The effect of regular consumption of lupin-containing foods on glycaemic control and blood pressure in people with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus is a metabolic disorder characterized by high glucose and insulin resistance. It is strongly linked to lifestyle, including poor diet and physical inactivity. Lupin is a novel food ingredient, rich in protein and fibre with negligible sugar and starch, which can be incorporated into various foods to reduce glycaemic load. Regular consumption of lupin-enriched foods may be a novel and easily achievable means of reducing overall glycaemic load and improving glycaemic control in diabetes. OBJECTIVE: To determine whether regular consumption of lupin-enriched foods can improve glycaemic control and lower blood pressure in people with type 2 diabetes mellitus. DESIGN: Fourteen men and 8 women (mean age 58.0 ± 6.6 years and BMI 29.0 ± 3.5 kg m-2) with type 2 diabetes mellitus were recruited from the general population to take part in a double-blind, randomised, controlled cross-over study. Participants consumed lupin or control foods for breakfast and lunch every day, and for dinner at least 3 days per week during the 8-week treatment periods. Lupin-enriched foods consisted of bread, pasta, Weetbix™ cereal and crumbs, with energy-matched control products. Treatments were completed in random order with an 8-week washout period. All participants monitored their blood glucose levels pre- and post-breakfast and lunch, and their blood pressure in the morning and evening, 3 days per week for the duration of each treatment period. RESULTS: Seventeen participants completed both treatment arms, with all 22 participants (14 males, 8 females) analysed on an intention-to-treat basis. Eight weeks consumption of lupin-enriched food had no significant effect on mean blood glucose levels (mean difference: -0.08 ± 0.06 mmol L-1, p = 0.214) or post-prandial blood glucose levels (-0.13 ± 0.10 mmol L-1, p = 0.196). There was no effect on home systolic (-0.4 ± 0.4 mmHg, p = 0.33) or diastolic (0.3 ± 0.3 mmHg, p = 0.321) blood pressure and heart rate (0.5 ± 0.3 bpm, p = 0.152), and no effect on body weight throughout the treatment periods. CONCLUSION: Regular consumption of lupin-enriched foods had no significant effect on glycaemic control or blood pressure in people with type 2 diabetes mellitus.

Alcohol and Hypertension-New Insights and Lingering Controversies.

PURPOSE OF REVIEW: To examine outstanding issues in the relationship of alcohol to hypertension. These include whether the increase in BP with alcohol is causally related, the nature of the relationship in women, the contribution of alcohol-related increases in BP to cardiovascular disease and the aetiology of alcohol-related hypertension. RECENT FINDINGS: Intervention studies and Mendelian randomisation analyses confirm the alcohol-BP relationship is causal. The concept that low-level alcohol intake reduces BP in women is increasingly unsustainable. Alcohol-related hypertension is in the causal pathway between alcohol use and increased risk for several cardiovascular outcomes. The aetiology of alcohol-related hypertension is multifactorial with recent data highlighting the effects of alcohol on the vasoconstrictor 20-HETE and oxidative stress. The high prevalence of both alcohol use and hypertension mandates a careful alcohol history in every patient with elevated BP. Early intervention for excessive alcohol use offers the promise of lower levels of BP and reduced risk of adverse cardiovascular outcomes.

Graduate doctors' rural work increases over time.

Background: The contribution of rural clinical school (RCS) and rural origin to developing a long-term rural medical workforce was examined. Methods: Longitudinal cohort study, after undergraduate location in either rural or urban setting, for all medical graduates 2004-2010, identified in the Australian Health Practitioner Regulation Agency, in the following groups: Urban origin/no RCS; Rural origin/no RCS; Urban origin/RCS; and Rural origin/RCS. Results: Proportions of all graduates working rurally increased from 2013 to 2018, including amongst urban origin/nonRCS graduates. Rural origin/RCS participants worked rurally at the highest rates across all time points, with an endpoint of 47%, and an odds ratio of 9.70 (5.41, 17.40) relative to the urban reference group. They had a cumulative duration of rural practice over 5 times higher than the urban reference group. RCS graduates were more likely to be working in remote areas than nonRCS graduates. Conclusion: All graduates' contribution to rural and remote workforce is dynamic and increasing. Both RCS participation and rural student recruitment make synergistic and increasing contributions to rural work. RCS effects workforce distribution to more remote areas. Single cross-sectional studies do not capture this dynamic growth in the rural workforce.

Relative progress and academic performance of graduate vs undergraduate entrants to an Australian medical school.

