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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.

Statement of Principle

Joint Statement of Principle from the EASD, ADA, AACE and TES (November 2014)

In the News

Study links insulin resistance with language problems in women

Download this new research by Dr Laura Ekblad, University of Turku and Turku University Hospital, Finland, and colleagues.
For further information contact Dr Ekblad (llekbl@utu.fi).


(posted online 22.01 h BST Wednesday 12th August 2015)

Physical activity attenuates the mid-adolescent peak in insulin resistance but by late adolescence the effect is lost: a longitudinal study with annual measures from 9-16 years (EarlyBird 66)

Download this new research by Brad Metcalf, Institute of Health Research, University of Exeter Medical School, Exeter, UK, and colleagues at the University of Exeter, Exeter, UK and Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
For further information contact Brad Metcalf (b.metcalf@exeter.ac.uk).


(posted online 09.00 h BST Thursday 6th August 2015)

Current issue: September 2015

September 2015 cover

Click here to view this month's contents

The cover picture shows a coloured scanning electron micrograph of podocytes with interdigitated foot processes in a glomerulus. Diabetic nephropathy is characterised by the accumulation of extracellular matrix, caused in part by connective tissue growth factor (CTGF), although the mechanisms involved remain elusive. In the present issue of Diabetologia, Koga et al provide evidence from human and mouse studies that miR-26a targets the CTGF gene, attenuating TGF-β/SMAD signalling, revealing a novel mechanism for the progression of diabetic nephropathy.

Cover credit: STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY

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Up front

Juleen Zierath

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. Juleen R. Zierath, Editor


The hitchhiker's guide to PGC-1α isoform structure and biological functions
by Vicente Martínez-Redondo, Amanda T. Pettersson, Jorge L. Ruas

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) proteins are highly regulated transcriptional coactivators that coordinate physiological adaptations in many tissues, usually in response to demands for higher nutrient and energy supply. In this issue, Martínez-Redondo and colleagues review how the biological actions of PGC-1α are mediated by several coactivator variants that are generated by alternative promoter usage and splicing of a single PGC-1α gene. These isoforms have differential regulation and tissue distribution and, most importantly, exert specific biological functions. However, the partial structural and functional overlap between PGC-1α transcripts and proteins creates challenges in the specific detection and identification of the different isoforms. This review discusses strategies to circumvent these obstacles and provides an integrated view of the PGC-1α system of transcriptional coactivators. [Text supplied by the authors.]

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Diagnosis of gestational diabetes mellitus: falling through the net
by Claire L. Meek, Hannah B. Lewis, Charlotte Patient, Helen R. Murphy, David Simmons

The National Institute for Health and Care Excellence (NICE) in the UK recently introduced new diagnostic criteria for gestational diabetes that differ from the WHO 2013 recommendations. In this issue, Meek and colleagues at the University of Cambridge, UK, report on a study in which they compared obstetric and neonatal outcomes using the two criteria in 25,543 women who delivered at The Rosie Hospital in 2004-2008. The authors found that using the WHO 2013 criteria would have diagnosed 126 more women with gestational diabetes than the NICE 2015 criteria over 5 years. However, these 126 women (0.5% of pregnancies) were at disproportionately high risk of adverse pregnancy outcomes such a pre-eclampsia, polyhydramnios and Caesarean section, and their babies had higher rates of macrosomia and large for gestational age. The authors conclude that the WHO 2013 criteria identify women at substantial risk of hyperglycaemia-associated pregnancy complications who would not be identified using the NICE 2015 criteria. This article is the subject of a commentary in this issue by Rudy Bilous. [Text supplied by the authors.]

