Reproducibility of sequential ambulatory blood pressure and pulse wave velocity measurements in normotensive and hypertensive individuals.

OBJECTIVE: Errors in blood pressure (BP) measurement account for a large proportion of misclassified hypertension diagnoses. Ambulatory blood pressure monitoring (ABPM) is often considered to be the gold standard for measurement of BP, but uncertainty remains regarding the degree of measurement error. The aim of this study was to determine reproducibility of sequential ABPM in a population of normotensive and well controlled hypertensive individuals. METHODS: Individual participant data from three randomized controlled trials, which had recorded ABPM and carotid-femoral pulse wave velocity (PWV) at least twice were combined ( n  = 501). We calculated within-individual variability of daytime and night-time BP and compared the variability between normotensive ( n  = 324) and hypertensive ( n  = 177) individuals. As a secondary analysis, variability of PWV measurements was also calculated, and multivariable linear regression was used to assess characteristics associated with blood pressure variability (BPV). RESULTS: Within-individual coefficient of variation (CoV) for systolic BP was 5.4% (day) and 7.0% (night). Equivalent values for diastolic BP were 6.1% and 8.4%, respectively. No statistically significant difference in CoV was demonstrated between measurements for normotensive and hypertensive individuals. Within-individual CoV for PWV exceeded that of BP measurements (10.7%). BPV was associated with mean pressures, and BMI for night-time measurements. PWV was not independently associated with BPV. CONCLUSION: The variability of single ABPM measurements will still yield considerable uncertainty regarding true average pressures, potentially resulting in misclassification of hypertensive status and incorrect treatment regimes. Repeated ABPM may be necessary to refine antihypertensive therapy.

Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism.

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease.

Hematological parameters and prevalence of anemia in white and British Indian vegetarians and nonvegetarians in the UK Biobank.

BACKGROUND: There may be differences in hematological parameters between meat-eaters and vegetarians. OBJECTIVE: The aim of this study was to perform cross-sectional analyses of hematological parameters by diet group in a large cohort in the United Kingdom. METHODS: A complete blood count was carried out in all UK Biobank participants at recruitment (2006-2010). We examined hemoglobin, red and white blood cell counts, and platelet counts and volume in regular meat eaters (>3 times/wk of red/processed meat consumption, n = 212,831), low meat eaters (n = 213,092), poultry eaters (n = 4815), fish eaters (n = 10,042), vegetarians (n = 6548), and vegans (n = 398) of white ethnicity and meat eaters (n = 3875) and vegetarians (n = 1362) of British Indian ethnicity. RESULTS: In both white and British Indian populations, compared with regular meat eaters (or meat eaters in Indians), the other diet groups had up to 3.7% lower age-adjusted hemoglobin concentrations (difference not significant in white vegan women) and were generally more likely to have anemia (e.g., 8.7% of regular meat eaters compared with 12.8% of vegetarians in white premenopausal women; P < 0.05 after Bonferroni correction). In the white population, compared with regular meat eaters, all other diet groups had lower age- and sex-adjusted total white cells, neutrophils, lymphocytes, monocytes, and eosinophils (P-heterogeneity < 0.001 for all), but basophil counts were similar across diet groups; in British Indians, there was no significant difference in any of the white blood cell counts by diet group. Compared with white regular meat eaters, the low meat eaters, poultry eaters, fish eaters, and vegans had significantly lower platelet counts and higher platelet volume, whereas vegetarians had higher counts and lower volume. Compared with British Indian meat eaters, vegetarians had higher platelet count and lower volume. CONCLUSIONS: In the UK Biobank, people with low or no red meat intake generally had lower hemoglobin concentrations and were slightly more likely to be anemic. The lower white blood cell counts observed in low and non-meat eaters, and differences in mean platelet counts and volume between diet groups, warrant further investigation. This observational study was registered at http://www.isrctn.com/ as ISRCTN10125697.

