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Younger age at diabetes diagnosis is linked to higher risk of death from heart disease and stroke, yet lower risk of cancer death

Read this new research by Professor Dianna Magliano and Professor Jonathan Shaw (Baker Heart and Diabetes Institute, Melbourne, Australia) and colleagues.
For further information contact Professor Dianna Magliano and Professor Jonathan Shaw via Suzana Talevski in the Baker Press Office (Suzana.talevski@baker.edu.au).

Current issue: June

June 2018 cover

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Electron tomography can be applied for the assessment of mitochondrial fine-structure in skeletal muscle biopsies. The cover picture shows an electron micrograph of a muscle biopsy obtained from a young and physically active individual with type 1 diabetes. The structural properties of mitochondria (red) and quantity of autophagy-associated structures in the subsarcolemmal (purple highlighting) and intermyofibrillar (highlighted in cyan) regions are visible. In the present issue of Diabetologia, Monaco et al report mitochondrial and metabolic impairments in muscles of young and physically active adults with type 1 diabetes at a very early stage of disease progression compared with individuals without type 1 diabetes. The authors propose that these changes may contribute to later clinical complications that characterise older adults with type 1 diabetes, such as frailty and physical disability.


Cover credit: Christian Lamberz (German Center for Neurodegenerative Diseases [DZNE], Bonn, Germany), Thomas Hawke (McMaster University, Hamilton, ON, Canada) and Christopher Perry (York University, Toronto, ON, Canada).

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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 some 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


Epidemiology of diabetes and diabetic complications in China
by Ronald C. W. Ma

Over the last few decades, China has witnessed one of the most dramatic increases in diabetes prevalence and currently has the largest population with diabetes in the world. In this issue, Ronald Ma (https://doi.org/10.1007/s00125-018-4557-7) summarises recent updates on the diabetes epidemic in China. He notes the increasing proportion of individuals with young-onset diabetes in China, as well as the increasing prevalence of gestational diabetes, with the potential for intergenerational effects on offspring. Cardiovascular and renal complications remain major causes of death in individuals with diabetes, though cancer and dementia are being increasingly recognised as important comorbidities of diabetes. Structured assessment and care delivery has been associated with improved risk factor control and reduced complications in some regions, such as Hong Kong. However, there remain significant challenges and notable treatment gaps, and multi-pronged strategies have been implemented to tackle these. The author highlights that prevention and optimal management will require good medical care, as well as improved health literacy, patient empowerment and a health-enabling environment. The figures from this review are available as a downloadable slideset. [Text supplied by the authors.]

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Extracellular matrix molecules and their potential contribution to the function of transplanted pancreatic islets
by L. Alberto Llacua, Marijke M. Faas, Paul de Vos

Understanding the nature of the extracellular matrix (ECM) and how it interacts with resident cells is the next step towards the recreation of biochemical cues for directing cell function in an artificial organ. Although transplantation of pancreatic islets has shown good clinical efficacy in patients with type 1 diabetes, the sudden loss of the pancreatic environment, subsequent interruption of cell-matrix interactions by isolation enzymes, and the lack of treatment to restore the ECM negatively impacts functional survival of pancreatic islet grafts. In this issue, Llacua et al (https://doi.org/10.1007/s00125-017-4524-8) summarise recent advances in our understanding of pancreatic islet cell membrane biology, specifically discussing the potential contribution of major ECM components to the function of transplanted pancreatic islets. The authors propose that developing knowledge of the crucial role the ECM plays in maintaining and driving endocrine function may facilitate the construction of supplemented bioartificial scaffolds to support islet function and improve glucose responsiveness and islet survival, advancing this therapeutic avenue for diabetes. The figures from this review are available as a downloadable slideset. [Text supplied by the authors.]

