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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

20-year study shows that higher levels of fitness reduce the risk of developing of diabetes and pre-diabetes

Read this new research by Dr Lisa Chow, University of Minnesota, Minnesota, USA, and colleagues.
For further information contact Dr Chow (chow0007@umn.edu).

Current issue: June 2016

June 2016 cover

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The cover picture shows evidence for compound exocytosis in a beta cell from a prediabetic db/db mouse that was stimulated with 15 mmol/l glucose. The image was produced by serial block-face scanning electron microscopy and shows a single image plane from a three-dimensional (3D) stack. Superimposed is a 3D cartoon reconstruction of a chain of granules. The granules in the chain were identified as being fused with each other and one granule (in green) was fused with the cell membrane (shown as a mesh). In this issue of Diabetologia, Do et al report that compound exocytosis is upregulated in prediabetes, demonstrating that beta cell function is affected prior to the development of frank diabetes.


Cover credit: Oanh Hoang Do, Charles Perkins Centre, University of Sydney

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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 plasticity: how fat depots respond differently to pathophysiological cues
by Vanessa Pellegrinelli, Stefania Carobbio, Antonio Vidal-Puig

Evidence for the existence of thermogenically active brown fat/beige cells in adult humans has fuelled new research aiming to cure obesity and related metabolic disorders. Strategies relying upon differentiation and activation of brown/beige fat are believed to halt the lipotoxic overspill resulting from dysfunctional white fat in obesity. In a review in this issue, Pellegrinelli et al summarise the current understanding of the specific origins, development and remodelling of different fat depots under physiological and pathophysiological conditions. Visceral and subcutaneous white fat depots differ at the structural and functional levels, particularly concerning progenitor number, adipocyte size and expandability capacity. Studies have also shed light on white/brown progenitor origins by identifying adipose niches adjacent to the vasculature. The integration of these recent reports with the current understanding of the impact of fibro-inflammation on adipogenesis promises to identify new molecular pathways for targeted strategies to improve brown/white fat plasticity, activation and global metabolic homeostasis. [Text supplied by the authors.]

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The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy
by Gernot Desoye, Christopher J. Nolan

Despite intense efforts to achieve glycaemic control, frustratingly, macrosomia (excessive fetal growth) still commonly occurs in mothers with diabetes. In a review in this issue, Desoye and Nolan provide a potential explanation. They state that the fetus acts as a glucose sink that steals glucose from the mother. Importantly, this 'fetal glucose steal' effect can be exaggerated in diabetic pregnancy as a consequence of fetal hyperinsulinaemia and can occur even at times of maternal normoglycaemia. An exaggerated glucose steal will attenuate maternal hyperglycaemia, giving clinicians a false sense that all is well. For similar reasons, some mothers with fetuses suspected of being affected by diabetes late in pregnancy may have 'normal' glucose tolerance, a point in favour of early screening for gestational diabetes. To prevent an exaggerated glucose steal driven by fetal hyperinsulinaemia, the authors argue that tight glycaemic control from early in pregnancy is necessary. [Text supplied by the authors.]

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Recent trends in life expectancy for people with type 1 diabetes in Sweden
by Dennis Petrie, Tom W. C. Lung, Adin Rawshani, Andrew J. Palmer, Ann-Marie Svensson, Björn Eliasson, Philip Clarke

Life expectancy estimates for those with type 1 diabetes allow gaps between them and the general population to be identified and improvements to be quantified. In this issue, Petrie et al report the results of their study in which they used health records from the National Diabetes Register and linked these with death records to examine mortality in those with type 1 diabetes in Sweden between 2002 and 2011. They found that for men the remaining life expectancy at age 20 increased significantly by about 2 years (from 47.7 in 2002-06 to 49.7 years in 2007-11), but for women there was no significant change, with a life expectancy at age 20 of 51.7 years in 2002-06 and 51.9 years in 2007-11. Recent gains have come from reductions in cardiovascular mortality; however, these gains were also seen in the general population, which meant that the life expectancy gaps between people with type 1 diabetes and the general population have stayed at about 11 years for men and 12 years for women over the last decade. More needs to be done to close this gap. This article is the subject of a commentary in this issue by Lars Stene. [Text supplied by the authors.]

