Vitamin D (vitD) deficiency has been suspected as a risk factor for type 2 diabetes mellitus (T2DM). It has been reported that an inverse relationship exists between vitD status and risk of T2DM. The aim of this study was to investigate whether there is an association between vitD status and glycemic profile and other metabolic parameters among postmenopausal women with T2DM (living in Saudi Arabia). A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. One thirty six (n = 136) postmenopausal females (age ≥ 50 years) living in Jeddah city, Saudi Arabia, with T2DM were randomly recruited in this study. Anthropometric measures, blood pressure readings and fasting blood samples were obtained fro all study participants. Several biochemical parameters were estimated in fasting serum samples including total 25(OH)D, HbA1c, insulin, glucose, c-peptide and lipid profile. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment for insulin resistance and beta cell activity (HOMA-IR, HOMA-β), Quantitative insulin sensitivity check index (QUICK-I) and McAuley's index. VitD deficiency was defined as serum total 25(OH)D level below 20 ng/ml.The Mean (± SD) serum levels of total 25(OH)D were 13.8 ± 8.6 ng/ml with 79% of the study cohort being vitD deficient. Furthermore, serum total 25(OH)D levels were found to be inversely correlated with fasting insulin (r = -0.24, p = 0.029), HOMA-IR (r = -0.24, p = 0.03), and positively correlated with McAuley's index (r = 0.22, p = 0.048) and QUICK-I (r = 0.25, p = 0.024). In conclusion, vitD deficiency is highly prevalent among postmenopausal women with T2DM living in Jeddah, Saudi Arabia. VitD was found to be associated with insulin resistance. Whether vitD supplements are able to improve insulin sensitivity and other parameters in T2DM postmenopausal women should be further investigated.

Increased postprandial glycaemia and reduced insulin sensitivity are associated with development of Type 2 Diabetes (T2D). Maintaining a normal glucose response is important both for healthy individuals, for disease prevention, and for those with T2D, to prevent development of diabetes-related complications. Chilling previously-cooked starchy carbohydrate (CHO) results in retrogradation of some of the starch to form resistant starch (RS). RS is not absorbed in the small intestine and consequently does not contribute to the postprandial glucose excursion. Reheating the CHO, however, reverses this process, reducing some of the RS content. RS type 5 is formed in the laboratory by heating starch with free fatty acids; there is limited evidence for its formation using domestic cooking methods and real foods. Furthermore it is unclear whether this would translate into a noticeable effect on postprandial glucose metabolism.

In this randomised crossover study, 8 participants attended two study days; at one they consumed a freshly cooked mashed potato meal (203 g boiled potato, 25 g butter) at the other they consumed an identical meal which had been chilled for 66 h then microwave reheated. The potatoes were intrinsically labelled with [U-13C]starch, and participants received a variable [6,6-2H2]glucose infusion, allowing detailed glucose flux modelling. Venous blood samples were taken for 6 h postprandially.

There was no significant effect on postprandial glucose, however repeated measures ANOVA on postprandial insulin time-point data found a significant difference between meals (p = 0.026), with a 24% reduction in incremental area under the curve (0–120 min) and 21% reduction in insulin peak between freshly cooked and reheated meals. There were no significant effects on rate of appearance of glucose into the plasma from the gut (Ra) or on endogenous (hepatic) glucose production (EGP), however there was a strong trend for a reduced rate of glucose disposal (uptake into tissues, Rd) following the reheated meal (p = 0.054).

It is hypothesised that RS was formed in the reheated meal by the chilling and reheating process; this will be verified by in vitro work later in the project. The attenuation of the postprandial insulin response with no significant effect on EGP suggests enhanced hepatic insulin sensitivity following the reheated meal as a possible mechanism for the effects of RS on postprandial glycaemia. This study demonstrates that making simple changes to the way a starchy carbohydrate meal is prepared can have significant beneficial effects on postprandial glucose metabolism.

