Graded Replacement of Carbohydrate-Rich Breakfast Products with Dairy Products: Effects on Postprandial Aminoacidemia, Glycemic Control, Bone Metabolism, and Satiety.

BACKGROUND: Postprandial metabolic responses following dairy consumption have mostly been studied using stand-alone dairy products or milk-derived nutrients. OBJECTIVE: Assessing the impact of ingesting dairy products as part of a common breakfast on postprandial aminoacidemia, glycemic control, markers of bone metabolism, and satiety. METHODS: In this randomized, crossover study, 20 healthy young males and females consumed on 3 separate occasions an iso-energetic breakfast containing no dairy (NO-D), 1 dairy (ONE-D), or 2 dairy (TWO-D) products. Postprandial concentrations of amino acids, glucose, insulin, glucagon-like peptide-1 (GLP-1), calcium, parathyroid hormone (PTH), and markers of bone formation (P1NP) and resorption (CTX-I) were measured before and up to 300 min after initiating the breakfast, along with VAS-scales to assess satiety. RESULTS: Plasma essential and branched-chained amino acids availability (expressed as total area under the curve (tAUC)) increased in a dose-dependent manner (P<0.05 for all comparisons). Plasma glucose tAUCs were lower in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons). Plasma GLP-1 tAUC increased in a dose-dependent manner (P<0.05 for all comparisons), whereas no differences were observed in plasma insulin tAUC between conditions (P>0.05 for all comparisons). Serum calcium tAUCs were higher in ONE-D and TWO-D compared with NO-D (P<0.05 for both comparisons), along with lower PTH tAUCs in ONE-D and TWO-D compared with NO-D (P=0.001 for both comparisons). In accordance, serum CTX-I concentrations were lower in the late postprandial period in ONE-D and TWO-D compared with NO-D (P<0.01 for both comparisons). No differences were observed in P1NP tAUCs between conditions (P>0.05). The tAUC for satiety was higher in TWO-D compared with NO-D and ONE-D (P<0.05 for both comparisons). CONCLUSIONS: Iso-energetic replacement of a carbohydrate-rich breakfast component with one serving of dairy improves postprandial amino acid availability, glycemic control, and bone metabolism. Adding a second serving of dairy in lieu of carbohydrates augments postprandial amino acid and GLP-1 concentrations while further promoting satiety. This study was registered at https://doi.org/10.1186/ISRCTN13531586 with Clinical Trial Registry number ISRCTN13531586.

Analysis of high-dimensional metabolomics data with complex temporal dynamics using RM-ASCA.

The intricate dependency structure of biological "omics" data, particularly those originating from longitudinal intervention studies with frequently sampled repeated measurements renders the analysis of such data challenging. The high-dimensionality, inter-relatedness of multiple outcomes, and heterogeneity in the studied systems all add to the difficulty in deriving meaningful information. In addition, the subtle differences in dynamics often deemed meaningful in nutritional intervention studies can be particularly challenging to quantify. In this work we demonstrate the use of quantitative longitudinal models within the repeated-measures ANOVA simultaneous component analysis+ (RM-ASCA+) framework to capture the dynamics in frequently sampled longitudinal data with multivariate outcomes. We illustrate the use of linear mixed models with polynomial and spline basis expansion of the time variable within RM-ASCA+ in order to quantify non-linear dynamics in a simulation study as well as in a metabolomics data set. We show that the proposed approach presents a convenient and interpretable way to systematically quantify and summarize multivariate outcomes in longitudinal studies while accounting for proper within subject dependency structures.

Nutritional content, protein quantity, protein quality and carbon footprint of plant-based drinks and semi-skimmed milk in the Netherlands and Europe.

