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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.

In the News

Study suggests consuming whey protein before meals could help improve blood glucose control in people with diabetes

Download this new research by Professor Daniela Jakubowicz and Dr Julio Wainstein (Wolfson Medical Center, Tel Aviv University), Professor Oren Froy (Hebrew University of Jerusalem), Professor Bo Ahrén (Lund University, Sweden) and colleagues.
For further information contact Professor Jakubowicz (daniela.jak@gmail.com), Dr Wainstein (vainstein@wolfson.health.gov.il), Professor Froy (oren.froy@mail.huji.ac.il) or Professor Ahrén (bo.ahren@med.lu.se).


(posted online 22:01 h BST Monday 7 July 2014)

Limited evidence suggests that combined aerobic and resistance training, rather than either method alone, is best for controlling blood sugar in people with diabetes

Download this new research by Lukas Schwingshackl from the University of Vienna and colleagues.
For further information contact Mr Schwingshackl (lukas.schwingshackl@univie.ac.at).


(posted online 22:01 h BST Wednesday 2 July 2014)

Current issue: August 2014

August 2014 cover

Click here to view this month's contents

The cover picture illustrates the idea that eating only two meals a day is more effective than six smaller meals in a reduced-energy regimen. In the present issue of Diabetologia Kahleova et al report findings from a randomised crossover study showing that, in patients with type 2 diabetes, eating only breakfast and lunch reduced body weight, hepatic fat content, fasting plasma glucose, C-peptide and glucagon, and increased insulin sensitivity, compared with the same energy-restricted diet split into six smaller meals. These results suggest that, for patients with type 2 diabetes following a hypoenergetic diet, eating a larger breakfast and lunch may be more beneficial than consuming six smaller meals during the day.

Cover credit: MAXDORF PUBLISHING, PRAGUE; HANA KAHLEOVÁ, M.D., PH.D., DIABETES CENTRE, INSTITUTE FOR CLINICAL AND EXPERIMENTAL MEDICINE, PRAGUE

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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


Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes
by Rinke Stienstra, Yulia Haim, Yael Riahi, Mihai Netea, Assaf Rudich, Gil Leibowitz

Autophagy is a lysosomal degradation pathway that recycles intracellular long-lived proteins and damaged organelles, thereby preserving cellular homeostasis. Beyond its ubiquitous role in maintaining cellular homeostasis, autophagy also regulates tissue-specific functions and modulates systemic metabolism and inflammation. Hence, altered autophagy may play a role in the pathophysiology of obesity and type 2 diabetes. In this issue, Stienstra et al review the complex regulation of autophagy and the impact of dysregulated autophagy on adipose tissue and beta cell inflammation and dysfunction in obesity and diabetes. The authors focus on adipose tissue and the beta cell, not only because of their central role in the pathogenesis of diabetes, but also because they exemplify the tissue-specific functions of autophagy in physiology and their dysregulation in obesity and diabetes. They review major concepts and highlight important questions and controversies related to the regulation and function of autophagy and discuss the potential implications of dysregulated autophagy for the pathophysiology of obesity. These issues need to be resolved before investigating autophagy as a potential therapeutic target for the treatment of obesity and diabetes. [Text supplied by the authors.]

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Diabetes as a risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events
by Sanne A. E. Peters, Rachel R. Huxley, Mark Woodward

In this issue, Peters et al present the results of the largest pooled analysis to date to reliably quantify the sex difference in the risk conferred by diabetes for incident coronary heart disease. They report that the relative risk associated with diabetes for both fatal and non-fatal coronary heart disease is significantly higher (by approximately 40%) in women than in men after adjusting for baseline differences in major cardiovascular risk factors between the sexes. There was little evidence to indicate that sex differences in pharmacotherapy account for much of the greater coronary hazard conferred by diabetes in women. Instead, the authors hypothesise that, compared with men, women are more likely to exist in a state of 'prediabetes' for longer before both developing and being diagnosed with overt diabetes, and that it is this chronic exposure to hyperglycaemia that underpins their greater coronary risk. [Text supplied by the authors.]

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Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study
by Hana Kahleova, Lenka Belinova, Hana Malinska, Olena Oliyarnyk, Jaroslava Trnovska, Vojtech Skop, Ludmila Kazdova, Monika Dezortova, Milan Hajek, Andrea Tura, Martin Hill, Terezie Pelikanova

A hypoenergetic diet results in loss of body weight and body fat and is crucial for both the prevention and treatment of type 2 diabetes. Typically, hypoenergetic diets are apportioned into five or six small meals during the day. Eating more frequently is presumed to reduce hunger and is therefore expected to reduce energy intake and body weight. However, the influence of meal frequency on health and longevity is unclear. In this issue, Kahleova et al provide evidence that a regimen of two meals a day (breakfast and lunch) is more beneficial for patients with type 2 diabetes than the same hypoenergetic diet divided into six small meals. The patients who ate two meals a day lost more weight, showed greater reductions in waist circumference and liver fat and became more sensitive to insulin. These findings suggest that, for patients with type 2 diabetes following a hypoenergetic diet, eating a larger breakfast and lunch may be more beneficial than consuming six smaller meals during the day. [Text supplied by the authors.]

