Vitamin D and Swimming Exercise Prevent Obesity in Rats under a High-Fat Diet via Targeting FATP4 and TLR4 in the Liver and Adipose Tissue.

The prevalence of obesity has risen in the last decades, and it has caused massive health burdens on people's health, especially metabolic and cardiovascular issues. The risk of vitamin D insufficiency is increased by obesity, because adipose tissue alters both the requirements for and bioavailability of vitamin D. Exercise training is acknowledged as having a significant and long-term influence on body weight control; the favorable impact of exercise on obesity and obesity-related co-morbidities has been demonstrated via various mechanisms. The current work illustrated the effects of vitamin D supplementation and exercise on obesity induced by a high-fat diet (HFD) and hepatic steatosis in rats and explored how fatty acid transport protein-4 (FATP4) and Toll-like receptor-4 antibodies (TLR4) might be contributing factors to obesity and related hepatic steatosis. Thirty male albino rats were divided into five groups: group 1 was fed a normal-fat diet, group 2 was fed an HFD, group 3 was fed an HFD and given vitamin D supplementation, group 4 was fed an HFD and kept on exercise, and group 5 was fed an HFD, given vitamin D, and kept on exercise. The serum lipid profile adipokines, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were analyzed, and the pathological changes in adipose and liver tissues were examined. In addition, the messenger-ribonucleic acid (mRNA) expression of FATP4 and immunohistochemical expression of TLR4 in adipose and liver tissues were evaluated. Vitamin D supplementation and exercise improved HFD-induced weight gain and attenuated hepatic steatosis, along with improving the serum lipid profile, degree of inflammation, and serum adipokine levels. The expression of FATP4 and TLR4 in both adipose tissue and the liver was downregulated; it was noteworthy that the group that received vitamin D and was kept on exercise showed also improvement in the histopathological picture of this group. According to the findings of this research, the protective effect of vitamin D and exercise against obesity and HFD-induced hepatic steatosis is associated with the downregulation of FATP4 and TLR4, as well as a reduction in inflammation.

Herbal medications and natural products for patients with covid-19 and diabetes mellitus: Potentials and challenges.

Background: The presence of diabetes mellitus (DM) among COVID-19 patients is associated with increased hospitalization, morbidity, and mortality. Evidence has shown that hyperglycemia potentiates SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection and plays a central role in severe COVID-19 and diabetes comorbidity. In this review, we explore the therapeutic potentials of herbal medications and natural products in the management of COVID-19 and DM comorbidity and the challenges associated with the preexisting or concurrent use of these substances. Methods: Research papers that were published from January 2016 to December 2021 were retrieved from PubMed, ScienceDirect, and Google Scholar databases. Papers reporting clinical evidence of antidiabetic activities and any available evidence of the anti-COVID-19 potential of ten selected natural products were retrieved and analyzed for discussion in this review. Results: A total of 548 papers (73 clinical trials on the antidiabetic activities of the selected natural products and 475 research and review articles on their anti-COVID-19 potential) were retrieved from the literature search for further analysis. A total of 517 articles (reviews and less relevant research papers) were excluded. A cumulative sum of thirty-one (31) research papers (20 clinical trials and 10 others) met the criteria and have been discussed in this review. Conclusion: The findings of this review suggest that phenolic compounds are the most promising phytochemicals in the management of COVID-19 and DM comorbidity. Curcumin and propolis have shown substantial evidence against COVID-19 and DM in humans and are thus, considered the best potential therapeutic options.

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

The role of bioactives in energy metabolism and metabolic syndrome.

