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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.

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In the News

Study links child obesity at age 9−11 years to gestational diabetes in mother

Read this new research by Dr Gang Hu, Pennington Biomedical Research Center, Baton Rouge, LA, USA, and colleagues.
For further information contact Dr Hu (Gang.Hu@pbrc.edu) or Alisha Prather in the PBRC Press Office (Alisha.Prather@pbrc.edu).

Current issue: September 2016

September 2016 cover

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The cover picture shows a reconstruction of positron emission tomography (PET) and computed tomography (CT) data of a db/db mouse 10 s after administration of [18F]fludeoxyglucose ([18F]FDG) via intravenous injection in the lateral tail vein. This image was used to determine input functions for each animal, allowing for kinetic modelling of tissue uptake parameters to be elucidated. In the present issue of Diabetologia Cochran et al use [18F]FDG PET/CT imaging and kinetic modelling to demonstrate that treatment with apolipoprotein A-I, the main lipoprotein component of HDL, improves glucose disposal in db/db mice by improving insulin sensitivity and enhancing glucose phosphorylation.


Cover credit: Blake J. Cochran, School of Medical Sciences, UNSW Australia, NSW, Australia

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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


Coming of age: the artificial pancreas for type 1 diabetes
by Hood Thabit, Roman Hovorka

The artificial pancreas is a device that monitors blood glucose in people with type 1 diabetes and, in response, automatically adjusts levels of insulin entering the body. In this issue, Thabit and Hovorka review the significant milestones that have been achieved in the past decade, moving the artificial pancreas from the laboratory into free-living, unsupervised home settings. Outpatient clinical studies have shown that the artificial pancreas controls glucose levels to a degree that is equal to or better than existing technologies, as measured by time spent in a target glucose range, with a reduced risk of hypoglycaemia. At present, prolonged 6-24 month multinational closed-loop clinical trials and pivotal studies are under way or in preparation. It is predicted that automated closed-loop systems may appear on the market by the end of 2018. However, to support access to and reimbursement for the closed-loop system, the cost-effectiveness of these devices is yet to be determined. Given the challenges of beta cell transplantation, with continuing innovation closed-loop technologies have the potential to provide a viable alternative for existing insulin pump therapy and multiple daily insulin injections. [Text supplied by the authors.]

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Novel phenotypes of prediabetes?
by Hans-Ulrich Häring

Prediabetes is characterised by an impaired balance of insulin sensitivity and insulin secretion. In this issue, Häring reviews the phenotypes observed in 3000 prediabetic individuals (those at increased risk of developing type 2 diabetes) using data collected at the Tübingen University Hospital (Tübingen, Germany). Data taken from a subgroup of these participants suggest that the combination of fatty liver, altered plasma hepatokines and possibly fatty pancreas, which is found in people with metabolically unhealthy obesity (MUHO), causes both insulin resistance and low insulin secretion. Interestingly, brain insulin resistance also seems to be associated with these phenotypes and, to some extent, may even be the cause of this condition. It is hypothesised that the chronological development of organ crosstalk is a key feature of the progression from normoglycaemia to the prediabetic and type 2 diabetic states. This speculation may provide a useful roadmap for further studies aimed at understanding the pathophysiology of prediabetes. [Text supplied by the authors.]

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Proteomics for prediction of disease progression and response to therapy in diabetic kidney disease
by Michelle J. Pena, Harald Mischak, Hiddo J. L. Heerspink

Over the past decade, high-throughput proteomics has revolutionised biomarker discovery, providing new insights into the pathophysiological and biological processes associated with diabetic kidney disease. In this issue, Pena et al review recent advances in proteomics for risk prediction of diabetic kidney disease and describe applications of proteomics for assessing response to therapy. The use of proteomics in clinical practice is promising but many studies stagnate in the discovery phase and do not move through the biomarker pipeline to validation, let alone to clinical use. Enhanced interactions and collaborations between academia, industry and regulatory agencies are needed to implement proteomics in clinical practice, with the ultimate goal of interrupting diabetic kidney disease progression thus improving patient outcomes. [Text supplied by the authors.]

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Neonatal vitamin D status is not associated with later risk of type 1 diabetes: results from two large Danish population-based studies
by Ramune Jacobsen, Steffen U. Thorsen, Arieh S. Cohen, Marika Lundqvist, Peder Frederiksen, Christian B. Pipper, Flemming Pociot, Lau C. Thygesen, Alberto Ascherio, Jannet Svensson, Berit L. Heitmann

The role of vitamin D in pregnancy as a risk factor for developing type 1 diabetes has been a hot topic for the last decade. However, results have been conflicting and this field of research has been in need of well-powered studies. In this issue, Jacobsen et al describe results from two large population-based studies. They report that neonatal vitamin D3 levels were not associated with later risk of developing type 1 diabetes in childhood or adolescence. The authors state that they cannot exclude the possibility that higher levels of vitamin D3 during late pregnancy, e.g. gained through high-dose maternal supplementation, could be protective against type 1 diabetes. However, the findings from this study provide evidence to conclude that there is no relation between neonatal vitamin D3 levels and the risk of type 1 diabetes in childhood and adolescence. [Text supplied by the authors.]

