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New study reveals adverse impact of both type 2 and type 1 diabetes on pregnancy outcomes

Read this new research by Dr Sharon Mackin and Dr Robert Lindsay from the University of Glasgow, UK and colleagues.
For further information contact Dr Mackin (sharonmackin@nhs.net) or Dr Lindsay (Robert.lindsay@glasgow.ac.uk)..

Current issue: February

February 2018 cover

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The cover shows a painting entitled 'Theodor Billroth Operating', by Adalbert F. Seligmann, circa 1890, depicting the surgeon in Vienna. Dr Billroth (1829-1894) pioneered gastrectomies for ulcers and cancer. Since the 1920s, rapid resolution of glycosuria was observed in patients with diabetes who underwent a Billroth II gastrectomy, which includes a bypass of the proximal small intestine. Modern-day gastric bypass surgery, which creates a similar bypass, is now recognised as a highly effective therapy for type 2 diabetes. In this issue of Diabetologia, Cummings and Rubino review basic and clinical evidence supporting new, widely endorsed recommendations by the second Diabetes Surgery Summit to place such 'metabolic surgery' in the diabetes treatment algorithm, including among individuals who are only mildly obese.


Cover credit: akg-images / ullstein bild

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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


Metabolic surgery for the treatment of type 2 diabetes in obese individuals
by David E. Cummings, Francesco Rubino

Several bariatric operations dramatically improve glucose homeostasis, causing type 2 diabetes remission in most cases. This results from weight loss and from diverse weight-independent glucose-lowering mechanisms. Results from large, long-term observational studies and numerous randomised clinical trials directly comparing surgery vs medical/lifestyle diabetes therapies uniformly show that surgery achieves better glycaemic control and reduction of cardiometabolic risk, including among people not obese enough to qualify for traditional bariatric surgery. Based on such evidence, bariatric operations are now being repurposed as specific therapy for type 2 diabetes, a practice dubbed 'metabolic surgery'. In a review in this issue (https://doi.org/10.1007/s00125-017-4513-y), Cummings and Rubino summarise mechanistic and clinical evidence supporting new guidelines developed during the second Diabetes Surgery Summit, an international consensus conference, for use of metabolic surgery. These recommendations, now ratified by 53 worldwide medical/scientific societies and incorporated into the ADA Standards of Diabetes Care in 2017, suggest considering metabolic surgery for inadequately controlled type 2 diabetes in individuals with a BMI as low as 30 kg/m2, or 27.5 kg/m2 for Asian individuals. The figures from this review are available as a downloadable slideset. [Text supplied by the authors.]

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Medication use for the treatment of diabetes in obese individuals
by John P. H. Wilding

People with type 2 diabetes are often also obese, and obesity can complicate type 1 diabetes. The newer glucose-lowering medications, namely the glucagon-like peptide-1 receptor agonists and the sodium-glucose cotransporter 2 inhibitors, also reduce body weight, and new anti-obesity drugs have become available that complement lifestyle weight management. In this issue (https://doi.org/10.1007/s00125-017-4288-1), John Wilding reviews the effects of different diabetes medications on body weight, and discusses how a weight-focussed approach to diabetes treatment, including appropriate use of glucose-lowering medicines that help weight loss, and anti-obesity medication, can help optimise outcomes for people with diabetes and obesity. Many novel medicines for obesity and diabetes, including combinations of drugs with complementary modes of action, are in development and may result in a much greater emphasis on this approach in the future. [Text supplied by the authors.]

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Translating aetiological insight into sustainable management of type 2 diabetes
by Roy Taylor and Alison C. Barnes

The aetiology of type 2 diabetes can now be simply described. The 2008 twin cycle hypothesis postulated that chronic energy excess leads to a vicious cycle progressively driving up liver fat content, increasing export of triacylglycerols to the pancreas and, in susceptible people, ultimately results in failure of the acute insulin response. In this issue (https://doi.org/10.1007/s00125-017-4504-z), Taylor and Barnes summarise studies testing the hypothesis in individuals with a short duration of type 2 diabetes using a low-energy diet and maintenance of reduced body weight. The beta cell defect can now be understood as de-differentiation, caused by cellular metabolic stress and reversible loss of specialised function. Longer-term management highlights the need for effective approaches to dietary advice. It is clear that one diet cannot suit all, therefore, a range of soundly based approaches, tailored to individual preferences, is described. The critical role of family and social circle in achieving sustainable changes in food habits is considered. The figures from this review are available as a downloadable slideset. [Text supplied by the authors.]

