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Whilst the interplay between type 2 diabetes and cardiovascular disease (CVD) has been recognised for many years, recent analyses of existing studies have helped refine several aspects of this relationship with relevance to clinical practice. First, recent data demonstrate that fasting glucose is not linearly related to CVD risk in those without diabetes; rather, risk levels escalate (modestly at first) only beyond specific glucose thresholds. Consequently, glucose-based measures may not necessarily enhance CVD risk prediction in those without diabetes. Second, other data confirm that new-onset diabetes is not a post-myocardial infarction ‘risk equivalent’ state and that, on average, several years of diabetes duration is needed to attain this level of risk. Third, meta-analyses and systemic reviews have confirmed that diabetes increases CVD risk by around twofold on average and this risk is subject to wide variation, being lowest in those newly diagnosed and highest in those with existing vascular disease, proteinuria or renal disease. Fourth, meta-analyses of major glucose-lowering trials suggest that, whilst glucose-lowering lessens vascular risk, risk reduction arising from statins and blood pressure-lowering is greater. Fifth, statins increase diabetes risk, albeit modestly, adding to the emerging concept that some agents that primarily target CVD risk may be diabetogenic, and vice versa. Finally, arising in part from the latter observation, as well as an understanding that CVD and diabetes risk overlap in some individuals but not others, the case for combined CVD/diabetes risk screening (generally using non-fasting lipids and HbA 1c ), has gained strength.

In severe untreated rheumatoid arthritis (RA), reductions in high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol and total cholesterol have been noted; this is in line with findings in other pathologies/conditions associated with inflammation or infection, such as sepsis, cancer, trauma or the postoperative period. Although the precise mechanisms remain to be established, cytokine-induced activation of the reticuloendothelial system is potentially critical to such changes. Consequently, dampening of inflammation in severe RA—as occurs with several biologics—may lead to increases, not only in high-density lipoprotein-cholesterol, but also with other lipid moieties, including total and low-density lipoprotein-cholesterol and, perhaps, triglycerides. This concept is consistent with findings following antitumour necrosis factor treatment and interleukin-6 receptor inhibition in patients with RA. At the same time, it is increasingly apparent that potent dampening of inflammation, however achieved, broadly reduces the risk of cardiovascular disease in RA. Therefore, changes in lipid profiles, particularly increases in cholesterol and triglycerides that occur with treatments for severe inflammation, may not represent increased cardiovascular risk as in the usual understanding of lipid-level elevations in individuals without significant inflammation. Rather, changes in lipid levels, in part or largely, may represent a predictable response to attenuation of inflammation. These observations are increasingly important clinically and should aid in the understanding and interpretation of lipid changes under inflammatory conditions, as well as in the context of potent anti-inflammatory interventions.

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.

This talk will overview the methods of assessing CVD risk in patients with Rheumatoid arthritis. It will give a rationale for why CVD risk screening in RA can be done using risk scores developed for the general population and also give two examples of scores which include RA as a risk stratifier. The talk will highlight that i) CVD risk scoring is easy to do in routine clinical practice, ii) requires simple additional of non-fasting lipids and blood pressure, iii) can be intergrated to existing RA clinics and iv) can be repeated at intervals of time which is pragmatic. The talk will further emphasise that consideration of usual CVD risk factors is critically important in determing who should be recommended statins and that having RA alone does not mean individuals are necessarily at high CVD risk. A case history will be used to highlight main points discussed in the talk. Finally, the talk will also discuss the pros and cons of additional tests and discuss the recommendations from recent guidelines which will fit in with the talks conclusions.Disclosure of InterestN. Sattar Consultant for: Roche, Astrazeneca, Amgen, Sanofi, Merck, Speakers bureau: Roche

Snake gourd (Trichosanthes cucumerina) plants exhibiting typical begomovirus-like symptoms of stunted growth, leaf yellowing and mottling were observed at an open field in the Eastern region of Saudi Arabia. Sequencing analysis of the amplified complete DNA molecules revealed that the plants were infected with watermelon chlorotic stunt virus (WmCSV), which is a bipartite begomovirus prevalent mostly in the Old World and a serious threat to cucurbit production in the Arabian Peninsula, Middle East and Africa. The two WmCSV DNA-A isolates (SG31A and SG52A) were 98.9% identical and showed their highest nucleotide (nt) sequence identities (98.7%) with the isolates from Iran and Saudi Arabia. The DNA-B isolates (SG31B and SG52B), on the other hand, were 97.4% identical and exhibited their highest nt sequence identities (99.5 and 97%) with isolates reported from Iran and Oman. In the phylogenetic dendrograms the identified isolates clustered closely with previously reported WmCSV isolates from Iran and Saudi Arabia. Infectivity assays revealed that the DNA-A components alone could not induce infection in Nicotiana benthamiana plants however, together with DNA-B these isolates successfully caused typical begomovirus symptoms and both components were detected successfully using Southern blot hybridization. This study highlights the importance of conducting extensive future begomovirus surveillance to detect spillover events that could threaten native vegetable production in Saudi Arabia.  This is crucial as begomoviruses pose a serious threat to vegetable cultivation throughout the Middle East.

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking 1 – 4 . Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with β-thalassaemia, a condition in which GDF15 levels are chronically high 5 , report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG. Elevated circulating levels of GDF15 in pregnant women are associated with severe nausea and vomiting, and sensitivity to such symptoms during pregnancy is partly determined by prepregnancy levels of this hormone.

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences.

A double-blind, randomized, placebo-controlled, parallel-group trial aimed to determine whether levothyroxine provided clinical benefits in older persons with subclinical hypothyroidism. No apparent benefits were observed. Subclinical hypothyroidism is defined as an elevated serum thyrotropin level and a serum free thyroxine level within the reference range. 1 Between 8% and 18% of adults 65 years of age or older have these biochemical features, and the prevalence is higher among women than among men. 2 Subclinical hypothyroidism is a possible contributor to many problems in older persons. Thyroid hormones have multiple effects, since they act as an essential regulatory factor in numerous physiological systems, including the vascular tree and the heart, 3 the brain (including cognition), 4 skeletal muscle, and bone. 5 Tiredness is the most important symptom of overt hypothyroidism, 6 but . . .

Objectives: Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. Subjects and methods: We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. Results: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z -scores between the intervention vs standard care arms (difference −0.14 s.d., 95% confidence interval −0.38 to 0.10, P =0.246), but subscapular skinfold thickness z -score was 0.26 s.d. (−0.49 to −0.02; P =0.03) lower in the intervention arm. Maternal dietary GL (−35.34; −48.0 to −22.67; P <0.001) and saturated fat intake (−1.93% energy; −2.64 to −1.22; P <0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. Conclusions: This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.