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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

New research shows each hour of sedentary time is associated with a 22% increased risk of developing type 2 diabetes

Read this new research by Julianne van der Berg, Maastricht University, the Netherlands, and colleagues.
For further information contact Mrs van der Berg (j.vanderberg@maastrichtuniversity.nl).

Women with sleeping problems far more likely to develop diabetes

Read this new research by Dr Yanping Li, Harvard T. H. Chan School of Public Health, Boston, MA, USA, and colleagues.
For further information contact Dr Li (yanping@hsph.harvard.edu).

Current issue: February 2016

February 2016 cover

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The cover picture shows computer-generated artwork of dendritic cells, which are involved in the priming, differentiation and expansion of effector T cells and may play a role in type 1 diabetes. Tolerogenic dendritic cell-based therapies represent a tool for immune-intervention strategies in autoimmune diseases. In this issue of Diabetologia, Favaro et al report that, in type 1 diabetes, mesenchymal stem cells, as well as the extracellular vesicles they release, induce immature IL-10-secreting tolerogenic dendritic cells. These cells contribute to the inhibition of inflammatory T cell responses to islet antigens and to the promotion of anti-inflammatory, regulatory responses. These findings therefore indicate that dendritic cells are involved in the multilevel immunomodulatory properties displayed by mesenchymal stem cells.


Cover credit: ANIMATED HEALTHCARE LTD/SCIENCE 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


G protein-coupled receptors as new therapeutic targets for type 2 diabetes
by Frank Reimann, Fiona M. Gribble

G protein-coupled receptors (GPCRs) in the membrane of intestinal endocrine cells detect digested nutrients. In a review in this issue, Frank Reimann and Fiona Gribble discuss how GPCRs are the targets for existing glucose-lowering therapies, as well as for a number of drugs in the pipeline. They explain how different GPCRs in gut endocrine cells, pancreatic islets and the brain are being targeted, with the aim of mimicking the postprandial state of enhanced insulin secretion and reduced appetite. Glucagon-like peptide-1 receptor agonists have highlighted the potential efficacy of targeting GPCRs for the treatment of diabetes, and are particularly popular because they exhibit glucose dependence at the level of the pancreatic beta cell and promote weight loss. By harnessing the tissue specificity and 'druggability' of GPCRs, it is hoped that new classes of diabetes therapies will emerge that target selected panels of tissues and exhibit superior side-effect profiles. This review is accompanied by a commentary by the Session Chair, Michael Nauck (DOI: 10.1007/s00125-015-3795-1). [Text supplied by the authors.]

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Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies
by Eileen Morgan, Sophia R. Halliday, Gemma R. Campbell, Chris R. Cardwell, Chris C. Patterson

There is continued debate about the environmental factors responsible for the increasing incidence of childhood type 1 diabetes, which, best-available evidence suggests, began in the middle of the last century. The fact that this increase coincides with the introduction of mass vaccination programmes in many countries has led to speculation that there may be a link. Although studies in the literature have generally provided little support for such an association, the power of many of these studies was low. In this issue, a systematic review and meta-analysis of observational studies by Morgan et al indicates that vaccination is not linked to any statistically significant increase in childhood diabetes risk. Although ongoing prospective studies of high-risk birth cohorts may add further evidence, the selective nature of these cohorts and the high vaccination rates in many populations mean that our meta-analysis may provide the most definitive answer to this issue. [Text supplied by the authors.]

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The impact of gender on the long-term morbidity and mortality of patients with type 2 diabetes receiving structured personal care: a 13 year follow-up study
by Marlene Ø. Krag, Lotte Hasselbalch, Volkert Siersma, Anni B. S. Nielsen, Susanne Reventlow, Kirsti Malterud, Niels de Fine Olivarius

There is an increasing focus on personally tailored diabetes treatment, but it is widely unknown how gender impacts the effect of treatment. In this issue, Krag et al report that tailored diabetes treatment and individual goal setting (in collaboration with a general practitioner) significantly reduces mortality in women. However, the same effect is not seen in men. The authors suggest that tailored treatment could provide women with attention and support, thus providing an incentive for treatment adherence. Furthermore, women accept disease and implement disease management more easily, whereas men may feel challenged by diabetes, which demands daily consideration and lifestyle changes. The authors propose a need to further explore whether gender-specific treatment schemes could provide a similar reduction in mortality in men. [Text supplied by the authors.]