Prevalence of type 2 diabetes mellitus has significantly increased in the last three decades and currently affects about 1 in 10 globally. A common therapeutic target for type 2 diabetes is α- glucosidase, an essential enzyme located at the brush border of the small intestinal epithelium. The inhibition of α-glucosidase results in a reduced digestion of carbohydrates and a decrease of postprandial blood glucose. Although, synthetic inhibitors are available in the market, these are usually associated with significant gastrointestinal side effects. In this study, natural inhibitors derived from edible brown algae are being investigated as an alternative.

Polysaccharide- and polyphenolic-enriched extracts from Ascophyllum nodosum and Fucus vesiculosus were characterized and screened for their inhibitory effects against α-glucosidase obtained from rat intestine using maltose, sucrose, and p-nitrophenyl (pNPG) as substrates. Acarbose was used as a synthetic inhibitor. Furthermore, enzyme kinetics and mechanism of inhibition of α- glucosidase were determined using linear and non-linear regression methods (GraphPad Prism ver. 6, GraphPad Software, La Jolla California USA).

All tested extracts showed a dose-dependent inhibitory effect against α-glucosidase. However, the type of inhibition varied between the extracts. Most importantly, the composition analysis showed that the seaweed extracts had different polysaccharide and phenolic contents, suggesting different mode of actions against α-glucosidase. The relation between chemical composition and inhibitory activity of the compounds are discussed.

In summary, the current study demonstrates the mechanisms in which different brown seaweed extracts with various composition effectively inhibit α-glucosidase. Therefore, this natural inhibitor can be considered as a potential candidate for the management of type 2 diabetes mellitus.

Orange juice is a natural source of sugars, vitamins, minerals and flavanones and is associated with health benefits. In addition, in-vitro study suggested that orange juice could modulate intestinal microbiota. This study investigated the impact of habitual consumption of 100% pure orange juice (OJ) on the intestinal microbiota and metabolic outcomes in a controlled clinical trial. Ten women were on regular diet without OJ (OJ free-diet) for 30 days followed by regular diet supplemented with 300 ml of orange juice for 60 days (OJ-diet) and a 30-day washout period without OJ (Washout). Biochemical, anthropometric and dietary parameters were monitored and samples of blood, urine and feces were taken at the beginning and every 30 days. Urinary metabolites were identified by UHPLC and the microbiota composition was evaluated by RNAr 16S. Analysis of the biochemical variables at the end of OJ-diet showed a decrease in glucose (-6.5%), insulin (-33%) and, insulin resistance (-44%). There was also reduction of total cholesterol (-14%), LDL (-16%) and triglycerides (-30%). After Washout, all biochemical parameters returned to the initial values. No changes on body weight and body fat were observed during the experimental time. Intestinal bacteria Bifidobacterium and Lactobacillaceae increased with daily consumption of orange juice, and were negatively correlated with blood serum triglycerides, cholesterol, LDL-C, glucose, insulin, and HOMA-IR, but positively correlated with HDL-C. In conclusion, daily consumption of orange juice did not influenced the body weight or body composition of healthy women, and showed a prebiotic effect on the intestinal microbiota, improving microbial colonization, and modulating the metabolic profile, by reducing glucose and lipids in the blood of young and healthy women. It is also suggested that, to obtain such benefits, orange juice should be consumed regularly and in moderate amounts along with a balanced diet.

Yerba mate is highly consumed in South America and has become a popular beverage worldwide because of its healthy properties: antioxidant, vaso-dilating, lipid-reducing, anti-glycation, anti-inflammatory and weight-reducing effects, among others. These effects have been attributed to its high content in polyphenols, mainly chlorogenic acidS, but also quercetin, kaempferol and rutin. Other components in mate are methylxhantines, saponins, vitamins, minerals and alkaloids.

The objective of this work was to evaluate the effects of regularly consuming a moderate, realistic amount of yerba mate (3 beverages/day) on cardiovascular health and anthropometric parameters, in healthy and cardiovascular risk subjects.

