Obesogenic dietary intake in families with 1-year-old infants at high and low obesity risk based on parental weight status: baseline data from a longitudinal intervention (Early STOPP)

PURPOSE: To compare dietary intake in 1-year-old infants and their parents between families with high and low obesity risk, and to explore associations between infant dietary intake and relative weight. METHODS: Baseline analyses of 1-year-old infants (n = 193) and their parents participating in a longitudinal obesity intervention (Early STOPP) were carried out. Dietary intake and diet quality indicators were compared between high- and low-risk families, where obesity risk was based on parental weight status. The odds for high diet quality in relation to parental diet quality were determined. Associations between measured infant relative weight and dietary intake were examined adjusting for obesity risk, socio-demographics, and infant feeding. RESULTS: Infant dietary intake did not differ between high- and low-risk families. The parents in high-risk families consumed soft drinks, French fries, and low-fat spread more frequently, and fish and fruits less frequently (p < 0.05) compared to parents in low-risk families. Paternal intake of vegetables and fish increased the odds for children being consumers of vegetables (OR 1.7; 95 % CI 1.0-2.9) and fish, respectively (OR 2.5; 95 % CI 1.4-4.4). Infant relative weight was weakly associated with a high intake of milk cereal drink (r = 0.15; p < 0.05), but not with any other aspect of dietary intake, obesity risk, or early feeding patterns. CONCLUSIONS: At the age of one, dietary intake in infants is not associated with family obesity risk, nor with parental obesogenic food intake. Milk cereal drink consumption but no other infant dietary marker reflects relative weight at this young age.published_or_final_versio

Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21

OBJECTIVE—Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) –dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPAR, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS—The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPAR activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS—Oleate and linoleate increased FGF-21 expression and secretion in a PPAR-dependent fashion, as demonstrated by small-interfering RNA–induced PPAR knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS—The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity

Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis

Background We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid [17:0], and trans-palmitoleic acid [t16:1n-7]) with CVD outcomes or all-cause mortality. Methods and findings We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were ≥3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. Conclusions In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms. Copyright

Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR

Alcohol consumption and body composition in a population-based sample of elderly Australian men

Background: Alcohol is calorie dense, and impacts&nbsp;activity, appetite and lipid processing. The aim of this&nbsp;study was to therefore investigate the association between&nbsp;alcohol consumption and components of body composition&nbsp;including bone, fat and lean tissue.Methods: Participants were recruited from a randomly&nbsp;selected, population-based sample of 534 men aged&nbsp;65 years and older enrolled in the Geelong Osteoporosis&nbsp;Study. Alcohol intake was ascertained using a food&nbsp;frequency questionnaire and the sample categorised as nondrinkers or alcohol users who consumed B2, 3&ndash;4 or C5&nbsp;standard drinks on a usual drinking day. Bone mineral&nbsp;density (BMD), lean body mass and body fat mass were&nbsp;measured using dual energy X-ray absorptiometry; overall&nbsp;adiposity (%body fat), central adiposity (%truncal fat) and&nbsp;body mass index (BMI) were calculated. Bone quality was&nbsp;determined by quantitative heel ultrasound (QUS).Results: There were 90 current non-drinkers (16.9 %),&nbsp;266 (49.8 %) consumed 1&ndash;2 drinks/day, 104 (19.5 %) 3&ndash;4&nbsp;drinks/day and 74 (13.8 %) C5 drinks/day. Those consuming C5 drinks/day had greater BMI (?4.8 %), fat mass&nbsp;index (?20.1 %), waist circumference (?5.0 %), %body&nbsp;fat (?15.2 %) and proportion of trunk fat (?5.3 %) and&nbsp;lower lean mass (-5.0 %) than non-drinkers after adjustment for demographic and lifestyle factors. Furthermore,&nbsp;they were more likely to be obese than non-drinkers&nbsp;according to criteria based on BMI (OR = 2.83, 95 %CI&nbsp;1.10&ndash;7.29) or waist circumference (OR = 3.36, 95 %CI&nbsp;1.32&ndash;8.54). There was an inverse relationship between&nbsp;alcohol consumption and QUS parameters and BMD at the&nbsp;mid forearm site; no differences were detected for BMD at&nbsp;other skeletal sites.Conclusion:&nbsp;Higher alcohol intake was associated with&nbsp;greater total and central adiposity and reduced bone&nbsp;quality.<br /

Associations of Type 2 Diabetes with Common Variants in PPARD and the Modifying Effect of Vitamin D among Middle-Aged and Elderly Chinese

BACKGROUND: Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1) whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2) whether the associations would be modified by the effect of vitamin D status. METHODS AND FINDINGS: We genotyped 9 tag single nucleotide polymorphisms (SNPs) that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056) and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22-2.53]; P = 0.0025) and combined type 2 diabetes and impaired fasting glucose (IFG) (odds ratio 1.47 [95%CI 1.12-1.92]; P = 0.0054). The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316) and HbA1c (P = 0.0180). In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347). CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OH)D levels and PPARD-rs6902123 on HbA1c

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research