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Background Cardiometabolic diseases are prevalent in aging Americans. Although some studies have implicated greater intake of dairy products, it is not clear how dairy intake is related to biomarkers of cardiometabolic health. Objective Our aim was to test the hypothesis that associations of dairy foods with biomarkers of lipid metabolism, insulin-like growth factor signaling, and chronic inflammation may provide clues to understanding how dairy can influence cardiometabolic health. Design This was a cross-sectional study in the Women's Health Initiative using baseline food frequency questionnaire data to calculate dairy intake. Participants/setting Participants were 35,352 postmenopausal women aged 50 to 79 years at 40 clinical centers in the United States. Main outcome measures Baseline (1993-1998) concentrations of 20 circulating biomarkers were measured. Statistical analyses Multivariable-adjusted linear regression was used to estimate percent difference in biomarker concentrations per serving of total dairy and individual foods (milk, cheese, yogurt, butter, and low-fat varieties). Results Lower triglyceride concentrations were associated with greater intake of total dairy (–0.8% [95% CI –1.2% to –0.3%]), mainly driven by full-fat varieties. Individual dairy foods had specific associations with circulating lipid components. For example, greater total milk intake was associated with lower concentrations of total cholesterol (–0.4% [95% CI –0.7% to –0.2%]) and high-density lipoprotein cholesterol (–0.5% [95% CI –0.9% to –0.1%]), whereas greater butter intake was associated with higher total cholesterol (0.6% [95% CI 0.2% to 1.0%]) and high-density lipoprotein cholesterol (1.6% [95% CI 1.1% to 2.0%]) concentrations. In contrast, higher total yogurt intake was associated with lower total cholesterol (–1.1% [95% CI –2.0% to –0.2%]) and higher high-density lipoprotein cholesterol (1.8% [95% CI 0.5% to 3.1%]). Greater total dairy intake (regardless of fat content), total cheese, full-fat cheese, and yogurt were consistently associated with lower concentrations of glucose, insulin, and C-reactive protein. However, milk and butter were not associated with these biomarkers. Conclusions Higher dairy intake, except butter, was associated with a favorable profile of lipids, insulin response, and inflammatory biomarkers, regardless of fat content. Yet, specific dairy foods might influence these markers uniquely. Findings do not support a putative role of dairy in cardiometabolic diseases observed in some previous studies.

Background: Patients with cancer are recommended to follow cancer prevention guidelines due to inadequate evidence for specific recommendations for cancer survivors. Methods: We examined whether diet and lifestyle scores measuring adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention guidelines were associated with colorectal cancer–specific and overall mortality among 1,491 patients with colorectal cancer in two prospective cohorts. Cox proportional hazards regression models were used to calculate the multivariable-adjusted HRs and 95% confidence intervals (CI). Results: During a median follow-up of 7.92 years, there were 641 deaths (179 colorectal cancer–specific deaths). Patients in the highest quartile of the post-diagnostic WCRF/AICR lifestyle score including diet, body mass index (BMI), and physical activity had a 24% lower risk (HR = 0.76, 95% CI: 0.49–1.18) of colorectal cancer–specific mortality and a 37% lower risk (HR = 0.63, 95% CI: 0.50–0.78) of overall mortality compared with the lowest quartile. When BMI was not included in the lifestyle score due to potential disease-related weight loss, stronger inverse associations were observed for both colorectal cancer–specific and overall mortality for the same comparison (colorectal cancer–specific: HR = 0.50, 95% CI: 0.32–0.79; overall: HR = 0.59, 95% CI: 0.47–0.75). The post-diagnostic WCRF/AICR diet score was not statistically significantly associated with either colorectal cancer–specific or overall mortality. Conclusions: Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with improved survival in patients with colorectal cancer. Impact: This study provides support for patients with colorectal cancer to follow cancer prevention recommendations after diagnosis. Future studies on cancer survivors will continue to contribute to evidence-based diet and lifestyle recommendations for patients with cancer.

Background: Results of observational studies of the association between dietary fat and risk of invasive breast cancer have been inconsistent. In the Women's Health Initiative dietary modification (DM) randomized trial designed to lower fat intake, the intervention was not associated with a statistically significant reduction of overall breast cancer risk. However, the DM association with risk of ductal carcinoma in situ (DCIS) of the breast, a putative breast cancer precursor, has not been reported. Methods: A total of 48,835 postmenopausal women, ages 50–79 years at enrollment, with no breast cancer history and ≥32% of total energy intake from fat, were randomly assigned either to a dietary intervention (n = 19,541) designed to reduce total fat intake to 20% of energy and to increase vegetable, fruit, and grain consumption, or to a comparison group (n = 29,294). Cox proportional hazards models were used to estimate HRs and 95% confidence intervals for the association between the intervention and DCIS risk. Results: During 18.7 years (median) cumulative follow-up, including intervention (∼8.7 years) and post-intervention phases (∼13.0 years), 817 DCIS cases were ascertained. No evidence of an association between the DM intervention and DCIS risk was observed overall, or by trial phase (intervention and post-intervention). Similarly, no associations were found in subgroups defined by potential risk factors for DCIS. Conclusions: DM aiming to reduce fat intake was not associated with altered risk of DCIS. Impact: These results do not provide evidence of an association between dietary fat reduction and the risk of DCIS among postmenopausal women.

Weight cycling is common in populations. However, it is unclear whether frequency and magnitude of weight cycling is associated with kidney cancer risk, independent of body mass index (BMI). A prospective cohort study followed 85,562 participants from Health Professionals Follow-up Study and Nurses’ Health Study (1992–2014). At baseline, participants reported frequency and magnitude of intentional weight loss in the past 4 years. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We also conducted a meta-analysis of all available observational studies including our two cohorts. During 22 years of follow-up, we identified 441 kidney cancer cases. Compared with non-weight cyclers (no attempt of intentional weight loss), severe cyclers (≥ 3 times of intentional weight loss of ≥ 4.5 kg) were at increased kidney cancer risk after adjusting for BMI before weight cycling (pooled multivariable-adjusted HR, 1.78; 95% CI, 1.19, 2.66). Additional adjustment for attained BMI after weight cycling had minimal influence. There was a positive trend between weight cycling by frequency and magnitude and kidney cancer risk (P-trend = 0.01). Moreover, the observed positive association did not differ by subtypes of cyclers (e.g., adiposity status, weight-loss methods). In the meta-analysis, we found a strong positive association between weight cycling and kidney cancer risk (summary relative risk for weight cyclers vs. non-cyclers, 1.51; 95% CI, 1.16, 1.96; I2: 52.2%; 6 studies). Frequent substantial weight cycling was associated with increased risk of kidney cancer, independent of BMI. Our study suggests that weight cycling may be an important risk factor for kidney cancer.

Background Although colorectal cancer (CRC) incidence in the USA is declining overall, its incidence is increasing among those younger than 50 years of age. The reasons underlying the increasing trend are largely unknown, although behavioral changes, such as unhealthy diet and lifestyle factors, may be partially responsible. Design A prospective cohort study included 94 217 women aged 26-45 years at baseline. Validated anthropometric measures and lifestyle information were self-reported biennially. Exposures were four recommendation-based dietary indices—the prime diet quality score and three plant-based dietary indices; and two mechanism-based indices—the empirical dietary and lifestyle index for hyperinsulinemia (EDIH and ELIH). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and for early-onset (before age 50) and after age 50 CRC separately. Results We documented 332 cases of CRC during 24 years of follow-up (2 113 655 person-years), with an average age of 52 ± 7 years at diagnosis. Hyperinsulinemic dietary and lifestyle patterns were associated with a higher risk of CRC. Multivariable-adjusted HRs (95% CIs) comparing participants in the highest versus lowest quartile were: 1.67 for EDIH (95% CI: 1.15-2.44, P-trend = 0.01) and 1.51 for ELIH (95% CI: 1.10-2.08, P-trend = 0.01). Moreover, per 75% increment in rank, ELIH appeared to be a stronger risk factor for early-onset CRC (HR = 1.86, 95% CI: 1.12-3.07) than after age 50 CRC (HR = 1.20, 95% CI: 0.83-1.73, P-heterogeneity = 0.16). The four recommendation-based indices were not significantly associated with overall, early-onset, or after age 50 CRC risk (per 75% increment in rank, HRs ranged from 0.75 to 1.28). Conclusion Dietary and lifestyle patterns contributing to hyperinsulinemia were associated with greater CRC risk in younger women. Moreover, the hyperinsulinemic lifestyle showed a suggestively stronger positive association with early-onset CRC risk, compared with after age 50 CRC. Our findings suggest that dietary and lifestyle interventions to reduce insulinemic potential may be effective for CRC prevention among younger women.

