The Link between Serum 25-Hydroxyvitamin D, Inflammation and Glucose/ Insulin Homeostasis Is Mediated by Adiposity Factors in American Adults

Prior studies have suggested a significant association between 25-hydroxyvitamin D (25(OH)D) concentrations with markers of inflammation and glucose and insulin homeostasis. However, it is unclear whether these associations are confounded or mediated by adiposity. We used an established mediation analysis to investigate the role of adiposity in the relation between serum 25(OH)D with markers of inflammation and glucose and insulin metabolism. We used data from National Health and Nutrition Examination Survey (2005-2010), to evaluate the associations between serum 25(OH)D and markers of insulin resistance or inflammation, and whether these associations are mediated by adiposity factors including body mass index (BMI, marker of body adiposity), waist circumference (WC, marker of central adiposity), anthropometrically predicted visceral adipose tissue (apVAT), and Visceral Adiposity Index (VAI). Analysis of co-variance and conceptual causal mediation analysis were conducted taking into consideration the survey design and sample weights. A total of 16,621 individuals were included; 8607 (48.3%) participants were men and the mean age of the population was 47.1 years. Mean 25(OH)D serum concentration for the overall population was 57.9\ub10.1 nmol/L with minimal differences between men and women (57.5\ub10.2 nmol/L and 58.2\ub10.2 nmol/L, respectively). After adjustment for age, sex, season and race/ethnicity, mean levels of C-reactive protein (CRP), apolipoprotein B (apo-B), fasting blood glucose (FBG), insulin, homeostatic model assessment of IR (HOMA-IR) and β cell function (HOMA-β), haemoglobin A1c (HbA1c), and 2-h glucose were lower for the top quartile of serum 25(OH)D (all p<0.001). Body mass index (BMI) was found to have significant mediation effects (to varied extent) on the associations between serum 25(OH)D and CRP, apo-B, fasting glucose, insulin, HOMA-IR, HOMA-B and HbA1c (all p<0.05). Both waist circumference and apVAT were also found to partly mediate the associations between serum 25(OH)D with CRP, FBG, HbA1c, triglycerides and HDL-cholesterol (all P < 0.05). VAI was found to have mediation effects on CRP only (p<0.001). Using a mediation model, our findings suggest that the relationship between serum 25(OH)D, insulin resistance and inflammation, may be in part mediated by adiposity. These findings support the importance of optimizing 25(OH)D status in conditions with abnormal adiposity (i.e., obesity) and treatments for the prevention of cardio-metabolic diseases affecting adipose tissue metabolism (i.e., weight loss)

Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity

BackgroundAgeing and type 2 diabetes mellitus (T2DM) are risk factors for skeletal muscle loss. We investigated whether anabolic resistance to feeding might underlie accelerated muscle loss in older people with T2DM and whether dysregulated mTOR signalling was implicated.Subjects8 obese men with T2DM, and 12 age-matched controls were studied (age 68±3 vs. 68±6y; BMI: 30±2 vs. 27±5 kg·m-2).MethodsBody composition was measured by dual-X-ray absorptiometry. Insulin and glucose were clamped at post-absorptive concentrations (13±2 vs. 9±3 mU·l-1; 7.4±1.9 vs. 4.6±0.4 mmol·l-1; T2DM vs. controls). Fractional synthetic rates (FSR) of myofibrillar and sarcoplasmic proteins were measured as the rate of incorporation of [13C] leucine during a primed, constant infusion of [1-13C] α-ketoisocaproic acid, 3 h after 10 or 20g of essential amino acids (EAA) were orally administered. Protein expression of total and phosphorylated mTOR signalling proteins was determined by Western blot analysis.ResultsDespite a significantly lower appendicular lean mass index and a greater fat mass index in T2DM vs. controls, basal myofibrillar and sarcoplasmic and post-prandial myofibrillar FSR were similar. After 20g EAA, stimulation of sarcoplasmic FSR was slightly blunted in T2DM patients. Furthermore, feeding 20g EAA increased phosphorylation of mTOR, p70S6k and 4E-BP1 by 60-100% in controls with no response observed in T2DM.ConclusionsThere was clear dissociation between changes in mTOR signalling versus changes in protein synthesis rates. However, the intact anabolic response of myofibrillar FSR to feeding in both groups suggests anabolic resistance may not explain accelerated muscle loss in T2DM

