The influence of long-term dietary patterns on weight gain and the underlying potential biological mechanisms are not fully understood.
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.
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..
The mean baseline body mass index (BMI, in kg/m2) 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 < 0.0001 for all comparisons). Associations were stronger among individuals who were overweight or obese, younger, less physically active, and had never smoked.
High dietary insulinemic and inflammatory potential is associated with substantial long-term weight gain in adult men and women independent of total energy intake. Dietary patterns with low insulinemic and inflammatory potential may aid in weight gain prevention.
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.
Multiple dietary patterns have been associated with different diseases; however, their comparability to improve overall health has yet to be determined. Here, in 205,852 healthcare professionals from ...three US cohorts followed for up to 32 years, we prospectively assessed two mechanism-based diets and six diets based on dietary recommendations in relation to major chronic disease, defined as a composite outcome of incident major cardiovascular disease (CVD), type 2 diabetes and cancer. We demonstrated that adherence to a healthy diet was generally associated with a lower risk of major chronic disease (hazard ratio (HR) comparing the 90th with the 10th percentile of dietary pattern scores = 0.58-0.80). Participants with low insulinemic (HR = 0.58, 95% confidence interval (CI) = 0.57, 0.60), low inflammatory (HR = 0.61, 95% CI = 0.60, 0.63) or diabetes risk-reducing (HR = 0.70, 95% CI = 0.69, 0.72) diet had the largest risk reduction for incident major CVD, type 2 diabetes and cancer as a composite and individually. Similar findings were observed across gender and diverse ethnic groups. Our results suggest that dietary patterns associated with markers of hyperinsulinemia and inflammation and diabetes development may inform on future dietary guidelines for chronic disease prevention.
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).
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).
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).
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.
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The 2018 physical activity guidelines for Americans recommend a minimum of 150 to 300 min/wk of moderate physical activity (MPA), 75 to 150 min/wk of vigorous physical activity (VPA), or an ...equivalent combination of both. However, it remains unclear whether higher levels of long-term VPA and MPA are, independently and jointly, associated with lower mortality.
A total of 116 221 adults from 2 large prospective US cohorts (Nurses' Health Study and Health Professionals Follow-up Study, 1988-2018) were analyzed. Detailed self-reported leisure-time physical activity was assessed with a validated questionnaire, repeated up to 15 times during the follow-up. Cox regression was used to estimate the hazard ratio and 95% CI of the association between long-term leisure-time physical activity intensity and all-cause and cause-specific mortality.
During 30 years of follow-up, we identified 47 596 deaths. In analyses mutually adjusted for MPA and VPA, hazard ratios comparing individuals meeting the long-term leisure-time VPA guideline (75-149 min/wk) versus no VPA were 0.81 (95% CI, 0.76-0.87) for all-cause mortality, 0.69 (95% CI, 0.60-0.78) for cardiovascular disease (CVD) mortality, and 0.85 (95% CI, 0.79-0.92) for non-CVD mortality. Meeting the long-term leisure-time MPA guideline (150-299 min/wk) was similarly associated with lower mortality: 19% to 25% lower risk of all-cause, CVD, and non-CVD mortality. Compared with those meeting the long-term leisure-time physical activity guidelines, participants who reported 2 to 4 times above the recommended minimum of long-term leisure-time VPA (150-299 min/wk) or MPA (300-599 min/wk) showed 2% to 4% and 3% to 13% lower mortality, respectively. Higher levels of either long-term leisure-time VPA (≥300 min/wk) or MPA (≥600 min/wk) did not clearly show further lower all-cause, CVD, and non-CVD mortality or harm. In joint analyses, for individuals who reported <300 min/wk of long-term leisure-time MPA, additional leisure-time VPA was associated with lower mortality; however, among those who reported ≥300 min/wk of long-term leisure-time MPA, additional leisure-time VPA did not appear to be associated with lower mortality beyond MPA.
The nearly maximum association with lower mortality was achieved by performing ≈150 to 300 min/wk of long-term leisure-time VPA, 300 to 600 min/wk of long-term leisure-time MPA, or an equivalent combination of both.
Diet modulates inflammation and inflammatory markers have been associated with cancer outcomes. In the Women's Health Initiative, we investigated associations between a dietary inflammatory index ...(DII) and invasive breast cancer incidence and death.
The DII was calculated from a baseline food frequency questionnaire in 122 788 postmenopausal women, enrolled from 1993 to 1998 with no prior cancer, and followed until 29 August 2014. With median follow-up of 16.02 years, there were 7495 breast cancer cases and 667 breast cancer deaths. We used Cox regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by DII quintiles (Q) for incidence of overall breast cancer, breast cancer subtypes, and deaths from breast cancer. The lowest quintile (representing the most anti-inflammatory diet) was the reference.