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Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose
by Jordi Merino, Aaron Leong, Ching-Ti Liu, Bianca Porneala, Geoffrey A. Walford, Marcin von Grotthuss, Thomas J. Wang, Jason Flannick, Josée Dupuis, Daniel Levy, Robert E. Gerszten, Jose C. Florez, James B. Meigs

Given the worldwide diabetes epidemic, it is important to evaluate novel approaches to improve type 2 diabetes prediction. This would allow us to identify people at elevated risk, who may benefit from focused prevention interventions. Prior studies have identified plasma metabolites which are associated with the development of type 2 diabetes among individuals initially without diabetes. However, the measurement of these metabolites does not greatly improve prediction of new diabetes beyond common clinical risk factors, such as BMI. In this issue, Merino et al (https://doi.org/10.1007/s00125-018-4599-x) report that metabolomic differences existed in individuals with normal blood glucose levels at baseline who developed diabetes over 20 years of follow-up, compared with individuals who remained diabetes free. Specifically, 19 metabolites were associated with type 2 diabetes incidence and measurement of these metabolites substantially improved prediction of future diabetes beyond common clinical risk factors. The authors propose that, if these findings are confirmed in other populations, we now have evidence that measurement of a defined set of metabolites could help identify individuals at risk of future type 2 diabetes, even when they appear clinically at low risk. [Text supplied by the authors.]

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Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents
by Daniel F. Vatner, Leigh Goedeke, Joao-Paulo G. Camporez, Kun Lyu, Ali R. Nasiri, Dongyan Zhang, Sanjay Bhanot, Susan F. Murray, Christopher D. Still, Glenn S. Gerhard, Gerald I. Shulman, Varman T. Samuel

Obese individuals do not all develop the same metabolic complications: some are metabolically healthy, while others develop insulin resistance, fatty liver and atherosclerosis. These metabolic complications are associated with ectopic lipid accumulation (e.g. in the liver, skeletal muscle) and, thus, improving adipose lipid storage could be beneficial. One possible approach is to enhance adipose lipoprotein lipase (LPL) activity, as this enzyme regulates tissue lipid uptake. In this issue, Vatner et al (https://doi.org/10.1007/s00125-018-4579-1) report that adipose tissue expression of ANGPTL8, an inhibitor of LPL, is higher in obese individuals with metabolic complications (insulin resistance and fatty liver) than in BMI-matched insulin-sensitive individuals. Decreasing angiopoietin-like 8 (ANGPTL8) expression using a synthetic Angptl8 antisense oligonucleotide in fat-fed rodents improved the clearance of meal-derived lipid molecules by adipose cells and, in turn, decreased the deposition of lipids in the liver and improved insulin sensitivity. These findings suggest that endogenous LPL inhibitors, such as ANGPTL8, could prove to be valuable targets to treat the metabolic complications of obesity. This article and the article by Janssen et al (see below) are the subject of a commentary in this issue by Brandon Davies (https://doi.org/10.1007/s00125-018-4604-4). [Text supplied by the authors.]

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Loss of angiopoietin-like 4 (ANGPTL4) in mice with diet-induced obesity uncouples visceral obesity from glucose intolerance partly via the gut microbiota
by Aafke W. F. Janssen, Saeed Katiraei, Barbara Bartosinska, Daniel Eberhard, Ko Willems van Dijk, Sander Kersten

The protein angiopoietin-like 4 (ANGPTL4) is known to reduce fat storage and raise circulating triacylglycerol levels by inhibiting the enzyme lipoprotein lipase (LPL). However, the role of ANGPTL4 in glucose homeostasis is less clear. In this issue, Janssen et al (https://doi.org/10.1007/s00125-018-4583-5) report that, despite having increased visceral adipose tissue mass and LPL activity, mice lacking ANGPTL4 (Angptl4-/- mice) have markedly improved glucose tolerance accompanied by elevated insulin levels compared with wild-type mice. Interestingly, suppression of the gut microbiota using antibiotics largely eliminated the differences in glucose tolerance and insulin levels between wild-type and Angptl4-/- mice. These findings indicate that ANGPTL4 uncouples the link between reduced adiposity and improved glucose tolerance, at least partly via a gut microbiota-dependent mechanism. The authors conclude that targeting ANGPTL4 might be therapeutically relevant beyond the lowering of plasma triacylglycerol levels. This article and the article by Vatner et al (see above) are the subject of a commentary in this issue by Brandon Davies (https://doi.org/10.1007/s00125-018-4604-4).[Text supplied by the authors.]

