Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK.

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts. Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient. Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.

Adequacy of Critical Nutrients Affecting the Quality of the Spanish Diet in the ANIBES Study.

Diet is one of the key modifiable behaviors that can help to control and prevent non-communicable chronic diseases. Therefore, it is important to evaluate the overall diet composition of the population through non-invasive and independent indexes or scores as diet quality indexes (DQIs). The primary aim of the present work was to estimate the adequacy of the intake of critical nutrients in the Spanish "Anthropometry, Intake, and Energy Balance Study" (ANIBES) (n = 2285; 9-75 years), considering, as a reference, the European Food Scientific Authority (EFSA) values for nutrients for the European Union. We also assessed the quality of the diet for adults and older adults using four internationally accepted DQIs, namely the Healthy Diet Indicator (HDI), the Mediterranean Diet Score (MDS), the Mediterranean Diet Score-modified (MDS-mod), and the Mediterranean-Diet Quality Index (MED-DQI), as well as the ANIBES-DQI, stratified by education and income. The ANIBES-DQI was based on compliance with EFSA and Food and Agriculture Organization recommendations for a selected group of nutrients (i.e., total fat, saturated fatty acids (SFAs), simple sugars, fiber, calcium, vitamin C, and vitamin A), with a total range of 0-7. Misreporting was assessed according to the EFSA protocol, which allowed us to assess the DQIs for both the general population and plausible reporters. The majority of the Spanish population had high intakes of SFAs and sugars and low intakes of fiber, folate, and vitamins A and C. In addition, about half of the population had low DQI scores and exhibited low adherence to the Mediterranean diet pattern. Overall, older adults (>65-75 years) showed better DQIs than adults (18-64 years), without major differences between men and women. Moreover, primary education and low income were associated with low MDS and ANIBES-DQI scores. For the ANIBES-DQI, the percentage of the population with low scores was higher in the whole population (69.5%) compared with the plausible energy reporters (49.0%), whereas for medium and high scores the percentages were higher in plausible reporters (41.2% vs. 26.2% and 9.8% vs. 4.3%, respectively). In conclusion, the present study adds support to marked changes in the Mediterranean pattern in Spain, and low education and income levels seem to be associated with a low-quality diet. Additionally, the misreported evaluation in the ANIBES population suggests that this analysis should be routinely included in nutrition surveys to give more precise and accurate data related to nutrient intake and diet quality.

Lactobacillus reuteri V3401 Reduces Inflammatory Biomarkers and Modifies the Gastrointestinal Microbiome in Adults with Metabolic Syndrome: The PROSIR Study.

Previous studies have reported that probiotics may improve clinical and inflammatory parameters in patients with obesity and metabolic syndrome (MetS). Lactobacillus (L.) reuteri V3401 has shown promising results on the components of MetS in animal studies. We aimed to evaluate the effects of L. reuteri V3401 together with healthy lifestyle recommendations on adult patients with MetS. METHODS: We carried out a randomized, crossover, placebo-controlled, single-center trial in which we included 53 adult patients newly diagnosed with MetS. Patients were block randomly allocated by body mass index (BMI) and sex to receive a capsule containing either the probiotic L. reuteri V3401 (5 × 109 colony-forming units) or a placebo once daily for 12 weeks. Anthropometric variables, biochemical and inflammatory biomarkers, as well as the gastrointestinal microbiome composition were determined. RESULTS: There were no differences between groups in the clinical characteristics of MetS. However, we found that interleukin-6 (IL-6) and soluble vascular cell adhesion molecule 1 (sVCAM-1) diminished by effect of the treatment with L. reuteri V3401. Analysis of the gastrointestinal microbiome revealed a rise in the proportion of Verrucomicrobia. CONCLUSIONS: Consumption of L. reuteri V3401 improved selected inflammatory parameters and modified the gastrointestinal microbiome. Further studies are needed to ascertain additional beneficial effects of other probiotic strains in MetS as well as the mechanisms by which such effects are exerted.