A randomized, crossover, controlled study was performed in normocholesterolemic (NC, n = 25) and hypercholesterolemic (HC, n = 27), non-smoker, non-vegetarian, men and women, with BMI 18–25 kg/m2. After a run-in stage, the effects of consuming three servings/day of mate during 8 weeks (mate stage) were compared with an isotonic drink during the same time (control stage). Along the study, polyphenol rich foods were restricted. At the beginning and the end of each intervention, blood pressure was measured, urine and blood samples were collected. Triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol concentrations were measured. Dietary records and physical activity questionnaires were completed in each stage. Results were statistically studied using a mix model with repeated measures and Bonferroni test (SPSS 23.0).

The regular consumption of yerba mate decreased blood lipid concentrations [TC (p < 0.001), LDL (p = 0.001), TG (p = 0.027)] and blood pressure [systolic (p < 0.001), diastolic (< 0.001)] in both groups, with greater effects in HC than NC. Thus, it may be concluded that moderate consumption of yerba mate reduces cardiovascular risk, particularly in hypercholesterolemic subjects.

Funded by the Spanish State Research Agency, projects AGL2010-18269 and AGL2015-69986-R

Endothelial dysfunction is a predictor for cardiovascular disease risk and is a key feature of atherosclerosis. Poor diet quality, including consumption of saturated fat-rich, high-refined carbohydrate snack foods, may have adverse effects on endothelial function. Thus, snack foods, which contribute an average of 20% of energy intake in the UK adult population, present an easily identifiable target to improve vascular health. Almonds are nutrient-dense foods that are rich in unsaturated fats, fibre, minerals and non-nutrient bioactives (NNB), and may have health benefits by displacing snacks high in refined carbohydrates, enriching the diet with micronutrients and NNB, and/or low lipid bioaccessibility. Human clinical trials have demonstrated LDL cholesterol-lowering effects of daily almond consumption, yet the effects on endothelial function are unclear. This study aimed to investigate whether replacing habitual snacks (20% estimated daily energy requirements) with almonds had any impact on endothelium-dependent vasodilation, measured by flow-mediated dilatation (FMD) using ultrasound imaging of the brachial artery following reactive hyperaemia. A randomised, controlled, parallel trial in adult regular snack consumers aged 30–70 y at moderate risk of cardiovascular disease was conducted, including a 2-week run-in period with control snacks and a 6-week intervention period. Control sweet and savoury mini muffin snacks were developed to replicate the average UK snack nutrient profile, which was calculated from snack foods identified in the UK National Diet and Nutrition Survey (NDNS) database (55% energy from carbohydrate, 36% total fat (14% saturated fat), and 10% protein). One hundred and nine volunteers (77 females and 32 males; mean age 56 y) were enrolled in the study and 107 were randomised to isocaloric treatments, 1) control muffins, or 2) dry roasted whole almonds; 105 participants completed the study. Almonds significantly increased FMD relative to control (mean difference 3.6%, 95% CI 1.7, 5.5; P < 0.001), indicating improved endothelial function, and LDL-cholesterol (mean difference -0.25 mmol/L, 95% CI -0.47, -0.03; P = 0.030) significantly decreased adjusted with sex, age and baseline BMI and baseline dependent outcome values. Snacking on whole almonds as a replacement for snacks high in refined starch and sugar, and low in fibre and unsaturated fatty acids, improves endothelial function. The results of this study provide further evidence for the importance of nuts in dietary strategies to reduce risk of cardiovascular disease.

Obesity and its associated comorbidities (type 2 diabetes mellitus, cardiovascular disease, etc.) are a major public health concern worldwide, with prevalence of obesity affecting in Europe up to 17% of the adult population (OCED/EU 2016). Strategies to lose weight mostly relay in lifestyle changes such as restriction in food intake and increased exercise. However, these are not always easily accepted by overweight/obese subjects and their long-term efficiency is limited. Nutraceuticals and functional foods might be an alternative means to help lose weight and reduce associated cardiometabolic risk factors in affected subjects. There are different nutraceuticals/functional foods containing dietary fibre (DF) or polyphenol-rich plant extracts, but to our knowledge there is no nutraceutical combining both bioactive compounds.

The objective of the present study was to assess the efficiency on different risk makers of a dietary supplement combining a soluble DF (oat beta-glucan -BG-) and a green coffee bean extract (GCBE) rich in polyphenols (PP) in overweight/obese subject.

