Diet-induced Weight Loss and Phenotypic Flexibility Among Healthy Overweight Adults: A Randomized Trial.

BACKGROUND: The capacity of an individual to respond to changes in food intake so that postprandial metabolic perturbations are resolved, and metabolism returns to its pre-prandial state, is called phenotypic flexibility. This ability may be a more important indicator of current health status than metabolic markers in a fasting state. AIM: In this parallel randomized controlled trial study, an energy-restricted healthy diet and 2 dietary challenges were used to assess the effect of weight loss on phenotypic flexibility. METHODS: Seventy-two volunteers with overweight and obesity underwent a 12-wk dietary intervention. The participants were randomized to a weight loss group (WLG) with 20% less energy intake or a weight-maintenance group (WMG). At weeks 1 and 12, participants were assessed for body composition by MRI. Concurrently, markers of metabolism and insulin sensitivity were obtained from the analysis of plasma metabolome during 2 different dietary challenges-an oral glucose tolerance test (OGTT) and a mixed-meal tolerance test. RESULTS: Intended weight loss was achieved in the WLG (-5.6 kg, P < 0.0001) and induced a significant reduction in total and regional adipose tissue as well as ectopic fat in the liver. Amino acid-based markers of insulin action and resistance such as leucine and glutamate were reduced in the postprandial phase of the OGTT in the WLG by 11.5% and 28%, respectively, after body weight reduction. Weight loss correlated with the magnitude of changes in metabolic responses to dietary challenges. Large interindividual variation in metabolic responses to weight loss was observed. CONCLUSION: Application of dietary challenges increased sensitivity to detect metabolic response to weight loss intervention. Large interindividual variation was observed across a wide range of measurements allowing the identification of distinct responses to the weight loss intervention and mechanistic insight into the metabolic response to weight loss.

Plasma Metabolic Signatures of Healthy Overweight Subjects Challenged With an Oral Glucose Tolerance Test.

Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as "at risk" for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values at the end of the test (at 240 min), except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT.

Effects of a 13-Week Personalized Lifestyle Intervention Based on the Diabetes Subtype for People with Newly Diagnosed Type 2 Diabetes.

A type 2 diabetes mellitus (T2DM) subtyping method that determines the T2DM phenotype based on an extended oral glucose tolerance test is proposed. It assigns participants to one of seven subtypes according to their ß-cell function and the presence of hepatic and/or muscle insulin resistance. The effectiveness of this subtyping approach and subsequent personalized lifestyle treatment in ameliorating T2DM was assessed in a primary care setting. Sixty participants, newly diagnosed with (pre)diabetes type 2 and not taking diabetes medication, completed the intervention. Retrospectively collected data of 60 people with T2DM from usual care were used as controls. Bodyweight (p < 0.01) and HbA1c (p < 0.01) were significantly reduced after 13 weeks in the intervention group, but not in the usual care group. The intervention group achieved 75.0% diabetes remission after 13 weeks (fasting glucose ≤ 6.9 mmol/L and HbA1c < 6.5% (48 mmol/mol)); for the usual care group, this was 22.0%. Lasting (two years) remission was especially achieved in subgroups with isolated hepatic insulin resistance. Our study shows that a personalized diagnosis and lifestyle intervention for T2DM in a primary care setting may be more effective in improving T2DM-related parameters than usual care, with long-term effects seen especially in subgroups with hepatic insulin resistance.

An altered microbiota pattern precedes Type 2 diabetes mellitus development: From the CORDIOPREV study.

Introduction: A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). Objectives: We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. Methods: All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. Results: A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. Conclusion: These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease.

The Effect of a Lifestyle Intervention on Type 2 Diabetes Pathophysiology and Remission: The Stevenshof Pilot Study.