Effects of X-chromosome Tenomodulin Genetic Variants on Obesity in a Children's Cohort and Implications of the Gene in Adipocyte Metabolism.

Tenomodulin (TNMD) is a type II transmembrane glycoprotein that has been recently linked to obesity, and it is highly expressed in obese adipose tissue. Several sex-dependent associations have been observed between single-nucleotide polymorphisms (SNPs) of the TNMD gene, which is located in the X-chromosome, and obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome in adults. On the other hand, results are lacking for children. We aimed (i) to study the association between TNMD genetic variants and metabolic complications related to childhood obesity and (ii) to investigate the function of TNMD in human adipocytes. We conducted a case-control, multicenter study in 915 Spanish children and demonstrated significant positive associations between TNMD genetic variants and BMI z-score, waist circumference, fasting glucose, and insulin resistance in boys, highlighting the SNP rs4828038. Additionally, we showed a BMI-adjusted inverse association with waist circumference in girls. Second, in vitro experiments revealed that TNMD is involved in adipogenesis, along with glucose and lipid metabolism in differentiated adipocytes, and these effects may be mediated through AMPK activation. Hence, these results suggest that TNMD genetic variants could be potentially useful as early life risk indicators for obesity and T2DM. In addition, we support the fact that TNMD exhibits significant metabolic functions in adipocytes.

Evaluation of the effect of Lactobacillus reuteri V3401 on biomarkers of inflammation, cardiovascular risk and liver steatosis in obese adults with metabolic syndrome: a randomized clinical trial (PROSIR).

BACKGROUND: Obesity is characterized by increased fat mass and is associated with the development of insulin resistance syndrome (IRS), usually known as metabolic syndrome. The alteration of the intestinal microbiota composition has a role in the development of IRS associated with obesity, and probiotics, which are live microorganisms that confer a health benefit to the host, contribute to restore intestinal microbiota homeostasis and lower peripheral tissue insulin resistance. We aim to evaluate the effects of the probiotic strain Lactobacillus reuteri (L. reuteri) V3401 on the composition of intestinal microbiota, markers of insulin resistance and biomarkers of inflammation, cardiovascular risk, and hepatic steatosis in patients with overweight and obesity exhibiting IRS. METHODS/DESIGN: We describe a randomized, double-blind, crossover, placebo-controlled, and single-centre trial. Sixty participants (aged 18 to 65 years) diagnosed with IRS will be randomized in a 1:1 ratio to receive either a daily dose of placebo or 5 × 109 colony-forming units of L. reuteri V3401. The study will consist of two intervention periods of 12 weeks separated by a washout period of 6 weeks and preceded by another washout period of 2 weeks. The primary outcome will be the change in plasma lipopolysaccharide (LPS) levels at 12 weeks. Secondary outcomes will include anthropometric parameters, lipid profile, glucose metabolism, microbiota composition, hepatic steatosis, and inflammatory and cardiovascular biomarkers. Blood and stool samples will be collected at baseline, at the midpoint (only stool samples) and immediately after each intervention period. Luminex technology will be used to measure interleukins. For statistical analysis, a mixed ANOVA model will be employed to calculate changes in the outcome variables. DISCUSSION: This is the first time that L. reuteri V3401 will be evaluated in patients with IRS. Therefore, this study will provide valuable scientific information about the effects of this strain in metabolic syndrome patients. TRIAL REGISTRATION: The trial has been retrospectively registered in ClinicalTrials.gov on the 23rd November 2016 (ID: NCT02972567 ), during the recruitment phase.

Dietary Intake and Food Sources of Niacin, Riboflavin, Thiamin and Vitamin B6 in a Representative Sample of the Spanish Population. The Anthropometry, Intake, and Energy Balance in Spain (ANIBES) Study †.