Adherence to UK dietary guidelines is associated with higher dietary intake of total and specific polyphenols compared with a traditional UK diet: further analysis of data from the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach (CRESSIDA) randomised controlled trial.

Adherence to dietary guidelines (DG) may result in higher intake of polyphenols via increased consumption of fruits, vegetables and whole grains. We compared polyphenol dietary intake and urinary excretion between two intervention groups in the Cardiovascular risk REduction Study: Supported by an Integrated Dietary Approach study: a 12-week parallel-arm, randomised controlled trial (n 161; sixty-four males, ninety-seven females; aged 40-70 years). One group adhered to UK DG, whereas the other group consumed a representative UK diet (control). We estimated polyphenol dietary intake, using a 4-d food diary (4-DFD) and FFQ, and analysed 24-h polyphenol urinary excretion by liquid chromatography-tandem MS on a subset of participants (n 46 control; n 45 DG). A polyphenol food composition database for 4-DFD analysis was generated using Phenol-Explorer and USDA databases. Total polyphenol intake by 4-DFD at endpoint (geometric means with 95 % CI, adjusted for baseline and sex) was significantly higher in the DG group (1279 mg/d per 10 MJ; 1158, 1412) compared with the control group (1084 mg/d per 10 MJ; 980, 1197). The greater total polyphenol intake in the DG group was attributed to higher intake of anthocyanins, proanthocyanidins and hydroxycinnamic acids, with the primary food sources being fruits, cereal products, nuts and seeds. FFQ estimates of flavonoid intake also detected greater intake in DG compared with the control group. 24-h urinary excretion showed consistency with 4-DFD in their ability to discriminate between dietary intervention groups for six out of ten selected, individual polyphenols. In conclusion, following UK DG increased total polyphenol intake by approximately 20 %, but not all polyphenol subclasses corresponded with this finding.

A randomised controlled trial of long-chain omega-3 polyunsaturated fatty acids in the management of rotator cuff related shoulder pain.

STUDY DESIGN: Multicentre, double-blind, placebo-controlled randomised clinical trial. OBJECTIVES: To compare the effectiveness of long chain omega-3 polyunsaturated fatty acids (PUFAs) as part of the management for people diagnosed with rotator cuff related shoulder pain (RCRSP). SUMMARY OF BACKGROUND: Although there is no robust evidence to support their use, omega-3 PUFAs have been recommended for those with tendinopathy due to their potential to moderate inflammation. METHODS: Participants with RCRSP (n=73) were randomised to take either nine MaxEPA capsules providing 1.53 g eicosapentaenoic acid, 1.04 g docosahexaenoic acid or nine matching placebo capsules containing oleic acid per day for 8 weeks. In addition, participants attended an exercise/education programme for 8 weeks. Participants were assessed at prerandomisation, 8 weeks (primary outcome point), 3 months, 6 months and 12 months (secondary outcome point). Primary outcome was the Oxford Shoulder Score (OSS). Secondary outcomes included the Shoulder Pain and Disability Index (SPADI), Patient Specific Functional Score, Euro Qol 5D-3L, Short Form 36, global rating of change and impairment measurements. Analysis was by intention to treat. RESULTS: Difference in the change in the OSS between the two groups at 2 months was -0.1 (95% CI -2.6 to 2.5, p=0.95). The change in SPADI scores was -8.3 (95% CI -15.6 to -0.94, p=0.03, analysed by analysis of covariance adjusted for baseline) at 3 months. CONCLUSION:  Omega-3 PUFA supplementation may have a modest effect on disability and pain outcomes in RCRSP.

Relationships between Maternal Obesity and Maternal and Neonatal Iron Status.

: Obesity in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ≥ 30 kg/m²) and normal weight (n = 245, BMI < 25 kg/m²) age matched pregnant women collected at approximately 15 weeks' gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.

Exploring experiences, barriers, and enablers to home- and class-based exercise in rotator cuff tendinopathy: A qualitative study.