Medium-term effects of dietary nitrate supplementation on systolic and diastolic blood pressure in adults

OBJECTIVES Dietary nitrate supplementation has been shown to lower blood pressure (BP) particularly in short-term clinical trials. Whether these effects are sustained in the long-term remains to be established. The objective was to conduct a meta-analysis of randomized controlled trials that examined whether dietary nitrate supplementation for more than 1 week has beneficial effects on SBP and DBP. METHODS Electronic databases were searched from inception until May 2016. Specific inclusion criteria were duration at least 1 week, report of effects on SBP or DBP or both and comparison of inorganic nitrate or beetroot juice supplementation with placebo control groups. Random-effects models were used to calculate the pooled BP effect sizes. RESULTS Thirteen trials met eligibility criteria. The trials included a total of 325 participants with seven to 65 participants per study. The duration of each intervention ranged from 1 to 6 weeks. Ten trials assessed BP in resting clinic conditions, whereas 24-h ambulatory and daily home monitorings were used in six and three trials, respectively. Overall, dietary nitrate was associated with a significant decline in SBP [-4.1 mmHg (95% confidence interval: -6.1, -2.2); P < 0.001] and DBP [-2.0 mmHg (95% confidence interval: -3.0, -0.9); P < 0.001]. However, the effect was only significant when measured in resting clinical settings as no significant changes in BP were observed using 24-h ambulatory and daily home BP monitorings. CONCLUSION Positive effects of medium-term dietary nitrate supplementation on BP were only observed in clinical settings, which were not corroborated by more accurate methods such as 24-h ambulatory and daily home monitorings

Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials

Background and Objectives: Physical activity is associated with lower cardiovascular and all-cause mortality. However, the effects of different exercise modalities on arterial stiffness are currently unclear. Our objectives were to investigate the effects of exercise modalities (aerobic, resistance or combined) on pulse wave velocity (PWV) and augmentation index (AIx), and to determine whether the effects on these indices differed according to the participants' or exercise characteristics. Methods: We searched the Medline, Embase and Cochrane Library databases from inception until April 2014 for randomized controlled trials lasting ≥4 weeks investigating the effects of exercise modalities on PWV and AIx in adults aged ≥18 years. Results: Forty-two studies (1627 participants) were included in this analysis. Aerobic exercise improved both PWV (WMD: −0.63 m/s, 95% CI: −0.90, −0.35) and AIx (WMD:−2.63%, 95% CI: −5.25 to −0.02) significantly. Aerobic exercise training showed significantly greater reduction in brachial-ankle (WMD: −1.01 m/s, 95% CI: −1.57, −0.44) than in carotid-femoral (WMD: -0.39 m/s, 95% CI: −0.52, −0.27) PWV. Higher aerobic exercise intensity was associated with larger reductions in AIx (β: −1.55%, CI −3.09, 0.0001). In addition, aerobic exercise had a significantly larger effect in reducing PWV (WMD:−1.0 m/s, 95% CI: −1.43, −0.57) in participants with stiffer arteries (PWV ≥8 m/s). Resistance exercise had no effect on PWV and AIx. There was no significant effect of combined exercise on PWV and AIx. Conclusions: We conclude that aerobic exercise improved arterial stiffness significantly and that the effect was enhanced with higher aerobic exercise intensity and in participants with greater arterial stiffness at baseline. Trial Registration PROSPERO: Database registration: CRD42014009744,

Association of Dietary Intakes and Genetically Determined Serum Concentrations of Mono and Poly Unsaturated Fatty Acids on Chronic Kidney Disease: Insights from Dietary Analysis and Mendelian Randomization