Background Hyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk. Objective To determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality. Design, setting, and participants We prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986–2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr. Outcome measurements and statistical analysis Total, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns—empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern—and prostate cancer risk estimated using Cox proportional hazard regression. Results and limitations During 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01–1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00–1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06–1.35) for advanced, 1.22 (1.04–1.42) for fatal, and 1.20 (1.04–1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00–1.35). Conclusions Hyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease. Patient summary Avoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.

Background: We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts. Methods: Five kinds of pattern scores, including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03; 95% CI, 1.31–3.16; Ptrend = 0.001), EDIH (HR, 1.61; 95% CI, 1.06–2.43; Ptrend = 0.02), and EDIR (HR, 1.62; 95% CI: 1.08–2.42; Ptrend = 0.02) was associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR, 1.89; 95% CI, 1.25–2.87; Ptrend = 0.001) and ELIR (HR, 2.05; 95% CI, 1.34–3.14, Ptrend = 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk. Conclusions: Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development. Impact: Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.

Most cohort studies have only a single physical activity (PA) measure and are thus susceptible to reverse causation and measurement error. Few studies have examined the impact of these potential biases on the association between PA and mortality. A total of 133,819 participants from Nurses' Health Study and Health Professionals Follow-up Study (1986-2014) reported PA through biennial questionnaires. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for PA and mortality using different analytic approaches comparing single (baseline, simple update = most recent) versus repeated (cumulative average) measures of PA and applying various lag times separating PA measurement and time at risk. Over 3.2 million person-years, we documented 47,273 deaths. The pooled multivariable-adjusted HR (95% CI) of all-cause mortality per 10 MET-hour/week was 0.95 (0.94-0.96) for baseline PA, 0.78 (0.77-0.79) for simple updated PA and 0.87 (0.86-0.88) for cumulative average PA in the range of 0-50 MET-hour/week. Simple updated PA showed the strongest inverse association, suggesting larger impact of reverse causation. Application of 2-year lag substantially reduced the apparent reverse causation (0.85 (0.84-0.86) for simple updated PA and 0.90 (0.89-0.91) for cumulative average PA), and 4-12-year lags had minimal additional effects. In the dose-response analysis, baseline or simple updated PA showed a J or U-shaped association with all-cause mortality while cumulative average PA showed an inverse association across a wide range of PA (0-150 MET-hour/week). Similar findings were observed for different specific mortality causes. In conclusion, PA measured at baseline or with short lag time was prone to bias. Cumulative average PA showed robust evidence that PA is inversely associated with mortality in a dose-response manner.

OBJECTIVE The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk. RESEARCH DESIGN AND METHODS We calculated dietary scores from baseline (1993–1998) food frequency questionnaires among 73,495 postmenopausal women in the Women’s Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes. RESULTS During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32–1.68; Ptrend < 0.0001) and EDIP 1.45 (1.29–1.63; Ptrend < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88–1.12; Ptrend = 0.46) and GL 1.01 (0.89–1.16; Ptrend = 0.30). CONCLUSIONS Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.

Background Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. Objectives Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. Methods This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses' Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. Results We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows: Q1: 0.14 ± 0.05; Q2: 0.04 ± 0.06; Q3: 0.008 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows: Q1: 0.25 ± 0.09; Q2: 0.23 ± 0.09; Q3: 0.07 ± 0.09; Q4: 0.02 ± 0.09; and Q5: -0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows: Q1: 0.16 ± 0.05; Q2: 0.07 ± 0.05; Q3: 0.01 ± 0.05; Q4: 0.01 ± 0.05; and Q5: -0.05 ± 0.05 (P-trend = 0.0004). Conclusions Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.

PURPOSE: Although evidence suggests an inverse association between yogurt consumption and the risk of disorders, such as type 2 diabetes and certain cancers, the mechanisms remain poorly understood. We aimed to examine the association between yogurt consumption and concentrations of plasma soluble CD14, a marker of gut barrier dysfunction. METHODS: We analyzed cross-sectional data from 632 women in the Nurses’ Health Study (1989-1990) and 444 men in the Health Professionals Follow-up Study (1993-1994) with soluble CD14 concentrations. We estimated yogurt consumption from food frequency questionnaires. We used multivariable -adjusted linear regression models to estimate the percentage difference (95% CI) of soluble CD14 concentrations by yogurt consumption. RESULTS: Among men, higher consumption was associated with a lower soluble CD14 concentration (at least 2 cups/week vs. non-consumers; unadjusted % difference: −7.6%; 95%CI: −13.0%, −2.1%; P(trend)=0.003). The inverse association was slightly attenuated following multivariable adjustment (% difference: −5.8%; 95%CI: −11.0%, −0.1%; P(trend)=0.01). For the same comparison, yogurt consumption was inverse but not statistically significant associated with soluble CD14 concentration in women (% difference: −1.2%; 95%CI: −5.6%, 3.5%; P(trend)=0.64). In stratified analyses, the inverse association between yogurt consumption and the concentrations of soluble CD14 was slightly stronger in men who consumed alcohol at least 20 g/day. CONCLUSIONS: Higher yogurt consumption was associated with lower soluble CD14 concentrations, especially in men. Our findings suggest the strengthening of gut barrier function as a plausible mechanism for the observed inverse associations of yogurt consumption with gastrointestinal diseases and disorders involving other systems.

Background Muscle-strengthening activities have been recommended for health benefits. However, it is unclear whether resistance training is associated with cancer risk, independent of total physical activity. Methods A prospective cohort study followed 33,787 men from the Health Professionals Follow-up Study (1992–2014). Cumulative average of resistance training (hours/week) was assessed through biennial questionnaires up to 2 years before cancer diagnosis. Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI). Results During 521,221 person-years of follow-up, we documented 5,158 cancer cases. Resistance training was not associated with total cancer risk (HR per 1-h/week increase: 1.01; 95% CI 0.97, 1.05). We found an inverse association between resistance training and bladder cancer (HR per 1-h/week increase: 0.80; 95% CI 0.66, 0.96) and kidney cancer (HR per 1-h/week increase 0.77; 95% CI 0.58, 1.03; Ptrend = 0.06), but the association was marginal for the latter after adjustment for confounders and total physical activity. Compared to participants engaging in aerobic activities only, combined resistance training and aerobic activities showed stronger inverse associations with kidney cancer risk. Conclusions Resistance training was associated with lower risk of bladder and kidney cancers. Future studies are warranted to confirm our findings.

Background:Dietary patterns promoting hyperinsulinemia and chronic inflammation, including the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and cancer. EDIH was developed using plasma C-peptide, whereas EDIP was based on plasma C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha receptor 2 (TNF-αR2). We investigated whether these dietary patterns were associated with a broader range of relevant biomarkers not previously tested.Methods:In this cross-sectional study, we included 35,360 women aged 50–79 years from the Women's Health Initiative with baseline (1993–1998) fasting blood samples. We calculated EDIH and EDIP scores from baseline food frequency questionnaire data and tested their associations with 40 circulating biomarkers of insulin response/insulin-like growth factor (IGF) system, chronic systemic inflammation, endothelial dysfunction, lipids, and lipid particle size. Multivariable-adjusted linear regression was used to estimate the percent difference in biomarker concentrations per 1 standard deviation increment in dietary index. FDR-adjustedp< 0.05 was considered statistically significant.Results:Empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) were significantly associated with altered concentrations of 25 of the 40 biomarkers examined. For EDIH, the percent change in biomarker concentration in the insulin-related biomarkers ranged from +1.3% (glucose) to +8% (homeostatic model assessment for insulin resistance) and −9.7% for IGF-binding protein-1. EDIH impacted inflammation and endothelial dysfunction biomarkers from +1.1% (TNF-αR2) to +7.8% (CRP) and reduced adiponectin by 2.4%; and for lipid biomarkers: +0.3% (total cholesterol) to +3% (triglycerides/total cholesterol ratio) while reducing high-density lipoprotein cholesterol by 2.4%. EDIP showed a similar trend of associations with most biomarkers, although the magnitude of association was slightly weaker for the insulin-related biomarkers and stronger for lipids and lipid particle size.Conclusions:Dietary patterns with high potential to contribute to insulin hypersecretion and to chronic systemic inflammation, based on higher EDIH and EDIP scores, were associated with an unfavorable profile of circulating biomarkers of glucose-insulin dysregulation, chronic systemic inflammation, endothelial dysfunction and dyslipidemia. The broad range of biomarkers further validates EDIH and EDIP as mechanisms-based dietary patterns for use in clinical and population-based studies of metabolic and inflammatory diseases.

