Apolipoprotein E gene variants shape the association between dietary fibre intake and cognitive decline risk in community-dwelling older adults.

BACKGROUND: healthy dietary patterns have been associated with lower risk for age-related cognitive decline. However, little is known about the specific role of dietary fibre on cognitive decline in older adults. OBJECTIVE: this study aimed to examine the association between dietary fibre and cognitive decline in older adults and to assess the influence of genetic, lifestyle and clinical characteristics in this association. DESIGN AND PARTICIPANTS: the Invecchiare in Chianti, aging in the Chianti area study is a cohort study of community-dwelling older adults from Italy. Cognitive function, dietary and clinical data were collected at baseline and years 3, 6, 9 and 15. Our study comprised 848 participants aged ≥ 65 years (56% female) with 2,038 observations. MAIN OUTCOME AND MEASURES: cognitive decline was defined as a decrease ≥3 units in the Mini-Mental State Examination score during consecutive visits. Hazard ratios for cognitive decline were estimated using time-dependent Cox regression models. RESULTS: energy-adjusted fibre intake was not associated with cognitive decline during the 15-years follow-up (P > 0.05). However, fibre intake showed a significant interaction with Apolipoprotein E (APOE) haplotype for cognitive decline (P = 0.02). In participants with APOE-ɛ4 haplotype, an increase in 5 g/d of fibre intake was significantly associated with a 30% lower risk for cognitive decline. No association was observed in participants with APOE-ɛ2 and APOE-ɛ3 haplotypes. CONCLUSIONS AND RELEVANCE: dietary fibre intake was not associated with cognitive decline amongst older adults for 15 years of follow-up. Nonetheless, older subjects with APOE-ɛ4 haplotype may benefit from higher fibre intakes based on the reduced risk for cognitive decline in this high-risk group.

Dietary polyphenols, metabolic syndrome and cardiometabolic risk factors: An observational study based on the DCH-NG subcohort.

BACKGROUND AND AIMS: Polyphenol-rich foods have beneficial properties that may lower cardiometabolic risk. We aimed to prospectively investigate the relationship between intakes of dietary polyphenols, and metabolic syndrome (MetS) and its components, in 676 Danish residents from the MAX study, a subcohort of the Danish Diet, Cancer and Health-Next Generations (DCH-NG) cohort. METHODS AND RESULTS: Dietary data were collected using web-based 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). The Phenol-Explorer database was used to estimate dietary polyphenol intake. Clinical variables were also collected at the same time point. Generalized linear mixed models were used to investigate relationships between polyphenol intake and MetS. Participants had a mean age of 43.9y, a mean total polyphenol intake of 1368 mg/day, and 75 (11.6%) had MetS at baseline. Compared to individuals with MetS in Q1 and after adjusting for age, sex, lifestyle and dietary confounders, those in Q4 - for total polyphenols, flavonoids and phenolic acids-had a 50% [OR (95% CI): 0.50 (0.27, 0.91)], 51% [0.49 (0.26, 0.91)] and 45% [0.55 (0.30, 1.00)] lower odds of MetS, respectively. Higher total polyphenols, flavonoids and phenolic acids intakes as continuous variable were associated with lower risk for elevated systolic blood pressure (SBP) and low high-density lipoprotein cholesterol (HDL-c) (p < 0.05). CONCLUSIONS: Total polyphenol, flavonoid and phenolic acid intakes were associated with lower odds of MetS. These intakes were also consistently and significantly associated with a lower risk for higher SBP and lower HDL-c concentrations.

Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects.

