chan, Steven N. Bock, Jeffrey T. Landers, Mario Kratz, Karen E. Foster-Schubert, David R. Flum

Roux-en-Y gastric bypass (RYGB) causes remission of type 2 diabetes in most cases, in part through weight-independent mechanisms. Hence, there is increasing interest in 'metabolic surgery', i.e. the use of RYGB and related operations primarily to treat type 2 diabetes, including among patients not obese enough to qualify for traditional bariatric surgery. In this issue, Cummings et al provide Level-1 evidence supporting that concept. They directly compared RYGB with the most intensive supervised lifestyle/medical intervention (with ≥45 min of aerobic exercise, ≥5 days/week) yet tested against surgery in a randomised controlled trial, including in patients with a BMI <35 kg/m2. Although the fitness of the lifestyle/medical patients greatly increased (whereas that of the surgical patients did not) and they showed substantial reductions in weight and blood glucose, at 1 year the rate of diabetes remission (HbA1c <6.0% [42.1 mmol/mol] off diabetes medications) in the surgery patients was ten times that in the lifestyle/medical group (60.0% vs 5.9%, p=0.002), and they showed greater reductions of other cardiovascular risk factors and fewer adverse events. This study supports new recommendations to consider metabolic surgery to treat type 2 diabetes in patients with a BMI as low as 30 kg/m2. This article is the subject of a commentary in this issue by Karl Neff and Carel le Roux. [Text supplied by the authors.]

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GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial
by Olivia M. Farr, Michail Sofopoulos, Michael A. Tsoukas, Fadime Dincer, Bindiya Thakkar, Ayse Sahin-Efe, Andreas Filippaios, Jennifer Bowers, Alexandra Srnka, Anna Gavrieli, Byung-Joon Ko, Chrysoula Liakou, Nickole Kanyuch, Sofia Tseleni-Balafouta, Christos S. Mantzoros

Glucagon-like peptide-1 (GLP-1) analogues have gained attention recently because of their ability to cause significant weight loss and are approved for the treatment for obesity and type 2 diabetes. In this issue, Farr et al present the results of their study to determine whether this weight-reducing effect stems from actions in the human brain. They report that GLP-1 receptors are present in the human brain, including the cortex. In a crossover, placebo-controlled, randomised, double-blinded trial (18 individuals with type 2 diabetes included in analysis), liraglutide, a GLP-1 analogue, given at doses approved for type 2 diabetes, decreased brain activations related to attention and reward signalling in the human brain to highly desirable (high energy or fat) as compared with less desirable food cues. These data indicate that a central mechanism is involved in the effects of liraglutide on metabolism and weight loss. Further studies in larger cohorts are needed to confirm and extend these findings. [Text supplied by the authors.]

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Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals
by Bendix Carstensen, Stephanie H. Read, Søren Friis, Reijo Sund, Ilmo Keskimäki, Ann-Marie Svensson, Rickard Ljung, Sarah H. Wild, Joannes J. Kerssens, Jessica L. Harding, Dianna J. Magliano, Soffia Gudbjörnsdottir, on behalf of the Diabetes and Cancer Research Consortium

Earlier studies of cancer in individuals with diabetes have not distinguished between diabetes types. As type 1 diabetes constitutes only a small proportion of all diabetes cases (<10%), the association between type 1 diabetes and cancer remains unclear. In this issue, Carstensen et al report on an analysis of people with type 1 diabetes who were identified from five nationwide registers. The authors found that type 1 diabetes was associated with an increased risk of cancers of the stomach, liver, pancreas, kidney, ovary and endometrium, whereas the risks of prostate and breast cancer were decreased. Overall, the excess risk was 1% for men and 7% for women. Increased risk of cancer among people with type 1 diabetes compared with the general population was highest in the first year following diabetes diagnosis, consistent with earlier cancer detection through increased medical attention. The absence of a dose-response relationship between diabetes duration (and hence duration of insulin use) and cancer incidence indicates that insulin therapy does not contribute substantially to the excess incidence. [Text supplied by the authors.]

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Inside this issue

Up front

Up front May 2016

Reviews

Adipose tissue macrophages: going off track during obesity
Lily Boutens, Rinke Stienstra

Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle
Taylor K. Soderborg, Sarah J. Borengasser, Linda A. Barbour, Jacob E. Friedman

Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism
Bo Ahrén, James E. Foley

EASD symposia

Is leptin coming back? A short introduction to the presentations in this symposium session at the 2015 annual meeting of the EASD
Ulf Smith

Renaissance of leptin for obesity therapy
Carmelo Quarta, Miguel A. Sánchez-Garrido, Matthias H. Tschöp , Christoffer Clemmensen

The role of leptin in diabetes: metabolic effects
Thomas H. Meek, Gregory J. Morton

Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis
Rachel J. Perry, Kitt Falk Petersen, Gerald I. Shulman

