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Welcome to Diabetologia

Diabetologia publishes original clinical, translational 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

Study of over 700 000 births shows increased risk of poor outcomes, including death, for babies born to mothers with gestational diabetes

Read this new research by Dr Sophie Jacqueminet, Pitié-Salpétrière Hospital, Paris, France; Professor Delphine Mitanchez, Armand Trousseau Hospital, Paris, France; and Cécile Billionnet, French National Health Insurance, Paris, France, and colleagues.
For further information contact Professor Mitanchez (delphine.mitanchez@aphp.fr) or Dr Billionnet (cecile.billionnet@cnamts.fr).

Current issue: March 2017

March 2017 cover

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The confocal image on this month's cover shows a section of injured femoral artery from a mouse, stained with antibodies labelling smooth muscle cells in green (anti-SM22α), the phosphatase SHP-1 in red and nuclei in blue (DAPI). In this issue of Diabetologia, Qi et al report that increasing SHP-1 expression in smooth muscle cells can inhibit their proliferation and migration, and could, therefore, reduce restenosis in insulin resistance and diabetes.



Cover credit: Weier Qi, Qian Li and George L. King, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA


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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


PCSK9 inhibition: the dawn of a new age in cholesterol lowering?
by David Preiss, Marion Mafham

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme that plays a key role in the metabolism of LDL-cholesterol. Since the complementary discoveries that individuals with gain-of-function PCSK9 mutations develop a severe form of familial hypercholesterolaemia while those with diminished PCSK9 have lower LDL-cholesterol levels and a reduced risk of coronary heart disease, various medicines have been developed to reduce PCSK9 levels. In this issue, Preiss and Mafham discuss the biology of PCSK9 and describe the lipid-modifying effects and safety of available PCSK9-lowering agents in individuals with and without diabetes. Monoclonal antibodies to PCSK9 lower circulating LDL-cholesterol by over 50% and are currently being evaluated in major cardiovascular endpoint trials, which will soon report their findings. Alternative modalities such as adnectin-based polypeptides and small interfering RNA are under investigation in earlier phase trials. The review concludes with a discussion of the potential benefit of monoclonal antibodies to PCSK9 and their position in clinical practice in the future. [Text supplied by the authors.]

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Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity
by Hanna Honkanen, Sami Oikarinen, Noora Nurminen, Olli H. Laitinen, Heini Huhtala, Jussi Lehtonen, Tanja Ruokoranta, Minna M. Hankaniemi, Valérie Lecouturier, Jeffrey W. Almond, Sisko Tauriainen, Olli Simell, Jorma Ilonen, Riitta Veijola, Hanna Viskari, Mikael Knip, Heikki Hyöty

Enteroviruses have been found in the pancreatic islets of people with type 1 diabetes and are associated with an increased risk of the disease in epidemiological studies. In this issue, Honkanen et al explore this association in a large cohort of children followed from birth in the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland. Enterovirus infections were detected by analysing the presence of viral nucleic acids in longitudinal stool samples. Infections were more common in the case group, who developed islet autoantibodies, compared with the control group. This excess of infections occurred several months before islet autoantibodies appeared, at which time case children had three times more infections than control children. The study supports the concept that enterovirus infections could contribute to the initiation of the beta cell-damaging process. Together with other evidence, this study encourages further exploration of whether some incidences of type 1 diabetes could be preventable by antiviral interventions, such as enterovirus vaccines or antiviral drugs. [Text supplied by the authors.]

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Loss of prohormone convertase 2 promotes beta cell dysfunction in a rodent transplant model expressing human pro-islet amyloid polypeptide
by Jaques A. Courtade, Evan Y. Wang, Paul Yen, Derek L. Dai, Galina Soukhatcheva, Paul C. Orban, Bruce Verchere

The beta cell peptide islet amyloid polypeptide (IAPP or amylin) forms toxic aggregates in both type 2 diabetes and islet transplants, although the underlying mechanism remains unknown. The IAPP precursor, proIAPP, is processed by prohormone convertases PC1/3 and PC2 in rodent beta cells. In this issue, Courtade et al show, in a mouse model of PC2 deficiency in islet transplantation, that defective beta cell prohormone processing accelerates islet graft failure. Interestingly, lack of PC2 did not accelerate formation of detectable amyloid, leaving open the possibility that precursors of mature IAPP may form toxic oligomeric aggregates. These findings point to a potential mechanism for beta cell loss in type 2 diabetes and islet transplantation, involving defects in proIAPP processing. [Text supplied by the authors.]

