SummaryBackground-Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease.

Diets rich in green, leafy vegetables have been shown to lower BP and reduce the risk of cardiovascular disease. Green, leafy vegetables and beetroots are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and NO, has previously been shown to lower BP and improve endothelial function in healthy humans.We sought to determine if supplementing dietary nitrate with beetroot juice, a rich source of nitrate, will lower BP, improve endothelial function and insulin sensitivity in individuals with type 2 diabetes (T2DM). Twenty-seven patients, age 67.2 +/-4.9 years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order a 2 week period of supplementation with 250 ml beetroot juice daily (active) or 250 ml nitratedepleted beetroot juice (placebo). At the conclusion of each intervention period 24 hour ambulatory blood pressure monitoring, tests of macro and microvascular endothelial function and a hyperinsulinaemic isoglycaemic clamp were performed. After two weeks administration of beetroot juice mean ambulatory systolic BP was unchanged: 134.6 ± 8.4 mmHg versus 135.1 ± 7.8 mmHg (mean ± SD) placebo vs. active -mean difference of -0.5 mmHg (placebo-active), p=0.737 (95% CI -3.9 to 2.8). There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity. Supplementation of the diet with 7.5 mmoles of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration, but did not lower BP, improve endothelial function or insulin sensitivity in individuals with T2DM.3

Plasma H(2)S levels are reduced in overweight participants and patients with type 2 diabetes. Increasing adiposity is a major determinant of plasma H(2)S levels.

Objective— Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in development and tissue repair. They have also been shown to have both protective and pathogenic effects in atherosclerosis, and experimental studies have suggested that MMP-12 contributes to plaque growth and destabilization. The objective of this study was to investigate the associations between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular disease with a particular focus on type 2 diabetes mellitus. Approach and Results— Plasma levels of MMP-1, -3, -7, -10, and -12 were analyzed by the Proximity Extension Assay technology in 1500 subjects participating in the SUMMIT (surrogate markers for micro- and macrovascular hard end points for innovative diabetes tools) study, 384 incident coronary cases, and 409 matched controls in the Malmö Diet and Cancer study and in 205 carotid endarterectomy patients. Plasma MMP-7 and -12 were higher in subjects with type 2 diabetes mellitus, increased with age and impaired renal function, and was independently associated with prevalent cardiovascular disease, atherosclerotic burden (as assessed by carotid intima-media thickness and ankle-brachial pressure index), arterial stiffness, and plaque inflammation. Baseline MMP-7 and -12 levels were increased in Malmö Diet and Cancer subjects who had a coronary event during follow-up. Conclusions— The plasma level of MMP-7 and -12 are elevated in type 2 diabetes mellitus, associated with more severe atherosclerosis and an increased incidence of coronary events. These observations provide clinical support to previous experimental studies, demonstrating a role for these MMPs in plaque development, and suggest that they are potential biomarkers of atherosclerosis burden and cardiovascular disease risk.

Blood concentrations of hydrogen sulfide (H(2)S) are markedly elevated in several animal models of inflammation. Pharmacological inhibition of H(2)S synthesis reduces inflammation and swelling, suggesting that H(2)S is a potential inflammatory mediator. However, it is currently unknown whether H(2)S synthesis is perturbed in human inflammatory conditions or whether H(2)S is present in synovial fluid. We analyzed paired plasma and synovial fluid (SF) aspirates from rheumatoid arthritis (RA; n= 20) and osteoarthritis (OA; n= 4) patients and plasma from age matched healthy volunteers (n= 20). Median plasma H(2)S concentrations from healthy volunteers and RA and OA patients were 37.6, 36.6, and 37.6 microM, respectively. In RA patients, median synovial fluid H(2)S levels (62.4 microM) were significantly higher than paired plasma (P= 0.002) and significantly higher than in synovial fluid from OA patients (25.1 microM; P= 0.009). SF H(2)S levels correlated with clinical indices of disease activity (tender joint count, r= 0.651; P < 0.05) and markers of chronic inflammation; Europhile count (r=-0.566; P < 0.01) and total white cell count (r=-0.703; P < 0.01). Our study shows for the first time that H(2)S is present in synovial fluid and levels correlated with inflammatory and clinical indices in RA patients.

Abstract. Shore AC, Colhoun HM, Natali A, Palombo

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This paper aims to summarize and map contemporary views on some contentious aspects of arterial hemodynamics that have remained unresolved despite years of research. These were discussed during a workshop entitled Arterial hemodynamics: past, present and future held in London on June 14 and 15, 2016. To do this we formulated a list of potential consensus statements informed by discussion at the meeting in London and quantified the degree of agreement and invited comments from the participants of the workshop. Overall the responses and comments show a high measure of quantitative agreement with the various proposed 'consensus' statements. Taken together, these statements seem a useful basis for proceeding with a more detailed and comprehensive consensus document on the current understanding and approaches to analysis of the pulse waveform. Future efforts should be directed at identifying remaining areas of dispute and future topics for research.