PURPOSE: Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively affect the gut microbiota-immune system-intestinal barrier (IB) axis. In this context, we tested the hypothesis that a PR-dietary intervention would affect the presence of bacterial factors in the bloodstream of older adults. METHODS: We collected blood samples within a randomized, controlled, crossover intervention trial in which older volunteers (n = 51) received a polyphenol-enriched and a control diet. We quantified the presence of bacterial DNA in blood by qPCR targeting the 16S rRNA gene (16S; bacterial DNAemia). Blood DNA was taxonomically profiled via 16S sequencing. RESULTS: Higher blood 16S levels were associated with higher BMI and markers of IP, inflammation, and dyslipidemia. PR-intervention did not significantly change bacterial DNAemia in the older population (P = 0.103). Nonetheless, the beneficial changes caused by the polyphenol-enriched diet were greatest in participants with higher bacterial DNAemia, specifically in markers related to IP, inflammation and dyslipidemia, and in fecal bacterial taxa. Finally, we found that the bacterial DNA detected in blood mostly belonged to γ-Proteobacteria, whose abundance significantly decreased after the polyphenol-rich diet in subjects with higher bacterial DNAemia at baseline. CONCLUSIONS: This study shows that older subjects with higher bacterial DNAemia experienced a beneficial effect from a polyphenol-rich diet. Bacterial DNAemia may be a further relevant marker for the identification of target populations that could benefit more from a protective dietary treatment. REGISTRATION: This trial was retrospectively registered at www.isrctn.org (ISRCTN10214981) on April 28, 2017.

Adherence to the Mediterranean diet assessed by a novel dietary biomarker score and mortality in older adults: the InCHIANTI cohort study.

BACKGROUND: Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality. METHODS: 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression. RESULTS: During the 20-year follow-up [median (Q1-Q3), 14 (8-18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56-0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38-0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant. CONCLUSIONS: A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people. TRIAL REGISTRATION: NCT01331512.

A healthy eating score is inversely associated with depression in older adults: results from the Chilean National Health Survey 2016-2017.

OBJECTIVE: To investigate the relationship of a healthy eating score with depression in Chilean older adults. DESIGN: Cross-sectional study. SETTING: Older adults from the Chilean National Health Survey 2016-2017. Associations were analysed using complex samples multivariable logistic regressions adjusted for age, sex, socio-demographic, lifestyles (physical activity, smoking, alcohol consumption and sleep duration), BMI and clinical conditions (hypertension, diabetes, hypercholesterolaemia and cardiovascular diseases). PARTICIPANTS: The number of participants was 2031 (≥ 60 years). The Composite International Diagnostic Interview-Short Form was applied to establish the diagnosis of major depressive episode. Six healthy eating habits were considered to produce the healthy eating score (range: 0-12): consumption of seafood, whole grain, dairy, fruits, vegetables and legumes. Participants were categorised according to their final scores as healthy (≥ 9), average (5-8) and unhealthy (≤ 4). RESULTS: Participants with a healthy score had a higher educational level, physical activity and regular sleep hours than participants with an average and unhealthiest healthy eating score. Participants classified in the healthiest healthy eating score had an inverse association with depression (OR: 0·28, (95 % CI 0·10, 0·74)). Food items that contributed the most to this association were legumes (15·2 %) and seafood (12·7 %). CONCLUSION: Older adults classified in the healthiest healthy eating score, characterised by a high consumption of legumes and seafood, showed a lower risk for depression in a representative sample of Chilean population.

Different alterations of glomerular filtration rate and their association with uric acid in children and adolescents with type 1 diabetes or with overweight/obesity.

BACKGROUND: Hyperfiltration (HF) occurs early in diabetes or obesity (OB)-associated renal disease. Alterations of glomerular filtration rate (GFR) in childhood OB remain unclear. OBJECTIVES: To compare the prevalence of GFR alterations and its association with uric acid in children and adolescents with type 1 diabetes (T1D) vs overweight (OW)/OB. METHODS: Cross-sectional study of 29 youths (aged: 13 ± 2 years) with T1D (disease duration: 7 ± 3 years) and 165 with OW/OB (aged: 11 ± 3 years). Patients with an albumin-creatinine ratio >3.39 mg/mmol were excluded. GFR was estimated with creatinine-cystatin C Zappitelli equation. HF and low GFR were defined by a GFR > 135 and <90 mL/min.1.73 m2 , respectively. RESULTS: HF was higher in children with T1D vs OW/OB (28% vs 10%, P < .005). Children with OW/OB also showed a 10% of low GFR. In patients with T1D, HbA1c (ß = .8, P < .001), and systolic blood pressure (ß = 11.4, P < .005) were independent predictors of GFR (R2 = .65). In OW/OB, HF cases were almost limited to prepubertal children and low GFR to pubertal ones. GFR in OW/OB was associated with age (ß = -2.2, P < .001), male sex (ß = -11.6, P < .001), and uric acid (ß = -.05, P < .001) in adjusted models (R2 = .33). CONCLUSIONS: GFR alterations were different between youths with T1D and with OW/OB. Higher uric acid, older age, and puberty were related to lower GFR values in OW/OB children. Longitudinal studies will determine if low GFR is consequence of a rapid GFR decline in pediatric patients with OW/OB.