BACKGROUND: Whether graduate entrants to medical school perform better academically than undergraduate entrants remains controversial. Differences in the discipline backgrounds of graduates may, at least in part, have accounted for differences in the results of comparative studies reported to date. This study aimed to address the dual issues of whether academic performance and progression rates were different between GE and UG students and the extent to which the discipline background of GE students may underpin any differences observed. METHODS: Relative academic performance as well as indicators of student progression (supplementary examinations, repeat years, leave of absence, withdrawal from the programme) were compared between graduate entrants (GE) (N = 410) and both school leaver entrants (SLE) (N = 865) and non-standard entrants (some prior tertiary education) (NSE) (N = 148) who combined for the final 4 yr. of a 6 yr. MBBS undergraduate programme in 8 consecutive cohorts from 2006 to 2013 in Western Australia. RESULTS: Examination scores were generally at or very close to a distinction grade or higher across all groups. Higher mean examination scores were seen for GE versus both SLE and NSE in the first 2 years with no significant differences in the final 2 years. GE from biological science / science backgrounds (N = 241) or physical science backgrounds (N = 26) performed the same as SLE and NSE throughout the programme. GE with a health / allied health background (N = 91), however, performed better throughout. They also performed better when compared to their GE counterparts from a humanities (N = 32) or a biological science / science background. GE had increased odds of withdrawing when compared to SLE (OR 2.50, 95% CI 1.30, 4.79, P = 0.006), but not compared to NSE. NSE had increased odds of repeating at least one level when compared to either GE (OR 2.74, 95% CI 1.21, 6.21, P = 0.016) or SLE (OR 4.10, 95% CI 1.93, 8.70, P < 0.001). There were no differences by entry category in the odds of sitting at least one supplementary examination during the programme. There was an increase in the odds of taking at least one leave of absence in both SLE (OR 2.55, 95% CI 1.79, 3.63, P < 0.001) and NSE (OR 2.47, 95% CI 1.50, 4.07, P < 0.001) compared to GE. CONCLUSIONS: Better academic performance by GE compared to SLE and NSE was predominantly due to higher scores for GE with a health / allied health background. GE were also less likely to have impeded progress during the course.

Likelihood of rural practice in medical school entrants with prior tertiary experience.

Background: Workforce decisions of medical students with prior tertiary education, relative to those without, are not known. Methods: Rural workforce outcomes for three separate streams of medical students were compared: school leaver entry (SLE) entered medical school direct (N = 682), non-standard entry (NSE) had some prior tertiary education (N = 123), and graduate entry (GE) (N = 317), had a prior completed degree. All students were at least in postgraduate year 3 in 2018, when current urban or rural medical workforce participation was ascertained. Results: Multivariate logistic regression allowing for the influences of rural background, rural clinical school participation, gender, being born overseas, socioeconomic status, and being a bonded rural scholar, showed that NSE students and GE students had increased odds of being in rural practice relative to SLE students. This increase was more than three-fold for NSE students (OR = 3.41, 95% CI 1.94, 5.99, p < 0.001) and greater than two-fold for GE students (OR = 2.54, 95% CI 1.57, 4.10, p < 0.001). Conclusion: Graduates with prior tertiary education were more likely to enter the rural medical workforce than direct school entrants. This suggests that increasing graduate entry programs may augment the rural medical workforce and that undergraduate programs allowing non-standard entry may have the same benefit.

Nitrate-rich vegetables do not lower blood pressure in individuals with mildly elevated blood pressure: a 4-wk randomized controlled crossover trial.