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CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion
by Mia Abels, Matteo Riva, Hedvig Bennet, Emma Ahlqvist, Oleg Dyachok, Vini Nagaraj, Liliya Shcherbina, Rikard G. Fred, Wenny Poon, Maria Sörhede-Winzell, Joao Fadista, Andreas Lindqvist, Lena Kask, Ramasri Sathanoori, Marloes Dekker-Nitert, Michael J. Kuhar, Bo Ahrén, Claes B. Wollheim, Ola Hansson, Anders Tengholm, Malin Fex, Erik Renström, Leif Groop, Valeriya Lyssenko, Nils Wierup

Cocaine- and amphetamine-regulated transcript (CART) is mostly known as a hypothalamic regulator of food intake. Based on previous observations in rodents regarding CART expression in islets and the effects of CART on islet hormone secretion in vitro, the role of CART in human islets and on glucose homeostasis in vivo in mice required addressing. In this issue, Abels et al report that in response to hyperglycaemia CART is overexpressed in the islets of diabetic humans and rodent models of diabetes. CART increased insulin secretion in islets from diabetic and healthy individuals and reduced glucagon secretion in human islets and in vivo in mice. The authors suggest that in type 2 diabetes CART is upregulated as part of a defence system that is activated to overcome hyperglycaemia by means of increasing insulin and reducing glucagon secretion. Since CART increases insulin secretion in the islets of diabetic individuals, the findings from this research hold promise for CART-based drugs as a therapy for diabetes. This article is the subject of a commentary in this issue by Patrick Gilon. [Text supplied by the authors.]

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Inside this issue

Up front

Up front September 2016

Reviews

Coming of age: the artificial pancreas for type 1 diabetes
Hood Thabit, Roman Hovorka

Novel phenotypes of prediabetes?
Hans-Ulrich Häring

Proteomics for prediction of disease progression and response to therapy in diabetic kidney disease
Michelle J. Pena, Harald Mischak, Hiddo J. L. Heerspink

EASD symposia

Can we make a better beta cell?
Shanta J. Persaud

Sources of beta cells inside the pancreas
Sofie De Groef, Willem Staels, Naomi Van Gassen, Marie Lemper, Yixing Yuchi, Mozhdeh Sojoodi, Leen Bussche, Yves Heremans, Gunter Leuckx, Nico De Leu, Mark Van de Casteele, Luc Baeyens, Harry Heimberg

Targeting insulin-producing beta cells for regenerative therapy
Adriana Migliorini, Sara S. Roscioni, Heiko Lickert

MST1: a promising therapeutic target to restore functional beta cell mass in diabetes
Amin Ardestani, Kathrin Maedler

Commentaries

Can genetic evidence help us to understand the fetal origins of type 2 diabetes?
Rachel M. Freathy

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells
Patrick Gilon

Articles

Clinical Science and Care

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes
David Cherney, Søren S. Lund, Bruce A. Perkins, Per-Henrik Groop, Mark E. Cooper, Stefan Kaspers, Egon Pfarr, Hans J. Woerle, Maximilian von Eynatten

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Epidemiology

Neonatal vitamin D status is not associated with later risk of type 1 diabetes: results from two large Danish population-based studies
Ramune Jacobsen, Steffen U. Thorsen, Arieh S. Cohen, Marika Lundqvist, Peder Frederiksen, Christian B. Pipper, Flemming Pociot, Lau C. Thygesen, Alberto Ascherio, Jannet Svensson, Berit L. Heitmann

MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study
Christine von Toerne, Cornelia Huth, Tonia de las Heras Gala, Florian Kronenberg, Christian Herder, Wolfgang Koenig, Christa Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Michael Roden, Annette Peters, Barbara Thorand, Stefanie M. Hauck

The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis
Joshua J. Joseph, Justin B. Echouffo-Tcheugui, Mercedes R. Carnethon, Alain G. Bertoni, Christina M. Shay, Haitham M. Ahmed, Roger S. Blumenthal, Mary Cushman, Sherita H. Golden

Copeptin and the risk of incident stroke, CHD and cardiovascular mortality in older men with and without diabetes: The British Regional Heart Study
S. Goya Wannamethee, Paul Welsh, Lucy Lennon, Olia Papacosta, Peter H. Whincup, Naveed Sattar

Prevalence of diabetic retinopathy in screening-detected diabetes mellitus: results from the Gutenberg Health Study (GHS)
Katharina A. Ponto, Jochem Koenig, Tunde Peto, Julia Lamparter, Philipp Raum, Philipp S. Wild, Karl J. Lackner, Norbert Pfeiffer, Alireza Mirshahi

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Genetics

Low birthweight and risk of type 2 diabetes: a Mendelian randomisation study
Tiange Wang, Tao Huang, Yanping Li, Yan Zheng, JoAnn E. Manson, Frank B. Hu, Lu Qi

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Islet Studies

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion
Mia Abels, Matteo Riva, Hedvig Bennet, Emma Ahlqvist, Oleg Dyachok, Vini Nagaraj, Liliya Shcherbina, Rikard G. Fred, Wenny Poon, Maria Sörhede-Winzell, Joao Fadista, Andreas Lindqvist, Lena Kask, Ramasri Sathanoori, Marloes Dekker-Nitert, Michael J. Kuhar, Bo Ahrén, Claes B. Wollheim, Ola Hansson, Anders Tengholm, Malin Fex, Erik Renström, Leif Groop, Valeriya Lyssenko, Nils Wierup

Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production
Francesca Semplici, Angeles Mondragon, Benedict Macintyre, Katja Madeyski-Bengston, Anette Persson-Kry, Sara Barr, Anna Ramne, Anna Marley, James McGinty, Paul French, Helen Soedling, Ryohsuke Yokosuka, Julien Gaitan, Jochen Lang, Stephanie Migrenne-Li, Erwann Philippe, Pedro L. Herrera, Christophe Magnan, Gabriela da Silva Xavier, Guy A. Rutter

A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia
Marie Lemper, Sofie De Groef, Geert Stangé, Luc Baeyens, Harry Heimberg

RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice
Kui Zhai, Lei Gu, Zhiguang Yang, Yang Mao, Meng Jin, Yan Chang, Qi Yuan, Veronique Leblais, Huiwen Wang, Rodolphe Fischmeister, Guangju Ji

Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes
Short Communication
Lina Carlbom, Daniel Espes, Mark Lubberink, Olof Eriksson, Lars Johansson, Leif Jansson, Olle Korsgren, Håkan Ahlström, Per-Ola Carlsson

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Immunology and Transplantation

Tetraspanin 7 autoantibodies in type 1 diabetes
Short Communication
Denise Walther, Anne Eugster, Sibille Jergens, Anita Gavrisan, Christina Weinzierl, Tanja Telieps, Christiane Winkler, Anette G. Ziegler, Ezio Bonifacio

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Metabolism

In vivo PET imaging with [18F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes
Blake J. Cochran, William J. Ryder, Arvind Parmar, Shudi Tang, Anthonin Reilhac, Andrew Arthur, Arnaud Charil, Hasar Hamze, Philip J. Barter, Leonard Kritharides, Steven R. Meikle, Marie-Claude Gregoire, Kerry-Anne Rye

Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes
Ana Temprano, Hiroshi Sembongi, Gil-Soo Han, David Sebastián, Jordi Capellades, Cristóbal Moreno, Juan Guardiola, Martin Wabitsch, Cristóbal Richart, Oscar Yanes, Antonio Zorzano, George M. Carman, Symeon Siniossoglou, Merce Miranda

Adipocyte-specific deletion of mTOR inhibits adipose tissue development and causes insulin resistance in mice
Tizhong Shan, Pengpeng Zhang, Qinyang Jiang, Yan Xiong, Yizhen Wang, Shihuan Kuang

Treatment of diet-induced lipodystrophic C57BL/6J mice with long-acting PASylated leptin normalises insulin sensitivity and hepatic steatosis by promoting lipid utilisation
Florian Bolze, Andrea Bast, Sabine Mocek, Volker Morath, Detian Yuan, Nadine Rink, Martin Schlapschy, Anika Zimmermann, Mathias Heikenwalder, Arne Skerra, Martin Klingenspor

Energy restriction and Roux-en-Y gastric bypass reduce postprandial a-dicarbonyl stress in obese women with type 2 diabetes
Short Communication
Dionne E. Maessen, Nordin M. Hanssen, Mirjam A. Lips, Jean L. Scheijen, Ko Willems van Dijk, Hanno Pijl, Coen D. Stehouwer, Casper G. Schalkwijk

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Pathophysiology and Complications

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

Extravascular modified lipoproteins: a role in the propagation of diabetic retinopathy in a mouse model of type 1 diabetes
Jeremy Y. Yu, Mei Du, Michael H. Elliott, Mingyuan Wu, Dongxu Fu, Shihe Yang, Arpita Basu, Xiaowu Gu, Jian-Xing Ma, Christopher E. Aston, Timothy J. Lyons

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Research Letter

Dapagliflozin reduces albuminuria over 2 years in patients with type 2 diabetes mellitus and renal impairment
Paola Fioretto, Bergur V. Stefansson, Eva Johnsson, Valerie A. Cain, C. David Sjöström

Letters

Diabetes remission off medications is not a suitable endpoint for comparing bariatric/metabolic surgery with pharmacotherapy
Bruno Halpern, Cintia Cercato, Marcio C. Mancini

Diabetes remission off medications is not a suitable endpoint for comparing bariatric/metabolic surgery with pharmacotherapy. Reply to Halpern B, Cercato C, Mancini MC [letter]
David E. Cummings

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