Thiamin, riboflavin, niacin, and vitamin B6 are essential micronutrients that are mainly involved in energy metabolism; they may prevent the occurrence of developmental abnormalities and chronic degenerative and neoplastic diseases. The aim was to analyze dietary intake and food sources of those four nutrients in subjects (n = 2009) aged 9⁻75 years old from the Spanish ANIBES (Anthropometry, Intake, and Energy Balance in Spain) study. Dietary data were collected by means of a validated, photo-based three-day dietary food record. Underreporting was analysed according to the European Food and Safety Authority (EFSA, Parma, Italy) protocol. Mean (max⁻min) reported intake for the whole population of thiamin was 1.17 ± 0.02 mg/day, (0.30⁻3.44 mg/day), riboflavin 1.44 ± 0.02 mg/day, (0.37⁻3.54 mg/day), niacin 29.1 ± 0.2 mg/day (6.7⁻109 mg/day), and vitamin B6 1.54 ± 0.01 mg/day (0.28⁻9.30 mg/day). The main sources of intake for thiamin, niacin, and vitamin B6 were meat and meat products, and for riboflavin were milk and dairy products. An elevated percentage of the Spanish ANIBES population meets the EFSA recommended intakes for thiamin (71.2%), riboflavin (72.0%), niacin (99.0%), and vitamin B6 (77.2%).

25-Hydroxyvitamin D levels of children are inversely related to adiposity assessed by body mass index

Vitamin D deficiency is associated with wide range of pathologies. Some evidences have shown that low vitamin D circulating levels in children and adolescent are related to fat mass and obesity. The objectives of the present study were to characterize vitamin D status in children and adolescents and to determine if serum 25-hydroxyvitamin D (25(OH)D) concentration is related to adiposity assessed by body mass index (BMI). Serum 25(OH)D levels were measured by LIAISON method in 471 children and adolescents (2 to 18 years age) and analyzed according to gender, pubertal period, age, and BMI. An overall prevalence of 25(OH)D insufficiency and deficiency was present in the 67.1%. Lower 25(OH)D levels were found in females (25.56 ± 14.03 vs 29.71 ± 17.10 ng ml−1; P = 0.004) and pubertal children (25.52 ± 13.97 vs 29.21 ± 16.83 ng ml−1; P = 0.011). In addition, an inverse relation of BMI and age on 25(OH)D concentrations was observed in children. In conclusion, low vitamin D status was highly prevalent among children and adolescents. Of note, a non-lineal regression model showed that 39.6% of vitamin D levels variability was explained by BMI. These results indicate that adiposity assessed by BMI impacts vitamin D status

25-Hydroxyvitamin D levels of children are inversely related to adiposity assessed by body mass index.

Vitamin D deficiency is associated with wide range of pathologies. Some evidences have shown that low vitamin D circulating levels in children and adolescent are related to fat mass and obesity. The objectives of the present study were to characterize vitamin D status in children and adolescents and to determine if serum 25-hydroxyvitamin D (25(OH)D) concentration is related to adiposity assessed by body mass index (BMI). Serum 25(OH)D levels were measured by LIAISON method in 471 children and adolescents (2 to 18 years age) and analyzed according to gender, pubertal period, age, and BMI. An overall prevalence of 25(OH)D insufficiency and deficiency was present in the 67.1%. Lower 25(OH)D levels were found in females (25.56 ± 14.03 vs 29.71 ± 17.10 ng ml-1; P = 0.004) and pubertal children (25.52 ± 13.97 vs 29.21 ± 16.83 ng ml-1; P = 0.011). In addition, an inverse relation of BMI and age on 25(OH)D concentrations was observed in children. In conclusion, low vitamin D status was highly prevalent among children and adolescents. Of note, a non-lineal regression model showed that 39.6% of vitamin D levels variability was explained by BMI. These results indicate that adiposity assessed by BMI impacts vitamin D status.