Background: Emerging evidence suggests that increasing intakes of nitrate-rich vegetables may be an effective approach to reduce blood pressure. Objective: Our primary aim was to determine whether daily consumption of nitrate-rich vegetables over 4 wk would result in lower blood pressure. Design: Thirty participants with prehypertension or untreated grade 1 hypertension were recruited to a randomized controlled crossover trial with 4-wk treatment periods separated by 4-wk washout periods. Participants completed 3 treatments in random order: 1) increased intake (∼200 g/d) of nitrate-rich vegetables [high-nitrate (HN); ∼150 mg nitrate/d], 2) increased intake (∼200 g/d) of nitrate-poor vegetables [low-nitrate (LN); ∼22 mg nitrate/d], and 3) no increase in vegetables (control; ∼6 mg nitrate/d). Compliance was assessed with the use of food diaries and by measuring plasma nitrate and carotenoids. Nitrate metabolism was assessed with the use of plasma, salivary, and urinary nitrate and nitrite concentrations. The primary outcome was blood pressure assessed by using 24-h ambulatory, home, and clinic measurements. Secondary outcomes included measures of arterial stiffness. Results: Plasma nitrate and nitrite concentrations increased with the HN treatment in comparison to the LN and control treatments (P < 0.001). Plasma carotenoids increased with the HN and LN treatments compared with the control (P < 0.01). HN treatment did not reduce systolic blood pressure [24-h ambulatory-HN: 127.4 ± 1.1 mm Hg; LN: 128.6 ± 1.1 mm Hg; control: 126.2 ± 1.1 mm Hg (P = 0.20); home-HN: 127.4 ± 0.7 mm Hg; LN: 128.7 ± 0.7 mm Hg; control: 128.3 ± 0.7 mm Hg (P = 0.36); clinic-HN: 128.4 ± 1.3 mm Hg; LN: 130.3 ± 1.3 mm Hg; control: 129.8 ± 1.3 mm Hg (P = 0.49)] or diastolic blood pressure compared with LN and control treatments (P > 0.05) after adjustment for pretreatment values, treatment period, and treatment order. Similarly, no differences were observed between treatments for arterial stiffness measures (P > 0.05). Conclusion: Increased intake of nitrate-rich vegetables did not lower blood pressure in prehypertensive or untreated grade 1 hypertensive individuals when compared with increased intake of nitrate-poor vegetables and no increase in vegetables. This trial was registered at www.anzctr.org.au as ACTRN12615000194561.

The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

BACKGROUND: Neutrophils release leukotriene (LT)B4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB4. OBJECTIVE: This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. DESIGN: In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. RESULTS: Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB5 (P < 0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive from DHA (all P < 0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. CONCLUSION: n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation.

The relative predictive value of undergraduate versus graduate selection tools in two Australian medical schools.

Context: Monash University and the University of Western Australia admit both school-leavers and graduates into their Bachelor of Medicine and Bachelor of Surgery (MBBS) courses. The Undergraduate Medicine and Health Sciences Admission Test (UMAT) and the Graduate Medical Schools Admissions Test (GAMSAT) are used for selection, along with an academic score and an interview score. The aim of this study was to compare the relative predictive validity of the selected components in the two entry streams, particularly UMAT versus GAMSAT. Methods: Aggregated scores for course outcomes were calculated in the categories of knowledge, clinical and total scores, at four-time points. A path analysis was conducted based on multivariate regressions with model constraint parameters defined across the outcome variables to investigate change over time. Results: Academic scores were the strongest predictors of knowledge scores and end of course results. Interview scores had a small positive increasing effect, being stronger for clinical than knowledge outcomes. The effect size for GAMSAT was greater than for UMAT. Conclusions: Aptitude tests and interview scores added small but significant incremental predictive value to previous academic achievement. GAMSAT showed larger predictive value on outcomes than UMAT, for which one section (UMAT 3) had a negative effect.

Predicting performance of junior doctors: Association of workplace based assessment with demographic characteristics, emotional intelligence, selection scores, and undergraduate academic performance.

INTRODUCTION: Predicting workplace performance of junior doctors from before entry or during medical school is difficult and has limited available evidence. This study explored the association between selected predictor variables and workplace based performance in junior doctors during their first postgraduate year. METHODS: Two cohorts of medical students (n = 200) from one university in Western Australia participated in the longitudinal study. Pearson correlation coefficients and multivariate analyses utilizing linear regression were used to assess the relationships between performance on the Junior Doctor Assessment Tool (JDAT) and its sub-components with demographic characteristics, selection scores for medical school entry, emotional intelligence, and undergraduate academic performance. RESULTS: Grade Point Average (GPA) at the completion of undergraduate studies had the most significant association with better performance on the overall JDAT and each subscale. Increased age was a negative predictor for junior doctor performance on the Clinical management subscale and understanding emotion was a predictor for the JDAT Communication subscale. Secondary school performance measured by Tertiary Entry Rank on entry to medical school score predicted GPA but not junior doctor performance. DISCUSSION: The GPA as a composite measure of ability and performance in medical school is associated with junior doctor assessment scores. Using this variable to identify students at risk of difficulty could assist planning for appropriate supervision, support, and training for medical graduates transitioning to the workplace.

A Randomized Trial of Effects of Alcohol on Cytochrome P450 Eicosanoids, Mediators of Inflammation Resolution, and Blood Pressure in Men.

