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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

Recurrent diabetic ketoacidosis is associated with substantial mortality, particularly amongst young, socially disadvantaged adults

Read this new research by Dr Fraser Gibb and colleagues at the Royal Infirmary of Edinburgh, UK.
For further information contact Dr Gibb (fraser.gibb@ed.ac.uk).

Artificial pancreas likely to be available by 2018

Read this new research by Dr Roman Hovorka and Dr Hood Thabit of the University of Cambridge, UK.
For further information contact Dr Hovorka (rh347@cam.ac.uk).

Current issue: August 2016

August 2016 cover

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The cover picture shows a false-color electron micrograph of lipid-filled lysosomes in liver of lysosomal acid lipase (LAL)-deficient mice. In humans, complete or partial loss of LAL activity results in severe cholesteryl ester storage diseases. In the present issue of Diabetologia, Radović et al report on a novel role of murine LAL in the regulation of insulin sensitivity. In contrast to the accumulation of cytoplasmic lipid droplets observed in hepatic steatosis, which is accompanied by insulin resistance, LAL-deficient mice accumulate triacylglycerols and cholesteryl esters in liver lysosomes and are highly glucose tolerant and insulin sensitive despite complete loss of adipose tissue depots.


Cover credit: Dagmar Kolb, Center for Medical Research/Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria

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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


Islet biology, the CDKN2A/B locus and type 2 diabetes risk
by Yahui Kong, Rohit B. Sharma, Benjamin U. Nwosu, Laura C. Alonso

Genome wide association studies have identified a range of genomic loci that influence type 2 diabetes risk in human populations. Despite this advance, the mechanistic pathways linking polymorphisms to disease occurrence mostly remain unclear. Even for CDKN2A/B, a locus that has been intensely scrutinised and has relevance to cancers and ageing as well as diabetes, diabetes risk mechanisms remain poorly understood. In this issue, Kong et al review the current understanding of how CDKN2A/B polymorphisms affect the function of diabetes-relevant tissues. In particular, this review includes an in-depth look at islet biology, which is widely assumed to be the site of action of CDKN2A/B polymorphisms since a CDKN2A/B locus gene product, p16, regulates beta cell proliferation. In combining literature relating to clinical phenotyping with basic scientific observations, Kong et al challenge the notion that CDKN2A/B polymorphisms act entirely through their effects on beta cell biology. [Text supplied by the authors.]

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Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study
by Sybil A. McAuley, Jodie C. Horsburgh, Glenn M. Ward, André La Gerche, Judith L. Gooley, Alicia J. Jenkins, Richard J. MacIsaac, David N. O'Neal

Maintaining normoglycaemia during and after exercise remains a challenge for many with type 1 diabetes. Clinical guidelines recommend halving insulin pump basal delivery 1 h pre-exercise to prevent hypoglycaemia. However, these guidelines are derived mainly from expert opinion in the absence of scientific evidence. In this issue, McAuley et al report that, when subcutaneous insulin pump basal delivery is halved 1 h pre-exercise, there is no significant reduction in circulating insulin levels by the time exercise commences. Subsequently, during 30 min of moderate-intensity aerobic exercise, a transient increase in circulating insulin occurs. The authors suggest this rise may relate to enhanced insulin absorption due to increased cutaneous blood flow. They also show that hypoglycaemia risk is higher for those with low-normal pre-exercise glucose. To prevent exercise-induced hypoglycaemia, the authors propose that basal reductions in insulin of more than 50% are instituted pre-exercise and that, if commencing exercise with low-normal glucose levels, supplemental carbohydrate should be considered. This article is the subject of a commentary in this issue by Thabit and Leelarathna. [Text supplied by the authors.]

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Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study
by Lisa S. Chow, Andrew O. Odegaard, Tyler A. Bosch, Anne E. Bantle, Qi Wang, John Hughes, Mercedes Carnethon, Katherine H. Ingram, Nefertiti Durant, Cora E. Lewis, Justin Ryder, Christina M. Shay, Aaron S. Kelly, Pamela J. Schreiner

It is generally presumed that higher fitness is associated with lower rates of prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and diabetes development. In this issue, Chow et al use data from the Coronary Artery Risk Development in Young Adults (CARDIA) study (N=4373) to analyse objectively and rigorously the link between cardiorespiratory fitness and development of either prediabetes or diabetes over a 20 year period. The main finding demonstrates that higher cardiorespiratory fitness is associated with lower risk for developing prediabetes and diabetes, even after adjusting for changes in BMI. Since this benefit remained significant even when adjusting for BMI, this study provides evidence that exercise programmes remain critically important for reducing the development of prediabetes and diabetes. [Text supplied by the authors.]