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Aberrant gut microbiota composition at the onset of type 1 diabetes in young children
by Marcus C. de Goffau, Susana Fuentes, Bartholomeus van den Bogert, Hanna Honkanen, Willem M. de Vos, Gjalt W. Welling, Heikki Hyöty, Hermie J. M. Harmsen

The incidence of type 1 diabetes is increasing worldwide, and this increase is especially rapid in children under the age of 5 years. Having studied the gut microbiota composition in children aged 1-5 years with new-onset type 1 diabetes and age-matched controls, in this issue, de Goffau et al report that the gut microbiota plays an important role in the development of type 1 diabetes. Even though the gut microbiota of healthy individuals changes rapidly during the first 5 years of life, they have a more balanced microbiota, in which butyrate-producing species appear to play a key role. Dietary intervention studies aimed at achieving or maintaining optimal butyrate production levels are needed to assess whether such interventions could measurably reduce the risk of developing type 1 diabetes, particularly in children with high-risk HLA genotypes. [Text supplied by the authors.]

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Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study
by Malene N. Demant, Gunnar H. Gislason, Lars Køber, Allan Vaag, Christian Torp-Pedersen, Charlotte Andersson

The poor prognosis associated with diabetes mellitus in heart failure patients has foxed researchers for at least 35 years. In this issue, Demant et al report that increasing severity of heart failure is associated with increasing risk of developing diabetes. Patients with the most severe heart failure were three times more likely to develop diabetes than those in the least severe group. Concomitant treatment with ACE inhibitors attenuated the risk of diabetes development. Patients who developed diabetes were 16% more likely to die than those who did not develop diabetes. The results of this study suggest that diabetes may be a marker of disease severity rather than a causal risk factor in some cases, because it was the sickest people who developed diabetes. The authors underline the need to monitor and treat patients with heart failure to prevent diabetes development and emphasise the importance of identifying the diabetic subgroup of patients with heart failure. [Text supplied by the authors.]

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Inside this issue

Reviews

Autophagy in adipose tissue and the beta cell: implications for obesity and diabetes
Rinke Stienstra, Yulia Haim, Yael Riahi, Mihai Netea, Assaf Rudich, Gil Leibowitz

Impaired proteostasis: role in the pathogenesis of diabetes mellitus
Stéphane Jaisson, Philippe Gillery

Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond
Niels Grarup, Camilla H. Sandholt, Torben Hansen, Oluf Pedersen

Meta-analysis

Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events
Sanne A. E. Peters, Rachel R. Huxley, Mark Woodward

Articles

Clinical Science and Care

Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study
Hana Kahleova, Lenka Belinova, Hana Malinska, Olena Oliyarnyk, Jaroslava Trnovska, Vojtech Skop, Ludmila Kazdova, Monika Dezortova, Milan Hajek, Andrea Tura, Martin Hill, Terezie Pelikanova

Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community-dwelling older men
Hong Xu, Ting Jia, Xiaoyan Huang, Ulf Risérus, Tommy Cederholm, Johan Ärnlöv, Per Sjögren, Bengt Lindholm, Juan-Jesús Carrero

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Epidemiology

Aberrant gut microbiota composition at the onset of type 1 diabetes in young children
Marcus C. de Goffau, Susana Fuentes, Bartholomeus van den Bogert, Hanna Honkanen, Willem M. de Vos, Gjalt W. Welling, Heikki Hyöty, Hermie J. M. Harmsen

Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV registries
David M. Maahs, Julia M. Hermann, Stephanie N. DuBose, Kellee M. Miller, Bettina Heidtmann, Linda A. DiMeglio, Birgit Rami-Merhar, Roy W. Beck, Edith Schober, William V. Tamborlane, Thomas M. Kapellen, Reinhard W. Holl

Changes in HbA1c and frequency of measuring HbA1c and adjusting glucose-lowering medications in the 10 years following diagnosis of type 2 diabetes: a population-based study in the UK
Marcus Lind, Aldina Pivodic, Lucia Cea-Soriano, Olle Nerman, Nils-Gunnar Pehrsson, Luis A. Garcia-Rodriguez

Association of heart failure severity with risk of diabetes: a Danish nationwide cohort study
Malene N. Demant, Gunnar H. Gislason, Lars Køber, Allan Vaag, Christian Torp-Pedersen, Charlotte Andersson

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Genetics

Type 2 diabetes-related genetic risk scores associated with variations in fasting plasma glucose and development of impaired glucose homeostasis in the prospective DESIR study
Martine Vaxillaire, Loïc Yengo, Stéphane Lobbens, Ghislain Rocheleau, Elodie Eury, Olivier Lantieri, Michel Marre, Beverley Balkau, Amélie Bonnefond, Philippe Froguel

Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification
Francesco Sambo, Alberto Malovini, Niina Sandholm, Monica Stavarachi, Carol Forsblom, Ville-Petteri Mäkinen, Valma Harjutsalo, Raija Lithovius, Daniel Gordin, Maija Parkkonen, Markku Saraheimo, Lena M. Thorn, Nina Tolonen, Johan Wadén, Bing He, Anne-May Österholm, Jaako Tuomilehto, Maria Lajer, Rany M. Salem, Amy Jayne McKnight, Lise Tarnow, Nicolae M. Panduru, Nicola Barbarini, Barbara Di Camillo, Gianna M. Toffolo, Karl Tryggvason, Riccardo Bellazzi, Claudio Cobelli, Per-Henrik Groop

GWAS identifies an NAT2 acetylator status tag single nucleotide polymorphism to be a major locus for skin fluorescence
Karen M. Eny, Helen L. Lutgers, John Maynard, Barbara E. K. Klein, Kristine E. Lee, Gil Atzmon, Vincent M. Monnier, Jana V. van Vliet-Ostaptchouk, Reindert Graaff, Pim van der Harst, Harold Snieder, Melanie M. van der Klauw, David R. Sell, S. Mohsen Hosseini, Patricia A. Cleary, Barbara H. Braffett, Trevor J. Orchard, Timothy J. Lyons, Kerri Howard, Ronald Klein, Jill P. Crandall, Nir Barzilai, Sofiya Milman, Danny Ben-Avraham, Bruce H. R. Wolffenbuttel, Andrew D. Paterson

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Islet Studies

Hypoxia lowers SLC30A8/ZnT8 expression and free cytosolic Zn2+ in pancreatic beta cells
Philipp A. Gerber, Elisa A. Bellomo, David J. Hodson, Gargi Meur, Antonia Solomou, Ryan K. Mitchell, Michael Hollinshead, Fabrice Chimienti, Domenico Bosco, Stephen J. Hughes, Paul R. V. Johnson, Guy A. Rutter

TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6
Dominika Nackiewicz, Meixia Dan, Wei He, Rosa Kim, Anisa Salmi, Sabine Rütti, Clara Westwell-Roper, Amanda Cunningham, Madeleine Speck, Carole Schuster-Klein, Beatrice Guardiola, Kathrin Maedler, Jan A. Ehses

Insulin secretion from beta cells in intact mouse islets is targeted towards the vasculature
Jiun T. Low, Michael Zavortink, Justin M. Mitchell, Wan J. Gan, Oanh Hoang Do, Christof J. Schwiening, Herbert Y. Gaisano, Peter Thorn

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Immunology and Transplantation

Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes
Enrica Favaro, Andrea Carpanetto, Sara Lamorte, Alberto Fusco, Cristiana Caorsi, Maria C. Deregibus, Stefania Bruno, Antonio Amoroso, Mirella Giovarelli, Massimo Porta, Paolo Cavallo Perin, Ciro Tetta, Giovanni Camussi, Maria M. Zanone

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Metabolism

Cathepsin S inhibition lowers blood glucose levels in mice
Jean-Charles Lafarge, Maria Pini, Véronique Pelloux, Gabriela Orasanu, Guido Hartmann, Nicolas Venteclef, Thierry Sulpice, Guo-Ping Shi, Karine Clément, Michèle Guerre-Millo

Altered amyloid precursor protein processing regulates glucose uptake and oxidation in cultured rodent myotubes
D. Lee Hamilton, John A. Findlay, Gemma Montagut, Paul J. Meakin, Dawn Bestow, Susan M. Jalicy, Michael L. J. Ashford

AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice
Hayley M. O’Neill, James S. Lally, Sandra Galic, Melissa Thomas, Paymon D. Azizi, Morgan D. Fullerton, Brennan K. Smith, Thomas Pulinilkunnil, Zhiping Chen, M. Constantine Samaan, Sebastian B. Jorgensen, Jason R. B. Dyck, Graham P. Holloway, Thomas J. Hawke, Bryce J. van Denderen, Bruce E. Kemp, Gregory R. Steinberg

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Pathophysiology and Complications

Intensified insulin treatment is associated with improvement in skin microcirculation and ischaemic foot ulcer in patients with type 1 diabetes mellitus: a long-term follow-up study
Björn Rathsman, Kerstin Jensen-Urstad, Thomas Nyström

Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome
Moaz A. Mojaddidi, Mohammed S. Ahmed, Razwan Ali, Maria Jeziorska, Ahmed Al-Sunni, Niels O. B. Thomsen, Lars B. Dahlin, Rayaz A. Malik

Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals
Short Communication
Jonatan I. Bagger, Filip K. Knop, Asger Lund, Jens J. Holst, Tina Vilsbøll

MiR-135a promotes renal fibrosis in diabetic nephropathy by regulating TRPC1
Feng He, Fenfen Peng, Xi Xia, Chen Zhao, Qimei Luo, Weiming Guan, Zhijian Li, Xueqing Yu, Fengxian Huang

Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3
Short Communication
Katharina Hess, Saad H. Alzahrani, Jackie F. Price, Mark W. Strachan, Natalie Oxley, Rhodri King, Tobias Gamlen, Verena Schroeder, Paul D. Baxter, Ramzi A. Ajjan

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