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Life expectancy of type 1 diabetic patients during 1997-2010: a national Australian registry-based cohort study
by Lili Huo, Jessica L. Harding, Anna Peeters, Jonathan E. Shaw, Dianna J. Magliano

There is limited information about the impact of type 1 diabetes on life expectancy in a contemporary population. In this issue, Huo et al report that Australians with type 1 diabetes had an estimated life loss of 11.6 years for men and 12.5 years for women compared with the general population. No narrowing of this gap was seen over a 7-year period. In addition to deaths from cardiovascular disease in older adults, deaths before the age of 60 years and mortality from endocrine and metabolic disease both contributed substantially to the years of life lost for type 1 diabetes. For improvements in life expectancy, greater attention must therefore be paid to both the acute metabolic and chronic cardiovascular complications of type 1 diabetes. A failure to address either one will continue to leave type 1 diabetic patients at risk of premature mortality. This article is the subject of a commentary in this issue by Lars Stene. [Text supplied by the authors.]

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Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes, respectively
by Andrew R. Wood, Jessica Tyrrell, Robin Beaumont, Samuel E. Jones, Marcus A. Tuke, Katherine S. Ruth, The GIANT consortium, Hanieh Yaghootkar, Rachel M. Freathy, Anna Murray, Timothy M. Frayling, Michael N. Weedon

Genome-wide association studies have identified hundreds of common genetic variants associated with diabetes and obesity. Most studies have tested additive effects, assuming that the risk of heterozygous individuals lies halfway between the two homozygous groups. Few studies have performed genome-wide analyses of dominant or recessive effects for common variants. In this issue, Wood et al analysed data from the UK Biobank on 119,688 individuals with measured BMI and 4,040 individuals with type 2 diabetes status. The authors tested for deviation from additive effects and showed that two common variants in CDKAL1 and FTO act partially recessively. These findings indicate that the large number of people carrying just one copy of the risk alleles at these loci are at little extra disease risk. The data also suggest that follow-up clinical or functional studies should focus on recessive mechanisms, and that non-additive effects of common variants only contribute a small amount to diabetes and obesity risk. [Text supplied by the authors.]

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Inside this issue

Up front

Up front June 2016

Reviews

Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues
Vanessa Pellegrinelli, Stefania Carobbio, Antonio Vidal-Puig

The fetal glucose steal: an underappreciated phenomenon in diabetic pregnancy
Gernot Desoye, Christopher J. Nolan

EASD symposia

The liver in focus
Michael Roden

Hepatic glucose and lipid metabolism
John G. Jones

Diagnosis of non-alcoholic fatty liver disease (NAFLD)
Hannele Yki-Järvinen

Treatment of patients with type 2 diabetes and non-alcoholic fatty liver disease: current approaches and future directions
Kenneth Cusi

Guidelines

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO)

Commentaries

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease: is universal screening appropriate?
Christopher D. Byrne, Giovanni Targher

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease: disease mongering or call to action?
Elisabetta Bugianesi

EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease: guidelines, clinical reality and health economic aspects
Hermann Toplak, Rudolf Stauber, Harald Sourij

Gaps in life expectancy for people with type 1 diabetes
Lars C. Stene

Articles

Clinical Science and Care

Antithymocyte globulin therapy for patients with recent-onset type 1 diabetes: 2 year results of a randomised trial
Stephen E. Gitelman, Peter A. Gottlieb, Eric I. Felner, Steven M. Willi, Lynda K. Fisher, Antoinette Moran, Michael Gottschalk, Wayne V. Moore, Ashley Pinckney, Lynette Keyes-Elstein, Kristina M. Harris, Sai Kanaparthi, Deborah Phippard, Linna Ding, Jeffrey A. Bluestone, Mario R. Ehlers, the ITN START Study Team

Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes
Short Communication
Tarig Babiker, Natascia Vedovato, Kashyap Patel, Nicholas Thomas, Roisin Finn, Roope Männikkö, Ali J. Chakera, Sarah E. Flanagan, Maggie H. Shepherd, Sian Ellard, Frances M. Ashcroft, Andrew T. Hattersley

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Epidemiology

Recent trends in life expectancy for people with type 1 diabetes in Sweden
Dennis Petrie, Tom W. C. Lung, Aidin Rawshani, Andrew J. Palmer, Ann-Marie Svensson, Björn Eliasson, Philip Clarke

Life expectancy of type 1 diabetic patients during 1997–2010: a national Australian registry-based cohort study
Lili Huo, Jessica L. Harding, Anna Peeters, Jonathan E. Shaw, Dianna J. Magliano

The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants
Farah A. Meah, Linda A. DiMeglio, Carla J. Greenbaum, Janice S. Blum, Jay M. Sosenko, Alberto Pugliese, Susan Geyer, Ping Xu, Carmella Evans-Molina, for the Type 1 Diabetes TrialNet Study Group

Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study
I-Ching Chou, Chung-Hsing Wang, Wei-De Lin, Fuu-Jen Tsai, Che-Chen Lin, Chia-Hung Kao

Egg consumption and risk of type 2 diabetes: a prospective study and dose–response meta-analysis
Alice Wallin, Nita G. Forouhi, Alicja Wolk, Susanna C. Larsson

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Genetics

Variants in the FTO and CDKAL1 loci have recessive effects on risk of obesity and type 2 diabetes, respectively
Andrew R. Wood, Jessica Tyrrell, Robin Beaumont, Samuel E. Jones, Marcus A. Tuke, Katherine S. Ruth, The GIANT consortium, Hanieh Yaghootkar, Rachel M. Freathy, Anna Murray, Timothy M. Frayling, Michael N. Weedon

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Islet Studies

Changes in beta cell function occur in prediabetes and early disease in the Lepr db mouse model of diabetes
Oanh H. Do, Jenny E. Gunton, Herbert Y. Gaisano, Peter Thorn

Extreme obesity induces massive beta cell expansion in mice through self-renewal and does not alter the beta cell lineage
Aaron R. Cox, Carol J. Lam, Matthew M. Rankin, Kourtney A. King, Pan Chen, Ramon Martinez, Changhong Li, Jake A. Kushner

ABCA1 deficiency and cellular cholesterol accumulation increases islet amyloidogenesis in mice
Short Communication
Nadeeja Wijesekara, Achint Kaur, Clara Westwell-Roper, Dominika Nackiewicz, Galina Soukhatcheva, Michael R. Hayden, C. Bruce Verchere

Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway
Huimin Lu, Liuyi Hao, Songtao Li, Song Lin, Lin Lv, Yang Chen, Hongli Cui, Tianqi Zi, Xia Chu, Lixin Na, Changhao Sun

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Metabolism

A short leucocyte telomere length is associated with development of insulin resistance
Simon Verhulst, Christine Dalgård, Carlos Labat, Jeremy D. Kark, Masayuki Kimura, Kaare Christensen, Simon Toupance, Abraham Aviv, Kirsten O. Kyvik, Athanase Benetos

Cell-autonomous programming of rat adipose tissue insulin signalling proteins by maternal nutrition
Malgorzata S. Martin-Gronert, Denise S. Fernandez-Twinn, Martin Bushell, Kenneth Siddle, Susan E. Ozanne

Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-γ and PPAR-α agonists on carbohydrate and lipid metabolism in db/db and diet-induced obese mice
Li Feng, Huan Luo, Zhijian Xu, Zhuo Yang, Guoxin Du, Yu Zhang, Lijing Yu, Kaifeng Hu, Weiliang Zhu, Qingchun Tong, Kaixian Chen, Fujiang Guo, Cheng Huang, Yiming Li

O-GlcNAcase deficiency suppresses skeletal myogenesis and insulin sensitivity in mice through the modulation of mitochondrial homeostasis
Xun Wang, Zhihui Feng, Xueqiang Wang, Liang Yang, Shujun Han, Ke Cao, Jie Xu, Lin Zhao, Yong Zhang, Jiankang Liu

Pathophysiology and Complications

Transcriptional networks of murine diabetic peripheral neuropathy and nephropathy: common and distinct gene expression patterns
Junguk Hur, Phillipe D. O’Brien, Viji Nair, Lucy M. Hinder, Brett A. McGregor, Hosagrahar V. Jagadish, Matthias Kretzler, Frank C. Brosius III, Eva L. Feldman

A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity
Munehiro Kitada, Yoshio Ogura, Taeko Suzuki, Shi Sen, Seon Myeong Lee, Keizo Kanasaki, Shinji Kume, Daisuke Koya

PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes
Ramzi Hassouneh, Rania Nasrallah, Joe Zimpelmann, Alex Gutsol, David Eckert, Jamie Ghossein, Kevin D. Burns, Richard L. Hébert

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Erratum

Erratum to: Low-energy diets differing in fibre, red meat and coffee intake equally improve insulin sensitivity in type 2 diabetes: a randomised feasibility trial
Bettina Nowotny, Lejla Zahiragic, Alessandra Bierwagen, Stefan Kabisch, Jan B. Groener, Peter J. Nowotny, Ann Kristin Fleitmann, Parnian Firouzi, Christian Herder, Giovanni Pacini, Iris Erlund, Rikard Landberg, Hans-Ulrich Haering, Andreas F. H. Pfeiffer, Peter P. Nawroth, Michael Roden

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