Some food bioactives potentially exert anti-obesity effects. Anthocyanins (ACN), catechins, ß-glucan (BG) and n-3 long chain PUFA (LCPUFA) are among the most promising candidates and have been considered as a strategy for the development of functional foods counteracting body weight gain. At present, clinical trials, reviews and meta-analyses addressing anti-obesity effects of various bioactives or bioactive-rich foods show contradictory results. Abdominal obesity is an important criterion for metabolic syndrome (MetS) diagnosis along with glucose intolerance, dyslipidaemia and hypertension. Food bioactives are supposed to exert beneficial effects on these parameters, therefore representing alternative therapy approaches for the treatment of MetS. This review summarises outcomes on MetS biomarkers in recent clinical trials supplementing ACN, catechins, BG and n-3 LCPUFA, focusing mainly on anti-obesity effects. Overall, it is clear that the level of evidence for the effectiveness varies not only among the different bioactives but also among the different putative health benefits suggested for the same bioactive. Limited evidence may be due to the low number of controlled intervention trials or to inconsistencies in trial design, i.e. duration, dose and/or the method of bioactive supplementation (extracts, supplements, rich or enriched food). At present, the question 'Are bioactives effective in weight management and prevention of metabolic syndrome?' remains inconclusive. Thus, a common effort to harmonise the study design of intervention trials focusing on the most promising bioactive molecules is urgently needed to strengthen the evidence of their potential in the treatment of obesity, MetS and related diseases.

Seafood intake and the development of obesity, insulin resistance and type 2 diabetes.

We provide an overview of studies on seafood intake in relation to obesity, insulin resistance and type 2 diabetes. Overweight and obesity development is for most individuals the result of years of positive energy balance. Evidence from intervention trials and animal studies suggests that frequent intake of lean seafood, as compared with intake of terrestrial meats, reduces energy intake by 4-9 %, sufficient to prevent a positive energy balance and obesity. At equal energy intake, lean seafood reduces fasting and postprandial risk markers of insulin resistance, and improves insulin sensitivity in insulin-resistant adults. Energy restriction combined with intake of lean and fatty seafood seems to increase weight loss. Marine n-3 PUFA are probably of importance through n-3 PUFA-derived lipid mediators such as endocannabinoids and oxylipins, but other constituents of seafood such as the fish protein per se, trace elements or vitamins also seem to play a largely neglected role. A high intake of fatty seafood increases circulating levels of the insulin-sensitising hormone adiponectin. As compared with a high meat intake, high intake of seafood has been reported to reduce plasma levels of the hepatic acute-phase protein C-reactive protein level in some, but not all studies. More studies are needed to confirm the dietary effects on energy intake, obesity and insulin resistance. Future studies should be designed to elucidate the potential contribution of trace elements, vitamins and undesirables present in seafood, and we argue that stratification into responders and non-responders in randomised controlled trials may improve the understanding of health effects from intake of seafood.

Dietary fat composition: replacement of saturated fatty acids with PUFA as a public health strategy, with an emphasis on α-linolenic acid.

SFA intakes have decreased in recent years, both in Ireland and across other European countries; however a large proportion of the population are still not meeting the SFA recommendation of <10% of total energy (TE). High SFA intakes have been associated with increased CVD and type-2 diabetes (T2D) risk, due to alterations in cholesterol homoeostasis and adipose tissue inflammation. PUFA, in particular EPA and DHA, have been associated with health benefits, including anti-inflammatory effects. It is well established that dietary fat composition plays an important role in biological processes. A recent review of evidence suggests that replacement of SFA with PUFA has potential to reduce risk of CVD and T2D. The public health and molecular impact of EPA and DHA have been well-characterised, while less is known of effects of α-linolenic acid (ALA). The current dietary guideline for ALA is 0·5% TE; however evidence from supplementation trials suggests that benefit is observed at levels greater than 2 g/d (0·6-1% TE). This review highlights the gap in the evidence base relating to effects of the replacement of SFA with ALA, identifying the need for randomised controlled trials to determine the optimal dose of ALA substitution to define the efficacy of dietary fat modification with ALA.

The controversial role of vitamin D as an antioxidant: results from randomised controlled trials.

Increased oxidative stress has been implicated as a potential causal factor in the development of several diseases. In the last decade, an extensive literature has been produced on vitamin D, not limited to its well-known function like a steroid hormone on skeletal tissue, but for its potential pleiotropic role in human health. Several researchers have suggested relationships between vitamin D intake and health outcomes such as cancer prevention and increased immunity, or possible role in preventing diabetes, and in inflammation. Little is known about its antioxidant effect. The aim of the present review was to explore major evidence regarding the potential scavenger capacity of vitamin D in high-evidence human studies. Studies considered by the present review suggest that the potential role of vitamin D as an antioxidant could not be confirmed. Current literature showed controversial effects about the ability of cholecalciferol to prevent or ameliorate oxidative stress biomarkers, and there is need of further and high-quality studies testing the antioxidant effect of vitamin D supplementation.