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Parenthood and the risk of diabetes in men and women: a 7 year prospective study of 0.5 million individuals
by Sanne A. E. Peters, Ling Yang, Yu Guo, Yiping Chen, Zheng Bian, Iona Y. Millwood, Fiona Bragg, Xue Zhou, Pengfei Ge, Biyun Chen, Yulian Gao, Yijun Li, Junshi Chen, Liming Li, Mark Woodward, Zhengming Chen, on behalf of the China Kadoorie Biobank Collaboration Group

In women, higher parity has been associated with an increased risk of diabetes. It is unclear whether the metabolic consequences of pregnancy and childbearing or socioeconomic and lifestyle factors associated with childrearing underpin this association. In this issue, Peters et al report the results of a large prospective study in which they assessed the association between number of children and diabetes risk separately among men and women. They report that both men and women without children or with multiple children had a higher risk of diabetes compared with those with one child. Each additional child increased the risk of diabetes by 3-4% in both sexes. This similarity in the relationship between the number of children and diabetes in both women and men suggests that parenthood may increase the risk of diabetes in women with larger families through factors associated with childrearing, rather than through the biological effects of pregnancy and childbearing. [Text supplied by the authors.]

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Morphology of the pancreas in type 2 diabetes: effect of weight loss with or without normalisation of insulin secretory capacity
by Ahmad Al-Mrabeh, Kieren G. Hollingsworth, Sarah Steven, Roy Taylor

In type 2 diabetes, the pancreas is recognized both as being smaller than normal and as having a characteristically irregular border. This leads us to ask: are individuals who are born with small pancreases at higher risk of developing type 2 diabetes, or does the pancreas shrink as the condition develops and progresses? Is it possible that smaller pancreas size in type 2 diabetes may be due to the loss of the trophic effects of surges in tissue insulin concentration after meals? In this issue, Al-Mrabeh et al attempt to answer these questions by studying individuals with a wide range of duration of type 2 diabetes before and after substantial weight loss. Increasing duration of diabetes was associated with a more irregular pancreas border. In individuals in whom insulin secretion returned to normal after a very low calorie diet, pancreas volume was higher and border irregularity was reduced compared with those who were unable to resume normal insulin secretory function (typically those with longer duration diabetes). These findings demonstrate that the morphology of the pancreas may provide important prognostic information in type 2 diabetes. [Text supplied by the authors.]

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Inside this issue

Up front

Up front August 2016

Reviews

Islet biology, the CDKN2A/B locus and type 2 diabetes risk
Yahui Kong, Rohit B. Sharma, Benjamin U. Nwosu, Laura C. Alonso

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance
Bobak Bahrami, Meidong Zhu, Thomas Hong, Andrew Chang

Cerebral cortex: a target and source of insulin?
Éva A. Csajbók, Gábor Tamás

Angiopoietins and diabetic nephropathy
Luigi Gnudi

EASD symposia

Novel anti-inflammatory drugs for the treatment of diabetic kidney disease
Hiddo J. L. Heerspink, Dick De Zeeuw

JAK inhibition in the treatment of diabetic kidney disease
Frank C. Brosius, Katherine R. Tuttle, Matthias Kretzler

Commentaries

Basal insulin delivery reduction for exercise in type 1 diabetes: finding the sweet spot
Hood Thabit, Lalantha Leelarathna

Can somatostatin antagonism prevent hypoglycaemia during exercise in type 1 diabetes?
Nadine Taleb, Rémi Rabasa-Lhoret

Articles

Clinical Science and Care

Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study
Sybil A. McAuley, Jodie C. Horsburgh, Glenn M. Ward, André La Gerche, Judith L. Gooley, Alicia J. Jenkins, Richard J. MacIsaac, David N. O’Neal

Once-daily delayed-release metformin lowers plasma glucose and enhances fasting and postprandial GLP-1 and PYY: results from two randomised trials
Ralph A. DeFronzo, John B. Buse, Terri Kim, Colleen Burns, Sharon Skare, Alain Baron, Mark Fineman

Interaction between rs10830963 polymorphism in MTNR1B and lifestyle intervention on occurrence of gestational diabetes
Short Communication
Nora E. Grotenfelt, Niko S. Wasenius, Kristiina Rönö, Hannele Laivuori, Beata Stach-Lempinen, Marju Orho-Melander, Christina-Alexandra Schulz, Hannu Kautiainen, Saila B. Koivusalo, Johan G. Eriksson

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Epidemiology

Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study
Lisa S. Chow, Andrew O. Odegaard, Tyler A. Bosch, Anne E. Bantle, Qi Wang, John Hughes, Mercedes Carnethon, Katherine H. Ingram, Nefertiti Durant, Cora E. Lewis, Justin Ryder, Christina M. Shay, Aaron S. Kelly, Pamela J. Schreiner