Dietary sources and intakes of folates and vitamin B12 in the Spanish population: Findings from the ANIBES study.

BACKGROUND: Folates and vitamin B12 are key nutrients in one-carbon metabolism and related diseases. Updated and plausible information on population intakes and their major dietary sources is scarce and urgently needed in Spain in order to increase the knowledge that can lead as previous step to prevention by fortification and supplementation policies. AIMS: The present study aims to evaluate main dietary folate and vitamin B12 sources and intakes in the Spanish population. MATERIALS AND METHODS: Results were derived from the ANIBES cross-sectional study using a nationally representative sample of the Spanish population (9-75 years, n = 2,009). RESULTS: Food groups with the highest mean proportional contribution to total folate intakes in both males and females were vegetables (21.7-24.9%) and cereals (10.7-11.2%), while meat and meat products (26.4%) and milk and dairy products (27.3%) were for B12. Total median folate and B12 intakes amongst women were 156.3 µg/d and 4.0 µg/d while for men were 163.6 µg/d and 4.5 µg/d, respectively. In all age groups, vitamin intakes were significantly higher in plausible than in non-plausible energy reporters. CONCLUSION: A limited number of participants had adequate folate intakes, whereas vitamin B12 intakes were adequate for practically the entire population. There is a clear need for improving folates intake in the Spanish population.

A New Personalized Cooling Protocol to Activate Brown Adipose Tissue in Young Adults.

Brown adipose tissue (BAT) activity is induced when humans are exposed to cold. Therefore, cold exposure prior to the 18F-FDG-PET/CT scan is used as a tool to quantify BAT. Several cooling protocols, including fixed and personalized ones are currently in use. The aim of the present study was to determine the effect of a new personalized cooling protocol where the shivering threshold was measured on a separate day, on BAT volume and activity in young adults. A total of 47 adults (n = 28 women) aged 22 ± 2 years participated in the study. We determined participants' shivering threshold (visually and self-reported) using a water perfused cooling vest in an air-conditioned cold room. 48-72 h later, participants wore the cooling vest set at ~4°C above the shivering threshold for 60 min prior to injection of 18F-FDG and ~5°C above the shivering threshold for ~60 min after injection, until PET/CT scan. We quantified BAT following BARCIST 1.0 recommendations. We identified 40 participants (85%, n = 25 women) as PET+ and 7 (n = 3 women) as PET-. The PET+ group presented significantly higher BAT volume and activity than PET- group (all P < 0.05). PET+ women had higher BAT mean activity than PET+ men (SUVmean: 5.0 ± 1.6 vs. 3.6 ± 0.9 g/ml respectively, P = 0.003), and there were no significant sex differences in BAT volume (P = 0.161). A total of 9 out of 47 participants did not shiver during the shivering threshold test. Our findings are similar to previous cold-stimulated human BAT studies; therefore, we conclude that our personalized cooling protocol is able to activate BAT in young adults.

Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study.

Leptin is an endocrine hormone that has a critical role in body weight homoeostasis and mediates its effects via the leptin receptor (LEPR). Common polymorphisms in the genes coding leptin receptors have been associated with metabolic abnormalities. We assessed the association of 28 LEPR polymorphisms with body mass index (BMI) and their relationship with obesity-related phenotypes, inflammation and cardiovascular disease risk biomarkers. A multicentre case-control study was conducted in 522 children (286 with obesity and 236 with normal-BMI). All anthropometric, metabolic factors and biomarkers were higher in children with obesity except apolipoprotein (Apo)-AI, cholesterol, high-density lipoprotein cholesterol (HDL-c), and adiponectin, which were lower in the obesity group; and glucose, low-density lipoprotein cholesterol (LDL-c), and matrix metalloproteinase-9 that did not differ between groups. We identified the associations between rs11208659, rs11804091, rs10157275, rs9436303 and rs1627238, and BMI in the whole population, as well as the association of rs11804091, rs10157275, and rs1327118 with BMI in the female group, although only the rs11804091 remained associated after Bonferroni correction (p = 0.038). This single nucleotide polymorphisms (SNP) was also associated with insulin (p = 0.004), homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.006), quantitative insulin sensitivity check index (QUICKI) (p = 0.005) and adiponectin (p = 0.046) after adjusting for age, Tanner stage and BMI. Our results show a sex-specific association between the rs11804091 and obesity suggesting an influence of this SNP on insulin resistance.