OBJECTIVE Insulin response is related to overall health. Diet modulates insulin response. We investigated whether insulinemic potential of diet is associated with risk of all-cause and cause-specific mortality. RESEARCH DESIGN AND METHODS We prospectively followed 63,464 women from the Nurses’ Health Study (1986–2016) and 42,880 men from the Health Professionals Follow-up Study (1986–2016). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using a food-based empirical dietary index for hyperinsulinemia (EDIH), which was predefined based on predicting circulating C-peptide concentrations. RESULTS During 2,792,550 person-years of follow-up, 38,329 deaths occurred. In the pooled multivariable-adjusted analyses, a higher dietary insulinemic potential was associated with an increased risk of mortality from all-cause (hazard ratio [HR] comparing extreme quintiles: 1.33; 95% CI 1.29, 1.38; P-trend CONCLUSIONS Higher insulinemic potential of diet was associated with increased risk of all-cause, CVD, and cancer mortality. Adopting a diet with low insulinemic potential might be an effective approach to improve overall health and prevent premature death.

Diabetic nephropathy (DN) causes much morbidity and mortality in T1D, necessitating better mechanistic insights for improved prevention and therapy. In addition to hyperglycemia, DN pathogenesis may involve inflammation or insulin resistance, and diets modulating these pathways may impact DN risk. In this cross-sectional study, we examined associations of inflammatory and insulinemic potentials of whole diets with DN in a subset of the Joslin 50-year Medalist Study, comprising 570 individuals with T1D >50 years and food frequency questionnaire data. Empirical dietary inflammatory pattern (EDIP) and empirical index for hyperinsulinemia (EDIH) scores were separately derived as weighted sums of foods and beverages previously shown to be predictive of circulating inflammatory biomarkers or C-peptide levels, respectively. In multivariable-adjusted logistic regression models, including age, sex, BMI, exercise, lipids, HbA1c, and hypertension as covariates, 1 S.D. increments in EDIP and EDIH associated with 0.46 (95% CI 0.26-0.84, p=0.01) and 0.31 (95% CI 0.15-0.68, p=0.003) reduced odds of being protected against DN (167 events, CKD-EPI eGFR < 60 ml/min/1.73 m2), respectively. Both scores inversely correlated with continuous eGFR (p=0.03 and 0.0003, respectively). Neither index associated with HbA1c, retinopathy severity, neuropathy or cardiovascular diseases. Both scores positively correlated (p Disclosure H. Shah: None. A. Adam: None. T. Boumenna: None. M. Yu: None. J. Li: None. F. Hu: None. F. K. Tabung: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc.

Inflammatory reaction has been linked to bladder cancer. Diet, which drives systemic inflammation, may be considered a modifiable risk factor for bladder cancer. We examined the association of diet with pro-inflammatory potential and bladder cancer risk using the novel EDIP (empirical dietary inflammatory pattern) score comprising predefined food groups determining a pattern most predictive of plasma inflammatory markers.We followed a total of 172,802 women in the NHS (Nurses' Health Study) from 1984 to 2012 and the NHS II from 1991 to 2013 as well as 45,272 men in the HPFS (Health Professionals Follow-Up Study) from 1986 to 2012. Multivariable adjusted Cox regression models were used to estimate the RR and 95% CI of bladder cancer across EDIP score quintiles. We performed inverse variance weighted meta-analysis to pool estimates across cohorts stratified by smoking status.During 4,872,188 person-years of observation 1,042 incident bladder cancer cases were identified. Overall, high EDIP scores reflecting dietary patterns with pro-inflammatory potential were not associated with a higher risk of bladder cancer (quintile 5 vs 1 pooled multivariable adjusted RR 0.92, 95% CI 0.75-1.12, pWe observed no association between diets with pro-inflammatory potential and bladder cancer risk. Although additional studies are needed to explore other nutritional pathways with the potential for bladder cancer prevention, our results suggest that diets associated with inflammation are not associated with bladder cancer risk.

BACKGROUND: The influence of long-term dietary patterns on weight gain and the underlying potential biological mechanisms are not fully understood. OBJECTIVE: We prospectively examined the association of changes in 2 empirical hypothesis-oriented dietary patterns (insulinemic and inflammatory) and weight gain over 24 y at 4-y intervals. METHODS: We followed 54,397 women in the Nurses’ Health Study and 33,043 men in the Health Professionals Follow-Up Study (1986–2010), and computed the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores from food frequency questionnaires administered every 4 y. Both scores are weighted sums of 18 food groups, which characterize dietary insulinemic or inflammatory potential based on plasma levels of insulin response or inflammatory biomarkers. We used multivariable-adjusted linear regression to examine 4-y changes in the dietary scores and weight change within the same period. RESULTS: The mean baseline body mass index (BMI, in kg/m(2)) was 25.4. Compared with participants who made minimal dietary changes (quintile 3) over 6 4-y periods; participants who changed their diets toward lower insulinemic or inflammatory potential (quintile 1) gained significantly less weight (in kilograms per 4 y) independent of total energy intake, BMI, physical activity, and smoking status: EDIH: −0.65 (95% CI: −0.73, −0.57), EDIP: −0.29 (−0.37, −0.21) among women; and EDIH: −0.60 (−0.71, −0.49), EDIP: −0.19 (−0.27, −0.07) among men. In contrast, those who changed their diets toward higher insulinemic or inflammatory potential (quintile 5) gained significantly more weight: EDIH: 0.43 (0.36, 0.51), EDIP: 0.15 (0.07, 0.23) among women; and EDIH: 0.49 (0.38, 0.59), EDIP: 0.22 (0.11, 0.33) among men (P-trend

Background Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. Objectives The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. Methods We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. Results Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. Conclusion Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.

Several biological mechanisms linking physical activity with cancer have been proposed. However, the influence of specific components of physical activity (volume, type and intensity), and their interaction with adiposity and diet, on cancer-related biomarkers remain unclear. We used cross-sectional data on 7,219 men in the Health Professionals Follow-up Study (1992-1994) with C-reactive protein (CRP), interleukin-6 (IL6), tumor necrosis factor alpha receptor 2 (TNFαR2), adiponectin, C-peptide and triglycerides/high-density lipoprotein cholesterol ratio (TG/HDL). Details on physical activity, diet and adiposity were assessed by questionnaires. We used multivariable-adjusted linear regression analyses to estimate relative concentrations of biomarkers by physical activity. Total physical activity was favorably associated with all biomarkers in a fairly linear manner. Comparing the highest (63+ metabolic equivalent (MET)-hr/week) to the lowest (0-8.9 MET-hr/week) physical activity groups, the percent relative difference in concentration of biomarkers was -31% for CRP, -22% for IL6, -8% for TNFαR2, +9% for adiponectin, -22% for C-peptide, and -20% for TG/HDL. These differences were modestly attenuated after adjustment for adiposity. For the same total MET-hours of physical activity, the association was stronger for men engaging in both aerobic and resistance exercises compared to those engaging in aerobic only. However, no difference was found between those engaging in vigorous activities (≥20% of total MET-hours) compared to those who did smaller amount of vigorous activities. Physical activity showed similar associations for these biomarkers regardless of adiposity and dietary pattern. In conclusion, high physical activity, preferably aerobic plus resistance training, was associated with favorable cancer-related biomarkers.

