A randomised, double blind, crossover study of the effects of CLA isomers on inflammation, body composition, metabolic profiles and vascular function in subjects with the metabolic syndrome

A variety of individual and population based approaches to prevention and management of obesity are required and there is an increasing interest in functional foods and natriceuticals. Conjugated linoleic acid (CLA) has generated enormous interest in this context due to their ability to modulate PPAR’s and the associated metabolic processes. ! AIMS & METHODS ! This study aimed to investigate the effects of CLA supplementation in a randomised, double blind crossover trial on inflammation, vascular function and metabolic profiles in subjects with the metabolic syndrome. !! RESULTS ! This study utilised a cross-over design to investigate any differences in outcomes using 9,11 CLA isomer in comparison to the CLA mixture. The results revealed no significant differences at baseline between the two groups and a relatively small number of significant outcomes (peripheral SBP, aPWV, HDL-cholesterol, adiponectin, platelet aggregation and HOMA B). As there was a lack of substantial differences in the two treatments and an inconsistency in specifying these differences to a specific isomer, further analysis was undertaken combining the data from both groups and comparing the outcomes at baseline and at the end of the treatment using a paired‘t’ test. Results from this sub analysis showed a significant increase in circulating sRAGE levels (‘p’=0.002) along with reductions in aortic PWV (‘p’=0.003) and markers of endothelial and platelet function. There were no changes in body composition or insulin sensitivity although adiponectin levels were elevated (‘p’=0.003) and resistin levels decreased markedly (‘p’<0.005) following the treatment. !! CONCLUSIONS ! Dietary supplementation with CLA seems to produce a number of vascular benefits which are noted to be independent of its metabolic effects and mediated possibly by attenuating inflammation through changes in circulatory sRAGE. This is of considerable clinical relevance and may open new perspectives and offer effective strategies to reduce the CVD burden in the metabolic syndrome.

Acute kidney injury risk assessment at the hospital front door: what is the best measure of risk?

Background We examined the prevalence of acute kidney injury (AKI) risk factors in the emergency medical unit, generated a modified risk assessment tool and tested its ability to predict AKI. Methods A total of 1196 patients admitted to medical admission units were assessed for patient-associated AKI risk factors. Subsequently, 898 patients were assessed for a limited number of fixed risk factors with the addition of hypotension and sepsis. This was correlated to AKI episodes. Results In the first cohort, the prevalence of AKI risk factors was 2.1 ± 2.0 per patient, with a positive relationship between age and the number of risk factors and a higher number of risk factors in patients ≥65 years. In the second cohort, 12.3% presented with or developed AKI. Patients with AKI were older and had a higher number of AKI risk factors. In the AKI cohort, 72% of the patients had two or more AKI risk factors compared with 43% of the cohort with no AKI. When age ≥65 years was added as an independent risk factor, 84% of those with AKI had two or more AKI risk factors compared with 55% of those with no AKI. Receiver operating characteristic analysis suggests that the use of common patient-associated known AKI risk factors performs no better than age alone as a predictor of AKI. Conclusions Detailed assessment of well-established patient-associated AKI risk factors may not facilitate clinicians to apportion risk. This suggests that additional work is required to develop a more sensitive validated AKI-predictive tool that would be useful in this clinical setting

Metformin Reduces Arterial Stiffness and Improves Endothelial Function in Young Women with Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled, Crossover Trial

Context: Patients with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance and display subclinical evidence of early cardiovascular disease. Metformin improves insulin sensitivity and circulating markers of cardiovascular risk in patients with PCOS, but it is unclear whether this translates into improvements in vascular function. Objective: Our objective was to evaluate the effects of metformin on arterial stiffness and endothelial function in women with PCOS. Design and Intervention: Thirty women with PCOS were assigned to consecutive 12-wk treatment periods of metformin or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. Main Outcome Measures: The primary outcome measures were assessments of arterial stiffness [augmentation index (AIx), central blood pressure, and brachial and aortic pulse wave velocity (PWV)] and endothelial function. Anthropometry, testosterone, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high-sensitivity C-reactive protein, adiponectin, and plasminogen activator inhibitor-1) were also assessed. Results: Metformin improved AIx [−6.1%; 95% confidence interval (CI) for the difference −8.5 to −3.5%; P < 0.001], aortic PWV (−0.76 m/sec; 95% CI for the difference −1.12 to −0.4 m/sec; P < 0.001), brachial PWV (−0.73 m/sec; 95% CI for the difference −1.09 to −0.38; P < 0.001), central blood pressure (P < 0.001), and endothelium-dependent (AIx after albuterol; P = 0.003) and endothelium-independent (AIx after nitroglycerin; P < 0.001) vascular responses. Metformin also reduced weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P = 0.004) and increased adiponectin (P = 0.001) but did not affect testosterone or other metabolic measures. Conclusions: Short-term metformin therapy improves arterial stiffness and endothelial function in young women with PCOS

Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: A randomized, placebo-controlled, crossover trial

Polycystic ovary syndrome (PCOS) is characterized by increased insulin resistance and an increased risk of type 2 diabetes. These abnormalities most likely are associated with increased risk of cardiovascular mortality in women with PCOS, although this has not been demonstrated in epidemiological studies. Endothelial dysfunction is an early marker of vascular damage in women with PCOS. Increased arterial stiffness (assessed by pulse wave velocity [PWV]) correlates with insulin resistance and is a strong independent predictor of cardiovascular mortality in patients with type 2 diabetes. Since it is also increased in women with PCOS, insulin resistance may be an important therapeutic target. The oral biguanide, metformin, improves insulin sensitivity in women with PCOS and reduces circulating concentrations of markers of cardiovascular risk. However, its effects on vascular function are unclear because of conflicting data and the absence of randomized controlled studies. This randomized, double-blind, placebo-controlled crossover study investigated the effects of short-term metformin therapy on arterial stiffness and endothelial function in women with PCOS. The participants were 30 obese women (mean body mass index: 34.9) with PCOS, who were assigned, using a crossover design, to receive consecutive 12-week treatment periods of metformin or placebo separated by an 8-week washout. The primary study outcomes were changes in measures of arterial stiffness (augmentation index [Alx], brachial PWV, aortic PWV, central blood pressure), and endothelial function. Secondary outcome measures were changes in anthropometric measures (weight, body mass index, and waist and hip circumference), androgens (testosterone), and metabolic biochemistry (adiponectin, high-sensitivity C-reactive protein, homeostasis model of assessment for insulin resistance, triglycerides, and plasminogen activator inhibitor-1). Metformin improved measures of arterial stiffness including AIx (−6.1%; 95% confidence interval (CI) for the difference −8.5% to −3.5%); bPWV (−0.73 m/s; 95% CI for the difference −1.09 to −0.38); aPWV (−0.76 m/s; 95% CI for the difference −1.12 to −0.4 m/s); and central blood pressure (all comparisons, P < 0.001). Endothelium-dependent (AIx after albuterol, P < 0.003) and endothelium-independent (Alx after nitroglycerin; P < 0.001) vascular responses also improved. Metformin significantly reduced body weight (P < 0.001), waist circumference (P < 0.001), and triglycerides (P < 0.004). Increases were observed for adiponectin (P < 0.001). No changes were observed in testosterone or other metabolic measures. Both the study medication and placebo were well tolerated. These findings suggest that metformin improves important parameters of vascular function in young obese women with PCOS and may have therapeutic benefits for this study population

Effects of dehydroepiandrosterone replacement on vascular function in primary and secondary adrenal insufficiency: A randomized crossover trial

Context: Patients with Addison’s disease and hypopituitarism have increased mortality, chiefly related to vascular disease. Both diseases are characterized by dehydroepiandrosterone (DHEA) deficiency, yet this is not usually corrected. It is unclear whether treatment of these conditions with DHEA improves cardiovascular risk. Objective: The aim of the study was to evaluate the effects of DHEA on arterial stiffness and endothelial function in subjects with Addison’s disease and hypopituitarism. Design and Intervention: Forty subjects (20 with Addison’s disease, 20 with panhypopituitarism) were assigned to consecutive 12-wk treatment periods of DHEA 50 mg or placebo in a randomized, double-blind, crossover design separated by an 8-wk washout. Main Outcome Measures: Primary outcome parameters were measures of arterial stiffness [augmentation index, central blood pressure, brachial and aortic pulse wave velocity (PWV)] and endothelial function. Serum androgens, anthropometry, and metabolic biochemistry (lipids, homeostasis model of assessment for insulin resistance, high sensitivity C-reactive protein, adiponectin, plasminogen activator inhibitor-1) were also assessed. Results: Despite normalization of DHEA sulfate, androstenedione, and testosterone (females), DHEA replacement did not affect augmentation index, aortic PWV, brachial PWV, central blood pressure, or endothelial function. DHEA did not affect any anthropometric or metabolic measures, apart from a small reduction in high-density lipoprotein cholesterol (−0.08 mmol/liter; P = 0.007; 95% confidence interval for the difference, −0.13 to −0.02 mmol/liter). Conclusions: Short-term DHEA supplementation does not significantly affect measures of arterial stiffness or endothelial function in patients with adrenal insufficiency