BACKGROUND: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress, and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesized by cytochrome P450 (CYP450) enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2 -isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs), and specialized pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). METHODS: Normotensive men (n = 22) were randomly allocated to drink RW (375 ml/d) or the equivalent volume of dealcoholized red wine (DRW) or water for 4 weeks in a 12-week, 3-period crossover trial. BP, heart rate, 20-HETE, F2 -isoprostanes, and SPM were measured at baseline, 4, 8, and 12 weeks. RESULTS: Drinking RW increased BP (p < 0.05), plasma and urinary 20-HETE (p < 0.05), plasma F2 -isoprostanes (p < 0.0001), and the SPMs 18-hydroxyeicosapentaenoic acid (18-HEPE) from EPA, and resolvin D1 (RvD1) and 17R-resolvin D1 (17R-RvD1) from DHA (all p < 0.05) compared with DRW and water. EETs and high-sensitivity C-reactive protein were unaffected by RW. Plasma 18-HEPE was positively related to urinary 20-HETE (p < 0.008) only after RW. CONCLUSIONS: This study has shown that men consuming moderate-to-high alcohol as RW for 4 weeks had increased BP, 20-HETE, and oxidative stress, as well as specific SPM that resolve inflammation. These paradoxical findings require further studies to determine whether alcohol stimulates different CYP450 enzymes and whether the findings can be replicated in females.

Opting for rural practice: the influence of medical student origin, intention and immersion experience.

OBJECTIVE: To compare the influence of rural background, rural intent at medical school entry, and Rural Clinical School (RCS) participation on the likelihood of later participation in rural practice. DESIGN: Analysis of linked data from the Medical School Outcomes Database Commencing Medical Students Questionnaire (CMSQ), routinely collected demographic information, and the Australian Health Practitioner Regulation Agency database on practice location. SETTING AND PARTICIPANTS: University of Western Australia medical students who completed the CMSQ during 2006-2010 and were practising medicine in 2016. MAIN OUTCOME MEASURES: Medical practice in rural areas (ASGC-RAs 2-5) during postgraduate years 2-5. RESULTS: Full data were available for 508 eligible medical graduates. Rural background (OR, 3.91; 95% CI, 2.12-7.21; P < 0.001) and experience in an RCS (OR, 1.93; 95% CI, 1.05-3.54; P = 0.034) were significant predictors of rural practice in the multivariate analysis of all potential factors. When interactions between intention, origin, and RCS experience were included, RCS participation significantly increased the likelihood of graduates with an initial rural intention practising in a rural location (OR, 3.57; 95% CI, 1.25-10.2; P = 0.017). The effect of RCS participation was not significant if there was no pre-existing intention to practise rurally (OR, 1.38; 95% CI, 0.61-3.16; P = 0.44). CONCLUSION: For students who entered medical school with the intention to later work in a rural location, RCS experience was the deciding factor for realising this intention. Background, intent and RCS participation should all be considered if medical schools are to increase the proportion of graduates working rurally.

On the validity of repeated assessments in the UMAT, a high-stakes admissions test.

The possibility that the validity of assessment is compromised by repeated sittings of highly competitive and high profile selection tests has been documented and is of concern to stake-holders. An illustrative example is the Undergraduate Medicine and Health Sciences Admission Test (UMAT) used by some medical and dental courses in Australia and New Zealand. The proficiencies of all applicants who sat the UMAT from one to four sittings between 2006 and 2012 were estimated on the same metric using the probabilistic Rasch model. A fit index characterising each profile's degree of conformity to the model was also calculated. Confirming expectations, mean proficiencies increased with repeated sittings on all three UMAT scales with the greatest difference (which was nevertheless relatively small) between the first two sittings. The fit index showed that the increases in proficiency estimates arose from additional easier items being answered correctly on repeated sittings rather than additional more difficult ones, suggesting that improvements are not on the substantive construct of the variable of assessment but in skills in answering the questions. Although strategies for dealing with the increase in proficiency estimates on repeated sittings could be canvassed, these results suggest that the validity of results on repeated sittings was not compromised. Accordingly, it might be concluded that although particular individuals might improve substantially between sittings, any validity is not likely to be compromised with the possibility that for some applicants, the second sitting might be the most valid.

Impact of medical student origins on the likelihood of ultimately practicing in areas of low vs high socio-economic status.