Association of glomerular hyperfiltration with serum chemokine levels and metabolic features in prepubertal children with overweight/obesity.

BACKGROUND AND AIMS: Glomerular hyperfiltration (GH) is proposed as one of the earliest events in obesity (OB)-associated renal disease. Children with GH and type-1 diabetes showed increased chemokine levels. Chemokine associations with glomerular filtration rate (GFR) and metabolic features in prepubertal children with overweight (OW)/OB are unknown. METHODS AND RESULTS: Cross-sectional study. 75 prepubertal children (aged: 9.0 ± 1.7 years) with OW/OB were studied. Clinical and metabolic characteristics (including non-esterified fatty acids, NEFA) and GFR (combined Zappitelli equation) were assessed. GH was defined as GFR >135 ml/min.1.73 m2. Serum levels of regulated on activation, normal T cell expressed and secreted (RANTES)/CCL5, interleukin-8 (IL-8)/CXCL8 and monokine-induced by interferon-γ (MIG)/CXCL9 were measured by ELISA. Age- and sex-adjusted correlations and differences were tested. 48% of the cohort was female and 13% were OW, 54% OB and 33% severe OB. Prepubertal children with GH showed lower z-BMI (-12%), NEFA (-26%) and uric acid (-22%) than those without GH (all p < 0.05). Similarly to high sensitivity C-reactive protein (hsCRP), there were no differences in serum chemokines between children with GH or not (all p > 0.05). Adjusted correlations were significant for RANTES and z-BMI (r = 0.26; p < 0.05) and for MIG with z-BMI (r = -0.26; p < 0.05) and with NEFA (r = 0.27; p < 0.05). CONCLUSION: GH was not associated with higher chemokine levels in prepubertal children with OW/OB. Decreased rather than elevated GFR values were correlated with obesity and worse metabolic profiles. Chemokines levels in children with severe OB suggest a regulation of the immune response. Follow-up studies are needed to address the clinical implications of these findings.

- 174 G>C IL-6 polymorphism and primary iron overload in male patients.

Primary iron overload (IO) is commonly associated with mutations in the hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may influence the development of IO beyond HFE mutations. There is a single nucleotide polymorphism (SNP) at - 174 G>C of the interleukin (IL)-6 gene which might be associated with primary IO. Our aim was to study the association between the SNP - 174 G>C gene promoter of IL-6 and primary IO in middle-aged male patients. We studied 37 men with primary IO diagnosed by liver histology. Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP - 174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was used to evaluate the association between primary IO and SNP - 174 G>C gene promoter of IL-6. Patients and control subjects were in Hardy-Weinberg equilibrium for the SNP - 174 G>C gene promoter of IL-6 (p = 0.17). Significantly different genotype frequencies were observed between patients (43% CC, 43% CG, and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI = 2.06-8.13; p < 0.0001). The multiple logistic regression analysis showed that IO was significantly associated with CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 (OR = 6.3, 95% CI = 1.9-21.4; p < 0.005) in a model adjusted by age and body mass index. In conclusion, CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 can be proposed as one of the gene variants influencing iron accumulation in male adults with HFE mutations. Studies in larger cohorts are warranted.

Poor glycemic control in type 2 diabetes enhances functional and compositional alterations of small, dense HDL3c.