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Enteroendocrine K and L cells in healthy and type 2 diabetic individuals
by Tina Jorsal, Nicolai A. Rhee, Jens Pedersen, Camilla D. Wahlgren, Brynjulf Mortensen, Sara L. Jepsen, Jacob Jelsing, Louise S. Dalbøge, Peter Vilmann, Hazem Hassan, Jakob W. Hendel, Steen S. Poulsen, Jens J. Holst, Tina Vilsbøll, Filip K. Knop

Hormones from enteroendocrine K and L cells are well-established regulators of glucose homeostasis and appetite. However, it is unclear how these enteroendocrine cells are distributed in the healthy human intestinal tract and whether this distribution is altered in type 2 diabetes. In this issue (https://doi.org/10.1007/s00125-017-4450-9), Jorsal et al report the results of anterograde and retrograde double-balloon enteroscopy with frequent mucosal biopsy retrieval (every 30 cm) along the entire intestinal tract in 12 individuals with type 2 diabetes and 12 healthy individuals. They found that K cells and L cells exhibit specific distribution patterns along the small and large intestine. Furthermore, they show differences between healthy and type 2 diabetic individuals in distribution patterns and expression profiles of K and L cells. These findings provide a reference work for scientists and clinicians and may promote the understanding of the integrative role of the gut in the regulation of glucose metabolism and appetite. [Text supplied by the authors.]

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Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT)
by Lily Agrawal, Nasrin Azad, Gideon D. Bahn, Ling Ge, Peter D. Reaven, Rodney A. Hayward, Domenic J. Reda, Nicholas V. Emanuele, for the VADT Study Group

Nephropathy in type 2 diabetes is associated with a progressive increase in proteinuria, decline in eGFR and eventual renal failure. Whether the pursuit of intensive glycaemic control to reduce the rate of chronic kidney disease (CKD) is worth the effort, cost and patient burden is an important clinical question that many trials have tried to answer. In this issue (https://doi.org/10.1007/s00125-017-4473-2), Agrawal et al report the results of an analysis of the Veterans Affairs Diabetes Trial (VADT) and follow-up study. Participants had advanced type 2 diabetes and prevalent cardiovascular disease, and received excellent blood pressure and lipid management. Intensive glycaemic control for a median of 5.6 years resulted in significantly more people maintaining an eGFR above 60 ml min-1 1.73 m-2 for up to almost 11 years. This benefit was most evident in those with a moderate-to-high risk of CKD at baseline. Drug-specific benefits could not be elucidated, however, the follow-up was much longer than in recent studies on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. [Text supplied by the authors.]

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Inside this issue

Up front

Up front February 2018

Reviews

Metabolic surgery for the treatment of type 2 diabetes in obese individuals
David E. Cummings, Francesco Rubino

Medication use for the treatment of diabetes in obese individuals
John P. H. Wilding

Translating aetiological insight into sustainable management of type 2 diabetes
Roy Taylor, Alison C. Barnes

Articles

Clinical Science and Care

Enteroendocrine K and L cells in healthy and type 2 diabetic individuals
Tina Jorsal, Nicolai A. Rhee, Jens Pedersen, Camilla D. Wahlgren, Brynjulf Mortensen, Sara L. Jepsen, Jacob Jelsing, Louise S. Dalbøge, Peter Vilmann, Hazem Hassan, Jakob W. Hendel, Steen S. Poulsen, Jens J. Holst, Tina Vilsbøll, Filip K. Knop

Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT)
Short Communication
Lily Agrawal, Nasrin Azad, Gideon D. Bahn, Ling Ge, Peter D. Reaven, Rodney A. Hayward, Domenic J. Reda, Nicholas V. Emanuele, for the VADT Study Group