Reported Dietary Intake and Food Sources of Zinc, Selenium, and Vitamins A, E and C in the Spanish Population: Findings from the ANIBES Study.

Zinc, selenium, and the vitamins A, E and C, all have specific biological functions that are involved mainly in the antioxidant defence system, which has important implications for the development of chronic diseases. We aimed to assess the reported intake of those six nutrients, as well as the food that contributes to their sources of intakes. Data were obtained from the Spanish ANIBES ("Anthropometry, Intake and Energy Balance in Spain") study, n = 2009 (9-75 years old). The analyses were performed in the whole population and in the plausible energy reporters after a misreporting analysis according to the European Food and Safety Authority (EFSA) protocol. A validated, photo-based three-day food record was used to collect the data. Mean (max-min) reported intake for the whole population of zinc was 8.1 ± 0.1 mg/day, (2.3-27.3 mg/day), selenium 75 ± 1 µg/day, (14-265 µg/day), vitamin A 668 µg RE/day (2-11,017 µg RE/day), retinol 364 ± 18 µg/day (0-10,881 µg/day), carotenes 1735 ± 35 µg/day (13-13,962 µg/day), vitamin E 7.0 ± 0.1 mg α-TE/day (0.7-55.2 mg α-TE/day) and vitamin C 84.4 ± 1.4 mg/day (5.0-802.7 mg/day). The main source intakes for zinc were meat and meat products, for selenium cereals and grains, for vitamin E oils and fat, and for vitamin A and C vegetables. There is an elevated percentage of the Spanish ANIBES population not meeting the EFSA recommended intakes for all analysed micronutrients: zinc (83%), vitamin A (60%), vitamin E (80%), vitamin C (36%) and selenium (25%).

Iron Intake and Dietary Sources in the Spanish Population: Findings from the ANIBES Study.

BACKGROUND: Iron deficiency is one of the most common nutritional problems in the world. It is frequent in both developed and developing countries and mainly affects women of childbearing age and children. METHODS: Results were derived from the ANIBES cross-sectional study using a nationally-representative sample of the Spanish population (9-75 years, n = 2009). A three-day dietary record, collected by means of a tablet device, was used to obtain information about food and beverage consumption and leftovers. RESULTS: Total median dietary iron intake was 9.8 mg/day for women and 11.3 mg/day for men. Highest intakes were observed among plausible adolescent reporters (13.3 mg/day), followed by adults (13.0 mg/day), elderly (12.7 mg/day), and children (12.2 mg/day). Prevalence of adequacy for iron intakes as assessed by EFSA criteria was higher than for the Spanish Recommended Iron Intake values in all age groups. Females had lower adequacy than males for both criteria, 27.3% and 17.0% vs. 77.2% and 57.0% respectively. Cereals or grains (26.7%-27.4%), meats and derivatives (19.8%-22.7%), and vegetables (10.3%-12.4%) were the major iron contributors. CONCLUSION: Higher iron intakes were observed in adolescents and were highest for non-heme iron. The prevalence of adequate iron intake according to EFSA criteria was higher than compared to national recommendations, and women had the lowest intakes. Therefore, there is a need to define standard dietary reference intake to determine inadequate iron intakes in the Spanish population.

Reported Dietary Intake, Disparity between the Reported Consumption and the Level Needed for Adequacy and Food Sources of Calcium, Phosphorus, Magnesium and Vitamin D in the Spanish Population: Findings from the ANIBES Study.