STUDY DESIGN: Qualitative study. INTRODUCTION: Adherence is paramount to the successful outcome of exercise-based treatment. PURPOSE OF STUDY: The barriers and enablers to adherence to a home- and class-based exercise program were explored in this qualitative study. METHODS: Semi-structured interviews were carried out to establish common themes relating to the participants' experiences during a year-long randomized controlled trial. RESULTS/DISCUSSION: Twelve participants were interviewed. The main enablers to exercise were highlighted as equipment, perceived benefit from the exercises, and longer and more intensive monitoring. Barriers included the lack of motivation, lack of equipment, and pain. CONCLUSIONS: Implications for practice are incorporating enablers and addressing barriers including self-discharge from classes; the importance of longer term follow-up and the benefits of adopting exercise into a well-established routine may provide potential benefits. LEVEL OF EVIDENCE: N/A.

A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores.

Low heart rate variability (HRV) predicts sudden cardiac death. Long-chain (LC) n-3 PUFA (C20-C22) status is positively associated with HRV. This cross-sectional study investigated whether vegans aged 40-70 years (n 23), whose diets are naturally free from EPA (20 : 5n-3) and DHA (22 : 6n-3), have lower HRV compared with omnivores (n 24). Proportions of LC n-3 PUFA in erythrocyte membranes, plasma fatty acids and concentrations of plasma LC n-3 PUFA-derived lipid mediators were significantly lower in vegans. Day-time interbeat intervals (IBI), adjusted for physical activity, age, BMI and sex, were significantly shorter in vegans compared with omnivores (mean difference -67 ms; 95 % CI -130, -3·4, P50 % and high-frequency power) were similarly lower in vegans, with no differences during sleep. In conclusion, vegans have higher 24 h SDNN, but lower day-time HRV and shorter day-time IBI relative to comparable omnivores. Vegans may have reduced availability of precursor markers for pro-resolving lipid mediators; it remains to be determined whether there is a direct link with impaired cardiac function in populations with low-n-3 status.

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

PURPOSE: Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet). METHODS: A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density). RESULTS: Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control. CONCLUSIONS: Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.

Adverse effects on insulin secretion of replacing saturated fat with refined carbohydrate but not with monounsaturated fat: A randomized controlled trial in centrally obese subjects.

BACKGROUND: Current dietary guidelines recommend the replacement of saturated fatty acids (SAFAs) with carbohydrates or monounsaturated fatty acids (MUFAs) based on evidence on lipid profile alone, the chronic effects of the mentioned replacements on insulin secretion and insulin sensitivity are however unclear. OBJECTIVE: To assess the chronic effects of the substitution of refined carbohydrate or MUFA for SAFA on insulin secretion and insulin sensitivity in centrally obese subjects. METHODS: Using a crossover design, randomized controlled trial in abdominally overweight men and women, we compared the effects of substitution of 7% energy as carbohydrate or MUFA for SAFA for a period of 6 weeks each. Fasting and postprandial blood samples in response to corresponding SAFA, carbohydrate, or MUFA-enriched meal-challenges were collected after 6 weeks on each diet treatment for the assessment of outcomes. RESULTS: As expected, postprandial nonesterified fatty acid suppression and elevation of C-peptide, insulin and glucose secretion were the greatest with high-carbohydrate (CARB) meal. Interestingly, CARB meal attenuated postprandial insulin secretion corrected for glucose response; however, the insulin sensitivity and disposition index were not affected. SAFA and MUFA had similar effects on all markers except for fasting glucose-dependent insulinotropic peptide concentrations, which increased after MUFA but not SAFA when compared with CARB. CONCLUSION: In conclusion, a 6-week lower-fat/higher-carbohydrate (increased by 7% refined carbohydrate) diet may have greater adverse effect on insulin secretion corrected for glucose compared with isocaloric higher-fat diets. In contrast, exchanging MUFA for SAFA at 7% energy had no appreciable adverse impact on insulin secretion.

