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.

Serum magnesium concentrations and all-cause, cardiovascular, and cancer mortality among U.S. adults: Results from the NHANES I Epidemiologic Follow-up Study.

BACKGROUND: Few studies have examined the associations of serum magnesium (Mg) concentrations with total and cause-specific mortality in a nationally representative sample of US adults. We investigate the dose-response relationships of baseline serum Mg concentrations with risk of mortalities in a large, nationally representative sample of US adults. METHODS: We analyzed prospective data of 14,353 participants aged 25-74 years with measures of serum Mg concentrations at baseline (1971-1975) from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS). Mortality data was linked through December 31, 2011. We estimated the mortality hazard ratios (HRs), for participants within serum Mg categories of <0.7, 0.7-0.74, 0.75-0.79, 0.8-0.89 (referent), 0.9-0.94, 0.95-0.99, and ≥1.0 mmol/L using weighted multivariate-adjusted Cox proportional hazards models. RESULTS: During a median follow-up of 28.6 years, 9012 deaths occurred, including 3959 CVD deaths, 1923 cancer deaths, and 708 stroke deaths. The multivariate-adjusted HRs (95% CIs) of all-cause mortality across increasing categories of Mg were 1.34 (1.02, 1.77), 0.94 (0.75, 1.18), 1.08 (0.97, 1.19), 1.00 (referent), 1.05 (0.95, 1.16), 0.96 (0.79, 1.15), and 0.98 (0.76, 1.26). Similar trends were observed for cancer (HRs for serum Mg < 0.7: 1.39, 95% CI: 0.83, 2.32) and CVD mortality (HRs for serum Mg < 0.7: 1.28, 95% CI: 0.81, 2.02) but were not statistically significant. An elevated risk for stroke mortality was observed among participants with serum Mg < 0.70 mmol/L (HR: 2.55, 95% CI: 1.18, 5.48). CONCLUSIONS: Very low serum Mg concentrations were significantly associated with an increased risk of all-cause mortality in US adults.

Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study.

OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.

Low serum magnesium concentrations are associated with a high prevalence of premature ventricular complexes in obese adults with type 2 diabetes.

BACKGROUND: Premature ventricular complexes (PVC) predict cardiovascular mortality among several adult populations. Increased arrhythmia prevalence has been reported during controlled magnesium (Mg) depletion studies in adults. We thus hypothesized that serum magnesium (sMg) concentrations are inversely associated with the prevalence of PVC in adults at high cardiovascular risk. METHODS: Anthropometric, demographic and lifestyle characteristics were assessed in 750 Cree adults, aged > 18 yrs, who participated in an age-stratified, cross-sectional health survey in Quebec, Canada. Holter electrocardiograms recorded heart rate variability and cardiac arrhythmias for two consecutive hours. Multivariate logistic regression was used to evaluate the associations between sMg and PVC. RESULTS: PVC prevalence in adults with hypomagnesemia (sMg ≤ 0.70 mmol/L) was more than twice that of adults without hypomagnesemia (50% vs. 21%, p = 0.015); results were similar when adults with cardiovascular disease history were excluded. All hypomagnesemic adults with PVC had type 2 diabetes (T2DM). Prevalence of PVC declined across the sMg concentration gradient in adults with T2DM only (p < 0.001 for linear trend). In multivariate logistic regressions adjusted for age, sex, community, body mass index, smoking, physical activity, alcohol consumption, kidney disease, antihypertensive and cholesterol lowering drug use, and blood docosahexaenoic acid concentrations, the odds ratio of PVC among T2DM subjects with sMg > 0.70 mmol/L was 0.24 (95% CI: 0.06-0.98) p = 0.046 compared to those with sMg ≤ 0.70 mmol/L. CONCLUSIONS: sMg concentrations were inversely associated with the prevalence of PVC in patients with T2DM in a dose response manner, indicating that suboptimal sMg may be a contributor to arrhythmias among patients with T2DM.

Serum 25-hydroxyvitamin D is not associated with insulin resistance or beta cell function in Canadian Cree.

Epidemiological studies report inverse associations between blood vitamin D, as measured by 25-hydroxyvitamin D [25(OH)D] concentrations, and insulin resistance (IR) among predominantly overweight individuals. In a cross-sectional survey of 5 Cree communities in Quebec, Canada, we determined if 25(OH)D is associated with IR and ß-cell function in a largely obese, ethnic minority at high risk of developing type 2 diabetes. A total of 510 participants (≥18 y) without type 1 or type 2 diabetes, assessed for serum 25(OH)D, fasting plasma glucose and insulin, and anthropometric and lifestyle variables, were included in the analyses. Multivariable linear regressions adjusted for covariates were performed for homeostasis model assessment of IR (HOMA-IR) and ß-cell function (HOMA-B) in relation to serum 25(OH)D. Serum 25(OH)D (per 10 nmol/L increment) was inversely associated with HOMA-IR (ß = -0.005; SE = 0.002; P = 0.004) and HOMA-B (ß = -0.004; SE = 0.002; P = 0.006) in models adjusted for age, sex, physical activity, education, alcohol consumption, and smoking. When further adjusted for BMI, associations were no longer significant for either HOMA-IR (ß = 0.001, SE = 0.002, P = 0.572) or HOMA-B (ß = 0.001, SE = 0.001, P = 0.498). The modest inverse associations between 25(OH)D and IR reported previously were not observed in this population after adjusting for adiposity. Future longitudinal studies investigating the interrelationship among 25(OH)D, adiposity, and the risk of developing metabolic syndrome and type 2 diabetes are warranted.