Vitamin D in the Middle East and North Africa.

PURPOSE: The Middle East and North Africa (MENA) region registers some of the lowest serum 25­hydroxyvitamin D [25(OH)D] concentrations, worldwide. We describe the prevalence and the risk factors for hypovitaminosis D, completed and ongoing clinical trials, and available guidelines for vitamin D supplementation in this region. METHODS: This review is an update of previous reviews published by our group in 2013 for observational studies, and in 2015 for randomized controlled trials (RCTs) from the region. We conducted a comprehensive search in Medline, PubMed, and Embase, and the Cochrane Library, using MeSH terms and keywords relevant to vitamin D, vitamin D deficiency, and the MENA region, for the period 2012-2017 for observational studies, and 2015-2017 for RCTs. We included large cross-sectional studies with at least 100 subjects/study, and RCTs with at least 50 participants per arm. RESULTS: We identified 41 observational studies. The prevalence of hypovitaminosis D, defined as a 25­hydroxyvitamin D [25(OH)D] level below the desirable level of 20 ng/ml, ranged between 12-96% in children and adolescents, and 54-90% in pregnant women. In adults, it ranged between 44 and 96%, and the mean 25(OH)D varied between 11 and 20 ng/ml. In general, significant predictors of low 25(OH)D levels were female gender, increasing age and body mass index, veiling, winter season, use of sun screens, lower socioeconomic status, and higher latitude.We retrieved 14 RCTs comparing supplementation to control or placebo, published during the period 2015-2017: 2 in children, 8 in adults, and 4 in pregnant women. In children and adolescents, a vitamin D dose of 1000-2000 IU/d was needed to maintain serum 25(OH)D level at target. In adults and pregnant women, the increment in 25(OH)D level was inversely proportional to the dose, ranging between 0.9 and 3 ng/ml per 100 IU/d for doses ≤2000 IU/d, and between 0.1 and 0.6 ng/ml per 100 IU/d for doses ≥3000 IU/d. While the effect of vitamin D supplementation on glycemic indices is still controversial in adults, vitamin D supplementation may be protective against gestational diabetes mellitus in pregnant women. In the only identified study in the elderly, there was no significant difference between 600 IU/day and 3750 IU/day doses on bone mineral density. We did not identify any fracture studies.The available vitamin D guidelines in the region are based on expert opinion, with recommended doses between 400 and 2000 IU/d, depending on the age category, and country. CONCLUSION: Hypovitaminosis D is prevalent in the MENA region, and doses of 1000-2000 IU/d may be necessary to reach a desirable 25(OH)D level of 20 ng/ml. Studies assessing the effect of such doses of vitamin D on major outcomes, and confirming their long term safety, are needed.

Postprandial glycaemic and lipaemic responses to chronic coffee consumption may be modulated by CYP1A2 polymorphisms.

There is much epidemiological evidence suggesting a reduced risk of development of type 2 diabetes (T2D) in habitual coffee drinkers, however to date there have been few longer-term interventions, directly examining the effects of coffee intake on glucose and lipid metabolism. Previous studies may be confounded by inter-individual variation in caffeine metabolism. Specifically, the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with carriers of the C allele considered to be of a 'slow' metaboliser phenotype. This study investigated the effects of regular coffee intake on markers of glucose and lipid metabolism in coffee-naïve individuals, with novel analysis by rs762551 genotype. Participants were randomised to either a coffee group (n 19) who consumed four cups/d instant coffee for 12 weeks or a control group (n 8) who remained coffee/caffeine free. Venous blood samples were taken pre- and post-intervention. Primary analysis revealed no significant differences between groups. Analysis of the coffee group by genotype revealed several differences. Before coffee intake, the AC genotype ('slow' caffeine metabolisers, n 9) displayed higher baseline glucose and NEFA than the AA genotype ('fast' caffeine metabolisers, n 10, P<0·05). Post-intervention, reduced postprandial glycaemia and reduced NEFA suppression were observed in the AC genotype, with the opposite result observed in the AA genotype (P<0·05). These observed differences between genotypes warrant further investigation and indicate there may be no one-size-fits-all recommendation with regard to coffee drinking and T2D risk.