INTRODUCTION: Medical schools are in general over-represented by students from high socio-economic status backgrounds. The University of Western Australia Medical School has been progressively widening the participation of students from a broader spectrum of the community both through expanded selection criteria and quota-based approaches for students of rural, indigenous and other socio-educationally disadvantaged backgrounds. We proposed that medical students entering medical school from such backgrounds would ultimately be more likely to practice in areas of increased socio-economic disadvantage. METHODS: The current practice address of 2829 medical students who commenced practice from 1980 to 2011 was ascertained from the Australian Health Practitioner Regulation Agency (AHPRA) Database. Logistic regression was utilised to determine the predictors of the likelihood of the current practice address being in the lower 8 socio-economic deciles versus the top 2 socio-economic deciles. RESULTS: Those who were categorised in the lower 8 socio-economic deciles at entry to medical school had increased odds of a current practice address in the lower 8 socio-economic deciles 5 or more years after graduation (OR 2.05, 95% CI 1.72, 2.45, P < 0.001). Other positive univariate predictors included age at medical degree completion (for those 25 years or older vs those 24 years or younger OR 1.53, 95% CI 1.27, 1.84, P < 0.001), being female (OR 1.26, 95% CI 1.07, 1.48, P = 0.005) and having a general practice versus specialist qualification (OR 4.16, 95% CI 3.33, 5.19, P < 0.001). Negative predictors included having attended an independent school vs a government school (OR 0.77, 95% CI 0.64, 0.92, P < 0.001) or being originally from overseas vs being born in Oceania (OR 0.80, 95% CI 0.67, 0.96, P = 0.017). After adjustment for potential confounders in multivariate logistic regression, those in the lower 8 socio-economic deciles at entry to medical school still had increased odds of having a current practice address in the lower 8 socio-economic deciles (OR 1.63, 95% CI 1.34, 1.99, P < 0.001). CONCLUSION: Widening participation in medical school to students from more diverse socio-educational backgrounds is likely to increase the distribution of the medical workforce to ultimate service across areas representative of a broader socio-economic spectrum.

Interest in rural clinical school is not enough: Participation is necessary to predict an ultimate rural practice location.

OBJECTIVE: Rural exposure during medical school is associated with increased rural work after graduation. How much of the increase in rural workforce by these graduates is due to pre-existing interest and plans to work rurally and how much is related to the extended clinical placement is not known. DESIGN: This cohort study compared the employment location of medical graduates who professed no rural interest as undergraduates (negative control), with those who applied but did not participate in Rural Clinical School of Western Australia (RCSWA) (positive control), and those who applied and participated in RCSWA (participants). PARTICIPANTS: All 1026 University of Western Australia students who had an opportunity to apply for a year-long rotation in RCSWA from 2004 to 2010, and who had subsequently graduated by the end of 2011, were included. MAIN OUTCOME MEASURE: Graduates' principal workplace location (AHPRA, Feb 2014). RESULT: The three groups differed significantly in their graduate work locations (χ2 = 39.2, P < 0.001). In multivariate analysis, only being of older age at graduation (OR 2.28 (95% CI 1.40, 3.72), P = 0.001), being from a rural background (OR 2.99 (95% CI 1.85, 4.85), P < 0.001), being a recipient of a Medical Rural Bonded Scholarship (OR 3.36 (95% CI 1.68, 6.73, P = 0.001) and actually participating in the RCSWA remained significantly related to rural work (OR 3.10 (95% CI 1.95, 4.93), P < 0.001). CONCLUSION: After accounting for other factors relating to rural work, RCSWA graduates were three times more likely to work rurally than either control group. These data suggest that RCSWA has a significant independent effect on rural workforce.

Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women.

Coffee is a rich source of polyphenols, primarily chlorogenic acids (CGA). Certain polyphenols and polyphenol-rich foods and beverages have been shown to improve endothelial function and lower blood pressure (BP). The aim of the present study was to investigate the acute effect of two doses of CGA (5-CGA) on endothelial function and BP. In a cross-over study, 16 healthy men and women received: (i) 0 mg purified 5-CGA (control group); (ii) 450 mg purified 5-CGA; (iii) 900 mg purified 5-CGA; and (iv) 200 mg purified (-)-epicatechin (positive control) in random order one week apart. Peak and continuous mean (60 to 240 s post ischaemia) flow-mediated dilation (FMD) was measured at baseline, 1 h and 4 h. BP was measured at baseline and every 30 min to 4 h. Plasma CGA and epicatechin levels were significantly increased at both 1 h and 4 h post their respective treatments. Peak FMD was not significantly altered by either dose of 5-CGA or the epicatechin, relative to control (p > 0.05). Relative to control, effects on continuous mean FMD response following 450 mg 5-CGA and 900 mg of 5-CGA (0.47 ± 0.16%, p = 0.016 and 0.65 ± 0.16%, p < 0.001, respectively) at 1 h and (0.18 ± 0.17%, p = 0.99 and 0.44 ± 0.16%, p < 0.05, respectively) at 4 h. There was no significant effect of any of the treatments on BP. In conclusion, the present study has found no significant effect of 5-CGA, at 450 and 900 mg, on peak FMD response. However, there were significant improvements in mean post-ischaemic FMD response, particularly at the 1 h time point in this group of healthy individuals.

