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Welcome to Diabetologia

Diabetologia publishes original clinical 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.

In the News

Maternal smoking during pregnancy and daughters' risk of gestational diabetes and obesity
by K. Mattsson, K. Källén, M. P. Longnecker, A. Rignell-Hydbom, L. Rylander

Contact Kristina Mattsson (kristina.mattsson@med.lu.se)

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(posted online 22.01 h BST Monday 20th May 2013)

Current issue: July 2013

July 2013 cover

Click here to view this month's contents

The cover image shows a coloured laser scan micrograph of insulin-secreting INS-1E cells. Under standard culture conditions the pro-apoptotic transcription factor FOXO1 (stained in green) displays a strong cytosolic localisation, while only minor levels reside in the nuclei (blue). Regulation of insulin secretion depends on a network of actin filaments (red) underneath the plasma membrane. Activation of insulin and IGF-1 receptor signalling pathways is crucial for translational and post-translational regulation of FOXO1. In this issue of Diabetologia, Kaiser et al decipher the differential regulation of cytosolic-nuclear trafficking of FOXO1 by AKT isoforms and glucocorticoids. The synergistic action of increased transcription and reduced phosphorylation of FOXO1, triggered by distinct pathways, contributes to beta cell dysfunction. This study helps us understand the circumstances that lead to the development of steroid diabetes.



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Cover credit: Felicia Gerst, University of Tübingen, Germany

Up front

Juleen Zierath

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. Juleen R. Zierath, Editor


Insulin resistance in type 1 diabetes: what is 'double diabetes' and what are the risks?
by S. J. Cleland, B. M. Fisher, H. M. Colhoun, N. Sattar, J. R. Petrie

Type 1 diabetes is not only a condition of insulin deficiency, but also of peripheral insulin resistance and altered fat partitioning, the latter caused by delivery of therapeutic insulin by the subcutaneous route. Moreover, relative portal insulinopenia alters lipoprotein dynamics. Lifestyle (weight gain/inactivity) and genetic (family history of type 2 diabetes) factors may adversely influence this phenotype, which has been described as 'double diabetes'. Increasing epidemiological evidence suggests that insulin resistance is relevant to premature cardiovascular disease in type 1 diabetes. In this issue, the review by Cleland et al highlights the current understanding of the pathophysiology of double diabetes. The authors underline a need for further research in this area; the resulting evidence will shape future clinical recommendations in terms of (1) insulin sensitising therapy (weight loss, physical activity and metformin), (2) use of statins and (3) targets for BP control. Appreciation of the risks, as well as benefits, of intensive insulin regimens might lead to improved prevention of complications. [Text supplied by the authors.]

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Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct
by The InterAct Consortium

Several studies have provided evidence for an association between high sugar-sweetened beverage consumption and an increased risk of type 2 diabetes; however, most of these studies were North American and comprised small sample sizes. In this issue, the InterAct Consortium present the results of one of the largest studies conducted in Europe on the association between consumption of sugar-sweetened soft drinks, artificially sweetened soft drinks, and juice and nectars and incidence of type 2 diabetes. The study included 12,403 incident type 2 diabetes cases identified within a cohort of more than 350,000 participants from eight European countries. The authors report that consuming only one glass per day of sugar-sweetened soft drinks could raise your risk of diabetes by 39% compared with non-consumption. This increased risk was only partly attenuated when the energy intake and BMI of participants were taken into account. Consumption of artificially sweetened soft drinks or juices and nectars was not associated with diabetes incidence. This study confirms that high consumption of sugar-sweetened soft drinks is associated with an increased risk of type 2 diabetes in European adults. [Text supplied by the authors.]