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Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young
by Molly M. Lamb, Brittni Frederiksen, Jennifer A. Seifert, Miranda Kroehl, Marian Rewers, Jill M. Norris

While the role of sugar intake in type 2 diabetes aetiology has been well defined, the influence of sugar intake on type 1 diabetes development is not yet understood. In this issue, Lamb et al analysed data from the Diabetes Autoimmunity Study in the Young (DAISY) cohort, and found that a higher sugar intake may increase the rate at which children with islet autoimmunity progress to type 1 diabetes. Furthermore, increased sugar-sweetened beverage intake was associated with more rapid type 1 diabetes development only among those children with islet autoimmunity with the highest genetic risk of developing type 1 diabetes. This study provides evidence that increased sugar intake may speed up the latter stage of the type 1 diabetes development process, and genes may interact with dietary factors to exacerbate this risk. The results suggest that dietary changes could potentially delay or prevent the development of type 1 diabetes in children with islet autoimmunity. [Text supplied by the authors.]

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The subcellular distribution of cyclin-D1 and cyclin-D3 within human islet cells varies according to the status of the pancreas donor
by Kazuto Taniguchi, Mark A. Russell, Sarah J. Richardson, Noel G. Morgan

Beta cell proliferation occurs only rarely after the postnatal period in humans. This may be due to the distribution of key cell cycle regulators, which, unusually, are cytoplasmic rather than nuclear in human islet cells. However, in this issue, Taniguchi et al report that the subcellular localisation of two such proteins, cyclin-D1 and cyclin-D3, is more variable than previously thought. Localisation was predominantly cytosolic in pancreases collected post mortem, whereas it was nuclear in tissue recovered from heart-beating organ donors. This suggests that the distribution of cell cycle regulators can change with tissue status in human islets and that caution is required when studying the localisation of these proteins. Importantly, the unexpected finding that cyclin-D1 and cyclin-D3 may reside in the nucleus of islet cells in situ raises the possibility that enhanced beta cell proliferation might be an achievable therapeutic goal. [Text supplied by the authors.]

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Contribution of brown adipose tissue activity to the control of energy balance by GLP-1 receptor signalling in mice
by Kristy M. Heppner, Sarah Marks, Jenna Holland, Nickki Ottaway, David Smiley, Richard Dimarchi, Diego Perez-Tilve

Glucagon-like peptide-1 receptor (GLP-1R) agonists, including liraglutide, improve glycaemic control and reduce body weight in animal models and humans. This weight loss is due to both reduced energy intake and food intake-independent mechanisms. One such proposed mechanism is increased brown adipose tissue (BAT) thermogenesis by GLP-1R signalling in the brain. In this issue, Heppner and colleagues combine genetic loss and pharmacological gain of GLP-1R function in mice to reveal that, although endogenous GLP-1R signalling plays a role in the development of diet-induced thermogenesis, liraglutide-induced weight loss is not the result of increased BAT activity. These findings are consistent with the efficacy of GLP-1 mimetics lowering body weight in humans and animal models, in which BAT activity makes a moderate or minimal contribution to the control of energy balance, and highlight the importance of mechanisms susceptible to pharmacological manipulation, other than BAT activity, to the control of energy balance. [Text supplied by the authors.]

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Inside this issue

Commentary

Diagnosis of gestational diabetes, defining the net, refining the catch
Rudy Bilous

Reviews

The hitchhiker’s guide to PGC-1α isoform structure and biological functions
Vicente Martínez-Redondo, Amanda T. Pettersson, Jorge L. Ruas

Circulating microRNAs and diabetes: potential applications in medical practice
Juliette Raffort, Charlotte Hinault, Olivier Dumortier, Emmanuel Van Obberghen

Fructose and uric acid in diabetic nephropathy
Petter Bjornstad, Miguel A. Lanaspa, Takuji Ishimoto, Tomoki Kosugi, Shinji Kume, Diana Jalal, David M. Maahs, Janet K. Snell-Bergeon, Richard J. Johnson, Takahiko Nakagawa

Articles

Clinical Science and Care

Diagnosis of gestational diabetes mellitus: falling through the net
Claire L. Meek, Hannah B. Lewis, Charlotte Patient, Helen R. Murphy, David Simmons