High-density lipoprotein (HDL) possesses multiple biological activities; small, dense HDL3c particles displaying distinct lipidomic composition exert potent antiatherogenic activities which can be compromised in dyslipidemic, hyperglycemic insulin-resistant states. However, it remains indeterminate (i) whether such functional HDL deficiency is related to altered HDL composition, and (ii) whether it originates from atherogenic dyslipidemia, dysglycemia, or both. In the present work we analyzed compositional characteristics of HDL subpopulations and functional activity of small, dense HDL3c particles in treatment-naïve patients with well-controlled (n=10) and poorly-controlled (n=8) type 2 diabetes (T2D) and in normolipidemic age- and sex-matched controls (n=11). Our data reveal that patients with both well- and poorly-controlled T2D displayed dyslipidemia and low-grade inflammation associated with altered HDL composition. Such compositional alterations in small, dense HDL subfractions were specifically correlated with plasma HbA1c levels. Further analysis using a lipidomic approach revealed that small, dense HDL3c particles from T2D patients with poor glycemic control displayed additional modifications of their chemical composition. In parallel, antioxidative activity of HDL3c towards oxidation of low-density lipoprotein was diminished. These findings indicate that defective functionality of small, dense HDL particles in patients with T2D is not only affected by the presence of atherogenic dyslipidemia, but also by the level of glycemic control, reflecting compositional alterations of HDL.

Metabolic alterations, HFE gene mutations and atherogenic lipoprotein modifications in patients with primary iron overload.

Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, P< 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n=7) presented a reduced ß-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, P< 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43±5; non-C282Y: 25±8; controls: 32±7%; P< 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23±5; non-C282Y: 39±10; controls: 26±4%; P< 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

CONDITIONING FACTORS FOR HIGH CARDIOVASCULAR RISK IN PATIENTS WITH CUSHING SYNDROME.

OBJECTIVE: To characterize the alterations in carbohydrate and lipoprotein metabolism, to evaluate markers of lipoprotein functionality, and to identify the presence of novel atherogenic risk factors in patients with Cushing syndrome (CS) in comparison with sex- and age-matched controls. METHODS: In an open, cross-sectional study, 32 nontreated patients with active CS were consecutively recruited from the Endocrinology Service at "José de San Martín" Clinical Hospital, University of Buenos Aires, Argentina, between April 11, 2010 and December 11, 2012. The patients were compared with sex- and age-matched controls. RESULTS: Versus controls, patients with CS presented with excess weight, central obesity, and hypercortisolism. They also exhibited an insulin-resistant state, with high resistin levels (median [interquartile range], 16 [10 to 22] ng/mL versus 6 [5 to 9] ng/mL; P<.0001), a more atherogenic lipoprotein profile, high oxidized low-density lipoprotein levels (oxLDL; mean ± SD, 100 ± 31 U/L versus 75 ± 32 U/L; P<.05) and high sensitive C-reactive protein levels (median [interquartile range], 1.2 [0.6 to 3.1] mg/L versus 0.6 [0.3 to 1.1] mg/L; P<.05), and increased leukocyte count (mean ± SD, 9.5 ± 2.6 × 10(3) cells/µL versus 6.5 ± 1.4 × 10(3) cells/µL; P<.0001). Multivariate analyses showed that the increase in waist circumference was associated with both the diagnosis of CS and the degree of insulin resistance. Resistin concentration was related to a greater extent to the diagnosis of CS than to homeostasis model assessment-insulin resistance. Triglyceride and oxLDL levels were only significantly associated with the diagnosis of CS. CONCLUSION: Hypercortisolism is related to the increase observed in triglycerides and oxLDL levels, and, in combination with insulin resistance, acts to increase waist circumference and amplify the inflammatory process, key factors for the development of cardiovascular disease.

Metabolome biomarkers linking dietary fibre intake with cardiometabolic effects: results from the Danish Diet, Cancer and Health-Next Generations MAX study.