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Inside this issue

Up front

Up front June 2018

Reviews

Promises and pitfalls of electronic health record analysis
Ruth Farmer, Rohini Mathur, Krishnan Bhaskaran, Sophie V. Eastwood, Nish Chaturvedi, Liam Smeeth

Epidemiology of diabetes and diabetic complications in China
Ronald C. W. Ma

Extracellular matrix molecules and their potential contribution to the function of transplanted pancreatic islets
L. Alberto Llacua, Marijke M. Faas, Paul de Vos

Commentaries

Defining outcomes for beta cell replacement therapy: a work in progress
Lorenzo Piemonti, Eelco J. P. de Koning, Thierry Berney, Jon S. Odorico, James F. Markmann, Peter G. Stock, Michael R. Rickels

Can targeting ANGPTL proteins improve glucose tolerance?
Brandon S. J. Davies

Articles

Clinical Science and Care

Short-term decreased physical activity with increased sedentary behaviour causes metabolic derangements and altered body composition: effects in individuals with and without a first-degree relative with type 2 diabetes
Kelly A. Bowden Davies, Victoria S. Sprung, Juliette A. Norman, Andrew Thompson, Katie L. Mitchell, Jason C. G. Halford, Jo A. Harrold, John P. H. Wilding, Graham J. Kemp, Daniel J. Cuthbertson

Fibre supplementation for the prevention of type 2 diabetes and improvement of glucose metabolism: the randomised controlled Optimal Fibre Trial (OptiFiT)
Caroline Honsek, Stefan Kabisch, Margrit Kemper, Christiana Gerbracht, Ayman M. Arafat, Andreas L. Birkenfeld, Ulrike Dambeck, Martin A. Osterhoff, Martin O. Weickert, Andreas F. H. Pfeiffer

Effect of screening for type 2 diabetes on healthcare costs: a register-based study among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009
Camilla Sortsø, Anastasija Komkova, Annelli Sandbæk, Simon J. Griffin, Martha Emneus, Torsten Lauritzen, Rebecca K. Simmons

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Epidemiology

Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose
Jordi Merino, Aaron Leong, Ching-Ti Liu, Bianca Porneala, Geoffrey A. Walford, Marcin von Grotthuss, Thomas J. Wang, Jason Flannick, Josée Dupuis, Daniel Levy, Robert E. Gerszten, Jose C. Florez, James B. Meigs

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries
Short Communication
Sherly X. Li, Fumiaki Imamura, Matthias B. Schulze, Jusheng Zheng, Zheng Ye, Antonio Agudo, Eva Ardanaz, Dagfinn Aune, Heiner Boeing, Miren Dorronsoro, Courtney Dow, Guy Fagherazzi, Sara Grioni, Marc J. Gunter, José María Huerta, Daniel B. Ibsen, Marianne Uhre Jakobsen, Rudolf Kaaks, Timothy J. Key, Kay-Tee Khaw, Cecilie Kyrø, Francesca Romana Mancini, Elena Molina-Portillo, Neil Murphy, Peter M. Nilsson, N. Charlotte Onland-Moret, Domenico Palli, Salvatore Panico, Alaitz Poveda, J. Ramón Quirós, Fulvio Ricceri, Ivonne Sluijs, Annemieke M. W. Spijkerman, Anne Tjonneland, Rosario Tumino, Anna Winkvist, Claudia Langenberg, Stephen J. Sharp, Elio Riboli, Robert A. Scott, Nita G. Forouhi, Nicholas J. Wareham

Overweight, obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study
Rebecka Hjort, Emma Ahlqvist, Per-Ola Carlsson, Valdemar Grill, Leif Groop, Mats Martinell, Bahareh Rasouli, Anders Rosengren, Tiinamaija Tuomi, Bjørn Olav Åsvold, Sofia Carlsson

Lp-PLA2 activity is associated with increased risk of diabetic retinopathy: a longitudinal disease progression study
Moneeza K. Siddiqui, Gwen Kennedy, Fiona Carr, Alexander S. F. Doney, Ewan R. Pearson, Andrew D. Morris, Toby Johnson, Megan M. McLaughlin, Rachel E. Williams, Colin N. A. Palmer

Impact of long-term air pollution exposure on metabolic control in children and adolescents with type 1 diabetes: results from the DPV registry
Stefanie Lanzinger, Joachim Rosenbauer, Dorothea Sugiri, Tamara Schikowski, Birgit Treiber, Daniela Klee, Wolfgang Rathmann, Reinhard W. Holl

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Islet Studies

Distribution of IL-1β immunoreactive cells in pancreatic biopsies from living volunteers with new-onset type 1 diabetes: comparison with donors without diabetes and with longer duration of disease
Shiva Reddy, Lars Krogvold, Charlton Martin, Rebecca Holland, Jaimin Choi, Hannah Woo, Fiona Wu, Knut Dahl-Jørgensen

The resident macrophages in murine pancreatic islets are constantly probing their local environment, capturing beta cell granules and blood particles
Bernd H. Zinselmeyer, Anthony N. Vomund, Brian T. Saunders, Michael W. Johnson, Javier A. Carrero, Emil R. Unanue

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Immunology and Transplantation

Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice
Yulin Chen, Jie Wu, Jiajia Wang, Wenjing Zhang, Bohui Xu, Xiaojun Xu, Li Zong

B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model
Larissa C. Da Rosa, Joanne Boldison, Evy De Leenheer, Joanne Davies, Li Wen, F. Susan Wong

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Metabolism

Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes
Cynthia M. F. Monaco, Meghan C. Hughes, Sofhia V. Ramos, Nina E. Varah, Christian Lamberz, Fasih A. Rahman, Chris McGlory, Mark A. Tarnopolsky, Matthew P. Krause, Robert Laham, Thomas J. Hawke, Christopher G. R. Perry

Ceramide stearic to palmitic acid ratio predicts incident diabetes
Mika Hilvo, Tuire Salonurmi, Aki S. Havulinna, Dimple Kauhanen, Eva Ringdal Pedersen, Grethe S. Tell, Klaus Meyer, Anna-Maria Teeriniemi, Tiina Laatikainen, Pekka Jousilahti, Markku J. Savolainen, Ottar Nygård, Veikko Salomaa, Reijo Laaksonen

Angptl8 antisense oligonucleotide improves adipose lipid metabolism and prevents diet-induced NAFLD and hepatic insulin resistance in rodents
Daniel F. Vatner, Leigh Goedeke, Joao-Paulo G. Camporez, Kun Lyu, Ali R. Nasiri, Dongyan Zhang, Sanjay Bhanot, Susan F. Murray, Christopher D. Still, Glenn S. Gerhard, Gerald I. Shulman, Varman T. Samuel

Loss of angiopoietin-like 4 (ANGPTL4) in mice with diet-induced obesity uncouples visceral obesity from glucose intolerance partly via the gut microbiota
Aafke W. F. Janssen, Saeed Katiraei, Barbara Bartosinska, Daniel Eberhard, Ko Willems van Dijk, Sander Kersten

Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes
Thomas Laeger, Teresa Castaño-Martinez, Martin W. Werno, Lukasz Japtok, Christian Baumeier, Wenke Jonas, Burkhard Kleuser, Annette Schürmann

Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets
Isabel González-Mariscal, Rodrigo A. Montoro, Máire E. Doyle, Qing-Rong Liu, Michael Rouse, Jennifer F. O’Connell, Sara Santa-Cruz Calvo, Susan M. Krzysik-Walker, Soumita Ghosh, Olga D. Carlson, Elin Lehrmann, Yongqing Zhang, Kevin G. Becker, Chee W. Chia, Paritosh Ghosh, Josephine M. Egan

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Pathophysiology and Complications

Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study
Anna E. Long, Isabel V. Wilson, Dorothy J. Becker, Ingrid M. Libman, Vincent C. Arena, F. Susan Wong, Andrea K. Steck, Marian J. Rewers, Liping Yu, Peter Achenbach, Rosaura Casas, Johnny Ludvigsson, Alistair J. K. Williams, Kathleen M. Gillespie

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Correction

Correction to: Epidemiology of diabetes and diabetic complications in China
Ronald C. W. Ma

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