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1.
Br J Nutr ; : 1-36, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33413729

RESUMO

The long-term inflammatory impact of diet could potentially elevate the risk of periodontal disease through modification of systemic inflammation. The aim of the present study was to prospectively investigate the associations between a food based, reduced rank regression (RRR) derived, empirical dietary inflammatory pattern (EDIP) and incidence of periodontitis. The study population was composed of 34,940 men from the Health Professionals Follow-Up Study, who were free of periodontal disease and major illnesses at baseline (1986). Participants provided medical and dental history through mailed questionnaires every 2 years, and dietary data through validated semi-quantitative food frequency questionnaires every 4 years. We used Cox proportional hazard models to examine the associations between EDIP scores and validated self-reported incidence of periodontal disease over a 24-year follow-up period. No overall association between EDIP and the risk of periodontitis was observed; the hazard ratio comparing the highest EDIP quintile (most proinflammatory diet) to the lowest quintile was 0.99 (95% confidence interval: 0.89 -1.10, p-value for trend = 0.97). A secondary analysis showed that among obese non-smokers (i.e. never and former smokers at baseline), the hazard ratio for periodontitis comparing the highest EDIP quintile to the lowest was 1.39 (95% confidence interval: 0.98 -1.96, p-value for trend = 0.03). In conclusion, no overall association was detected between EDIP and incidence of self-reported periodontitis in the study population. From the subgroups evaluated EDIP was significantly associated with increased risk of periodontitis only among nonsmokers who were obese. Hence, this association must be interpreted with caution.

2.
Diabetes Care ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441419

RESUMO

OBJECTIVE: We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively followed 76,530 women in the Nurses' Health Study (NHS) (1986-2012), 81,569 women in NHS II (1991-2017), and 34,468 men in the Health Professionals Follow-up Study (1986-2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis. RESULTS: We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12-23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7-9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0-35.6% of the associations between changes in PDI and hPDI and diabetes risk. CONCLUSIONS: Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.

3.
J Nutr ; 151(1): 50-58, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33296468

RESUMO

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.

4.
Clin Chem ; 67(1): 288-297, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33257943

RESUMO

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.

6.
J Clin Periodontol ; 48(1): 2-13, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33020936

RESUMO

AIM: To prospectively investigate the associations between major dietary patterns and incidence of periodontitis. METHODS: We included 34,940 men from the Health Professionals Follow-Up Study, free of periodontal disease and major illnesses at baseline. Detailed medical and dental history was collected through biennial mailed questionnaires, and dietary information was provided through quadrennial food frequency questionnaires. Using principal component analysis, we identified two major dietary patterns ("prudent" and "Western"). We used Cox proportional hazard models to examine the associations between the two dietary patterns and self-reported incidence of periodontitis over a 24-year follow-up period. We investigated each pattern separately. RESULTS: There was no overall association between Western or prudent dietary patterns and periodontitis. Among obese, however, the Western dietary pattern was significantly associated with incident periodontitis. The hazard ratio for those in the highest quintile of Western diet versus those in the lowest (reference) was 1.83 (95% confidence interval: 1.21-2.76). CONCLUSIONS: There was no overall association between Western or prudent dietary patterns and periodontitis; however, in subgroups analysis, the Western diet was significantly associated with higher periodontitis risk only among obese men, a finding that requires replication and biological explication.

7.
Gastroenterology ; 160(1): 158-173.e10, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32860791

RESUMO

BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 µIU/mL vs placebo, 1.64 ± 4.7 µIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05). CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.