Biomarkers associated with dietary fibre intake, as complements to traditional dietary assessment tools, may improve the understanding of its role in human health. Our aim was to discover metabolite biomarkers related to dietary fibre intake and investigate their association with cardiometabolic risk factors. We used data and samples from the Danish Diet Cancer and Health Next Generation (DCH-NG) MAX-study, a one-year observational study with evaluations at baseline, six and 12 months (n = 624, 55% female, mean age: 43 years, 1353 observations). Direct associations between fibre intake and plasma concentrations of 2,6-dihydroxybenzoic acid (2,6-DHBA) and indolepropionic acid were observed at the three time-points. Both metabolites showed an intraclass-correlation coefficient (ICC) > 0.50 and were associated with the self-reported intake of wholegrain cereals, and of fruits and vegetables, respectively. Other metabolites associated with dietary fibre intake were linolenoyl carnitine, 2-aminophenol, 3,4-DHBA, and proline betaine. Based on the metabolites associated with dietary fibre intake we calculated predicted values of fibre intake using a multivariate, machine-learning algorithm. Metabolomics-based predicted fibre, but not self-reported fibre values, showed negative associations with cardiometabolic risk factors (i.e. high sensitivity C-reactive protein, systolic and diastolic blood pressure, all FDR-adjusted p-values <0.05). Furthermore, different correlations with gut microbiota composition were observed. In conclusion, 2,6-DHBA and indolepropionic acid in plasma may better link dietary fibre intake with its metabolic effects than self-reported values. These metabolites may represent a novel class of biomarkers reflecting both dietary exposure and host and/or gut microbiota characteristics providing a read-out that is differentially related to cardiometabolic risk.

Biomarkers of Berry Intake: Systematic Review Update.

Berries are rich in (poly)phenols, and these compounds may be beneficial to human health. Estimating berry consumption through self-reported questionnaires has been challenging due to compliance issues and a lack of precision. Estimation via food-derived biomarkers in biofluids was proposed as a complementary alternative. We aimed to review and update the existing evidence on biomarkers of intake for six different types of berries. A systematic literature search was performed to update a previous systematic review on PubMed, Web of Science, and Scopus from January 2020 until December 2022. Out of 42 papers, only 18 studies were eligible. A multimetabolite panel is suggested for blueberry and cranberry intake. Proposed biomarkers for blueberries include hippuric acid and malvidin glycosides. For cranberries, suggested biomarkers are glycosides of peonidin and cyanidin together with sulfate and glucuronide conjugates of phenyl-γ-valerolactone derivatives. No new metabolite candidates have been found for raspberries, strawberries, blackcurrants, and blackberries. Further studies are encouraged to validate these multimetabolite panels for improving the estimation of berry consumption.

Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-kB dependent manner: Results from the ATTACH-study a randomized, controlled, crossover trial in healthy subjects.

Pancreatic cancer is primarily considered to be a metastatic disease with a low 5-year survival rate. We aimed to detect if plasma-isolated anthocyanins and their metabolites (PAMs) modulate pancreatic cancer cells migration and to describe molecular targets of PAMs in this process. Plasma metabolites were isolated by solid-phase extraction before and after a 28-days intervention trial involving 35 healthy subjects comparing effects of a daily anthocyanin-rich juice intake vs. placebo. Plasma extracts were used for migration and mechanistic in vitro studies as well as for metabolomic analysis. Pancreatic PANC-1 and AsPC-1 were used for migration studies in a Boyden chamber co-cultured with endothelial cells. Expression of adhesion molecules on cancer and endothelial cells were determined by flow cytometry and NF-kB (nuclear factor-kappa B) p65 and focal adhesion kinase activation were measured by immunoassays. UHPLC-MS/MS metabolomics was done in plasma and urine samples. Plasma extracts isolated after the intake of the anthocyanin-rich juice significantly reduced PANC-1 migration, but not AsPC-1 migration. In PANC-1, and to a lower extent in endothelial cells, plasma extracts after juice intake decreased the expression of ß1- and ß4-integrins and intercellular adhesion molecule-1. Pooled plasma from volunteers with the highest inhibition of PANC-1 migration (n = 10) induced a reduction of NF-kB-p65 and FAK-phosphorylation in cancer and in endothelial cells. Concerning metabolites, 14 were significantly altered by juice intervention and PANC-1 migration was inversely associated with the increase of o-coumaric acid and peonidin-3-galactoside. PAMs were associated with lower PANC-1 cell migration opening new strategies for metastatic pancreatic cancer treatment.

Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Background: Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Methods: Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Results: Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. Conclusion: In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

Dietary Sources of Anthocyanins and Their Association with Metabolome Biomarkers and Cardiometabolic Risk Factors in an Observational Study.

Anthocyanins (ACNs) are (poly)phenols associated with reduced cardiometabolic risk. Associations between dietary intake, microbial metabolism, and cardiometabolic health benefits of ACNs have not been fully characterized. Our aims were to study the association between ACN intake, considering its dietary sources, and plasma metabolites, and to relate them with cardiometabolic risk factors in an observational study. A total of 1351 samples from 624 participants (55% female, mean age: 45 ± 12 years old) enrolled in the DCH-NG MAX study were studied using a targeted metabolomic analysis. Twenty-four-hour dietary recalls were used to collect dietary data at baseline, six, and twelve months. ACN content of foods was calculated using Phenol Explorer and foods were categorized into food groups. The median intake of total ACNs was 1.6mg/day. Using mixed graphical models, ACNs from different foods showed specific associations with plasma metabolome biomarkers. Combining these results with censored regression analysis, metabolites associated with ACNs intake were: salsolinol sulfate, 4-methylcatechol sulfate, linoleoyl carnitine, 3,4-dihydroxyphenylacetic acid, and one valerolactone. Salsolinol sulfate and 4-methylcatechol sulfate, both related to the intake of ACNs mainly from berries, were inversely associated with visceral adipose tissue. In conclusion, plasma metabolome biomarkers of dietary ACNs depended on the dietary source and some of them, such as salsolinol sulfate and 4-methylcatechol sulfate may link berry intake with cardiometabolic health benefits.

Plasma metabolomic profiles of plant-based dietary indices reveal potential pathways for metabolic syndrome associations.

BACKGROUND AND AIMS: Plant-based dietary patterns have been associated with improved health outcomes. This study aims to describe the metabolomic fingerprints of plant-based diet indices (PDI) and examine their association with metabolic syndrome (MetS) and its components in a Danish population. METHODS: The MAX study comprised 676 participants (55% women, aged 18-67 y) from Copenhagen. Sociodemographic and dietary data were collected using questionnaires and three 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). Mean dietary intakes were computed, as well as overall PDI, healthful (hPDI) and unhealthful (uPDI) scores, according to food groups for each plant-based index. Clinical variables were also collected at the same time points in a health examination that included complete blood tests. MetS was defined according to the International Diabetes Federation criteria. Plasma metabolites were measured using a targeted metabolomics approach. Metabolites associated with PDI were selected using random forest models and their relationships with PDIs and MetS were analyzed using generalized linear mixed models. RESULTS: The mean prevalence of MetS was 10.8%. High, compared to low, hPDI and uPDI scores were associated with a lower and higher odd of MetS, respectively [odds ratio (95%CI); hPDI: 0.56 (0.43-0.74); uPDI: 1.61 (1.26-2.05)]. Out of 411 quantified plasma metabolites, machine-learning metabolomics fingerprinting revealed 13 metabolites, including food and food-related microbial metabolites, like hypaphorine, indolepropionic acid and lignan-derived enterolactones. These metabolites were associated with all PDIs and were inversely correlated with MetS components (p < 0.05). Furthermore, they had an explainable contribution of 12% and 14% for the association between hPDI or uPDI, respectively, and MetS only among participants with overweight/obesity. CONCLUSIONS: Metabolites associated with PDIs were inversely associated with MetS and its components, and may partially explain the effects of plant-based diets on cardiometabolic risk factors.

Association of fasting orexin-A levels with energy intake at breakfast and subsequent snack in Chilean adolescents.

