Dietary fat, telomere length and cognitive function: unravelling the complex relations.

PURPOSE OF REVIEW: The review aims to explore the recent evidence on the associations between different dietary fat intake and cognitive function, and to understand the role of telomere length in this relationship. RECENT FINDINGS: Clinical and preclinical studies included in this review suggest that dietary fat intake is associated with cognitive function and telomere length. High intake of saturated fats and trans fats, commonly found in ultra-processed foods, appears to have negative effects on cognitive function and telomere length, while other dietary fats, such as omega-3 polyunsaturated fatty acids and monounsaturated fatty acids are associated with improved cognitive performance and reduced telomere attrition. Controversial results related to omega-6 polyunsaturated fatty acids intake and its impact on cognitive function were found. Dietary fats may affect telomere length and cognition through oxidative stress, inflammation, and insulin resistance. SUMMARY: The current review illustrated the relationship between dietary fat and cognitive function by focusing on the role of telomere length as a potential intermediator. More future studies are required, however, in order to develop targeted interventions aimed at preserving cognitive well-being throughout life.

Cross-Sectional Associations between HDL Structure or Function, Cell Membrane Fatty Acid Composition, and Inflammation in Elderly Adults.

BACKGROUND: Cell membrane fatty acid composition has been related to inflammation and cardiovascular disease (CVD) risk. Dysregulation of HDL function is also considered a CVD risk factor. OBJECTIVES: We aimed to investigate whether the content of cell membrane fatty acids and HDL functionality are linked to each other as well as to inflammation. METHODS: This cross-sectional analysis involved 259 participants (mean age: 67.9 y) with overweight/obesity (mean BMI: 29.5 kg/m2) from a coronary artery disease case-control study nested within the PREDIMED (PREvención con DIeta MEDiterránea) trial for which HDL functional parameters [apoA-I, apoA-IV, and apoC-III; cholesterol efflux capacity (CEC); HDL oxidative inflammatory index (HOII); sphingosine-1-phosphate (S1P); serum amyloid A (SAA); and complement-3 (C3) protein] were quantified. We also assessed 22 fatty acids in blood cell membranes using GC and inflammatory markers (IFN-γ and IL-1b, IL-6, IL-8, and IL-10) in serum. Associations of HDL-related variables with cell membrane fatty acids and with inflammatory markers were assessed using multivariable linear regression analyses with elastic net penalty. RESULTS: ApoA-I, apoC-III, CEC, HOII, S1P, and SAA, but not apoA-IV and C3 protein, were associated with membrane fatty acids. S1P and SAA were directly associated with IL-6, whereas apoA-I and C3 protein showed inverse associations with IL-6. Specific fatty acids including myristic acid (14:0) and long-chain n-6 fatty acids being negatively and positively associated with IL-8, respectively, were also found to be positively associated with SAA. CONCLUSIONS: This study suggests interrelations between indicators of inflammation and both blood cell membrane fatty acid composition and HDL structure/functional parameters in a Mediterranean population at high CVD risk.This trial was registered at www.isrctn.com as ISRCTN35739639.

Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study.

BACKGROUND: Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. METHODS: Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. RESULTS: After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. CONCLUSIONS: Our findings support the role of the choline metabolic pathway in the pathogenesis of AF and HF.

Plasma Metabolomic Profiles of Glycemic Index, Glycemic Load, and Carbohydrate Quality Index in the PREDIMED Study.