8.
Circ Res ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33272114

RESUMO

Rationale: Altered lipid metabolism has been implicated in heart failure (HF) development, but no prospective studies have examined comprehensive lipidomics data and subsequent risk of HF. Objective: We aimed to link single lipid metabolites and lipidomics networks to the risk of developing heart failure. Methods and Results: Discovery analyses were based on 216 targeted lipids in a case-control study (331 incident HF cases and 507 controls, matched by age, sex, and study center), nested within the PREDIMED study. Associations of single lipids were examined in conditional logistic regression models. Furthermore, lipidomics networks were linked to HF risk in a multi-step workflow, including machine learning-based identification of the HF-related network-clusters, and regression-based discovery of the HF-related lipid patterns within these clusters. If available, significant findings were externally validated in a subsample of the EPIC-Potsdam cohort (2414 at-risk-participants, including 87 incident HF-cases). After confounder-adjustments, two lipids were significantly associated with HF risk in both cohorts: ceramide 16:0 (HR per SD in PREDIMED 1.28, 95%CI 1.13, 1.47) and phosphatidylcholine 32_0 (HR per SD in PREDIMED 1.23, 95%CI 1.08, 1.41). Additionally, lipid patterns in several network clusters were associated with HF risk in PREDIMED. Adjusted for standard risk factors, an internally cross-validated score based on the significant HF-related lipids that were identified in the network analysis in PREDIMED was associated with a higher HF risk (20 lipids, HR per SD 2.33, 95%CI 1.93, 2.81%). Moreover, a lipid score restricted to the externally available lipids was significantly associated with HF incidence in both cohorts (6 lipids, HRs per SD 1.30, 95%CI 1.14, 1.47 in PREDIMED, and 1.46, 95%CI, 1.17, 1.82 in EPIC-Potsdam). Conclusions: Our study identified and validated two lipid metabolites and several lipidomics patterns as potential novel biomarkers of HF risk. Lipid profiling may capture preclinical molecular alterations that predispose for incident HF.

9.
BMJ ; 371: m4141, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268459

RESUMO

OBJECTIVES: To study total, processed, and unprocessed red meat in relation to risk of coronary heart disease (CHD) and to estimate the effects of substituting other protein sources for red meat with CHD risk. DESIGN: Prospective cohort study with repeated measures of diet and lifestyle factors. SETTING: Health Professionals Follow-Up Study cohort, United States, 1986-2016. PARTICIPANTS: 43 272 men without cardiovascular disease or cancer at baseline. MAIN OUTCOME MEASURES: The primary outcome was total CHD, comprised of acute non-fatal myocardial infarction or fatal CHD. Cox models were used to estimate hazard ratios and 95% confidence intervals across categories of red meat consumption. Substitution analyses were conducted by comparing coefficients for red meat and the alternative food in models, including red meat and alternative foods as continuous variables. RESULTS: During 1 023 872 person years of follow-up, 4456 incident CHD events were documented of which 1860 were fatal. After multivariate adjustment for dietary and non-dietary risk factors, total, unprocessed, and processed red meat intake were each associated with a modestly higher risk of CHD (hazard ratio for one serving per day increment: 1.12 (95% confidence interval 1.06 to 1.18) for total red meat, 1.11 (1.02 to 1.21) for unprocessed red meat, and 1.15 (1.06 to 1.25) for processed red meat). Compared with red meat, the intake of one serving per day of combined plant protein sources (nuts, legumes, and soy) was associated with a lower risk of CHD (0.86 (0.80 to 0.93) compared with total red meat, 0.87 (0.79 to 0.95) compared with unprocessed red meat, and 0.83 (0.76 to 0.91) compared with processed red meat). Substitutions of whole grains and dairy products for total red meat and eggs for processed red meat were also associated with lower CHD risk. CONCLUSIONS: Substituting high quality plant foods such as legumes, nuts, or soy for red meat might reduce the risk of CHD. Substituting whole grains and dairy products for total red meat, and eggs for processed red meat, might also reduce this risk.