Although lifestyle interventions can lead to diabetes remission, it is unclear to what extent type 2 diabetes (T2D) remission alters or improves the underlying pathophysiology of the disease. Here, we assess the effects of a lifestyle intervention on T2D reversal or remission and the effects on the underlying pathology. In a Dutch primary care setting, 15 adults with an average T2D duration of 13.4 years who were (pharmacologically) treated for T2D received a diabetes subtyping ("diabetyping") lifestyle intervention (DLI) for six months, aiming for T2D remission. T2D subtype was determined based on an OGTT. Insulin and sulphonylurea (SU) derivative treatment could be terminated for all participants. Body weight, waist/hip ratio, triglyceride levels, HbA1c, fasting, and 2h glucose were significantly improved after three and six months of intervention. Remission and reversal were achieved in two and three participants, respectively. Indices of insulin resistance and beta cell capacity improved, but never reached healthy values, resulting in unchanged T2D subtypes. Our study implies that achieving diabetes remission in individuals with a longer T2D duration is possible, but underlying pathology is only minimally affected, possibly due to an impaired beta cell function. Thus, even when T2D remission is achieved, patients need to continue adhering to lifestyle therapy.

Current and Future Nutritional Strategies to Modulate Inflammatory Dynamics in Metabolic Disorders.

Obesity, type 2 diabetes, and other metabolic disorders have a large impact on global health, especially in Western countries. An important hallmark of metabolic disorders is chronic low-grade inflammation. A key player in chronic low-grade inflammation is dysmetabolism, which is defined as the inability to keep homeostasis resulting in loss of lipid control, oxidative stress, inflammation, and insulin resistance. Although often not yet detectable in the circulation, chronic low-grade inflammation can be present in one or multiple organs. The response to a metabolic challenge containing lipids may magnify dysfunctionalities at the tissue level, causing an overflow of inflammatory markers into the circulation and hence allow detection of early low-grade inflammation. Here, we summarize the evidence of successful application of metabolic challenge tests in type 2 diabetes, metabolic syndrome, obesity, and unhealthy aging. We also review how metabolic challenge tests have been successfully applied to evaluate nutritional intervention effects, including an "anti-inflammatory" mixture, dark chocolate, whole grain wheat and overfeeding. Additionally, we elaborate on future strategies to (re)gain inflammatory flexibility. Through epigenetic and metabolic regulation, the inflammatory response may be trained by regular mild and metabolic triggers, which can be understood from the perspective of trained immunity, hormesis and pro-resolution. New strategies to optimize dynamics of inflammation may become available.

Postprandial endotoxemia may influence the development of type 2 diabetes mellitus: From the CORDIOPREV study.

BACKGROUND & AIMS: Insulin resistance (IR) and impaired beta-cell function are key determinants of type 2 diabetes mellitus (T2DM). Intestinal absorption of bacterial components activates the toll-like receptors inducing inflammation, and this in turn IR. We evaluated the role of endotoxemia in promoting inflammation-induced insulin resistance (IR) in the development of T2DM, and its usefulness as predictive biomarker. METHODS: We included in this study 462 patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months (Incident-DIAB group), whereas 355 patients did not developed it during this period of time (Non-DIAB group). RESULTS: We observed a postprandial increase in lipopolysaccharides (LPS) levels in the Incident-DIAB at baseline (P < 0.001), whereas LPS levels were not modified in the Non-DIAB. Disease-free survival curves based on the LPS postprandial fold change improved T2DM Risk Assessment as compared with the previously described FINDRISC score (hazard ratio of 2.076, 95% CI 1.149-3.750 vs. 1.384, 95% CI 0.740-2.589). Moreover, disease-free survival curves combining the LPS postprandial fold change and FINDRISC score together showed a hazard ratio of 3.835 (95% CI 1.323-11.114), linked to high values of both parameters. CONCLUSION: Our results suggest that a high postprandial endotoxemia precedes the development of T2DM. Our results also showed the potential use of LPS plasma levels as a biomarker predictor of T2DM development. CLINICAL TRIALS.GOV. IDENTIFIER: NCT00924937.

Environmental Forces that Shape Early Development: What We Know and Still Need to Know.