BACKGROUND: The quality of carbohydrate consumed, assessed by the glycemic index (GI), glycemic load (GL), or carbohydrate quality index (CQI), affects the postprandial glycemic and insulinemic responses, which have been implicated in the etiology of several chronic diseases. However, it is unclear whether plasma metabolites involved in different biological pathways could provide functional insights into the role of carbohydrate quality indices in health. OBJECTIVES: We aimed to identify plasma metabolomic profiles associated with dietary GI, GL, and CQI. METHODS: The present study is a cross-sectional analysis of 1833 participants with overweight/obesity (mean age = 67 y) from 2 case-cohort studies nested within the PREDIMED (Prevención con Dieta Mediterránea) trial. Data extracted from validated FFQs were used to estimate the GI, GL, and CQI. Plasma concentrations of 385 metabolites were profiled with LC coupled to MS and associations of these metabolites with those indices were assessed with elastic net regression analyses. RESULTS: A total of 58, 18, and 57 metabolites were selected for GI, GL, and CQI, respectively. Choline, cotinine, γ-butyrobetaine, and 36:3 phosphatidylserine plasmalogen were positively associated with GI and GL, whereas they were negatively associated with CQI. Fructose-glucose-galactose was negatively and positively associated with GI/GL and CQI, respectively. Consistent associations of 21 metabolites with both GI and CQI were found but in opposite directions. Negative associations of kynurenic acid, 22:1 sphingomyelin, and 38:6 phosphatidylethanolamine, as well as positive associations of 32:1 phosphatidylcholine with GI and GL were also observed. Pearson correlation coefficients between GI, GL, and CQI and the metabolomic profiles were 0.30, 0.22, and 0.27, respectively. CONCLUSIONS: The GI, GL, and CQI were associated with specific metabolomic profiles in a Mediterranean population at high cardiovascular disease risk. Our findings may help in understanding the role of dietary carbohydrate indices in the development of cardiometabolic disorders. This trial was registered at isrctn.com as ISRCTN35739639.

High sleep variability predicts a blunted weight loss response and short sleep duration a reduced decrease in waist circumference in the PREDIMED-Plus Trial.

BACKGROUND: Whether short sleep duration or high sleep variability may predict less weight loss and reduction in measures of adiposity in response to lifestyle interventions is unknown. The aim of this study was to compare the 12-month changes in weight and adiposity measures between those participants with short or adequate sleep duration and those with low or high sleep variability (intra-subject standard deviation of the sleep duration) in PREvención con DIeta MEDiterránea (PREDIMED)-Plus, a primary prevention trial based on lifestyle intervention programs. METHODS: Prospective analysis of 1986 community-dwelling subjects (mean age 65 years, 47% females) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus trial was conducted. Accelerometry-derived sleep duration and sleep variability and changes in average weight, body mass index (BMI), and waist circumference (WC) attained after 12-month interventions were analyzed. RESULTS: The adjusted difference in 12-month changes in weight and BMI in participants in the third tertile of sleep variability was 0.5 kg (95% CI 0.1 to 0.9; p = 0.021) and 0.2 kg/m2 (0.04 to 0.4; p = 0.015), respectively, as compared with participants in the first tertile. The adjusted difference in 12-month changes from baseline in WC was -0.8 cm (-1.5 to -0.01; p = 0.048) in participants sleeping <6 h, compared with those sleeping between 7 and 9 h. CONCLUSIONS: Our findings suggest that the less variability in sleep duration or an adequate sleep duration the greater the success of the lifestyle interventions in adiposity.

High Plasma Glutamate and a Low Glutamine-to-Glutamate Ratio Are Associated with Increased Risk of Heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study.

BACKGROUND: Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown. OBJECTIVES: We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk. METHODS: The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC-tandem MS. ORs were estimated with multivariable conditional logistic regression models. RESULTS: In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed. CONCLUSIONS: Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribute to the development of HF in Mediterranean individuals at high CVD risk.This trial was registered at www.isrctn.com as ISRCTN35739639.

Association Between Fatty Acids of Blood Cell Membranes and Incidence of Coronary Heart Disease.

Objective- To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk. Approach and Results- This is a case-control study nested in the PREDIMED trial (Prevención con Dieta Mediterránea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. After adjustment for classical CHD risk factors and multiple testing, 1 SD increase in baseline levels of C22:0, C24:0 and the sum of individual very long chain saturated fatty acids was associated with 56% (OR, 0.44 [95% CI, 0.28-0.69]), 59% (OR, 0.41 [95% CI, 0.25-0.65]), and 55% (OR, 0.45 [95% CI, 0.29-0.70]) a decreased odds of developing CHD, respectively. Baseline C20:1n9 was associated with higher odds of CHD (OR, 1.58 [95% CI, 1.25-2.00]). Conclusions- Higher levels of C22:0 and C24:0 were associated with a lower CHD incidence, whereas higher levels of C20:1n9 were associated with a higher risk. This study adds to the growing body of evidence suggesting potential differences in the cardiovascular disease effects of different types of circulating saturated fatty acids.