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Epidemiology

The association between Helicobacter pylori seropositivity and risk of new-onset diabetes: a prospective cohort study
Mengge Zhou, Jing Liu, Yue Qi, Miao Wang, Ying Wang, Fan Zhao, Yongchen Hao, Dong Zhao

Dietary antioxidant capacity and risk of type 2 diabetes in the large prospective E3N-EPIC cohort
Francesca Romana Mancini, Aurélie Affret, Courtney Dow, Beverley Balkau, Fabrice Bonnet, Marie-Christine Boutron-Ruault, Guy Fagherazzi

Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis
Nicola M. McKeown, Hassan S. Dashti, Jiantao Ma, Danielle E. Haslam, Jessica C. Kiefte-de Jong, Caren E. Smith, Toshiko Tanaka, Mariaelisa Graff, Rozenn N. Lemaitre, Denis Rybin, Emily Sonestedt, Alexis C. Frazier-Wood, Dennis O. Mook-Kanamori, Yanping Li, Carol A. Wang, Elisabeth T. M. Leermakers, Vera Mikkilä, Kristin L. Young, Kenneth J. Mukamal, L. Adrienne Cupples, Christina-Alexandra Schulz, Tzu-An Chen, Ruifang Li-Gao, Tao Huang, Wendy H. Oddy, Olli Raitakari, Kenneth Rice, James B. Meigs, Ulrika Ericson, Lyn M. Steffen, Frits R. Rosendaal, Albert Hofman, Mika Kähönen, Bruce M. Psaty, Louise Brunkwall, Andre G. Uitterlinden, Jorma Viikari, David S. Siscovick, Ilkka Seppälä, Kari E. North, Dariush Mozaffarian, Josée Dupuis, Marju Orho-Melander, Stephen S. Rich, Renée de Mutsert, Lu Qi, Craig E. Pennell, Oscar H. Franco, Terho Lehtimäki, Mark A. Herman

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease
Akiko Kishi Svensson, Thomas Svensson, Mariusz Kitlinski, Peter Almgren, Gunnar Engström, Peter M. Nilsson, Olle Melander

Why childhood-onset type 1 diabetes impacts labour market outcomes: a mediation analysis
Sofie Persson, Gisela Dahlquist, Ulf-G. Gerdtham, Katarina Steen Carlsson, for the Swedish Childhood Diabetes Study Group

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Genetics

DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels: a systematic review and replication in a case–control sample of the Lifelines study
Eliza Walaszczyk, Mirjam Luijten, Annemieke M. W. Spijkerman, Marc J. Bonder, Helen L. Lutgers, Harold Snieder, Bruce H. R. Wolffenbuttel, Jana V. van Vliet-Ostaptchouk

Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
Michele Longo, Gregory A. Raciti, Federica Zatterale, Luca Parrillo, Antonella Desiderio, Rosa Spinelli, Ann Hammarstedt, Shahram Hedjazifar, Jenny M. Hoffmann, Cecilia Nigro, Paola Mirra, Francesca Fiory, Pietro Formisano, Claudia Miele, Ulf Smith, Francesco Beguinot

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Immunology and Transplantation

Enterovirus-associated changes in blood transcriptomic profiles of children with genetic susceptibility to type 1 diabetes
Niina Lietzen, Le T. T. An, Maria K. Jaakkola, Henna Kallionpää, Sami Oikarinen, Juha Mykkänen, Mikael Knip, Riitta Veijola, Jorma Ilonen, Jorma Toppari, Heikki Hyöty, Riitta Lahesmaa, Laura L. Elo

Oral histone deacetylase inhibitor synergises with T cell targeted immunotherapy to preserve beta cell metabolic function and induce stable remission of new-onset autoimmune diabetes in NOD mice
Alix Besançon, Tania Goncalves, Fabrice Valette, Mattias S. Dahllöf, Thomas Mandrup-Poulsen, Lucienne Chatenoud, Sylvaine You