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Effect of atorvastatin on glycaemia progression in patients with diabetes: an analysis from the Collaborative Atorvastatin in Diabetes Trial (CARDS)
by Shona J. Livingstone, Helen C. Looker, Tahira Akbar, D. John Betteridge, Paul N. Durrington, Graham A. Hitman, H. Andrew W. Neil, John H. Fuller, Helen M. Colhoun

Statins are known to increase diabetes incidence, but information on the frequency, size and persistence of effects on glycaemia among individuals with established diabetes are lacking. In this issue, Livingstone et al present the results of an analysis of data from the Collaborative Atorvastatin Diabetes Study (CARDS) randomised trial of atorvastatin 10 mg in people with type 2 diabetes. According to their findings, the effect of atorvastatin 10 mg on glycaemia progression among those with diabetes is common but very small, is apparent soon after statins are started but does not increase with duration of statin treatment and does not have an impact on the magnitude of the reduction in risk for cardiovascular disease with atorvastatin. These findings provide useful and reassuring data for balancing the risks and benefits of statin use in those with diabetes. [Text supplied by the authors.]

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Protein kinase STK25 controls lipid partitioning in hepatocytes and correlates with liver fat content in humans
by Manoj Amrutkar, Matthias Kern, Esther Nuñez-Durán, Marcus Ståhlman, Emmelie Cansby, Urszula Chursa, Elin Stenfeldt, Jan Borén, Matthias Blüher, Margit Mahlapuu

Type 2 diabetes is closely associated with pathological lipid accumulation in the liver, which is suggested to be involved in the development of insulin resistance. Serine/threonine protein kinase 25 (STK25) was recently identified as a regulator of liver steatosis, whole-body glucose and insulin homoeostasis in a mouse model system. In this issue, Amrutkar et al present the results of a study that investigated the role of STK25 in the regulation of lipid metabolism in human liver cells. Overexpression of STK25 in human hepatocytes enhanced lipid deposition by suppressing β-oxidation and triacylglycerol secretion while increasing lipid synthesis. Knockdown of STK25 in human hepatocytes produced the opposite effect. STK25 mRNA expression in human liver tissue samples was positively correlated with liver fat content. These data suggest that STK25 is a novel regulator of lipid partitioning in human liver and could be a potential drug target for the prevention/treatment of type 2 diabetes. [Text supplied by the authors.]

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Inside this issue

Up front

Up front February 2016

EASD symposia

Novel approaches to treating type 2 diabetes
Michael A. Nauck

G protein-coupled receptors as new therapeutic targets for type 2 diabetes
Frank Reimann, Fiona M. Gribble

Commentary

Night-time blood pressure: a role in the prediction and prevention of diabetes?
Martin K. Rutter

Systematic Reviews/Meta-analyses

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies
Eileen Morgan, Sophia R. Halliday, Gemma R. Campbell, Chris R. Cardwell, Chris C. Patterson

Articles

Clinical Science and Care

Sleep-time BP: prognostic marker of type 2 diabetes and therapeutic target for prevention
Ramón C. Hermida, Diana E. Ayala, Artemio Mojón, José R. Fernández

Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial
Ramón C. Hermida, Diana E. Ayala, Artemio Mojón, José R. Fernández

Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise
Michael A. Nauck, Murray W. Stewart, Christopher Perkins, Angela Jones-Leone, Fred Yang, Caroline Perry, Rickey R. Reinhardt, Marc Rendell

The impact of gender on the long-term morbidity and mortality of patients with type 2 diabetes receiving structured personal care: a 13 year follow-up study
Marlene Ø. Krag, Lotte Hasselbalch, Volkert Siersma, Anni B. S. Nielsen, Susanne Reventlow, Kirsti Malterud, Niels de Fine Olivarius

Association of the average rate of change in HbA1c with severe adverse events: a longitudinal evaluation of audit data from the Bavarian Disease Management Program for patients with type 2 diabetes mellitus
Florian C. Bonke, Ewan Donnachie, Antonius Schneider, Michael Mehring