Dietary patterns in obese pregnant women; influence of a behavioral intervention of diet and physical activity in the UPBEAT randomized controlled trial.

BACKGROUND: Understanding dietary patterns in obese pregnant women will inform future intervention strategies to improve pregnancy outcomes and the health of the child. The aim of this study was to investigate the effect of a behavioral intervention of diet and physical activity advice on dietary patterns in obese pregnant woman participating in the UPBEAT study, and to explore associations of dietary patterns with pregnancy outcomes. METHODS: In the UPBEAT randomized controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city populations were randomly assigned to receive a diet/physical activity intervention or standard antenatal care. The dietary intervention aimed to reduce glycemic load and saturated fat intake. Diet was assessed using a food frequency questionnaire (FFQ) at baseline (15+0-18+6 weeks' gestation), post intervention (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were characterized using factor analysis of the baseline FFQ data, and changes compared in the control and intervention arms. Patterns were related to pregnancy outcomes in the combined control/intervention cohort (n = 1023). RESULTS: Four distinct baseline dietary patterns were defined; Fruit and vegetables, African/Caribbean, Processed, and Snacks, which were differently associated with social and demographic factors. The UPBEAT intervention significantly reduced the Processed (-0.14; 95% CI -0.19, -0.08, P <0.0001) and Snacks (-0.24; 95% CI -0.31, -0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI 1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI 1.23, 3.41) patterns in the entire cohort were associated with increased risk of gestational diabetes. CONCLUSIONS: In a diverse cohort of obese pregnant women an intensive dietary intervention improved Processed and Snack dietary pattern scores. African/Caribbean and Processed patterns were associated with an increased risk of gestational diabetes, and provide potential targets for future interventions. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

The Increasing Use of Interesterified Lipids in the Food Supply and Their Effects on Health Parameters.

A variety of modified fats that provide different functionalities are used in processed foods to optimize product characteristics and nutrient composition. Partial hydrogenation results in the formation of trans FAs (TFAs) and was one of the most widely used modification processes of fats and oils. However, the negative effects of commercially produced TFAs on serum lipoproteins and risk for cardiovascular disease resulted in the Institute of Medicine and the 2010 US Dietary Guidelines for Americans both recommending that TFA intake be as low as possible. After its tentative 2013 determination that use of partially hydrogenated oils is not generally regarded as safe, the FDA released its final determination of the same in 2015. Many food technologists have turned to interesterified fat as a replacement. Interesterification rearranges FAs within and between a triglyceride molecule by use of either a chemical catalyst or an enzyme. Although there is clear utility of interesterified fats for retaining functional properties of food, the nutrition and health implications of long-term interesterified fat consumption are less well understood. The Technical Committee on Dietary Lipids of the North American Branch of the International Life Sciences Institute sponsored a workshop to discuss the health effects of interesterified fats, identify research needs, and outline considerations for the design of future studies. The consensus was that although interesterified fat production is a feasible and economically viable solution for replacing dietary TFAs, outstanding questions must be answered regarding the effects of interesterification on modifying certain aspects of lipid and glucose metabolism, inflammatory responses, hemostatic parameters, and satiety.

How important is the relative balance of fat and carbohydrate as sources of energy in relation to health?

Both the intake of fat, especially saturated trans fatty acids, and refined carbohydrates, particularly sugar, have been linked to increased risk of obesity, diabetes and CVD. Dietary guidelines are generally similar throughout the world, restrict both intake of SFA and added sugar to no more than 10 and 35 % energy for total fat and recommend 50 % energy from carbohydrates being derived from unrefined cereals, tubers, fruit and vegetables. Current evidence favours partial replacement of SFA with PUFA with regard to risk of CVD. The translation of these macronutrient targets into food-based dietary guidelines is more complex because some high-fat foods play an important part in meeting nutrient requirements as well as influencing the risk of chronic disease. Some of the recent controversies surrounding the significance of sugar and the type of fat in the diet are discussed. Finally, data from a recently published randomised controlled trial are presented to show the impact of following current dietary guidelines on cardiovascular risk and nutrient intake compared with a traditional UK diet.