n-3 Fatty Acid Supplementation and Leukocyte Telomere Length in Patients with Chronic Kidney Disease.

DNA telomere shortening associates with the age-related increase cardiovascular disease (CVD) risk. Reducing oxidative stress, could modify telomere erosion during cell replication, and CVD risk in patients with chronic kidney disease (CKD). The effect of n-3 fatty acids and coenzyme Q10 (CoQ) on telomere length was studied in a double-blind placebo-controlled trial in CKD. Eighty-five CKD patients were randomized to: n-3 fatty acids (4 g); CoQ (200 mg); both supplements; or control (4 g olive oil), daily for 8 weeks. Telomere length was measured in neutrophils and peripheral blood mononuclear cells (PBMC) at baseline and 8 weeks, with and without correction for cell counts. Main and interactive effects of n-3 fatty acids and CoQ on telomere length were assessed adjusting for baseline values. F2-isoprostanes were measured as markers of oxidative stress. There was no effect of n-3 fatty acids or CoQ on neutrophil or PBMC telomere length. However, telomere length corrected for neutrophil count was increased after n-3 fatty acids (p = 0.015). Post-intervention plasma F2-isoprostanes were negative predictors of post-intervention telomere length corrected for neutrophil count (p = 0.025).The effect of n-3 fatty acids to increased telomere length corrected for neutrophil count may relate to reduced oxidative stress and increased clearance of neutrophils with shorter telomeres from the circulation. This may be a novel mechanism of modifying CVD risk in CKD patients.

The effects of alcohol on ambulatory blood pressure and other cardiovascular risk factors in type 2 diabetes: a randomized intervention.

OBJECTIVE: Although prospective studies suggest light-to-moderate chronic alcohol intake protects against coronary artery disease in type 2 diabetic patients, the balance of effects on individual cardiovascular risk factors needs further assessment. We examined the effects of alcohol consumption on 24-h ambulatory blood pressure (BP) and heart rate (HR), high-density lipoprotein cholesterol, fibrinogen, C-reactive protein, homocysteine, and glycaemic control in well controlled type 2 diabetes. METHODS: Twenty-four participants aged 49-66 year were randomized to a three-period crossover study with women drinking red wine 230  ml/day (∼24  g alcohol/day) and men drinking red wine 300  ml/day (∼31  g alcohol/day), or equivalent volumes of dealcoholized red wine (DRW) or water, each for 4 weeks. Ambulatory BP and HR were monitored every 30  min for 24  h at the end of each period. Home blood glucose monitoring was carried out twice weekly throughout. RESULTS: Red wine increased awake SBP and DBP relative to water by 2.5 ±â€Š1.2 /1.9 ±â€Š0.7  mmHg (P = 0.033, P = 0.008, respectively), with a similar nonsignificant trend relative to DRW. Asleep DBP fell with red wine relative to DRW (2.0 ±â€Š0.8  mmHg, P = 0.016) with a similar nonsignificant trend relative to water. Red wine increased 24-h, awake and asleep HR relative to water and DRW. Relative to DRW, red wine did not affect glycaemic control or any other cardiovascular risk factor. CONCLUSION: In well controlled type 2 diabetic individuals 24-31  g alcohol/day (∼2-3 standard drinks) raises awake BP and 24-h HR and lowers asleep BP but does not otherwise favourably or adversely modify cardiovascular risk factors.

A randomized controlled trial of the effects of n-3 fatty acids on resolvins in chronic kidney disease.

BACKGROUND AND OBJECTIVE: The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD. METHODS: In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatography-tandem mass spectrometry before and after intervention. RESULTS: Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased (P < 0.0001) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the E- and D-series resolvins, respectively. RvD1 was significantly increased (P = 0.036) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively. CONCLUSION: SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD.