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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

People with low birthweight due to genetic factors are more likely to develop type 2 diabetes

Read this new research by Dr Tiange Wang, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA, and colleagues.
For further information contact Dr Wang (tiwang@hsph.harvard.edu) or Dr Lu Qi (lqi1@tulane.edu)

Mouse model suggests possible new link between diabetes and Alzheimer's disease

Read this new research by Professor Bettina Platt and Professor Mirela Delibegovic (University of Aberdeen Institute of Medical Sciendes) and colleagues.
Press release issued by the University of Aberdeen: for further information contact Dr Wendy Skene, Communications Officer (w.skene@abdn.ac.uk).

Current issue: July 2016

July 2016 cover

Click here to view this month's contents

The cover picture shows a section of embryonic mouse pancreas (E15.5) stained with antibodies labelling the epithelial cell membrane in green (anti-E-cadherin) and antibodies raised against PW1/PEG3, which label the nuclei in red. In the present issue of Diabetologia, Sojoodi et al report that PW1/PEG3 is a co-regulator of the beta cell cycle.


Cover credit: P. Bonfanti, Vrije Universiteit Brussel, University College London; L. Stradiot and H. Heimberg, Vrije Universiteit Brussel

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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


SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?
by Naveed Sattar, James McLaren, Søren L. Kristensen, David Preiss, John J. McMurray

The 30–40% reductions in hospitalisation for heart failure, cardiovascular mortality and total mortality yielded by empagliflozin treatment in the placebo-controlled EMPA-REG Outcomes trial took the research community by surprise. This pattern of benefit and its rapid emergence, along with the lack of clear reductions in myocardial infarction or stroke, point towards non-atherothrombotic mechanisms. In a review in this issue, Sattar et al argue that the beneficial effects of empagliflozin are likely to stem from its corrective actions on the abnormal renal glucose and sodium handling, along with the intraglomerular hypertension, which occur in type 2 diabetes. The authors explain how these actions reduce the development and progression of heart failure via improvements in cardiac function and speculate which other groups of patients may benefit from the sodium-glucose linked transporter-2 (SGLT2) inhibitor class of glucose-lowering therapy. Finally, the authors suggest that the EMPA-REG Outcome trial findings highlight our limited appreciation of the marked risk for developing heart failure in many patients with type 2 diabetes. [Text supplied by the authors.]

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In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use
by Olof Eriksson, Maren Laughlin, Maarten Brom, Pirjo Nuutila, Michael Roden, Albert Hwa, Riccardo Bonadonna, Martin Gotthardt

Beta cell dysfunction and death are presumed to be central events in the pathogenesis of type 1 and type 2 diabetes in humans, but until recently there have been few direct observations regarding the fate of beta cells during the course of disease. In this issue, Eriksson and colleagues review recent advances in beta cell imaging by radiolabelled ligands (radiotracers). During the last decade, the non-invasive imaging technologies positron emission tomography (PET) and single photon emission computed tomography (SPECT) have been applied to the direct in situ radiolabelling of beta cells, potentially permitting repeated measurements of beta cell mass in humans. Preclinical and clinical data indicate that the scientific community now has access to several radiolabelled ligands with variable but high specificity for human beta cells. Further clinical validation of these imaging biomarkers may improve our understanding of the natural history of the human beta cell and its fate in diabetes. [Text supplied by the authors.]

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Islet-intrinsic effects of CFTR mutation
by Fiona N. Manderson Koivula, Neville H. McClenaghan, Alan G. S. Harper, Catriona Kelly

Cystic fibrosis (CF) is primarily associated with lung disease, which is the main cause of morbidity and mortality in this genetic condition and arises as a result of chronic/recurring lung infections. However, diabetes is the most common extra-pulmonary comorbidity and presents significant problems to those with CF, since hyperglycaemia accelerates microbial colonisation and lung decline. In a review in this issue, Manderson Koivula et al present emerging evidence that mutations in the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR) that are responsible for CF development cause significant dysregulation of islet cell function, leading to altered glucose homeostasis and insulin secretion. The authors discuss recent research findings that support the view that CFTR deficiency or mutation has a negative impact on beta and islet cell function, highlighting the need for an enhanced understanding of the cellular mechanisms underlying the clinical development of CF-related diabetes in order to better treat the disease. [Text supplied by the authors.]