Comparing eating behaviours, and symptoms of depression and anxiety between Spain and Greece during the COVID-19 outbreak: Cross-sectional analysis of two different confinement strategies.

OBJECTIVE: We compared eating behaviours, and depressive and anxiety symptoms in two countries with different confinement strictness strategies and different levels of COVID-19 pandemic. METHOD: A web-based cross-sectional survey was administered during and shortly after the COVID-19 related lockdown in Spain and Greece. Multivariable linear regression analyses were performed to identify country differences associated with eating behaviour, and symptoms of depression and anxiety. RESULTS: This study included 1,002 responders in Spain and 839 in Greece. The mean ± SD of restraint, emotional and external eating was 2.5 ± 0.79, 2.1 ± 0.81 and 2.6 ± 0.65 in Spain, whereas 2.7 ± 0.85, 2.3 ± 0.99 and 2.9 ± 0.74 in Greece. Spanish participants had lower average scores of restraint and external eating compared to Greek participants (p < .001), but no difference was seen for emotional eating. In Spain, 13.6%, and 12.3% of the survey respondents reported moderate to severe depressive and anxiety symptoms, respectively, whereas in Greece the respective values were 18.8 and 13.2%. After adjusting for several risk factors, a higher prevalence of anxiety symptoms was observed in Spain compared to Greece (p = .001), but no difference was seen for depressive symptoms. CONCLUSIONS: This study demonstrated high scores of inappropriate eating behaviours and a high frequency of depressive and anxiety symptoms in two Mediterranean countries during the COVID-19 outbreak. Our findings revealed that compared to Greek participants, Spanish participants, that faced more severe COVID-19 pandemic and stricter lockdown measures, were associated with lower restraint and external eating and increased anxiety symptoms, but not with depressive symptoms or emotional eating.

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial.

The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year changes in arginine (adjusted hazard ratio [HR] per SD 0.68, 95% confidence interval [CI] 0.49, 0.95; Q4 vs. Q1 0.46, 95% CI 0.21, 1.04; P trend = 0.02) and arginine/ADMA ratio (adjusted HR per SD 0.73, 95% CI 0.51, 1.04; Q4 vs. Q1 0.52, 95% CI 0.22, 1.25; P trend = 0.04) were associated with a lower risk of T2D. Positive changes of citrulline and ornithine, and negative changes in SDMA and arginine/(ornithine + citrulline) were associated with concurrent 1-year changes in homeostatic model assessment of insulin resistance. Individuals in the low-fat-diet group had a higher risk of T2D for 1-year changes in NMMA than individuals in Mediterranean-diet groups (P interaction = 0.02). We conclude that arginine bioavailability is important in T2D pathophysiology.

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study.

BACKGROUND: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. METHODS: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. RESULTS: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). CONCLUSIONS: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

High plasma glutamate and low glutamine-to-glutamate ratio are associated with type 2 diabetes: Case-cohort study within the PREDIMED trial.

BACKGROUND AND AIMS: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). METHODS AND RESULTS: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95% CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). CONCLUSION: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639.

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial.

AIMS/HYPOTHESIS: Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial. METHODS: We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvención con DIeta MEDiterránea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n = 273), a MedDiet+nuts (n = 324) or a control diet (n = 295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial. RESULTS: Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend = 0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD = 1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p = 0.005 vs the control group). CONCLUSIONS/INTERPRETATION: Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence. Clinical trial number: SRCTN35739639 ( www.controlled-trials.com ).

Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case-Cohort Study.

