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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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Precision Medicine Series

In the News

Early menopause is independently linked to an increased risk of developing type 2 diabetes

Read this new research by Dr Taulant Muka and Dr Eralda Asllanaj of the Department of Epidemiology, Erasmus University Medical Centre, Netherlands, and colleagues.
For further information contact Dr Muka (t.muka@erasmusmc.nl) or Dr Asllanaj (e.asllanaj@erasmusmc.nl).

Current issue: August 2017

August 2017 cover

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An overweight man considers which kinds of food to eat. Excess dietary fats strengthen the preference for fatty foods via dysregulation of the brain reward system. The cover shows oil droplets containing a variety of foods, including vegetables, brown rice, pizza and desserts. In the present issue of Diabetologia, Kozuka et al report that the brown rice-specific bioactive substance γ-oryzanol acts as a potent inhibitor of DNA methyltransferases in brain striatum in mice, thereby attenuating the preference for dietary fat via the epigenetic modulation of the dopamine D2 receptor. The study highlights γ-oryzanol as a promising anti-obesity treatment with a distinct property as an epigenetic modulator in humans.

Cover credit: Chisayo Kozuka, University of the Ryukyus, Japan, using © Martin Cooper Ipswich, under the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)

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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 four 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


Beta cell heterogeneity: an evolving concept
by Dana Avrahami, Agnes Klochendler, Yuval Dor, Benjamin Glaser

It is well known that beta cells are functionally heterogeneous, but the significance of this in health and disease is not known. Studies using emerging technologies are now addressing this question. In this issue, Avrahami et al (DOI 10.1007/s00125-017-4326-z) provide a concise overview of the impact of novel technologies on our understanding of the emerging field of beta cell heterogeneity. At the whole-islet level, a functional control network was discovered that coordinates insulin secretion within the islet. On the single-cell level, cell surface markers, transcriptomics and proteomics can classify beta cells into different groups and demonstrate that the relative size of these groups changes with age and disease. Single-cell technologies provide information on rare cell types such as proliferating islet cells. While many questions remain unanswered, it is clear that with these novel technologies we are at the brink of a new era in our understanding of islet cell function. [Text supplied by the authors.]

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Early prediction of autoimmune (type 1) diabetes
by Simon E. Regnell, Åke Lernmark

Prospective studies from birth of children at increased genetic risk for autoimmune (type 1) diabetes have provided novel insights into the aetiology and pathogenesis of this disease. In this issue, Regnell and Lernmark (DOI 10.1007/s00125-017-4308-1) summarise recent advances that suggest it should eventually be possible to dissect fully the autoimmune reaction against islet beta cells. Genes in the HLA-DR-DQ region on chromosome 6 seem to play a role in the response to a hypothetical environmental insult. One such insult might result in the appearance of insulin autoantibodies with an incidence peak at 1-3 years of age, primarily in children with the DR4-DQ8 haplotype. Another insult might occur later, reaching a plateau of GAD autoantibodies at about 3 years of age, primarily in children with the DR3-DQ2 haplotype. The subsequent pathogenesis seems to be related to a non-HLA-related appearance of a second, third or fourth islet autoantibody resulting in a variable rate of progression to beta cell loss and clinical onset. Staging pathogenesis should prove useful in dissecting the specific mechanisms of beta cell destruction with a view to achieving secondary prevention of type 1 diabetes. [Text supplied by the authors.]

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Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes
by Isaac V. Snowhite, Gloria Allende, Jay Sosenko, Ricardo L. Pastori, Shari Messinger Cayetano, Alberto Pugliese

Screening for autoantibodies against islet cell autoantigens identifies individuals at risk for type 1 diabetes; yet, progression to overt disease is heterogeneous and additional biomarkers could improve prediction and risk stratification for prevention trials. In this issue, Snowhite et al (DOI 10.1007/s00125-017-4294-3) identify circulating microRNAs associated with disease progression in autoantibody-positive children and adolescents participating in the TrialNet Pathway to Prevention Study. Increased levels of these microRNAs were associated with higher risk of disease progression and correlated with measures of impaired insulin secretion assessed during an OGTT. Several of these microRNAs play a role in beta cell function and insulin secretion, and some may be induced by viruses. Replication in additional longitudinal cohorts may validate these microRNAs as novel biomarkers and functional studies may reveal mechanisms of beta cell dysfunction during the development of type 1 diabetes. [Text supplied by the authors.]

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HSF1 acetylation decreases its transcriptional activity and enhances glucolipotoxicity-induced apoptosis in rat and human beta cells
by Indri Purwana, Jun J. Liu, Bernard Portha, Jean Buteau

Diabetes is characterised by a progressive deterioration of beta cell mass and function. However, the precise mechanisms underlying beta cell loss remain elusive. In this issue, Purwana et al (DOI 10.1007/s00125-017-4310-7) report that metabolic stress induces acetylation and inhibition of the transcription factor heat shock factor protein 1 (HSF1) in beta cells, thereby causing apoptosis. Conversely, restoration of HSF1 activity alleviates stress and promotes beta cell survival. The authors also demonstrate that expression of HSF1 and its target genes are altered in islets from diabetic Goto-Kakizaki rats, a well characterised model of spontaneous type 2 diabetes. These findings unveil a critical role for HSF1 in the regulation of beta cell survival and support the therapeutic potential of HSF1-targeting agents in diabetes treatment. [Text supplied by the authors.]

