While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30–40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such trials to have reported, as a precursor to understanding why the EMPA-REG Outcomes results came as a surprise. Thereafter, we discuss potential mechanisms that could explain the EMPA-REG Outcomes results, concentrating on non-atherothrombotic effects. We suggest that the main driver of benefit may derive from the specific effects of sodium-glucose linked transporter-2 (SGLT2) inhibition on renal sodium and glucose handling, leading to both diuresis and improvements in diabetes-related maladaptive renal arteriolar responses. These haemodynamic and renal effects are likely to be beneficial in patients with clinical or subclinical cardiac dysfunction. The net result of these processes, we argue, is an improvement in cardiac systolic and diastolic function and, thereby, a lower risk of HFH and sudden cardiac death. We also discuss whether other drugs in this class are likely to show similar cardiovascular benefits. Finally, areas for future research are suggested to better understand the relevant mechanisms and to identify other groups who may benefit from SGLT2 inhibitor therapy.

Celis-Morales, C. A. et al. (2017) Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study. Diabetes Care, 40(12), pp. 1710Care, 40(12), pp. -1718Care, 40(12), pp. . (doi:10.2337 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/148158/ Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but it is not known whether these risk factors interact in predisposing to adverse health outcomes. The aim of the current study was to determine the interactions between diabetes and grip strength and their association with health outcomes. Research Design and MethodsWe undertook a prospective, general population cohort study using UK Biobank. Cox proportional hazard models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality, and to test for interactions between diabetes and grip strength. ResultsOf 347

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The movements of age‐II and older striped bass (Morone saxatilis), tagged during 1976 and 1977 within a 70‐km section of the lower Hudson River, were determined from recaptures of fish within and outside the river. Movements within the river prior to and during the spawning period are related to maturity, age, and sex. During March and April, mature and immature fish coexist downriver from the principal spawning grounds. By late April, immature fish tend to migrate downriver and mature fish upriver. Males precede females to the spawning grounds. Following spawning, most striped bass leave the Hudson River and move generally northeast‐ward in Long Island Sound and the Atlantic Ocean, but the majority are restricted to within 50 km of the river mouth. There is no correlation between distance moved and fish size, sex, or age. The migratory patterns of striped bass within the Hudson River system contrast markedly with those in the Chesapeake Bay system.

Incidental observations of Atlantic tomcod during routine laboratory processing revealed that a portion of the adult population, collected during the 1977-78 spawning season had enlarged livers containing dark coloured tumours and other abnormalities. Ofthe total of 264 livers collected between 16 January and 27 February 1978 and grossly examined for prevalence of abnormalities, 25% appeared to contain neoplastic nodules and hepatocellular carcinoma. One liver contained a massive tumour (7 x 12 mm) that involved approximately 60% ofthe liver. The exact causes of the high prevalence of hepatocellular carcinoma are unknown but polychlorinated biphenyls (PCBs) are suspected of having a possible role. The Hudson River is known to contain elevated concentrations of PCBs. Twelve tomcod livers from the 1977-78 spawning population representing both normal and hepatoma conditions contained concentrations of PCBs ranging from 10-9 to 98-2 ppm (mean of37-5ppm).