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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 suggests enterovirus infections linked with autoimmunity that leads to type 1 diabetes

Read this new research by Professor Heikki Hyöty and Hanna Honkanen, University of Tampere, Finland, and colleagues.
For further information contact Professor Hyöty (heikki.hyoty@uta.fi) or Hanna Honkanen (Hanna.Honkanen@staff.uta.fi).

Interrupting sitting time improves blood sugar control in people with type 2 diabetes

Read this new research by Bernard Duvivier of the Department of Human Biology and Movement Science and NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, and colleagues.
For further information contact Bernard Duvivier (bernard.duvivier@maastrichtuniversity.nl) or Hans Savelberg (hans.savelberg@maastrichtuniversity.nl).

Current issue: February 2017

February 2017 cover

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The cover shows a confocal fluorescence microscopy image of a differentiated 3T3-L1 adipocyte expressing the fatty acid chaperone, fatty acid binding protein 5 (FABP5; green fluorescent protein [GFP]-FABP5, green), and immunostained for the cytoskeletal protein septin 11 (SEPT11, red) and the caveolae component caveolin-1 (CAV1, blue) after exposure to oleate. In the present issue of Diabetologia, Moreno-Castellanos et al report that SEPT11 associates with CAV1 in adipocyte caveolae and, together with CAV1 and FABP5, binds to lipid droplets upon fatty acid loading, contributing to lipid traffic. SEPT11 in adipose tissue is increased in human obesity and relates to markers of adiposity in omental fat and to variables of insulin resistance in subcutaneous fat.


Cover credit: A. Fernández-Vega, R. Vázquez-Martínez, and M. M. Malagón, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Córdoba, Spain


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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


Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition
by Volker Vallon, Scott C. Thomson

The EMPA-REG OUTCOME trial revealed that the addition of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin to standard care for patients with type 2 diabetes and high cardiovascular risk delayed the progression of kidney disease and lowered rates of clinically relevant renal and cardiovascular events. This exciting and promising news for the diabetes field provided a new glucose lowering approach, for which the primary target is the kidney. In this issue, Vallon and Thomson summarise the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption. The authors outline the metabolic benefits of enhancing urinary glucose excretion while leaving metabolic regulation and counterregulation intact. They also discuss the pleiotropic impact of SGLT2 inhibition, which creates a favourable environment for beneficial and synergistic effects on metabolism and the renal and cardiovascular systems. In doing so, they outline the unexpected logic of inhibiting SGLT2 in the kidney of individuals with diabetes. [Text supplied by the authors.]

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Glia: silent partners in energy homeostasis and obesity pathogenesis
by John D. Douglass, Mauricio D. Dorfman, Joshua P. Thaler

The discovery of new brain mechanisms for governing food intake and energy expenditure is critical for the development of novel drugs to target obesity. In this issue, Douglass et al review recent studies, revealing a previously unappreciated role for non-neuronal cells in the regulation of energy homeostasis and obesity susceptibility. Glia, the most numerous cells of the central nervous system, are involved in nearly all brain functions, from neurovascular coupling and blood-brain barrier maintenance to modulation of synaptic activity and protection against pathogens. In the context of energy homeostasis, glia promote hypothalamic inflammation, neuronal stress and overconsumption in response to high-fat diets. In addition, glial cells directly respond to circulating nutrients and critical adiposity hormones, such as leptin and insulin, providing an additional mechanism for body weight regulation. Thus, investigating glial contributions to energy balance holds great promise for identification of new targets for the treatment of obesity and metabolic disease. [Text supplied by the authors.]

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A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort
by Shristi Rawal, Stefanie N. Hinkle, Wei Bao, Yeyi Zhu, Jagteshwar Grewal, Paul S. Albert, Natalie L. Weir, Michael Y. Tsai, Cuilin Zhang

Iron overload is implicated in impaired glucose metabolism among non-pregnant populations. Iron status changes dramatically throughout pregnancy, yet the trimester-specific association between iron levels in pregnancy and subsequent risk of gestational diabetes (GDM) is unknown. In this issue, Rawal et al report prospective findings from a longitudinal study that examined the associations between GDM risk and gestational iron status. Iron status was characterised by a comprehensive panel of traditional and novel iron biomarkers. Pregnant women with very high levels of iron biomarkers (i.e. ferritin and hepcidin) in either the first or second trimester of pregnancy had an increased risk of GDM, with stronger associations appearing in the second trimester. Although there are known benefits of iron supplementation for iron-deficiency in pregnancy, findings from the present study suggest that elevated iron stores in pregnant women may be involved in the development of GDM and, thus, raise potential concerns about routine iron supplementation among pregnant women with sufficient iron levels. This article is the subject of a commentary in this issue by Aidan McElduff. [Text supplied by the authors.]

