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

In the News

Anaemia distorts regular method of diabetes diagnosis and questions its reliability

Download this new research by Dr Emma English, University of Nottingham, UK, and colleagues.
To contact Dr English please contact Charlotte Anscombe, Media Relations Manager, University of Nottingham (Charlotte.Anscombe@nottingham.ac.uk).


(posted online 22.01h BST Wednesday 13th May 2015)

Current issue: June 2015

June 2015 cover

Click here to view this month's contents

The cover picture is a visual metaphor for low birthweight and lists its effects on metabolism. The feather indicates the light weight of the newborn, and the text above the left-hand side of the feather shows the metabolic changes that an infant born with low birthweight may already carry, which may lead to type 2 diabetes in later life. In the present issue of Diabetologia, Song et al report that low birthweight is a direct predictor of a higher risk of the development of type 2 diabetes. The effect of low birthweight on type 2 diabetes risk seems to be mainly mediated by insulin resistance, which is further explained by circulating levels of sex hormone-binding globulin and E-selectin and systolic blood pressure.


Cover credit: The image was created by Yimeng Bai using iStock photo 37690984 ©iStock.com/inarik

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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


Biomarkers related to severe hypoglycaemia and lack of good glycaemic control in ACCORD
by Lisa S. Chow, Haiying Chen, Michael E. Miller, Santica M. Marcovina, Elizabeth R. Seaquist

In type 2 diabetic patients, intensification of glycaemic control lowers the risk of microvascular complications, but this approach can produce severe hypoglycaemia. In this issue, Chow et al report on their analysis of data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which aimed to identify blood biomarkers that predict the response of type 2 diabetic patients to intensification of glucose-lowering treatment. Using a nested case-control design to examine only those participants with type 2 diabetes who received intensive treatment, the authors report that insulin deficiency and islet antibodies were higher in those who experienced severe hypoglycaemia and failed to achieve the intensive glycaemia target of HbA1c <6.0% (<42 mmol/mol) than in participants who achieved the target without experiencing severe hypoglycaemia. These findings suggest that fasting C-peptide and islet autoantibodies may serve as blood biomarkers to predict those individuals at risk of severe hypoglycaemia in response to intensification of glycaemia treatment. This article is the subject of a commentary in this issue by Sankalpa Neupane and Mark Evans. [Text supplied by the authors.]

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Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes
by William T. Cefalu, Kaj Stenlöf, Lawrence A. Leiter, John P. H. Wilding, Lawrence Blonde, David Polidori, John Xie, Daniel Sullivan, Keith Usiskin, William Canovatchel, Gary Meininger

Weight loss and the sodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozin have both been associated with reductions in HbA1c and blood pressure (BP). In addition, canagliflozin has been associated with weight loss. In this issue, Cefalu et al report on an analysis of pooled data from four placebo-controlled Phase 3 studies on the contribution of weight loss with canagliflozin to reductions in HbA1c and systolic BP. Significant reductions in body weight, HbA1c and systolic BP were observed; ~85% of HbA1c lowering and ~60% of systolic BP lowering were weight loss-independent, with the remainder of HbA1c- and systolic BP-lowering effects attributable to weight loss. These findings add to our understanding of the clinical effects of SGLT2 inhibition, and provide evidence that weight loss associated with canagliflozin also contributes to improved glycaemic control and BP reduction in patients with type 2 diabetes. [Text supplied by the authors.]

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Experience of a serious life event increases the risk for childhood type 1 diabetes: the ABIS population-based prospective cohort study
by Maria Nygren, John Carstensen, Felix Koch, Johnny Ludvigsson, Anneli Frostell

Several retrospective studies have suggested a traumatic life event to be a possible risk factor for type 1 diabetes. According to the beta cell stress hypothesis, all factors that increase the need for insulin or increase insulin resistance might be risk factors; hence, psychological stress with increased stress hormone concentrations may contribute to type 1 diabetes risk. In this issue, Nygren et al report that, in their prospective study, childhood experience of serious life events (such as death/illness in the family, divorce, new adult/child in the family) was associated with increased risk of diagnosis of type 1 diabetes up to 14 years of age after controlling for other diabetes-related factors and BMI. These findings indicate that psychological stress may be involved in the immunological process leading to the onset of type 1 diabetes. [Text supplied by the authors.]