A randomized, parallel, blind, dose-response study was performed in 60 overweight/obese subjects divided into four groups (n = 15) who consumed during 6 weeks two servings per day of one of four nutraceutical formulations containing low (3 g/d) or high (5 g/d) doses of BG of different purity (35 & 70%) and a fixed amount of GCBE providing 600 mg/d PP. Food intake, anthropometry and different cardiometabolic markers were assessed at the beginning and end of the intervention.

Results showed reduced levels of total cholesterol (p = 0.0001), LDL-cholesterol (p = 0.01), VLDL-cholesterol (p = 0.014) and triglycerides (p = 0.023). There were differences among both types of BG, with the 35% BG being more effective reducing lipid plasma levels than the 70% BG. Percentage of body fat significantly decreased after the intervention, the 70% BG being more efficient than the 35% BG. However, there was no effect on body weight and body mass index, which were not significantly modified

It can be concluded that DF and PP might have a synergistic effect reducing cardiometabolic risk factors in overweight/obese subjects.

Funded by Spanish State Research Agency, project AGL2015-69986-R

Up to 20% of the population in industrialised countries are employed as shift workers. Shift work is an independent risk factor for metabolic diseases, such as type-2 diabetes, cardiovascular disease (CVD) and obesity. This may be associated with shift workers’ typical habit of eating during the night, as it forces the body to process nutrients when the body is expecting a period of fast. This study aimed to examine whether redistributing meal times, to create a defined overnight fast period, can improve CVD risk factors in night shift workers.

Eligible participants were permanent or rotating night shift workers who habitually ate on night shift between 1am to 6am and had abdominal obesity as assessed by waist circumference, but were otherwise healthy. This randomised crossover trial comprised a four-week control period and a four-week intervention period separated by a minimum two-week washout period. During the intervention period, participants were advised to rearrange meal and snack times to create a five hour nightly fast between 1am and 6am. Up to four random 24-hour food recalls per participant were performed during both periods of the study, to check compliance and to assess energy intake. All recall periods included a night shift. Participants attended the research facility at the end of each period to be weighed (seca, gmbh & co. kg, Hamburg, Germany). Work schedule and meals were standardised 24 hours prior to attending the research facility. Data were analysed using paired t-test and reported as mean (SD).

Participants (n = 19) were aged 41(10) years. Daily energy intake was not markedly different between the two study periods, intake was 10633 (3591) kJ/ day in the intervention period vs. 10919 (4276) kJ/ day in the control period (n = 60 recalls in each period, p = 0.670). Body weight was significantly lower at the end of the intervention period compared with at the end of the control period (86.2 (17) vs. 87.1 (18) kg, p = 0.001). Similarly, BMI was lower at the end of the intervention period compared with end of control period (30.7 (6) vs. 31.1 (6) kg/m2, p = 0.001).

Increasing evidence indicates that working night shifts potentiates weight gain. We show that advising shift workers to avoid eating during 1am and 6am for a four-week period had a positive impact on body weight. Manipulating meal and snack times for shift workers may be a simple strategy to assist in weight management.

Excess body fat is associated with the production of pro-inflammatory molecules from dysfunctional adipose tissue resulting in systemic inflammation. Inflammation stimulates expression of the iron regulatory hormone hepcidin, resulting in elevated serum ferritin and iron overload in metabolic tissues. Hepcidin driven iron maldistribution may be implicated in the development of metabolic diseases such as Type 2 diabetes and CVD. The aim of this study was to investigate the effect of body fat and the associated inflammation on markers of iron homeostasis.

Analyses were based on data from the cross-sectional National Adult Nutrition Survey (2008–2010) (www.iuna.net). Percentage body fat (BF%) of participants (n = 1211) was measured by a Tanita BC420MA device. Participants were classified as healthy, overweight or obese based on age and gender-specific BF% ranges. Serum ferritin and serum hepcidin were measured using immunoturbidimetric immunoassays. ANCOVA with Bonferroni post hoc (p < 0.05) was used to compare anthropometric parameters, biochemical markers of iron status and inflammation and nutrient intakes between BF% groups. Predictors of serum hepcidin and serum ferritin were determined using linear regression analysis.

