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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: March 2016

March 2016 cover

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The cover picture shows a false-colour transmission electron micrograph of mammalian mitochondria (green) in cross-section. Mitochondria are remarkably plastic and dynamic organelles that interact with other subcellular organelles to regulate metabolism and intracellular signalling. In particular, mitochondria form physical interactions with the endoplasmic reticulum (ER) in order to exchange Ca2+ through the IP3R–GRP75–VDAC complex. Defects in structural ER–mitochondria interactions have been previously linked to hepatic insulin resistance. In the present issue of Diabetologia Rieusset et al report that Ca2+ transfer from ER to mitochondria is an essential cellular process involved in the control of hepatic insulin action. In particular, they show that disruption of IP3R-mediated Ca2+ signalling in the liver of CypD-knockout mice leads to hepatic insulin resistance, mainly by disrupting organelle crosstalk, increasing lipid accumulation and activating PKCε.


Cover credit: DR GOPAL MURTI/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


Blood-based signatures in type 1 diabetes
by Susanne M. Cabrera, Yi-Guang Chen, William A. Hagopian, Martin J. Hessner

Since the late 1990s there have been major developments in the fields of genetics, genomics, proteomics and computational biology. These advances have greatly enhanced our understanding of type 1 diabetes progression as well as non-progression among those with inherited risk. These tools also have the potential to inform the development of new biomarkers of disease risk and progression, as well as therapeutic responses. In this issue, Cabrera et al review blood-based signatures in type 1 diabetes, specifically summarising both direct transcriptomic analyses of whole blood and immunocyte subsets, and plasma/serum-induced transcriptional signatures. Proteomic analyses, microRNA assays and markers of beta cell death are also discussed. The findings of these blood-based profiling efforts are placed within the context of the genetic and environmental factors implicated in the natural history of autoimmune diabetes.

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Metformin and the gastrointestinal tract
by Laura J. McCreight, Clifford J. Bailey, Ewan R. Pearson

Metformin, as the first-line agent in the medical management of type 2 diabetes, is extensively prescribed on a global scale. However, the mechanism of action of metformin has yet to be fully elucidated, and inter-individual variability in tolerance and response is poorly understood. Current understanding suggests that metformin exerts its glucose-lowering effects predominantly via a reduction in hepatic glucose production. Yet, evidence is mounting in support of the gastrointestinal tract playing an important role in metformin response and tolerance—metformin may even exert a pre-absorptive effect on glycaemia. In this issue, McCreight et al summarise the evidence regarding metformin's complex relationship with the gastrointestinal tract (including its effect on incretin hormones, bile acids and the microbiome), and argue that further research into this relationship is key to our understanding of metformin.

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Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study
by Alaitz Poveda, Robert W. Koivula, Shafqat Ahmad, Inês Barroso, Göran Hallmans, Ingegerd Johansson, Frida Renström, Paul W. Franks

Type 2 diabetes is caused by unhealthy lifestyles set against the backdrop of genetic susceptibility. Diabetes prediction algorithms usually include intermediate biomarkers of diabetes that are consequences of poor lifestyle and genetic predisposition, but not the primordial risk factors themselves. In this issue, Poveda et al used a prospective study of a Swedish cohort to assess the predictive ability of genetic and self-reported lifestyle information for the development of type 2 diabetes 10 years later. They found that models including established common genetic variants and lifestyle risk factors, respectively, had similar predictive accuracy; the combined model was superior to either component model and yielded a clinically relevant level of predictive accuracy. These findings may be informative for the long-term prediction of type 2 diabetes for the purpose of preventive intervention, particularly when biochemical risk markers are unavailable.

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Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets
by Ionel Sandovici, Constanze M. Hammerle, Wendy N. Cooper, Noel H. Smith, L. Tarry-Adkins, Benjamin J. Dunmore, Julien Bauer, Simon R. Andrews, Giles S. H. Yeo, Susan E. Ozanne, Miguel Constância

Type 2 diabetes prevalence increases with age and is associated with progressive failure of pancreatic islets. The cellular and molecular mechanisms underlying this age-associated decline in islet function are poorly understood. In this issue, Sandovici et al provide evidence that islet ageing is associated with inflammation and cellular senescence. Using genome-wide technology, they compared mRNA expression in islets from young and aged rats and demonstrated that expression of genes related to inflammation and fibrosis increased with age. Some of these expression changes could be explained by alterations in DNA methylation. Consistent with these molecular signatures, aged animals displayed macrophage infiltration and altered endocrine cell ratios. These findings identify genetic, epigenetic and cellular signatures that may explain age-associated decline in islet function and consequently increased risk of type 2 diabetes. They point towards inflammation being a key triggering event and thus an important therapeutic target.