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The impact of lifestyle intervention on sedentary time in individuals at high risk of diabetes
by Bonny Rockette-Wagner, Sharon Edelstein, Elizabeth M. Venditti, Deepti Reddy, George A. Bray, Mary Lou Carrion-Petersen, Dana Dabelea, Linda M. Delahanty, Hermes Florez, Paul W. Franks, Maria G. Montez, Richard Rubin, Andrea M. Kriska for the Diabetes Prevention Program Research Group

Whether interventions focusing on increasing physical activity also reduce time spent sitting is unclear. Having conducted a post hoc analysis of data from the Diabetes Prevention Program (DPP), in this issue, Rockette-Wagner et al provide evidence that a lifestyle intervention for individuals at high risk of type 2 diabetes focusing on increasing moderate intensity activity and reducing weight (but without a sit-reduction goal) was also able to reduce TV watching and sitting at work. In addition, there was an increased risk of developing diabetes for each hour/day of TV watching after adjusting for age, sex and reported leisure activity (adjusting for weight attenuated the relationship). The authors suggest that lifestyle intervention programmes with a specific sit-reduction goal could result in greater changes in sitting and more health improvements than observed in this study. Therefore, intervention efforts that focus on increasing physical activity and reducing weight should also consider aiming to reduce sitting time. [Text supplied by the authors.]

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Long-term risk of type 2 diabetes mellitus in relation to BMI and weight change among women with a history of gestational diabetes mellitus: a prospective cohort study
by Wei Bao, Edwina Yeung, Deirdre K. Tobias, Frank B. Hu, Allan A. Vaag, Jorge E. Chavarro, James L. Mills, Louise G. Grunnet, Katherine Bowers, Sylvia H. Ley, Michele Kiely, Sjurdur F. Olsen, Cuilin Zhang

Women who develop gestational diabetes during pregnancy are at exceptionally high risk of type 2 diabetes after pregnancy; it is therefore critical to identify modifiable factors that may help prevent the development of this disease. In this issue, Bao et al report that baseline BMI, most recent BMI and weight gain after GDM were significantly and positively associated with risk of progression from GDM to type 2 diabetes. Moreover, for obese women (BMI ≥30 kg/m2) who put on 5 kg or more after giving birth, the risk of developing type 2 diabetes was 43 times that for women who were lean and gained less than 5 kg. These findings provide evidence that for women with a history of gestational diabetes it is important to achieve and maintain a healthy weight after pregnancy to prevent future development of type 2 diabetes. [Text supplied by the authors.]

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Inside this issue

Commentaries

Predicting risk of severe hypoglycaemia in type 2 diabetes
Sankalpa Neupane, Mark L. Evans

Tuning to the right signal
Mark O. Huising

Review

Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes
Jessica A. Pane, Barbara S. Coulson

Articles

Clinical Science and Care

Biomarkers related to severe hypoglycaemia and lack of good glycaemic control in ACCORD
Lisa S. Chow, Haiying Chen, Michael E. Miller, Santica M. Marcovina, Elizabeth R. Seaquist

CGM-measured glucose values have a strong correlation with C-peptide, HbA1c and IDAAC, but do poorly in predicting C-peptide levels in the two years following onset of diabetes
Bruce Buckingham, Peiyao Cheng, Roy W. Beck, Craig Kollman, Katrina J. Ruedy, Stuart A. Weinzimer, Robert Slover, Andrew A. Bremer, John Fuqua, William Tamborlane, for the Diabetes Research in Children Network (DirecNet) and Type 1 Diabetes TrialNet Study Groups

Upper gastrointestinal motility and symptoms in individuals with diabetes, prediabetes and normal glucose tolerance
Georgios C. Boronikolos, Björn A. Menge, Nina Schenker, Thomas G. K. Breuer, Jan-Michel Otte, Sascha Heckermann, Freimut Schliess, Juris J. Meier

Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes
Short Communication
William T. Cefalu, Kaj Stenlöf, Lawrence A. Leiter, John P. H. Wilding, Lawrence Blonde, David Polidori, John Xie, Daniel Sullivan, Keith Usiskin, William Canovatchel, Gary Meininger

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Epidemiology

Experience of a serious life event increases the risk for childhood type 1 diabetes: the ABIS population-based prospective cohort study
Maria Nygren, John Carstensen, Felix Koch, Johnny Ludvigsson, Anneli Frostell

The impact of lifestyle intervention on sedentary time in individuals at high risk of diabetes
Bonny Rockette-Wagner, Sharon Edelstein, Elizabeth M. Venditti, Deepti Reddy, George A. Bray, Mary Lou Carrion-Petersen, Dana Dabelea, Linda M. Delahanty, Hermes Florez, Paul W. Franks, Maria G. Montez, Richard Rubin, Andrea M. Kriska, for the Diabetes Prevention Program Research Group

Blood pressure level and risk of major cardiovascular events and all-cause of mortality in patients with type 2 diabetes and renal impairment: an observational study from the Swedish National Diabetes Register
Hanri Afghahi, Maria K. Svensson, Mirnabi Pirouzifard, Björn Eliasson, Ann-Marie Svensson

Long-term risk of type 2 diabetes mellitus in relation to BMI and weight change among women with a history of gestational diabetes mellitus: a prospective cohort study
Wei Bao, Edwina Yeung, Deirdre K. Tobias, Frank B. Hu, Allan A. Vaag, Jorge E. Chavarro, James L. Mills, Louise G. Grunnet, Katherine Bowers, Sylvia H. Ley, Michele Kiely, Sjurdur F. Olsen, Cuilin Zhang

Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women
Yan Song, Yen-Tsung Huang, Yiqing Song, Andrea L. Hevener, Kelli K. Ryckman, Lihong Qi, Erin S. LeBlanc, Rasa Kazlauskaite, Kathleen M. Brennan, Simin Liu

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Genetics

Common variants in or near ZNRF1, COLEC12, SCYL1BP1 and API5 are associated with diabetic retinopathy in Chinese patients with type 2 diabetes
Danfeng Peng, Jie Wang, Rong Zhang, Feng Jiang, Shanshan Tang, Miao Chen, Jing Yan, Xue Sun, Shiyun Wang, Tao Wang, Dandan Yan, Yuqian Bao, Cheng Hu, Weiping Jia

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Islet Studies

A live-cell, high-content imaging survey of 206 endogenous factors across five stress conditions reveals context-dependent survival effects in mouse primary beta cells
Yu Hsuan Carol Yang, Quin F. Wills, James D. Johnson

Syntaxin-4 mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose-stimulated insulin secretion in human pancreatic beta cells
Li Xie, Dan Zhu, Subhankar Dolai, Tao Liang, Tairan Qin, Youhou Kang, Huanli Xie, Ya-Chi Huang, Herbert Y. Gaisano

The p66Shc redox adaptor protein is induced by saturated fatty acids and mediates lipotoxicity-induced apoptosis in pancreatic beta cells
Annalisa Natalicchio, Federica Tortosa, Rossella Labarbuta, Giuseppina Biondi, Nicola Marrano, Emanuele Carchia, Anna Leonardini, Angelo Cignarelli, Marco Bugliani, Piero Marchetti, Gian Paolo Fadini, Marco Giorgio, Angelo Avogaro, Sebastio Perrini, Luigi Laviola, Francesco Giorgino

Forkhead box O1 mediates defects in palmitate-induced insulin granule exocytosis by downregulation of calcium/calmodulin-dependent serine protein kinase expression in INS-1 cells
Yao Wang, Haiyan Lin, Nana Hao, Zhengqiu Zhu, Dong Wang, Yuan Li, Hong Chen, Yunxia Zhu, Xiao Han