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Inside this issue

Up front

Up front August 2017

Reviews

Beta cell heterogeneity: an evolving concept
Dana Avrahami, Agnes Klochendler, Yuval Dor, Benjamin Glaser

Early prediction of autoimmune (type 1) diabetes
Simon E. Regnell, Åke Lernmark

Commentary

Metabolically inactive insulin: friend or foe in the prevention of autoimmune diabetes?
Mikael Knip

Articles

Clinical Science and Care

SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA Adverse Event Reporting System
Short Communication
Gian Paolo Fadini, Benedetta Maria Bonora, Angelo Avogaro

Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial
Christoph Kapitza, Kirsten Dahl, Jacob B. Jacobsen, Mads B. Axelsen, Anne Flint

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Epidemiology

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes
Sara J. Jenks, Bryan R. Conway, Stela McLachlan, Wei Leng Teoh, Rachel M. Williamson, David J. Webb, Paul Welsh, Naveed Sattar, Mark W. J. Strachan, Jackie F. Price

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Genetics

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes
Isaac V. Snowhite, Gloria Allende, Jay Sosenko, Ricardo L. Pastori, Shari Messinger Cayetano, Alberto Pugliese

In vivo measurement and biological characterisation of the diabetes-associated mutant insulin p.R46Q (GlnB22-insulin)
Julie Støy, Jørgen Olsen, Soo-Young Park, Søren Gregersen, Claudia U. Hjørringgaard, Graeme I. Bell

Islet Studies

HSF1 acetylation decreases its transcriptional activity and enhances glucolipotoxicity-induced apoptosis in rat and human beta cells
Indri Purwana, Jun J. Liu, Bernard Portha, Jean Buteau

GLP-1 signalling compensates for impaired insulin signalling in regulating beta cell proliferation in βIRKO mice
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N. Kulkarni

Identification of a small molecule that facilitates the differentiation of human iPSCs/ESCs and mouse embryonic pancreatic explants into pancreatic endocrine cells
Yasushi Kondo, Taro Toyoda, Ryo Ito, Michinori Funato, Yoshiya Hosokawa, Satoshi Matsui, Tomomi Sudo, Masahiro Nakamura, Chihiro Okada, Xiaotong Zhuang, Akira Watanabe, Akira Ohta, Nobuya Inagaki, Kenji Osafune

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Immunology and Transplantation

Antibodies to post-translationally modified insulin as a novel biomarker for prediction of type 1 diabetes in children
Rocky Strollo, Chiara Vinci, Nicola Napoli, Paolo Pozzilli, Johnny Ludvigsson, Ahuva Nissim

Metabolically inactive insulin analogue does not prevent autoimmune diabetes in NOD mice
Juha Grönholm, Philippe P. Pagni, Minh N. Pham, Claire B. Gibson, Paul F. Macomber, José Luis Vela, Matthias von Herrath, Michael J. Lenardo

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Metabolism

Glucose metabolism during rotational shift-work in healthcare workers
Anu Sharma, Marcello C. Laurenti, Chiara Dalla Man, Ron T. Varghese, Claudio Cobelli, Robert A. Rizza, Aleksey Matveyenko, Adrian Vella

Bed rest and resistive vibration exercise unveil novel links between skeletal muscle mitochondrial function and insulin resistance
Helena C. Kenny, Floriane Rudwill, Laura Breen, Michele Salanova, Dieter Blottner, Tim Heise, Martina Heer, Stephane Blanc, Donal J. O’Gorman

Impact of brown rice-specific γ-oryzanol on epigenetic modulation of dopamine D2 receptors in brain striatum in high-fat-diet-induced obesity in mice
Chisayo Kozuka, Tadashi Kaname, Chigusa Shimizu-Okabe, Chitoshi Takayama, Masato Tsutsui, Masayuki Matsushita, Keiko Abe, Hiroaki Masuzaki

Unravelling the regulation of insulin transport across the brain endothelial cell
Sarah M. Gray, Kevin W. Aylor, Eugene J. Barrett

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Pathophysiology and Complications

The human serum protein C4b-binding protein inhibits pancreatic IAPP-induced inflammasome activation
Klaudia Kulak, Gunilla T. Westermark, Nikolina Papac-Milicevic, Erik Renström, Anna M. Blom, Ben C. King

Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy
Klemens Fondi, Piotr A. Wozniak, Kinga Howorka, Ahmed M. Bata, Gerold C. Aschinger, Alina Popa-Cherecheanu, Katarzyna J. Witkowska, Anton Hommer, Doreen Schmidl, René M. Werkmeister, Gerhard Garhöfer, Leopold Schmetterer

Retinopathy with central oedema in an INS C94Y transgenic pig model of long-term diabetes
Kristina J. H. Kleinwort, Barbara Amann, Stefanie M. Hauck, Sieglinde Hirmer, Andreas Blutke, Simone Renner, Patrizia B. Uhl, Karina Lutterberg, Walter Sekundo, Eckhard Wolf, Cornelia A. Deeg

Metformin prevents ischaemic ventricular fibrillation in metabolically normal pigs
Li Lu, Shuyu Ye, Rebecca L. Scalzo, Jane E. B. Reusch, Clifford R. Greyson, Gregory G. Schwartz

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