OBJECTIVE: To compare the nutritional composition of bovine milk and several plant-based drinks with a focus on protein and essential amino acid content and to determine the ratio of essential amino acids to greenhouse gas emission. DESIGN: Nutritional information on the label was extracted for semi-skimmed milk, soy, oat, almond, coconut and rice drink from the Innova database between January 2017 and March 2020 for the Netherlands, Belgium, Germany, Spain, Italy, and Sweden. Protein and amino acids were measured and carbon footprint was calculated for a selection of Dutch products. Protein quality was determined by calculating the contribution to the WHO essential amino acids requirements. SETTING: The bovine milk and plant-based drinks market in Netherlands, Belgium, Germany, Spain, Italy, and Sweden. PARTICIPATING PRODUCTS: Semi-skimmed bovine milk and soy-, oat-, almond-, coconut- and rice drink. RESULTS: Nutritional label information was collected for 399 products. Milk naturally contains many micronutrients, e.g. vitamin B2, B12, and calcium. Approximately 50% of the regular plant-based drinks was fortified with calcium, whereas the organic plant-based drinks were mostly unfortified. Protein quantity and quality were highest in milk. Soy drink had the best protein quality to carbon footprint ratio and milk came second. CONCLUSIONS: The nutrition - climate change balance presented in this study, is in line with previous literature, which shows that semi-skimmed bovine milk and fortified soy drink deserve a place in a sustainable diet.

Dairy product consumption is associated with pre-diabetes and newly diagnosed type 2 diabetes in the Lifelines Cohort Study.

Previous studies show associations between dairy product consumption and type 2 diabetes, but only a few studies conducted detailed analyses for a variety of dairy subgroups. Therefore, we examined cross-sectional associations of a broad variety of dairy subgroups with pre-diabetes and newly diagnosed type 2 diabetes (ND-T2DM) among Dutch adults. In total, 112 086 adults without diabetes completed a semi-quantitative FFQ and donated blood. Pre-diabetes was defined as fasting plasma glucose (FPG) between 5·6 and 6·9 mmol/l or HbA1c% of 5·7-6·4 %. ND-T2DM was defined as FPG ≥7·0 mmol/l or HbA1c ≥6·5 %. Logistic regression analyses were conducted by 100 g or serving increase and dairy tertiles (T1ref), while adjusting for demographic, lifestyle and dietary covariates. Median dairy product intake was 324 (interquartile range 227) g/d; 25 549 (23 %) participants had pre-diabetes; and 1305 (1 %) had ND-T2DM. After full adjustment, inverse associations were observed of skimmed dairy (OR100 g 0·98; 95 % CI 0·97, 1·00), fermented dairy (OR100 g 0·98; 95 % CI 0·97, 0·99) and buttermilk (OR150 g 0·97; 95 % CI 0·94, 1·00) with pre-diabetes. Positive associations were observed for full-fat dairy (OR100 g 1·003; 95 % CI 1·01, 1·06), non-fermented dairy products (OR100 g 1·01; 95 % CI 1·00, 1·02) and custard (ORserving/150 g 1·13; 95 % CI 1·03, 1·24) with pre-diabetes. Moreover, full-fat dairy products (ORT3 1·16; 95 % CI 0·99, 1·35), non-fermented dairy products (OR100 g 1·05; 95 % CI 1·01, 1·09) and milk (ORserving/150 g 1·08; 95 % CI 1·02, 1·15) were positively associated with ND-T2DM. In conclusion, our data showed inverse associations of skimmed and fermented dairy products with pre-diabetes. Positive associations were observed for full-fat and non-fermented dairy products with pre-diabetes and ND-T2DM.

Reduced-fat Gouda-type cheese enriched with vitamin D3 effectively prevents vitamin D deficiency during winter months in postmenopausal women in Greece.

OBJECTIVE: The primary aim of the present study was to examine the effectiveness of daily consumption of vitamin D3-enriched, reduced-fat Gouda-type cheese on 25-hydroxyvitamin D (25(OH)D) concentration in postmenopausal women. Health-related quality of life (HRQL) indices were examined as secondary outcomes. DESIGN: This is a single-blinded (i.e., to study participants), randomized, controlled food-based dietary intervention study. METHODS: A sample of 79 postmenopausal women (55-75 years old) was randomized either to a control group (CG: n = 39) or an intervention group (IG: n = 40) that consumed, as part of their usual diet, 60 g of either non-enriched or vitamin D3 enriched Gouda-type cheese, respectively, for eight consecutive weeks (i.e., from January to March 2015). Sixty grams of enriched cheese provided a daily dose of 5.7 µg of vitamin D3. RESULTS: There was a differential response of mean (95 % CI) serum 25(OH)D levels in the IG and CG, with the former increasing and the latter decreasing significantly over the eight weeks of the trial [i.e., by 5.1 (3.4, 6.9) nmol/L vs. -4.6 (-6.4, -2.8) nmol/L, P < 0.001, respectively]. The percentages of study participants with 25(OH)D levels <30 (deficiency) and <50 nmol/L (insufficiency) were significantly higher at follow-up in the CG compared to the IG (41.0 vs. 0 %, P < 0.001 and 74.4 vs. 47.5 %, P < 0.001, respectively). The emotional well-being scale of the HRQL score increased in the IG compared to a decrease in the CG (3.2 vs. -3.8, P = 0.028). However, none of the other seven scales of the HRQL score significantly differentiated between study groups (P > 0.1). CONCLUSIONS: Consumption of 60 g of vitamin D3-enriched, reduced-fat Gouda-type cheese provided a daily dose of 5.7 µg of additional vitamin D3 and was effective in increasing mean serum 25(OH)D concentration and in counteracting vitamin D deficiency during winter months in postmenopausal women in Greece.