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Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient
by D. Jacobs-Tulleneers-Thevissen, M. Chintinne, Z. Ling, P. Gillard, L. Schoonjans, G. Delvaux, B. L. Strand, F. Gorus, B. Keymeulen, D. Pipeleers on behalf of the Beta Cell Therapy Consortium EU-FP7

Intraportal human islet implants can correct hyperglycaemia in type 1 diabetic patients, but they progressively lose function. Their decline can be attributed to (auto)immune reactivity, inadequate grafts or the implant site. Alginate encapsulation has an immunoprotective effect on rodent islet allografts. In this issue, Jacobs-Tulleneers-Thevissen et al report that alginate-encapsulated human islet cells implanted in the peritoneal cavity of diabetic immunodeficient mice achieve sustained metabolic correction, more reproducibly than free implants of similar composition implanted under the kidney capsule. Retrieved capsules contained well-granulated endocrine cells exhibiting rapid insulin secretory responses to glucose and glucagon. A pilot study in a type 1 diabetic patient showed that intact human endocrine islet cells with glucose-inducible insulin release were also present in fibrosis-free capsules retrieved after 3 months. However, the cells were too few in number to achieve metabolic function. The methods reported and data obtained from this study can be used to guide the further development of encapsulation towards clinical success. This article is the subject of a commentary in this issue by G. C. Weir. [Text supplied by the authors.]

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Expression of anti-inflammatory macrophage genes within skeletal muscle correlates with insulin sensitivity in human obesity and type 2 diabetes
by L. N. Fink, A. Oberbach, S. R. Costford, K. L. Chan, A. Sams, M. Blüher, A. Klip

Type 2 diabetes accompanied by obesity is considered an inflammatory disease, since the expanding adipose tissue contains multiple types of leucocytes and insulin resistance correlates with an increase in inflammatory cells. Skeletal muscle is a key organ for glucose disposal, but the importance of skeletal muscle leucocytes in obesity and diabetes is debated. In the present issue, Fink et al investigate evidence for leucocytes in skeletal muscle biopsies from overweight and obese individuals by gene expression analysis. Expression of the gene encoding the anti-inflammatory cytokine TGF-β was higher in muscle from non-diabetic compared to diabetic patients, and was inversely correlated with HbA1c. The expression of genes for three markers of anti-inflammatory macrophages correlated with higher insulin sensitivity, as measured by euglycaemic-hyperinsulinaemic clamps after a 1 year exercise regimen. These findings raise the possibility that increasing the number of anti-inflammatory macrophages in skeletal muscle through diet or exercise might help to improve insulin sensitivity. [Text supplied by the authors.]

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Inside this issue

In Memoriam

Harry Keen, 1925–2013
John C. Pickup

Commentary

Islet encapsulation: advances and obstacles
G. C. Weir

Review

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?
S. J. Cleland, B. M. Fisher, H. M. Colhoun, N. Sattar, J. R. Petrie

Systematic Review

Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodological approaches
S. Fazeli Farsani, M. P. van der Aa, M. M. J. van der Vorst, C. A. J. Knibbe, A. de Boer

Meta-analysis

Progression rates from HbA1c 6.0–6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis
D. H. Morris, K. Khunti, F. Achana, B. Srinivasan, L. J. Gray, M. J. Davies, D. Webb

Articles

Clinical Science and Care

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative
H. M. den Ruijter, S. A. E. Peters, K. A. Groenewegen, T. J. Anderson, A. R. Britton, J. M. Dekker, G. Engström, M. J. Eijkemans, G. W. Evans, J. de Graaf, D. E. Grobbee, B. Hedblad, A. Hofman, S. Holewijn, A. Ikeda, M. Kavousi, K. Kitagawa, A. Kitamura, H. Koffijberg, M. A. Ikram, E. M. Lonn, M. W. Lorenz, E. B. Mathiesen, G. Nijpels, S. Okazaki, D. H. O’Leary, J. F. Polak, J. F. Price, C. Robertson, C. M. Rembold, M. Rosvall, T. Rundek, J. T. Salonen, M. Sitzer, C. D. A. Stehouwer, J. C. Witteman, K. G. Moons, M. L. Bots

Efficacy and safety over 26 weeks of an oral treatment strategy including sitagliptin compared with an injectable treatment strategy with liraglutide in patients with type 2 diabetes mellitus inadequately controlled on metformin: a randomised clinical trial
B. Charbonnel, H. Steinberg, E. Eymard, L. Xu, P. Thakkar, V. Prabhu, M. J. Davies, S. S. Engel

