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1.
PLoS Biol ; 17(10): e3000443, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626640

RESUMO

Obesity is associated with changes in the plasma lipids. Although simple lipid quantification is routinely used, plasma lipids are rarely investigated at the level of individual molecules. We aimed at predicting different measures of obesity based on the plasma lipidome in a large population cohort using advanced machine learning modeling. A total of 1,061 participants of the FINRISK 2012 population cohort were randomly chosen, and the levels of 183 plasma lipid species were measured in a novel mass spectrometric shotgun approach. Multiple machine intelligence models were trained to predict obesity estimates, i.e., body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and body fat percentage (BFP), and validated in 250 randomly chosen participants of the Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC). Comparison of the different models revealed that the lipidome predicted BFP the best (R2 = 0.73), based on a Lasso model. In this model, the strongest positive and the strongest negative predictor were sphingomyelin molecules, which differ by only 1 double bond, implying the involvement of an unknown desaturase in obesity-related aberrations of lipid metabolism. Moreover, we used this regression to probe the clinically relevant information contained in the plasma lipidome and found that the plasma lipidome also contains information about body fat distribution, because WHR (R2 = 0.65) was predicted more accurately than BMI (R2 = 0.47). These modeling results required full resolution of the lipidome to lipid species level, and the predicting set of biomarkers had to be sufficiently large. The power of the lipidomics association was demonstrated by the finding that the addition of routine clinical laboratory variables, e.g., high-density lipoprotein (HDL)- or low-density lipoprotein (LDL)- cholesterol did not improve the model further. Correlation analyses of the individual lipid species, controlled for age and separated by sex, underscores the multiparametric and lipid species-specific nature of the correlation with the BFP. Lipidomic measurements in combination with machine intelligence modeling contain rich information about body fat amount and distribution beyond traditional clinical assays.

2.
PLoS One ; 14(10): e0223692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644575

RESUMO

BACKGROUND: GlycA is a nuclear magnetic resonance (NMR) spectroscopy biomarker that predicts risk of disease from myriad causes. It is heterogeneous; arising from five circulating glycoproteins with dynamic concentrations: alpha-1 antitrypsin (AAT), alpha-1-acid glycoprotein (AGP), haptoglobin (HP), transferrin (TF), and alpha-1-antichymotrypsin (AACT). The contributions of each glycoprotein to the disease and mortality risks predicted by GlycA remain unknown. METHODS: We trained imputation models for AAT, AGP, HP, and TF from NMR metabolite measurements in 626 adults from a population cohort with matched NMR and immunoassay data. Levels of AAT, AGP, and HP were estimated in 11,861 adults from two population cohorts with eight years of follow-up, then each biomarker was tested for association with all common endpoints. Whole blood gene expression data was used to identify cellular processes associated with elevated AAT. RESULTS: Accurate imputation models were obtained for AAT, AGP, and HP but not for TF. While AGP had the strongest correlation with GlycA, our analysis revealed variation in imputed AAT levels was the most predictive of morbidity and mortality for the widest range of diseases over the eight year follow-up period, including heart failure (meta-analysis hazard ratio = 1.60 per standard deviation increase of AAT, P-value = 1×10-10), influenza and pneumonia (HR = 1.37, P = 6×10-10), and liver diseases (HR = 1.81, P = 1×10-6). Transcriptional analyses revealed association of elevated AAT with diverse inflammatory immune pathways. CONCLUSIONS: This study clarifies the molecular underpinnings of the GlycA biomarker's associated disease risk, and indicates a previously unrecognised association between elevated AAT and severe disease onset and mortality.