In the population 42% were classified as healthy, 33% as overfat and 25% as obese. Serum hepcidin was significantly elevated in obese participants (8.42ng/ml ± 4.2) compared to their healthy counterparts (6.49ng/ml ± 3.9)(p < 0.001). Significantly higher serum ferritin was observed in obese (223ng/ml ± 170) and overfat males (166ng/ml ± 120) compared to healthy males (135ng/ml ± 91)(p < 0.001). A significant percentage of overweight (20%) and obese (32%) participants were at severe risk of iron overload compared to healthy participants (8%)(p < 0.001). No significant differences in dietary iron intakes were observed between BF% groups. Linear regression analysis indicated that BF% was a significant (p < 0.001) predictor of hepcidin in males (β = 0.327) and females (β = 0.226). IL-6 (β = 0.317,p < 0.001) and TNFα (β = 0.229,p < 0.001) were the strongest inflammatory predictors of hepcidin in females only. In males, leptin was a positive predictor (β = 0.159,p = 0.003) of hepcidin, while adiponectin displayed a negative predictive relationship (β = -0.145,p = 0.001)

Our results indicate that excessive adiposity is associated with elevated serum ferritin and hepcidin independent of dietary intake. Cytokines are a potential driver of hepcidin in females, with adipose-derived hormones seeming to have the greater effect in males. These results may help to elucidate the relationship between obesity and dysregulated iron metabolism. Further research is required to investigate the metabolic effects of hepcidin-induced iron overload in those with excess body fat.

The risk of sudden cardiac death (SCD) is doubled when a patient with chronic kidney disease (CKD) stage 5 starts haemodialysis. Low heart rate variability (HRV) has been reported to be independently associated with increased risk of SCD and all cardiac death in haemodialysis patients. Long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA; 20:5n-3, EPA and 22:6n-3, DHA) may exert anti-arrhythmic effects on cardiac myocytes. Haemodialysis patients have lower serum LC n-3 PUFA levels compared to populations without CKD. Few studies have investigated the relationship between LC n-3 PUFA and HRV in patients with CKD. This study aimed to characterise the variability of LC n-3 PUFA status in patients who recently commenced haemodialysis, and to investigate relationships between LC n-3 PUFA status and HRV. A cross-sectional study was conducted in adults aged 40–80 years with CKD commencing haemodialysis (within 6–10 weeks) (NRES research ethics committee ref: 14/LO/0186). At 2 separate study days, pre-dialysis blood samples were taken to measure fatty acid composition by GC, and HRV monitors (Actiheart, CamNtech Ltd, UK) were fitted after dialysis had started to monitor parameters of cardiac autonomic function during dialysis, during the night, and for a total of 24 h. Forty-five patients (mean age 58 y, SD 9, 20 females/25 males) completed data collection at least once; 91% presented hypertension and 39% had type 2 diabetes. Sample mean omega-3 index (O3I; EPA + DHA as a % of fatty acids in erythrocyte membranes) was very low (3.45%, SD 1.25; median 3.26 %, IQR 1.32); only 2 individuals had O3I > 5%. Variability in erythrocyte EPA (median 0.66 %, IQR 0.42) and DHA (median 2.40 %, IQR 1.32) was limited. Most HRV parameters did not significantly correlate with O3I following adjustment (e.g. age, BMI, β-blockers). Plasma EPA significantly positively correlated with overall and longer phase components of HRV and significantly negatively correlated with beat-to-beat variability over 24 h after full adjustment for confounders. This suggests that although higher circulating EPA concentrations were associated with better cardiac responsivity to environmental stimulations over 24 h, they were also associated with poorer parasympathetic tone (the predominant influence on beat-to-beat HRV). No correlations were observed between plasma DHA and HRV. The divergent pattern of relationships between plasma EPA versus DHA and HRV raises the theory that patients commencing haemodialysis may have compromised conversion of EPA to DHA which may impair vagally-mediated regulation of cardiac autonomic function, a potential mechanism for high risk of SCD.