Orexin-A, a hormone secreted by orexin neurons, is involved in caloric-intake regulation. Current understanding is based primarily on animal studies. Studies of orexin in humans are scarce, and to our knowledge there are no prior studies in adolescents. We studied fasting Orexin-A levels related to energy intake at breakfast and a subsequent snack in adolescents (n = 668) from a longitudinal study in Chile. Body-Mass Index (BMI), components of the metabolic syndrome and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured. Energy intake was calculated based on food weights before and after the standardized breakfast and subsequent snack. High energy intake was defined as ≥ 75th percentile. We assessed the relationship between orexin-A and high energy intake, adjusting for confounders. Higher orexin levels were associated with high breakfast energy intake (OR: 1.21; 95%CI: 0.98-1.49). Conversely, those with higher orexin levels showed a non-significant trend for lower odds of high energy intake for the snack (OR: 0.87; 95%CI: 0.70-1.07). There was a significant interaction between high breakfast energy intake and orexin levels. Those who ate more calories at breakfast displayed a lower inhibitory effect of orexin on eating at the snack (p < 0.05). There was no significant interaction between weight status and orexin. In conclusion, orexin-A levels were associated with breakfast energy intake and inversely related with subsequent snack energy intake in participants whose caloric intake at breakfast was within the normal range. Based on these findings, it appears that the association of orexin-A with energy intake depends on eating behavior.

Association of fasting Orexin-A levels with energy intake at breakfast and subsequent snack in Chilean adolescents.

Orexin-A, a hormone secreted by orexin neurons, is involved in caloric-intake regulation. Current understanding is based primarily on animal studies. Studies of orexin in humans are scarce, and to our knowledge there are no prior studies in adolescents. We studied fasting Orexin-A levels related to energy intake at breakfast and a subsequent snack in adolescents (n = 668) from a longitudinal study in Chile. Body-Mass Index (BMI), components of the metabolic syndrome and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured. Energy intake was calculated based on food weights before and after the standardized breakfast and subsequent snack. High energy intake was defined as ≥ 75th percentile. We assessed the relationship between orexin-A and high energy intake, adjusting for confounders. Higher orexin levels were associated with high breakfast energy intake (OR: 1.21; 95%CI: 0.98-1.49). Conversely, those with higher orexin levels showed a non-significant trend for lower odds of high energy intake for the snack (OR: 0.87; 95%CI: 0.70-1.07). There was a significant interaction between high breakfast energy intake and orexin levels. Those who ate more calories at breakfast displayed a lower inhibitory effect of orexin on eating at the snack (p < 0.05). There was no significant interaction between weight status and orexin. In conclusion, orexin-A levels were associated with breakfast energy intake and inversely related with subsequent snack energy intake in participants whose caloric intake at breakfast was within the normal range. Based on these findings, it appears that the association of orexin-A with energy intake depends on eating behavior.

Animal Protein Intake Is Inversely Associated With Mortality in Older Adults: The InCHIANTI Study.

BACKGROUND: In general, plant protein intake was inversely associated with mortality in studies in middle-aged adults. Our aim was to evaluate the long-term associations of animal and plant protein intake with mortality in older adults. METHODS: A prospective cohort study including 1 139 community-dwelling older adults (mean age 75 years, 56% women) living in Tuscany, Italy, followed for 20 years (InCHIANTI study) was analyzed. Dietary intake by food frequency questionnaires and clinical information were assessed 5 times during the follow-up. Protein intakes were expressed as percentages of total energy. Time-dependent Cox regression models adjusted for confounders were used to assess the association between plant and animal protein intake, and mortality. RESULTS: During the 20 years of follow-up (mean: 12 years), 811 deaths occurred (292 of cardiovascular- and 151 of cancer-related causes). Animal protein intake was inversely associated with all-cause (hazard ratio [HR] per 1% of total energy from protein increase, 95% confidence interval [CI]: 0.96, 0.93-0.99) and cardiovascular mortality (HR per 1% of total energy from protein increase, 95% CI: 0.93, 0.87-0.98). Plant protein intake showed no association with any of the mortality outcomes, but an interaction with baseline hypertension was found for all-cause and cardiovascular mortality (p < .05). CONCLUSIONS: Animal protein was inversely associated with all-cause and cardiovascular mortality in older adults. Further studies are needed to provide recommendations on dietary protein intake for older adults.