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Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes
by Bernard M. F. M. Duvivier, Nicolaas C. Schaper, Matthijs K. C. Hesselink, Linh van Kan, Nathalie Stienen, Bjorn Winkens, Annemarie Koster, Hans H. C. M. Savelberg

Structured exercise is one of the cornerstones of type 2 diabetes treatment, but adherence to exercise guidelines is frequently poor and the time spent sitting is increasing in modern society. In this issue, Duvivier et al report that breaking sitting time with light activities is a promising alternative to structured exercise in sedentary adults with type 2 diabetes. When energy expenditure was matched, standing and light walking had, after 4 days, the same beneficial effect on 24 h glycaemic control as a daily bout of moderate-to-vigorous intensity cycling. Moreover, insulin sensitivity improved to a greater extent with standing and walking. Hence, decreasing sitting time seems to improve insulin sensitivity independent of energy expenditure. These findings provide further support for recommending less sitting and more light activity in adults with type 2 diabetes. This article is the subject of a commentary in this issue by Dempsey et al.[Text supplied by the authors.]

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Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits
by Antonius Baartscheer, Cees A. Schumacher, Rob C. I. Wüst, Jan W. T. Fiolet, Ger J. M. Stienen, Ruben Coronel, Coert J. Zuurbier

The EMPA-REG OUTCOME trial revealed the long-awaited possibility of pharmacologically combatting the cardiovascular complications of type 2 diabetes, reducing cardiovascular death and hospitalisation for heart failure. How the kidney-targeted medicine, empagliflozin, reduced cardiac complications is, however, an enigma, as the molecular target (SGLT2) is absent in heart. It is known, however, that raised cardiac cellular sodium is often an early driver of cardiovascular death and heart failure. In this issue, Baartscheer, Schumacher et al demonstrate that empagliflozin does work directly on cardiac cells in animal models, lowering cellular sodium through inhibition of the Na+/H+ exchanger. In addition, they show that hyperglycaemia itself raises cellular sodium and that lowering cellular sodium directly improves mitochondrial activation status. This work suggests that empagliflozin's effects against diabetes, cardiovascular death and heart failure relate to its capacity to combat two important metabolic phenomena in our current society: cellular overload of sodium and glucose. This article is the subject of a commentary in this issue by Vettor et al. [Text supplied by the authors.]

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Inside this issue

Up front

Up front March 2017

Review

PCSK9 inhibition: the dawn of a new age in cholesterol lowering?
David Preiss, Marion Mafham

Commentaries

Adding exercise or subtracting sitting time for glycaemic control: where do we stand?
Paddy C. Dempsey, Megan S. Grace, David W. Dunstan

The cardiovascular benefits of empagliflozin: SGLT2-dependent and -independent effects
Roberto Vettor, Silvio E. Inzucchi, Paola Fioretto

Articles

Clinical Science and Care

Increased fetal adiposity prior to diagnosis of gestational diabetes in South Asians: more evidence for the ‘thin–fat’ baby
Hema Venkataraman, Uma Ram, Sam Craik, Anuradhai Arungunasekaran, Suresh Seshadri, Ponnusamy Saravanan

Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a pilot study
Megan L. Gow, Louise A. Baur, Nathan A. Johnson, Chris T. Cowell, Sarah P. Garnett

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Epidemiology

Are the Institute of Medicine weight gain targets applicable in women with gestational diabetes mellitus?
Tang Wong, Robyn A. Barnes, Glynis P. Ross, Ngai W. Cheung, Jeff R. Flack

Detection of enteroviruses in stools precedes islet autoimmunity by several months: possible evidence for slowly operating mechanisms in virus-induced autoimmunity
Hanna Honkanen, Sami Oikarinen, Noora Nurminen, Olli H. Laitinen, Heini Huhtala, Jussi Lehtonen, Tanja Ruokoranta, Minna M. Hankaniemi, Valérie Lecouturier, Jeffrey W. Almond, Sisko Tauriainen, Olli Simell, Jorma Ilonen, Riitta Veijola, Hanna Viskari, Mikael Knip, Heikki Hyöty

Discriminatory ability of simple OGTT-based beta cell function indices for prediction of prediabetes and type 2 diabetes: the CODAM study
Louise J. C. J. den Biggelaar, Simone J. S. Sep, Simone J. P. M. Eussen, Andrea Mari, Ele Ferrannini, Marleen M. J. van Greevenbroek, Carla J. H. van der Kallen, Casper G. Schalkwijk, Coen D. A. Stehouwer, Pieter C. Dagnelie

The heritable basis of gene–environment interactions in cardiometabolic traits
Alaitz Poveda, Yan Chen, Anders Brändström, Elisabeth Engberg, Göran Hallmans, Ingegerd Johansson, Frida Renström, Azra Kurbasic, Paul W. Franks