Effects of insulin degludec and insulin glargine on day-to-day fasting plasma glucose variability in individuals with type 1 diabetes: a multicentre, randomised, crossover study
Tomoaki Nakamura, Kazuhiko Sakaguchi, Anna So, Shinsuke Nakajima, Michinori Takabe, Hisako Komada, Yoko Okuno, Yushi Hirota, Takehiro Nakamura, Keiji Iida, Michiko Kajikawa, Masao Nagata, Wataru Ogawa, Susumu Seino

Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial
Wolfgang Kothny, Valentina Lukashevich, James E. Foley, Marc S. Rendell, Anja Schweizer

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Epidemiology

Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young
Molly M. Lamb, Brittni Frederiksen, Jennifer A. Seifert, Miranda Kroehl, Marian Rewers, Jill M. Norris

Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study
Kwok-Leung Ong, Andrzej S. Januszewski, Rachel O’Connell, Luke Buizen, Alicia J. Jenkins, Aimin Xu, David R. Sullivan, Philip J. Barter, Russell S. Scott, Marja-Riitta Taskinen, Kerry-Anne Rye, Anthony C. Keech, on behalf of the FIELD study investigators

No evidence of seasonality of birth in adult type 2 diabetes in Denmark
Camilla B. Jensen, Esther Zimmermann, Michael Gamborg, Berit L. Heitmann, Jennifer L. Baker, Allan Vaag, Thorkild I. A. Sørensen

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Genetics

The loss-of-function PCSK9 p.R46L genetic variant does not alter glucose homeostasis
Short Communication
Amélie Bonnefond, Loïc Yengo, Cédric Le May, Fréderic Fumeron, Michel Marre, Beverley Balkau, Guillaume Charpentier, Sylvia Franc, Philippe Froguel, Bertrand Cariou, for the DESIR study group

Islet Studies

The subcellular distribution of cyclin-D1 and cyclin-D3 within human islet cells varies according to the status of the pancreas donor
Kazuto Taniguchi, Mark A. Russell, Sarah J. Richardson, Noel G. Morgan

Prolactin-stimulated survivin induction is required for beta cell mass expansion during pregnancy in mice
Yili Xu, Xiaojing Wang, Li Gao, Jiayu Zhu, Hui Zhang, Houxia Shi, Minna Woo, Xiaohong Wu

High-fat diet increases autophagic flux in pancreatic beta cells in vivo and ex vivo in mice
Short Communication
Kwan Yi Chu, Liam O’Reilly, Georg Ramm, Trevor J. Biden

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Immunology and Transplantation

Heritability of thyroid peroxidase autoantibody levels in type 1 diabetes: evidence from discordant twin pairs
Bin Wang, Mohammed I. Hawa, Frühling V. Rijsdijk, Pamela R. Fain, Stavroula A. Paschou, Bernhard O. Boehm, Andrea K. Steck, Harold Snieder, R. David G. Leslie

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Metabolism

Markers of autophagy are adapted to hyperglycaemia in skeletal muscle in type 2 diabetes
Rikke Kruse, Birgitte F. Vind, Stine J. Petersson, Jonas M. Kristensen, Kurt Højlund

BAIBA attenuates insulin resistance and inflammation induced by palmitate or a high fat diet via an AMPK–PPARδ-dependent pathway in mice
Tae Woo Jung, Hwan-Jin Hwang, Ho Cheol Hong, Hye Jin Yoo, Sei Hyun Baik, Kyung Mook Choi

Human adipose tissue expansion in pregnancy is impaired in gestational diabetes mellitus
Raziel Rojas-Rodriguez, Lawrence M. Lifshitz, Karl D. Bellve, So Yun Min, Jacqueline Pires, Katherine Leung, Crina Boeras, Aylin Sert, Jacqueline T. Draper, Silvia Corvera, Tiffany A. Moore Simas

MAFB as a novel regulator of human adipose tissue inflammation
Annie M. L. Pettersson, Juan R. Acosta, Christel Björk, Johan Krätzel, Britta Stenson, Lennart Blomqvist, Nathalie Viguerie, Dominique Langin, Peter Arner, Jurga Laurencikiene