Consumption of dairy foods in relation to impaired glucose metabolism and type 2 diabetes mellitus: the Maastricht Study.

Observational studies suggest an inverse association between total dairy product intake and diabetes risk. However, there is a lack of information on the relationship of specific dairy products with impaired glucose metabolism (IGM) and type 2 diabetes mellitus (T2DM). Individuals aged 40-75 years were recruited for the Maastricht Study. All the participants filled out a 253-food item FFQ, covering fifty specific dairy items that captured differences between full-fat, semi-skimmed and skimmed products, as well as fermented and non-fermented products. Glucose metabolism status was assessed by an oral glucose tolerance test, and participants were informed on their glucose metabolism status after returning the FFQ. Data of 2391 individuals were available to estimate OR (95 % CI) for IGM (n 470) and newly diagnosed (ND) T2DM (n 125), with adjustment for age, sex, BMI, physical activity, smoking status, education, energy intake and intakes of vegetables, fruits, meat and fish. For IGM, fully adjusted analyses revealed inverse associations, with OR comparing the highest with the lowest tertile of intake of 0·73 (95 % CI 0·55, 0·96) for skimmed products and 0·74 (95 % CI 0·54, 0·99) for fermented products. These dairy products were not associated with ND T2DM. In contrast, full-fat products were positively associated with ND T2DM (OR 2·01; 95 % CI 1·16, 3·47), whereas total dairy product intake was inversely associated with ND T2DM (OR 0·50; 95 % CI 0·26, 0·93). In conclusion, individuals with a high consumption of skimmed and fermented products had lower odds of having IGM, and individuals with a high consumption of total dairy products had lower odds of having ND T2DM. High intake of full-fat products was not related to IGM but was positively related to ND T2DM.

A cross-sectional study on the dietary patterns of multiethnic Malaysian preschoolers and their sociodemographic determinants.

Early childhood is a critical developmental stage where established dietary patterns can impact lifelong health outcomes. This study investigates dietary patterns and their relationships with sociodemographic factors among Malaysian preschoolers. A total of 643 preschoolers of Malay, Indian, Chinese and other ethnicities participating in South East Asian Nutrition Surveys (SEANUTS II) were included. Dietary intake was assessed using a single triple-pass 24-h dietary recall method. Dietary patterns were derived using principal component analysis and their association with sociodemographic factors was determined using complex sampling logistic regressions. Five dietary patterns were identified: "healthy eating," "wholegrains and starchy vegetables," "high salt and sugar," "Western food," and "sugary drinks and legumes". Having older siblings was inversely associated with a "healthy eating" pattern (adjusted OR: 0.54, 95% CI: 0.33-0.87). Malay ethnicity was associated with higher odds of adhering to the "high salt and sugar" pattern (adjusted OR: 4.12, 95% CI: 2.20-7.75). Meanwhile, children living in urban areas (adjusted OR: 1.76, 95% CI: 1.03-3.01), those from middle-income families (adjusted OR: 3.20, 95% CI: 1.38-7.40) and whose fathers were overweight (adjusted OR: 2.79, 95% CI: 1.58-4.94) showed a higher association with "Western food" pattern. Conversely, children whose mothers had overweight were less likely to adhere to the "Western food" pattern (adjusted OR: 0.50, 95% CI: 0.30-0.83). Older age was significantly associated with a greater likelihood of the "sugary drinks and legumes" pattern (adjusted OR: 3.99, 95% CI: 1.75-9.06). There was no significant association between "wholegrains and starchy vegetables" pattern with sociodemographic characteristics (all p > 0.05). These findings suggest that ethnicity, age, residence area, having older siblings, parental weight status and household income level are associated with dietary patterns among multiethnic preschoolers in Malaysia. Thus, these sociodemographic characteristics should be considered when designing targeted dietary strategies and interventions for preschoolers.

Effects of Early and Late Time-Restricted Feeding on Parameters of Metabolic Health: An Explorative Literature Assessment.

Chrono-nutrition (meal timing) aligns food consumption with one's circadian rhythm. The first meal (e.g., breakfast) likely promotes synchronization of peripheral circadian clocks, thereby supporting metabolic health. Time-restricted feeding (TRF) has been shown to reduce body weight (BW) and/or improve cardiovascular biomarkers. In this explorative literature assessment, 13 TRF randomized controlled trials (RCTs) were selected from PubMed and Scopus to evaluate the effects of early (eTRF: first meal before 10:30 a.m.) and late TRF (lTRF: first meal after 11:30 a.m.) on parameters of metabolic health. Although distinct variations in study design were evident between reports, TRF consistently decreased energy intake (EI) and BW, and improved insulin resistance as well as systolic blood pressure. eTRF seemed to have a greater beneficial effect than lTRF on insulin resistance (HOMA-IR). Importantly, most studies did not appear to consider chronotype in their evaluation, which may have underestimated TRF effects. TRF intervention may be a promising approach for risk reduction of human metabolic diseases. To conclusively determine benefits of TRF and identify clear differences between eTRF and lTRF, future studies should be longer-term (≥8 weeks) with well-defined (differences in) feeding windows, include participants chronotypically matching the intervention, and compare outcomes to those of control groups without any dietary limitations.

E-DES-PROT: A novel computational model to describe the effects of amino acids and protein on postprandial glucose and insulin dynamics in humans.

Current computational models of whole-body glucose homeostasis describe physiological processes by which insulin regulates circulating glucose concentrations. While these models perform well in response to oral glucose challenges, interaction with other nutrients that impact postprandial glucose metabolism, such as amino acids (AAs), is not considered. Here, we developed a computational model of the human glucose-insulin system, which incorporates the effects of AAs on insulin secretion and hepatic glucose production. This model was applied to postprandial glucose and insulin time-series data following different AA challenges (with and without co-ingestion of glucose), dried milk protein ingredients, and dairy products. Our findings demonstrate that this model allows accurate description of postprandial glucose and insulin dynamics and provides insight into the physiological processes underlying meal responses. This model may facilitate the development of computational models that describe glucose homeostasis following the intake of multiple macronutrients, while capturing relevant features of an individual's metabolic health.

Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial.

Precision nutrition based on metabolic phenotype may increase the effectiveness of interventions. In this proof-of-concept study, we investigated the effect of modulating dietary macronutrient composition according to muscle insulin-resistant (MIR) or liver insulin-resistant (LIR) phenotypes on cardiometabolic health. Women and men with MIR or LIR (n = 242, body mass index [BMI] 25-40 kg/m2, 40-75 years) were randomized to phenotype diet (PhenoDiet) group A or B and followed a 12-week high-monounsaturated fatty acid (HMUFA) diet or low-fat, high-protein, and high-fiber diet (LFHP) (PhenoDiet group A, MIR/HMUFA and LIR/LFHP; PhenoDiet group B, MIR/LFHP and LIR/HMUFA). PhenoDiet group B showed no significant improvements in the primary outcome disposition index, but greater improvements in insulin sensitivity, glucose homeostasis, serum triacylglycerol, and C-reactive protein compared with PhenoDiet group A were observed. We demonstrate that modulating macronutrient composition within the dietary guidelines based on tissue-specific insulin resistance (IR) phenotype enhances cardiometabolic health improvements. Clinicaltrials.gov registration: NCT03708419, CCMO registration NL63768.068.17.

Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study.

BACKGROUND: Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms with MetS. METHODS: In a random sample of the EPIC-NL study (n = 1886), 38 SNPs associated with waist circumference, insulin resistance, triglycerides, HDL cholesterol and inflammation in genome wide association studies (GWAS) were selected from the 50K IBC array and one additional SNP was measured with KASPar chemistry. The five groups of SNPs, each belonging to one of the metabolic endpoints mentioned above, were associated with MetS and MetS-score using Goeman's global test. For groups of SNPs significantly associated with the presence of MetS or MetS-score, further analyses were conducted. RESULTS: The group of waist circumference SNPs was associated with waist circumference (P=0.03) and presence of MetS (P=0.03). Furthermore, the group of SNPs related to insulin resistance was associated with MetS score (P<0.01), HDL cholesterol (P<0.01), triglycerides (P<0.01) and HbA1C (P=0.04). Subsequent analyses showed that MC4R rs17782312, involved in weight regulation, and IRS1 rs2943634, related to insulin resistance were associated with MetS (OR 1.16, 95%CI 1.02-1.32 and OR 0.88, 95% CI 0.79; 0.97, respectively). The groups of inflammation and lipid SNPs were neither associated with presence of MetS nor with MetS score. CONCLUSIONS: In this study we found support for the hypothesis that weight regulation and insulin metabolism are involved in MetS development.MC4R rs17782312 and IRS1 rs2943634 may explain part of the genetic variation in MetS.

Genetic variants in lipid metabolism are independently associated with multiple features of the metabolic syndrome.

BACKGROUND: Our objective was to find single nucleotide polymorphisms (SNPs), within transcriptional pathways of glucose and lipid metabolism, which are related to multiple features of the metabolic syndrome (MetS). METHODS: 373 SNPs were measured in 3575 subjects of the Doetinchem cohort. Prevalence of MetS features, i.e. hyperglycemia, abdominal obesity, decreased HDL-cholesterol levels and hypertension, were measured twice in 6 years. Associations between the SNPs and the individual MetS features were analyzed by log-linear models. For SNPs related to multiple MetS features (P < 0.01), we investigated whether these associations were independent of each other. RESULTS: Two SNPs, CETP Ile405Val and APOE Cys112Arg, were associated with both the prevalence of low HDL-cholesterol level (Ile405Val P = < .0001; Cys112Arg P = 0.001) and with the prevalence of abdominal obesity (Ile405Val P = 0.007; Cys112Arg P = 0.007). For both SNPs, the association with HDL-cholesterol was partly independent of the association with abdominal obesity and vice versa. CONCLUSION: Two SNPs, mainly known for their role in lipid metabolism, were associated with two MetS features i.e., low HDL-cholesterol concentration, as well as, independent of this association, abdominal obesity. These SNPs may help to explain why low HDL-cholesterol levels and abdominal obesity frequently co-occur.

Effect of high compared with low dairy intake on blood pressure in overweight middle-aged adults: results of a randomized crossover intervention study.

BACKGROUND: Observational studies suggest that high dairy intake is associated with a lower blood pressure (BP). OBJECTIVE: We aimed to investigate the effect of a high-dairy diet (HDD) as compared with a low-dairy diet (LDD) on BP in overweight middle-aged adults. METHODS: Fifty-two overweight men and women were included in a randomized crossover intervention study. Each subject consumed 2 isocaloric diets for 6 wk, an LDD (≤1 dairy portion per day) and an HDD (6 or 5 reduced-fat dairy portions for men and women, respectively), with a 4-wk washout period in between the diets during which the subjects consumed their habitual diet. BP was measured at the start and at the end of the intervention diets. The effect of the intervention study was evaluated by 2-sample t tests. Mixed-model analyses were used for adjustment for the potential influence of changes in dietary protein and mineral intake and risk factors for hypertension including body weight and plasma cholesterol. RESULTS: Consumption of an HDD as compared with an LDD resulted in a reduction of both systolic BP (mean ± SD: 4.6 ± 11.2 mm Hg, P < 0.01) and diastolic BP (3.0 ± 6.7 mm Hg, P < 0.01). In further analyses, these reductions appeared dependent on the concomitant increase in calcium intake. CONCLUSIONS: This intervention study shows that an HDD results in a reduction of both systolic and diastolic BP in overweight middle-aged men and women. If the results of our study are reproduced by other studies, advice for high dairy intake may be added to treatment and prevention of high BP. This trial was registered at trialregister.nl as NTR4899.

The effect of high compared with low dairy consumption on glucose metabolism, insulin sensitivity, and metabolic flexibility in overweight adults: a randomized crossover trial.

BACKGROUND: Dairy products contain many nutritious components that may benefit metabolic health. There are indications that glucose metabolism and insulin sensitivity, which are generally disturbed in overweight and obese individuals, may improve by increased dairy intake. This may also affect one's metabolic flexibility. OBJECTIVE: The aim of this study was to investigate the effects of high compared with low dairy intake on glucose metabolism, insulin sensitivity, and metabolic flexibility in overweight adults (aged 45-65 y). METHODS: In this randomized intervention study, subjects consumed a high- and a low-dairy diet [HDD (5-6 dairy portions) and LDD (≤1 dairy portion), respectively] for 6 wk in a crossover design, with a washout period of 4 wk. Dairy portions were 200 g semi-skimmed yoghurt, 30 g reduced-fat (30+) cheese, and 250 mL semiskimmed milk and buttermilk. After 6 wk, a 75-g oral-glucose-tolerance test (13C-labeled) and a subsequent fasting challenge were performed. Metabolic flexibility was studied by determining the respiratory quotient (RQ) using indirect calorimetry. Fasting and postprandial plasma concentrations of glucose and insulin were analyzed. The dual isotope technique enabled calculation of glucose kinetics. RESULTS: The study was completed by 45 overweight men and postmenopausal women [age 58.9 ± 4.3 y, BMI 27.9 ± 1.9 kg/m2 (mean ± SD)]. Fasting RQ and ΔRQ, reflecting metabolic flexibility, did not differ after both diets. Fasting glucose concentrations were similar, whereas fasting insulin concentrations were lower after the LDD (LDD: 8.1 ± 2.8 mU/L; HDD: 8.9 ± 3.3 mU/L; P = 0.024). This resulted in a higher HOMA-IR after the HDD (P = 0.027). Postprandial glucose and insulin responses as well as glucose kinetics were similar after both diets. CONCLUSIONS: The amount of dairy intake during a 6-wk period had a neutral effect on metabolic flexibility or postprandial glucose metabolism in middle-aged overweight subjects. More trials are needed to study the effects of specific dairy types and to differentiate between metabolic subgroups. This trial was registered at trialregister.nl as NTR4899.

Dietary Protein Sources and Muscle Mass over the Life Course: The Lifelines Cohort Study.

The influence of dietary protein intake on muscle mass in adults remains unclear. Our objective was to investigate the association between protein intake and muscle mass in 31,278 men and 45,355 women from the Lifelines Cohort. Protein intake was estimated by food frequency questionnaire and muscle mass was estimated from 24 h urinary creatinine excretion. The age range was 18⁻91 years and mean total protein intake was 1.0 ± 0.3 g/kg/day. Across increasing quartiles of total protein intake, animal protein intake, and fish/meat/egg protein intake, creatinine excretion significantly increased in both men (+4% for total and +6% for fish/meat/egg protein intake, p < 0.001) and women (+3% for total and +6% for fish/meat/egg protein intake, p < 0.001). The associations were not systematically stronger or weaker with increasing age, but associations were strongest for young men (26⁻45 years) and older women (>75 years). The association between total protein intake and muscle mass was dependent on physical activity in women (p interaction < 0.001). This study suggests that total protein intake, animal protein intake, and in particular fish/meat/egg protein intake may be important for building and preserving muscle mass. Dietary protein sources should be further studied for their potential to build and preserve muscle mass.

Associations of Milk Consumption and Vitamin B2 and Β12 Derived from Milk with Fitness, Anthropometric and Biochemical Indices in Children. The Healthy Growth Study.

The benefits of dairy consumption seem to extend beyond its significant contribution to ensuring nutrient intake adequacy as indicated by the favourable associations with several health outcomes reported by different studies. The aims of the present study were to examine the associations of milk consumption with fitness, anthropometric and biochemical indices in children and further explore whether the observed associations are attributed to vitamins B2 and B12 derived from milk. A representative subsample of 600 children aged 9-13 years participating in the Healthy Growth Study was examined. Data were collected on children's dietary intake, using 24 h recalls, as well as on fitness, anthropometric and biochemical indices. Regression analyses were performed for investigating the research hypothesis, adjusting for potential confounders and for B-vitamin status indices (i.e., plasma riboflavin, methylmalonic acid and total homocysteine concentrations), dietary calcium intake and plasma zinc concentrations that could possibly act as effect modifiers. Milk consumption was positively associated with the number of stages performed in the endurance run test (ERT) (ß = 0.10; p = 0.017) and negatively with body mass index (BMI) (ß = -0.10; p = 0.014), after adjusting for several potential confounders and effect modifiers. Dietary intakes of vitamin B2 and B12 derived from milk were also positively associated with the number of ERT stages (ß = 0.10; p = 0.015 and ß = 0.10; p = 0.014 respectively). In conclusion, higher intake of milk as well as vitamin B2 and B12 derived from milk were independently associated with higher cardiorespiratory fitness in Greek preadolescents. The key roles of these B-vitamins in substrate oxidation, energy production, haemoglobin synthesis and erythropoiesis could provide a basis for interpreting these associations. However, further research is needed to confirm this potential interpretation.

Metabolic syndrome model definitions predicting type 2 diabetes and cardiovascular disease.

OBJECTIVE: Metabolic syndrome (MetS) is a cluster of abdominal obesity, hyperglycemia, hypertension, and dyslipidemia, which increases the risk for type 2 diabetes and cardiovascular diseases (CVDs). Some argue that MetS is not a single disorder because the traditional MetS features do not represent one entity, and they would like to exclude features from MetS. Others would like to add additional features in order to increase predictive ability of MetS. The aim of this study was to identify a MetS model that optimally predicts type 2 diabetes and CVD while still representing a single entity. RESEARCH DESIGN AND METHODS: In a random sample (n = 1,928) of the EPIC-NL cohort and a subset of the EPIC-NL MORGEN study (n = 1,333), we tested the model fit of several one-factor MetS models using confirmatory factor analysis. We compared predictive ability for type 2 diabetes and CVD of these models within the EPIC-NL case-cohort study of 545 incident type 2 diabetic subjects, 1,312 incident CVD case subjects, and the random sample, using survival analyses and reclassification. RESULTS: The standard model, representing the current MetS definition (EPIC-NL comparative fit index [CFI] = 0.95; MORGEN CFI = 0.98); the standard model excluding blood pressure (EPIC-NL CFI = 0.95; MORGEN CFI = 1.00); and the standard model extended with hsCRP (EPIC-NL CFI = 0.95) had an acceptable model fit. The model extended with hsCRP predicted type 2 diabetes (integral discrimination index [IDI]: 0.34) and CVD (IDI: 0.07) slightly better than did the standard model. CONCLUSIONS: It seems valid to represent the traditional MetS features by a single entity. Extension of this entity with hsCRP slightly improves predictive ability for type 2 diabetes and CVD.

Hemochromatosis (HFE) genotype and atherosclerosis: Increased susceptibility to iron-induced vascular damage in C282Y carriers?

BACKGROUND: The C282Y mutation of the hemochromatosis (HFE)-gene increases body iron status. Among Caucasians, the carrier frequency of this mutation is 8-9%. C282Y carriers may be more susceptible to iron-induced atherosclerosis due to higher iron levels. It has also been postulated that the C282Y mutation could alter aspects of iron metabolism. We examined the relationship between the C282Y mutation, iron status, and carotid intima-media thickness (IMT) as a marker of atherosclerosis. METHODS AND RESULTS: The present study comprised 764 Dutch men and post-menopausal women aged 50-70 years. Mean and maximum carotid IMT were assessed by B-mode ultrasonography. Blood was sampled for assessment of the C282Y mutation and body iron status. Parameters of iron status (e.g. ferritin and non-transferrin bound iron) were significantly higher in C282Y carriers (n=80; 10%) compared to non-carriers (P-values <0.001), however, there was no difference in the carotid IMT measures. Among non-smokers (n=222), carotid IMT was 0.051 mm (95% CI: 0.005; 0.096) lower in carriers compared to non-carriers (P=0.03), which remained after adjustment for iron parameters. Within the subgroup of carriers, higher carotid IMT values were observed across sex-specific quartiles of ferritin (mean IMT: 0.789, 0.787, 0.814, and 0.865 mm; P-trend=0.08), whereas this association was absent in non-carriers. CONCLUSION: Overall, we found no association of HFE genotype with carotid IMT, despite higher iron status. Interestingly, C282Y carriers may be hyper responsive to vascular damage which needs to be confirmed in prospective cohort studies.