Calcium, phosphorus, magnesium and vitamin D have important biological roles in the body, especially in bone metabolism. We aimed to study the reported intake, the disparity between the reported consumption and the level needed for adequacy and food sources of these four nutrients in the Spanish population. We assessed the reported intake for both, general population and plausible reporters. Results were extracted from the ANIBES survey, n = 2009. Three-day dietary reported intake data were obtained and misreporting was assessed according to the European Food Safety Authority (EFSA). Mean ± SEM (range) total reported consumption of calcium, phosphorus, magnesium, and vitamin D for the whole population were 698 ± 7 mg/day (71-2551 mg/day), 1176 ± 8 mg/day, (331-4429 mg/day), 222 ± 2 mg/day (73-782 mg/day), and 4.4 ± 0.1 µg/day (0.0-74.2 µg/day), respectively. In the whole group, 76% and 66%; 79% and 72%; and 94% and 93% of the population had reported intakes below 80% of the national and European recommended daily intakes for calcium, magnesium and vitamin D, respectively; these percentages were over 40% when the plausible reporters were analysed separately. The main food sources were milk and dairy products for calcium and phosphorus, cereals and grains for magnesium and fish for vitamin D. In conclusion, there is an important percentage of the Spanish ANIBES population not meeting the recommended intakes for calcium, magnesium and vitamin D.

Fatty acid status and antioxidant defense system in mothers and their newborns after salmon intake during late pregnancy.

OBJECTIVE: The aim of the present study was to assess the maternal and newborn status of erythrocyte fatty acids and the antioxidant defense system after the intake of two portions of salmon per week during late pregnancy. METHODS: Pregnant women (N = 123) were randomly assigned to continue their habitual diet, which was low in oily fish (control group, n = 61) or to consume two 150-g salmon portions per week (salmon group, n = 62) beginning at 20 wk of gestation and lasting until delivery. Fatty acids, selenium, and glutathione concentrations and antioxidant defense enzyme activities were measured in maternal erythrocytes at 20, 34, and 38 wk of pregnancy, and in cord erythrocytes collected at birth. Plasma concentrations of antioxidant molecules were measured. RESULTS: Compared with the control group, consuming salmon had little effect on erythrocyte fatty acids in either mothers or newborns. Components of the antioxidant defense system did not differ between groups. Glutathione peroxidase activity and the concentrations of tocopherols, retinol, and coenzyme Q10 were significantly lower in cord blood compared with maternal blood at week 38 in both groups. CONCLUSION: Maternal and newborn erythrocyte fatty acids are not strongly affected by the intake of two portions of salmon per week during the second half of pregnancy, although erythrocyte docosahexaenoic acid might be increased in newborns. Maternal and newborn antioxidant defense systems are not impaired by intake of salmon from 20 wk gestation.

Inflammatory Response Using Different Lipid Parenteral Nutrition Formulas in Children After Hematopoietic Stem Cell Transplantation.

Nutritional support is an integral part of the supportive care of hematopoietic stem cell transplantation (HSCT) patients. Omega-3 fatty acids (n-3 FA) emulsions in parenteral nutrition (PN) may modify the inflammatory response. The purpose of this study is to compare plasma cytokine levels in children after HSCT using an n-3 FA-containing lipid emulsion (LE) and a soybean oil-based formulation in PN. A randomized double-blind controlled trial was conducted on 14 children following HSCT. Children were randomized to receive either a fish oil or a soybean oil LE. Blood samples were drawn at baseline, on Day 10 and after completion of PN to analyze plasma interleukin 1 beta (IL-1ß), 2 (IL-2), 6 (IL-6), 8 (IL-8), 10 (IL-10), and tumor necrosis factor alpha (TNF-α). After 10 days of PN, there were no significant changes in interleukins levels when comparing the two groups or time points (baseline vs. Day 10 of PN). In children requiring PN >21 days, IL-10 and TNF-α levels (P ≤ 0.05) were lower in the fish-oil-containing LE group. Fish oil- and soybean oil-supplemented PN administered for at least 10 days does not cause inflammatory changes. Prolonged PN based on fish oil LE may modulate the inflammatory response.