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Burden of diabetes in Australia: life expectancy and disability-free life expectancy in adults with diabetes
by Lili Huo, Jonathan E. Shaw, Evelyn Wong, Jessica L. Harding, Anna Peeters, Dianna J. Magliano

The rising prevalence of diabetes, together with improvements in the life expectancy of individuals with this condition, has prompted a greater emphasis to be placed on health-related quality of life. In this issue, using Australian national datasets for mortality (2011) and disability prevalence (2012), Huo et al report that the estimated loss of life expectancy of individuals with diabetes at age 50 years was approximately 3 years compared with their counterparts without diabetes. However, the corresponding estimated loss of disability-free life expectancy (DFLE) was much greater, at 8.2 years for men and 9.1 years for women. Women with diabetes spend more absolute years, and a larger proportion of their life with disability compared with men with diabetes and women without diabetes. The loss of DFLE in people with diabetes is likely to be multifactorial, and may include physical and cognitive impairment as well as traditional diabetes complications. Moving forward, efforts to identify the specific causes of disability may potentiate effective interventions for loss of DFLE in diabetes. [Text supplied by the authors.]

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Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank
by Wei Gan, Robin G. Walters, Michael V. Holmes, Fiona Bragg, Iona Y. Millwood, Karina Banasik, Yiping Chen, Huaidong Du, Andri Iona, Anubha Mahajan, Ling Yang, Zheng Bian, Yu Guo, Robert J. Clarke, Liming Li, Mark I. McCarthy, Zhengming Chen, on behalf of the China Kadoorie Biobank Collaborative Group

Over the past decade, researchers have used large-scale genetic studies to identify over 90 regions of the genome at which DNA sequence differences influence the risk that an individual will develop type 2 diabetes. However, most of these studies have been conducted in European individuals, and the designs used may have overestimated the size of these genetic effects. In this issue, Gan, Walters and colleagues report on the impact of 56 known diabetes risk variants on predisposition to type 2 diabetes in a prospective cohort study of 93,000 Chinese adults. Although many of these signals were first detected in Europeans, the results of this study demonstrate that most also influence diabetes risk in the Chinese population, albeit with somewhat lesser effects. These data establish shared patterns of genetic risk factors for diabetes in ethnically distinct populations, and will support ongoing research efforts to map the pathways responsible for diabetes development. This article is the subject of a commentary in this issue by Marco Dauriz and James Meigs. [Text supplied by the authors.]

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Inside this issue

Up front

Up front July 2016

Reviews

SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?
Naveed Sattar, James McLaren, Søren L. Kristensen, David Preiss, John J. McMurray

In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use
Olof Eriksson , Maren Laughlin, Maarten Brom, Pirjo Nuutila, Michael Roden, Albert Hwa, Riccardo Bonadonna, Martin Gotthardt

Islet-intrinsic effects of CFTR mutation
Fiona N. Manderson Koivula, Neville H. McClenaghan, Alan G. S. Harper, Catriona Kelly

Serotonin competence of mouse beta cells during pregnancy
Lotte Goyvaerts, Anica Schraenen, Frans Schuit

EASD symposia

An overview of glucagon research
Isabel Valverde

Glucagon action in the brain
Mona A. Abraham, Tony K. T. Lam

Glucagon is the key factor in the development of diabetes
Young H. Lee, May-Yun Wang, Xin-Xin Yu, Roger H. Unger

Glucagon: acute actions on hepatic metabolism
Russell A. Miller, Morris J. Birnbaum