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The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes
by Polly J. Bingley, David C. Boulware, Jeffrey P. Krischer, the Type 1 Diabetes TrialNet Study Group

Islet autoantibodies are the best validated markers of an ongoing autoimmune process and allow accurate prediction of type 1 diabetes. The development of multiple islet autoantibodies seems to represent a 'point of no return' in the disease process. This generally occurs in early childhood, but some individuals with autoantibodies to a single antigen develop further autoantibodies after this age. The characteristics of this later progression are, however, unknown. In this issue, Bingley and colleagues report findings from a large cohort of single antibody positive relatives (median age 16 years). The cumulative risk of developing additional antibodies within 5 years was 22%, with high risk of subsequent diabetes. This progression of islet autoimmunity in late childhood/adulthood was associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. The authors conclude that this evidence of heterogeneity in the disease process has potentially important implications for type 1 diabetes prevention.

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Inside this issue

Up front

Up front March 2016

EASD symposia

Gastrointestinal autonomic neuropathy in diabetes: the unattended borderline between diabetology and gastroenterology
Péter Kempler, Tamás Várkonyi, Anna E. Körei, Viktor J. Horváth

Diabetic neuropathy in the gut: pathogenesis and diagnosis
Fernando Azpiroz, Carolina Malagelada

Treatment of gastrointestinal autonomic neuropathy
Hans Törnblom

Reviews

Blood-based signatures in type 1 diabetes
Susanne M. Cabrera, Yi-Guang Chen, William A. Hagopian, Martin J. Hessner

Metformin and the gastrointestinal tract
Laura J. McCreight, Clifford J. Bailey, Ewan R. Pearson

Articles

Clinical Science and Care

The cost-effectiveness of screening for gestational diabetes mellitus in primary and secondary care in the Republic of Ireland
Andriy Danyliv, Paddy Gillespie, Ciaran O’Neill, Marie Tierney, Angela O’Dea, Brian E. McGuire, Liam G. Glynn, Fidelma P. Dunne

Random plasma glucose in early pregnancy is a better predictor of gestational diabetes diagnosis than maternal obesity
Claire L. Meek, Helen R. Murphy, David Simmons

Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial
Hitoshi Kuwata, Masahiro Iwasaki, Shinobu Shimizu, Kohtaro Minami, Haruyo Maeda, Susumu Seino, Koji Nakada, Chihiro Nosaka, Kenta Murotani, Takeshi Kurose, Yutaka Seino, Daisuke Yabe

Innate biology versus lifestyle behaviour in the aetiology of obesity and type 2 diabetes: the GLACIER Study
Alaitz Poveda, Robert W. Koivula, Shafqat Ahmad, Inês Barroso, Göran Hallmans, Ingegerd Johansson, Frida Renström, Paul W. Franks

Age at menarche and the risk of diabetic microvascular complications in patients with type 1 diabetes
Valma Harjutsalo, Christine Maric-Bilkan, Carol Forsblom, Per-Henrik Groop, on behalf of the FinnDiane Study Group

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Genetics

Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians
Anup K. Nair, Paolo Piaggi, Nellie A. McLean, Manmeet Kaur, Sayuko Kobes, William C. Knowler, Clifton Bogardus, Robert L. Hanson, Leslie J. Baier

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Islet Studies

Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes
Lars Krogvold, Anna Wiberg, Bjørn Edwin, Trond Buanes, Frode Lars Jahnsen, Kristian F. Hanssen, Erik Larsson, Olle Korsgren, Oskar Skog, Knut Dahl-Jørgensen

Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets
Ionel Sandovici, Constanze M. Hammerle, Wendy N. Cooper, Noel H. Smith, Jane L. Tarry-Adkins, Benjamin J. Dunmore, Julien Bauer, Simon R. Andrews, Giles S. H. Yeo, Susan E. Ozanne, Miguel Constância

The non-canonical NF-κB pathway is induced by cytokines in pancreatic beta cells and contributes to cell death and proinflammatory responses in vitro
Kira Meyerovich, Makiko Fukaya, Leticia F. Terra, Fernanda Ortis, Decio L. Eizirik, Alessandra K. Cardozo