In Western societies, unbalanced diets may lead to intestinal allostatic stress, with microbial dysbiosis and alteration of the gut barrier function. These local modifications may induce a low-grade inflammation via endotoxemic process, which contribute to systemic alterations clustering into the metabolic syndrome (MetS) and increasing the risk of cardiovascular diseases and type 2 diabetes. We investigated the sequence of events initiating the MetS in rats challenged with a diet that differed moderately from the dietary guidelines, regarding the proportions and nature of energy, carbohydrates, lipids and fibre.

Male Wistar rats (265 g upon arrival) were with either a standard diet (Con, n = 10, 3730 kcalkg, 4.0% lipids, 6.3% sucrose, 58.0% starch, 5.0% fibre) or a westernized induction diet (Ind, n = 10, moderately enriched in energy (4120 kcal/kg), lipid (24.0%), and sugars (15%, half sucrose-half fructose), and low in starch (25.5%) and fibre (1.25%). An oral glucose tolerance test (OGTT) was performed after 3 weeks. Rats were euthanized after a further week for body composition and collection of caecum content and tissue samples. LPS-binding protein (LPS-BP) was assayed in plasma; ileum and colon samples were used for measurement of wall barrier function (using Ussing chambers) and microbial activity was assessed in caecum (enzymes and metabolites).

Body weight did not differ between Con and Ind groups at any time, as well as the absolute masses and proportions of visceral adipose tissue and liver. Fasting triglyceride, glucose, insulin and LPS-BP concentrations, HOMA index and glucose AUC during the OGTT were similar in both groups. When compared to the Con group, Ind rats showed significantly higher risk markers, i.e.: (1) Insulin AUC (x2); (2) Hepatic triglyceride content (x2.8); (3) Wall permeability at both the para- and transcellular levels (x2.6 and 4.3, respectively) in the ileum (but not in the colon). In the caecum, H2S absolute and relative amounts were twice higher in the Ind group, in relation with 2–3-fold increases in specific and total activities of microbial cysteine desulfhydrase and proteases.

Multiple dietary changes mimicking a moderately westernized diet induced an increased ileal permeability and changes in the caecal microbial activity, without evidence of endotoxemia. These perturbations were associated with detrimental rupture of homeostasis at both the splanchnic (hepatic steatosis) and systemic (insulin resistance) levels. In this realistic model, these alterations preceded the occurrence of clinical markers of the MetS (obesity and elevated plasma concentrations of glucose and triglyceride).

High glucose condition impairs neuronal integrity and function by regulating amyloidogenesis and neuroinflammation. Here, we pursue to investigate whether high glucose condition leads impairments in neuronal integrity/function by inducing amyloidogenesis and neuroinflammation, and whether piceatannol (PIC) restores high glucose condition-induced deteriorations in neuronal cells. High glucose condition was induced by maintaining SH-SY5Y neuroblastoma cells in 25 mM glucose. In addition, amyloid-beta was applied to make the cells having amyloidogenesis-mediated deleterious alterations. Cells were maintained in low glucose (2.5 mM glucose) or high glucose (25 mM glucose) condition. And, two doses (10 and 20 μM) of PIC and/or 10 μM of amyloid-beta were treated in a subset of cells for 24 h. There were no significant differences in cell morphology and cell viability among groups. PIC treatment did not show cell toxicity based on cell viability assessed by PrestoBlue assay. High concentration of glucose and amyloid-beta treatments increased amyloid-beta concentrations in cell lysates and conditioned media, which were reduced by PIC. 10 μM PIC treatment for 24 h decreased amyloid precursor protein (APP), beta-site amyloid precursor protein cleaving enzyme-1, presenilin (PS) 1 and tau. Among analyzed inflammatory markers, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were reduced in conditioned media by 10 μM PIC administration for 24 h. These data indicate that high glucose condition may result in excessive levels of amyloidogenesis and neuroinflammation as well as subsequent changes in neuronal integrity/function, and that PIC treatment may ameliorate the deleterious consequences from high glucose and amyloid-beta treatments.