Inflammation and hyperinsulinemia may drive associations between adiposity and colorectal cancer (CRC) risk, but few studies have examined this hypothesis using mediation analysis. We used inverse odds ratio weighting and logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for estimated total effects (OR(TE)) of body mass index, waist circumference, and adult weight gain on CRC risk, and estimated effects operating through seven inflammatory and metabolic biomarkers (natural indirect effect; OR(NIE)) or through paths independent of these biomarkers (natural direct effect; OR(NDE)) among 209 CRC cases and 382 matched controls nested within the Health Professionals Follow-up Study, a prospective cohort of male health professionals. A one-interquartile range (IQR) increase in body mass index (3.6 kg/m(2)) was associated with an OR(TE) of 1.40 (95% CI: 1.13, 1.73), which decomposed into an OR(NIE) of 1.26 (95% CI: 0.97, 1.52) and an OR(NDE) of 1.11 (0.87, 1.42), with possibly stronger mediation by these biomarkers for adult weight gain (IQR = 10.4kg; OR(TE) = 1.32 [95% CI: 1.06, 1.64]; OR(NIE) = 1.47 [95% CI: 1.01, 1.81]; OR(NDE) = 0.89 [95% CI: 0.72, 1.11]), but no mediation for waist circumference. Mediation appeared to be stronger for the metabolic biomarkers than the inflammatory biomarkers. Inflammatory and metabolic mechanisms may mediate associations between both body mass index and adult weight gain with CRC risk.

Background Many dietary indexes exist for chronic disease prevention, but the optimal dietary pattern for colorectal cancer prevention is unknown. Objective We sought to determine associations between adherence to various dietary indexes and incident colorectal cancer in 2 prospective cohort studies. Design We followed 78,012 women in the Nurses' Health Study and 46,695 men in the Health Professionals Follow-up Study from 1986 and 1988, respectively, until 2012. We created dietary index scores for the Dietary Approaches to Stop Hypertension (DASH) diet, Alternative Mediterranean Diet (AMED), and Alternative Healthy Eating Index-2010 (AHEI-2010) and used Cox regression to estimate HRs and 95% CIs for risk of colorectal cancer (CRC) and by anatomic subsite. We also conducted latency analyses to examine associations between diet and CRC risk during different windows of exposure. We conducted analyses in men and women separately, and subsequently pooled these results in a random-effects meta-analysis. Results We documented 2690 colorectal cancer cases. Pooled multivariable HRs for colorectal cancer risk comparing the highest to lowest quintile of diet scores were 0.89 (95% CI: 0.74, 1.08; P-trend = 0.10) for DASH, 0.89 (95% CI: 0.73, 1.10; P-trend = 0.31) for AMED, and 0.95 (95% CI: 0.83, 1.09; P-trend = 0.56) for AHEI-2010 (P-heterogeneity ≥ 0.07 for all). In sex-specific analyses, we observed stronger associations in men for all dietary indexes (DASH: multivariable HR = 0.81, 95% CI: 0.66, 0.98; P-trend = 0.003; AMED: multivariable HR = 0.80, 95% CI: 0.65, 0.98; P-trend = 0.02; AHEI-2010: multivariable HR = 0.88, 95% CI: 0.72, 1.07; P-trend = 0.04) than in women (multivariable HRs range from 0.98 to 1.01). Conclusions Adherence to the DASH, AMED, and AHEI-2010 diets was inversely associated with colorectal cancer risk in men. These diets were not associated with colorectal cancer risk in women. This observational study was registered at http://www.clinicaltrials.gov as NCT03364582.

Background & aims Recent increasing trends in early-onset colorectal cancer (CRC) strongly supports that early-life diet is involved in CRC development. However, data are lacking on the relationship with high sugar intake during early life. Methods We prospectively investigated the association of adolescent simple sugar (fructose, glucose, added sugar, total sugar) and sugar-sweetened beverage (SSB) intake with CRC precursor risk in 33,106 participants of the Nurses' Health Study II who provided adolescent dietary information in 1998 and subsequently underwent lower gastrointestinal endoscopy between 1999 and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression for clustered data. Results During follow-up, 2909 conventional adenomas (758 high-risk) and 2355 serrated lesions were identified (mean age at diagnoses, 52.2 ± 4.3 years). High sugar and SSB intake during adolescence was positively associated with risk of adenoma, but not serrated lesions. Per each increment of 5% of calories from total fructose intake, multivariable ORs were 1.17 (95% CI, 1.05–1.31) for total and 1.30 (95% CI, 1.06–1.60) for high-risk adenoma. By subsite, ORs were 1.12 (95% CI, 0.96–1.30) for proximal, 1.24 (95% CI, 1.05–1.47) for distal, and 1.43 (95% CI, 1.10–1.86) for rectal adenoma. Per 1 serving/day increment in SSB intake, ORs were 1.11 (95% CI, 1.02–1.20) for total and 1.30 (95% CI, 1.08–1.55) for rectal adenoma. Contrary to adolescent intake, sugar and SSB intake during adulthood was not associated with adenoma risk. Conclusions High intake of simple sugars and SSBs during adolescence was associated with increased risk of conventional adenoma, especially rectal adenoma.

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 FFQ 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) with the lowest quintile was 0·99 (95 % CI 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 with the lowest was 1·39 (95 % CI 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 non-smokers who were obese. Hence, this association must be interpreted with caution.

Background: Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI). Methods: We calculated dietary scores from baseline (1993–1998) food frequency questionnaires among 129,241 women, 50–79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk. Results: During a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06–1.66); EDIP, 1.26 (0.98–1.63); GI, 1.26 (0.96–1.67); and GL, 1.23 (0.96–1.57); although interactions were not significant (all Pinteraction >0.05). Separately, we observed inverse associations between GI [0.86 (0.76–0.96), Pinteraction = 0.0068] and GL [0.83 (0.73–0.93), Pinteraction = 0.0075], with pancreatic cancer risk among normal-weight women. Conclusions: We observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk. Impact: The elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.

BackgroundThe influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood.MethodsWe 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.ResultsIn 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.ConclusionsIncident 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.

Purpose: Inflammatory contributions from diet and adiposity may interact with respect to the development of type 2 diabetes mellitus (T2DM). We investigated the degree to which adiposity modified the association between dietary inflammatory potential and incident T2DM. Methods: Data from 6,016 US men in the Aerobics Center Longitudinal Study who completed a 3-day diet record were used. The inflammatory potential of diet was characterized by the Dietary Inflammatory Index (DII®), and adiposity was assessed with body mass index, waist circumference, body fat percentage (BF) and waist-to-height ratio. Inverse probability weights were used in modified Poisson regression models to examine whether adiposity modifies the relationship between the DII and T2DM, while accounting for selection bias from participants who were lost to follow-up. Results: There were 336 incident cases of T2DM after a mean follow-up of 6.5 years. DII scores were not significantly associated with T2DM incidence in multivariable models, but point estimates were consistently elevated across increasing DII quartiles compared to the most anti-inflammatory DII quartile. In the model that evaluated BF, the term for overall effect modification was significant (p = 0.02), but there was no evidence of effect modification on the multiplicative and additive scales when examined further. Effect modification was not present for any other adiposity measures. Conclusions: We did not observe evidence that a pro-inflammatory diet, as measured by the DII, is associated with incidence of T2DM, nor evidence that adiposity modifies a potential relationship. Further investigation is needed in larger cohorts with longer follow-up. Keywords: Adiposity, Obesity, Effect modification, Dietary pattern, Epidemiology, Inflammation

The dietary insulin index directly estimates the postprandial insulin secretion potential of foods, whereas the empirical dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemic potential of usual diets based on fasting plasma C-peptide, and is primarily reflective of insulin resistance. It is unknown whether these insulin-related indices are predictive of an integrated measure of insulin secretion. We conducted a cross-sectional analysis that included 293 non-diabetic men with 24-h urinary C-peptide data from the Men’s Lifestyle Validation Study. EDIH, dietary insulin index and dietary insulin load were calculated using validated FFQ. We conducted multivariable-adjusted linear regression to estimate relative and absolute concentrations of 24-h urinary C-peptide. In multivariable-adjusted models, we found a significant positive association between all three insulin-related dietary indices and 24-h urinary C-peptide (P < 0·05). Relative concentrations of 24-h urinary C-peptide per 1-sd increase in insulin-related dietary indices were 1·12 (95 % CI 1·02, 1·23) for EDIH, 1·18 (95 % CI 1·07, 1·29) for dietary insulin index and 1·16 (95 % CI 1·06, 1·27) for dietary insulin load. When we further adjusted for BMI, the association was attenuated for EDIH, to 1·07 (95 % CI 0·98, 1·16), and remained unchanged for dietary insulin index and dietary insulin load. In conclusion, EDIH, dietary insulin index and dietary insulin load were predictive of integrated insulin secretion assessed by 24-h urinary C-peptide. Findings after adjustment for BMI appear to confirm the relation of EDIH to insulin resistance and dietary insulin index/load to insulin secretion; the respective constructs of the two dietary indices.