Hyperglycaemia attenuates in vivo reprogramming of pancreatic exocrine cells to beta cells in mice
Claudia Cavelti-Weder, Weida Li, Adrian Zumsteg, Marianne Stemann-Andersen, Yuemei Zhang, Takatsugu Yamada, Max Wang, Jiaqi Lu, Agnes Jermendy, Yong Mong Bee, Susan Bonner-Weir, Gordon C. Weir, Qiao Zhou

Pancreatic glucose-dependent insulinotropic polypeptide (GIP) (1–30) expression is upregulated in diabetes and PEGylated GIP(1–30) can suppress the progression of low-dose-STZ-induced hyperglycaemia in mice
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Kuralay K. Atageldiyeva, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J. Kieffer, Masakazu Haneda

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Immunology and Transplantation

The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes
Polly J. Bingley, David C. Boulware, Jeffrey P. Krischer, the Type 1 Diabetes TrialNet Study Group

Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging
Corinne Berclaz, Anja Schmidt-Christensen, Daniel Szlag, Jerome Extermann, Lisbeth Hansen, Arno Bouwens, Martin Villiger, Joan Goulley, Frans Schuit, Anne Grapin-Botton, Theo Lasser, Dan Holmberg

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Metabolism

Increased fat cell size: a major phenotype of subcutaneous white adipose tissue in non-obese individuals with type 2 diabetes
Juan R. Acosta, Iyadh Douagi, Daniel P. Andersson, Jesper Bäckdahl, Mikael Rydén, Peter Arner, Jurga Laurencikiene

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice
Jin Woo Choi, Anna Jo, Min Kim, Ho Seon Park, Sung Soo Chung, Shinae Kang , Kyong Soo Park

The PARsylation activity of tankyrase in adipose tissue modulates systemic glucose metabolism in mice
Linlin Zhong, Yun Ding, Gautam Bandyopadhyay, Jo Waaler, Emma Börgeson, Susan Smith, Mingchen Zhang, Susan A. Phillips, Sepi Mahooti, Sushil K. Mahata, Jianhua Shao, Stefan Krauss, Nai-Wen Chi

Pharmacological inhibition of S6K1 increases glucose metabolism and Akt signalling in vitro and in diet-induced obese mice
Michael Shum, Kerstin Bellmann, Philippe St-Pierre, André Marette

Adipose-derived lipocalin 14 alleviates hyperglycaemia by suppressing both adipocyte glycerol efflux and hepatic gluconeogenesis in mice
Jimmy Tsz Hang Lee, Zhe Huang, Kewu Pan, Herbert Jialiang Zhang, Connie Waihong Woo, Aimin Xu, Chi-Ming Wong

Disruption of calcium transfer from ER to mitochondria links alterations of mitochondria-associated ER membrane integrity to hepatic insulin resistance
Jennifer Rieusset, Jeremy Fauconnier, Melanie Paillard, Elise Belaidi, Emily Tubbs, Marie-Agnès Chauvin, Annie Durand, Amélie Bravard, Geoffrey Teixeira, Birke Bartosch, Maud Michelet, Pierre Theurey, Guillaume Vial, Marie Demion, Emilie Blond, Fabien Zoulim, Ludovic Gomez, Hubert Vidal, Alain Lacampagne, Michel Ovize

Muscle-specific inflammation induced by MCP-1 overexpression does not affect whole-body insulin sensitivity in mice
Inkie J. A. Evers-van Gogh, Antwi-Boasiako Oteng, Sheril Alex, Nicole Hamers, Milene Catoire, Rinke Stienstra, Eric Kalkhoven, Sander Kersten

LXRα improves myocardial glucose tolerance and reduces cardiac hypertrophy in a mouse model of obesity-induced type 2 diabetes
Megan V. Cannon, Herman H. W. Silljé, Jürgen W. A. Sijbesma, Mohsin A. F. Khan, Knut R. Steffensen, Wiek H. van Gilst, Rudolf A. de Boer

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Pathophysiology and Complications

miR-23b-3p induces the cellular metabolic memory of high glucose in diabetic retinopathy through a SIRT1-dependent signalling pathway
Shuzhi Zhao, Tao Li, Jun Li, Qianyi Lu, Changjing Han, Na Wang, Qinghua Qiu, Hui Cao, Xun Xu, Haibing Chen, Zhi Zheng

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Retraction Note

Retraction Note: Abstracts of 51st EASD Annual Meeting
J. Pereira, S. Oliveira, I. Tavares, C. Morgado

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