Previous studies have examined dairy products with various fat contents in relation to type 2 diabetes (T2D) risk, although data regarding dairy fat intake per se are sparse.
We aimed to evaluate the ...association between dairy fat intake and risk of T2D in 3 prospective cohorts. We also examined associations for isocalorically replacing dairy fat with other macronutrients.
We prospectively followed 41,808 men in the Health Professionals Follow-Up Study (HPFS; 1986–2012), 65,929 women in the Nurses’ Health Study (NHS; 1984–2012), and 89,565 women in the NHS II (1991–2013). Diet was assessed quadrennially using validated FFQs. Fat intake from dairy products and other relevant sources was expressed as percentage of total energy. Self-reported incident T2D cases were confirmed using validated supplementary questionnaires. Time-dependent Cox proportional hazards regression was used to estimate the HR for dairy fat intake and T2D risk.
During 4,219,457 person-years of follow-up, we documented 16,511 incident T2D cases. Dairy fat was not associated with risk of T2D when compared with calories from carbohydrates (HR for extreme quintiles: 0.98; 95% CI: 0.95, 1.02). Replacing 5% of calories from dairy fat with other sources of animal fat or carbohydrate from refined grains was associated with a 17% (HR: 1.17; 95% CI: 1.13, 1.21) and a 4% (HR: 1.04; 95% CI: 1.00, 1.08) higher risk of T2D, respectively. Conversely, a 5% calorie replacement with carbohydrate from whole grains was associated with a 7% lower risk of T2D (HR: 0.93; 95% CI: 0.88, 0.98).
Dairy fat intake was not associated with T2D risk in these cohort studies of US men and women when compared with calories from carbohydrate. Replacing dairy fat with carbohydrates from whole grains was associated with lower risk of T2D. Replacement with other animal fats or refined carbohydrates was associated with higher risk.
To review the contribution of the Nurses' Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes.
We carried out a narrative review of 1976 to 2016 NHS ...and NHS II publications.
The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene-environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention.
Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes.
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CEKLJ, DOBA, FSPLJ, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Very-long-chain SFAs (VLCSFAs), such as arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), have demonstrated inverse associations with cardiometabolic conditions, although more ...evidence is needed to characterize their relation with risk of type 2 diabetes (T2D). In addition, little is known regarding their potential dietary and lifestyle predictors.
We aimed to examine the association of plasma and erythrocyte concentrations of VLCSFAs with incident T2D risk.
We used existing measurements of fatty acid concentrations in plasma and erythrocytes among 2854 and 2831 participants in the Nurses´ Health Study (NHS) and Health Professionals Follow-Up Study (HPFS), respectively. VLCSFAs were measured using GLC, and individual fatty acid concentrations were expressed as a percentage of total fatty acids. Incident T2D cases were identified by self-reports and confirmed by a validated supplementary questionnaire. Cox proportional hazards regression was used to evaluate the association between VLCSFAs and T2D, adjusting for demographic, lifestyle, and dietary variables.
During 39,941 person-years of follow-up, we documented 243 cases of T2D. Intakes of peanuts, peanut butter, vegetable fat, dairy fat, and palmitic/stearic (16:0–18:0) fatty acids were significantly, albeit weakly, correlated with plasma and erythrocyte VLCSFA concentrations (|rs| = 0.19). Comparing the highest with the lowest quartiles of plasma concentrations, pooled HRs (95% CIs) were 0.51 (0.35, 0.75) for arachidic acid, 0.43 (0.28, 0.64) for behenic acid, 0.40 (0.27, 0.61) for lignoceric acid, and 0.41 (0.27, 0.61) for the sum of VLCSFAs, after multivariate adjustments for demographic, lifestyle, and dietary factors. For erythrocyte VLCSFAs, only arachidic acid and behenic acid concentrations were inversely associated with T2D risk.
Our findings suggest that, in US men and women, higher plasma concentrations of VLCSFAs are associated with lower risk of T2D. More research is needed to understand the mechanistic pathways underlying these associations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Conventionally grown FVs are the main source of exposure to pesticides.•Overall exposure to pesticides through FV intake is not related to cancer risk.•We cannot dismiss other associations with ...sub-types of specific cancers.•We cannot rule out other relationships with specific chemicals.
Conventionally grown fruits and vegetables (FVs) are the main source of general population exposure to pesticide residues.
To evaluate the relation of intake of high- and low-pesticide-residue FVs with cancer risk.
We followed 150,830 women (Nurses’ Health Study, 1998–2016, and Nurses’ Health Study II, 1999–2017) and 29,486 men (Health Professionals Follow-up Study, 1998–2016) without a history of cancer. We ascertained FV intake via validated food frequency questionnaires and categorized FVs as having high or low pesticide residue levels based on USDA surveillance data. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and site-specific cancer related to quintiles of high- and low-pesticide-residue FV intake.