Assuntos
Doença das Coronárias/epidemiologia , Dieta/estatística & dados numéricos , Manipulação de Alimentos , Infarto do Miocárdio/epidemiologia , Carne Vermelha/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Laticínios , Proteínas na Dieta , Ovos , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Grãos Integrais
10.
Circ Genom Precis Med ; 13(6): e002769, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33321069

RESUMO

BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

11.
PLoS Med ; 17(12): e1003453, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33290392

RESUMO

BACKGROUND: Consumption of sugar-sweetened beverages (SSBs) has been consistently associated with a higher risk of obesity, type 2 diabetes, cardiovascular disease, and premature mortality, whereas evidence for artificially sweetened beverages (ASBs) and fruit juices on health is less solid. The aim of this study was to evaluate the consumption of SSBs, ASBs, and fruit juices in association with frailty risk among older women. METHODS AND FINDINGS: We analyzed data from 71,935 women aged ≥60 (average baseline age was 63) participating in the Nurses' Health Study (NHS), an ongoing cohort study initiated in 1976 among female registered nurses in the United States. Consumption of beverages was derived from 6 repeated food frequency questionnaires (FFQs) administered between 1990 and 2010. Frailty was defined as having at least 3 of the following 5 criteria from the FRAIL scale: fatigue, poor strength, reduced aerobic capacity, having ≥5 chronic illnesses, and weight loss ≥5%. The occurrence of frailty was assessed every 4 years from 1992 to 2014. During 22 years of follow-up, we identified 11,559 incident cases of frailty. Consumption of SSBs was associated with higher risk of frailty after adjustment for diet quality, body mass index (BMI), smoking status, and medication use, specifically, the relative risks (RRs) and 95% confidence interval (95% CI) for ≥2 serving/day versus no SSB consumption was 1.32 (1.10, 1.57); p-value <0.001. ASBs were also associated with frailty [RR ≥2 serving/day versus no consumption: 1.28 (1.17, 1.39); p-value <0.001]. Orange juice was associated with lower risk of frailty [RR ≥1 serving/day versus no consumption: 0.82 (0.76, 0.87); p-value <0.001], whereas other juices were associated with a slightly higher risk [RR ≥1 serving/day versus no consumption: 1.15 (1.03, 1.28); p-value <0.001]. A limitation of this study is that, due to self-reporting of diet and frailty, certain misclassification bias cannot be ruled out; also, some residual confounding may persist. CONCLUSIONS: In this study, we observed that consumption of SSBs and ASBs was associated with a higher risk of frailty. However, orange juice intake showed an inverse association with frailty. These results need to be confirmed in further studies using other frailty definitions.

12.
J Nutr ; 2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33382410

RESUMO

BACKGROUND: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. OBJECTIVES: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. METHODS: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training-validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. RESULTS: A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001). CONCLUSIONS: A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.

13.
JAMA Netw Open ; 3(11): e2025466, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33211107

RESUMO

Importance: Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear. Objective: To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population. Design, Setting, and Participants: This cohort study was conducted among 25 317 apparently healthy women. The participants with missing information regarding all traditional and novel metabolic biomarkers or those with baseline diabetes were excluded. Participants were invited for baseline assessment between September 1992 and May 1995. Data were collected from November 1992 to December 2017 and analyzed from December 2018 to December 2019. Exposures: MED intake score (range, 0 to 9) was computed from self-reported dietary intake, representing adherence to Mediterranean diet intake. Main Outcomes and Measures: Incident cases of type 2 diabetes, identified through annual questionnaires; reported cases were confirmed by either telephone interview or supplemental questionnaire. Proportion of reduced risk of type 2 diabetes explained by clinical risk factors and a panel of 40 biomarkers that represent different physiological pathways was estimated. Results: The mean (SD) age of the 25 317 female participants was 52.9 (9.9) years, and they were followed up for a mean (SD) of 19.8 (5.8) years. Higher baseline MED intake (score ≥6 vs ≤3) was associated with as much as a 30% lower type 2 diabetes risk (age-adjusted and energy-adjusted hazard ratio, 0.70; 95% CI, 0.62-0.79; when regression models were additionally adjusted with body mass index [BMI]: hazard ratio, 0.85; 95% CI, 0.76-0.96). Biomarkers of insulin resistance made the largest contribution to lower risk (accounting for 65.5% of the MED-type 2 diabetes association), followed by BMI (55.5%), high-density lipoprotein measures (53.0%), and inflammation (52.5%), with lesser contributions from branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%), and minimal contribution (≤2%) from hemoglobin A1c. In post hoc subgroup analyses, the inverse association of MED diet with type 2 diabetes was seen only among women who had BMI of at least 25 at baseline but not those who had BMI of less than 25 (eg, women with BMI <25, age- and energy-adjusted HR for MED score ≥6 vs ≤3, 1.01; 95% CI, 0.77-1.33; P for trend = .92; women with BMI ≥25: HR, 0.76; 95% CI, 0.67-0.87; P for trend < .001). Conclusions and Relevance: In this cohort study, higher MED intake scores were associated with a 30% relative risk reduction in type 2 diabetes during a 20-year period, which could be explained in large part by biomarkers of insulin resistance, BMI, lipoprotein metabolism, and inflammation.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Dieta Mediterrânea/estatística & dados numéricos , Adiposidade , Adulto , Aminoácidos de Cadeia Ramificada/metabolismo , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Apolipoproteínas/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dieta/estatística & dados numéricos , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Inflamação/metabolismo , Resistência à Insulina , Molécula 1 de Adesão Intercelular/metabolismo , Lipoproteína(a)/metabolismo , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Proteção , Espectroscopia de Prótons por Ressonância Magnética , Triglicerídeos/metabolismo
14.
J Natl Cancer Inst ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-33225344