Understanding health requires more than knowledge of the genome. Environmental factors regulate gene function through epigenetics. Collectively, environmental exposures have been called the "exposome." Caregivers are instrumental in shaping exposures in a child's initial years. Maternal dietary patterns, physical activity, degree of weight gain, and body composition while pregnant will influence not only fetal growth, but also the infant's metabolic response to nutrients and energy. Maternal over- or underweight, excess caloric intake, nutrient imbalances, glucose dysregulation, and presence of chronic inflammatory states have been shown to establish risk for many later chronic diseases. During the period from birth to age 3 y, when the infant's metabolic rate is high and synaptogenesis and myelination of the brain are occurring extremely rapidly, the infant is especially prone to damaging effects from nutrient imbalances. During this period, the infant changes from a purely milk-based diet to one including a wide variety of foods. The process, timing, quality, and ultimate dietary pattern acquired are a direct outcome of the caregiver-infant feeding relationship, with potentially lifelong consequences. More research on how meal time interactions shape food acceptance is needed to avoid eating patterns that augment existing disease risk. Traditional clinical trials in nutrition, meant to isolate single factors for study, are inadequate to study the highly interconnected realm of environment-gene interactions in early life. Novel technologies are being used to gather broad exposure data on disparate populations, employing pioneering statistical approaches and correlations applied specifically to the individual, based on their genetic make-up and unique environmental experiences.

Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements.

Health has been defined as the capability of the organism to adapt to challenges. In this study, we tested to what extent comprehensively phenotyped individuals reveal differences in metabolic responses to a standardized mixed meal tolerance test (MMTT) and how these responses change when individuals experience moderate weight loss. Metabolome analysis was used in 70 healthy individuals. with profiling of ∼300 plasma metabolites during an MMTT over 8 h. Multivariate analysis of plasma markers of fatty acid catabolism identified 2 distinct metabotype clusters (A and B). Individuals from metabotype B showed slower glucose clearance, had increased intra-abdominal adipose tissue mass and higher hepatic lipid levels when compared with individuals from metabotype A. An NMR-based urine analysis revealed that these individuals also to have a less healthy dietary pattern. After a weight loss of ∼5.6 kg over 12 wk, only the subjects from metabotype B showed positive changes in the glycemic response during the MMTT and in markers of metabolic diseases. Our study in healthy individuals demonstrates that more comprehensive phenotyping can reveal discrete metabotypes with different outcomes in a dietary intervention and that markers of lipid catabolism in plasma could allow early detection of the metabolic syndrome.-Fiamoncini, J., Rundle, M., Gibbons, H., Thomas, E. L., Geillinger-Kästle, K., Bunzel, D., Trezzi, J.-P., Kiselova-Kaneva, Y., Wopereis, S., Wahrheit, J., Kulling, S. E., Hiller, K., Sonntag, D., Ivanova, D., van Ommen, B., Frost, G., Brennan, L., Bell, J. Daniel, H. Plasma metabolome analysis identifies distinct human metabotypes in the postprandial state with different susceptibility to weight loss-mediated metabolic improvements.

Associations of vitamin D status with dietary intakes and physical activity levels among adults from seven European countries: the Food4Me study.

PURPOSE: To report the vitamin D status in adults from seven European countries and to identify behavioural correlates. METHODS: In total, 1075 eligible adult men and women from Ireland, Netherlands, Spain, Greece, UK, Poland and Germany, were included in the study. RESULTS: Vitamin D deficiency and insufficiency, defined as 25-hydroxy vitamin D3 (25-OHD3) concentration of <30 and 30-49.9 nmol/L, respectively, were observed in 3.3 and 30.6% of the participants. The highest prevalence of vitamin D deficiency was found in the UK and the lowest in the Netherlands (8.2 vs. 1.1%, P < 0.05). In addition, the prevalence of vitamin D insufficiency was higher in females compared with males (36.6 vs. 22.6%, P < 0.001), in winter compared with summer months (39.3 vs. 25.0%, P < 0.05) and in younger compared with older participants (36.0 vs. 24.4%, P < 0.05). Positive dose-response associations were also observed between 25-OHD3 concentrations and dietary vitamin D intake from foods and supplements, as well as with physical activity (PA) levels. Vitamin D intakes of ≥5 µg/day from foods and ≥5 µg/day from supplements, as well as engagement in ≥30 min/day of moderate- and vigorous-intensity PA were associated with higher odds (P < 0.05) for maintaining sufficient (≥50 nmol/L) 25-OHD3 concentrations. CONCLUSIONS: The prevalence of vitamin D deficiency varied considerably among European adults. Dietary intakes of ≥10 µg/day of vitamin D from foods and/or supplements and at least 30 min/day of moderate- and vigorous-intensity PA were the minimum thresholds associated with vitamin D sufficiency.