Polyunsaturated fatty acid (PUFA) intake is generally associated with better renal function, while the association of monounsaturated fatty acids (MUFAs) remains unconfirmed. Mendelian randomization (MR) analysis was used to obtain unconfounded estimates of the causal association of dietary intake and genetically determined serum PUFA and MUFA levels with measures of renal function. Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were used. Data from the largest genome-wide association studies (GWAS) on MUFAs, PUFAs, eGFR, and chronic kidney disease (CKD) were analysed for the entire sample. A total of 16,025 participants were included. eGFR improved across increasing quartiles of total PUFA intake from 86.3 &plusmn; 0.5 (Q1) to 96.2 &plusmn; 0.5 mL/min/1.73 m&sup2; (Q4), (p &lt; 0.001). Conversely, there was no association between MUFA intake and measures of renal function (all p &gt; 0.21). In multivariable models, the top quartile of PUFA intake had a 21% lower risk for CKD, but there was no significant association between CKD risk and MUFA intake. Genetically determined serum MUFA (heptadecenoate (17:1), myristoleic acid (14:1), and palmitoleic acid (16:1)) and PUFA (&alpha;-linolenic acid and eicosapentaenoic acid) concentrations had no significant association with eGFR and CKD risk. Additionally, no association was found in the analyses stratified by diabetes status. Higher dietary PUFA intake is associated with lower risk of CKD, while there was no association with serum levels of MUFAs or PUFAs. Additional studies including clinical trials are warranted

Fright but not fight‐or‐flight: Violent video games elevated stress markers, but did not impact muscle function, memory recall or food intake, in a randomized trial in healthy young men

Objectives: Regular video game playing has been linked with obesity, but the underlying mechanisms remain unclear. Drawing on evolutionary life history theory, we hypothesized that playing violent video games, through activating the stress response, might increase the immediate demand for fuel by muscle and brain tissue, resulting in elevated appetite and food consumption. // Methods: We randomized 71 young adult men to play video games, involving either violent content or nonviolent puzzle-solving, for 1 h. Over this period, we measured stress markers (blood pressure [BP], heart rate, visual-analogue scale [VAS] self-ratings), muscle function (handgrip strength) and cognitive function (memory recall test). Appetite was assessed by VAS, and by food intake using a test-meal after the intervention. Linear mixed-effects models were fitted to assess group effects and group:time effects. // Results: During the intervention, the violent video game group showed elevated systolic BP (∆ = 4.7 mm Hg, 95% CI 1.0, 8.4) and reported feeling more alert but less calm or happy. They showed no difference in grip strength or memory recall. They reported lower feelings of “fullness” but consumed similar food-energy during the test-meal. // Conclusions: Although playing a video game with violent content elevated physiological and perceived stress markers compared with a nonviolent game, this was not associated with markers of altered fuel distribution toward two tissues (muscle and brain) that contribute to the “fight-or-flight” response. Rather than more energy being allocated to the brain overall, energy may have been reallocated within the brain. This may explain why there was no compensatory increase in energy intake in the violent video game group

The Association of Red Meat Intake with Inflammation and Circulating Intermediate Biomarkers of Type 2 Diabetes Is Mediated by Central Adiposity

\ua9 The Author(s) 2019. We explored the role of lipid accumulation products and visceral adiposity on the association between red meat consumption and markers of insulin resistance (IR) and inflammation in US adults. Data on red meat consumption, and health outcome measurements were extracted from the 2005-2010 US National Health and Nutrition Examination Surveys. Overall 16,621 participants were included in the analysis (mean age = 47.1 years, 48.3% men). Analysis of co-variance and "conceptus causal mediation" models were applied, while accounting for survey design. In adjusted models, a lower red meat consumption was significantly associated with a cardio-protective profile of IR and inflammation. Body mass index (BMI) had significant mediation effects on the associations between red meat consumption and C-reactive protein (CRP), Apolipoprotein-B, fasting glucose (FBG), insulin, homeostatic model assessment (HOMA) IR and β-cell function, glycated haemoglobin (HbA1c), triglyceride to high density lipoprotein (TG:HDL) ratio and triglyceride-glucose (TyG) index (all p &lt; 0.05). Both waist circumference and anthropometrically predicted visceral adipose tissue (apVAT) mediated the association between red meat consumption with CRP, FBG, HbA1c, TG: HDL ratio and TyG index (all p &lt; 0.05). Our findings suggest that adiposity, particularly the accumulation of abdominal fat, accounts for a significant proportion of the associations between red meat consumption IR and inflammation