Bone morphogenetic protein 4 inhibits insulin secretion from rodent beta cells through regulation of calbindin1 expression and reduced voltage-dependent calcium currents
Gitte L. Christensen, Maria L. B. Jacobsen, Anna Wendt, Ines G. Mollet, Josefine Friberg, Klaus S. Frederiksen, Michael Meyer, Christine Bruun, Lena Eliasson, Nils Billestrup

Slow potentials encode intercellular coupling and insulin demand in pancreatic beta cells
Fanny Lebreton, Antoine Pirog, Isma Belouah, Domenico Bosco, Thierry Berney, Paolo Meda, Yannick Bornat, Bogdan Catargi, Sylvie Renaud, Matthieu Raoux, Jochen Lang

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Immunology and Transplantation

Islet transplantation from a nationally funded UK centre reaches socially deprived groups and improves metabolic outcomes
Shareen Forbes, Neil W. A. McGowan, Kirsty Duncan, Debbie Anderson, Janet Barclay, Donna Mitchell, Kevin Docherty, David Turner, John D. M. Campbell, John J. Casey

PD-1-dependent restoration of self-tolerance in the NOD mouse model of diabetes after transient anti-TCRβ mAb therapy
Paul M. Schroder, Mithun Khattar, Caitlin E. Baum, Yoshihiro Miyahara, Wenhao Chen, Rohit Vyas, Shravan Muralidharan, Beata Mierzejewska, Stanislaw M. Stepkowski

Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice
Georgia Fousteri, Tatiana Jofra, Roberta Di Fonte, Nicola Gagliani, Cristina Morsiani, Angela Stabilini, Manuela Battaglia

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Metabolism

Metabolomic profiling in the prediction of gestational diabetes mellitus
Short Communication
Rhonda Bentley-Lewis, Jennifer Huynh, Grace Xiong, Hang Lee, Julia Wenger, Clary Clish, David Nathan, Ravi Thadhani, Robert Gerszten

Beta cell response to nutrient overload involves phospholipid remodelling and lipid peroxidation
Guy Cohen, Ofer Shamni, Yossef Avrahami, Ofir Cohen, Esther C. Broner, Natalie Filippov-Levy, Chryssostomos Chatgilialoglu, Carla Ferreri, Nurit Kaiser, Shlomo Sasson

Caveolin-1 phosphorylation regulates vascular endothelial insulin uptake and is impaired by insulin resistance in rats
Hong Wang, Aileen X. Wang, Kevin Aylor, Eugene J. Barrett

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Pathophysiology and Complications

Delayed timing of post-challenge peak blood glucose predicts declining beta cell function and worsening glucose tolerance over time: insight from the first year postpartum
Caroline K. Kramer, Chang Ye, Anthony J. G. Hanley, Philip W. Connelly, Mathew Sermer, Bernard Zinman, Ravi Retnakaran

Protein biomarkers for the prediction of cardiovascular disease in type 2 diabetes
Helen C. Looker, Marco Colombo, Felix Agakov, Tanja Zeller, Leif Groop, Barbara Thorand, Colin N. Palmer, Anders Hamsten, Ulf de Faire, Everson Nogoceke, Shona J. Livingstone, Veikko Salomaa, Karin Leander, Nicola Barbarini, Riccardo Bellazzi, Natalie van Zuydam, Paul M. McKeigue, Helen M. Colhoun, on behalf of the SUMMIT Investigators

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Letters

Co-ordinating meals and exercise for diabetes management
Elsamma Chacko

Within-class differences of the sulfonylureas should be accounted for
Dennis Schrijnders, Nanne Kleefstra, Gijs W. D. Landman

Within-class differences of the sulfonylureas should be accounted for. Reply to Schrijnders D, Kleefstra N and Landman GWD [letter]
Jonathan C. Levy, Axel Riefflin, Rury R. Holman

Impact of cancer on use of glucose-lowering drug treatment in individuals with diabetes: potential mechanisms
Frans Pouwer

Impact of cancer on use of glucose-lowering drug treatment in individuals with diabetes: potential mechanisms. Reply to Pouwer F [letter]
Marjolein M. J. Zanders, Harm R. Haak, Myrthe P. P. van Herk-Sukel, Lonneke V. van de Poll-Franse, Jeffrey A. Johnson

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