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Adipocyte STAT5 deficiency promotes adiposity and impairs lipid mobilisation in mice
by Doris Kaltenecker, Kristina M. Mueller, Pia Benedikt, Ursula Feiler, Madeleine Themanns, Michaela Schlederer, Lukas Kenner, Martina Schweiger, Guenter Haemmerle, Richard Moriggl

Dysfunctional lipid metabolism in white adipose tissue contributes to various diseases. Thus, it is essential to delineate molecular mechanisms that regulate lipid handling in adipocytes. In this issue, Kaltenecker, Mueller et al report that the transcription factor signal transducer and activator of transcription 5 (STAT5) is an important modulator of white adipose tissue function in mice. Adipocyte-specific STAT5 deficiency markedly reduced basal lipolysis rates, resulting in a higher body fat content in STAT5-deficient mice vs controls. They demonstrate that STAT5 is directly involved in the gene regulation of the lipid-cleaving enzyme adipose triglyceride lipase (ATGL, encoded by Pnpla2), uncovering a new mechanism for the regulation of lipolysis in adipose tissue. Interestingly, despite the increased adiposity, STAT5-deficient mice were metabolically healthier and remained more insulin sensitive with ageing compared with controls. This study provides a basis for future investigation into the extent to which the inhibition of STAT5 in adipose tissue might constitute a therapeutic intervention strategy for metabolic diseases. [Text supplied by the authors.]

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Insulitis in human diabetes: a histological evaluation of donor pancreases
by Marcus Lundberg, Peter Seiron, Sofie Ingvast, Olle Korsgren, Oskar Skog

According to the consensus criteria developed for type 1 diabetes, an individual can be diagnosed with insulitis when ≥ 15 CD45+ cells are found within the parenchyma or in the islet-exocrine interface in ≥ 3 islets. In this issue, Lundberg et al report that, overall, 28% (14 out of 50) of donors with type 2 diabetes and 31% of donors with type 1 diabetes (four of 14 donors) fulfilled these consensus criteria for insulitis. In contrast, only type 1 diabetic donors had ≥ 15 CD3+ cells in ≥ 3 islets. From these findings, the authors conclude that the current definition of insulitis cannot be used to distinguish pancreases retrieved from individuals with type 1 diabetes from those with type 2 diabetes. As a consequence, they propose a revised definition of insulitis in type 1 diabetes, with a positive diagnosis when ≥ 15 CD3+ cells (not CD45+ cells) are found in ≥ 3 islets. [Text supplied by the authors.]

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Inside this issue

Up front

Up front February 2017

Reviews

Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition
Volker Vallon, Scott C. Thomson

Glia: silent partners in energy homeostasis and obesity pathogenesis
John D. Douglass, Mauricio D. Dorfman, Joshua P. Thaler

Commentary

Iron: how much is too much?
Aidan McElduff

Articles

Systematic Reviews/Meta-analyses

Nonlinear association of BMI with all-cause and cardiovascular mortality in type 2 diabetes mellitus: a systematic review and meta-analysis of 414,587 participants in prospective studies
Francesco Zaccardi,Nafeesa N. Dhalwani, Dimitris Papamargaritis, David R. Webb, Gavin J. Murphy, Melanie J. Davies, Kamlesh Khunti

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Epidemiology

A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort
Shristi Rawal, Stefanie N. Hinkle, Wei Bao, Yeyi Zhu, Jagteshwar Grewal, Paul S. Albert, Natalie L. Weir, Michael Y. Tsai, Cuilin Zhang

