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.
Diabet. Med. 29, 5–13 (2012)
An ideal biomarker should refine identification of those at risk of disease occurrence or progression, improve prediction of complications of disease, and/or guide and ...help tailor responses to different therapies. Biomarkers that give insights into disease pathogenesis are also of interest. With this in mind, this review describes biomarker studies relevant to diabetes, focusing on those conducted by the author, his colleagues and collaborators. The review highlights several points. (1) Novel biomarkers may not improve prediction of new‐onset diabetes in a meaningful way beyond what can be achieved with simple measures combined with HbA1c, and a sensible way ahead may be to combine diabetes and cardiovascular disease prediction using HbA1c and such measures. (2) In terms of disease pathogenesis, associations do not necessarily infer causality; potential for residual confounding and reverse causality should always be borne in mind. The potential relevance of such issues to understanding the relationship of some topical variables/pathways, namely adiponectin, inflammation and vitamin D, with diabetes will be highlighted. (3) How baseline and serial data on biomarkers arising from the liver have improved our understanding of the role of hepatic fat in diabetes pathogenesis will be explored. (4) Future goals for diabetes biomarker research should focus on predicting complications and determining subgroups who may respond better to particular therapies. (5) All novel biomarker research (regardless of analytical platforms used) needs to be tested against information available from commonly measured variables in clinical practice. Otherwise, many claims of clinical utility can be exaggerated. In summary, biomarker research in diabetes is continuing apace in a number of areas, but it remains to be seen whether the promise of biomarker research to improve the care of our patients becomes a reality.
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.
Durable resin-ceramic adhesion may influence the clinical success of ceramic restorations, which has been one of the challenging issues in dentistry. The present study assessed the bond strength and ...chemical interaction of 10-methacryloxydecyl dihydrogen phosphate (MDP), MDP+silane, and MDP-salt primers to alumina-blasted zirconia ceramic by tensile bond strength test, surface elemental composition with x-ray photoelectron spectroscopy analysis, contact angle measurement, surface morphology with scanning electron microscopy, and surface topography with 3-dimensional confocal laser scanning microscope analyses. MDP-salt showed the highest tensile bond strength before and after thermocycling when compared with MDP and MDP+silane (P < 0.05). The measured contact angle values differed significantly (P < 0.001) in the order of MDP-salt > control (no chemical pretreatment) > MDP+silane > MDP. There was no difference in surface roughness (P = 0.317) and surface topography among all tested groups. Zirconia treated with MDP-salt showed phosphorus peaks in addition to zirconia and alumina peaks. MDP-salt has zirconia priming properties, which improves bonding performance to resin cement.
Pre-eclampsia, which complicates 2-4% of pregnancies, remains one of the commonest causes of maternal and fetal morbidity and mortality. However, early findings conflict with more recent data on the ...long term consequences for mothers.
To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA).
A ...multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis.
Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk.
Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.
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.
Aims
Conventional definitions of obesity, e.g. body mass index (BMI) ≥ 30 kg/m2 or waist circumference cut‐points of 102 cm (men) and 88 cm (women), may underestimate metabolic risk in non‐Europeans. ...We prospectively identified equivalent ethnicity‐specific obesity cut‐points for the estimation of diabetes risk in British South Asians, African‐Caribbeans and Europeans.
Methods
We studied a population‐based cohort from London, UK (1356 Europeans, 842 South Asians, 335 African‐Caribbeans) who were aged 40–69 years at baseline (1988–1991), when they underwent anthropometry, fasting and post‐load (75 g oral glucose tolerance test) blood tests. Incident Type 2 diabetes was identified from primary care records, participant recall and/or follow‐up biochemistry. Ethnicity‐specific obesity cut‐points in association with diabetes incidence were estimated using negative binomial regression.
Results
Diabetes incidence rates (per 1000 person years) at a median follow‐up of 19 years were 20.8 (95% CI: 18.4, 23.6) and 12.0 (8.3, 17.2) in South Asian men and women, 16.5 (12.7, 21.4) and 17.5 (13.0, 23.7) in African‐Caribbean men and women, and 7.4 (6.3, 8.7), and 7.2 (5.3, 9.8) in European men and women. For incidence rates equivalent to those at a BMI of 30 kg/m2 in European men and women, age‐ and sex‐adjusted cut‐points were: South Asians, 25.2 (23.4, 26.6) kg/m2; and African‐Caribbeans, 27.2 (25.2, 28.6) kg/m2. For South Asian and African‐Caribbean men, respectively, waist circumference cut‐points of 90.4 (85.0, 94.5) and 90.6 (85.0, 94.5) cm were equivalent to a value of 102 cm in European men. Waist circumference cut‐points of 84.0 (74.0, 90.0) cm in South Asian women and 81.2 (71.4, 87.4) cm in African‐Caribbean women were equivalent to a value of 88 cm in European women.
Conclusions
In prospective analyses, British South Asians and African‐Caribbeans had equivalent diabetes incidence rates at substantially lower obesity levels than the conventional European cut‐points.
What's new?
Ethnicity‐appropriate obesity cut‐points as predictors of diabetes risk are much debated.
Few longitudinal studies have addressed this topic, and none in the UK.
This study followed a group of over 2500 people from three ethnic backgrounds for 19 years and identified that BMI levels of 25 kg/m2 in South Asians and 27 kg/m2 in African Caribbeans posed equivalent risk of developing diabetes to BMI of 30 kg/m2 in Europeans. Waist circumference equivalents were also lower in South Asians and African Caribbeans.
These findings highlight the potential importance of public health measures for the prevention of metabolic risk long before the current conventional cut‐points for obesity are reached in South Asian and African‐Caribbean populations.
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