Background Chronic inflammation may promote initiation and progression of pancreatic cancer, but no studies have examined the association between inflammation in the period before diagnosis and pancreatic cancer survival. Methods We prospectively examined the association of prediagnostic plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 with survival among 492 participants from 5 large US prospective cohort studies who developed pancreatic cancer. Using an empirical dietary inflammatory pattern (EDIP) score, we evaluated whether long-term proinflammatory diets were associated with survival among 1153 patients from 2 of the 5 cohorts. Cox proportional hazards regression was used to estimate hazard ratios for death with adjustment for potential confounders. All statistical tests were 2-sided. Results Higher prediagnostic levels of C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor 2 were individually associated with reduced survival (Ptrend = .03, .01, and .04, respectively). Compared with patients with a combined inflammatory biomarker score of 0 (all 3 marker levels below medians), those with a score of 3 (all 3 marker levels above medians) had a hazard ratio for death of 1.57 (95% confidence interval = 1.16 to 2.12; Ptrend = .003), corresponding to median overall survival times of 8 vs 5 months. Patients consuming the most proinflammatory diets (EDIP quartile 4) in the prediagnostic period had a hazard ratio for death of 1.34 (95% confidence interval = 1.13 to 1.59; Ptrend = .01), compared with those consuming the least proinflammatory diets (EDIP quartile 1). Conclusion Prediagnostic levels of inflammatory biomarkers and long-term proinflammatory diets were inversely associated with pancreatic cancer survival.

Key Points Question Is the length of the interscreening period associated with breast cancer prognostic factors and mortality in interval breast cancers compared with cancers detected by screening? Findings In this study using data from the Women’s Health Initiative, a national study among postmenopausal women, interval breast cancers diagnosed within 1 year from a mammogram with negative results were associated with worse breast cancer–specific mortality compared with breast cancers detected by screening. Mortality remained statistically significantly higher after adjustment for trial group, molecular subtype, other risk factors, histologic characteristics, and either tumor size or lymph node but not when tumor size and lymph node were included in the model; no differences were observed between interval cancers diagnosed between 1 and 2.5 years from a mammogram with negative results and breast cancers detected by screening. Meaning Interval cancers occurring within 1 year from a mammogram with negative results may have a unique biology that accounts for aggressive features., Importance Interval breast cancers (IBCs) are cancers that emerge after a mammogram with negative results but before the patient’s next scheduled screening. Interval breast cancer has a worse prognosis than cancers detected by screening; however, it is unknown whether the length of the interscreening period is associated with prognostic features and mortality. Objective To compare the prognostic features and mortality rate of women with IBCs diagnosed within 1 year or between 1 and 2.5 years of a mammogram with negative results with the prognostic features and mortality rate of women with breast cancers detected by screening. Design, Setting, and Participants This cohort study used mammography data, tumor characteristics, and patient demographic data from the Women’s Health Initiative study, which recruited participants from 1993 to 1998 and followed up with participants for a median of 19 years. The present study sample for these analyses included women aged 50 to 79 years who participated in the Women’s Health Initiative study and includes data collected through March 31, 2018. There were 5455 incidents of breast cancer; only 3019 women compliant with screening were retained in analyses. Statistical analysis was performed from October 25, 2018, to November 24, 2019. Breast cancers detected by screening and IBCs were defined based on mammogram history, date of last mammogram, type of visit, and results of examination. Interval breast cancers were subdivided into those occurring within 1 year or between 1 and 2.5 years after the last protocol-mandated mammogram with negative results. Main Outcomes and Measures The primary outcome of this study was breast cancer–specific mortality for each case of breast cancer detected by screening and IBCs detected within 1 year or between 1 and 2.5 years from a mammogram with negative results. Secondary outcomes included prognostic and tumor characteristics for each group. Comparisons between groups were made using the t test, the χ2 test, and Fine-Gray multivariable cumulative incidence regression analyses. Results Among the 3019 participants in this analysis, all were women with a mean (SD) age of 63.1 (6.8) years at enrollment and 68.5 (7.1) years at diagnosis. A total of 1050 cases of IBC were identified, with 324 (30.9%) diagnosed within 1 year from a mammogram with negative results and 726 (69.1%) diagnosed between 1 and 2.5 years after last mammogram with negative results. The remaining 1969 cases were breast cancers detected by screening. Interval breast cancers diagnosed within 1 year from a mammogram with negative results had significantly more lobular histologic characteristics (13.0% vs. 8.1%), a larger tumor size (1.97 cm vs 1.43 cm), a higher clinical stage (28.4% vs 17.3% regional and 3.7% vs 0.6% distant), and more lymph node involvement (27.1% vs 17.0%) than cancers detected by screening. Unadjusted breast cancer–specific mortality hazard ratios were significantly higher for IBCs diagnosed within 1 year from a mammogram with negative results compared with breast cancers detected by screening (hazard ratio, 1.92; 95% CI, 1.39-2.65). Higher breast cancer–specific mortality remained statistically significant for IBCs diagnosed within 1 year after adjusting for trial group, molecular subtype, waist to hip ratio, histologic characteristics, and either tumor size (hazard ratio, 1.46; 95% CI, 1.03-2.08) or lymph node involvement (hazard ratio, 1.44; 95% CI, 1.03-2.01). However, significance was lost when tumor size and lymph node involvement were both included in the model (hazard ratio, 1.34; 95% CI, 0.96-1.88). Interval breast cancers diagnosed between 1 and 2.5 years from a mammogram with negative results were not different from breast cancers detected by screening based on prognostic factors or mortality. Conclusions and Relevance Women with IBCs diagnosed within 1 year of negative mammogram results overall were associated with worse survival than women with breast cancers detected by screening. These differences in survival may be due to a uniquely aggressive biology among IBC cases., This cohort study uses data from the Women’s Health Initiative study to compare the prognostic features and mortality rate of women with interval breast cancers diagnosed within 1 year or between 1 and 2.5 years of a mammogram with negative results with the prognostic features and mortality rate of women with breast cancers detected by screening.

Prostate cancer is common in countries with affluent dietary patterns and represents a heterogeneous collection of subtypes with varying behavior. Reductionist strategies focusing on individual nutrients or foods have not clearly defined risk factors. We have developed mechanisms-based dietary patterns focusing upon inflammation and chronic insulin hypersecretion, processes that are hypothesized to impact prostate carcinogenesis. In the Prostate, Lung, Colorectal, and Ovarian cancer cohort, we calculated the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores from food frequency questionnaire data among 3,517 men and women who provided a blood sample at enrollment. We used these scores in multivariable-adjusted linear regression to validate EDIH and EDIP against relevant circulating biomarkers. In a separate sample of 49,317 men, we used multivariable-adjusted Cox regression to evaluate associations of EDIH and EDIP with prostate cancer (total and subtypes) risk. Participants consuming the most hyperinsulinemic diets (EDIH quintile 5) had significantly higher concentrations of C-peptide, insulin, c-reactive protein, TNFα-R2, and lower adiponectin, than those in quintile 1. Similarly, participants consuming the most proinflammatory diets had significantly higher concentrations of IL6, TNFα-R2, C-peptide, insulin, and lower adiponectin. Men consuming hyperinsulinemic diets were at higher total prostate cancer risk: HRquintile5vs1, 1.11; 95% confidence interval (CI), 1.01–1.23; P trend = 0.03, especially high-grade cancer: HRquintile5vs1, 1.18; 95% CI, 1.02–1.37; P trend = 0.06. The EDIP was not associated with prostate cancer risk. In summary, EDIH and EDIP predicted concentrations of known insulinemic and inflammatory biomarkers, and EDIH further predicted risk of future prostate cancer. Interventions to reduce the adverse role of hyperinsulinemic diets may be a means of prostate cancer prevention.