Metabolism

Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes
Anaïs Szpigel, Isabelle Hainault, Aurélie Carlier, Nicolas Venteclef, Anne-Françoise Batto, Eric Hajduch, Catherine Bernard, Alain Ktorza, Jean-François Gautier, Pascal Ferré, Olivier Bourron, Fabienne Foufelle

GIP(3-30)NH2 is an efficacious GIP receptor antagonist in humans: a randomised, double-blinded, placebo-controlled, crossover study
Lærke S. Gasbjerg, Mikkel B. Christensen, Bolette Hartmann, Amalie R. Lanng, Alexander H. Sparre-Ulrich, Maria B. N. Gabe, Flemming Dela, Tina Vilsbøll, Jens J. Holst, Mette M. Rosenkilde, Filip K. Knop

FAK tyrosine phosphorylation is regulated by AMPK and controls metabolism in human skeletal muscle
David G. Lassiter, Carolina Nylén, Rasmus J. O. Sjögren, Alexander V. Chibalin, Harriet Wallberg-Henriksson, Erik Näslund, Anna Krook, Juleen R. Zierath

α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats
Cynthia M.F. Monaco, Ross Proudfoot, Paula M. Miotto, Eric A.F. Herbst, Rebecca E.K. MacPherson, Graham P. Holloway

Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats
Haiyun Qi, Per M. Nielsen, Marie Schroeder, Lotte B. Bertelsen, Fredrik Palm, Christoffer Laustsen

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Pathophysiology and Complications

Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes Cohort Study
Claudia R. L. Cardoso, Nathalie C. Leite, Guilherme C. Salles, Marcel T. Ferreira, Gil F. Salles

Impact of prolonged overfeeding on skeletal muscle mitochondria in healthy individuals
Frederico G. S. Toledo, Darcy L. Johannsen, Jeffrey D. Covington, Sudip Bajpeyi, Bret Goodpaster, Kevin E. Conley, Eric Ravussin

A Coxsackievirus B vaccine protects against virus-induced diabetes in an experimental mouse model of type 1 diabetes
Short Communication
Virginia M. Stone, Minna M. Hankaniemi, Emma Svedin, Amirbabak Sioofy-Khojine, Sami Oikarinen, Heikki Hyöty, Olli H. Laitinen, Vesa P. Hytönen, Malin Flodström-Tullberg

Annexin A1 attenuates microvascular complications through restoration of Akt signalling in a murine model of type 1 diabetes
Gareth S. D. Purvis, Fausto Chiazza, Jianmin Chen, Rodrigo Azevedo-Loiola, Lukas Martin, Dennis H. M. Kusters, Chris Reutelingsperger, Nikolaos Fountoulakis, Luigi Gnudi, Muhammed M. Yaqoob, Massimo Collino, Christoph Thiemermann, Egle Solito

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Letter

Exercise training response heterogeneity: statistical insights
Greg Atkinson, Philip Williamson, Alan M. Batterham

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Correction

Correction to: Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort
Pia Deichgræber, Daniel R. Witte, Holger J. Møller, Mette V. Skriver, Bjørn Richelsen, Marit E. Jørgensen, Nanna B. Johansen, Annelli Sandbæk

Correction to: Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans
Rebecca K. C. Loh, Melissa F. Formosa, Nina Eikelis, David A. Bertovic, Mitchell J. Anderson, Shane A. Barwood, Shane Nanayakkara, Neale D. Cohen, Andre La Gerche, Anne T. Reutens, Kenneth S. Yap, Thomas W. Barber, Gavin W. Lambert, Martin H. Cherk, Stephen J. Duffy, Bronwyn A. Kingwell, Andrew L. Carey

Correction to: Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes
Toma Keser, Ivan Gornik, Frano Vučković, Najda Selak, Tamara Pavić, Edita Lukić, Ivan Gudelj, Hrvoje Gašparović, Bojan Biočina, Therese Tilin, Annika Wennerström, Satu Männistö, Veikko Salomaa, Aki Havulinna, Wei Wang, James F. Wilson, Nish Chaturvedi, Markus Perola, Harry Campbell, Gordan Lauc, Olga Gornik

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