Insights into metabolic disease from studying genetics in isolated populations: stories from Greece to Greenland
Eleftheria Zeggini, Anna L. Gloyn, Torben Hansen

Commentary

Bariatric surgery: traversing the CROSSROADS into mainstream diabetes care
Karl J. Neff, Carel W. le Roux

Articles

Clinical Science and Care

Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial
David E. Cummings , David E. Arterburn, Emily O. Westbrook, Jessica N. Kuzma, Skye D. Stewart, Chun P. Chan, Steven N. Bock, Jeffrey T. Landers, Mario Kratz, Karen E. Foster-Schubert, David R. Flum

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial
Olivia M. Farr , Michail Sofopoulos, Michael A. Tsoukas, Fadime Dincer, Bindiya Thakkar, Ayse Sahin-Efe, Andreas Filippaios, Jennifer Bowers, Alexandra Srnka, Anna Gavrieli, Byung-Joon Ko, Chrysoula Liakou, Nickole Kanyuch, Sofia Tseleni-Balafouta, Christos S. Mantzoros

The insulinotropic effect of pulsatile compared with continuous intravenous delivery of GLP-1
Short Communication
Mark P. Plummer , Palash Kar, Caroline E. Cousins, Kylie Lange, Marianne J. Chapman, Michael A. Nauck, Michael Horowitz, Juris J. Meier, Adam M. Deane

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry
Tina Ravnsborg, Lise Lotte T. Andersen, Natacha D. Trabjerg, Lars M. Rasmussen, Dorte M. Jensen, Martin Overgaard

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Epidemiology

Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals
Bendix Carstensen, Stephanie H Read , Søren Friis, Reijo Sund, Ilmo Keskimäki, Ann-Marie Svensson, Rickard Ljung, Sarah H Wild, Joannes J Kerssens, Jessica L Harding, Dianna J Magliano, Soffia Gudbjörnsdottir, on behalf of the Diabetes and Cancer Research Consortium

Incidence of register-based diabetes 10 years after a stepwise diabetes screening programme: the ADDITION-Denmark study
Signe S. Rasmussen , Nanna B. Johansen, Daniel R. Witte, Knut Borch-Johnsen, Annelli Sandbaek, Torsten Lauritzen, Marit E. Jørgensen

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Genetics

Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes
Symen Ligthart, Rebecca V. Steenaard, Marjolein J. Peters, Joyce B. J. van Meurs, Eric J. G. Sijbrands, André G. Uitterlinden, Marc J. Bonder, BIOS consortium, Albert Hofman, Oscar H. Franco, Abbas Dehghan

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Islet Studies

The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice
Yusuf Ali , Juan Diez, Lars Selander, Xiaofeng Zheng, Helena Edlund, Per-Olof Berggren

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis
Joan Mir-Coll, Jordi Duran, Felipe Slebe, Mar García-Rocha, Ramon Gomis, Rosa Gasa , Joan J. Guinovart

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Immunology and Transplantation

Methylation of insulin DNA in response to proinflammatory cytokines during the progression of autoimmune diabetes in NOD mice
Jinxiu Rui, Songyan Deng, Jasmin Lebastchi, Pamela L. Clark, Sahar Usmani-Brown, Kevan C. Herold

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Metabolism

ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity
Lauren M. Sparks, Anne Gemmink, Esther Phielix, Madeleen Bosma, Gert Schaart, Esther Moonen-Kornips, Johanna A. Jörgensen, Emmani B. M. Nascimento, Matthijs K. C. Hesselink, Patrick Schrauwen, Joris Hoeks

Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting-induced insulin resistance and lipotoxicity in humans
Anne Gemmink, Madeleen Bosma, Helma J. H. Kuijpers, Joris Hoeks, Gert Schaart, Marc A. M. J. van Zandvoort, Patrick Schrauwen, Matthijs K. C. Hesselink

Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice
Audrey Jalabert, Guillaume Vial, Claudiane Guay, Oscar P. B. Wiklander, Joel Z. Nordin, Hala Aswad, Alexis Forterre, Emmanuelle Meugnier, Sandra Pesenti, Romano Regazzi, Emmanuelle Danty-Berger, Sylvie Ducreux, Hubert Vidal, Samir El-Andaloussi, Jennifer Rieusset, Sophie Rome

GLP-1 receptor agonist promotes brown remodelling in mouse white adipose tissue through SIRT1
Fen Xu, Beisi Lin, Xiaobin Zheng, Zonglan Chen, Huanyi Cao, Haixia Xu, Hua Liang, Jianping Weng

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Research Letter

Insomnia does not mediate or modify the association between MTNR1B risk variant rs10830963 and glucose levels
Hanna M Ollila, Erkki Kronholm, Johannes Kettunen, Kaisa Silander, Markus Perola, Tarja Porkka-Heiskanen, Veikko Salomaa, Tiina Paunio

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