Background The empirical dietary index for hyperinsulinemia (EDIH) score is a validated food-based dietary score that assesses the ability of whole-food diets to predict plasma c-peptide concentrations. Although the EDIH has been extensively applied and found to be predictive of risk of developing major chronic diseases, its influence on cancer survival has not been evaluated. We applied the EDIH score in a large cohort of colorectal cancer patients to assess the insulinemic potential of their dietary patterns after diagnosis and determine its influence on survival outcomes. Methods We calculated EDIH scores to assess the insulinemic potential of post-diagnosis dietary patterns and examined survival outcomes in a sample of 1718 stage I-III colorectal cancer patients in the Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific mortality and all-cause mortality. We also examined the influence of change in diet from pre- to post-diagnosis period, on mortality. Results During a median follow-up of 9.9 years, there were 1008 deaths, which included 272 colorectal cancer-specific deaths (27%). In the multivariable-adjusted analyses, colorectal cancer patients in the highest compared to lowest EDIH quintile, had a 66% greater risk of dying from colorectal cancer: HR, 1.66; 95% CI, 1.03, 2.69; and a 24% greater risk of all-cause death: HR, 1.24; 95%CI, 0.97, 1.58. Compared to patients who consumed low insulinemic diets from pre- to post-diagnosis period, patients who persistently consumed hyperinsulinemic diets were at higher risk of colorectal cancer death (HR,1.51; 95%CI, 0.98, 2.32) and all-cause death (HR, 1.31; 95%CI, 1.04, 2.64). Conclusion Our findings suggest that a hyperinsulinemic dietary pattern after diagnosis of colorectal cancer is associated with poorer survival. Interventions with dietary patterns to reduce insulinemic activity and impact survivorship are warranted.

OBJECTIVE To examine whether proinflammatory and hyperinsulinemic diets are associated with increased risk of type 2 diabetes. RESEARCH DESIGN AND METHODS We prospectively followed 74,767 women from the Nurses’ Health Study (1984–2016), 90,786 women from the Nurses’ Health Study II (1989–2017), and 39,442 men from the Health Professionals Follow-up Study (1986–2016). Using repeated measures of food-frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores, which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide. Diagnoses of type 2 diabetes were confirmed by validated supplementary questionnaires. RESULTS We documented 19,666 incident type 2 diabetes cases over 4.9 million person-years of follow-up. In the pooled multivariable-adjusted analyses, individuals in the highest EDIP or EDIH quintile had 3.11 times (95% CI 2.96–3.27) and 3.40 times (95% CI 3.23–3.58) higher type 2 diabetes risk, respectively, compared with those in the lowest quintile. Additional adjustment for BMI attenuated the associations (hazard ratio 1.95 [95% CI 1.85–2.05] for EDIP and hazard ratio 1.87 [95% CI 1.78–1.98] for EDIH), suggesting adiposity partly mediates the observed associations. Moreover, individuals in both highest EDIP and EDIH quintiles had 2.34 times higher type 2 diabetes risk (95% CI 2.17–2.52), compared with those in both lowest quintiles, after adjustment for BMI. CONCLUSIONS Higher dietary inflammatory and insulinemic potential were associated with increased type 2 diabetes incidence. Findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking dietary patterns and type 2 diabetes development.

Background: Individuals predisposed to higher genetic risk of obesity may need early dietary interventions to prevent obesity and its comorbidities. Hypothesis: Proinflammatory diets may interact with genetic background to modify risks of obesity, long-term weight gain, and cardiovascular disease (CVD). Methods: We prospectively followed 16 281 and 11 832 women in the Nurses’ Health Study I and II, and 10 172 men in Health Professionals Follow-up Study, with available genetic data, for up to 28 years. Diet and weight were assessed every 4 years. Dietary inflammatory potential was assessed by an empirical dietary inflammatory pattern (EDIP) score pre-defined based on associations of foods with inflammatory markers. Polygenic risk scores (PRS) of body mass index (BMI), waist-hip ratio, and body fat mass, developed based on genome-wide association data of 9 million variants in 389 972 UK Biobank participants using LDpred, were applied to characterize genetic predispositions to obesity, central obesity, and adiposity. Results: All 3 PRS were highly predictive for BMI ( Fig. A ). In pooled multivariable analyses, higher EDIP scores were associated with a higher BMI, with the association 2-3 folds stronger comparing participants in the highest 10% to the lowest 10% of genetic risk of obesity/adiposity ( P interaction ≤0.001; Fig. B ). The positive association between EDIP and CVD incidence was 1.6-fold stronger in participants at a higher genetic risk of central obesity ( P interaction =0.04; Fig. C ). In addition, an increase in EDIP scores was associated with a greater long-term weight gain, while a reduction in EDIP was associated with a greater weight loss, comparing participants in the highest 10% of genetic risk to those at lower risks, among participants aged P interaction Fig. D ). Conclusions: Polygenic background modifies associations of proinflammatory diets with obesity, long-term weight change, and CVD risk. PRS may be useful tools to identify individuals in need for early dietary interventions.

BACKGROUND: Symptomatic gallstones cause high financial and disease burden for public health systems. The combined role of diet and other lifestyle factors has not been studied so far. OBJECTIVES: We aimed to investigate the association between an a priori defined healthy lifestyle score (HLS, including healthy diet, moderate alcohol and regular coffee intakes, never smoking, physical activity, and normal weight) and the risk of symptomatic gallstone disease, and to estimate the proportion of cases potentially preventable by lifestyle modification. METHODS: We followed 60,768 women from the Nurses’ Health Study (NHS) and 40,744 men from the Health Professionals Follow-up Study (HPFS), both ongoing prospective cohort studies, from baseline (1986) until 2012. Symptomatic gallstone disease was self-reported and validated by review of medical records. The association between the HLS and the risk of symptomatic gallstone disease was investigated using Cox proportional hazards regression. RESULTS: During 1,156,079 and 769,287 person-years of follow-up, respectively, 6946 women and 2513 men reported symptomatic gallstone disease. Comparing 6 with 0 points of the HLS, the multivariable HR of symptomatic gallstone disease was 0.26 (95% CI: 0.15, 0.45) for women, and 0.17 (95% CI: 0.07, 0.43) for men. For individual lifestyle factors, multivariable and mutually adjusted partial population attributable risks (women and men) were 33% and 23% for BMI

Background & Aims Inflammation is a potential mechanism through which diet modulates the onset of inflammatory bowel disease. We analyzed data from 3 large prospective cohorts to determine the effects of dietary inflammatory potential on the risk of developing Crohn's disease (CD) and ulcerative colitis (UC). Methods We collected data from 166,903 women and 41,931 men in the Nurses' Health Study (1984–2014), Nurses' Health Study II (1991–2015), and Health Professionals Follow-up Study (1986–2012). Empirical dietary inflammatory pattern (EDIP) scores were calculated based on the weighted sums of 18 food groups obtained via food frequency questionnaires. Self-reported CD and UC were confirmed by medical record review. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results We documented 328 cases of CD and 428 cases of UC over 4,949,938 person-years of follow-up. The median age at IBD diagnosis was 55 years (range 29–85 years). Compared with participants in the lowest quartile of cumulative average EDIP score, those in the highest quartile (highest dietary inflammatory potential) had a 51% higher risk of CD (HR 1.51; 95% CI 1.10–2.07; Ptrend = .01). Compared with participants with persistently low EDIP scores (at 2 time points, separated by 8 years), those with a shift from a low to high inflammatory potential of diet or persistently consumed a proinflammatory diet had greater risk of CD (HR 2.05; 95% CI 1.10–3.79 and HR 1.77; 95% CI 1.10–2.84). In contrast, dietary inflammatory potential was not associated with the risk of developing UC (Ptrend = .62). Conclusions In an analysis of 3 large prospective cohorts, we found dietary patterns with high inflammatory potential to be associated with increased risk of CD but not UC.