We documented 23,678 incident cancer cases during 2,862,118 person-years of follow-up. In the pooled multivariable analysis, neither high- nor low-pesticide-residue FV intake was associated with cancer. The HRs (95% CI) per 1 serving/day increase in intake were 0.99 (0.97–1.01) for high- and 1.01 (0.99–1.02) for low-pesticide-residue FVs. Additionally, we found no association between high-pesticide-residue FV intake and risk of specific sites, including malignancies previously linked to occupational pesticide exposure (HR, 95% CI comparing extreme quintiles of intake lung 1.17 (0.95–1.43), non-Hodgkin lymphoma 0.89 (0.72–1.09), prostate 1.31 (0.88–1.93)) or inversely related to intake of organic foods (breasts 1.03 (0.94–1.31)).
These findings suggest that overall exposure to pesticides through FV intake is not related to cancer risk, although they do not rule out associations with specific chemicals or sub-types of specific cancers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of ...self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk.
To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes.
We conducted a nested case–control study in Nurses’ Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989–1090 and 1994–1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013–2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression.
Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk n = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P = 0.015, driven by trans 18:1n–9(ω-9)/elaidic acid OR (95% CI): 1.34 (1.08, 1.66); P = 0.007, trans 18:1n–7/vaccenic acid OR (95% CI): 1.28 (1.04, 1.58); P = 0.023, and trans 18:2n–6t,t OR (95% CI): 1.26 (1.01, 1.57); P = 0.037.
Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype.
We aimed to investigate the association of serum pentadecanoic acid (15:0), a biomarker of dairy fat intake, with incident cardiovascular disease (CVD) and all-cause mortality in a Swedish cohort ...study. We also systematically reviewed studies of the association of dairy fat biomarkers (circulating or adipose tissue levels of 15:0, heptadecanoic acid 17:0, and trans-palmitoleic acid t16:1n-7) with CVD outcomes or all-cause mortality. We measured 15:0 in serum cholesterol esters at baseline in 4,150 Swedish adults (51% female, median age 60.5 years). During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using Swedish registers. In multivariable-adjusted models, higher 15:0 was associated with lower incident CVD risk in a linear dose-response manner (hazard ratio 0.75 per interquintile range; 95% confidence interval 0.61, 0.93, P = 0.009) and nonlinearly with all-cause mortality (P for nonlinearity = 0.03), with a nadir of mortality risk around median 15:0. In meta-analyses including our Swedish cohort and 17 cohort, case-cohort, or nested case-control studies, higher 15:0 and 17:0 but not t16:1n-7 were inversely associated with total CVD, with the relative risk of highest versus lowest tertile being 0.88 (0.78, 0.99), 0.86 (0.79, 0.93), and 1.01 (0.91, 1.12), respectively. Dairy fat biomarkers were not associated with all-cause mortality in meta-analyses, although there were less than or equal to3 studies for each biomarker. Study limitations include the inability of the biomarkers to distinguish different types of dairy foods and that most studies in the meta-analyses (including our novel cohort study) only assessed biomarkers at baseline, which may increase the risk of misclassification of exposure levels. In a meta-analysis of 18 observational studies including our new cohort study, higher levels of 15:0 and 17:0 were associated with lower CVD risk. Our findings support the need for clinical and experimental studies to elucidate the causality of these relationships and relevant biological mechanisms.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants ...of circulating PUFA proportions.
We explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions.
We studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses’ Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models.
After adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype.
Carriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.
Protein intake plays an important role in maintaining the health status of older adults. However, few epidemiologic studies examined midlife protein intake in relation to healthy aging.
The objective ...of this study was to evaluate the long-term role of dietary protein intake in healthy aging among female participants in the prospective Nurses' Health Study (NHS) cohort.
We included 48,762 NHS participants aged <60 y in 1984. Total protein, animal protein, dairy protein (a subset of animal protein), and plant protein were derived from validated food frequency questionnaires. Healthy aging was defined as being free from 11 major chronic diseases, having good mental health, and not having impairments in either cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. We used multivariate logistic regression adjusted for lifestyle, demographics, and health status to estimate the odds ratios (ORs) and 95% confidence intervals for protein intake in relation to healthy aging.
A total of 3721 (7.6%) NHS participants met our healthy aging definition. Protein intake was significantly associated with higher odds of healthy aging. The ORs (95% confidence intervals) per 3%-energy increment with healthy aging were 1.05 (1.01, 1.10) for total protein, 1.07 (1.02, 1.11) for animal protein, 1.14 (1.06, 1.23) for dairy protein, and 1.38 (1.24, 1.54) for plant protein. Plant protein was also associated with higher odds of absence of physical function limitations and good mental status. In substitution analyses, we observed significant positive associations for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein (ORs for healthy aging: 1.22-1.58 for 3% energy replacement with plant protein).
Dietary protein intake, especially plant protein, in midlife, is associated with higher odds of healthy aging and with several domains of positive health status in a large cohort of female nurses.
Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study ...and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk; cis 20:2n-6 was associated with follicular lymphoma risk (OR 95% CI per one standard deviation increase: 1.35 1.03-1.77), and the omega-6/omega-3 PUFA ratio was associated with diffuse large B-cell lymphoma risk (2.33 1.23-4.43). Overall, PUFA did not demonstrate a role in NHL etiology; the two unexpected positive associations lack clear biologic explanations.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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