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Diabetologia May 2017 issue now available

30 April 2017 (07:08 PM) - Medical Journals

The May 2017 content of Diabetologia, the official journal of EASD is now available. Below you will find a link to the full content, and an abstract of open access articles selected by the editor, Sally Marshall.

The whole table of contents can be found here


Melatonin signalling and type 2 diabetes risk: is it a case of too little or too much? by Commentaries by: Amélie Bonnefond, Philippe Froguel; Hindrik Mulder

Sweet dreams or nightmares? Human genetics provides a powerful tool for identifying causal pathways and relationships of disease risk. In the field, it is well recognised that genetic variation in and near MTNR1B influences type 2 diabetes risk but finding consensus on the molecular mechanisms that bring about this effect is still an area of hot debate and current research activity. In this issue, we feature a review by Forrestel et al (DOI 10.1007/s00125-016-4175-1; see below), summarising our current knowledge of melatonin in diabetes. In addition, because this is currently such a controversial field, we have commissioned two articles from laboratories that are leading research to understand the role of genetic variation in the melatonin receptor in diabetes risk: Bonnefond and Froguel (DOI 10.1007/s00125-017-4255-x) make a case for the detrimental impact of too little melatonin signalling on type 2 diabetes risk, whilst Hindrik Mulder (DOI 10.1007/s00125-017-4249-8) outlines evidence for the negative effect of both elevated and reduced melatonin signalling on diabetes risk. These authors present their opinions on the interpretation of the current landscape and thoughts on how the field might resolve them. [Text supplied by the authors.]


Chronomedicine and type 2 diabetes: shining some light on melatonin by Andrew C. Forrestel, Susanne U. Miedlich, Michael Yurcheshen, Steven D. Wittlin, Michael T. Sellix

Circadian timing systems are almost universally present in living organisms, from unicellular to mammalian species. In mammals (including humans), the timing system makes a sizeable contribution to insulin secretion and glucose metabolism processes. Pineal melatonin, known primarily for its role as a 'sleep hormone', is a principal mediator of human circadian rhythms. Disruption of this system is associated with obesity, dysglycaemia and other metabolic disturbances. In this issue, Forrestal et al (DOI 10.1007/s00125-016-4175-1) review the regulation of circadian rhythmicity, paying specific attention to the metabolic consequences of its disruption. Focus is placed on the impact of melatonin on metabolic processes, especially insulin secretion, and the consequences of melatonin receptor polymorphisms on glucose homeostasis and diabetes risk. Interestingly, melatonin levels are reduced in individuals with diabetes. In line with this, the authors provide a clinical perspective on the use of melatonin as a potential chronotherapy for the management of diabetes, discussing the pros and cons of melatonin therapy for glycaemic control. They conclude by highlighting the need for more dedicated study of chronopharmacological agents, such as melatonin, for the treatment of metabolic diseases. [Text supplied by the authors.]


Prolonged sitting may increase diabetes risk in physically inactive individuals: an 11 year follow-up of the HUNT Study, Norway by Bjørn O. Åsvold, Kristian Midthjell, Steinar Krokstad, Vegar Rangul, Adrian Bauman

Emerging evidence indicates that prolonged sitting may have adverse effects on blood glucose levels and insulin sensitivity, but few studies have examined the association between total daily sitting time and the risk of diabetes. In this issue, Åsvold et al (DOI 10.1007/s00125-016-4193-z) report the association between total sitting time and the risk of diabetes during an 11 year follow-up of the population-based Nord-Trøndelag Health Study (the HUNT Study). Total sitting time had little association with diabetes risk in the population as a whole. However, among physically inactive individuals, sitting ≥8 h/day was associated with a 30% increased risk of diabetes compared with sitting ≤4 h/day. The results suggest that prolonged sitting may contribute to increased risk of diabetes among physically inactive people. [Text supplied by the authors.]


Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels by Yuvaraj Mahendran, Anna Jonsson, Christian T. Have, Kristine H. Allin, Daniel R. Witte, Marit E. Jørgensen, Niels Grarup, Oluf Pedersen, Tuomas O. Kilpeläinen, Torben Hansen

Fasting plasma levels of branched-chain amino acids (BCAA) are associated with peripheral insulin resistance. However, it is unclear whether this association is due to a causal link between BCAA levels and insulin resistance. In this issue, Mahendran et al (DOI 10.1007/s00125-017-4222-6) report that a genetically-determined increase in circulating BCAA levels does not lead to more severe insulin resistance. In contrast, a genetically-determined increase in the severity of insulin resistance resulted in elevated circulating BCAA levels. The authors conclude that the association between circulating BCAA levels and insulin resistance likely reflects a causal effect of insulin resistance on BCAA levels; this may be explained by the impact of insulin (a chief regulator of amino acid metabolism) on the rate of appearance and clearance of BCAA together with decreased activity of catabolic enzymes involved in BCAA metabolism. In summary, increased BCAA levels in individuals with insulin resistance appears to be a marker of impaired insulin action rather than a causative factor. [Text supplied by the authors.]


Glucose and fatty acids synergistically and reversibly promote beta cell proliferation in rats by Valentine S. Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout

The mechanisms by which glucose homeostasis is maintained in the face of insulin resistance involve, at least in part, an increase in pancreatic beta cell mass via proliferation. Since failure of this compensatory response leads to type 2 diabetes, understanding its underlying mechanism is clinically relevant. In this issue, Moullé et al (DOI 10.1007/s00125-016-4197-8) report the effects of glucose and NEFA, alone or in combination, on beta cell proliferation. Using complementary in vivo studies in rats and ex vivo studies in isolated rat and human islets, the authors showed that glucose and NEFA synergistically and reversibly stimulated beta cell proliferation via several mechanisms, including via direct effect of these nutrients. Furthermore, nutrient-induced endogenous circulating factors released in response to insulin resistance potentiated beta cell proliferation. Importantly, nutrient-induced beta cell proliferation was independent from secreted insulin. These findings underscore the complexity of the beta cell response to nutrient excess in vivo. [Text supplied by the authors.]


Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent reno- and atheroprotection even in established micro- and macrovascular disease by Stephen P. Gray, Jay C. Jha, Kit Kennedy, Erik van Bommel, Phyllis Chew, Cedric Szyndralewiez, Rhian M. Touyz, Harald H. H. W. Schmidt, Mark E. Cooper, Karin A. M. Jandeleit-Dahm

Oxidative stress derived from NADPH oxidase (NOX)1 and NOX4 has been reported to contribute to the development of diabetic complications, in particular diabetes-accelerated atherosclerosis and kidney disease. However, it has not yet been tested whether NOX-targeted drug intervention in established disease can prevent diabetes progression. In this issue, Gray et al (DOI 10.1007/s00125-017-4215-5) report that administration of a novel NOX inhibitor that prevents NOX1- and NOX4-derived oxidative stress halts the progression of kidney disease and the development of atherosclerosis. Tissue-specific and dose-dependent effects were evident in the response to NOX inhibition, particularly with regards to its impact on atherosclerosis progression. These studies highlight the importance of defining the optimal relative balance between NOX1 and NOX4 inhibition in the micro- and macrovasculature for the management of diabetes. [Text supplied by the authors.]