RESUMO

BACKGROUND: The influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood. METHODS: We prospectively followed for cancer incidence 113 429 women in the Nurses' Health Study (1978-2014) and 45 604 men in the Health Professionals Follow-up Study (1988-2014) who were free of diabetes and cancer at baseline. Cancer incidences were ascertained by review of medical records. RESULTS: In the multivariable-adjusted model incident, T2D was associated with higher risk of cancers in the colorectum, lung, pancreas, esophagus, liver, thyroid, breast, and endometrium. The pooled hazard ratios (HRs) ranged from 1.21 (95% confidence interval [CI] = 1.06 to 1.38) for colorectal cancer to 3.39 (95% CI = 2.24 to 5.12) for liver cancer. For both composite cancer outcomes and individual cancers, the elevated risks did not further increase after 8 years of T2D duration. The hazard ratio for total cancer was 1.28 (95% CI = 1.17 to 1.40) for T2D duration of 4.1-6.0 years, 1.37 (95% CI = 1.25 to 1.50) for 6.1-8.0 years, 1.21 (95% CI = 1.09 to 1.35) for 8.1-10.0 years, and 1.04 (95% CI = 0.95 to 1.14) after 15.0 years. In a cross-sectional analysis, a higher level of plasma C-peptide was found among participants with prevalent T2D of up to 8 years than those without T2D, whereas a higher level of HbA1c was found for those with prevalent T2D of up to 15 years. CONCLUSIONS: Incident T2D was associated with higher cancer risk, which peaked at approximately 8 years after diabetes diagnosis. Similar duration-dependent pattern was observed for plasma C-peptide. Our findings support a role of hyperinsulinemia in cancer development.

15.
Sci Rep ; 10(1): 19507, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33177548

RESUMO

Exhaled carbon monoxide (COex) level has been proposed as a noninvasive and easily-obtainable cardiovascular risk marker, however, with limited prospective evidence, and its association with stroke risk has been rarely explored. Measurements of COex were performed during 2004-2008 baseline examinations in the China Kadoorie Biobank study among 512,891 adults aged 30-79 years from 10 diverse study areas. After excluding participants with baseline cardiopulmonary diseases, stroke and cancer, 178,485 men and 267,202 women remained. Cox regression yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of cardio-cerebral-vascular disease (CCVD) associated with COex levels, with sequential addition of adjustment for proxy variables for CO exposure, including study area indexing ambient CO variations at large, and smoking and solid fuel use, apart from adjusting for traditional cardiovascular risk factors. During 7-year follow-up, we documented 1744 and 1430 major coronary events (myocardial infarction plus fatal ischemic heart disease), 8849 and 10,922 ischemic strokes, and 2492 and 2363 hemorrhagic strokes among men and women, respectively. The HRs with 95% CIs comparing the highest with lowest COex quintile were 2.15 [1.72, 2.69] for major coronary events, 1.65 [1.50, 1.80] for ischemic stroke, and 1.35 [1.13, 1.61] for hemorrhagic stroke among men, while among women higher associated risk was only observed for major coronary events (1.64 [1.35, 2.00]) and ischemic stroke (1.87 [1.73, 2.01]). The elevated risks were consistent when COex level was over 3 ppm. However, these associations were all attenuated until null by sequential addition of stratification by study areas, and adjustments of smoking and solid fuel use. Nevertheless, the association with ischemic stroke was maintained among the subgroup of male smokers even with adjustment for the depth and amount of cigarette smoking (HR [95% CI]: 1.37 [1.06, 1.77]), while a negative association with hemorrhagic stroke also appeared within this subgroup. Higher COex level (over 3 ppm) was associated with elevated risk of ischemic CCVD, but not independently of CO exposure. Our finding suggests that, though not an independent risk factor, COex could potentially provide a cost-effective biomarker for ischemic cardio-cerebral-vascular risk, given that CO exposure is ubiquitous.