Serum osmolarity and haematocrit do not modify the association between the impedance index (Ht2/Z) and total body water in the very old: The Newcastle 85+ Study

Bioelectrical impedance is a non-invasive technique for the assessment of body composition; however, information on its accuracy in the very old (80+ years) is limited. We investigated whether the association between the impedance index and total body water (TBW) was modified by hydration status as assessed by haematocrit and serum osmolarity. This was a cross-sectional analysis of baseline data from the Newcastle 85+ Cohort Study. Anthropometric measurements [weight, height (Ht)] were taken and body mass index (BMI) calculated. Leg-to-leg bioimpedance was used to measure the impedance value (Z) and to estimate fat mass, fat free mass and TBW. The impedance index (Ht2/Z) was calculated. Blood haematocrit, haemoglobin, glucose, sodium, potassium, urea and creatinine concentrations were measured. Serum osmolarity was calculated using a validated prediction equation. 677 men and women aged 85 years were included. The average BMI of the population was 24.3±4.2kg/m2 and the prevalence of overweight and obesity was 32.6% and 9.5%, respectively. The impedance index was significantly associated with TBW in both men (n=274, r=0.76, p<0.001) and women (n=403, r=0.96, p<0.001); in regression models, the impedance index remained associated with TBW after adjustment for height, weight and gender, and further adjustment for serum osmolarity and haematocrit. The impedance index values increased with BMI and the relationship was not modified by hydration status in women (p=0.69) and only marginally in men (p=0.02). The association between the impedance index and TBW was not modified by hydration status, which may support the utilisation of leg-to-leg bioimpedance for the assessment of body composition in the very old

Tomato and lycopene supplementation and cardiovascular risk factors: a systematic review and meta-analysis

Background and aims Epidemiological evidence suggests an association between consumption of tomato products or lycopene and lower risk for cardiovascular diseases (CVD). Our aim was to evaluate the state of the evidence from intervention trials on the effect of consuming tomato products and lycopene on markers of cardiovascular (CV) function. We undertook a systematic review and meta-analysis on the effect of supplementing tomato and lycopene on CV risk factors. Methods Three databases including Medline, Web of science, and Scopus were searched from inception to August 2016. Inclusion criteria were: intervention randomised controlled trials reporting effects of tomato products and lycopene supplementation on CV risk factors among adult subjects >18 years of age. The outcomes of interest included blood lipids (total-, HDL-, LDL-cholesterol, triglycerides, oxidised-LDL), endothelial function (flow-mediated dilation (FMD), pulse wave velocity (PWV)) and blood pressure (BP) inflammatory factors (CRP, IL-6) and adhesion molecules (ICAM-1). Random-effects models were used to determine the pooled effect sizes. Results Out of 1189 publications identified, 21 fulfilled inclusion criteria and were meta-analysed. Overall, interventions supplementing tomato were associated with significant reductions in LDL-cholesterol (−0.22 mmol/L; p = 0.006), IL-6 (standardised mean difference −0.25; p = 0.03), and improvements in FMD (2.53%; p = 0.01); while lycopene supplementation reduced Systolic-BP (−5.66 mmHg; p = 0.002). No other outcome was significantly affected by these interventions. Conclusions The available evidence on the effects of tomato products and lycopene supplementation on CV risk factors supports the view that increasing the intake of these has positive effects on blood lipids, blood pressure and endothelial function. These results support the development of promising individualised nutritional strategies involving tomatoes to tackle CVD

The effect of age on the relationship between cardiac and vascular function

Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P < 0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P < 0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P < 0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P < 0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r = −0.73, P = 0.02) and cardiac output (r = −0.69, P = 0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people