Isolation of human monoclonal autoantibodies derived from pancreatic lymph node and peripheral blood B cells of islet autoantibody-positive patients
Short Communication
Mara Catani, Denise Walther, Michael R. Christie, Kerry A. McLaughlin, Ezio Bonifacio, Anne Eugster

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Epidemiology

Effect of atorvastatin on glycaemia progression in patients with diabetes: an analysis from the Collaborative Atorvastatin in Diabetes Trial (CARDS)
Shona J. Livingstone, Helen C. Looker, Tahira Akbar, D. John Betteridge, Paul N. Durrington, Graham A. Hitman, H. Andrew W. Neil, John H. Fuller, Helen M. Colhoun

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Genetics

Discrete associations of the GCKR variant with metabolic risk in a Chinese population: longitudinal change analysis
Min Xu, Xiaofei Lv, Lan Xie, Xiaolin Huang, Ya Huang, Ying Chen, Kui Peng, Po Wang, Weiqing Wang, Lu Qi, Yufang Bi, Yimin Sun, Guang Ning

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Islet Studies

Transcription factor Ets-1 links glucotoxicity to pancreatic beta cell dysfunction through inhibiting PDX-1 expression in rodent models
Fang Chen, Min Sha, Yanyang Wang, Tijun Wu, Wei Shan, Jia Liu, Wenbo Zhou, Yunxia Zhu, Yujie Sun, Yuguang Shi, David Bleich, Xiao Han

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Immunology and Transplantation

Human mesenchymal stem cells and derived extracellular vesicles induce regulatory dendritic cells in type 1 diabetic patients
Enrica Favaro, Andrea Carpanetto, Cristiana Caorsi, Mirella Giovarelli, Costanza Angelini, Paolo Cavallo-Perin, Ciro Tetta, Giovanni Camussi, Maria M. Zanone

Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes
Carolyn C. Richardson, Kerry A. McLaughlin, Diana Morgan, Richard G. Feltbower, Michael R. Christie

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Metabolism

Protein kinase STK25 controls lipid partitioning in hepatocytes and correlates with liver fat content in humans
Manoj Amrutkar, Matthias Kern, Esther Nuñez-Durán, Marcus Ståhlman, Emmelie Cansby, Urszula Chursa, Elin Stenfeldt, Jan Borén, Matthias Blüher, Margit Mahlapuu

RBP4 functions as a hepatokine in the regulation of glucose metabolism by the circadian clock in mice
Xiang Ma, Zan Zhou, Yaqiong Chen, Yuting Wu, Yi Liu

Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes
Vivi R. Steenberg, Signe M. Jensen, Jens Pedersen, Andreas N. Madsen, Johanne A. Windeløv, Birgitte Holst, Bjørn Quistorff, Steen S. Poulsen, Jens J. Holst

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Pathophysiology and Complications

Cardiac 82Rb PET/CT for fast and non-invasive assessment of microvascular function and structure in asymptomatic patients with type 2 diabetes
Bernt J. von Scholten, Philip Hasbak, Thomas E. Christensen, Adam A. Ghotbi, Andreas Kjaer, Peter Rossing, Tine W. Hansen

Podocyte-specific Nox4 deletion affords renoprotection in a mouse model of diabetic nephropathy
Jay C. Jha, Vicki Thallas-Bonke, Claudine Banal, Stephen P. Gray, Bryna S. M. Chow, Georg Ramm, Susan E. Quaggin, Mark E. Cooper, Harald H. H. W. Schmidt, Karin A. Jandeleit-Dahm

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Letters

Antihypertensive medication prior to nocturnal sleep reduces the risk of new-onset type 2 diabetes in hypertensive patients: a role for slow-wave sleep?
Christian Benedict

Elevated asleep BP as predictor of type 2 diabetes and therapeutic target for prevention
Ramón C. Hermida, Diana E. Ayala, Artemio Mojón, José R. Fernández

Errata

Erratum to: Bedtime ingestion of hypertension medications reduces the risk of new-onset type 2 diabetes: a randomised controlled trial
Ramón C. Hermida, Diana E. Ayala, Artemio Mojón, José R. Fernández

Erratum to: Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals
Ghadi Antoun, Fiona McMurray, A. Brianne Thrush, David A. Patten, Alyssa C. Peixoto, Ruth S. Slack, Ruth McPherson, Robert Dent, Mary-Ellen Harper

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