3.
Nutrients ; 11(8)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382439

RESUMO

Dieting attempts have become popular worldwide. Dieting, however, seems to have both positive and negative health-related consequences. So far, only a few studies have focused on the determinants of dieting in detail. This study explores the association between self-report dieting attempts and intentional weight loss (IWL) during the previous year and several demographic, lifestyle, health, and psychological factors in a cross-sectional study design using data from the representative Finnish Health 2000 Survey. The sample comprised 2147 men and 2378 women, aged 30-69. Information for potential determinants was assembled via health examinations, interviews, and questionnaires. Approximately 24% of the men and 39% of the women reported dieting attempts and 10% of the men and 15% of the women reported IWL. Dieting attempts were associated with younger age, education, BMI, formerly smoking, more favourable values in lifestyle variables, and unfavorable values in serum HDL and triglycerides, a worse sense of coherence, concerns about one's appearance, and concerns about one's health. Among men, diabetics and those sleeping ≤6 h a night more frequently reported dieting attempts and those with osteoarthritis reported IWL. Moreover, the gradient between BMI and dieting attempts was significantly stronger in men than in women. Men seem to attempt dieting when they have actual health-related reasons, while such reasons are not so strongly associated with dieting in women. These findings can be used for determining subpopulations with obesity and real weight-loss needs and, alternatively, subpopulations with normal weight unnecessarily attempting dieting.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31255807

RESUMO

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the major causes for nonviral liver cirrhosis in the population. Whereas the typical NAFLD patient is one with abdominal obesity, metabolic syndrome (MetS), and no or minimal alcohol use, the patient with pure alcoholic liver cirrhosis has, according to cohort studies, typically consumed >5-10 daily alcohol drinks for several years.1 However, both alcohol use and components of the MetS are continuous variables and, as such, not dichotomic. Recent evidence suggests harmful synergistic effects of obesity, MetS, and alcohol intake for the risk of future liver disease.2 Consequently, given an increasing population prevalence of overweight and obese alcohol users, expectedly, there will be many patients that do not fit either the typical NAFLD or typical ALD phenotype, but share features of both disease entities. Current case-finding strategies focusing on either pure NAFLD or pure ALD3,4 may underestimate the true risk in individuals who will develop liver disease as the result of interaction between alcohol and metabolic disorders.1.

5.
Hepatology ; 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31323122

RESUMO

BACKGROUND AND AIMS: The effects of alcohol use in nonalcoholic fatty liver disease are unclear. We investigated the impact of alcohol use in fatty liver disease on incident liver, cardiovascular, and malignant disease, as well as death. APPROACH AND RESULTS: Our study comprised 8,345 persons with hepatic steatosis (fatty liver index >60) who participated in health-examination surveys (FINRISK 1992-2012 or Health 2000), with available data on baseline alcohol intake. Main exclusions were baseline clinical liver disease, viral hepatitis, ethanol intake >50 g/day, and current abstainers. Data were linked with national registers for hospital admissions, malignancies, and death regarding liver, cardiovascular, and malignant disease, as well as all-cause death. Adjustment were for multiple confounders. Alcohol consumption showed a dose-dependent risk increase for incident advanced liver disease and malignancies. Consuming 10-19 g/day of alcohol in general or 0-9 g/day as nonwine beverages doubled the risk for advanced liver disease compared to lifetime abstainers. In contrast, alcohol intake up to 49 g/day was associated with a 22%-40% reduction of incident cardiovascular disease (CVD). We observed a J-shaped association between alcohol intake and all-cause death with a maximal risk reduction of 21% (95% confidence interval, 5%-34%) at alcohol intake of 0-9 g/day compared to lifetime abstainers. However, these benefits on CVD and mortality were only observed in never smokers. Alcohol intake >30 g/day yielded increased risk estimates for mortality compared to lifetime abstainers. In a subpopulation with longitudinal data, alcohol intake remained stable over time in >80% of subjects. CONCLUSIONS: Even low alcohol intake in fatty liver disease is associated with increased risks for advanced liver disease and cancer. Low to moderate alcohol use is associated with reduced mortality and CVD risk but only among never smokers.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31260143

RESUMO

BACKGROUND AND AIM: Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. METHODS: Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41 260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. RESULTS: A total of 355 liver events occurred during the mean 12.4-year follow-up (511 789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P = 0.0083 for men; HR 1.04, P = 0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P = 0.0006 for men; HR 1.58, P = 0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P = 0.024 for men; HR 2.7, P = 0.0109 for women), and weekly binge drinking (HR 2.4, P = 0.0024 for men; HR 7.4, P < 0.0001 for women) predicted development of severe liver disease. Among men, diabetes (HR 2.7, P = 0.0002), average alcohol consumption (HR for 10 g/day 1.1, P = 0.0022), non-married status (HR 1.9, P = 0.0397 for single; HR 2.4, P = 0.0002 for widowed/separated), and serum high-density lipoprotein (HR 2.2, P = 0.0022) and non-high-density lipoprotein cholesterol (HR 1.2, P = 0.0237) were additional risk factors. Alcohol intake increased the risk especially among persons with high WHR (P for interaction 0.009). CONCLUSIONS: Age, patatin-like phospholipase-containing domain 3 haplotype, and WHR increase the risk for development of severe liver disease. We found strong synergism between alcohol and central obesity. Binge drinking is an additional risk factor.

7.
Am J Clin Nutr ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31161197

RESUMO

BACKGROUND: Food neophobia is considered a behavioral trait closely linked to adverse eating patterns and reduced dietary quality, which have been associated with increased risk of obesity and noncommunicable diseases. OBJECTIVES: In a cross-sectional and prospective study, we examined how food neophobia is associated with dietary quality, health-related biomarkers, and disease outcome incidence in Finnish and Estonian adult populations. METHODS: The study was conducted based on subsamples of the Finnish DIetary, Lifestyle, and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) cohort (n = 2982; age range: 25-74 y) and the Estonian Biobank cohort (n = 1109; age range: 18-83 y). The level of food neophobia was assessed using the Food Neophobia Scale, dietary quality was evaluated using the Baltic Sea Diet Score (BSDS), and biomarker profiles were determined using an NMR metabolomics platform. Disease outcome information was gathered from national health registries. Follow-up data on the NMR-based metabolomic profiles and disease outcomes were available in both populations. RESULTS: Food neophobia associated significantly (adjusted P < 0.05) with health-related biomarkers [e.g., ω-3 (n-3) fatty acids, citrate, α1-acid glycoprotein, HDL, and MUFA] in the Finnish DILGOM cohort. The significant negative association between the severity of food neophobia and ω-3 fatty acids was replicated in all cross-sectional analyses in the Finnish DILGOM and Estonian Biobank cohorts. Furthermore, food neophobia was associated with reduced dietary quality (BSDS: ß: -0.03 ± 0.006; P = 8.04 × 10-5), increased fasting serum insulin (ß: 0.004 ± 0.0013; P = 5.83 × 10-3), and increased risk of type 2 diabetes during the ∼8-y follow-up (HR: 1.018 ± 0.007; P = 0.01) in the DILGOM cohort. CONCLUSIONS: In the Finnish and Estonian adult populations, food neophobia was associated with adverse alteration of health-related biomarkers and risk factors that have been associated with an increased risk of noncommunicable diseases. We also found that food neophobia associations with ω-3 fatty acids and associated metabolites are mediated through dietary quality independent of body weight.

8.
Circ Res ; 125(1): 29-40, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31219752

RESUMO

RATIONALE: Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted. OBJECTIVE: Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations. METHODS AND RESULTS: We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and ß-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001), and significantly decreased mortality from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, and other causes, with risk reductions from 17% to 47% for the highest versus lowest quintile. The α-tocopherol association with overall mortality was similar across subgroups of smoking intensity, years of smoking, alcohol consumption, trial supplementation, and duration of follow-up. The association was, however, significantly modified by baseline age and body mass index, with stronger inverse associations for younger men and men with a lower body mass index ( Pinteraction≤0.006). CONCLUSIONS: In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.

9.
Endocrinology ; 160(7): 1731-1742, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125048

RESUMO

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age- and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied proton nuclear magnetic resonance-based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits: glutamine (P = 0.011) and histidine (P = 0.012), with Westfall-Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of glutamine and a 2.2-fold increased risk for the lowest 20% of histidine. Stratification by time to diagnosis suggested glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and histidine in a process closer to the actual onset (<2 years). Our data did not support the branched-chain amino acids identified earlier in several US cohorts as potential biomarkers for pancreatic cancer. Thus, although we identified glutamine and histidine as potential biomarkers of biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers.

10.
Int J Cancer ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.

11.
J Natl Cancer Inst ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077299

RESUMO

BACKGROUND: Epidemiologic data are inconsistent regarding the vitamin E-lung cancer association, and no study has examined serologic changes in vitamin E status in relation to subsequent risk. METHODS: In a cohort of 22,781 male smokers in the ATBC Study, we ascertained 3,184 lung cancer cases during up to 28 years of observation. Cox proportional hazards models examined whether higher serum alpha-tocopherol concentrations at baseline, 3 years, or the interval change were associated with lower lung cancer risk. All statistical tests were two-sided. RESULTS: After adjustment for age, body mass index, smoking intensity and duration, serum total cholesterol, and trial intervention group, we found lower lung cancer risk in men with high baseline alpha-tocopherol (5th quintile (Q5) vs Q1, hazard ratio (HR)=0.76, 95%CI =0.66 to 0.87; Ptrend<0.001). A similar reduction in risk was seen for serum alpha-tocopherol at 3 years (Q5 vs Q1, HR = 0.78, 95%CI =0.67 to 0.91; Ptrend=0.004). The inverse risk association appeared stronger for younger men and those having smoked fewer years, but was similar across trial intervention groups. We also found reduced risk among un-supplemented men with a lower serum alpha-tocopherol at baseline who had greater increases in concentrations at 3 years (3rd tertile vs 1st tertile of serum alpha-tocopherol change, HR = 0.74, 95% CI = 0.59 to 0.91, P=0.005). CONCLUSION: Higher vitamin E status, as measured by serum alpha-tocopherol concentration, as well as repletion of a low vitamin E state, was related to decreased lung cancer risk during a 28-year period. Our findings provide evidence supporting the importance of adequate physiological vitamin E status for lung cancer risk reduction.

12.
Int J Behav Nutr Phys Act ; 16(1): 28, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894189

RESUMO

BACKGROUND: Emotional eating (i.e. eating in response to negative emotions) has been suggested to be one mechanism linking depression and subsequent development of obesity. However, studies have rarely examined this mediation effect in a prospective setting and its dependence on other factors linked to stress and its management. We used a population-based prospective cohort of adults and aimed to examine 1) whether emotional eating mediated the associations between depression and 7-year change in body mass index (BMI) and waist circumference (WC), and 2) whether gender, age, night sleep duration or physical activity moderated these associations. METHODS: Participants were Finnish 25- to 74-year-olds who attended the DILGOM study at baseline in 2007 and follow-up in 2014. At baseline (n = 5024), height, weight and WC were measured in a health examination. At follow-up (n = 3735), height, weight and WC were based on measured or self-reported information. Depression (Center for Epidemiological Studies - Depression Scale), emotional eating (Three-Factor Eating Questionnaire-R18), physical activity and night sleep duration were self-reported. Age- and gender-adjusted structural equation models with full information maximum likelihood estimator were used in the analyses. RESULTS: Depression and emotional eating were positively associated and they both predicted higher 7-year increase in BMI (R2 = 0.048) and WC (R2 = 0.045). The effects of depression on change in BMI and WC were mediated by emotional eating. Night sleep duration moderated the associations of emotional eating, while age moderated the associations of depression. More specifically, emotional eating predicted higher BMI (P = 0.007 for the interaction) and WC (P = 0.026, respectively) gain in shorter sleepers (7 h or less), but not in longer sleepers (9 h or more). Depression predicted higher BMI (P < 0.001 for the interaction) and WC (P = 0.065, respectively) increase in younger participants, but not in older participants. CONCLUSIONS: Our findings offer support for the hypothesis that emotional eating is one behavioural mechanism between depression and development of obesity and abdominal obesity. Moreover, adults with a combination of shorter night sleep duration and higher emotional eating may be particularly vulnerable to weight gain. Future research should examine the clinical significance of our observations by tailoring weight management programs according to these characteristics.


Assuntos
Depressão/epidemiologia , Ingestão de Alimentos/psicologia , Comportamento Alimentar/psicologia , Adulto , Idoso , Emoções , Finlândia/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Ganho de Peso
13.
Br J Nutr ; 121(8): 938-944, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30898176

RESUMO

The insulin-like growth factor (IGF) axis may be involved in the development of type 2 diabetes. We examined the associations of IGF-I and IGF binding proteins (IGFBP)-1 and -3 with diabetes risk and evaluated macronutrient intakes related to the observed associations. In a nested case-control study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers aged 50-69 years, the IGF variables were measured from baseline serum samples for a random sample of 310 men with diabetes diagnosed during a 12-year follow-up and for 310 controls matched by age, recruitment day and intervention group. Diet at baseline was assessed using a validated FFQ. The associations of IGF proteins with diabetes risk were estimated using conditional logistic regression and the associations with macronutrient intakes using linear regression. IGF-I and IGFBP-3 were not associated with the incidence of diabetes. Higher IGFBP-1 was associated with lower diabetes risk in an unadjusted crude model (OR 0·25; 95 % CI 0·15, 0·42 in the highest quartile compared with the lowest), but not after adjustment for BMI (corresponding OR 0·76; 95 % CI 0·41, 1·40). Intakes of carbohydrates, plant protein and milk protein associated positively and intake of meat protein and fat negatively with IGFBP-1 (P<0·005). IGFBP-1 was inversely associated with diabetes risk, but the association was substantially dependent on BMI. The associations between macronutrient intakes and IGFBP-1 may reflect influences of nutrients or foods on insulin concentrations.

14.
Eur J Clin Nutr ; 73(10): 1352-1360, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30643221

RESUMO

BACKGROUND: Telomeres are repeats of DNA that contain the sequence TTAGGG at the ends of each chromosome, and their function is to protect DNA from damage. Little evidence exists regarding the relationship between dietary patterns and telomere length, especially derived applying longitudinal design. The aim was to study if overall dietary pattern is associated with leukocyte telomere length (LTL) or faster telomere attrition or both. METHODS: The setting was longitudinal and observational. Participants were 456 men and 590 women whose birth settled in between 1934 and 1944 and who participated in the Helsinki Birth Cohort Study. Baltic sea diet score (BSDS), modified Mediterranean diet score (mMED), and dietary inflammatory index (DII®) were calculated based on a 128-item food frequency questionnaire (FFQ) collected in 2001-2004. LTL was measured twice, in 2001-2004 and in 2011-2013 by quantitative real-time polymerase chain reaction. Association between the dietary patterns and LTL were analysed by general linear models with appropriate contrasts. RESULTS: BSDS, mMED, and DII did not associate with LTL in the cross-sectional analysis in men or women. Higher mMED at baseline (2001-2004) was associated with slightly faster LTL shortening during the follow-up (standardized ß -0.08, 95% CI -0.15, -0.01). No association between mMED and LTL change was found in men. Adherence to BSDS and DII did not associate with LTL change in men or women. CONCLUSION: Baltic sea diet, Mediterranean diet, and diet's inflammatory potential seem to have only little impact on telomere length and telomere attrition in elderly Finnish men and women.

15.
Circ Res ; 123(12): 1339-1349, 2018 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-30566060

RESUMO

RATIONALE: Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. OBJECTIVE: Explore whether serum beta carotene is associated with overall and cause-specific mortality and to elucidate the strength and dose-response of the association. METHODS AND RESULTS: We conducted a prospective serological analysis of 29 103 men in the ATBC study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). During 31 years of follow-up, 23 796 deaths occurred, including deaths because of cardiovascular disease (9869), cancer (7692), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2700). Serum beta carotene was assayed using high-performance liquid chromatography. Adjusting for major risk factors measured, men with higher serum beta carotene had significantly lower all-cause mortality (hazard ratios=0.81, 0.71, 0.69, and 0.64 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001). Serum beta carotene was significantly associated with risk of death from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, diabetes mellitus, injuries and accidents, and other causes (Q5 versus Q1, hazard ratio=0.21-0.73, all Ptrend<0.0001). The all-cause mortality association was not materially impacted by adjustment for fruit and vegetable consumption (albeit, estimated with some measurement error) and was generally similar across subgroups of smoking intensity, alcohol consumption, trial supplementation, and duration of follow-up, but was significantly modified by age, years of smoking, and body mass index, with stronger inverse associations among men who were younger, smoked fewer years, and had a lower body mass index (all Pinteraction≤0.0025). CONCLUSIONS: This study provides evidence that higher beta carotene biochemical status is associated with lower overall, cardiovascular disease, heart disease, stroke, cancer, and other causes of mortality. The dose-response associations over a 30-year period were not attenuated by adjustment for other important risk factors and support greater fruit and vegetable consumption as a means to increase beta carotene status and promote longevity.


Assuntos
Doenças Cardiovasculares/mortalidade , Diabetes Mellitus/mortalidade , Mortalidade , Neoplasias/mortalidade , Doenças Respiratórias/mortalidade , Ferimentos e Lesões/mortalidade , beta Caroteno/sangue , Idoso , Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Doenças Respiratórias/sangue , Ferimentos e Lesões/sangue
16.
Circ Genom Precis Med ; 11(11): e002234, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30571186

RESUMO

BACKGROUND: Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker-a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality; however, the underlying detailed associations of GlycA's morbidity and mortality risk are currently unknown. METHODS: We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up. RESULTS: New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45-9.65) and 5.00 (95% CI, 2.38-10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals. When modeled together, both hsCRP and GlycA were attenuated but remained significant. CONCLUSIONS: GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings.


Assuntos
Ciências Biocomportamentais , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias , Angiografia por Ressonância Magnética , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico por imagem , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Intervalo Livre de Doença , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
17.
J Am Med Dir Assoc ; 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30366763

RESUMO

BACKGROUND/OBJECTIVE: Diet has a major impact on a person's health. However, limited information exists on the long-term role of the whole diet on disability. We investigated the association of the healthy Nordic diet and the Mediterranean diet with incident disability 10 years later. DESIGN: Longitudinal, with a follow-up of 10 years. SETTINGS/PARTICIPANTS: A total of 962 home-dwelling men and women from the Helsinki Birth Cohort Study, mean age 61.6 years, who were free of disability at baseline. MEASUREMENTS: At baseline, 2001-2004, the Nordic diet score (NDS) and modified Mediterranean diet score (mMDS) were calculated using a validated 128-item food-frequency questionnaire. Higher scores indicated better adherence to the diet. Participants' incident disability was assessed during 2011-2013 by a self-reported questionnaire and was based on mobility limitations and difficulties to perform self-care activities. Analyses were performed using logistic regression and adjusted for potential confounding factors. RESULTS: In total, 94 participants (9.8%) developed mobility limitations and 45 participants (4.7%) developed difficulties in self-care activities during 10 year follow-up. The likelihood of having mobility limitations (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.22-0.80) and difficulties in self-care activities (OR 0.38, 95% CI 0.15-0.94) were lower among those in the highest NDS tertile than among those in the lowest NDS tertile. Greater mMDS was associated with a lower disability incidence; however, the association was not statistically significant. CONCLUSIONS/IMPLICATIONS: Adherence to the healthy Nordic diet predicts 10-year incidence of mobility limitations and difficulties to perform self-care activities in old age and may thus be protective against disability in Nordic population.

18.
Chronobiol Int ; : 1-15, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30212231

RESUMO

Individuals with a later preference for the daily activities (evening types) tend to have unhealthier behaviors, which could increase their risk for obesity when compared those with an earlier preference (morning types). Furthermore, later food intake timing, another behavior more characteristic of evening types, has been associated with obesity. However, chronotype differences in the long-term weight change and the role of chronotype in the association between energy intake timing and obesity risk are not clear. To study this we first examined the independent associations of chronotype and energy intake timing with anthropometric changes and then whether chronotype modified the association between energy intake timing and obesity risk. Our data included 1097 Finns from DILGOM (DIetary Lifestyle and Genetic Determinants of Obesity and Metabolic syndrome) 2007 (baseline) and 2014 (follow-up) and from Findiet 2007. Chronotype was assessed with a shortened version of Horne and Östberg's morningness-eveningness questionnaire. Energy intake timing (as percentages of the total energy intake in the morning/evening) was assessed with 48-h dietary recalls. Weight, body mass index (BMI), and waist circumference were based on measured and self-reported values. Analysis of co-variance and multivariable logistic regression models were used for statistical analyses. Evening typed women had greater weight gain (+ 2.3 kg vs. + 0.3 kg, P = 0.016) and increase in BMI (0.7 kg/m2 vs. -0.1 kg/m2, P = 0.024) than morning typed women. After excluding participants with depression, these associations attenuated to non-significant. Compared to participants whose energy intake was proportionally lowest during evening, those with proportionally highest energy intake during evening were more likely with obesity (BMI≥ 30 kg/m2) after follow-up (OR 1.97, 95% CI 1.21-3.21, Ptrend = 0.042). Participants' chronotype did not modify this association (Pinteract = 0.95). In conclusion, our findings indicated that evening energy intake may play a role in obesity regardless of the chronotype. Furthermore, evening typed women were more prone to increases in their anthropometrics, which seem to be at least partly explained by depression. Further studies of this topic are warranted.

19.
Sleep Sci ; 11(2): 85-91, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30083295

RESUMO

The seasonal pattern for mood and behaviour, the behavioural trait of morningness-eveningness, and sleep are interconnected features, that may serve as etiological factors in the development or exacerbation of medical conditions. Methods: The study was based on a random sample of inhabitants aged 25 to 74 years living in Finland. As part of the national FINRISK 2012 study participants were invited (n=9905) and asked whether the doctor had diagnosed or treated them during the past 12 months for chronic diseases. Results: A total of 6424 participants filled in the first set of questionnaires and 5826 attended the physical health status examination, after which the second set of questionnaires were filled. Regression models were built in which each condition was explained by the seasonal, diurnal and sleep features, after controlling for a range of background factors. Of the chronic diseases, depressive disorder was associated with longer total sleep duration (p<.0001) and poor sleep quality (p<.0001). Of the measurements for health status assessment, none associated with sleep features, but systolic blood pressure yielded significant (p<.0001) associations with both seasonal and diurnal features at large. Conclusion: Sleep quality was the most sensitive probe in yielding associations with chronic diseases in this population-based study. The seasonal variations in mood and social activity, and the ease in getting up and tiredness in the morning were the most sensitive probes in yielding associations with blood pressure and waist circumference. Assessment of sleep quality, seasonal and diurnal features provides thus added value for health surveys of the general population.

20.
Eur Urol ; 74(5): 585-594, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30077399

RESUMO

BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

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