A plasma circulating miRNAs profile predicts type 2 diabetes mellitus and prediabetes: from the CORDIOPREV study.

We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p (HRT3-T1 = 4.218 and HRT3-T1 = 2.527, respectively) and low levels (T1) of miR-15a and miR-375 (HRT1-T3 = 3.269 and HRT1-T3 = 1.604, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice.

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art 'evidence-based nutrition'. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether 'actionable'. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases.

HDL cholesterol efflux normalised to apoA-I is associated with future development of type 2 diabetes: from the CORDIOPREV trial.

This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes (T2DM) in cardiovascular patients. We measured cholesterol efflux in all CORDIOPREV study (NCT00924937) participants free of T2DM at baseline (n = 462) and assessed its relationship with T2DM incidence during a 4.5 years of follow-up. Cholesterol efflux was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma. Disposition index was estimated as beta-cell function indicator. During follow-up 106 individuals progressed to T2DM. The cholesterol efflux/apoA-1 ratio was inversely associated with T2DM development independently of traditional risk factors (model-1, OR: 0.647, 95%CI: 0.495-0.846), and after additional adjustment for glycaemic parameters (model-2, OR: 0.670, 95%CI: 0.511-0.878). When cumulative incidence of diabetes was analysed by quartiles of cholesterol efflux/apoA-I, incidence of T2DM was reduced by 54% in subjects who were in the higher cholesterol efflux/apoA-I quartile compared to subjects in the lowest quartile (p = 0.018 and p = 0.042 for model-1 and 2). Moreover, participants who were in the higher cholesterol efflux/apoA-I presented significantly higher disposition index (ß = 0.056, SE = 0.026; p = 0.035). In conclusion, HDL-cholesterol efflux normalised to apoA-I was inversely associated with T2DM development in cardiovascular patients. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function.

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study.

Mediterranean Diet (MedDiet) adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS) was derived from risk alleles and a Mediterranean Diet Score (MDS), based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI), waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers.

Systems biology of personalized nutrition.

Personalized nutrition is fast becoming a reality due to a number of technological, scientific, and societal developments that complement and extend current public health nutrition recommendations. Personalized nutrition tailors dietary recommendations to specific biological requirements on the basis of a person's health status and goals. The biology underpinning these recommendations is complex, and thus any recommendations must account for multiple biological processes and subprocesses occurring in various tissues and must be formed with an appreciation for how these processes interact with dietary nutrients and environmental factors. Therefore, a systems biology-based approach that considers the most relevant interacting biological mechanisms is necessary to formulate the best recommendations to help people meet their wellness goals. Here, the concept of "systems flexibility" is introduced to personalized nutrition biology. Systems flexibility allows the real-time evaluation of metabolism and other processes that maintain homeostasis following an environmental challenge, thereby enabling the formulation of personalized recommendations. Examples in the area of macro- and micronutrients are reviewed. Genetic variations and performance goals are integrated into this systems approach to provide a strategy for a balanced evaluation and an introduction to personalized nutrition. Finally, modeling approaches that combine personalized diagnosis and nutritional intervention into practice are reviewed.

Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge.