BACKGROUND: Metabolites of the tryptophan-kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case-cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS: Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS: Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04-1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09-1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS: Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity.

Seven Countries Study cohort in Crete, Greece: gluteal adipose-tissue fatty-acid profiles of survivors, at 2010.

OBJECTIVE: To analyse the gluteal adipose-tissue fatty-acid profiles from Cretan cohort survivors of the Seven Countries Study (SCS) at 2010 and to compare them with those of survivors assessed in 2000, as well as with literature data on male Cretans at 1965. DESIGN: We analysed data concerning the gluteal adipose-tissue fatty acids (analysed by GC) from three studies. SETTING: The island of Crete (rural areas and the city of Heraklion). SUBJECTS: Twenty-two of the 2010 SCS survivors aged 90 years and over; seventy-eight men aged 80 years of the 2000 SCS survivors; and 280 men assessed in 1965. RESULTS: In comparison to 1965 and 2000, the SCS survivors in 2010 had a higher amount of 18:1n-9 (P<0·05) in their gluteal adipose tissue and a lower amount of PUFA (P<0·05). On the other hand, a constant decrease in adipose-tissue 14:1n-5 and 16:1n-7 was recorded between 1965 and 2010 (P<0·001), and between 2000 and 2010 (P<0·05), while 18:2n-6 appeared to decrease between the 1965 and 2010 assessments (P<0·001). CONCLUSIONS: Comparison with a 1965 representative Cretan sample and 2000 SCS survivors indicated an increased concentration of oleic acid (known for its protective role against mortality) and a decreased concentration of PUFA (known for their susceptibility to oxidation) in our surviving sample at 2010. These changes may reflect internal physiological processes due to diet change within these years and/or ageing.

Female sex, small size at birth and low family income increase the likelihood of insulin resistance in late childhood: the Healthy Growth Study.

OBJECTIVE: To identify among a wide range of perinatal indices, as well as certain family sociodemographic and parental characteristics, those independently associated with insulin resistance (IR) in late childhood. METHODS: A representative sample of 2195 Greek schoolchildren, aged 9-13 yr, was examined, and based on the biochemical indices collected IR was estimated using the homeostasis model assessment (HOMA-IR < 3.16). Perinatal data were recorded from children's medical records, retrospectively, while family sociodemographics and parental anthropometrics were reported by parents. RESULTS: The overall prevalence of IR was 28.4%, with a higher prevalence observed for girls compared with boys (p <0.05). Examination of univariate associations, per se, showed that maternal current and pre-pregnancy overweight/obesity, maternal smoking at early pregnancy, children's small birth weight, and rapid growth at infancy as well as female sex and non-Caucasian race increased the likelihood of IR. In contrast, folate supplementation during pregnancy, as well as higher paternal education and annual family income decreased the likelihood of IR in children. Inclusion of all above variables at a multivariable regression model highlighted female sex [odds ratios (OR): 1.67, 95% confidence intervals (CI): 1.30-2.13], small birth weight (OR: 1.41, 95% CI: 1.03-2.01), and higher annual family income (OR: 0.71, 95% CI: 0.53-0.95 for 12 000-30 000 € and OR: 0.68, 95% CI: 0.48-0.96 for >30 000 €) as the only significant correlates of IR after also controlling for children's body mass index (BMI) and Tanner stage. CONCLUSIONS: The current study highlighted small birth weight and female sex as the only perinatal factors independently associated with the occurrence of IR in late childhood, when examined at a multivariable level with a wide range of perinatal indices as well as certain family sociodemographic and parental characteristics.

Identification of lifestyle patterns associated with obesity and fat mass in children: the Healthy Growth Study.

