Individual serum saturated fatty acids and markers of chronic subclinical inflammation: the Insulin Resistance Atherosclerosis Study.

Recent evidence has documented distinct effects of individual saturated FAs (SFAs) on cardiometabolic outcomes, with potential protective effects from odd- and very long-chain SFAs (VLSFAs). Cross-sectional and prospective associations of individual serum SFAs (12:0, 14:0, 15:0, 16:0, 18:0, 20:0, 22:0, and total SFA) with proinflammatory biomarkers and adiponectin were investigated in 555 adults from the IRAS. Principal component analysis (PCA) of proinflammatory markers yielded three clusters: principal component (PC) 1: fibrinogen, white cell count, C-reactive protein; PC 2: plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-18; PC 3: IL-6 and IL-8. Cross-sectional analyses on proinflammatory PCs and adiponectin, and prospective analyses on 5 year PAI-1 and fibrinogen concentrations were conducted with multiple regression. Total SFA and 16:0 were positively associated with PC 1 and PC 2, and negatively associated with adiponectin. The 14:0 was positively associated with PC 1 and negatively associated with adiponectin. In contrast, 15:0, 20:0, and 22:0 were negatively associated with PC 2, and 20:0 and 22:0 were positively associated with adiponectin. The 18:0 was negatively associated with PC 3. Prospectively, 15:0, 18:0, 20:0, and 22:0 were negatively associated with 5 year PAI-1 concentrations. The results demonstrate that individual SFAs have distinct roles in subclinical inflammation, highlighting the unique metabolic impacts of individual SFAs.

Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts.

OBJECTIVES: Although most controlled feeding trials have failed to show an adverse effect of fructose on blood pressure, concerns continue to be raised regarding the role of fructose in hypertension. To quantify the association between fructose-containing sugar (high-fructose corn syrup, sucrose, and fructose) intake and incident hypertension, a systematic review and meta-analysis of prospective cohort studies was undertaken. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Library (through February 5, 2014) were searched for relevant studies. Two independent reviewers reviewed and extracted relevant data. Risk estimates were aggregated comparing the lowest (reference) quintile with highest quintile of intake using inverse variance random effect models and expressed as risk ratios (RR) with 95% confidence intervals (CIs). Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). The Newcastle-Ottawa Scale assessed study quality. Clinicaltrials.gov NCT01608620. RESULTS: Eligibility criteria were met by 3 prospective cohorts (n = 37,375 men and 185,855 women) with 58,162 cases of hypertension observed over 2,502,357 person-years of follow-up. Median fructose intake was 5.7-6.0% total energy in the lowest quintile and 13.9-14.3% total energy in the highest quintile. Fructose intake was not associated with incident hypertension (RR = 1.02, 95% CI, 0.99-1.04), with no evidence of heterogeneity (I(2) = 0%, p = 0.59). Spline curve modeling showed a U-shaped relationship with a negative association at intakes ≤50th percentile (∼10% total energy) and a positive association at higher intakes. CONCLUSIONS: Total fructose intake was not associated with an increased risk of hypertension in 3 large prospective cohorts of U.S. men and women.

Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS).

Objective: To examine the associations of fatty acids in the de novo lipogenesis (DNL) pathway, specifically myristic acid (14:0), palmitic acid (16:0), cis-palmitoleic acid (c16:1 n-7), cis-myristoleic acid (c14:1n5), stearic acid (18:0) and cis-oleic acid (c18:1 n-9), with 5-year risk of type 2 diabetes. We hypothesized that DNL fatty acids are associated with risk of type 2 diabetes independent of insulin sensitivity. Research design and methods: We evaluated 719 (mean age 55.1±8.5 years, 44.2% men, 42.3% Caucasians) participants from the Insulin Resistance Atherosclerosis Study. Multivariable logistic regression models with and without adjustment of insulin sensitivity were used to assess prospective associations of DNL fatty acids with incident type 2 diabetes. Results: Type 2 diabetes incidence was 20.3% over 5 years. In multivariable regression models, palmitic, palmitoleic, myristic, myristoleic and oleic acids were associated with increased risk of type 2 diabetes (p<0.05). Palmitic acid had the strongest association (OR per standard unit of palmitic acid 1.46; 95% CI 1.23 to 1.76; p<0.001), which remained similar with addition of insulin sensitivity and acute insulin response (AIR) to the model (OR 1.36; 95% CI 1.09 to 1.70, p=0.01). Oleic and palmitoleic acids were also independently associated with incident type 2 diabetes. In multivariable models, ratios of fatty acids corresponding to stearoyl CoA desaturase-1 and Elovl6 enzymatic activity were significantly associated with risk of type 2 diabetes independent of insulin sensitivity and AIR. Conclusions: We observed associations of DNL fatty acids with type 2 diabetes incidence independent of insulin sensitivity.

The Distribution of Fatty Acid Biomarkers of Dairy Intake across Serum Lipid Fractions: The Prospective Metabolism and Islet Cell Evaluation (PROMISE) Cohort.

Circulating fatty acids (FA) derived largely from dairy consumption have most commonly been measured in total human serum or phospholipid (PL) fractions, and have been used as validated biomarkers of dairy intake in a growing number of epidemiological studies. Nevertheless, measurement and characterization of a wider spectrum of FA biomarkers of dairy across the four major serum lipid fractions is lacking. This study aimed to (1) quantify FA biomarkers of dairy in PL, triacylglycerol (TAG), cholesteryl ester (CE), and unesterified fatty acid (FFA) serum lipid fractions; and (2) identify potential demographic and metabolic factors that may modify the proportions of these FA across serum fractions. Baseline data from 444 adults in the PROMISE cohort were analyzed. FA biomarkers, 15:0, t16:1n-7, 18:2-c9,t11, and t18:1n-7 were quantified from serum. Dairy intake was estimated using the validated Canadian Diet History Questionnaire. Our results show that t18:1n-7 was the most abundant FA biomarker in all fractions except CE, where 18:2-c9,t11 was the most abundant. Positive correlations within fractions, and across FA in the PL, CE, and FFA fractions were found, however, TAG FA were negatively correlated with the other fractions. PL and CE FA were positively associated with dairy intake, and negatively associated with markers of dysmetabolism while, in contrast, these markers were predictors of higher TAG dairy FA. This study is the first to demonstrate distinct proportions of dairy FA in different serum lipid fractions. PL and CE FA marked dairy intake in this cohort, while TAG FA appeared to be markers of dysmetabolism.

Serum pentadecanoic acid (15:0), a short-term marker of dairy food intake, is inversely associated with incident type 2 diabetes and its underlying disorders.

BACKGROUND: Growing evidence suggests that dairy consumption is associated with lower type 2 diabetes risk. However, observational studies have reported inconsistent results, and few have examined dairy's association with the underlying disorders of insulin resistance and ß-cell dysfunction. OBJECTIVE: We investigated the association of the dairy fatty acid biomarkers pentadecanoic acid (15:0) and trans-palmitoleic acid (trans 16:1n-7) with type 2 diabetes traits by evaluating 1) prospective associations with incident diabetes after 5 y of follow-up and 2) cross-sectional associations with directly measured insulin resistance and ß-cell dysfunction. DESIGN: The study analyzed 659 adults without diabetes at baseline from the triethnic multicenter Insulin Resistance Atherosclerosis Study (IRAS). Diabetes status was assessed by using oral-glucose-tolerance tests. Frequently sampled intravenous-glucose-tolerance tests measured insulin sensitivity (SI) and ß-cell function [disposition index (DI)]. Serum fatty acids were quantified by using gas chromatography. Logistic and linear regression models were adjusted for demographic, lifestyle, and dietary variables. RESULTS: Serum 15:0 was a significant biomarker for total dairy intake in the IRAS cohort. It was associated with a decreased incident diabetes risk (OR: 0.73, P = 0.02) and was positively associated with log SI (ß: 0.84, P = 0.03) and log DI (ß: 2.21, P = 0.02) in fully adjusted models. trans 16:1n-7 was a marker of total partially hydrogenated dietary fat intake and was not associated with outcomes in fully adjusted models. CONCLUSIONS: Serum 15:0, a marker of short-term intake of this fatty acid, was inversely associated with diabetes risk in this multiethnic cohort. This study may contribute to future recommendations regarding the benefits of dairy products on type 2 diabetes risk.