A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study.

It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38-0·87, P for trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43-0·95, P for trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.

A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (P<0·05) of genes coding for v-Akt murine thymoma viral oncogene homolog 2, resistin and v-Raf-1 murine leukaemia viral oncogene homolog 1 (Raf1) in offspring skeletal muscle and acetyl-CoA carboxylase (Acaca), fatty acid synthase and phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit ß in offspring liver. Skeletal muscle neuropeptide Y and hepatic Kruppel-like factor 10 were up-regulated in HFS v. CON offspring (P<0·05). Compared with CON, Acaca and Raf1 protein expression levels were significantly lower in HFS offspring. Maternal HFS induced higher homoeostasis model of assessment index of insulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

High intake of fatty fish, but not of lean fish, improved postprandial glucose regulation and increased the n-3 PUFA content in the leucocyte membrane in healthy overweight adults: a randomised trial.

The prevalence of type 2 diabetes (T2D) is low in populations with a high fish intake; however prospective studies with fish intake have shown positive, negative or no association between fish intake and the risk for T2D. The aim of this study was to investigate the effects of high intake of lean or fatty fish on glucose tolerance, leucocyte membrane fatty acid composition and leucocyte function in overweight/obese adults. In this randomised clinical trial, sixty-eight healthy overweight/obese participants consumed 750 g/week of either lean or fatty fish as dinners, or were instructed to continue their normal eating habits but to avoid fish intake (control group), for 8 weeks. Energy and macronutrient intake and physical activity were not changed within the groups during the study period. High intake of fatty fish, but not of lean fish, significantly improved glucose regulation 120 min postprandially (P=0·012), but did not affect fasting glucose concentration. A smaller increase in fasting to 120 min postprandial insulin C-peptide concentration was seen after fatty fish intake (P=0·012). Lean fish increased the DHA content in leucocyte membranes (P=0·010), and fatty fish increased the total content of n-3 PUFA (P=0·00016) and reduced the content of n-6 PUFA (P=0·00057) in leucocyte membranes. Lean and fatty fish intake did not affect phagocytosis of bacteria ex vivo. The findings suggest that high intake of fatty fish, but not of lean fish, beneficially affected postprandial glucose regulation in overweight/obese adults, and may therefore prevent or delay the development of T2D in this population.

Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling.

The hypothalamic arcuate nucleus (ARC) is a major integration center for energy and glucose homeostasis that responds to leptin. Resistance to leptin in the ARC is an important component of the development of obesity and type 2 diabetes. Recently, we showed that Endospanin1 (Endo1) is a negative regulator of the leptin receptor (OBR) that interacts with OBR and retains the receptor inside the cell, leading to a decreased activation of the anorectic STAT3 pathway. Endo1 is up-regulated in the ARC of high fat diet (HFD)-fed mice, and its silencing in the ARC of lean and obese mice prevents and reverses the development of obesity. OBJECTIVE: Herein we investigated whether decreased Endo1 expression in the hypothalamic ARC, associated with reduced obesity, could also ameliorate glucose homeostasis accordingly. METHODS: We studied glucose homeostasis in lean or obese mice silenced for Endo1 in the ARC via stereotactic injection of shRNA-expressing lentiviral vectors. RESULTS: We observed that despite being leaner, Endo1-silenced mice showed impaired glucose homeostasis on HFD. Mechanistically, we show that Endo1 interacts with p85, the regulatory subunit of PI3K, and mediates leptin-induced PI3K activation. CONCLUSIONS: Our results thus define Endo1 as an important hypothalamic integrator of leptin signaling, and its silencing differentially regulates the OBR-dependent functions.

Host-microbiome interactions in human type 2 diabetes following prebiotic fibre (galacto-oligosaccharide) intake.

Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia, which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test. Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r -0·90, P=0·042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding. We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.

Nutritional management of hyperapoB.

Plasma apoB is a more accurate marker of the risk of CVD and type 2 diabetes (T2D) than LDL-cholesterol; however, nutritional reviews targeting apoB are scarce. Here we reviewed eighty-seven nutritional studies and present conclusions in order of strength of evidence. Plasma apoB was reduced in all studies that induced weight loss of 6-12 % using hypoenergetic diets (seven studies; 5440-7110 kJ/d; 1300-1700 kcal/d; 34-50 % carbohydrates; 27-39 % fat; 18-24 % protein). When macronutrients were compared in isoenergetic diets (eleven studies including eight randomised controlled trials (RCT); n 1189), the diets that reduced plasma apoB were composed of 26-51 % carbohydrates, 26-46 % fat, 11-32 % protein, 10-27 % MUFA, 5-14 % PUFA and 7-13 % SFA. Replacement of carbohydrate by MUFA, not SFA, decreased plasma apoB. Moreover, dietary enriching with n-3 fatty acids (FA) (from fish: 1·1-1·7 g/d or supplementation: 3·2-3·4 g/d EPA/DHA or 4 g/d EPA), psyllium (about 8-20 g/d), phytosterols (about 2-4 g/d) or nuts (30-75 g/d) also decreased plasma apoB, mostly in hyperlipidaemic subjects. While high intake of trans-FA (4·3-9·1 %) increased plasma apoB, it is unlikely that these amounts represent usual consumption. Inconsistent data existed on the effect of soya proteins (25-30 g/d), while the positive association of alcohol consumption with low plasma apoB was reported in cross-sectional studies only. Five isoenergetic studies using Mediterranean diets (including two RCT; 823 subjects) reported a decrease of plasma apoB, while weaker evidence existed for Dietary Approaches to Stop Hypertension (DASH), vegetarian, Nordic and Palaeolithic diets. We recommend using a Mediterranean dietary pattern, which also encompasses the dietary components reported to reduce plasma apoB, to target hyperapoB and reduce the risks of CVD and T2D.

Reversibility of endothelial dysfunction in diabetes: role of polyphenols.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

Berries and anthocyanins: promising functional food ingredients with postprandial glycaemia-lowering effects.

The prevalence of type 2 diabetes (T2D) is predicted to reach unprecedented levels in the next few decades. In addition to excess body weight, there may be other overlapping dietary drivers of impaired glucose homeostasis that are associated with an obesogenic diet, such as regular exposure to postprandial spikes in blood glucose arising from diets dominated by highly refined starches and added sugars. Strategies to reduce postprandial hyperglycaemia by optimising the functionality of foods would strengthen efforts to reduce the risk of T2D. Berry bioactives, including anthocyanins, are recognised for their inhibitory effects on carbohydrate digestion and glucose absorption. Regular consumption of berries has been associated with a reduction in the risk of T2D. This review aims to examine the evidence from in vitro, animal and human studies, showing that berries and berry anthocyanins may act in the gut to modulate postprandial glycaemia. Specifically, berry extracts and anthocyanins inhibit the activities of pancreatic α-amylase and α-glucosidase in the gut lumen, and interact with intestinal sugar transporters, sodium-dependent glucose transporter 1 and GLUT2, to reduce the rate of glucose uptake into the circulation. Growing evidence from randomised controlled trials suggests that berry extracts, purées and nectars acutely inhibit postprandial glycaemia and insulinaemia following oral carbohydrate loads. Evidence to date presents a sound basis for exploring the potential for using berries/berry extracts as an additional stratagem to weight loss, adherence to dietary guidelines and increasing physical exercise, for the prevention of T2D.

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood.

Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people.

The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46·3 % female; 76·7 (sd 5·9) years) and 466 non-diabetic (57·9 % female; 77·8 (sd 7·1) years) individuals were included in the analysis. In overweight/obese (BMI≥27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1·0 (reference), 0·82 (95 % CI 0·31, 2·18), 0·56 (95 % CI 0·21, 1·52) and 0·22 (95 % CI 0·06, 0·82) (P trend=0·015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences.