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Background: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D)., Methods and Findings: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors., Conclusions: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: JYW and RM report research support from Unilever for other projects on fatty acid biomarkers. LCDG reported receiving ad hoc consulting fees from the Life Sciences Research Organization. CH reported receiving fees for a conference from Novartis. IAB reported involvement in a research project partly funded by Unilever. JGR received research grants from Amarin and Astra-Zeneca. DM reported receiving ad hoc honoraria from Bunge, Pollock Institute, and Quaker Oats; ad hoc consulting for Foodminds, Life Sciences Research Organization, Nutrition Impact, Amarin, AstraZeneca, Winston, and Strawn LLP; membership in Unilever North America Scientific Advisory Board; and chapter royalties from UpToDate. SSSM reported receiving an international award and unrestricted grants for meta-analysis work on dairy foods and cardiometabolic diseases from Global and Dutch Dairy Associations. Other authors do not have any conflict of interest to declare.

Objective: To study plasma and dietary linoleic acid (LA) in relation to type 2 diabetes risk in post-myocardial infarction (MI) patients., Research Design and Methods: We included 3,257 patients aged 60-80 years (80% male) with a median time since MI of 3.5 years from the Alpha Omega Cohort and who were initially free of type 2 diabetes. At baseline (2002-2006), plasma LA was measured in cholesteryl esters, and dietary LA was estimated with a 203-item food-frequency questionnaire. Incident type 2 diabetes was ascertained through self-reported physician diagnosis and medication use. Hazard ratios (with 95% CIs) were calculated by Cox regressions, in which dietary LA isocalorically replaced the sum of saturated (SFA) and trans fatty acids (TFA)., Results: Mean ± SD circulating and dietary LA was 50.1 ± 4.9% and 5.9 ± 2.1% energy, respectively. Plasma and dietary LA were weakly correlated (Spearman r = 0.13, P < 0.001). During a median follow-up of 41 months, 171 patients developed type 2 diabetes. Plasma LA was inversely associated with type 2 diabetes risk (quintile [Q]5 vs. Q1: 0.44 [0.26, 0.75]; per 5%: 0.73 [0.62, 0.86]). Substitution of dietary LA for SFA+TFA showed no association with type 2 diabetes risk (Q5 vs. Q1: 0.78 [0.36, 1.72]; per 5% energy: 1.18 [0.59, 2.35]). Adjustment for markers of de novo lipogenesis attenuated plasma LA associations., Conclusions: In our cohort of post-MI patients, plasma LA was inversely related to type 2 diabetes risk, whereas dietary LA was not related. Further research is needed to assess whether plasma LA indicates metabolic state rather than dietary LA in these patients., (© 2019 by the American Diabetes Association.)

Purpose of Review: Dairy products contain both beneficial and harmful nutrients in relation to cardiometabolic diseases. Here, we provide the latest scientific evidence regarding the relationship between dairy products and cardiometabolic diseases by reviewing the literature and updating meta-analyses of observational studies., Recent Findings: We updated our previous meta-analyses of cohort studies on type 2 diabetes, coronary heart disease (CHD), and stroke with nine studies and confirmed previous results. Total dairy and low-fat dairy (per 200 g/d) were inversely associated with a 3-4% lower risk of diabetes. Yogurt was non-linearly inversely associated with diabetes (RR = 0.86, 95% CI: 0.83-0.90 at 80 g/d). Total dairy and milk were not associated with CHD (RR~1.0). An increment of 200 g of daily milk intake was associated with an 8% lower risk of stroke. The latest scientific evidence confirmed neutral or beneficial associations between dairy products and risk of cardiometabolic diseases.

Background: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D)., Methods and Findings: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist., Conclusions: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JHYW and RM report research support from Unilever for other projects of the FORCE on other fatty acid biomarkers. RM reports personal fees from the World Bank and Bunge outside the submitted work. IAB reported involvement in a research project partly funded by Unilever. JMG and JdG received funding from Unilever for epidemiological studies of dietary and circulating fatty acids and cardiometabolic disease and for research on assessment of fatty acids. LCdG reported receiving ad hoc consulting fees from the Life Sciences Research Organization. CH reported receiving fees for a conference from Novartis. NGF is an invited member (unpaid) of ILSI-Europe Qualitative Fat Intake Task Force Expert Group on update on health effects of different saturated fats. DM reports research funding from the NIH and the Gates Foundation; personal fees from GOED, DSM, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin, Acasti Pharma, and America’s Test Kitchen; scientific advisory board, Omada Health, Elysium Health, and DayTwo; and chapter royalties from UpToDate; all outside the submitted work. Patents US8889739 and US9987243 to Tufts University (unlicensed), listing DM as a co-inventor, for use of trans-palmitoleic acid to prevent and treat insulin resistance, type 2 diabetes, and related conditions, as well as reduce metabolic risk factors. SSSM reported receiving an international award and unrestricted grants for meta-analysis work on dairy foods and cardiometabolic diseases from Global and Dutch Dairy Associations. Other authors do not have any conflict of interest to declare. The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes., Methods: We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis., Findings: Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m 2 , who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio [RR] per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I 2 =53·9%, p heterogeneity =0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I 2 =63·0%, p heterogeneity <0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p heterogeneity ≥0·13)., Interpretation: Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful., Funding: Funders are shown in the appendix., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: A growing number of cohort studies suggest a potential role of dairy consumption in type 2 diabetes (T2D) prevention. The strength of this association and the amount of dairy needed is not clear., Objective: We performed a meta-analysis to quantify the associations of incident T2D with dairy foods at different levels of intake., Design: A systematic literature search of the PubMed, Scopus, and Embase databases (from inception to 14 April 2015) was supplemented by hand searches of reference lists and correspondence with authors of prior studies. Included were prospective cohort studies that examined the association between dairy and incident T2D in healthy adults. Data were extracted with the use of a predefined protocol, with double data-entry and study quality assessments. Random-effects meta-analyses with summarized dose-response data were performed for total, low-fat, and high-fat dairy, (types of) milk, (types of) fermented dairy, cream, ice cream, and sherbet. Nonlinear associations were investigated, with data modeled with the use of spline knots and visualized via spaghetti plots., Results: The analysis included 22 cohort studies comprised of 579,832 individuals and 43,118 T2D cases. Total dairy was inversely associated with T2D risk (RR: 0.97 per 200-g/d increment; 95% CI: 0.95, 1.00;P= 0.04;I(2)= 66%), with a suggestive but similar linear inverse association noted for low-fat dairy (RR: 0.96 per 200 g/d; 95% CI: 0.92, 1.00;P= 0.072;I(2)= 68%). Nonlinear inverse associations were found for yogurt intake (at 80 g/d, RR: 0.86 compared with 0 g/d; 95% CI: 0.83, 0.90;P< 0.001;I(2)= 73%) and ice cream intake (at ∼10 g/d, RR: 0.81; 95% CI: 0.78, 0.85;P< 0.001;I(2)= 86%), but no added incremental benefits were found at a higher intake. Other dairy types were not associated with T2D risk., Conclusion: This dose-response meta-analysis of observational studies suggests a possible role for dairy foods, particularly yogurt, in the prevention of T2D. Results should be considered in the context of the observed heterogeneity., (© 2016 American Society for Nutrition.)