The DII was not associated with incidence of overall breast cancer (HRQ5vsQ1, 0.99; 95% CI, 0.91-1.07; Ptrend=0.83 for overall breast cancer). In a full cohort analysis, a higher risk of death from breast cancer was associated with consumption of more pro-inflammatory diets at baseline, after controlling for multiple potential confounders (HRQ5vsQ1, 1.33; 95% CI, 1.01-1.76; Ptrend=0.03).
Future studies are needed to examine the inflammatory potential of post-diagnosis diet given the suggestion from the current study that dietary inflammatory potential before diagnosis is related to breast cancer death.
Abstract
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 < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28–0.37 between the signature and MEDAS; P = 3 × 10−35 to 4 × 10−118). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: hazard ratio HR per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001).
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.
Insulin and insulin-like growth factor (IGF)-1 signaling is a proposed mechanism linking dietary protein and major chronic diseases. However, it is unclear whether animal and plant proteins are ...associated with biomarkers of insulin and IGF axis.
We analyzed a total of 14,709 participants from Nurses’ Health Study and Health Professionals Follow-up Study who had provided a blood sample. Detailed dietary information was assessed using validated food frequency questionnaires. We assessed C-peptide, insulin, IGF-1, and IGF binding proteins (BP). Multivariable-adjusted linear regressions were used to examine associations of animal and plant protein intake with biomarkers after adjusting for confounders.
The medians (5th-95th percentiles) of animal and plant protein intake (% of total energy) were 13% (8–19%) and 5% (4–7%), respectively. Compared to participants in the lowest quintile, those in the highest quintile of animal protein had 4.8% (95% CI: 1.9, 7.9; P-trend<0.001) higher concentration of IGF-1 and -7.2% (95% CI: −14.8, 1.1; P for trend = 0.03) and −11.8% (95% CI: −20.6, −1.9; P-trend<0.001) lower concentration of IGFBP-1 and IGFBP-2, respectively, after adjustment for major lifestyle factors and diet quality. In contrast, no association was observed between animal protein intake and C-peptide, insulin and IGFBP-3. The associations were restricted to participants with at least one unhealthy lifestyle risk factor (i.e., overweight/obese, physical inactivity, smoking, and heavy alcohol intake). Plant protein tended to be strongly associated with numerous biomarkers in age-adjusted analyses but these became largely attenuated or non-significant in multivariable adjustment. Plant protein intake remained positively associated with IGF-1 (P-trend = 0.002) and possibly IGFBP-1 (P-trend = 0.02) after multivariable adjustment. Substitution of plant protein with animal protein sources was associated with lower IGFBP-1. In additional analysis, IGF-1 and IGFBPs were estimated to mediate approximately 5–20% of the association between animal protein and type 2 diabetes.
Higher animal protein intake was associated with higher IGF-1 and lower IGFBP-1 and IGFBP-2, whereas higher plant protein intake was associated with higher IGF-1 and IGFBP-1.
The dietary insulin index (II) directly quantifies dietary effects on postprandial insulin secretion, whereas the empirical dietary index for hyperinsulinemia (EDIH), based on fasting C-peptide ...concentrations, is primarily reflective of insulin resistance. How these scores are related to nonfasting C-peptide in cohort studies has not been examined.
We investigated the extent to which EDIH and II scores predict plasma C-peptide concentrations, in cross-sectional analyses by postprandial duration at blood collection from 1 to ≥15 h.
Both EDIH and II scores were calculated from food-frequency questionnaire data reported by 3964 men in the Health Professionals Follow-up Study (1993–1995) and 6215 women in the Nurses’ Health Study (1989–1990) who were not diabetic. We constructed 12 multivariable-adjusted linear regression models separately in men and women, by postprandial duration, to calculate relative differences and absolute values of plasma C-peptide concentrations in dietary index quintiles.
In both men and women, C-peptide concentrations were elevated 1–2 h after eating and declined with increasing postprandial duration. In men, percent differences in C-peptide concentration in the highest compared with lowest dietary index quintile were: EDIH: 0–1 h: 50%; 2 h: 22%; 14 h: 14%; ≥15 h: 30% (all P-trend< 0.05). II: 0–1 h: 19% (P-trend = 0.09); 2 h: 3% (P-trend = 0.09); 14 h: −6% (P-trend = 0.17); ≥15 h: −15% (P-trend = 0.02). Corresponding results among women were: EDIH: 0–1 h: 29% (P-trend = 0.002); 2 h: 33% (P-trend = 0.009); 14 h: 44% (P-trend < 0.0001); ≥15 h: 40% (P-trend < 0.0001). II: 0–1 h: −12% (P-trend = 0.09); 2 h: 17% (P-trend = 0.09); 14 h: −14% (P-trend = 0.009); ≥15 h: −3% (P-trend = 0.37).
The EDIH was superior to the II in predicting both fasting and nonfasting C-peptide concentrations, suggesting that the EDIH may be better in assessing dietary effects of hyperinsulinemia on disease risk in adult men and women.
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