Changes in Oxidative Stress and Inflammatory Biomarkers in Fragile Adults over Fifty Years of Age and in Elderly People Exclusively Fed Enteral Nutrition.

We aim to evaluate whether exclusive feeding of an enteral formula enriched with n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) affects oxidative stress and the antioxidant defence system and may improve the levels of some relevant inflammatory, and cardiovascular biomarkers in frail adults over fifty years of age and in elderly subjects. Fifty-five patients were divided into two groups and were exclusively fed a newly designed normoproteic and isocaloric enteral formula enriched with eicosapentaenoic (98 mg/d) and docosahexaenoic acids (46 mg/d) (n = 26) or a reference enteral diet (n = 29). Oxidative, inflammatory and cardiovascular risk biomarkers and red blood cell fatty acid profiles were determined at the beginning and after 90 and 180 days of feeding. The n-3 LC-PUFA percentage tended to be higher (P = 0.053) in the experimental group than in the reference group. Administration of the n-3 LC-PUFA diet did not increase oxidative stress or modify plasma antioxidant capacity but decreased antioxidant enzymatic activities. MMP-9 plasma concentration decreased with both formulae, whereas tPAI-1 tended to decrease (P = 0.116) with the administration of the experimental formula. In conclusion, administration of the new n-3 LC-PUFA-enriched product for 6 months did not negatively alter the oxidative status and improved some cardiovascular risk biomarkers.

Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism.

BACKGROUND: The marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin. METHODS: In a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA + DHA concentrate (5 g/day, containing ~2.8 g EPA + DHA; Omega-3), or (iv) pioglitazone and EPA + DHA concentrate (Pio& Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA + DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers. RESULTS: Omega-3 and Pio& Omega-3 increased EPA + DHA content in serum phospholipids. Pio and Pio& Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio& Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio& Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio& Omega-3. CONCLUSION: Besides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA + DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy. TRIAL REGISTRATION: EudraCT number 2009-011106-42.

Activating brown adipose tissue through exercise (ACTIBATE) in young adults: Rationale, design and methodology.

AIMS: The energy expenditure capacity of brown adipose tissue (BAT) makes it an attractive target as a therapy against obesity and type 2 diabetes. BAT activators namely catecholamines, natriuretic peptides and certain myokines, are secreted in response to exercise. ACTIBATE will determine the effect of exercise on BAT activity and mass measured by positron emission tomography/computed tomography (PET/CT, primary outcome) in young adults. ACTIBATE will also investigate the physiological consequences of activating BAT (secondary outcomes). METHODS: ACTIBATE will recruit 150 sedentary, healthy, young adults (50% women) aged 18-25 years. Eligible participants will be randomly assigned to a non-exercise group (n ≈ 50) or one of two exercise groups (n=50 each). Participants in the exercise groups will perform aerobic and strength training 3-4 days/week at a heart rate equivalent to 60% of heart rate reserve (HRres), and at 50% of 1 repetition maximum (RM) for the moderate-intensity group, and at 80% of HRres and 70% RM for the vigorous-intensity group. Laboratory measures completed at baseline and 6 months include BAT activity and mass, resting energy expenditure, meal and cold-induced thermogenesis, body temperature regulation and shivering threshold, body composition and cardiovascular disease risk factors. We will also obtain biopsies from abdominal subcutaneous white adipose tissue and skeletal muscle to analyse the expression of genes encoding proteins involved in the thermogenic machinery. DISCUSSION: Findings from ACTIBATE will have significant implications for our understanding of exercise and its protective effects against the development of type 2 diabetes, obesity and related metabolic diseases. ClinicalTrials.gov ID: NCT02365129.