Gestational diabetes: what’s up?
Kerstin E. Berntorp

Risk factors for gestational diabetes: is prevention possible?
Cuilin Zhang, Shristi Rawal, Yap Seng Chong

Is it worth treating gestational diabetes: if so, when and how?
Marja Vääräsmäki

Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark
Peter Damm, Azadeh Houshmand-Oeregaard, Louise Kelstrup, Jeannet Lauenborg, Elisabeth R. Mathiesen, Tine D. Clausen

Commentary

The power of numbers
Marco Dauriz, James B. Meigs

Articles

Systematic Reviews/Meta-analyses

Quantification of the type 2 diabetes risk in women with gestational diabetes: a systematic review and meta-analysis of 95,750 women
Girish Rayanagoudar, Amal A. Hashi, Javier Zamora, Khalid S. Khan, Graham A. Hitman, Shakila Thangaratinam

Clinical Science and Care

Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial
Lennart Tonneijck, Mark M. Smits, Marcel H. A. Muskiet, Trynke Hoekstra, Mark H. H. Kramer, A. H. Jan Danser, Michaela Diamant, Jaap A. Joles, Daniël H. van Raalte

Higher body fat percentage is associated with enhanced temperature perception in NAFLD: results from the randomised Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy trial (WELCOME) trial
Geraldine F. Clough, Keith G. McCormick, Eleonora Scorletti, Lokpal Bhatia, Philip C. Calder, Michael J. Griffin, Christopher D. Byrne

Neonatal diabetes caused by a homozygous KCNJ11 mutation demonstrates that tiny changes in ATP sensitivity markedly affect diabetes risk
Natascia Vedovato, Edward Cliff, Peter Proks, Varadarajan Poovazhagi, Sarah E. Flanagan, Sian Ellard, Andrew T. Hattersley, Frances M. Ashcroft

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Epidemiology

Burden of diabetes in Australia: life expectancy and disability-free life expectancy in adults with diabetes
Lili Huo, Jonathan E. Shaw, Evelyn Wong, Jessica L. Harding, Anna Peeters, Dianna J. Magliano

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Genetics

Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank
Wei Gan, Robin G. Walters, Michael V. Holmes, Fiona Bragg, Iona Y. Millwood, Karina Banasik, Yiping Chen, Huaidong Du, Andri Iona, Anubha Mahajan, Ling Yang, Zheng Bian, Yu Guo, Robert J. Clarke, Liming Li, Mark I. McCarthy, Zhengming Chen, on behalf of the China Kadoorie Biobank Collaborative Group

Impaired pancreatic beta cell compensatory function is the main cause of type 2 diabetes in individuals with high genetic risk: a 9 year prospective cohort study in the Chinese population
Jing Yan, Danfeng Peng, Feng Jiang, Rong Zhang, Miao Chen, Tao Wang, Dandan Yan, Shiyun Wang, Xuhong Hou, Yuqian Bao, Cheng Hu, Weiping Jia

Differential regulation of serum microRNA expression by HNF1β and HNF1α transcription factors
Wojciech Fendler, Joanna Madzio, Kamil Kozinski, Kashyap Patel, Justyna Janikiewicz, Magdalena Szopa, Adam Tracz, Maciej Borowiec, Przemyslawa Jarosz-Chobot, Malgorzata Mysliwiec, Agnieszka Szadkowska, Andrew T. Hattersley, Sian Ellard, Maciej T. Malecki, Agnieszka Dobrzyn, Wojciech Mlynarski

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Islet Studies

The zinc finger transcription factor PW1/PEG3 restrains murine beta cell cycling
Mozhdeh Sojoodi, Leslie Stradiot, Karo Tanaka, Yves Heremans, Gunter Leuckx, Vanessa Besson, Willem Staels, Mark Van de Casteele, Giovanna Marazzi, David Sassoon, Harry Heimberg, Paola Bonfanti