OBJECTIVE: To investigate possible associations of lifestyle patterns with obesity and fat mass in children. DESIGN: Cross-sectional epidemiological study. Principal component analysis was used to identify lifestyle patterns. SETTING: Primary schools from four regions in Greece. SUBJECTS: A total of 2073 schoolchildren (aged 9-13 years). RESULTS: Children in the fourth quartile of the lifestyle pattern combining higher dairy foods with more adequate breakfast consumption were 39·4%, 45·2% and 32·2% less likely to be overweight/obese and in the highest quartile of sum of skinfold thicknesses and fat mass, respectively, than children in the first quartile of this pattern. Similarly, children in the fourth quartile of a lifestyle pattern comprising consumption of high-fibre foods, such as fruits, vegetables and wholegrain products, were 27·4% less likely to be in the highest quartile of sum of skinfold thicknesses than children in the first lifestyle pattern quartile. Finally, children in the fourth quartile of a lifestyle pattern characterized by more time spent on moderate-to-vigorous physical activity and more frequent meals were 38·0%, 26·3% and 29·5% less likely to be overweight, centrally obese and in the highest quartile of fat mass, respectively, than their peers in the first quartile of this lifestyle pattern (all P < 0·05). CONCLUSIONS: The current study identified three lifestyle patterns (i.e. one pattern comprising higher dairy consumption with a more adequate breakfast; a second pattern characterized by increased consumption of high-fibre foods; and a third pattern combining higher physical activity levels with more frequent meals), which were all related with lower odds of obesity and/or increased fat mass levels. From a public health perspective, promotion of these patterns among children and their families should be considered as one of the components of any childhood obesity preventive initiative.

The effects of an exercise program on inflammation in adults who differ according to obstructive sleep apnea severity.

Exercise improves chronic inflammation and is recommended as a first-line medical or behavioral treatment for OSA with obesity. We examined whether the effects of an exercise program on inflammatory blood markers differed according to severity of OSA among obese adults. Overweight (BMI > 27 kg/m2) adults were evaluated for OSA using overnight polysomnography and subsequently classified as exhibiting no-to-mild OSA (AHI < 15 events/hour) or moderate-to-severe OSA (AHI ≥ 15 events/hour). Cardiorespiratory fitness, body composition assessed by DXA, fasting metabolic parameters and adipokines (i.e., glucose, insulin, leptin and adioponectin), and multiple markers of inflammation (i.e., CRP, IL-4, IL-8 and TNF-α) were measured at baseline (Pre) and following a 6-week (3 days per week) comprehensive exercise program (Post). Ten adults (Age: 48 ± 8 years; W:6; M:4) with no/mild OSA and 12 adults (Age: 54 ± 8 years; W:5; M:7) with moderate/severe OSA completed all aspects of the trial. No significant differences in age, cardiorespiratory fitness, body composition, fasting metabolic parameters and most inflammatory markers were observed between groups at baseline. Exercise training decreased total fat mass (Pre: 41,167 ± 13,315 g; Post: 40,311 ± 12,657 g; p = 0.008), leptin (Pre: 26.7 ± 29.6 pg/ml; Post: 22.7 ± 19.4 pg/ml; p = 0.028) and adiponectin (Pre: 16.6 ± 10.9 µg/ml; Post: 11.0 ± 10.6 µg/ml; p = 0.004) in those with moderate/severe OSA. Among those with no/mild OSA, exercise training resulted in a decrease in total fat mass (Pre = 37,332 ± 20,258 g; Post: 37,068 ± 18,268 g, p = 0.037). These data suggest that while 6 weeks of exercise reduced adipokines in those with moderate-to-severe OSA, it was not sufficient to improve common markers of inflammation among overweight adults with OSA.

Dietary Glycemic Index and Load and Semen Quality: A Cross-Sectional and Prospective Analysis within the FERTINUTS Trial.

PURPOSE: Infertility is a global health issue and nutrition plays a significant role in fertility outcomes. We aimed to investigate the cross-sectional and prospective associations of glycemic index (GI) and glycemic load (GL) with semen quality parameters in a cohort of healthy young men. MATERIALS AND METHODS: The study included 106 men aged 18-35 years from the FERTINUTS trial. Dietary intake was estimated through 3-day dietary records and several semen parameters were assessed. Multivariable linear regression analysis with the Least Absolute Shrinkage and Selection Operator (LASSO) approach was employed. RESULTS: The cross-sectional analysis revealed positive associations between GI and GL and total sperm count, sperm concentration, and total motility. In the prospective analysis, baseline GI was associated with increases in pH, vitality, immotile sperm or abnormal midpiece and decreases in total sperm count and motility. Conversely, GL was positively associated with changes in vitality and total sperm count. CONCLUSIONS: While these findings suggest that GI may have adverse effects on several sperm quality parameters, the results were not consistently observed in the cross-sectional analysis. However, GL was consistently associated with better sperm quality in both analyses. The impact of carbohydrate quality and quantity on fertility remains uncertain and larger prospective studies are needed.

Bile Acids and Risk of Adverse Cardiovascular Events and All-Cause Mortality in Patients with Acute Coronary Syndrome.

The relationship between bile acids (BAs) and adverse cardiovascular events following acute coronary syndrome (ACS) have been little investigated. We aimed to examine the associations of BAs with the risk of cardiovascular events and all-cause mortality in ACS. We conducted a prospective study on 309 ACS patients who were followed for 10 years. Plasma BAs were quantified by liquid chromatography coupled to tandem mass spectrometry. Cox regression analyses with elastic net penalties were performed to associate BAs with MACE and all-cause mortality. Weighted scores were computed using the 100 iterated coefficients corresponding to each selected BA, and the associations of these scores with these adverse outcomes were assessed using multivariable Cox regression models. A panel of 10 BAs was significantly associated with the increased risk of MACE. The hazard ratio of MACE per SD increase in the estimated BA score was 1.35 (95% CI 1.12-1.63). Furthermore, four BAs were selected from the elastic net model for all-cause mortality, although their weighted score was not independently associated with mortality. Our findings indicate that primary and secondary BAs may play a significant role in the development of MACE. This insight holds potential for developing strategies to manage ACS and prevent adverse outcomes.

Exploring small non-coding RNAs as blood-based biomarkers to predict Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) diagnosis relies on clinical symptoms complemented with biological biomarkers, the Amyloid Tau Neurodegeneration (ATN) framework. Small non-coding RNA (sncRNA) in the blood have emerged as potential predictors of AD. We identified sncRNA signatures specific to ATN and AD, and evaluated both their contribution to improving AD conversion prediction beyond ATN alone. METHODS: This nested case-control study was conducted within the ACE cohort and included MCI patients matched by sex. Patients free of type 2 diabetes underwent cerebrospinal fluid (CSF) and plasma collection and were followed-up for a median of 2.45-years. Plasma sncRNAs were profiled using small RNA-sequencing. Conditional logistic and Cox regression analyses with elastic net penalties were performed to identify sncRNA signatures for A+(T|N)+ and AD. Weighted scores were computed using cross-validation, and the association of these scores with AD risk was assessed using multivariable Cox regression models. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) enrichment analysis of the identified signatures were performed. RESULTS: The study sample consisted of 192 patients, including 96 A+(T|N)+ and 96 A-T-N- patients. We constructed a classification model based on a 6-miRNAs signature for ATN. The model could classify MCI patients into A-T-N- and A+(T|N)+ groups with an area under the curve of 0.7335 (95% CI, 0.7327 to 0.7342). However, the addition of the model to conventional risk factors did not improve the prediction of AD beyond the conventional model plus ATN status (C-statistic: 0.805 [95% CI, 0.758 to 0.852] compared to 0.829 [95% CI, 0.786, 0.872]). The AD-related 15-sncRNAs signature exhibited better predictive performance than the conventional model plus ATN status (C-statistic: 0.849 [95% CI, 0.808 to 0.890]). When ATN was included in this model, the prediction further improved to 0.875 (95% CI, 0.840 to 0.910). The miRNA-target interaction network and functional analysis, including GO and KEGG pathway enrichment analysis, suggested that the miRNAs in both signatures are involved in neuronal pathways associated with AD. CONCLUSIONS: The AD-related sncRNA signature holds promise in predicting AD conversion, providing insights into early AD development and potential targets for prevention.