Type 1 diabetes mellitus and risk of incident epilepsy: a population-based, open-cohort study
Short Communication
George E. Dafoulas, Konstantinos A. Toulis, Dougall Mccorry, Balachadran Kumarendran, G. Neil Thomas, Brian H. Willis, Krishna Gokhale, George Gkoutos, Parth Narendran, Krishnarajah Nirantharakumar

Exposure to severe famine in the prenatal or postnatal period and the development of diabetes in adulthood: an observational study
Ningjian Wang, Jing Cheng, Bing Han, Qin Li, Yi Chen, Fangzhen Xia, Boren Jiang, Michael D. Jensen, Yingli Lu

Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studies
Jessica C. Kiefte-de Jong, Yanping Li, Mu Chen, Gary C. Curhan, Josiemer Mattei, Vasanti S. Malik, John P. Forman, Oscar H. Franco, Frank B. Hu

ADAMTS13 activity as a novel risk factor for incident type 2 diabetes mellitus: a population-based cohort study
Paul S. de Vries, Thijs T. W. van Herpt, Symen Ligthart, Albert Hofman, M. Arfan Ikram, Mandy van Hoek, Eric J. G. Sijbrands, Oscar H. Franco, Moniek P. M. de Maat, Frank W. G. Leebeek, Abbas Dehghan

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Immunology and Transplantation

Peptide serum markers in islet autoantibody-positive children
Christine von Toerne, Michael Laimighofer, Peter Achenbach, Andreas Beyerlein, Tonia de las Heras Gala, Jan Krumsiek, Fabian J. Theis, Anette G. Ziegler, Stefanie M. Hauck

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Metabolism

Adipocyte STAT5 deficiency promotes adiposity and impairs lipid mobilisation in mice
Doris Kaltenecker, Kristina M. Mueller, Pia Benedikt, Ursula Feiler, Madeleine Themanns, Michaela Schlederer, Lukas Kenner, Martina Schweiger, Guenter Haemmerle, Richard Moriggl

Liver triacylglycerol content and gestational diabetes: effects of moderate energy restriction
Kenneth Hodson, Chiara Dalla Man, Fiona E Smith, Alison Barnes, Catherine McParlin, Claudio Cobelli, Stephen C Robson, Vera Araújo-Soares, Roy Taylor

Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals: implications for insulin signalling and glucose uptake in human adipocytes
Johanna Säll, Annie M. L. Pettersson, Christel Björk, Emma Henriksson, Sebastian Wasserstrom, Wilhelm Linder, Yuedan Zhou, Ola Hansson, Daniel P. Andersson, Mikael Ekelund, Eva Degerman, Karin G. Stenkula, Jurga Laurencikiene, Olga Göransson

The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism
Natalia Moreno-Castellanos, Amaia Rodríguez, Yoana Rabanal-Ruiz, Alejandro Fernández-Vega, José López-Miranda, Rafael Vázquez-Martínez, Gema Frühbeck, María M. Malagón

A Tbc1d1 Ser231Ala-knockin mutation partially impairs AICAR- but not exercise-induced muscle glucose uptake in mice
Qiaoli Chen, Bingxian Xie, Sangsang Zhu, Ping Rong, Yang Sheng, Serge Ducommun, Liang Chen, Chao Quan, Min Li, Kei Sakamoto, Carol MacKintosh, Shuai Chen, Hong Yu Wang

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Pathophysiology and Complications

Insulitis in human diabetes: a histological evaluation of donor pancreases
Marcus Lundberg, Peter Seiron, Sofie Ingvast, Olle Korsgren, Oskar Skog

Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus
Nasim Samandari, Aashiq H. Mirza, Lotte B. Nielsen, Simranjeet Kaur, Philip Hougaard, Siri Fredheim, Henrik B. Mortensen, Flemming Pociot

The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE -/- mice fed a western diet
Ji Hye Han, Tae Jung Oh, Ghayoung Lee, Hyo Jin Maeng, Dong Hwa Lee, Kyoung Min Kim, Sung Hee Choi, Hak Chul Jang, Hye Seung Lee, Kyong Soo Park, Young-Bum Kim, Soo Lim

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Erratum

Erratum to: Glucose concentrations of less than 3.0 mmol/l (54 mg/dl) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes
The International Hypoglycaemia Study Group

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