This review critically appraises studies examining the association of novel factors with diabetes. We show that many of the most studied novel and apparently 'independent' risk factors are correlated with each other by virtue of their common origins or pathways, and that residual confounding is likely. Available studies also have other limitations, including differences in methodology or inadequate statistical analyses. Furthermore, although most relevant work in this area has focused on improving our understanding of the pathogenesis of diabetes, association studies in isolation cannot prove causality; intervention studies with specific agents (if available) are required, and genetic studies may help. With respect to the potential value of novel risk factors for diabetes risk prediction, we illustrate why this work is very much in its infancy and currently not guaranteed to reach clinical utility. Indeed, the existence of several more easily measured powerful predictors of diabetes, suggests that the additional value of novel markers may be limited. Nevertheless, several suggestions to improve relevant research are given. Finally, we show that several risk factors for diabetes are only weakly associated with the risk of incident vascular events, an observation that highlights the limitations of attempting to devise unified criteria (e.g. metabolic syndrome) to identify individuals at risk of both CHD and diabetes.

Both early and late onset of diabetes are associated with increased risk of major CHD events and mortality, but only early onset of diabetes (associated with >10 years' duration) appears to be a CHD equivalent.

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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 HbA 1c , and a sensible way ahead may be to combine diabetes and cardiovascular disease prediction using HbA 1c 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. Diabet. Med. 29, 5-13 (2012)

AimsThe effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. Methods and resultsWe searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary-and secondary-prevention statin trials with .1000 participants followed for .1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring ,30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects metaanalyses. In up to 17 trials with 132 538 participants conducted over 4. ConclusionIn primary-and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and acomposite of nonfatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.--

Objective: Much has been written on the metabolic syndrome and related recent criteria. However, it remains unclear whether such criteria help clinical practice. This review will evaluate the usefulness of metabolic syndrome criteria to enhance risk prediction for either cardiovascular disease or diabetes. Design: This is a narrative review that is based on the author's experience from relevant publications from his group and from other related research. Results: Although the presence of metabolic syndrome, however defined, is clearly associated with higher risk for vascular disease, the criteria do not enhance coronary heart disease (CHD) prediction from simpler Framingham-based risk scores. The dichotomous nature of metabolic syndrome criteriaFeither you have it or you do notFcombined with the lack of age, low-density lipoprotein cholesterol and smoking account for their inferior predictive value. Metabolic syndrome criteria are, in fact, more strongly associated with incident diabetes, an observation demonstrated in the West of Scotland Coronary Prevention Study (WOSCOPS). This is because three of the five parameters within metabolic syndrome criteria (waist, glucose and triglyceride) are more closely linked to risk for diabetes than risk for CHD. However, screening for prevalent or high risk of incident diabetes is a complex and debated issue and is by no means guaranteed to be widely adopted. Conclusions: Metabolic syndrome criteria do not offer benefits beyond established methods of vascular risk assessment. Thus, the focus in clinical practice should remain on established risk factors (for example, smoking, lipids, blood pressure) both to determine CHD risk, through established charts, and to reduce it.

Precis: Flushing postmenopausal women appear to have better vascular responses than non-flushing women but paradoxically, such women appear to have worse (not better) CVD risk factors. 2 ABSTRACTBackground: 70% of postmenopausal women suffer from hot flushes causing significant morbidity in

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