Autophagy is a major regulator of beta cell insulin homeostasis
Yael Riahi, Jakob D. Wikstrom, Etty Bachar-Wikstrom, Nava Polin, Hava Zucker, Myung-Shik Lee, Wenying Quan, Leena Haataja, Ming Liu, Peter Arvan, Erol Cerasi, Gil Leibowitz

Hypoxia reduces ER-to-Golgi protein trafficking and increases cell death by inhibiting the adaptive unfolded protein response in mouse beta cells
Mohammed Bensellam, Emma L. Maxwell, Jeng Yie Chan, Jude Luzuriaga, Phillip K. West, Jean-Christophe Jonas, Jenny E. Gunton, D. Ross Laybutt

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Metabolism

Inactivation of class II PI3K-C2α induces leptin resistance, age-dependent insulin resistance and obesity in male mice
Samira Alliouachene, Benoit Bilanges, Claire Chaussade, Wayne Pearce, Lazaros C. Foukas, Cheryl L. Scudamore, Larissa S. Moniz, Bart Vanhaesebroeck

Neuronal human BACE1 knockin induces systemic diabetes in mice
Kaja Plucinska, Ruta Dekeryte, David Koss, Kirsty Shearer, Nimesh Mody, Phillip D. Whitfield, Mary K. Doherty, Marco Mingarelli, Andy Welch, Gernot Riedel, Mirela Delibegovic, Bettina Platt

A decrease in hepatic microRNA-9 expression impairs gluconeogenesis by targeting FOXO1 in obese mice
Caifeng Yan, Jinfeng Chen, Min Li, Wenying Xuan, Dongming Su, Hui You, Yujie Huang, Nuoqi Chen, Xiubin Liang

Endogenous GIP ameliorates impairment of insulin secretion in proglucagon-deficient mice under moderate beta cell damage induced by streptozotocin
Atsushi Iida, Yusuke Seino, Ayako Fukami, Ryuya Maekawa, Daisuke Yabe, Shinobu Shimizu, Keita Kinoshita, Yusuke Takagi, Takako Izumoto, Hidetada Ogata, Kota Ishikawa, Nobuaki Ozaki, Shin Tsunekawa, Yoji Hamada, Yutaka Oiso, Hiroshi Arima, Yoshitaka Hayashi

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Pathophysiology and Complications

Prospective study on microangiopathy in type 2 diabetic foot ulcer
Fabio Fiordaliso, Giacomo Clerici, Serena Maggioni, Maurizio Caminiti, Cinzia Bisighini, Deborah Novelli, Daniela Minnella, Alessandro Corbelli, Riccardo Morisi, Alberto De Iaco, Ezio Faglia

Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria
Bernt Johan von Scholten, Henrik Reinhard, Tine W. Hansen, Jens Oellgaard, Hans-Henrik Parving, Peter K. Jacobsen, Peter Rossing

C66 ameliorates diabetic nephropathy in mice by both upregulating NRF2 function via increase in miR-200a and inhibiting miR-21
Hao Wu, Lili Kong, Yi Tan, Paul N. Epstein, Jun Zeng, Junlian Gu, Guang Liang, Maiying Kong, Xiangmei Chen, Lining Miao, Lu Cai

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Letters

The intriguing relationship between epilepsy and type 1 diabetes mellitus
Josemir W. Sander, Jan Novy, Mark R. Keezer

The intriguing relationship between epilepsy and type 1 diabetes mellitus. Reply to Sander JW, Novy J, Keezer MR [letter]
I-Ching Chou, Chia-Hung Kao

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Errata

Erratum to: SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms?
Naveed Sattar, James McLaren, Søren L. Kristensen, David Preiss, John J. McMurray

Erratum to: Autophagy is a major regulator of beta cell insulin homeostasis
Yael Riahi, Jakob D. Wikstrom, Etty Bachar-Wikstrom, Nava Polin, Hava Zucker, Myung-Shik Lee, Wenying Quan, Leena Haataja, Ming Liu, Peter Arvan, Erol Cerasi, Gil Leibowitz

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