Differential acute effects of carbohydrate- and protein-rich drinks compared with water on cardiac output during rest and exercise in healthy young men.

The acute effects of drinks rich in protein (PRO) versus carbohydrate (CHO) on cardiovascular hemodynamics and reactivity are uncertain. A randomized crossover design was used to compare 400-mL isoenergetic (1.1 MJ) drinks containing whey protein (PRO; 44 g) or carbohydrate (CHO; 57 g) versus 400 mL of water in 14 healthy men. The primary and secondary outcomes were changes in cardiac output, blood pressure, systemic vascular resistance (SVR) and digital volume pulse measured prior to and 30 min following consumption at rest, during 12 min of multi-stage bicycle ergometry, and 15 min postexercise. The mean change (95% confidence interval (CI)) in resting cardiac output at 30 min was greater for CHO than for PRO or water: 0.7 (0.4 to 1.0), 0.1 (-0.2 to 0.40), and 0.0 (-0.3 to 0.3) L/min (P < 0.001), respectively; the higher cardiac output following CHO was accompanied by an increase in stroke volume and a lower SVR. The mean increments (95% CI) in cardiac output during exercise were CHO 4.7 (4.4 to 5.0), PRO 4.9 (4.6 to 5.2), and water 4.6 (4.3 to 4.9) L/min with the difference between PRO versus water being significant (P < 0.025). There were no other statistically significant differences. In summary, a CHO-rich drink increased cardiac output and lowered SVR in the resting state compared with a PRO-rich drink or water but the effect size of changes in these variables did not differ during or after exercise between CHO and PRO. Neither protein nor carbohydrate affected blood pressure reactivity to exercise.

Participation in a Structured Weight Loss Program and All-Cause Mortality and Cardiovascular Morbidity in Obese Patients With Chronic Kidney Disease.

OBJECTIVE: To determine if participation in a weight loss program impacted upon a composite end point of all-cause mortality and cardiovascular morbidity in obese patients with chronic kidney disease (CKD). DESIGN: Retrospective cohort study. SUBJECTS: All patients with a body mass index (BMI) >30 kg/m(2) or >28 kg/m(2) with at least 1 comorbidity (hypertension, diabetes, or dyslipidemia) referred to an established weight management program (WMP) from 2005 to 2009 at a metropolitan tertiary teaching hospital were eligible for inclusion in the study cohort. INTERVENTION: Twelve-month structured weight loss program. MAIN OUTCOME MEASURES: Combined outcome of all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure; kidney transplantation waitlisting. RESULTS: A total of 169 obese patients with CKD commenced the WMP and 169 did not-becoming the observational control group (CON). There were no significant differences between groups for age, BMI, sex, ethnicity, smoking, hypertension, or kidney function at baseline, although CON included more patients with diabetes than WMP (49% vs. 38%, P = .03). Kaplan-Meier survival analysis with log-rank test differed between groups for the combined outcome (P = .03). Cox regression analysis with adjustment for age, sex, ethnicity, hypertension, diabetes, kidney function, baseline BMI, and smoking status, indicated that patients in WMP had a significantly longer event-free period for the combined outcome, than those in CON (adjusted hazard ratio 0.53; 95% confidence interval [CI] 0.29-0.97; P = .04). Participation in the WMP did not increase the likelihood of kidney transplantation waitlisting (odds ratio [OR] 1.06; 95% CI 0.39-2.87; P = .9). Lower baseline BMI and greater weight loss over 12 months were the only factors related to kidney transplantation waitlisting (adjusted R(2) = 0.426). CONCLUSIONS: Participation in a structured weight loss program may be associated with improved outcomes in obese patients with CKD.

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. FUNDING: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

How effective are current dietary guidelines for cardiovascular disease prevention in healthy middle-aged and older men and women? A randomized controlled trial.

