Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

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.

Kidney function and specific mortality in 60-80 years old post-myocardial infarction patients: A 10-year follow-up study.

Chronic kidney disease (CKD) is highly prevalent among older post-myocardial infarction (MI) patients. It is not known whether CKD is an independent risk factor for mortality in older post-MI patients with optimal cardiovascular drug-treatment. Therefore, we studied the relation between kidney function and all-cause and specific mortality among older post-MI patients, without severe heart failure, who are treated with state-of-the-art pharmacotherapy. From 2002-2006, 4,561 Dutch post-MI patients were enrolled and followed until death or January 2012. We estimated Glomerular Filtration Rate (eGFR) with cystatin C (cysC) and creatinine (cr) using the CKD-EPI equations and analyzed the relation with any and major causes of death using Cox models and restricted cubic splines. Mean (SD) for age was 69 years (5.6), 79% were men, 17% smoked, 21% had diabetes, 90% used antihypertensive drugs, 98% used antithrombotic drugs and 85% used statins. Patients were divided into four categories of baseline eGFRcysC: ≥90 (33%; reference), 60-89 (47%), 30-59 (18%), and <30 (2%) ml/min/1.73m2. Median follow-up was 6.4 years. During follow-up, 873 (19%) patients died: 370 (42%) from cardiovascular causes, 309 (35%) from cancer, and 194 (22%) from other causes. After adjustment for age, sex and classic cardiovascular risk factor, hazard ratios (95%-confidence intervals) for any death according to the four eGFRcysC categories were: 1 (reference), 1.4 (1.1-1.7), 2.9 (2.3-3.6) and 4.4 (3.0-6.4). The hazard ratios of all-cause and cause-specific mortality increased linearly below kidney functions of 80 ml/min/1.73 m2. Weaker results were obtained for eGFRcr. To conclude, we found in optimal cardiovascular drug-treated post-MI patients an inverse graded relation between kidney function and mortality for both cardiovascular as well as non-cardiovascular causes. Risk of mortality increased linearly below kidney function of about 80 ml/min/1.73 m2.

Kidney dysfunction, systemic inflammation and mental well-being in elderly post-myocardial infarction patients.

BACKGROUND: The aim was to investigate whether mild kidney dysfunction and low-grade inflammation in post-myocardial infarction patients are independently associated with markers of mental well-being (i.e. depressive and apathy symptoms, and dispositional optimism). METHODS: In post-myocardial infarction patients, kidney function was assessed by estimated glomerular filtration rate (eGFR) calculated from the combined CKD-EPI formula based on serum levels of both creatinine and cystatine C. Systemic inflammation was assessed using high sensitivity C-reactive protein (hs-CRP) levels. The 15-item Geriatric Depression Scale (GDS-15), the 3-item apathy subscale and the 4-item optimism questionnaire (4Q) were used to measure mental well-being and were analyzed using linear multivariable regression analysis. RESULTS: Of the 2355 patients, mean age was 72.3 (range 63-84) years and 80.1% were men. After multivariable adjustment, a poorer kidney function was associated with more depressive symptoms (ß = -0.084, p < 0.001), more apathy symptoms (ß = -0.101, p < 0.001), and less dispositional optimism (ß = 0.072, p = 0.002). Moreover, higher levels of hs-CRP were associated with more depressive symptoms (ß = 0.051, p = 0.013), more apathy symptoms (ß = 0.083, p < 0.001) and less dispositional optimism (ß = -0.047 p = 0.024). Apathy showed the strongest independent relation with both low eGFR and high hs-CRP. CONCLUSIONS: In post-myocardial infarction patients, impaired kidney function and systemic inflammation showed a stronger association with apathy than with depressive symptoms and dispositional optimism.

Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA): results from the alpha omega trial.

BACKGROUND: Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer. METHODS: The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60-80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL). FINDINGS: Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: -0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58). INTERPRETATION: An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

Association of n-3 long-chain PUFA and fish intake with depressive symptoms and low dispositional optimism in older subjects with a history of myocardial infarction.

Individuals with CHD are at increased risk of poor mental well-being. Dietary intake of EPA and DHA, the main n-3 fatty acids from fish, may be beneficial to mental well-being. We examined the association of EPA+DHA and fish intake with mental well-being in 644 participants, aged 60-80 years, with a history of myocardial infarction. Habitual food intake was assessed with a 203-item FFQ. Depressive symptoms were assessed with the self-report geriatric depression scale, and dispositional optimism was assessed with the revised life orientation test (LOT-R) and a four-item questionnaire (4Q). In Cox-regression models modified for cross-sectional analyses, we adjusted for sex, age, energy intake, BMI, family history of depression, education, marital status, smoking, physical activity and intake of saturated fat, alcohol and fibre. Compared with the lower tertile, subjects in the higher tertile of EPA+DHA intake had a lower prevalence of depressive symptoms, but this association was not statistically significant (prevalence ratio (PR) 0.78; 95 % CI 0.50, 1.22, P-trend 0.27). The higher tertile of EPA+DHA intake was positively associated with dispositional optimism measured with the 4Q (PR 0.69; 95 % CI 0.46, 1.03, P-trend 0.05), but not according to the LOT-R. Fish intake was not related to either depressive symptoms or dispositional optimism. In conclusion, intake of EPA+DHA was positively associated with dispositional optimism assessed with the 4Q, but not with optimism assessed with the LOT-R or with depressive symptoms.