BACKGROUND: A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes. Currently, applied challenge tests are largely non-standardized. A systematic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). This study aimed to prove that PFT modulates all relevant processes governing metabolic health thereby allowing to distinguish subjects with different metabolic health status. Therefore, 20 healthy and 20 type 2 diabetic (T2D) male subjects were challenged both by PFT and oral glucose tolerance test (OGTT). During the 8-h response time course, 132 parameters were quantified that report on 26 metabolic processes distributed over 7 organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress. RESULTS: In healthy subjects, 110 of the 132 parameters showed a time course response. Patients with T2D showed 18 parameters to be significantly different after overnight fasting compared to healthy subjects, while 58 parameters were different in the post-challenge time course after the PFT. This demonstrates the added value of PFT in distinguishing subjects with different health status. The OGTT and PFT response was highly comparable for glucose metabolism as identical amounts of glucose were present in both challenge tests. Yet the PFT reports on additional processes, including vasculature, systemic stress, and metabolic flexibility. CONCLUSION: The PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Studying both healthy subjects and subjects with impaired metabolic health showed that the PFT revealed new processes laying underneath health. This study provides the first evidence towards adopting the PFT as gold standard in nutrition research.

Determinants of postprandial plasma bile acid kinetics in human volunteers.

Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women (n = 72, 62 ± 8 yr, mean ± SE) were enrolled into a 12-wk weight loss intervention. All subjects underwent an oral glucose tolerance test and a mixed-meal tolerance test before and after the intervention. BA were quantified in plasma by liquid chromatography-tandem mass spectrometry combined with whole genome exome sequencing and fecal microbiota profiling. Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma BA profiles. Fasting and postprandial BA profiles revealed high interindividual variability, and three main patterns in postprandial BA response were identified using multivariate analysis. Although the women enrolled were postmenopausal, effects of sex difference in BA response were evident. Exome data revealed the contribution of preselected genes to the observed interindividual variability. In particular, a variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases. Fecal microbiota analysis did not reveal evidence for a significant influence of bacterial diversity and/or composition on plasma BA profiles. The analysis of plasma BA profiles in response to two different dietary challenges revealed a high interindividual variability, which was mainly determined by genetics and sex difference of host with minimal effects of the microbiota.NEW & NOTEWORTHY Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma bile acid (BA) profiles. Despite high interindividual variability, three main patterns in postprandial BA response were identified using multivariate analysis. A variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases in response to both the oral glucose tolerance test and the mixed-meal tolerance test.

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.

The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility.

BACKGROUND: Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the response of relevant phenotypic processes. In this study, we assessed the correlation of three fat-soluble vitamins, (i.e., vitamin A or retinol, vitamin D3, two homologues of vitamin E) and four carotenoids (i.e., α-carotene, ß-carotene, ß-cryptoxanthin, and lycopene), with characteristics of metabolic and inflammatory parameters at baseline and in response to a nutritional challenge test (NCT) in a group of 36 overweight and obese male subjects, using proteomics and metabolomics platforms. The phenotypic flexibility concept implies that health can be measured by the ability to adapt to a NCT, which may offer a more sensitive way to assess changes in health status of healthy subjects. RESULTS: Correlation analyses of results after overnight fasting revealed a rather evenly distributed network in a number of relatively strong correlations per micronutrient, with minor overlap between correlation profiles of each compound. Correlation analyses of challenge response profiles for metabolite and protein parameters with micronutrient status revealed a network that is more skewed towards α-carotene and γ-tocopherol suggesting a more prominent role for these micronutrients in the maintenance of phenotypic flexibility. Comparison of the networks revealed that there is merely overlap of two parameters (inositol and oleic acid (C18:1)) affirming that there is a specific biomarker response profile upon NCT. CONCLUSIONS: Our study shows that applying the challenge test concept is able to reveal previously unidentified correlations between specific micronutrients and health-related processes, with potential relevance for maintenance of health that were not observed by correlating homeostatic measurements. This approach will contribute to insights on the influence of micronutrients on health and help to create efficient micronutrient intervention programs.