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Karavitaki N.,Oxford Center for Diabetes
Journal of Endocrinological Investigation | Year: 2014

Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct. Their pathogenesis remains uncertain and they can present with a variety of manifestations attributed to pressure effects to surrounding structures. The optimal management of craniopharyngiomas remains challenging mainly due to their sharp, irregular borders and their tendency to adhere to vital neurovascular structures making surgical manipulations potentially hazardous to vital brain areas. Non-aggressive surgery followed by radiotherapy is currently the most widely used option possibly achieving the most optimal long-term outcome. Other treatment modalities including intracystic irradiation, intracystic instillation of antineoplasmatic agents and stereotactic radiotherapy are also available in our armamentarium. The long-term morbidities related with the craniopharyngiomas and their treatment remain significant, with hypothalamic damage playing the protagonist role and requiring further studies to identify measures that will improve the prognosis of the patients. © Italian Society of Endocrinology (SIE) 2014. Source

Gough S.C.L.,Oxford Center for Diabetes
Diabetes, Obesity and Metabolism | Year: 2012

Liraglutide, a once-daily glucagon-like peptide-1 receptor agonist, is approved for use as monotherapy in the USA and Japan (but not in Europe or Canada) and in combination with selected oral agents (all regions) for the treatment of patients with type 2 diabetes. Guidance from local advisory bodies is emerging on the most appropriate place for liraglutide in the treatment pathway. It is apparent from its phase 3 clinical trial programme that liraglutide provides superior glycaemic control compared with that achieved with other antidiabetic agents used early in the treatment pathway (e.g. glimepiride and sitagliptin). Key additional benefits include a low incidence of hypoglycaemia and clinically relevant weight loss, although these benefits may be ameliorated by concomitant sulphonylurea (SU) treatment and, in the case of hypoglycaemia, reduction of the SU dose may be necessary. Overall, the profile of liraglutide is similar and, in some aspects, superior to twice-daily exenatide. The implementation of liraglutide therapy is straightforward, with simple dose titration from the starting dose of 0.6 to 1.2 mg/day after 1 week; some patients may benefit from additional titration to 1.8 mg/day. Treatment is self-administered by subcutaneous injection. This contrasts with other agents used early in the treatment pathway, but clinical data suggest patients' overall treatment satisfaction with liraglutide is similar (1.2 mg) or better (1.8 mg) than that with sitagliptin despite differing administration methods. Some patients may experience nausea when initiating liraglutide treatment, but the titration regimen is designed to improve tolerability and clinical data indicate nausea is transient. © 2012 Blackwell Publishing Ltd. Source

Visscher P.M.,University of Queensland | Brown M.A.,University of Queensland | McCarthy M.I.,University of Oxford | McCarthy M.I.,Oxford Center for Diabetes | Yang J.,Queensland Institute of Medical Research
American Journal of Human Genetics | Year: 2012

The past five years have seen many scientific and biological discoveries made through the experimental design of genome-wide association studies (GWASs). These studies were aimed at detecting variants at genomic loci that are associated with complex traits in the population and, in particular, at detecting associations between common single-nucleotide polymorphisms (SNPs) and common diseases such as heart disease, diabetes, auto-immune diseases, and psychiatric disorders. We start by giving a number of quotes from scientists and journalists about perceived problems with GWASs. We will then briefly give the history of GWASs and focus on the discoveries made through this experimental design, what those discoveries tell us and do not tell us about the genetics and biology of complex traits, and what immediate utility has come out of these studies. Rather than giving an exhaustive review of all reported findings for all diseases and other complex traits, we focus on the results for auto-immune diseases and metabolic diseases. We return to the perceived failure or disappointment about GWASs in the concluding section. © 2012 The American Society of Human Genetics. Source

Frayn K.,Oxford Center for Diabetes
Journal of the American Heart Association | Year: 2012

Inappropriate storage of fatty acids as triglycerides in adipocytes and their removal from adipocytes through lipolysis and subsequent oxidation may cause the atherogenic dyslipidemia phenotype of elevated apolipoprotein B levels and subsequent hypertriglyceridemia. We tested whether turnover of triglycerides in fat cells was related to dyslipidemia. The age of triglycerides (reflecting removal) and triglyceride storage in adipocytes was determined under free living conditions by measuring incorporation of atmospheric (14)C into these lipids within the adipocytes in 47 women and 26 men with a large interindividual variability in body mass index. Because limited (14)C data were available, triglyceride age was also determined in 97 men and 233 women by using an algorithm based on adipocyte lipolysis, body fat content, waist-to-hip ratio, and insulin sensitivity. This cohort consisted of nonobese subjects since obesity per se is related to all components in the algorithm. Triglyceride turnover (age and storage) was compared with plasma levels of apolipoproteins and lipids. Plasma levels of apolipoprotein B and triglycerides were positively related to triglyceride age in adipocytes, when measured directly using radiocarbon analyses (r=0.45 to 0.47; P<0.0001). This effect was independent of subject age, waist circumference measures, and insulin sensitivity (partial r=0.29 to 0.45; P from 0.03 to <0.0001). Triglyceride storage showed no independent correlation (partial r=0.02 to 0.11; P=0.42 to 0.91). Algorithm-based values for adipocyte removal of triglycerides were positively associated with plasma triglycerides and apolipoprotein B (r=0.44 to 0.45; P<0.0001) and (also positively) with the inflammation status of adipose tissue (r=0.39 to 0.47; P<0.05). These correlations were statistically independent of subject age and observed in men and women as well as in lean and overweight subjects when subgroups were examined separately. Decreased removal of adipocyte triglycerides (as indicated by a high triglyceride age in fat cells) is independently associated with circulating apolipoprotein B and triglycerides. This suggests a hitherto unknown role of triglyceride turnover in adipocytes for the development and/or maintenance of atherogenic dyslipidemia. Source

Christodoulides C.,Oxford Center for Diabetes | Vidal-Puig A.,University of Cambridge
Molecular and Cellular Endocrinology | Year: 2010

For long viewed as passive lipid storage depots, adipocytes are now recognised as key players in the pathogenesis of insulin resistance and metabolic disease. In parallel, the last two decades of research have seen the emergence of transcription factors of the peroxisome proliferator-activated receptor (PPAR) family as central regulators of lipid and glucose homeostasis and molecular targets for drugs to treat hyper-lipidaemia and type 2 diabetes mellitus. In this review we discuss the characteristics of PPARs and the role of the different isotypes in adipocyte biology. © 2009 Elsevier Ireland Ltd. All rights reserved. Source

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