Family history of myocardial infarction, stroke and diabetes and cardiometabolic markers in children
Nina E. Berentzen, Alet H. Wijga, Lenie van Rossem, Gerard H. Koppelman, Bo van Nieuwenhuizen, Ulrike Gehring, Annemieke M. W. Spijkerman, Henriëtte A. Smit

Parenthood and the risk of diabetes in men and women: a 7 year prospective study of 0.5 million individuals
Sanne A. E. Peters, Ling Yang, Yu Guo, Yiping Chen, Zheng Bian, Iona Y. Millwood, Fiona Bragg, Xue Zhou, Pengfei Ge, Biyun Chen, Yulian Gao, Yijun Li, Junshi Chen, Liming Li, Mark Woodward, Zhengming Chen, on behalf of the China Kadoorie Biobank Collaboration Group

Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men
Rachel Dankner, Paolo Boffetta, Lital Keinan-Boker, Ran D. Balicer, Alla Berlin, Liraz Olmer, Havi Murad, Barbara Silverman, Moshe Hoshen, Laurence S. Freedman

Incidence, prevalence and mortality of type 2 diabetes requiring glucose-lowering treatment, and associated risks of cardiovascular complications: a nationwide study in Sweden, 2006–2013
Anna Norhammar, Johan Bodegård, Thomas Nyström, Marcus Thuresson, Jan W. Eriksson, David Nathanson

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Genetics

Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes
Rashmi B. Prasad, Anna Lessmark, Peter Almgren, Györgyi Kovacs, Ola Hansson, Nikolay Oskolkov, Marta Vitai, Claes Ladenvall, Peter Kovacs, Joao Fadista, Michael Lachmann, Yuedan Zhou, Emily Sonestedt, Wenny Poon, Claes B. Wollheim, Marju Orho-Melander, Michael Stumvoll, Tiinamaija Tuomi, Svante Pääbo, Laszlo Koranyi, Leif Groop

DNA hypermethylation of CD3+ T cells from cord blood of infants exposed to intrauterine growth restriction
Lyda Williams, Yoshinori Seki, Fabien Delahaye, Alex Cheng, Mamta Fuloria, Francine Hughes Einstein, Maureen J. Charron

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Metabolism

Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes
Erwan Leclair, Richard T. Liggins, Ashley J. Peckett, Trevor Teich, David H. Coy, Mladen Vranic, Michael C. Riddell

A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes
Hung-Tsung Wu, Horng-Yih Ou, Hao-Chang Hung, Yu-Chu Su, Feng-Hwa Lu, Jin-Shang Wu, Yi-Ching Yang, Chao-Liang Wu, Chih-Jen Chang

Lysosomal acid lipase regulates VLDL synthesis and insulin sensitivity in mice
Branislav Radović, Nemanja Vujic, Christina Leopold, Stefanie Schlager, Madeleine Goeritzer, Jay V. Patankar, Melanie Korbelius, Dagmar Kolb, Julia Reindl, Martin Wegscheider, Tamara Tomin, Ruth Birner-Gruenberger, Matthias Schittmayer, Lukas Groschner, Christoph Magnes, Clemens Diwoky, Saša Frank, Ernst Steyrer, Hong Du, Wolfgang F. Graier, Tobias Madl, Dagmar Kratky

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Pathophysiology and Complications

Morphology of the pancreas in type 2 diabetes: effect of weight loss with or without normalisation of insulin secretory capacity
Ahmad Al-Mrabeh, Kieren G. Hollingsworth, Sarah Steven, Roy Taylor

Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice
Edson M. de Oliveira, Thais P. Ascar, Jacqueline C. Silva, Silvana Sandri, Silene Migliorini, Ricardo A. Fock, Ana Campa

Loss of BMP receptor type 1A in murine adipose tissue attenuates age-related onset of insulin resistance
Tim J. Schulz, Antonia Graja, Tian Lian Huang, Ruidan Xue, Ding An, Sophie Poehle-Kronawitter, Matthew D. Lynes, Alexander Tolkachov, Lindsay E. O’Sullivan, Michael F. Hirshman, Michael Schupp, Laurie J. Goodyear, Yuji Mishina, Yu-Hua Tseng

The angiotensin II type 2 receptor agonist Compound 21 is protective in experimental diabetes-associated atherosclerosis
Bryna S. M. Chow, Christine Koulis, Pooja Krishnaswamy, Ulrike M. Steckelings, Thomas Unger, Mark E. Cooper, Karin A. Jandeleit-Dahm, Terri J. Allen

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Erratum

Erratum to: A proposal for the use of uniform diagnostic criteria for gestational diabetes in Europe: an opinion paper by the European Board & College of Obstetrics and Gynaecology (EBCOG)
Katrien Benhalima, Chantal Mathieu, Peter Damm, André Van Assche, Roland Devlieger, Gernot Desoye, Rosa Corcoy, Tahir Mahmood, Jacky Nizard, Charles Savona-Ventura, Fidelma Dunne

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