BACKGROUND: Controversy surrounds the effectiveness of dietary guidelines for cardiovascular disease (CVD) prevention in healthy middle-aged and older men and women. OBJECTIVE: The objective was to compare effects on vascular and lipid CVD risk factors of following the United Kingdom dietary guidelines with a traditional British diet (control). DESIGN: With the use of a parallel-designed randomized controlled trial in 165 healthy nonsmoking men and women (aged 40-70 y), we measured ambulatory blood pressure (BP) on 5 occasions, vascular function, and CVD risk factors at baseline and during 12 wk after random assignment to treatment. The primary outcomes were differences between treatments in daytime ambulatory systolic BP, flow-mediated dilation, and total cholesterol/HDL cholesterol. Secondary outcomes were differences between treatment in carotid-to-femoral pulse wave velocity, high-sensitivity C-reactive protein, and a measure of insulin sensitivity (Revised Quantitative Insulin Sensitivity Check Index). RESULTS: Data were available on 162 participants, and adherence to the dietary advice was confirmed from dietary records and biomarkers of compliance. In the dietary guidelines group (n = 80) compared with control (n = 82), daytime systolic BP was 4.2 mm Hg (95% CI: 1.7, 6.6 mm Hg; P < 0.001) lower, the treatment effect on flow-mediated dilation [-0.62% (95% CI: -1.48%, 0.24%)] was not significant, the total cholesterol:HDL cholesterol ratio was 0.13 (95% CI: 0, 0.26; P = 0.044) lower, pulse wave velocity was 0.29 m/s (95% CI: 0.07, 0.52 m/s; P = 0.011) lower, high-sensitivity C-reactive protein was 36% (95% CI: 7%, 48%; P = 0.017) lower, the treatment effect on the Revised Quantitative Insulin Sensitivity Check Index [2% (95% CI: -2%, 5%)] was not significant, and body weight was 1.9 kg (95% CI: 1.3, 2.5 kg; P < 0.001) lower. Causal mediated effects analysis based on urinary sodium excretion indicated that sodium reduction explained 2.4 mm Hg (95% CI: 1.0, 3.9 mm Hg) of the fall in blood pressure. CONCLUSION: Selecting a diet consistent with current dietary guidelines lowers BP and lipids, which would be expected to reduce the risk of CVD by one-third in healthy middle-aged and older men and women. This study is registered at www.isrctn.com as 92382106.

Vitamin D and risk of CVD: a review of the evidence.

This review summarises evidence for an association between vitamin D status and CVD and the mechanisms involved. Vitamin D3 is predominantly provided by the action of UVB from sunlight on skin. Average UK diets supply 2-3 µg/d vitamin D but diets containing at least one portion of oily fish per week supply about 7 µg/d. Pharmacological doses of vitamin D2 (bolus injection of 7500 µg or intakes >50 µg/d) result in a smaller increase in plasma 25(OH)D than those of D3 but physiological doses 5-25 µg/d seem equivalent. Plasma 25(OH)D concentrations are also influenced by clothing, obesity and skin pigmentation. Up to 40 % of the population have plasma 25(OH)D concentrations <25 nmol/l in the winter compared with <10 % in the summer. The relative risk of CVD death is 1·41 (95 % CI 1·18, 1·68) greater in the lowest quintile of plasma 25(OH)D according to meta-analysis of prospective cohort studies. Acute deficiency may inhibit insulin secretion and promote inflammation thus increasing the risk of plaque rupture and arterial thrombosis. Chronic insufficiency may increase arterial stiffness. There is no evidence to support claims of reduced CVD from existing trials with bone-related health outcomes where vitamin D was usually co-administered with calcium. Although several trials with cardiovascular endpoints are in progress, these are using pharmacological doses. In view of the potential toxicity of pharmacological doses, there remains a need for long-term trials of physiological doses of D2 and D3 with CVD incidence as the primary outcome.