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Epidemiology

Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry
H. U. Irgens, J. Molnes, B. B. Johansson, M. Ringdal, T. Skrivarhaug, D. E. Undlien, O. Søvik, G. Joner, A. Molven, P. R. Njølstad

Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct
The InterAct consortium

Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes (2000–2007)
J. J. Walker, D. H. Brewster, H. M. Colhoun, C. M. Fischbacher, R. S. Lindsay, S. H. Wild

The pro-inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with incident type 2 diabetes among overweight but not obese individuals with impaired glucose regulation: effect modification by smoking and body weight status
A. Heraclides, T. M. Jensen, S. S. Rasmussen, J. Eugen-Olsen, S. B. Haugaard, K. Borch-Johnsen, A. Sandbæk, T. Lauritzen, D. R. Witte

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Genetics

Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2 β: identification of miR-153 target genes with functions related to IA-2β in pancreas and brain
W. Mandemakers, L. Abuhatzira, H. Xu, L. A. Caromile, S. S. Hébert, A. Snellinx, V. A. Morais, S. Matta, T. Cai, A. L. Notkins, B. De Strooper

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Islet Studies

Functional differences between aggregated and dispersed insulin-producing cells
A. Chowdhury, O. Dyachok, A. Tengholm, S. Sandler, P. Bergsten

A novel mechanism regulating insulin secretion involving Herpud1 in mice
N. Wong, G. Morahan, M. Stathopoulos, J. Proietto, S. Andrikopoulos

Oscillations of sub-membrane ATP in glucose-stimulated beta cells depend on negative feedback from Ca2+
J. Li, H. Y. Shuai, E. Gylfe, A. Tengholm

Regulation of forkhead box O1 (FOXO1) by protein kinase B and glucocorticoids: different mechanisms of induction of beta cell death in vitro
G. Kaiser, F. Gerst, D. Michael, S. Berchtold, B. Friedrich, N. Strutz-Seebohm, F. Lang, H.-U. Häring, S. Ullrich

Effects of immunosuppression on alpha and beta cell renewal in transplanted mouse islets
C. Krautz, S. Wolk, A. Steffen, K.-P. Knoch, U. Ceglarek, J. Thiery, S. Bornstein, H.-D. Saeger, M. Solimena, S. Kersting

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Immunology and Transplantation

Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient
D. Jacobs-Tulleneers-Thevissen, M. Chintinne, Z. Ling, P. Gillard, L. Schoonjans, G. Delvaux, B. L. Strand, F. Gorus, B. Keymeulen, D. Pipeleers

Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children
P. Achenbach, M. Hummel, L. Thümer, H. Boerschmann, D. Höfelmann, A. G. Ziegler

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Metabolism

Expression of anti-inflammatory macrophage genes within skeletal muscle correlates with insulin sensitivity in human obesity and type 2 diabetes
Short Communication
L. N. Fink, A. Oberbach, S. R. Costford, K. L. Chan, A. Sams, M. Blüher, A. Klip

Skeletal muscle-specific overexpression of SIRT1 does not enhance whole-body energy expenditure or insulin sensitivity in young mice
A. T. White, C. E. McCurdy, A. Philp, D. L. Hamilton, C. D. Johnson, S. Schenk

Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding
N. Turner, G. M. Kowalski, S. J. Leslie, S. Risis, C. Yang, R. S. Lee-Young, J. R. Babb, P. J. Meikle, G. I. Lancaster, D. C. Henstridge, P. J. White, E. W. Kraegen, A. Marette, G. J. Cooney, M. A. Febbraio, C. R. Bruce

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Pathophysiology and Complications

Heterogeneous nuclear ribonucleoproteins F and K mediate insulin inhibition of renal angiotensinogen gene expression and prevention of hypertension and kidney injury in diabetic mice
S. Abdo, C.-S. Lo, I. Chenier, A. Shamsuyarova, J. G. Filep, J. R. Ingelfinger, S.-L. Zhang, J. S. D. Chan

Fractalkine and its receptor mediate extracellular matrix accumulation in diabetic nephropathy in mice
K. H. Song, J. Park, J. H. Park, R. Natarajan, H. Ha

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