OBJECTIVE: To investigate the association between three diet-quality scores corresponding to adherence to healthy dietary patterns [alternate Mediterranean (aMed), Alternate Healthy Eating Index (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH)] and the risk of symptomatic gallstone disease. METHODS: The study comprised 43 635 men of the Health Professionals Follow-up Study—an ongoing prospective cohort study of US health professionals. Participants were free of symptomatic gallstone disease and diabetes and provided dietary information every 4 years from 1986 (baseline) until 2012. The aMed, AHEI-2010 and DASH scores were generated and associated with the risk of symptomatic gallstone disease using Cox proportional hazards regression. RESULTS: During 716 904 person-years of follow-up, 2382 incident cases of symptomatic gallstone disease were identified. All three scores were inversely associated with risk of symptomatic gallstone disease after adjustment for potential confounders including age, smoking, physical activity, energy and coffee intake [hazard ratios (HRs) and 95% confidence intervals (CIs)] comparing the highest with the lowest quintiles: aMed: 0.66 (0.57–0.77), AHEI-2010: 0.64 (0.56–0.74) and DASH: 0.66 (0.58–0.76)]. Findings were similar after additional adjustment for body mass index and after inclusion of asymptomatic cases. Associations were stronger when analysis was restricted to cases who had undergone cholecystectomy. CONCLUSIONS: In this prospective cohort of male US health professionals, higher adherence to the aMed, AHEI-2010 and DASH diets was associated with lower risk of symptomatic gallstone disease. Dietary recommendations focusing on high-quality diets targeting symptomatic gallstone disease may lower the incidence of this prevalent disease.

The empirical dietary inflammatory pattern (EDIP) assesses the inflammatory potential of diet in the US population. The aim of this study was to assess the applicability of the EDIP to a Brazilian population.Data from 19- to 75-y-old participants of two editions of the cross-sectional population-based Health Survey of Sao Paulo (HS-SP) were used to validate the EDIP (n = 269; HS-SP 2008), develop an EDIP adapted to a Sao Paulo population, the EDIP-SP (n = 441; HS-SP 2008), and replicate EDIP-SP results in an independent sample (n = 501; HS-SP 2015). Dietary data was assessed through two 24-h recalls and one validated food frequency questionnaire. Plasma C-reactive protein (CRP), and nine other inflammatory biomarkers were determined. EDIP was tested for its association with the 10 inflammatory biomarkers. For development of the EDIP-SP, 21 food groups and their contributions to plasma CRP levels were modeled using a stepwise multiple linear regression adjusted for age and sex.The EDIP was not associated with concentrations of inflammatory biomarkers in a Brazilian population. The components of EDIP-SP were processed meats (β = 0.27; P = 0.082), fruits and vegetables (β = -0.12; P = 0.018), and rice and beans (β = -0.27; P = 0.007). EDIP-SP significantly predicted dietary quality (β = -6.1; P0.001) and its inflammatory potential was replicated among men (β = 0.36; P = 0.01), but not among women (β = 0.05; P = 0.82).EDIP was adapted to the Sao Paulo population. EDIP-SP, composed of high processed meat intake and low intake of fruits and vegetables, and rice and beans, constitutes an important tool to investigate dietary quality based on its inflammatory potential, in Brazilian populations.

BACKGROUND: Insulin response may be important in colorectal cancer development. Diet modulates insulin response and may be a modifiable factor in colorectal cancer prevention. OBJECTIVE: We examined associations between hyperinsulinemic diets and colorectal cancer risk with the use of an empirical dietary index for hyperinsulinemia (EDIH), a food-based index that characterizes dietary insulinemic potential on the basis of circulating C-peptide concentrations. DESIGN: Diet was assessed every 4 y with food-frequency questionnaires in 46,210 men (Health Professionals Follow-Up Study, 1986–2012) and 74,191 women (Nurses’ Health Study, 1984–2012) to calculate EDIH scores. Multivariable-adjusted Cox regression was used to calculate HRs and 95% CIs for colorectal, proximal/distal colon, and rectal cancer risk. RESULTS: During 26 y of follow-up, we documented 2683 incident colorectal cancer cases. Comparing participants in the highest with those in the lowest quintiles, higher EDIH scores were associated with 33% (men: HR: 1.33; 95% CI: 1.11, 1.61; P-trend = 0.0005), 22% (women: HR: 1.22; 95% CI: 1.03, 1.45; P-trend = 0.01), and 26% (men and women: pooled HR: 1.26; 95% CI: 1.12, 1.42; P-trend

Background: Inflammation is important in chronic disease and can be modulated by dietary exposures. Our aim was to examine whether the inflammatory potential of diet after cancer diagnosis, assessed using the dietary inflammatory index (DII), is associated with all-cause and cause-specific mortality among women diagnosed with invasive breast cancer in the Women's Health Initiative (WHI).Methods: Our analytic cohort included 2,150 postmenopausal women, ages 50 to 79 years at baseline, who developed invasive breast cancer during follow-up and completed a food frequency questionnaire (FFQ) on average 1.5 years after diagnosis. Women were followed from breast cancer diagnosis until death or the end of follow-up by October 2014. Energy-adjusted DII (E-DII) scores were calculated from food plus supplements using a nutrient–density approach. Cox proportional hazards models were fit to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, breast cancer–specific, and cardiovascular disease (CVD) mortality.Results: After a median 13.3 years of follow-up, 580 deaths from any cause occurred, including 212 breast cancer deaths and 103 CVD deaths. Lower (i.e., more anti-inflammatory) E-DII scores were associated with a lower risk of CVD mortality (HRQ1VSQ4 = 0.44; 95% CI, 0.24–0.82; Ptrend = 0.005), but not with breast cancer–specific mortality (HRQ1VSQ4 = 0.96; 95% CI, 0.62–1.49; Ptrend = 0.96) or all-cause mortality (HRQ1VSQ4 = 0.82; 95% CI, 0.63–1.05; Ptrend = 0.17).Conclusions: Consuming a more anti-inflammatory diet after breast cancer diagnosis may be a means for reducing risk of death from CVD.Impact: Survival after invasive breast cancer diagnosis may be improved by consumption of an anti-inflammatory diet. Cancer Epidemiol Biomarkers Prev; 27(4); 454–63. ©2018 AACR.

Hazard Ratios (95% CI) of Overall Mortality by Comparing Early-onset and Later-onset CRCAgeUnadjustedAdjusted for Stage OnlyFully Adjusted except StageFully Adjusted Despite significantly reduced colorectal cancer (CRC) incidence in Americans aged 50 and older since 2000, the incidence of CRC among those Citation Format: En Cheng, Holly N. Blackburn, Kimmie Ng, Donna Spiegelman, Melinda L. Irwin, Xiaomei Ma, Cary P. Gross, Fred K. Tabung, Edward L. Giovannucci, Pamela L. Kunz, Xavier Llor, Kevin Billingsley, Jeffrey A. Meyerhardt, Nita Ahuja, Charles S. Fuchs. Survival for patients with early-onset colorectal cancer - An overall survival analysis from the National Cancer Database, 2004-2015 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 898.

While increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC.To characterize the overall survival for individuals with early-onset CRC.This cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020.Early-onset CRC was defined as age younger than 50 years at diagnosis.Overall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression.Among 769 871 individuals with CRC (377 890 [49.1%] women; 636 791 White individuals [82.7%]), 353 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 168 individuals (13.3%) had early-onset CRC, and 78 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%]; P .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96]; P .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90; P .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92]; P .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93]; P .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90]; P .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV.These findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.

Colorectal cancer (CRC) is a global public health problem, with an estimated 1.4 million cases diagnosed worldwide in 2012. Evidence suggests that diet may be important for primary prevention. The 2017 WCRF/AICR Continuous Update Project on colorectal cancer concluded that there is convincing evidence linking several individual dietary factors with CRC risk but the evidence for dietary patterns was limited and inconclusive. In addition, previous reviews and meta-analyses have not critically synthesized various dietary patterns. This review synthesized data from dietary patterns studies over a 17-year period from 2000 to 2016. We included 49 studies (28 cohort and 21 case-control) that examined the association of index-based and empirically derived dietary patterns and CRC risk. A synthesis of food group components comprising the different index-based and empirically derived patterns revealed two distinct dietary patterns associated with CRC risk. A “healthy” pattern, generally characterized by high intake of fruits and vegetables, whole grains, nuts and legumes, fish and other seafood, milk, and other dairy products, was associated with lower CRC risk. In contrast, the “unhealthy” pattern, characterized by high intakes of red meat, processed meat, sugar-sweetened beverages, refined grains, desserts, and potatoes was associated with higher CRC risk. It is notable that the number of food groups, the intake quantity, and the exact types of foods in each food group differed between populations, yet the two dietary patterns remained consistent across regions, especially in empirically derived patterns, an indication of the high reproducibility of these patterns. However, findings for CRC risk in both index-based and empirically derived patterns, differed by sex, with stronger associations among men than women; study design, a higher proportion of case-control studies reported significant findings compared to prospective studies. Consuming a dietary pattern high in fruits and vegetables and low in meats and sweets is protective against CRC risk. However, important questions remain about the mechanisms underlying differences by sex; life-course timing of exposure to dietary patterns; interaction of dietary patterns with the microbiome or with lifestyle factors including physical activity; and elucidation of subsite differences.