16.
J Am Coll Cardiol ; 76(19): 2181-2193, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33153576

RESUMO

BACKGROUND: Inflammation plays an important role in cardiovascular disease (CVD) development. Diet modulates inflammation; however, it remains unknown whether dietary patterns with higher inflammatory potential are associated with long-term CVD risk. OBJECTIVES: This study sought to examine whether proinflammatory diets are associated with increased CVD risk. METHODS: We prospectively followed 74,578 women from the Nurses' Health Study (NHS) (1984-2016), 91,656 women from the NHSII (1991-2015), and 43,911 men from the Health Professionals Follow-up Study (1986-2016) who were free of CVD and cancer at baseline. Diet was assessed by food frequency questionnaires every 4 years. The inflammatory potential of diet was evaluated using a food-based empirical dietary inflammatory pattern (EDIP) score that was pre-defined based on levels of 3 systemic inflammatory biomarkers. RESULTS: During 5,291,518 person-years of follow-up, we documented 15,837 incident CVD cases, including 9,794 coronary heart disease (CHD) cases and 6,174 strokes. In pooled analyses of the 3 cohorts, after adjustment for use of anti-inflammatory medications and CVD risk factors including body mass index, a higher dietary inflammatory potential, as indicated by higher EDIP scores, was associated with an increased risk of CVD (hazard ratio [HR] comparing the highest to lowest quintiles: 1.38; 95% confidence interval [CI]: 1.31 to 1.46; p for trend <0.001), CHD (HR: 1.46; 95% CI: 1.36 to 1.56; p for trend <0.001), and stroke (HR: 1.28; 95% CI: 1.17- to 1.39; p for trend <0.001). These associations were consistent across cohorts and between sexes, and they remained significant after further adjustment for other dietary quality indices. In a subset of study participants (n = 33,719), a higher EDIP was associated with a higher circulating profile of proinflammatory biomarkers, lower levels of adiponectin, and an unfavorable blood lipid profile (p < 0.001). CONCLUSIONS: Dietary patterns with a higher proinflammatory potential were associated with higher CVD risk. Reducing the inflammatory potential of the diet may potentially provide an effective strategy for CVD prevention.

17.
Circ Genom Precis Med ; 13(6): e002977, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33141616

RESUMO

BACKGROUND: In the WHI-HT trials (Women's Health Initiative Hormone Therapy), treatment with oral conjugated equine estrogens and medroxyprogesterone acetate (CEE+MPA) resulted in increased risk of coronary heart disease (CHD), whereas oral conjugated equine estrogens (CEE) did not. METHODS: Four hundred eighty-one metabolites were measured at baseline and at 1-year in 503 and 431 participants in the WHI CEE and CEE+MPA trials, respectively. The effects of randomized HT on the metabolite profiles at 1-year was evaluated in linear models adjusting for baseline metabolite levels, age, body mass index, race, incident CHD, prevalent hypertension, and diabetes. Metabolites with discordant effects by HT type were evaluated for association with incident CHD in 944 participants (472 CHD cases) in the WHI-OS (Women's Health Initiative Observational Study), with replication in an independent cohort of 980 men and women at high risk for cardiovascular disease. RESULTS: HT effects on the metabolome were profound; 62% of metabolites significantly changed with randomized CEE and 52% with CEE+MPA (false discovery rate-adjusted P value<0.05) in multivariable models. Concerted increases in abundance were seen within various metabolite classes including triacylglycerols, phosphatidylethanolamines, and phosphatidylcholines; decreases in abundance was observed for acylcarnitines, lysophosphatidylcholines, quaternary amines, and cholesteryl/cholesteryl esters. Twelve metabolites had discordant effects by HT type and were associated with incident CHD in the WHI-OS; a metabolite score estimated in a Least Absolute Shrinkage and Selection Operator regression was associated with CHD risk with an odds ratio of 1.47 per SD increase (95% CI, 1.27-1.70, P<10-6). All twelve metabolites were altered in the CHD protective direction by CEE treatment. One metabolite (lysine) was significantly altered in the direction of increased CHD risk by CEE+MPA; the remaining 11 metabolites were not significantly changed by CEE+MPA. The CHD associations of a subset of 4 metabolites including C58:11 triacylglycerol, C54:9 triacylglycerol, C36:1 phosphatidylcholine and sucrose replicated in an independent dataset of 980 participants in the PREDIMED trial (Prevención con Dieta Mediterránea). CONCLUSIONS: Randomized treatment with oral HT resulted in large metabolome shifts that generally favored CEE alone over CEE+MPA in term of CHD risk. Discordant metabolite effects between HT regimens may partially mediate the differences in CHD risk between the 2 WHI-HT trials.

18.
Am J Clin Nutr ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33094800

RESUMO

BACKGROUND: Greater consumption of red meat has been associated with a higher risk of type 2 diabetes mellitus (T2DM). A decreased intake of red meat and simultaneous increased intake of other high-protein foods may be associated with a lower risk of T2DM. These analyses of specific food replacements for red meat may provide more accurate dietary advice. OBJECTIVE: We examined the association between a decrease in intake of red meat accompanied by an increase in other major dietary protein sources and risk of T2DM. METHODS: We prospectively followed 27,634 males in the Health Professionals Follow-up Study, 46,023 females in the Nurses' Health Study, and 75,196 females in the Nurses' Health Study II. Diet was assessed by a validated FFQ and updated every 4 y. Cox proportional hazards models adjusted for T2DM risk factors were used to model the food replacements. We calculated HRs and 95% CIs for the T2DM risk associated with replacements of 1 daily serving of red meat with another protein source. RESULTS: During 2,113,245 person-years of follow-up, we identified 8763 incident T2DM cases from 1990 to 2013. In the pooled analyses, a decrease in total red meat intake during a 4-y period replaced with another common protein food was associated with a lower risk of T2DM in the subsequent 4-y period. The HR (95% CI) per 1 serving/d was 0.82 (0.75, 0.90) for poultry, 0.87 (0.77, 0.98) for seafood, 0.82 (0.78, 0.86) for low-fat dairy, 0.82 (0.77, 0.86) for high-fat dairy, 0.90 (0.81, 0.99) for eggs, 0.89 (0.82, 0.98) for legumes, and 0.83 (0.78, 0.89) for nuts. The associations were present for both unprocessed and processed red meat, although stronger for the replacement of processed red meat. CONCLUSIONS: Replacing red meat consumption with other protein sources was associated with a lower risk of T2DM.

19.
Am J Clin Nutr ; 112(6): 1492-1503, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022701

RESUMO

BACKGROUND: Hyperinsulinemia and higher insulin-like growth factors may increase breast cancer risk. We evaluated a diabetes risk reduction diet (DRRD) and breast cancer risk. OBJECTIVES: We prospectively evaluated the association between adherence to a DRRD and the incidence of breast cancer. METHODS: We followed 88,739 women from the Nurses' Health Study (NHS; 1980-2016) and 93,915 women from the NHSII (1991-2017). Incident breast cancer cases (n = 11,943) were confirmed with medical records, and subtypes were determined by tissue microarray data and pathology reports. Information on diet and breast cancer risk factors was repeatedly ascertained in follow-up questionnaires. A DRRD score was derived with 9 factors: lower glycemic index of diet; lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red/processed meat; higher intakes of cereal fiber, coffee, nuts, and whole fruits; and a higher ratio of polyunsaturated to saturated fat (score range: 9-45). Multivariable-adjusted hazard ratios (MVHRs) and 95% CIs were calculated with Cox proportional hazards models. RESULTS: Being in the highest compared with the lowest DRRD adherence quintile was associated with a modestly lower breast cancer risk (MVHRQ5vsQ1: 0.89; 95% CI: 0.84, 0.95; P-trend = 0.0002); this was attenuated after adjusting for weight change since age 18 y (MVHRQ5vsQ1: 0.92; 95% CI: 0.87, 0.98; P-trend = 0.01). The inverse association was strongest among women with current BMI < 25 kg/m2 (MVHRQ5vsQ1: 0.89; 95% CI: 0.81, 0.98; P-trend = 0.004; P-interaction = 0.04). Among tumor molecular subtypes, the strongest inverse association was observed with basal-type tumors (MVHRQ5vsQ1: 0.67; 95% CI: 0.45, 1.01; P-trend = 0.04). CONCLUSIONS: Greater DRRD-adherence was associated with lower breast cancer risk, likely mediated by less weight gain with a DRRD; however, independently of weight change, DRRD-adherence was modestly associated with lower breast cancer risk, particularly among lean women.


Assuntos
Neoplasias da Mama/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Comportamento de Redução do Risco
20.
Artigo em Inglês | MEDLINE | ID: mdl-33115816

RESUMO

INTRODUCTION: Longer duration of lactation is associated with lower cardiometabolic disease risk, but pathogenic pathways involved in the disease progression are unclear, especially among high-risk women. We aimed to examine the associations of lifetime lactation duration with cardiometabolic biomarkers among middle-aged women with a history of gestational diabetes (GDM). RESEARCH DESIGN AND METHODS: Women with a history of GDM participating in the Nurses' Health Study II, a prospective cohort study, were identified and followed through biennial questionnaires beginning in 1991. Lactation history was asked in three follow-up questionnaires to calculate lifetime duration. In 2012-2014, fasting blood samples were collected through the Diabetes & Women's Health Study to measure inflammatory (C-reactive protein (CRP), interleukin (IL) 6), liver enzyme (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase), and lipid biomarkers (total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol). RESULTS: At follow-up blood collection, women were at median age 58.2 (95% CI 51 to 65) years and 26.3 (95% CI 15.7 to 34.1) years since GDM index pregnancy. After multiple adjustment including prepregnancy body mass index (BMI), longer duration of lactation was significantly associated with lower CRP (least squares (LS) mean 1.90 mg/L (95% CI 1.47 to 2.45) for 0-month lactation, 1.98 mg/L (95% CI 1.68 to 2.32) for up to 12-month lactation, 1.67 mg/L (95% CI 1.42 to 1.97) for 12-24 month lactation, and 1.39 mg/L (95% CI 1.19 to 1.62) for >24-month lactation; p trend=0.003) and IL-6 (1.25 pg/L (95% CI 0.94 to 1.68), 1.19 pg/L (95% CI 0.99 to 1.42), 1.04 pg/L (95% CI 0.87 to 1.25), and 0.93 pg/L (95% CI 0.78 to 1.11); p trend=0.04). Longer duration of lactation was associated with lower risk for chronic inflammation using CRP 3 mg/L cut-off in middle-aged women (OR 0.81 (95% CI 0.69 to 0.940 per 1-year increase) with multiple adjustment. CONCLUSIONS: Longer lifetime duration of lactation was associated with favorable inflammatory biomarker concentrations in middle-aged women with a history of GDM. Chronic inflammatory pathways may be responsible for previously reported associations between lactation and long-term risk for cardiometabolic diseases.

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