Contribution of brown adipose tissue activity to the control of energy balance by GLP-1 receptor signalling in mice
Kristy M. Heppner, Sarah Marks, Jenna Holland, Nickki Ottaway, David Smiley, Richard Dimarchi, Diego Perez-Tilve

Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes
Pieter Giesbertz, Inken Padberg, Dietrich Rein, Josef Ecker, Anja S. Höfle, Britta Spanier, Hannelore Daniel

Sequential induction of beta cell rest and stimulation using stable GIP inhibitor and GLP-1 mimetic peptides improves metabolic control in C57BL/KsJ db/db mice
Varun Pathak, Srividya Vasu, Victor A. Gault, Peter R. Flatt, Nigel Irwin

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Pathophysiology and Complications

Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals
Manja Reimann, Walthard Vilser, Matthias Gruber, Stefan R. Bornstein, Tjalf Ziemssen

Increased aortic stiffness predicts future development and progression of peripheral neuropathy in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study
Claudia R. L. Cardoso, Camila B. M. Moran, Fernanda S. Marinho, Marcel T. Ferreira, Gil F. Salles

MicroRNA-26a inhibits TGF-β-induced extracellular matrix protein expression in podocytes by targeting CTGF and is downregulated in diabetic nephropathy
Kenichi Koga, Hideki Yokoi, Kiyoshi Mori, Masato Kasahara, Takashige Kuwabara, Hirotaka Imamaki, Akira Ishii, Keita P. Mori, Yukiko Kato, Shoko Ohno, Naohiro Toda, Moin A. Saleem, Akira Sugawara, Kazuwa Nakao, Motoko Yanagita, Masashi Mukoyama

Enhanced endoplasmic reticulum stress in bone marrow angiogenic progenitor cells in a mouse model of long-term experimental type 2 diabetes
Maulasri Bhatta, Jacey Hongjie Ma, Joshua J. Wang, Jonna Sakowski, Sarah X. Zhang

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Letters

Management of nicotinamide N-methyltransferase overexpression: inhibit the enzyme or reduce nicotinamide intake?
Shi-Sheng Zhou, Da Li, Yiming Zhou

Management of nicotinamide N-methyltransferase overexpression: inhibit the enzyme or reduce nicotinamide intake? Reply to Zhou S, Li D, Zhou Y [letter]
Aimo Kannt, Anja Pfenninger, Anke Tönjes, Matthias Blüher

On the role of gut bacteria and infant diet in the development of autoimmunity for type 1 diabetes
Arno L. M. Hänninen, Raine K. Toivonen

On the role of gut bacteria and infant diet in the development of autoimmunity for type 1 diabetes. Reply to Hänninen ALM and Toivonen RK [letter]
Austin G. Davis-Richardson, Eric W. Triplett

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Errata

Erratum to: A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control
Noha A. Yousri, Dennis O. Mook-Kanamori, Mohammed M. El-Din Selim, Ahmed H. Takiddin, Hala Al-Homsi, Khoulood A. S. Al-Mahmoud, Edward D. Karoly, Jan Krumsiek, Kieu Trinh Do, Ulrich Neumaier, Marjonneke J. Mook-Kanamori, Jillian Rowe, Omar M. Chidiac, Cindy McKeon, Wadha A. Al Muftah, Sara Abdul Kader, Gabi Kastenmüller, Karsten Suhre

Erratum to: Favourable effects of fenofibrate on lipids and cardiovascular disease in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study
Michael C. d’Emden, Alicia J. Jenkins, Liping Li, Diana Zannino, Kristy P. Mann, James D. Best, Bronwyn G. A. Stuckey, Kris Park, Juha Saltevo, Anthony C. Keech, on behalf of the FIELD Study Investigators

Erratum to: Purinergic P2X7 receptors regulate secretion of interleukin-1 receptor antagonist and beta cell function and survival
R. Glas, N. S. Sauter, F. T. Schulthess, L. Shu, J. Oberholzer, K. Maedler

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