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Islet Studies

Loss of prohormone convertase 2 promotes beta cell dysfunction in a rodent transplant model expressing human pro-islet amyloid polypeptide
Jaques A. Courtade, Evan Y. Wang, Paul Yen, Derek L. Dai, Galina Soukhatcheva, Paul C. Orban, C. Bruce Verchere

APPL1 prevents pancreatic beta cell death and inflammation by dampening NFκB activation in a mouse model of type 1 diabetes
Xue Jiang, Yawen Zhou, Kelvin K. L. Wu, Zhanrui Chen, Aimin Xu, Kenneth K. Y. Cheng

Early differences in islets from prediabetic NOD mice: combined microarray and proteomic analysis
Inne Crèvecoeur, Valborg Gudmundsdottir, Saurabh Vig, Fernanda Marques Câmara Sodré, Wannes D’Hertog, Ana Carolina Fierro, Leentje Van Lommel, Conny Gysemans, Kathleen Marchal, Etienne Waelkens, Frans Schuit, Søren Brunak, Lut Overbergh, Chantal Mathieu

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Metabolism

Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes
Bernard M. F. M. Duvivier, Nicolaas C. Schaper, Matthijs K. C. Hesselink, Linh van Kan, Nathalie Stienen, Bjorn Winkens, Annemarie Koster, Hans H. C. M. Savelberg

Interrupting prolonged sitting in type 2 diabetes: nocturnal persistence of improved glycaemic control
Paddy C. Dempsey, Jennifer M. Blankenship, Robyn N. Larsen, Julian W. Sacre, Parneet Sethi, Nora E. Straznicky, Neale D. Cohen, Ester Cerin, Gavin W. Lambert, Neville Owen, Bronwyn A. Kingwell, David W. Dunstan

The effects of 2 weeks of interval vs continuous walking training on glycaemic control and whole-body oxidative stress in individuals with type 2 diabetes: a controlled, randomised, crossover trial
Kristian Karstoft, Margaret A. Clark, Ida Jakobsen, Ida A. Müller, Bente K. Pedersen, Thomas P. J. Solomon, Mathias Ried-Larsen

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes
Victoria Sandler, Anna C. Reisetter, James R. Bain, Michael J. Muehlbauer, Michael Nodzenski, Robert D. Stevens, Olga Ilkayeva, Lynn P. Lowe, Boyd E. Metzger, Christopher B. Newgard, Denise M. Scholtens, William L. Lowe Jr, for the HAPO Study Cooperative Research Group

Critical role for GLP-1 in symptomatic post-bariatric hypoglycaemia
Colleen M. Craig, Li-Fen Liu, Carolyn F. Deacon, Jens J. Holst, Tracey L. McLaughlin

An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice
Annie Hasib, Ming T. Ng, Victor A. Gault, Dawood Khan, Vadivel Parthsarathy, Peter R. Flatt, Nigel Irwin

Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle
Urszula Chursa, Esther Nuñez-Durán, Emmelie Cansby, Manoj Amrutkar, Silva Sütt, Marcus Ståhlman, Britt-Marie Olsson, Jan Borén, Maria E. Johansson, Fredrik Bäckhed, Bengt R. Johansson, Carina Sihlbom, Margit Mahlapuu

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Pathophysiology and Complications

Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits
Short Communication
Antonius Baartscheer, Cees A. Schumacher, Rob C. I. Wüst, Jan W. T. Fiolet, Ger J. M. Stienen, Ruben Coronel, Coert J. Zuurbier

Frequent and intensive physical activity reduces risk of cardiovascular events in type 1 diabetes
Heidi Tikkanen-Dolenc, Johan Wadén, Carol Forsblom, Valma Harjutsalo, Lena M. Thorn, Markku Saraheimo, Nina Elonen, Milla Rosengård-Bärlund, Daniel Gordin, Heikki O. Tikkanen, Per-Henrik Groop, on behalf of the FinnDiane Study Group

Assessment of urinary microparticles in normotensive patients with type 1 diabetes
Short Communication
Yuliya Lytvyn, Fengxia Xiao, Christopher R. J. Kennedy, Bruce A. Perkins, Heather N. Reich, James W. Scholey, David Z. Cherney, Dylan Burger

SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes
Weier Qi, Qian Li, Chong Wee Liew, Christian Rask-Madsen, Samuel M. Lockhart, Lars Melholt Rasmussen, Yu Xia, Xuanchun Wang, Mogher Khamaisi, Kevin Croce, George L. King

Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes
Takeru Shima, Takashi Matsui, Subrina Jesmin, Masahiro Okamoto, Mariko Soya, Koshiro Inoue, Yu-Fan Liu, Ignacio Torres-Aleman, Bruce S. McEwen, Hideaki Soya

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