Background: We used a food-based empirical dietary inflammatory pattern (EDIP) score to investigate whether diets with higher inflammatory potential are associated with increased ovarian cancer risk. Methods: We followed 186 314 women in the Nurses’ Health Study and Nurses’ Health Study-II, from 1984 to 2013, to examine associations between EDIP scores and ovarian cancer risk, using Cox regression analyses. Results: During 3 454 514 person-years of follow-up, 989 ovarian cancer cases were identified. In pooled multivariable-adjusted analyses, higher EDIP scores (more pro-inflammatory diets) were not significantly associated with ovarian cancer risk (HRquintile5vs1 0.99; 95% CI: 0.80–1.22; P-trend=0.97). Similarly, we found no evidence of heterogeneity by histologic subtype (P-heterogeneity=0.52) or by tumour aggressiveness (P-heterogeneity=0.63). Conclusions: In contrast with two previous case-control studies that found a positive association between a literature-derived nutrient-based dietary inflammatory index and ovarian cancer risk, our prospective analyses using a food-based score observed no evidence of an association.

Background: Although studies to date have confirmed the association between nutrition and frailty, the impact of dietary intake and dietary patterns on survivorship in those with frailty is yet to be examined in a well-powered cohort with validated frailty status. Moreover, previous studies were limited by measurement error from dietary self-reports.Objective: We derived biomarker-calibrated dietary energy and protein intakes to address dietary self-report error. Using these data, we then evaluated the association of mortality in older women with frailty and dietary intake and healthy diet indexes, such as the alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII).Design: The analytic sample included 10,034 women aged 65-84 y with frailty and complete dietary data from the Women's Health Initiative Observational Study. Frailty was assessed with modified Fried's criteria. Dietary data were collected by food-frequency questionnaire.Results: Over a mean follow-up period of 12.4 y, 3259 (31%) deaths occurred. The HRs showed progressively decreased rates of mortality in women with higher calibrated dietary energy intakes (P-trend = 0.003), higher calibrated dietary protein intakes (P-trend = 0.03), higher aMED scores (P-trend = 0.006), and higher DASH scores (P-trend = 0.02). Although the adjusted point estimates of HRs (95% CIs) for frail women scoring in the second, third, and fourth quartiles on DII measures were 1.15 (1.03, 1.27), 1.28 (1.15, 1.42), and 1.24 (1.12, 1.38), respectively, compared with women in the first quartile, no overall effect was observed across quartiles (P-trend = 0.35). Subgroup analyses by chronic morbidity or smoking status or by excluding women with early death did not substantially change these findings.Conclusions: The current study highlights the importance of nutrition in older, frail women. Diet quality and quantity should be considered in managing persons with frailty.

Introduction The Mediterranean and Dietary Approaches to Stop Hypertension diets have been associated with lower dementia risk. We evaluated dietary inflammatory potential in relation to mild cognitive impairment (MCI)/dementia risk. Methods Baseline food frequency questionnaires from n = 7085 women (aged 65–79 years) were used to calculate Dietary Inflammatory Index (DII) scores that were categorized into four groups. Cognitive function was evaluated annually, and MCI and all-cause dementia cases were adjudicated centrally. Mixed effect models evaluated cognitive decline on over time; Cox models evaluated the risk of MCI or dementia across DII groups. Results Over an average of 9.7 years, there were 1081 incident cases of cognitive impairment. Higher DII scores were associated with greater cognitive decline and earlier onset of cognitive impairment. Adjusted hazard ratios (HRs) comparing lower (anti-inflammatory; group 1 referent) DII scores to the higher scores were group 2-HR: 1.01 (0.86–1.20); group 3-HR: 0.99 (0.82–1.18); and group 4-HR: 1.27 (1.06–1.52). Conclusions Diets with the highest pro-inflammatory potential were associated with higher risk of MCI or dementia.

Adherence to the 2007 WCRF/AICR cancer prevention recommendations has been associated with lower cancer risk but the underlying biological mechanisms have not been elucidated. We utilized dietary and lifestyle data from 11,342 women in the Nurses' Health Study and 8,136 men in the Health Professionals Follow-up Study, to investigate associations between adherence scores and markers of inflammation, hormonal and insulin response. Two scores ranging from 0 to 3 were constructed to assess adherence to the energy balance-related recommendations (weight management, physical activity, energy density); and the plant, animal foods and alcohol intake recommendations; with higher scores indicating greater adherence. The following biomarkers were assessed in plasma samples donated by chronic disease-free women (1990) and men (1994): C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α receptor 2 (TNFαR2) and adiponectin for inflammation; estrone and estradiol for hormonal response in women, C-peptide for hyperinsulinemia; and triglycerides/high density lipoprotein-cholesterol (TG/HDL) ratio for insulin resistance. In multivariable-adjusted linear regression analyses, we estimated relative concentrations of biomarkers across adherence categories. There was a significant trend of lower (higher for adiponectin) biomarker concentrations with higher adherence to the energy balance recommendations (all p trend

The glycaemic and insulin indices assess postprandial glycaemic and insulin response to foods, respectively, which may not reflect the long-term effects of diet on insulin response. We developed and evaluated the validity of four empirical indices to assess the insulinaemic potential of usual diets and lifestyles, using dietary, lifestyle and biomarker data from the Nurses’ Health Study (NHS, n 5812 for hyperinsulinaemia, n 3929 for insulin resistance). The four indices were as follows: the empirical dietary index for hyperinsulinaemia (EDIH) and the empirical lifestyle index for hyperinsulinaemia (ELIH); the empirical dietary index for insulin resistance (EDIR) and the empirical lifestyle index for insulin resistance (ELIR). We entered thirty-nine FFQ-derived food groups in stepwise linear regression models, and defined indices as patterns most predictive of fasting plasma C-peptide, for the hyperinsulinaemia pathway (EDIH and ELIH), and of theTAG:HDL-cholesterol ratio, for the insulin-resistance pathway (EDIR and ELIR). We evaluated the validity of indices in two independent samples from NHS-II and Health Professionals Follow-up Study (HPFS) using multivariable-adjusted linear regression analyses to calculate relative concentrations of biomarkers. The EDIH is comprised of eighteen food groups; thirteen were positively associated with C-peptide and five were inversely associated. The EDIR is comprised of eighteen food groups; ten were positively associated with TAG:HDL-cholesterol and eight were inversely associated. Lifestyle indices had fewer dietary components, and included BMI and physical activity as components. In the validation samples, all indices significantly predicted biomarker concentrations – for example, the relative concentrations of the corresponding biomarkers comparing extreme index quintiles in the HPFS were EDIH, 1·29 (95 % CI 1·22, 1·37); ELIH, 1·78 (95 % CI 1·68, 1·88); EDIR, 1·44 (95 % CI 1·34, 1·55); and ELIR, 2·03 (95 % CI 1·89, 2·19); all Ptrend

Inflammation and endogenous growth factors are important in multiple myeloma (MM) pathogenesis. Although diets that modulate these biologic pathways may influence MM patient survival, studies have not examined the association of dietary pattern with MM survival. We conducted pooled prospective survival analyses of 423 MM patients from the Nurses’ Health Study (1986–2016) and the Health Professionals Follow-up Study (1988–2016) using Cox regression models. We used data from repeated food frequency questionnaires (FFQ) to compute dietary patterns as of the last pre-diagnosis FFQ, including the Alternate Healthy Eating Index (AHEI)-2010, alternate Mediterranean Diet, Dietary Approaches to Stop Hypertension, Prudent, Western and empirical dietary inflammatory patterns and empirical dietary indices for insulin resistance and hyperinsulinemia. During follow-up, we documented 295 MM-related deaths among 345 total deaths. MM-specific mortality was 15% to 24% lower per one standard deviation (SD) increase (e.g., towards healthier habits) in favorable dietary pattern scores. For example, the multivariable-adjusted hazard ratio [HR] and 95% confidence interval [CI] per 1-SD increase in AHEI-2010 score were 0.76, 0.67 to 0.87 (P

Aims To investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk. Methods and results Our primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses’ Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate Conclusions We identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.